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WO2025207944A1 - Fgfr3-iiib-binding antibodies - Google Patents

Fgfr3-iiib-binding antibodies

Info

Publication number
WO2025207944A1
WO2025207944A1 PCT/US2025/021849 US2025021849W WO2025207944A1 WO 2025207944 A1 WO2025207944 A1 WO 2025207944A1 US 2025021849 W US2025021849 W US 2025021849W WO 2025207944 A1 WO2025207944 A1 WO 2025207944A1
Authority
WO
WIPO (PCT)
Prior art keywords
seq
amino acid
acid sequence
chain variable
variable domain
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/021849
Other languages
French (fr)
Inventor
Ziyong Sun
Ryan Bruce CORCORAN
Eric Anthony MURPHY
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sidewinder Therapeutics Inc
Original Assignee
Sidewinder Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sidewinder Therapeutics Inc filed Critical Sidewinder Therapeutics Inc
Publication of WO2025207944A1 publication Critical patent/WO2025207944A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • Cancer is a complex and multifaceted disease characterized by uncontrolled cell growth and is a global health challenge causing significant morbidity and mortality worldwide.
  • Existing cancer therapies including chemotherapy and radiation, often produce debilitating side effects, can fail to target cancer cells exclusively, thereby damaging healthy cells and tissues, and may lead to resistance or relapse.
  • Fibroblast growth factors and their receptors (FGFRs) are known oncologic drivers of cancers, however, currently approved therapies target FGFR receptors in pan-specific manner, leading to toxicity and side effects that impair overall treatment outcomes.
  • FGFs Fibroblast growth factors
  • FGFRs Fibroblast growth factors
  • FGFR3-IIIb target specific isoforms of the FGFR3 receptor: FGFR3-IIIb or FGFR3-IIIb and FGFR3-IIIc.
  • the antibodies provided and exemplified herein are advantageous in that they specifically target FGFR3-IIIb or FGFR3-IIIb and FGFR3-IIIc.
  • the antibodies are additionally advantageous in that they are internalized by cells expressing FGFR3-IIIb, such as tumor cells.
  • an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 4; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 6; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 7; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 8; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 9; and a light chain variable domain comprising: a CDRH1 comprising the
  • an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 121; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 122; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 123; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 124; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 125; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 126; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 127; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 128; a CDRH3 comprising the amino acid sequence of SEQ ID NO
  • an antibody or antibody fragment that binds FGFR3- Illb comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising:
  • an antibody or antibody fragment that binds FGFR3- Illb comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 657; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising:
  • an antibody or antibody fragment that binds FGFR3- Illb comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising:
  • an antibody or antibody fragment that binds FGFR3- Illb comprising a heavy chain variable region and a light chain variable region, wherein: the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 677, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 676; the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 683, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 206; the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 677, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 206; or the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 684, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 682.
  • an antibody or antibody fragment that binds FGFR3- Illb comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19-21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 61-63, 64-66; 67-69, 70-72; 73- 75, 76-78; 79-81, 82-84; 85-87, 88-90; 91-93, 94-96; 97-99, 100-102; 103-105, 106-108; 109- 111, 112-114; 115-117, 118-120; 121-123, 124-126;
  • an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19-21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 121-123, 124-126; 127- 129, 130-132; 133-135, 136-138; 139-141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; DY, 158-159, SY, 161-162; DY, 176-177, SKY, 179-180; 211-2
  • the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 97%, 98%, 99%,
  • an antibody or antibody fragment that binds FGFR3- Illb comprising: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%
  • an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%
  • the antibody or antibody fragment does not bind with an affinity of about or less than about 10 X 10' 8 M to FGFR1, FGFR2, or FGFR4. In some embodiments, the antibody or antibody fragment binds to a FGFR3- Illb protein with an equilibrium dissociation constant (KD) equal to or less than 10 x 10' 8 M. In some embodiments, the FGFR3-IIIb protein comprises the amino acid sequence of SEQ ID NO: 191, 195, or 197. In some embodiments, the antibody is internalized by a cell expressing FGFR3-IIIb. In some embodiments, the cell is a HEK-293 cell expressing FGFR3-IIIb.
  • composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb; and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb and internalizing into a cell expressing FGFR3-IIIb; and a pharmaceutically acceptable carrier.
  • a method of inhibiting proliferation of a cell expressing FGFR3-IIIb comprising: contacting a cell with the antibody or antibody fragment described herein or the pharmaceutical composition described herein.
  • the antibody or antibody fragment is internalized by the cell.
  • the cell is a Ba/F3 cell expressing FGFR3-IIIb.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 67; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 673; a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 661; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 662; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 663
  • CDRL1 light chain complementarity determining region 1
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 4; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 6; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 7; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 8; a CDRH3 comprising the amino acid sequence of SEQ
  • antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 31; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 32; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 33; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 34; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 36; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 37; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 38; a CDRH3 comprising the amino acid sequence of SEQ ID NO
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 121; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 122; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 123; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 124; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 125; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 126; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 127; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 128; a CDRH3 comprising:
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of S
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of S
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19- 21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 61-63, 64-66; 67-69, 70-72; 73-75, 76-78; 79-81, 82-84; 85-87, 88-90; 91-93, 94-96; 97-99, 100-102; 103-105, 106-108; 109-111, 112-114; 115-
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19- 21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 121-123, 124-126; 127-129, 130-132; 133-135, 136-138; 139-141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; DY, 158-159, SY, 161-162; DY, 176-177,
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the light chain variable region and the CDRs of the heavy chain variable region comprise SEQ ID NOS: 70-72, 67, 689, 69; 70-72, 67, 673, 69; or 70, 71, 660, 67, 673, 69.
  • the antibody or antibody fragment that binds FGFR3-IIIb comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 9
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the light chain variable region and the CDRs of the heavy chain variable region comprise SEQ ID NOS: 10-12, 7-9.
  • the antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202.
  • VH heavy chain variable region
  • VL light chain variable region
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the light chain variable region and the CDRs of the heavy chain variable region comprise SEQ ID NOS: 130-132, 127-129.
  • the antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
  • VH heavy chain variable region
  • VL light chain variable region
  • the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 97%, 98%, 99%,
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or
  • the antibody or antibody fragment comprises a CHI domain, e.g., of SEQ ID NO: 685.
  • the antibody or antibody fragment comprises a CH2 domain, e.g., of SEQ ID NO: 686.
  • the antibody or antibody fragment comprises a CH3 domain, e.g., of SEQ ID NO: 687.
  • the antibody or antibody fragment comprises a Kappa domain, e.g., of SEQ ID NO: 688.
  • the antibody or antibody fragment comprises an Fc domain, e.g., SEQ ID NO: 611 or 612.
  • the antibody or antibody fragment that binds FGFR3-IIIb comprises: a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 677 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 676; a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 614 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 615; a heavy chain having at least 80%, 85%, 90%, 91%, 92%
  • the antibody or antibody fragment does not bind with an affinity of about or less than about 10 X 10' 8 M to FGFR1, FGFR2, or FGFR4. In some embodiments, the antibody or antibody fragment binds to a FGFR3-IIIb protein with an equilibrium dissociation constant (KD) equal to or less than 10 x 10" 8 M. In some embodiments, FGFR3-IIIb protein comprises the amino acid sequence of SEQ ID NO: 191, 195, or 197. In some embodiments, the antibody is internalized by a cell expressing FGFR3-IIIb. In some embodiments, the cell is a HEK-293 cell expressing FGFR3-IIIb.
  • composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb; and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb and internalizing into a cell expressing FGFR3-IIIb; and a pharmaceutically acceptable carrier.
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 7; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 8; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 9; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 10; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 12;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 19; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 20; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 21; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 22; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 23; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 24;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 25; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 26; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 27; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 28; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 29; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 30; or
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 43; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 44; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 45; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 46; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 47; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 48;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb comprising:
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666; (iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL1 comprising
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb comprising:
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb comprising:
  • an antibody or antibody fragment that binds to FGFR3-IIIb binds to FGFR3-IIIb with a KD of less than about 10 x 10' 8 M.
  • an antibody or antibody fragment that binds to FGFR3-IIIb is specific for FGFR3-IIIb.
  • an antibody or antibody fragment specific for FGFR3-IIIb does not bind to another FGFR antigen with a KD of less than about 10 X 10' 8 M.
  • Another FGFR antigen may include FGFR1, FGFR2, and/or FGFR3.
  • another FGFR antigen is FGFR3-IIIc.
  • Non-limiting example binding assays are provided in the Examples, e.g., Example 5.
  • Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
  • An antibody or antibody fragment that binds to FGFR3-IIIb may include an antibody or antibody fragment that binds to FGFR3-IIIb and FGFR3-IIIc.
  • An antibody or antibody fragment that binds to FGFR3-IIIb and FGFR3-IIIc may include an antibody or antibody fragment that is specific for FGFR3-IIIb and specific for FGFR3-IIIc.
  • an antibody or antibody fragment specific for FGFR3-IIIb and FGFR3-IIIc does not bind to another FGFR antigen with a KD about or less than about 10 X 10' 8 M.
  • Another FGFR antigen may include FGFR1, FGFR2, and/or FGFR3.
  • the antibodies and antibody fragments are useful in that they specifically bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc (e.g., they are not pan-specific across FGFR1-4). In certain instances, the antibodies and antibody fragments herein do not bind to FGFR1, FGFR2, or FGFR4 with a KD about or less than about 10 X 10' 8 . Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
  • the antibodies and antibody fragments are useful in that they are internalized by cells expressing FGFR3-IIIb and/or FGFR3-IIIc.
  • Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
  • antibodies and antibody fragments having means for binding FGFR3-IIIb In some embodiments, provided are antibodies and antibody fragments having means for binding FGFR3-IIIb and internalizing into a cell expressing FGFR3-IIIb. In some embodiments, provided are antibodies and antibody fragments having means for binding FGFR3-IIIb and FGFR3-IIIc. In certain embodiments, provided are antibodies and antibody fragments having means for binding FGFR3-IIIb and FGFR3-IIIc and internalizing into a cell expressing FGFR3-IIIb and/or FGFR3-IIIc. Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb are internalized by a cell expressing FGFR3-IIIb.
  • the cell is a HEK-293 cell expressing FGFR3-IIIb.
  • Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
  • the antibodies and/or antibody fragments that bind FGFR3-IIIb bind to a FGFR3-IIIb protein with an equilibrium dissociation constant (KD) equal to or less than 100 * 10' 9 M, less than 50 x 10' 9 M, less than 25 x 10' 9 M, less than 10 x 10' 9 M, or less than 5 x 10' 9 M.
  • the FGFR3-IIIb protein comprises the amino acid sequence of SEQ ID NO: 191, 193, 195, or 197.
  • antibodies and/or antibody fragments bind FGFR3-IIIc.
  • the FGFR3- Illc-binding antibody or FGFR3-IIIc-binding antibody fragment binds to a FGFR3-IIIc protein (e.g., as measured by ELISA or cell-binding in the Examples).
  • the FGFR3-IIIc protein comprises the amino acid sequence of SEQ ID NO: 192, 194, 196, or 198.
  • the antibody and/or antibody fragment that binds FGFR3-IIIb e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc
  • Nonlimiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
  • a FGFR3-IIIc-binding antibody or FGFR3-IIIc-binding antibody fragment generally refers to and/or includes an antibody that binds a FGFR3-3-IIIc protein comprising a protein having the amino acid sequence of SEQ ID NO: 192.
  • a FGFR3-IIIc antibody or FGFR3-IIIc-binding antibody fragment is specific for a FGFR3-IIIc protein (e.g., selectively recognize and bind to a FGFR3-IIIc protein). Binding can be determined by bio-layer interferometry, surface plasmon resonance, isothermal titration calorimetry, and/or ELISA.
  • Affinity generally refers to and/or includes the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen such as FGFR3-IIIb, and FGFR3-IIIc).
  • binding affinity generally encompasses and refers to intrinsic binding affinity which reflects a 1 : 1 interaction between members of a binding pair (e.g., antibody and antigen).
  • the affinity of an antibody for an antigen can generally be represented by the dissociation constant (KD).
  • FGFR3 generally refers to and/or includes the protein encoded by the FGFR3 gene and functions in cell division, cell maturation, formation of new blood vessels, wound healing, and bone growth, development, and maintenance.
  • FGFR3 alternative splice variants result in FGFR3-IIIb and FGFR3-IIIc isoforms of the FGFR3 protein.
  • FGFR3-IIIb generally refers to and/or includes a protein encoded by the FGFR3 gene.
  • FGFR3-IIIc generally refers to and/or includes a protein encoded by the FGFR3 gene.
  • the FGFR3 gene refers to NCBI GenelD 2261 and/or HGNC ID: HGNC: 3690, which includes sequence information on isoform Illb.
  • a FGFR3-IIIb protein refers to and includes the protein(s) of UniProt ID: P22607-2.
  • FGFR3-IIIb comprises a protein comprising the amino acid sequence of SEQ ID NO: 191 or a homologue or an orthologue or variant thereof (e.g., as referenced in NCBI GenelD 2261 and/or HGNC ID: HGNC: 3690).
  • a FGFR3-IIIc protein refers to and includes the protein(s) of UniProt ID: P22607-1.
  • FGFR3-IIIc comprises a protein comprising the amino acid sequence of SEQ ID NO: 192 or a homologue or an orthologue or variant thereof (e.g., as referenced in NCBI GenelD 2261 and/or HGNC ID: HGNC: 3690).
  • FGFR3-IIIb comprises an amino acid sequence having at least 70, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to of SEQ ID NO: 191. In certain instances, FGFR3-IIIb comprises an amino acid sequence having at least 70, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to of SEQ ID NO: 195.
  • FGFR3-IIIb comprises an amino acid sequence having at least 70, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to of SEQ ID NOs: 197.
  • FGFR3-IIIc comprises an amino acid sequence having at least 70, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to of SEQ ID NO: 192.
  • the antibodies and/or antibody fragments that bind FGFR3-IIIb comprise an Fc region.
  • the Fc region is an IgG Fc region.
  • the Fc region may comprise a sequence of SEQ ID NO: 611 or 612.
  • the antibodies and/or antibody fragments that bind FGFR3-IIIb comprise a light chain constant region.
  • FGFR3-IIIb e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc
  • FGFR3-IIIb e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc
  • FGFR3-IIIb FGFR3-IIIb
  • FGFR3-IIIc FGFR3-IIIc
  • the antibodies and/or antibody fragments that bind FGFR3-IIIb comprise a Kappa domain, e.g., of SEQ ID NO: 688.
  • the antibodies and/or antibody fragments that bind FGFR3-IIIb comprise a heavy chain constant region.
  • human IgGl constant region having SEQ ID NO: 200, or a sequence at least about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to of SEQ ID NO: 200.
  • the antibodies and/or antibody fragments that bind FGFR3-IIIb comprise a CHI domain, e.g., of SEQ ID NO: 685.
  • the antibodies and/or antibody fragments that bind FGFR3-IIIb comprise a CH2 domain, e.g., of SEQ ID NO: 686.
  • the antibodies and/or antibody fragments that bind FGFR3-IIIb comprise a CH3 domain, e.g., of SEQ ID NO: 687.
  • Antibodies and antigenbinding fragments of antibodies generally encompass genetically engineered, and/or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multi-specific antibodies, multi-valent antibodies, diabodies, triabodies, and tetrabodies, tandem di-scFv, tandem tri-scFv.
  • immunoglobulins such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multi-specific antibodies, multi-valent antibodies, diabodies, triabodies, and tetrabodies, tandem di-scFv, tandem tri-scFv.
  • a full-length antibody, intact antibody, and/or whole antibody are interchangeable, and generally include and/or refer to an antibody having a structure substantially similar to a native antibody structure having heavy chains that contain an Fc region and/or include antibodies of any class or sub-class, including IgG and sub-classes thereof (e.g., IgGl and IgG4), IgM, IgE, IgA, and IgD.
  • Fc region generally encompasses and/or refers to a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region.
  • the Fc region includes an immunoglobulin CH2 and CH3 domain (e.g., an IgG CH2 and CH3 domain).
  • the term includes native sequence Fc regions and variant Fc regions.
  • a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-terminus of the heavy chain, per EU numbering.
  • the C-terminal lysine (Lys447) of the Fc region may or may not be present.
  • the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 617. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 203 and the light chain variable domain has the CDRs of SEQ ID NO: 204.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 31-33, and the light chain variable domain has CDRs of SEQ ID NOS: 34-36. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 37-39, and the light chain variable domain has CDRs of SEQ ID NOS: 40-42. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 43-45, and the light chain variable domain has CDRs of SEQ ID NOS: 46-48. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 49-51, and the light chain variable domain has CDRs of SEQ ID NOS: 52-54.
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 68; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72;
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 82-84. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 88-90. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 163-165, and the light chain variable domain has CDRs of the amino acid sequence EIS and SEQ ID NOS: 166 and 168.
  • the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 206.
  • the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 206.
  • the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 206.
  • the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 206.
  • the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 206.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of SEQ ID NOS: 64-66. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 70-72. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 76-78. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79- 81, and the light chain variable domain has CDRs of SEQ ID NOS: 82-84.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 88-90. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 163-165, and the light chain variable domain has CDRs of the amino acid sequence EIS and SEQ ID NOS: 166 and 168.
  • the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 619.
  • the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 619.
  • the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 619.
  • the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 619.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 88-90. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 163-165, and the light chain variable domain has CDRs of the amino acid sequence EIS and SEQ ID NOS: 166 and 168.
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 91; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 92; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 93; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 94; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 96;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 97; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 98; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 99; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 100; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 102;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 103; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 104; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 105; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 106; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 108;
  • CDRL2 comprising the amino acid sequence of SEQ ID NO: 113
  • CDRL3 comprising the amino acid sequence of SEQ ID NO: 114
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 115; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 116; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 117; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 118; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 119; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 120; or
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of NY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 170; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 171; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of NSY; a CDRL2 comprising the amino acid sequence of RAN; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 174.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 187; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 188.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 187 and the light chain variable domain has the CDRs of SEQ ID NO: 188. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 91-93, and the light chain variable domain has CDRs of SEQ ID NOS: 94-96. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 97-99, and the light chain variable domain has CDRs of SEQ ID NOS: 100-102. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 103-105, and the light chain variable domain has CDRs of SEQ ID NOS: 106-108.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 109-111, and the light chain variable domain has CDRs of SEQ ID NOS: 112-114. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 115-117, and the light chain variable domain has CDRs of SEQ ID NOS: 118-120. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence NY and SEQ ID NOS: 170-171, and the light chain variable domain has CDRs of the amino acid sequence NSY, RAN and SEQ ID NOS: 174.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 207.
  • the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 208.
  • the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 208.
  • the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 208.
  • the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 208.
  • the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 208.
  • the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 208.
  • the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 208.
  • the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 208. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 207 and the light chain variable domain has the CDRs of SEQ ID NO: 208.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 91-93, and the light chain variable domain has CDRs of SEQ ID NOS: 94-96. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 97-99, and the light chain variable domain has CDRs of SEQ ID NOS: 100-102. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 103-105, and the light chain variable domain has CDRs of SEQ ID NOS: 106-108. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 109-111, and the light chain variable domain has CDRs of SEQ ID NOS: 112-114.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 115-117, and the light chain variable domain has CDRs of SEQ ID NOS: 118-120. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence NY and SEQ ID NOS: 170- 171, and the light chain variable domain has CDRs of the amino acid sequence NSY, RAN and SEQ ID NOS: 174.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 620.
  • the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 621.
  • the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 621.
  • the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 621.
  • the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 621.
  • the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 621.
  • the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 621.
  • the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 621. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 207 and the light chain variable domain has the CDRs of SEQ ID NO: 208.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 91-93, and the light chain variable domain has CDRs of SEQ ID NOS: 94-96. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 97-99, and the light chain variable domain has CDRs of SEQ ID NOS: 100-102. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 103-105, and the light chain variable domain has CDRs of SEQ ID NOS: 106-108. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 109-111, and the light chain variable domain has CDRs of SEQ ID NOS: 112-114.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 115-117, and the light chain variable domain has CDRs of SEQ ID NOS: 118- 120. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence NY and SEQ ID NOS: 170-171, and the light chain variable domain has CDRs of the amino acid sequence NS Y, RAN and SEQ ID NOS: 174.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc comprising:
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 121; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 122; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 123; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 124; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 125; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 126;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 133; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 134; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 135; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 136; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 137; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 138;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 139; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 140; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 141; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 142; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 143; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 144;
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 189; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 190.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 189 and the light chain variable domain has the CDRs of SEQ ID NO: 190. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 121-123, and the light chain variable domain has CDRs of SEQ ID NOS: 124-126. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 127-129, and the light chain variable domain has CDRs of SEQ ID NOS: 130-132. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 133-135, and the light chain variable domain has CDRs of SEQ ID NOS: 136-138.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 139-141, and the light chain variable domain has CDRs of SEQ ID NOS: 142-144. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 145-147, and the light chain variable domain has CDRs of SEQ ID NOS: 148-150. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 176- 177, and the light chain variable domain has CDRs of the amino acid sequence SKY and SEQ ID NOS: 179-180.
  • the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 210.
  • the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 210. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 209 and the light chain variable domain has the CDRs of SEQ ID NO: 210.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 121-123, and the light chain variable domain has CDRs of SEQ ID NOS: 124-126. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 127-129, and the light chain variable domain has CDRs of SEQ ID NOS: 130-132. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 133-135, and the light chain variable domain has CDRs of SEQ ID NOS: 136-138. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 139-141, and the light chain variable domain has CDRs of SEQ ID NOS: 142-144.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 145-147, and the light chain variable domain has CDRs of SEQ ID NOS: 148-150. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 176-177, and the light chain variable domain has CDRs of the amino acid sequence SKY and SEQ ID NOS: 179-180.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 622.
  • the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 623.
  • the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 623.
  • the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 623.
  • the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 623.
  • the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 623.
  • the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 623.
  • the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 623.
  • the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 623. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 209 and the light chain variable domain has the CDRs of SEQ ID NO: 210.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 121-123, and the light chain variable domain has CDRs of SEQ ID NOS: 124- 126. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 127- 129, and the light chain variable domain has CDRs of SEQ ID NOS: 130-132. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 133-135, and the light chain variable domain has CDRs of SEQ ID NOS: 136-138. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 139-141, and the light chain variable domain has CDRs of SEQ ID NOS: 142-144.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 145-147, and the light chain variable domain has CDRs of SEQ ID NOS: 148-150. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 176-177, and the light chain variable domain has CDRs of the amino acid sequence SKY and SEQ ID NOS: 179-180.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising: (i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 185; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 185 and the light chain variable domain has the CDRs of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 205.
  • the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 674. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 674.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 618.
  • the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 624.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb comprising:
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 657; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 661; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 662; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 663;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; or
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 626.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 625 and the light chain variable domain has the CDRs of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 658 and 660. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 657, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 661-663.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 664-666. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 667-669. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 670-672.
  • [OHl] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 675.
  • the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 658 and 660. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 657, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 661-663. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 664-666.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb comprising:
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
  • the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 674.
  • the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 674. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 677 and the light chain variable domain has the CDRs of SEQ ID NO: 674.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 673, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653.
  • the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 624.
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
  • the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 676.
  • the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 676. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 677 and the light chain variable domain has the CDRs of SEQ ID NO: 676.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 658 and 660. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 673, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 661-663. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 664-666.
  • the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 667-669. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 670-672.
  • the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 626.
  • the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 626.
  • the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 626.
  • the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 626.
  • the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 626.
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 235; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 236; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 237; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 238; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 239; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 240;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 241; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 242; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 243; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 244; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 245; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 246;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 247; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 248; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 249; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 250; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 251; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 252;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 253; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 254; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 255; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 256; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 257; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 258;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 259; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 260; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 261; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 262; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 263; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 264;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 265; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 266; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 267; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 268; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 269; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 270;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 271; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 272; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 273; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 274; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 275; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 276;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 277; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 278; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 279; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 280; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 281; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 282;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 289; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 290; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 291; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 292; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 293; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 294;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 295; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 296; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 297; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 298; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 299; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 300;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 301; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 302; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 303; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 304; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 305; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 306; or
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 511; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 512.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 511 and the light chain variable domain has the CDRs of SEQ ID NO: 512. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 211- 213, and the light chain variable domain has CDRs of SEQ ID NOS: 214-216.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 513; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 514.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 513, and the light chain variable domain has the CDRs of SEQ ID NO: 514. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 217- 219, and the light chain variable domain has CDRs of SEQ ID NOS: 220-222.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 515; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 516.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 515, and the light chain variable domain has the CDRs of SEQ ID NO: 516. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 223- 225, and the light chain variable domain has CDRs of SEQ ID NOS: 226-228.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 517; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 518.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 519; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 520.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 519, and the light chain variable domain has the CDRs of SEQ ID NO: 520. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 235- 237, and the light chain variable domain has CDRs of SEQ ID NOS: 238-240.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 521, and the light chain variable domain has the CDRs of SEQ ID NO: 522. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 241- 243, and the light chain variable domain has CDRs of SEQ ID NOS: 244-246.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 523; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 524.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 523, and the light chain variable domain has the CDRs of SEQ ID NO: 524. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 247- 249, and the light chain variable domain has CDRs of SEQ ID NOS: 250-252.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 525; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 526.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 525, and the light chain variable domain has the CDRs of SEQ ID NO: 526. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 253- 255, and the light chain variable domain has CDRs of SEQ ID NOS: 256-258.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 527; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 528.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 527, and the light chain variable domain has the CDRs of SEQ ID NO: 528. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 259- 261, and the light chain variable domain has CDRs of SEQ ID NOS: 262-264.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 529; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 530.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 529, and the light chain variable domain has the CDRs of SEQ ID NO: 530. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 265- 267, and the light chain variable domain has CDRs of SEQ ID NOS: 268-270.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 531; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 532.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 531, and the light chain variable domain has the CDRs of SEQ ID NO: 532. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 271- 273, and the light chain variable domain has CDRs of SEQ ID NOS: 274-276.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 533; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 534.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 533, and the light chain variable domain has the CDRs of SEQ ID NO: 534. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 277- 279, and the light chain variable domain has CDRs of SEQ ID NOS: 280-282.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 535; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 536.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 535, and the light chain variable domain has the CDRs of SEQ ID NO: 536. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 283- 285, and the light chain variable domain has CDRs of SEQ ID NOS: 286-288.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 537; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 538.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 537, and the light chain variable domain has the CDRs of SEQ ID NO: 538. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 289- 291, and the light chain variable domain has CDRs of SEQ ID NOS: 292-294.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 539; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 540.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 539, and the light chain variable domain has the CDRs of SEQ ID NO: 540. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 295- 297, and the light chain variable domain has CDRs of SEQ ID NOS: 298-300.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 541; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 542.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 541, and the light chain variable domain has the CDRs of SEQ ID NO: 542. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 301- 303, and the light chain variable domain has CDRs of SEQ ID NOS: 304-306.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 543; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 544.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 543, and the light chain variable domain has the CDRs of SEQ ID NO: 544. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 307- 309, and the light chain variable domain has CDRs of SEQ ID NOS: 310-312. [0139] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 313; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 314; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 315; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO:
  • CDRL2 comprising the amino acid sequence of SEQ ID NO: 317
  • CDRL3 comprising the amino acid sequence of SEQ ID NO: 318
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 319; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 320; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 321; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 322; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 323; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 324;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 325; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 326; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 327; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 328; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 329; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 330;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 331; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 332; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 333; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 334; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 335; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 336;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 337; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 338; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 339; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 340; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 341; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 342;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 343; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 344; a CDRH3 comprising the amino acid sequence of DDY; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 346; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 347; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 348;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 349; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 350; a CDRH3 comprising the amino acid sequence of TTH; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 352; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 353; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 354;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 355; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 356; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 357; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 358; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 359; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 360;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 361; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 362; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 363; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 364; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 365; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 366;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 367; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 368; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 369; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 370; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 371; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 372;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 373; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 374; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 375; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 376; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 377; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 378;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 379; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 380; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 381; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 382; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 383; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 384;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 385; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 386; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 387; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 388; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 389; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 390;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 391; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 392; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 393; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 394; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 395; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 396;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 397; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 398; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 399; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 400; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 401; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 402;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 403; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 404; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 405; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 406; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 407; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 408;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 409; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 410; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 411; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 412; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 413; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 414; (xviii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 415; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 416; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 417; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 418;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 421; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 422; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 423; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 424; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 425; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 426;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 427; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 428; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 429; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 430; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 431; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 432;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 433; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 434; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 435; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 436; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 437; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 438;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 439; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 440; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 441; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 442; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 443; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 444;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 445; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 446; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 447; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 448; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 449; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 450;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 451; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 452; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 453; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 454; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 455; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 456;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 457; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 458; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 459; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 460; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 461; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 462;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 463; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 464; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 465; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 466; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 467; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 468;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 469; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 470; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 471; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 472; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 473; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 474;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 475; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 476; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 477; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 478; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 479; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 480;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 481; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 482; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 483; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 484; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 485; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 486;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 487; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 488; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 489; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 490; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 491; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 492;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 493; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 494; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 495; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 496; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 497; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 498;
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 499; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 500; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 501; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 502; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 503; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 504; or
  • a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 505; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 506; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 507; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 508; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 509; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 510.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 545; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 546.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 545, and the light chain variable domain has the CDRs of SEQ ID NO: 546. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 313-315, and the light chain variable domain has CDRs of SEQ ID NOS: 316-318.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 547; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 548.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 547, and the light chain variable domain has the CDRs of SEQ ID NO: 548. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 319-321, and the light chain variable domain has CDRs of SEQ ID NOS: 322-324.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 549; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 550.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 549, and the light chain variable domain has the CDRs of SEQ ID NO: 550. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 325-327, and the light chain variable domain has CDRs of SEQ ID NOS: 328-330.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 551; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 552.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 551, and the light chain variable domain has the CDRs of SEQ ID NO: 552. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 331-333, and the light chain variable domain has CDRs of SEQ ID NOS: 334-336.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 553; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 554.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 553, and the light chain variable domain has the CDRs of SEQ ID NO: 554. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 337-339, and the light chain variable domain has CDRs of SEQ ID NOS: 340-342.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 555; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 556.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 555, and the light chain variable domain has the CDRs of SEQ ID NO: 556. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 343-344 and the amino acid sequence DDY, and the light chain variable domain has CDRs of SEQ ID NOS: 346- 348.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 557; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 558.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 557, and the light chain variable domain has the CDRs of SEQ ID NO: 558. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 349-350 and the amino acid sequence TTH, and the light chain variable domain has CDRs of SEQ ID NOS: 352- 354.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 559; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 560.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 559, and the light chain variable domain has the CDRs of SEQ ID NO: 560. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 355-357, and the light chain variable domain has CDRs of SEQ ID NOS: 358-360.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 561; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 562.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 563, and the light chain variable domain has the CDRs of SEQ ID NO: 564. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 367-369, and the light chain variable domain has CDRs of SEQ ID NOS: 370-372.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 565; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 566.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 567, and the light chain variable domain has the CDRs of SEQ ID NO: 568. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 379-381, and the light chain variable domain has CDRs of SEQ ID NOS: 382-384.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 569; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 570.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 569, and the light chain variable domain has the CDRs of SEQ ID NO: 570. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 385-387, and the light chain variable domain has CDRs of SEQ ID NOS: 388-390.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 571; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 572.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 573, and the light chain variable domain has the CDRs of SEQ ID NO: 574. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 397-399, and the light chain variable domain has CDRs of SEQ ID NOS: 400-402.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 575; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 576.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 575, and the light chain variable domain has the CDRs of SEQ ID NO: 576. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 403-405, and the light chain variable domain has CDRs of SEQ ID NOS: 406-408.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 577; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 578.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 577, and the light chain variable domain has the CDRs of SEQ ID NO: 578. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 409-411, and the light chain variable domain has CDRs of SEQ ID NOS: 412-414.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 581; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 582.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 581, and the light chain variable domain has the CDRs of SEQ ID NO: 582. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 421-423, and the light chain variable domain has CDRs of SEQ ID NOS: 424-426.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 583; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 584.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 583, and the light chain variable domain has the CDRs of SEQ ID NO: 584. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 427-429, and the light chain variable domain has CDRs of SEQ ID NOS: 430-432.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 585; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 586.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 585, and the light chain variable domain has the CDRs of SEQ ID NO: 586. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 433-435, and the light chain variable domain has CDRs of SEQ ID NOS: 436-438.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 587; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 588.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 595, and the light chain variable domain has the CDRs of SEQ ID NO: 596. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 463-465, and the light chain variable domain has CDRs of SEQ ID NOS: 466-468.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 607, and the light chain variable domain has the CDRs of SEQ ID NO: 608. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 499-501, and the light chain variable domain has CDRs of SEQ ID NOS: 502-504.
  • the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 632; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 633.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 632 and the light chain
  • the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 634; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 635.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 634 and the light chain
  • the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 636; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 637.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 636 and the light chain
  • the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 638; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 633.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 632 and the light chain
  • the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 632; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 640.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 641 and the light chain
  • the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 680; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 681.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 680 and the light chain
  • the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 683; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 682.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 683 and the light chain
  • the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 684; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 682.
  • the heavy chain variable domain has the CDRs of SEQ ID NO: 684 and the light chain
  • antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the antibodies and/or antibody fragments comprise a constant region having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 611-613.
  • antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the antibodies and/or antibody fragments comprise a constant region having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 685-688.
  • the antibodies and antibody fragments that bind (e.g., specifically) FGFR3-IIIb can be useful in methods that include and/or require specific recognition of FGFR3-IIIb and/or internalization of antibodies and antibody fragments that FGFR3-IIIb.
  • methods inhibiting proliferation of a cell expressing FGFR3-IIIb comprising: contacting a cell with the antibody or antibody fragment that binds FGFR3-IIIb (as those described herein).
  • the antibody or antibody fragment is internalized by the cell.
  • the cell is a Ba/F3 cell expressing FGFR3-IIIb.
  • cell proliferation is measured by the assay described in Example 6.
  • percent (%) sequence identity is the percentage of amino acid residues or nucleic acid residues in a candidate sequence that are identical with the amino acid residues or nucleic acid residues, respectively, in a selected sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity.
  • Alignment for purposes of determining percent amino acid sequence identity or percent nucleic acid identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as Clustal Omega, BLAST, BLAST-2, ALIGN, ALIGN-2 or Megalign (DNASTAR) software, with BLAST being the alignment algorithm of preference. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full-length of the sequences being compared, although for simplicity it maybe preferred to use default parameters.
  • the term “individual” is synonymous with patient and/or subject and includes and/or refers to a human and may be a human that has been diagnosed as needing to treat a disease or condition as disclosed herein. However, examples are not limited to humans and include, chimpanzees, marmosets, cows, horses, sheep, goats, pigs, rabbits, dogs, cats, rats, mice, guinea pigs, and the like.
  • the term individual includes vertebrates. The individual is typically a human and may be a human that has been diagnosed as needing to treat a disease or condition as disclosed herein.
  • treating or treatment of includes and/or refers to ameliorating the disease or disorder or symptoms thereof (e.g., slowing or arresting or reducing the development of the disease or at least one of the clinical symptoms thereof).
  • treating or treatment also includes and/or refers to alleviating or ameliorating at least one physical and/or biological parameters including those which may not be discernible by the patient.
  • treating or treatment includes and/or refers to modulating a disease, disorder, or biological process either physically, (e.g., stabilization of a discernible symptom), physiologically, e.g., stabilization of a physical and/or biological parameter), or both.
  • treating or treatment includes and/or refers to preventing or delaying the onset or development or progression of the disease or disorder. In certain embodiments, treating or treatment includes and/or refers to preventing or delaying or inhibiting the deterioration of (i) a healthy physiological state or (ii) a baseline physiological state (e.g., the progression of a disease or disorder).
  • “about X” may include a range of values that are ⁇ 10%, ⁇ 5%, ⁇ 2%, ⁇ 1%, ⁇ 0.5%, ⁇ 0.2%, or ⁇ 0.1% of X, where X is a numerical value.
  • the term “and/or” is to be taken as specific disclosure of each of the two specified features or components with or without the other.
  • a and/or B is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each were set out individually herein.
  • mice were immunized subcutaneously every 2 weeks for 6 weeks with hFGFR3-IIIb-HisTag and hFGFR3-IIIc-HisTag (100 pg/mouse) emulsified with an equal volume of Freund's complete/incomplete adjuvant.
  • mice were boosted by intravenous injection of the antigen without adjuvant.
  • Spleen cells (1 * 10 8 ) from immunized mouse were fused with SP2/0 myeloma cells (1.5> ⁇ 10 7 ) with PEG Hybri-Max (Sigma Inc., Cat. No: 7181).
  • the cells were distributed into 96-well plates at 0.1 ml per well and incubated at 37°C, 5% CO2 incubator. On day 1, an additional 0.1 ml media containing serum and HAT plus 2* methotrexate was added to each well. On day 3 and day 7, 0.1 ml of media from each well was replaced with 0.1 ml of fresh HT media. The screening typically occurred between days 8-9, and the culture supernatant from each well was tested for hFGFR3-IIIb- HisTag and hFGFR3-IIIc-HisTag binding by ELISA and cell binding analysis.
  • Example 3 hFGFR3 hybridoma antibody screening based on FACS binding assay
  • hybridoma antibody with hFGFR3-IIIb and hFGFR3-IIIc was further measured by FACS using 293T cell line stably expressing FGFR3-IIIb.
  • l * 10 A 5 FGFR3- IIIb-293T cells were added to each well of 96-well plate and incubated with 10 pg/mL hybridoma antibody at 4 °C for 1 hr. After the cells were washed three times with FACS buffer (PBS + 3% FBS (ExCell Bio, Cat. No: FND500) (v/v)), the secondary antibody (APC Goat antimouse (BioLegend, Cat.
  • Table 6 ELISA EC50 values for binding of FGFR3-IIIb antibodies to cells expressing FGFR3-IIIb or -IIIc
  • Example 4 Internalization of hFGFR3-IIIb antibody
  • Example 5 hFGFR3 hybridoma antibody gene cloning, chimeric antibody generation and characterization
  • RNA of each hFGFR3 hybridoma clone was isolated by RNeasy Mini Kit (Qiagen, Cat. No: 74104) and used as the template to synthesize first-strand cDNA with SuperScript® II Reverse Transcriptase (Life Technology, Cat. No: 18064-14) according to the manufacturer's instructions.
  • the cDNA product was then subjected to PCR in a 50 pL volume reaction mixture using degenerate mouse IgG primers (Kettleborough et al., (1993) European Journal of Immunology 23:206; Strebe et al., (2010) Antibody Engineering 1 :3).
  • the reaction was carried out in a S1000TM Thermal Cycler (Bio-Rad, Cat.
  • 3 pL of purified PCR product were cloned into the pMD-18T vector (Takara, Cat. No: D101A) and transformed into One Shot® TOPIO chemically competent E. coli (Invitrogen, CAT. NO:C4040-03). Clones were screened by colony PCR using universal M13 forward and reverse primers, and 5 positive clones from each reaction were picked for DNA sequencing in both directions using Ml 3 forward and Ml 3 reverse primers.
  • the light chain of chimeric antibody was constructed by inserting the cDNA encoding mouse light chain various region (VL) to the upstream of human kappa chain constant region (SEQ ID NO: 199), and the heavy chain of chimeric antibody was constructed by linking the cDNA encoding mouse heavy chain various region (VH) to the upstream of human IgGl constant region (SEQ ID NO: 200).
  • the 5'-ends of the mouse cDNA sequences were modified using PCR primers designed to add a leader sequence to both light chain and heavy chain, and the DNAs encoding the light chain and heavy chain of each chimeric antibody were subcloned into expression vector pcDNA3.1 (Invitrogen Cat. No: V-790), respectively.
  • Binding of the chimeric antibody with hFGFR3 was also measured by FACS using the same methods described above in Example 3. Binding of FGFR3-IIIb chimeric antibodies chi8511, chi287, chil012, chi295, and chi547 was also tested against FGFR3-IIIb mutants R248C and S249C. Table 8 shows binding data to FGFR3-IIIb to cells expressing FGFR3-IIIb mutants R248C and S249C.
  • Binding of chimeric antibodies with hFGFR3-IIIb and FGFR3-IIIc was also measured by ELISA (FIG. 4) using the same methods described above in Example 2. Binding of FGFR3-IIIb antibodies chi8511, chi287, chil012, chi295, and chi547 was also tested against FGFR3-IIIb, FGFR1, FGFR2, and FGFR4 (FIG. 6). The results demonstrate the specificity of the antibodies for hFGFR3-IIIb or hFGFR3-IIIb and FGFR3-IIIc and inability to bind FGFR1, FGFR2, and FGFR4.
  • Table 8 Binding of FGFR3-IIIb chimeric antibodies to cells expressing FGFR3- Illb or -IIIc
  • FGFR3-IIIb chimeric antibody The internalization capability of FGFR3-IIIb chimeric antibody was measured using Incucyte. Briefly, 1.6* 10 4 FGFR3-IIIb-293T cells were seeded in 96-well plate (Coming, Cat. No:3610) and incubate overnight at 37 °C. After mixing FGFR3-IIIb antibody with Incucyte Human Fabfluor-pH Red (Statorius, Cat. No: 4722), the mixture was incubated at room temperature for 5 min before being added to the cells. The 96-well plate was loaded to Incucyte S3 Live Cell Analysis System and incubated at 37°C for 24 hrs.
  • hFGFR3-IIIb-HisTag analyte series were prepared by diluting the stocks with running buffer to 100 nM followed by 2-fold serial dilution in the same buffer down to 0.78 nM. Analytes were injected in series over the reference and experiment flow cells for 3 minutes at a flow rate of 30 pL/minute. Running buffer (PBS with 0.05% P20) was allowed to flow over for 10 minutes at a flow rate of 30 pL/minute. At the end of each cycle, the biosensor surface was regenerated via 30-second injection of Glycine pH 2.0 (Cytiva, Cat. No: BR100355) buffer at a flow rate of 10 pL/minute.
  • binding responses obtained from the experimental biosensor surface were double referenced by subtracting simultaneously recorded responses from the reference surface followed by additional subtraction of responses from a single referenced running buffer sample.
  • the association and dissociation rate constants (ka and kd) were determined simultaneously by fitting double-referenced sensorgrams of the entire titration series to Langmuir model (1 :1) using Biaevaluation software.
  • Example 6 Generation of FGFR3-IIIb/BaF3 stable cell lines and cell proliferation assay
  • cDNA encoding full length FGFR3-IIIb was subcloned into pLVX vector (YouBio, Cat. No: VT4005) to generate pLVX-FGFR3-IIIb plasmid, which was used to generate Ba/F3 cell lines by co-transfecting with psPAX2 (Qualit Yard, Cat. No: QYV0052) and pMD2.G (Qualit Yard, Cat. No: QYV0053).
  • FGFR3- IIIb/BaF3 cells After drug selection with 1 ug/mL puromycin for 2 weeks, the surviving cells were subcloned to generate cell lines stably expressing FGFR3-IIIb (FGFR3- IIIb/BaF3).
  • FGFR3-IIIb/BaF3 cells (l x lO A 4/mL) were seeded in RPMI 1640 medium supplemented with 10% fetal bovine serum, 10 ng/mL FGF1 and 10 ug/mL heparin (Stemcell, Cat. No: 07980).
  • FGFR3-IIIb antibodies were added at a final concentration from 30,000 ng/mL to 4.6 ng/mL (three-fold serial dilution).
  • FGFR3-IIIb antibodies 8511, 287, 1012, 295, and 547 reduced proliferation of FGFR3-IIIb/BaF3 cells.
  • Human antibody germlines which have high sequence homology with mouse antibody 547, 8511, 287, 295 and 1012 were selected by searching the IMGT/Domain Gap Align 3D structure database (http://www.imgt.org/3Dstructure-DB/cgi/DomainGapAlign.cgi).
  • the frameworks of human germline antibodies were used as templates for grafting the complementary determining regions (CDRs) from the heavy chain and light chain variable regions of the mouse antibodies.
  • CDRs complementary determining regions
  • some amino acids in the frameworks of the human germline templates were back mutated to the corresponding mouse sequences to give a functional humanized antibody.
  • mouse antibody 547 a combination of human germline IGHV1-2*O6 and IGHJ4*01 was selected as the template for heavy chain humanization, and a combination of IGKV1-9*O3 and IGKJ4*01 was chosen as the template for light chain humanization.
  • Several sites in the frameworks of the human germline templates were back mutated to the corresponding amino acid sequences in mouse antibody.
  • the amino acid at position 1 was mutated from Ala (A) to Asp (D)
  • the amino acid at position 43 was mutated from Ala (A) to Thr (T)
  • the amino acid at position 44 was mutated from Pro (P) to Asn (N);
  • the amino acid at position 38 was mutated from Arg (R) to Lys (K)
  • the amino acid at position 48 was mutated from Met (M) to He (I)
  • the amino acid at position 67 was mutated from Arg (R) to Lys (K)
  • the amino acid at position 70 was mutated from Met (M) to Leu (L)
  • the amino acid at position 72 was mutated from Arg (R) to Vai (V)
  • the amino acid at position 74 was mutated from Thr (T) to Lys (K)
  • the amino acid at position 84 was mutated from Ser (S) to His (H)
  • the amino acid at position 85 was
  • mouse antibody 8511 For mouse antibody 8511, a combination of human germline IGHV1-2*O6 and IGHJ6*01 was selected as the template for heavy chain humanization, and a combination of IGKVl-33*01 and IGKJ2*01 was chosen as the template for light chain humanization.
  • the amino acid at position 3 was mutated from Gin (Q) to Vai (V)
  • the amino acid at position 49 was mutated from Tyr (Y) to Asn (N);
  • the amino acid at position 48 was mutated from Met (M) to He (I)
  • the amino acid at position 67 was mutated from Arg (R) to Lys (K)
  • the amino acid at position 70 was mutated from Ser (S) to Leu (L)
  • the amino acid at position 72 was mutated from Arg (R) to Vai (V)
  • the amino acid at position 74 was mutated from Thr (T) to Lys (K)
  • the amino acid at position 84 was mutated from Ser (S) to Arg (R)
  • the amino acid at position 85 was mutated from Arg (R) to Ser (S).
  • mouse antibody 287 a combination of human germline IGHV1-2*O6 and IGHJ4*01 was selected as the template for heavy chain humanization, and a combination of IGKV6-21*02 and IGKJ4*01 was chosen as the template for light chain humanization.
  • the amino acid at position 45 was mutated from Leu (L) to Arg (R)
  • the amino acid at position 46 was mutated from Leu (L) to Trp (W)
  • the amino acid at position 48 was mutated from Lys (K) to Tyr (Y)
  • the amino acid at position 69 was mutated from Asp (D) to Ser (S)
  • the amino acid at position 70 was mutated from Phe (F) to Tyr (Y);
  • the amino acid at position 48 was mutated from Met (M) to He (I)
  • the amino acid at position 66 was mutated from Arg (R) to Lys (K)
  • the amino acid at position 70 was mutated from Met (M) to Leu (L)
  • the amino acid at position 72 was mutated from Arg (R) to Vai (V)
  • the amino acid at position 74 was mutated from Thr (T) to Lys (K)
  • the amino acid at position 84 was
  • mouse antibody 1012 For mouse antibody 1012, a combination of human germline IGHV3-21*01 and IGHJ5*01 was selected as the template for heavy chain humanization, and a combination of IGKV1-9*O3 and IGKJ2*01 was chosen as the template for light chain humanization.
  • the amino acid at position 3 was mutated from Gin (Q) to Vai (V)
  • the amino acid at position 45 was mutated from Leu (L) to Pro (P)
  • the amino acid at position 46 was mutated from Leu (L) to Trp (W)
  • the amino acid at position 70 was mutated from Phe (F) to Tyr (Y);
  • the amino acid at position 49 was mutated from Ser (S) to Ala (A)
  • the amino acid at position 76 was mutated from Lys (K) to Arg (R)
  • the amino acid at position 84 was mutated from Asn (N) to Ser (S)
  • the amino acid at position 97 was mutated from Ala (A) to Thr (T).
  • the CDR2 of heavy chain and the CDR3 of light chain were further modified at the sites which may cause fragmentation, isomerization, and deamidation.
  • the amino acid at position 60 of heavy chain CDR2 was mutated from Asp (D) to Ser (S) and Tyr (Y); the amino acid at position 62 of heavy chain CDR2 was mutated from Asp (D) to Glu (E);
  • the amino acid at position 91 of light chain CDR3 was mutated from Asn (N) to Gin (Q); the amino acid at position 92 of light chain CDR3 was mutated from Ser (S) to Thr (T).
  • hlO12/S92T SEQ ID NO: 618 and SEQ ID NO: 624
  • hl012/D60Y/N91Q SEQ ID NO: 625 and SEQ ID NO: 626
  • hl012/D60S62E/S92T SEQ ID NO: 627 and SEQ ID NO: 624
  • hl012/D60S62E/N91Q SEQ ID NO: 627 and SEQ ID NO: 626
  • Example 8 FACS analysis of antibodies generated from hybridoma clones
  • binding experiments using FGFR3-IIIb antibodies were performed using bladder tumor cells (e.g., RT112/84 and SW780 cell lines) as well as 293T cells over-expressing FGFR3-IIIb, FGFR3-IIIb with S249C mutation, and FGFR3-IIIc. FACS analysis was performed to calculate EC50 of these antibodies.
  • RT11/84 cells, SW780 cells, and 293T cells over-expressing FGFR3-IIIb, FGFR3-IIIb with S249C mutation, and FGFR3-IIIc were prepared as described in Example 3. Bindings of antibodies generated from clones (see Table 3) to bladder cancer cell lines, RT112/84 and SW780, are shown in FIG. 7A and FIG. 7B. Further, bindings of antibodies were tested in 293T cells over-expressing FGFR3-IIIb, FGFR3-IIIb with S249C mutation, and FGFR3-IIIc, which were shown in FIG. 7C, FIG. 7D, and FIG. 7E, respectively.
  • FACS analysis was also performed to determine binding of hybridoma antibodies to different isoforms of FGFR3, FGFR3-IIIb and FGFR3-IIIc, and results are shown in FIG. 7G.
  • Example 9 FACS analysis of chimeric antibodies
  • binding experiments of chimeric antibodies as described in example 5 were performed using 293T cells over-expressing FGFR3.
  • FACS analysis was performed to analyze binding affinity and specificity as described in Example 3.
  • FACS results of binding of chimeric antibodies to 293T cells over-expressing FGFR3-IIIb (first column), FGFR3-IIIc (second column 2), FGFR3-IIIb with R248C mutation (third column), or FGFR3-IIIb with S249C mutation (fourth column), are shown in Table 12 and FIG.
  • chimeric 1012 and chimeric 295 antibodies bind to wildtype FGFR3-IIIb or mutant R248C or R249C FGFR3-IIIb, but not FGFR3-IIIc, while chimeric 8511, chimeric 547, and chimeric 287 antibodies bind to both FGFR3-IIIb and FGFR3-IIIc.
  • RT4 cell line isolated from urinary bladder tissue
  • NCI-H1781 cell line isolated from lung tissue with stage 3B bronchoalveolar carcinoma
  • FaDu cell line head and neck squamous cell carcinoma (HNSCC)
  • binding experiments of humanized antibodies as described in Example 7 and Table 10 were performed using 293T cells over-expressing FGFR3-IIIb or FGFR3-IIIc, as well as cancer cell lines, e.g., RT112/84 and RT4, as described in Example 3.
  • Results of binding experiments of humanized antibodies tested in 293T cells over-expressing FGFR3-IIIb, 293T cells over-expressing FGFR3-IIIc, RT112/84 cell line, and RT4 cell line are shown in FIG. 9A, FIG. 9B, FIG. 9C, and FIG. 9D, respectively
  • Example 11 Analysis of humanized antibodies derived from hl012
  • ADCC Antibody Dependent Cellular Cytotoxicity
  • ADCP Antibody-Dependent Cellular Phagocytosis
  • RT112/84 cell line and Jurkat cells Antibody dependent cell-mediated cytotoxicity
  • ADCC is one of the main mechanisms of antibody drugs eliminating tumor cells.
  • Jurkat-NFAT-Luc2-CD16a-V158 cells were used as effector cells.
  • CD16a transmitted the activation signal and activated the NFAT-luc2 luciferase reporter gene, giving rise to chemiluminescence after substrate addition.
  • the ADCC activity of the test articles was determined by measuring the signal of luminescence using luciferase Assay System Kit. Luciferase is an enzyme catalyzed luminescence reaction.
  • the transcriptional activation of target gene was directly proportional to the expression of luciferase.
  • the cells were dissolved by the luciferase substrate containing D- luciferin.
  • the ATP and Mg 2+ were as co substrates, catalyzes the conversion of D-luciferase extracted from reporter cells to oxidized luciferase.
  • the amount of light emitted was proportional to the amount of luciferase. Therefore, gene activation can be detected by using one-step TM luciferase Assay System Kit.
  • Cells were grown in cell culture and harvested during the logarithmic growth period. Cells were counted using a blood counting chamber. The cell viability was found to be >90% as determined by a trypan blue assay. Cells were centrifuged at 1000 RPM for 5 minutes and supernatant discarded. Cell concentration was adjusted with the culture medium. 45 pl cell suspension of effector cells (Jurkat) and target cells (RT112/84) was added to each well in a 96- well plate at 25,000 cells/well each. The plate was incubated in a humidified incubator at 37°C with 5% CO2 while preparing samples.
  • Jurkat effector cells
  • RT112/84 target cells
  • lOx dilution of test antibodies was prepared, the initial concentration is 10000 ng/ml, with 5-fold dilution for 9 gradients. Add 10 pL of lOx dilutions to each well (triplicate for each concentration). The plates were incubated in the humidified incubator at 37°C with 5% CO2 for 6 hours. The plates were then read for luminescence signal. Plates are equilibrated to room temperature and 100 pL/well Bright-Glo reagent was added to each well and incubated for 15 minutes on a shaker to lyse the cells. The plates were then read for luminescence signal.
  • ADCC assays were also performed using 293T cells over-expressing FGFR3-IIIb. Protocol was used as described above for Chi8511, Chi287, Chi295, Chil012, Chi547, Reference mAb 2, and Reference mAb 3, isotype hlgGl, and IgGl. Results are shown in FIG. HE and Table 17 Limited ADCC effect on 293T cells over-expressing FGFR3-IIIb of chi295 and chil012 antibodies were observed.
  • ADCs of chi295 and chil012 conjugated with MMAE show similar cytotoxicity as Reference mAb 2 conjugated with MMAE.
  • cytotoxicity of additional chimeric antibodies was tested.
  • RT112/84 cell lines were used and were cultured in 2D.
  • Chimeric antibodies were added at a range of concentrations from 0.01 nM to 1,000 nM. After incubation for a set period of time at 37 °C, cell viability was measured with CellTiter-Glo (Promega, Cat. No: G7572).
  • CellTiter-Glo Promega, Cat. No: G7572.
  • the effect of FGFR3-IIIb chimeric antibody drug conjugates on the proliferation of cells was measured (chi8511, chi287, chi295, chi547, and chil012, each conjugated to MMAE). Cytotoxicity of chimeric antibodies was shown in FIG. 12A.

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Abstract

Provided and exemplified herein are antibodies and antibody fragments thereof that bind FGFR3-IIIb and/or FGFR3-IIIc. In certain instances, the antibodies and antibody fragments thereof are useful in that they specifically bind FGFR3-IIIb (e.g., they are not pan-specific across FGFR1-4). Further, provided herein are pharmaceutical compositions comprising antibodies and antibody fragments and methods of using antibodies and antibody fragments described herein.

Description

FGFR3-IIIb-BINDING ANTIBODIES
CROSS-REFERENCE
[0001] This application claims the benefit of U.S. Provisional Application No. 63/572,015, filed March 29, 2024; U.S. Provisional Application No. 63/653,116, filed May 29, 2024; and U.S. Provisional Application No. 63/741,769, filed January 3, 2025, the entirety of which are incorporated herein by reference in their entirety.
SEQUENCE LISTING
[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on March 26, 2025, is named 65440-702.601_SL. xml and is 620,661 bytes in size.
BACKGROUND
[0003] Cancer is a complex and multifaceted disease characterized by uncontrolled cell growth and is a global health challenge causing significant morbidity and mortality worldwide. Existing cancer therapies, including chemotherapy and radiation, often produce debilitating side effects, can fail to target cancer cells exclusively, thereby damaging healthy cells and tissues, and may lead to resistance or relapse.
SUMMARY
[0004] Fibroblast growth factors (FGFs) and their receptors (FGFRs) are known oncologic drivers of cancers, however, currently approved therapies target FGFR receptors in pan-specific manner, leading to toxicity and side effects that impair overall treatment outcomes. Provided herein are antibodies that, unlike pan-specific modalities, target specific isoforms of the FGFR3 receptor: FGFR3-IIIb or FGFR3-IIIb and FGFR3-IIIc. Accordingly, in certain instances, the antibodies provided and exemplified herein are advantageous in that they specifically target FGFR3-IIIb or FGFR3-IIIb and FGFR3-IIIc. Moreover, in certain instances, the antibodies are additionally advantageous in that they are internalized by cells expressing FGFR3-IIIb, such as tumor cells.
[0005] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR- Illb comprising: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 67; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 673; a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 661; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 662; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 663; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 689; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 64; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 65; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 66; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 68; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 76; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 77; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 78; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 82; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 83; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 84; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 88; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 89; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 90; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 163; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 164; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 165; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 166; a CDRL2 comprising the amino acid sequence of EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 168; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 91; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 92; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 93; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 94; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 96; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 97; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 98; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 99; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 100; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 102; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 103; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 104; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 105; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 106; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 108; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 109; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 110; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 111; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 112; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 113; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 114; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 115; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 116; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 117; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 118; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 119; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 120; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of NY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 170; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 171; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1 comprising the amino acid sequence of NSY; a CDRL2 comprising the amino acid sequence of RAN; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 174.
[0006] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 4; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 6; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 7; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 8; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 9; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 10; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 12; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 13; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 14; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 15; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 16; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 17; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 18; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 19; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 20; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 21; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 22; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 23; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 24; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 25; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 26; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 27; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 28; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 29; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 30; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 152; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 153; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of STE; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 155; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 156.
[0007] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 31; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 32; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 33; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 34; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 36; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 37; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 38; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 39; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 40; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 41; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 42; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 43; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 44; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 45; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 46; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 47; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 48; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 49; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 50; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 51; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 52; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 53; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 54; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 55; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 56; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 57; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 58; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 59; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 60; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of GY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 158; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 159; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 161; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 162.
[0008] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 121; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 122; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 123; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 124; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 125; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 126; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 127; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 128; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 129; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 130; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 131; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 132; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 133; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 134; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 135; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 136; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 137; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 138; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 139; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 140; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 141; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 142; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 143; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 144; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 145; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 146; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 147; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 148; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 149; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 150; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 176; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 177; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SKY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 179; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 180.
[0009] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
[0010] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 657; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 661; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 662; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 663; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
[0011] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
[0012] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb comprising a heavy chain variable region and a light chain variable region, wherein: the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 677, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 676; the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 683, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 206; the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 677, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 206; or the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 684, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 682.
[0013] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising a heavy chain variable region and a light chain variable region, wherein: the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 209, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 210; or the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 201, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 202.
[0014] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19-21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 61-63, 64-66; 67-69, 70-72; 73- 75, 76-78; 79-81, 82-84; 85-87, 88-90; 91-93, 94-96; 97-99, 100-102; 103-105, 106-108; 109- 111, 112-114; 115-117, 118-120; 121-123, 124-126; 127-129, 130-132; 133-135, 136-138; 139- 141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; GY, 158-159, SY, 161-162; 163- 165, 166, EIS, 168; NY, 170-171, NS Y, RAN, 174; DY, 176-177, SKY, 179-180; 211-213, 214- 216; 217-219, 220-222; 223-225, 226-228; 229-231, 232-234; 235-237, 238-240; 241-243, 244- 246; 247-249, 250-252; 253-255, 256-258; 259-261, 262-264; 265-267, 268-270; 271-273, 274-
276; 277-279, 280-282; 283-285, 286-288; 289-291, 292, 294; 295-297, 298-300; 301-303, 304-
306; 307-309, 310-312; 313-315, 316-318; 319-321, 322-324; 325-327, 328-330; 331-333, 334-
336; 337-339, 340-342; 343-344, DDY, 346-348; 349-350, TTH, 352-354; 355-357, 358-360;
361-363, 364-366; 367-369, 370-372; 373-375, 376-378; 379-381, 382-384; 385-387, 388-390; 391-393, 394-396; 397-399, 400-402; 403-405, 406-408; 409-411, 412-414; 415-417, 418-420; 421-423, 424-426; 427-429, 430-432; 433-435, 436-438; 439-441, 442-444; 445-447, 448-450; 451-453, 454-456; 457-459, 460-462; 463-465, 466-468; 469-471, 472-474; 475-477, 478-480; 481-483, 484-486; 487-489, 490-492; 493-495, 496-498; 499-501, 502-504; or 505-507, 508- 510; respectively.
[0015] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19-21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 121-123, 124-126; 127- 129, 130-132; 133-135, 136-138; 139-141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; DY, 158-159, SY, 161-162; DY, 176-177, SKY, 179-180; 211-213, 214-216; 217-219, 220-222; 223-225, 226-228; 229-231, 232-234; 235-237, 238-240; 241-243, 244-246; 247-249, 250-252; 253-255, 256-258; 259-261, 262-264; 265-267, 268-270; 271-273, 274-276; 277-279, 280-282; 283-285, 286-288; 289-291, 292, 294; 295-297, 298-300; 301-303, 304-306; 307-309, or 310-312; respectively.
[0016] In some embodiments, the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 684 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 682; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 203 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 204; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 207 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 208; or a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
[0017] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb comprising: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 684 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 682; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 203 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 204; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 207 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 208; or a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
[0018] Provided and exemplified herein is an antibody or antibody fragment that binds FGFR3- Illb and FGFR3-IIIc comprising: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 207 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 208; or a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
[0019] In some embodiments, the antibody or antibody fragment comprises an Fc domain. In some embodiments, the antibody or antibody fragment that binds FGFR3-IIIb comprises: a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 614 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 615; a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 616 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 617; a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 618 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 619; a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 620 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 621; or a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 622 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 623. In some embodiments, the antibody or antibody fragment does not bind with an affinity of about or less than about 10 X 10'8 M to FGFR1, FGFR2, or FGFR4. In some embodiments, the antibody or antibody fragment binds to a FGFR3- Illb protein with an equilibrium dissociation constant (KD) equal to or less than 10 x 10'8 M. In some embodiments, the FGFR3-IIIb protein comprises the amino acid sequence of SEQ ID NO: 191, 195, or 197. In some embodiments, the antibody is internalized by a cell expressing FGFR3-IIIb. In some embodiments, the cell is a HEK-293 cell expressing FGFR3-IIIb.
[0020] Provided and exemplified herein is a pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb; and a pharmaceutically acceptable carrier.
[0021] Provided and exemplified herein is a pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb and internalizing into a cell expressing FGFR3-IIIb; and a pharmaceutically acceptable carrier.
[0022] Provided and exemplified herein is a method of inhibiting proliferation of a cell expressing FGFR3-IIIb, the method comprising: contacting a cell with the antibody or antibody fragment described herein or the pharmaceutical composition described herein. In some embodiments, the antibody or antibody fragment is internalized by the cell. In some embodiments, the cell is a Ba/F3 cell expressing FGFR3-IIIb.
[0023] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 67; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 673; a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 661; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 662; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 663; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 64; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 65; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 66; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 68; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 76; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 77; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 78; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 82; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 83; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 84; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 88; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 89; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 90; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 163; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 164; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 165; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 166; a CDRL2 comprising the amino acid sequence of EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 168; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 91; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 92; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 93; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 94; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 96; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 97; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 98; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 99; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 100; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 102; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 103; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 104; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 105; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 106; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 108; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 109; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 110; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 111; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 112; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 113; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 114; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 115; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 116; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 117; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 118; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 119; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 120; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of NY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 170; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 171; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1 comprising the amino acid sequence of NSY; a CDRL2 comprising the amino acid sequence of RAN; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 174.
[0024] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 4; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 6; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 7; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 8; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 9; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 10; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 12; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 13; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 14; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 15; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 16; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 17; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 18; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 19; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 20; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 21; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 22; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 23; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 24; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 25; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 26; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 27; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 28; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 29; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 30; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 152; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 153; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of STE; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 155; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 156.
[0025] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 31; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 32; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 33; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 34; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 36; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 37; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 38; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 39; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 40; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 41; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 42; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 43; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 44; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 45; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 46; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 47; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 48; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 49; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 50; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 51; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 52; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 53; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 54; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 55; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 56; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 57; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 58; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 59; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 60; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of GY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 158; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 159; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 161; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 162.
[0026] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 121; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 122; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 123; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 124; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 125; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 126; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 127; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 128; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 129; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 130; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 131; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 132; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 133; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 134; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 135; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 136; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 137; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 138; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 139; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 140; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 141; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 142; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 143; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 144; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 145; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 146; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 147; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 148; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 149; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 150; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 176; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 177; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SKY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 179; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 180.
[0027] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; ora heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
[0028] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 657; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 661; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 662; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 663; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
[0029] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain
- 1 - variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
[0030] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19- 21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 61-63, 64-66; 67-69, 70-72; 73-75, 76-78; 79-81, 82-84; 85-87, 88-90; 91-93, 94-96; 97-99, 100-102; 103-105, 106-108; 109-111, 112-114; 115-117, 118-120; 121-123, 124-126; 127-129, 130-132; 133-135, 136-138; 139-141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; GY, 158-159, SY, 161-162; 163-165, 166, EIS, 168; NY, 170-171, NS Y, RAN, 174; DY, 176- 177, SKY, 179-180; 211-213, 214-216; 217-219, 220-222; 223-225, 226-228; 229-231, 232- 234; 235-237, 238-240; 241-243, 244-246; 247-249, 250-252; 253-255, 256-258; 259-261, 262-
264; 265-267, 268-270; 271-273, 274-276; 277-279, 280-282; 283-285, 286-288; 289-291, 292,
294; 295-297, 298-300; 301-303, 304-306; 307-309, 310-312; 313-315, 316-318; 319-321, 322-
324; 325-327, 328-330; 331-333, 334-336; 337-339, 340-342; 343-344, DDY, 346-348; 349-
350, TTH, 352-354; 355-357, 358-360; 361-363, 364-366; 367-369, 370-372; 373-375, 376- 378; 379-381, 382-384; 385-387, 388-390; 391-393, 394-396; 397-399, 400-402; 403-405, 406-
408; 409-411, 412-414; 415-417, 418-420; 421-423, 424-426; 427-429, 430-432; 433-435, 436-
438; 439-441, 442-444; 445-447, 448-450; 451-453, 454-456; 457-459, 460-462; 463-465, 466-
468; 469-471, 472-474; 475-477, 478-480; 481-483, 484-486; 487-489, 490-492; 493-495, 496-
498; 499-501, 502-504; or 505-507, 508-510; respectively.
[0031] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19- 21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 121-123, 124-126; 127-129, 130-132; 133-135, 136-138; 139-141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; DY, 158-159, SY, 161-162; DY, 176-177, SKY, 179-180; 211- 213, 214-216; 217-219, 220-222; 223-225, 226-228; 229-231, 232-234; 235-237, 238-240; 241- 243, 244-246; 247-249, 250-252; 253-255, 256-258; 259-261, 262-264; 265-267, 268-270; 271- 273, 274-276; 277-279, 280-282; 283-285, 286-288; 289-291, 292, 294; 295-297, 298-300; 301- 303, 304-306; 307-309, or 310-312; respectively. [0032] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the light chain variable region and the CDRs of the heavy chain variable region comprise SEQ ID NOS: 70-72, 67, 689, 69; 70-72, 67, 673, 69; or 70, 71, 660, 67, 673, 69. In some embodiments, the antibody or antibody fragment that binds FGFR3-IIIb comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 684 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 682. [0033] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the light chain variable region and the CDRs of the heavy chain variable region comprise SEQ ID NOS: 10-12, 7-9. In some embodiments, the antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202.
[0034] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the light chain variable region and the CDRs of the heavy chain variable region comprise SEQ ID NOS: 130-132, 127-129. In some embodiments, the antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
[0035] In some embodiments, the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 684 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 682; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 203 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 204; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 207 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 208; or a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210. [0036] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 203 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 204; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 207 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 208; or a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
[0037] In some embodiments, the antibody or antibody fragment comprises a CHI domain, e.g., of SEQ ID NO: 685. In some embodiments, the antibody or antibody fragment comprises a CH2 domain, e.g., of SEQ ID NO: 686. In some embodiments, the antibody or antibody fragment comprises a CH3 domain, e.g., of SEQ ID NO: 687. In some embodiments, the antibody or antibody fragment comprises a Kappa domain, e.g., of SEQ ID NO: 688. In some embodiments, the antibody or antibody fragment comprises an Fc domain, e.g., SEQ ID NO: 611 or 612.
[0038] In some embodiments, the antibody or antibody fragment that binds FGFR3-IIIb comprises: a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 677 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 676; a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 614 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 615; a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 616 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 617; a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 618 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 619; a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 620 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 621; or a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 622 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 623. In some embodiments, the antibody or antibody fragment does not bind with an affinity of about or less than about 10 X 10'8 M to FGFR1, FGFR2, or FGFR4. In some embodiments, the antibody or antibody fragment binds to a FGFR3-IIIb protein with an equilibrium dissociation constant (KD) equal to or less than 10 x 10" 8 M. In some embodiments, FGFR3-IIIb protein comprises the amino acid sequence of SEQ ID NO: 191, 195, or 197. In some embodiments, the antibody is internalized by a cell expressing FGFR3-IIIb. In some embodiments, the cell is a HEK-293 cell expressing FGFR3-IIIb.
[0039] Provided and exemplified herein is a pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb; and a pharmaceutically acceptable carrier.
[0040] Provided and exemplified herein is a pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb and internalizing into a cell expressing FGFR3-IIIb; and a pharmaceutically acceptable carrier.
[0041] Provided and exemplified herein is a method of inhibiting proliferation of a cell expressing FGFR3-IIIb, the method comprising: contacting a cell with the antibody or antibody fragment described herein or the pharmaceutical described herein. In some embodiments, the antibody or antibody fragment is internalized by the cell. In some embodiments, the cell is a Ba/F3 cell expressing FGFR3-IIIb.
[0042] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprising: (i) a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 2; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 4; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 5; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 6;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 7; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 8; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 9; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 10; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 12;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 13; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 14; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 15; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 16; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 17; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 18;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 19; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 20; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 21; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 22; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 23; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 24;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 25; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 26; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 27; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 28; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 29; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 30; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 152; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 153; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of STE a CDRL2 comprising the amino acid sequence of SEQ ID NO: 155; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 156.
[0043] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 31; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 32; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 33; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 34; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 36;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 37; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 38; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 39; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 40; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 41; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 42;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 43; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 44; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 45; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 46; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 47; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 48;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 49; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 50; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 51; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 52; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 53; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 54;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 55; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 56; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 57; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 58; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 59; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 60; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of GY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 158; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 159; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 161; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 162.
[0044] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 64; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 65; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 66;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 68; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 76; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 77; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 78;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 82; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 83; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 84; (v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 88; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 89; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 90; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 163; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 164; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 165; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 166; a CDRL2 comprising the amino acid sequence of EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 168.
[0045] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 91; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 92; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 93; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 94; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 96;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 97; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 98; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 99; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 100; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 102;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 103; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 104; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 105; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 106; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 108;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 109; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 110; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 111; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 112; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 113; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 114;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 115; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 116; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 117; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO:
118; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 119; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 120; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of NY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 170; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 171; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of NSY; a CDRL2 comprising the amino acid sequence of RAN; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 174.
[0046] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 121; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 122; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 123; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 124; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 125; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 126;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 127; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 128; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 129; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 130; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 131; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 132;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 133; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 134; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 135; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 136; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 137; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 138; (iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 139; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 140; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 141; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 142; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 143; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 144;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 145; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 146; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 147; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 148; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 149; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 150; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 176; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 177; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SKY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 179; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 180.
[0047] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
[0048] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 657; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 661; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 662; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 663;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666; (iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
[0049] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
[0050] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 661; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 662; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 663;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; or (v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
[0051] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19-21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 61-63, 64-66; 67-69, 70-72; 73- 75, 76-78; 79-81, 82-84; 85-87, 88-90; 91-93, 94-96; 97-99, 100-102; 103-105, 106-108; 109- 111, 112-114; 115-117, 118-120; 121-123, 124-126; 127-129, 130-132; 133-135, 136-138; 139- 141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; GY, 158-159, SY, 161-162; 163- 165, 166, EIS, 168; NY, 170-171, NS Y, RAN, 174; DY, 176-177, SKY, 179-180; 211-213, 214- 216; 217-219, 220-222; 223-225, 226-228; 229-231, 232-234; 235-237, 238-240; 241-243, 244-
246; 247-249, 250-252; 253-255, 256-258; 259-261, 262-264; 265-267, 268-270; 271-273, 274-
276; 277-279, 280-282; 283-285, 286-288; 289-291, 292, 294; 295-297, 298-300; 301-303, 304-
306; 307-309, 310-312; 313-315, 316-318; 319-321, 322-324; 325-327, 328-330; 331-333, 334-
336; 337-339, 340-342; 343-344, DDY, 346-348; 349-350, TTH, 352-354; 355-357, 358-360; 361-363, 364-366; 367-369, 370-372; 373-375, 376-378; 379-381, 382-384; 385-387, 388-390; 391-393, 394-396; 397-399, 400-402; 403-405, 406-408; 409-411, 412-414; 415-417, 418-420; 421-423, 424-426; 427-429, 430-432; 433-435, 436-438; 439-441, 442-444; 445-447, 448-450; 451-453, 454-456; 457-459, 460-462; 463-465, 466-468; 469-471, 472-474; 475-477, 478-480;
481-483, 484-486; 487-489, 490-492; 493-495, 496-498; 499-501, 502-504; or 505-507, 508- 510; respectively.
[0052] Also provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19-21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 121-123, 124-126; 127-129, 130-132; 133-135, 136-138; 139-141, 142-144; 145-147, 148-150; DY 152-153, DY, 152-153, STE, 155-156; GY, 158-159, SY, 161-162; DY, 176-177, SKY, 179-180; 211-213, 214-216; 217-219, 220-222; 223-225, 226-228; 229-231, 232-234; 235-237, 238-240; 241-243, 244-246; 247-249, 250-252; 253-255, 256-258; 259-261, 262-264; 265-267, 268-270; 271-273, 274-276; 277-279, 280-282; 283-285, 286-288; 289-291, 292, 294; 295-297, 298-300; 301-303, 304-306; 307-309, or 310-312; respectively.
BRIEF DESCRIPTION OF THE DRAWINGS
[0053] FIGS. 1A-1B show binding data for FGFR3-IIIb antibodies against FGFR3-IIIb (FIG. 1A) or FGFR3-IIIc (FIG. IB).
[0054] FIGS. 2A-2B show binding profiles and EC50 data for binding of FGFR3-IIIb antibodies to cells expressing FGFR3-IIIb (FIG. 2A) or FGFR3-IIIc (FIG. 2B).
[0055] FIG. 3 shows the internalization of chimeric FGFR3-IIIb antibodies on FGFR3-IIIb- 293T cells as measured by Incucyte.
[0056] FIG. 4 shows the binding of the chimeric antibody with hFGFR3 as measured by ELISA.
[0057] FIG. 5 shows the effect of FGFR3-IIIb antibody on the proliferation of FGFR3- IIIb/BaF3 cells.
[0058] FIG. 6 shows the binding of the chimeric antibody with FGFR3-IIIb, FGFR1, FGFR2, and FGFR4 as measured by ELISA.
[0059] FIGS. 7A-7B show binding profile of antibodies tested in bladder cancer cell line, RT112/84 (FIG. 7A) and SW780 (FIG. 7B). FIGS. 7C-7E show binding profile of antibodies tested in 293T cells over-expressing FGFR3-IIIb (FIG. 7C), 293T cells over-expressing FGFR3-IIIb with S249C mutation (FIG. 7D), and 293T cells over-expressing FGFR3-IIIc (FIG. 7E). FIG. 7F shows graph of EC50 of antibodies binding to 293T cells over-expressing FGFR3- Illb. FIG. 7G shows binding profiles of antibodies against FGFR3-IIIb and FGFR3-IIIc by FACS.
[0060] FIG. 8A shows binding profiles of chimeric antibodies to 293T cells over-expressing FGFR3-IIIb, FGFR3-IIIc, FGFR3-IIIb with R248C mutation, or FGFR3-IIIb with S249C mutation (for each grouping from left to right: 85B11 (non-blocking), 54H7, 28A7, 10C12, 29E5, hlgGl, 309-hIgGl (non-blocking), and FAYA hlgGl). FIG. 8B shows FACS results of EC50 of chimeric antibodies binding to 293T cells over-expressing FGFR3. FIG. 8C shows ELISA results of EC50 of chimeric antibodies binding to 293T cells over-expressing FGFR3- Illb. FIGS. 8D-8F show additional binding profiles of chimeric antibodies tested in RT4 cell line (FIG. 8D), NCI-H1781 cell line (FIG. 8E), and FaDu cell line (FIG. 8F).
[0061] FIGS. 9A-9D show binding profiles of humanized antibodies to in 293T cells overexpressing FGFR3-IIIb (FIG. 9A), 293T cells over-expressing FGFR3-IIIc (FIG. 9B), RT112/84 cell line (FIG. 9C), and RT4 cell line (FIG. 9D). [0062] FIG. 10 show FACS results of EC50 of hl012 antibodies binding to 293T cells overexpressing FGFR3-IIIb.
[0063] FIGS. 11A-11B show results of antibody internalization of humanized antibodies in two repeat experiments with 293T cells overexpressing FGFR3-IIIb. FIGS. 11C-11G show results of Antibody Dependent Cellular Cytotoxicity (ADCC) Assays (FIG. 11C) and Antibody- Dependent Cellular Phagocytosis (ADCP) Assay (FIG. 11D) using RT112/84 cell line. FIG. HE shows results of ADCC assays using 293T cells over-expressing FGFR3-IIIb. FIG. HF shows results of antibody internalization rate. FIG. 11G shows results of cytotoxicity assay. [0064] FIGS. 12A-12C show cytotoxicity of antibodies tested in 2D culture using RT112/84 cell line (FIG. 12A), in 3D culture using RT112/84 cell line (FIG. 12B), and in 293T cells overexpressing FGFR3-IIIb (FIG. 12C).
DETAILED DESCRIPTION
[0065] Fibroblast growth factor receptors (FGFRs) are highly conserved single-pass transmembrane proteins, composed of an extracellular domain (ECD), a transmembrane domain, and an intracellular tyrosine kinase domain. The ECD consists of three immunoglobulin-like subdomains (D1-D3) with an acidic box and a heparin-binding site. Fibroblast growth factors (FGFs) and heparin or heparan sulfate proteoglycans bind to the D2 and D3 subdomains of FGFR, leading to receptor dimerization and trans-autophosphorylation, and each specific phosphorylation site can bind and phosphorylate substrates to activate multiple signal transduction pathways. The DI subdomain generally engages in weak interactions with the D2- D3 subdomains, which was shown to induce sustainable autoinhibition.
[0066] FGFR3 is one of four members of the FGFR family, and has two major alternatively spliced isoforms, designated Illb and IIIc. Both isoforms differ in the second half of D3 subdomain, and consequently in ligand-binding affinity and specificity. The alternative splicing events occur in a tissue specific fashion, resulting in distinct tissue distribution of isoforms. While the Illb isoform is expressed in epithelial cells, IIIc isoform is mainly expressed in mesenchymal cells.
[0067] FGFR3 plays an important role in different important physiological cellular processes, such as regulation of cell survival, proliferation, differentiation, migration and angiogenesis. Aberrantly activated and/or overexpressed FGFR3 has been observed in various human malignancies.
FGFR3-IIIb-binding antibodies
[0068] Provided and exemplified herein are antibodies and antibody fragments that bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc. As such, an antibody fragment that binds to FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc, comprises an antigen-binding fragment, where the antigen is FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc. Non-limiting example antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and 18.
Table 1: FGFR3-IIIb antibody CDRs binding FGFR3-IIIb
Table 2: FGFR3-IIIb/IIIc antibody CDRs binding FGFR3-IIIb and FGFR3-IIIc 307-309, 310-312
[0069] In some instances, an antibody or antibody fragment that binds to FGFR3-IIIb binds to FGFR3-IIIb with a KD of less than about 10 x 10'8 M. In some instances, an antibody or antibody fragment that binds to FGFR3-IIIb is specific for FGFR3-IIIb. In some instances, an antibody or antibody fragment specific for FGFR3-IIIb does not bind to another FGFR antigen with a KD of less than about 10 X 10'8 M. Another FGFR antigen may include FGFR1, FGFR2, and/or FGFR3. In some instances, another FGFR antigen is FGFR3-IIIc. Non-limiting example binding assays are provided in the Examples, e.g., Example 5. Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
[0070] An antibody or antibody fragment that binds to FGFR3-IIIb may include an antibody or antibody fragment that binds to FGFR3-IIIb and FGFR3-IIIc. An antibody or antibody fragment that binds to FGFR3-IIIb and FGFR3-IIIc may include an antibody or antibody fragment that is specific for FGFR3-IIIb and specific for FGFR3-IIIc. In some instances, an antibody or antibody fragment specific for FGFR3-IIIb and FGFR3-IIIc does not bind to another FGFR antigen with a KD about or less than about 10 X 10'8 M. Another FGFR antigen may include FGFR1, FGFR2, and/or FGFR3. In some instances, an antibody or antibody fragment specific for FGFR3-IIIb and FGFR3-IIIc binds to FGFR3-IIIb with a KD about or less than about 10 X 10'8 M and binds to FGFR3-IIIc with a KD about or less than about 10 X 10'8 M Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
[0071] In certain instances, the antibodies and antibody fragments are useful in that they specifically bind FGFR3-IIIb, or FGFR3-IIIb and FGFR3-IIIc (e.g., they are not pan-specific across FGFR1-4). In certain instances, the antibodies and antibody fragments herein do not bind to FGFR1, FGFR2, or FGFR4 with a KD about or less than about 10 X 10'8. Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
[0072] In certain instances, the antibodies and antibody fragments are useful in that they are internalized by cells expressing FGFR3-IIIb and/or FGFR3-IIIc. Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
[0073] In some embodiments, provided are antibodies and antibody fragments having means for binding FGFR3-IIIb. In certain embodiments, provided are antibodies and antibody fragments having means for binding FGFR3-IIIb and internalizing into a cell expressing FGFR3-IIIb. In some embodiments, provided are antibodies and antibody fragments having means for binding FGFR3-IIIb and FGFR3-IIIc. In certain embodiments, provided are antibodies and antibody fragments having means for binding FGFR3-IIIb and FGFR3-IIIc and internalizing into a cell expressing FGFR3-IIIb and/or FGFR3-IIIc. Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
[0074] In some embodiments, antibodies and/or antibody fragments that bind FGFR3-IIIb (e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) are internalized by a cell expressing FGFR3-IIIb. In some embodiments, the cell is a HEK-293 cell expressing FGFR3-IIIb. Non-limiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
[0075] In some embodiments, the antibodies and/or antibody fragments that bind FGFR3-IIIb (e g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) bind to a FGFR3-IIIb protein with an equilibrium dissociation constant (KD) equal to or less than 100 * 10'9 M, less than 50 x 10'9 M, less than 25 x 10'9 M, less than 10 x 10'9 M, or less than 5 x 10'9 M. In certain embodiments, the FGFR3-IIIb protein comprises the amino acid sequence of SEQ ID NO: 191, 193, 195, or 197. In certain embodiments, antibodies and/or antibody fragments bind FGFR3-IIIc. The FGFR3- Illc-binding antibody or FGFR3-IIIc-binding antibody fragment binds to a FGFR3-IIIc protein (e.g., as measured by ELISA or cell-binding in the Examples). In certain embodiments, the FGFR3-IIIc protein comprises the amino acid sequence of SEQ ID NO: 192, 194, 196, or 198. In certain embodiments, the antibody and/or antibody fragment that binds FGFR3-IIIb (e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) does not bind to FGFR1, FGFR2, or FGFR4. Nonlimiting examples antibodies and antibody fragments are provided herein, e.g., at Tables 1, 2, 10 and/or 18.
[0076] An antibody and/or antibody fragment that binds FGFR3-IIIb generally refers to and/or includes an antibody that binds a FGFR3-3-IIIb protein comprising a protein having the amino acid sequence of SEQ ID NO: 191. Generally, a FGFR3-IIIb antibody or FGFR3-IIIb-binding antibody fragment is specific for a FGFR3-IIIb protein (e.g., selectively recognize and bind to a FGFR3-IIIb protein). A FGFR3-IIIc-binding antibody or FGFR3-IIIc-binding antibody fragment generally refers to and/or includes an antibody that binds a FGFR3-3-IIIc protein comprising a protein having the amino acid sequence of SEQ ID NO: 192. Generally, a FGFR3-IIIc antibody or FGFR3-IIIc-binding antibody fragment is specific for a FGFR3-IIIc protein (e.g., selectively recognize and bind to a FGFR3-IIIc protein). Binding can be determined by bio-layer interferometry, surface plasmon resonance, isothermal titration calorimetry, and/or ELISA. Affinity generally refers to and/or includes the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen such as FGFR3-IIIb, and FGFR3-IIIc). Unless indicated otherwise, binding affinity generally encompasses and refers to intrinsic binding affinity which reflects a 1 : 1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of an antibody for an antigen (e.g., FGFR3-IIIb or FGFR3-IIIc) can generally be represented by the dissociation constant (KD). Affinity can be measured and determined by bio-layer interferometry, surface plasmon resonance, isothermal titration calorimetry, and/or ELISA. [0077] FGFR3 generally refers to and/or includes the protein encoded by the FGFR3 gene and functions in cell division, cell maturation, formation of new blood vessels, wound healing, and bone growth, development, and maintenance. FGFR3 alternative splice variants result in FGFR3-IIIb and FGFR3-IIIc isoforms of the FGFR3 protein. FGFR3-IIIb generally refers to and/or includes a protein encoded by the FGFR3 gene. FGFR3-IIIc generally refers to and/or includes a protein encoded by the FGFR3 gene. In certain embodiments, the FGFR3 gene refers to NCBI GenelD 2261 and/or HGNC ID: HGNC: 3690, which includes sequence information on isoform Illb. In certain embodiments, a FGFR3-IIIb protein refers to and includes the protein(s) of UniProt ID: P22607-2. In certain instances, FGFR3-IIIb comprises a protein comprising the amino acid sequence of SEQ ID NO: 191 or a homologue or an orthologue or variant thereof (e.g., as referenced in NCBI GenelD 2261 and/or HGNC ID: HGNC: 3690). In certain embodiments, a FGFR3-IIIc protein refers to and includes the protein(s) of UniProt ID: P22607-1. In certain instances, FGFR3-IIIc comprises a protein comprising the amino acid sequence of SEQ ID NO: 192 or a homologue or an orthologue or variant thereof (e.g., as referenced in NCBI GenelD 2261 and/or HGNC ID: HGNC: 3690).
[0078] In certain instances, FGFR3-IIIb comprises an amino acid sequence having at least 70, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to of SEQ ID NO: 191. In certain instances, FGFR3-IIIb comprises an amino acid sequence having at least 70, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to of SEQ ID NO: 195. In certain instances, FGFR3-IIIb comprises an amino acid sequence having at least 70, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to of SEQ ID NOs: 197. In certain instances, FGFR3-IIIc comprises an amino acid sequence having at least 70, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% sequence identity to of SEQ ID NO: 192.
[0079] In certain embodiments, the antibodies and/or antibody fragments that bind FGFR3-IIIb (e g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) comprise an Fc region. In certain embodiments, the Fc region is an IgG Fc region. The Fc region may comprise a sequence of SEQ ID NO: 611 or 612.
[0080] In certain embodiments, the antibodies and/or antibody fragments that bind FGFR3-IIIb (e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) comprise a light chain constant region. For example, human kappa having SEQ ID NO: 199, or a sequence at least about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to of SEQ ID NO: 199. In certain embodiments, the antibodies and/or antibody fragments that bind FGFR3-IIIb (e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) comprise a Kappa domain, e.g., of SEQ ID NO: 688. In certain embodiments, the antibodies and/or antibody fragments that bind FGFR3-IIIb (e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) comprise a heavy chain constant region. For example, human IgGl constant region having SEQ ID NO: 200, or a sequence at least about 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to of SEQ ID NO: 200. In certain embodiments, the antibodies and/or antibody fragments that bind FGFR3-IIIb (e g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) comprise a CHI domain, e.g., of SEQ ID NO: 685. In certain embodiments, the antibodies and/or antibody fragments that bind FGFR3-IIIb (e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) comprise a CH2 domain, e.g., of SEQ ID NO: 686. In certain embodiments, the antibodies and/or antibody fragments that bind FGFR3-IIIb (e.g., FGFR3-IIIb, FGFR3-IIIb and FGFR3-IIIc) comprise a CH3 domain, e.g., of SEQ ID NO: 687.
[0081] Antibody is used in the broadest sense and generally refers to and/or includes monoclonal antibodies, multi-valent antibodies, multi-specific, antigen-binding fragments of antibodies that bind a FGFR3-IIIb protein. Antigen-binding fragments of antibodies (antigenbinding antibody fragments) generally refer to and/or include antibody -derived proteins that comprise a functional set of CDRs (e.g., a CDR-H1-3 and CDR-L1-3) that bind a FGFR3-IIIb protein and have a molecule weight less than a full length IgG antibody (e.g., a molecular weight less than -150,00 Daltons). In certain embodiments, an antigen-binding antibody fragment (e.g., a FGFR3 -binding fragment) includes: fragment antigen binding (Fab) fragments, F(ab’)2 fragments, Fab' fragments, Fv fragments, IgG (rlgG) fragments, and single chain antibody fragments, including single chain variable fragments (sFv or scFv). Antibodies and antigenbinding fragments of antibodies generally encompass genetically engineered, and/or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multi-specific antibodies, multi-valent antibodies, diabodies, triabodies, and tetrabodies, tandem di-scFv, tandem tri-scFv. A full-length antibody, intact antibody, and/or whole antibody are interchangeable, and generally include and/or refer to an antibody having a structure substantially similar to a native antibody structure having heavy chains that contain an Fc region and/or include antibodies of any class or sub-class, including IgG and sub-classes thereof (e.g., IgGl and IgG4), IgM, IgE, IgA, and IgD.
[0082] Complementarity determining regions (CDRs) generally include amino acids (e.g., noncontiguous or contiguous) within antibody variable regions that confer antigen specificity and/or binding affinity (e.g., to FGFR3-IIIb or FGFR3-IIIc). In general, there are three CDRs in each heavy chain variable region (CDR-H1, CDR-H2, CDR-H3) and three CDRs in each light chain variable region (CDR-L1, CDR-L2, CDR-L3). Framework regions (FRs) generally refer to and/or include non-CDR regions of the heavy and light chain variable regions. In general, there are four FRs in each full-length heavy chain variable region (FR-H1, FR-H2, FR-H3, and FR- H4), and four FRs in each full-length light chain variable region (FR-L1, FR-L2, FR-L3, and FR-L4).
[0083] Variable regions (also referred to as variable domains) generally refer to and/or include the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen (e.g., a single variable domain comprises a CDR 1, CDR 2, and CDR 3). The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three CDRs. In certain instances, a single VH or VL domain can be sufficient to confer antigen-binding specificity (e.g., binding to FGFR3-IIIb).
[0084] Fc region generally encompasses and/or refers to a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. Generally, the Fc region includes an immunoglobulin CH2 and CH3 domain (e.g., an IgG CH2 and CH3 domain). The term includes native sequence Fc regions and variant Fc regions. In one embodiment, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-terminus of the heavy chain, per EU numbering. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. In certain embodiments, the Fc region include IgG and sub-classes thereof (e.g., IgGl and IgG4), IgM, IgE, IgA, and/or IgD heavy chain constant regions and/or heavy chain constant regions derived from IgG and sub-classes thereof (e.g., IgGl and IgG4), IgM, IgE, IgA, and IgD.
[0085] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising:
(i) a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 2; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 4; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 5; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 6; (ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 7; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 8; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 9; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 10; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 12;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 13; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 14; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 15; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 16; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 17; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 18;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 19; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 20; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 21; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 22; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 23; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 24;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 25; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 26; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 27; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 28; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 29; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 30; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 152; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 153; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of STE; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 155; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 156.
[0086] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 181; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 182. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 181 and the light chain variable domain has the CDRs of SEQ ID NO: 182. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 1-3, and the light chain variable domain has CDRs of SEQ ID NOS: 4-6. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 7-9, and the light chain variable domain has CDRs of SEQ ID NOS: 10-12. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 13- 15, and the light chain variable domain has CDRs of SEQ ID NOS: 16-18. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 19-21, and the light chain variable domain has CDRs of SEQ ID NOS: 22-24. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 25-27, and the light chain variable domain has CDRs of SEQ ID NOS: 28-30. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 152-153, and the light chain variable domain has CDRs of the amino acid sequence STE and SEQ ID NOS: 155-156.
[0087] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 201. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 202. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 201; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 202. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 201 and the light chain variable domain has the CDRs of SEQ ID NO: 202. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 1-3, and the light chain variable domain has CDRs of SEQ ID NOS: 4-6. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 7-9, and the light chain variable domain has CDRs of SEQ ID NOS: 10-12. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 13-15, and the light chain variable domain has CDRs of SEQ ID NOS: 16-18. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 19-21, and the light chain variable domain has CDRs of SEQ ID NOS: 22-24. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 25-27, and the light chain variable domain has CDRs of SEQ ID NOS: 28-30 In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 152-153, and the light chain variable domain has CDRs of the amino acid sequence STE and SEQ ID NOS: 155-156.
[0088] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:
614. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO:
615. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 615. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 614; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 615. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 201 and the light chain variable domain has the CDRs of SEQ ID NO: 202. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 1-3, and the light chain variable domain has CDRs of SEQ ID NOS: 4-6. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 7-9, and the light chain variable domain has CDRs of SEQ ID NOS: 10-12. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 13-15, and the light chain variable domain has CDRs of SEQ ID NOS: 16-18. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 19-21, and the light chain variable domain has CDRs of SEQ ID NOS: 22-24. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 25- 27, and the light chain variable domain has CDRs of SEQ ID NOS: 28-30. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 152-153, and the light chain variable domain has CDRs of the amino acid sequence STE and SEQ ID NOS: 155-156.
[0089] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 31; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 32; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 33; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 34; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 36;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 37; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 38; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 39; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 40; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 41; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 42; (iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 43; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 44; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 45; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 46; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 47; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 48;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 49; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 50; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 51; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 52; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 53; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 54;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 55; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 56; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 57; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 58; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 59; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 60; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of GY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 158; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 159; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 161; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 162.
[0090] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 183; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 184. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 183 and the light chain variable domain has the CDRs of SEQ ID NO: 184. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 31-33, and the light chain variable domain has CDRs of SEQ ID NOS: 34-36. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 37-39, and the light chain variable domain has CDRs of SEQ ID NOS: 40-42. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 43-45, and the light chain variable domain has CDRs of SEQ ID NOS: 46-48. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 49-51, and the light chain variable domain has CDRs of SEQ ID NOS: 52-54. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 55-57, and the light chain variable domain has CDRs of SEQ ID NOS: 58-60. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence GY and SEQ ID NOS: 158-159, and the light chain variable domain has CDRs of the amino acid sequence SY and SEQ ID NOS: 161-162.
[0091] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 203. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 204. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 203; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 204. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 203 and the light chain variable domain has the CDRs of SEQ ID NO: 204. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 31-33, and the light chain variable domain has CDRs of SEQ ID NOS: 34-36. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 37-39, and the light chain variable domain has CDRs of SEQ ID NOS: 40-42. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 43- 45, and the light chain variable domain has CDRs of SEQ ID NOS: 46-48. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 49-51, and the light chain variable domain has CDRs of SEQ ID NOS: 52-54. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 55-57, and the light chain variable domain has CDRs of SEQ ID NOS: 58-60. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence GY and SEQ ID NOS: 158-159, and the light chain variable domain has CDRs of the amino acid sequence SY and SEQ ID NOS: 161-162.
[0092] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 616. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO:
617. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 617. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 616; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 617. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 203 and the light chain variable domain has the CDRs of SEQ ID NO: 204. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 31-33, and the light chain variable domain has CDRs of SEQ ID NOS: 34-36. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 37-39, and the light chain variable domain has CDRs of SEQ ID NOS: 40-42. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 43-45, and the light chain variable domain has CDRs of SEQ ID NOS: 46-48. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 49-51, and the light chain variable domain has CDRs of SEQ ID NOS: 52-54. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 55-57, and the light chain variable domain has CDRs of SEQ ID NOS: 58-60. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence GY and SEQ ID NOS: 158-159, and the light chain variable domain has CDRs of the amino acid sequence SY and SEQ ID NOS: 161-162.
[0093] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 64; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 65; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 66;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 68; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 76; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 77; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 78; (iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 82; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 83; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 84;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 88; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 89; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 90; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 163; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 164; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 165; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 166; a CDRL2 comprising the amino acid sequence of EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 168.
[0094] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 185; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 186. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 185 and the light chain variable domain has the CDRs of SEQ ID NO: 186. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of SEQ ID NOS: 64-66. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 70-72. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73- 75, and the light chain variable domain has CDRs of SEQ ID NOS: 76-78. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 82-84. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 88-90. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 163-165, and the light chain variable domain has CDRs of the amino acid sequence EIS and SEQ ID NOS: 166 and 168.
[0095] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 205. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 206. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 206. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 206. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of SEQ ID NOS: 64-66. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 70-72. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 76-78. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79- 81, and the light chain variable domain has CDRs of SEQ ID NOS: 82-84. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 88-90. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 163-165, and the light chain variable domain has CDRs of the amino acid sequence EIS and SEQ ID NOS: 166 and 168.
[0096] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 618. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 619. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 619. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 206. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of SEQ ID NOS: 64-66. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 70-72. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 76-78. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 82-84. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 88-90. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 163-165, and the light chain variable domain has CDRs of the amino acid sequence EIS and SEQ ID NOS: 166 and 168.
[0097] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 91; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 92; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 93; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 94; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 96;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 97; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 98; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 99; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 100; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 102;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 103; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 104; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 105; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 106; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 108;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 109; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 110; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 111; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO:
112; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 113; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 114;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 115; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 116; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 117; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 118; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 119; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 120; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of NY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 170; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 171; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of NSY; a CDRL2 comprising the amino acid sequence of RAN; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 174.
[0098] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 187; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 188. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 187 and the light chain variable domain has the CDRs of SEQ ID NO: 188. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 91-93, and the light chain variable domain has CDRs of SEQ ID NOS: 94-96. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 97-99, and the light chain variable domain has CDRs of SEQ ID NOS: 100-102. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 103-105, and the light chain variable domain has CDRs of SEQ ID NOS: 106-108. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 109-111, and the light chain variable domain has CDRs of SEQ ID NOS: 112-114. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 115-117, and the light chain variable domain has CDRs of SEQ ID NOS: 118-120. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence NY and SEQ ID NOS: 170-171, and the light chain variable domain has CDRs of the amino acid sequence NSY, RAN and SEQ ID NOS: 174.
[0099] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 207. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 208. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 207; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 208. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 207 and the light chain variable domain has the CDRs of SEQ ID NO: 208. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 91-93, and the light chain variable domain has CDRs of SEQ ID NOS: 94-96. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 97-99, and the light chain variable domain has CDRs of SEQ ID NOS: 100-102. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 103-105, and the light chain variable domain has CDRs of SEQ ID NOS: 106-108. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 109-111, and the light chain variable domain has CDRs of SEQ ID NOS: 112-114. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 115-117, and the light chain variable domain has CDRs of SEQ ID NOS: 118-120. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence NY and SEQ ID NOS: 170- 171, and the light chain variable domain has CDRs of the amino acid sequence NSY, RAN and SEQ ID NOS: 174.
[0100] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 620. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 621. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 620; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 621. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 207 and the light chain variable domain has the CDRs of SEQ ID NO: 208. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 91-93, and the light chain variable domain has CDRs of SEQ ID NOS: 94-96. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 97-99, and the light chain variable domain has CDRs of SEQ ID NOS: 100-102. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 103-105, and the light chain variable domain has CDRs of SEQ ID NOS: 106-108. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 109-111, and the light chain variable domain has CDRs of SEQ ID NOS: 112-114. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 115-117, and the light chain variable domain has CDRs of SEQ ID NOS: 118- 120. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence NY and SEQ ID NOS: 170-171, and the light chain variable domain has CDRs of the amino acid sequence NS Y, RAN and SEQ ID NOS: 174.
[0101] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 121; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 122; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 123; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 124; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 125; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 126;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 127; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 128; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 129; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 130; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 131; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 132;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 133; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 134; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 135; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 136; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 137; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 138;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 139; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 140; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 141; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 142; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 143; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 144;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 145; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 146; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 147; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 148; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 149; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 150; or (vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 176; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 177; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SKY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 179; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 180.
[0102] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 189; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 190. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 189 and the light chain variable domain has the CDRs of SEQ ID NO: 190. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 121-123, and the light chain variable domain has CDRs of SEQ ID NOS: 124-126. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 127-129, and the light chain variable domain has CDRs of SEQ ID NOS: 130-132. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 133-135, and the light chain variable domain has CDRs of SEQ ID NOS: 136-138. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 139-141, and the light chain variable domain has CDRs of SEQ ID NOS: 142-144. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 145-147, and the light chain variable domain has CDRs of SEQ ID NOS: 148-150. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 176- 177, and the light chain variable domain has CDRs of the amino acid sequence SKY and SEQ ID NOS: 179-180.
[0103] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 209. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 210. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 209; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 210. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 209 and the light chain variable domain has the CDRs of SEQ ID NO: 210. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 121-123, and the light chain variable domain has CDRs of SEQ ID NOS: 124-126. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 127-129, and the light chain variable domain has CDRs of SEQ ID NOS: 130-132. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 133-135, and the light chain variable domain has CDRs of SEQ ID NOS: 136-138. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 139-141, and the light chain variable domain has CDRs of SEQ ID NOS: 142-144. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 145-147, and the light chain variable domain has CDRs of SEQ ID NOS: 148-150. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 176-177, and the light chain variable domain has CDRs of the amino acid sequence SKY and SEQ ID NOS: 179-180. [0104] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 622. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 623. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 622; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 623. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 209 and the light chain variable domain has the CDRs of SEQ ID NO: 210. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 121-123, and the light chain variable domain has CDRs of SEQ ID NOS: 124- 126. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 127- 129, and the light chain variable domain has CDRs of SEQ ID NOS: 130-132. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 133-135, and the light chain variable domain has CDRs of SEQ ID NOS: 136-138. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 139-141, and the light chain variable domain has CDRs of SEQ ID NOS: 142-144. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 145-147, and the light chain variable domain has CDRs of SEQ ID NOS: 148-150. In some embodiments, the heavy chain variable domain has CDRs of the amino acid sequence DY and SEQ ID NOS: 176-177, and the light chain variable domain has CDRs of the amino acid sequence SKY and SEQ ID NOS: 179-180.
[0105] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising: (i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
[0106] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 185; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 185 and the light chain variable domain has the CDRs of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653.
[0107] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 205. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 205; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 674. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 674. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. [0108] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 618. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 618; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67-69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653.
[0109] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 657; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 661; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 662; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 663;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
[0110] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 625 and the light chain variable domain has the CDRs of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 658 and 660. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 657, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 661-663. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 664-666. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 667-669. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 670-672.
[OHl] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 675. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 675; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 676. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 675 and the light chain variable domain has the CDRs of SEQ ID NO: 676. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 658 and 660. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 657, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 661-663. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 664-666. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 667-669. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 670-672.
[0112] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 625. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 625; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 658 and 660. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 657, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 661-663. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 664-666. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 667-669. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 670-672.
[0113] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
[0114] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 627 and the light chain variable domain has the CDRs of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 673, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653.
[0115] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 677. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 674. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 674. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 677 and the light chain variable domain has the CDRs of SEQ ID NO: 674. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 673, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653.
[0116] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 627. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 624. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 624. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 642 and 644. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 673, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 645-647. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 648-650. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 651-653. In some embodiments, the light chain variable domain has the CDRs of SEQ ID NO: 689. In some embodiments, provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 690; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 691. In some embodiments, provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 690; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 692. In some embodiments, provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3- IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 690; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 693.
[0117] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising: (i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 661; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 662; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 663;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
[0118] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 627 and the light chain variable domain has the CDRs of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 658 and 660. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 673, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 661-663. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 664-666. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 667-669. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 670-672.
[0119] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 677. In certain embodiments, the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 676. In certain embodiments, the heavy chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 677; and the light chain variable domain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 676. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 677 and the light chain variable domain has the CDRs of SEQ ID NO: 676. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 61-63, and the light chain variable domain has CDRs of amino acid sequence EIS and SEQ ID NOS: 658 and 660. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 67, 673, and 69, and the light chain variable domain has CDRs of SEQ ID NOS: 661-663. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 73-75, and the light chain variable domain has CDRs of SEQ ID NOS: 664-666. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 79-81, and the light chain variable domain has CDRs of SEQ ID NOS: 667-669. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 85-87, and the light chain variable domain has CDRs of SEQ ID NOS: 670-672.
[0120] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 627. In certain embodiments, the light chain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 80% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 85% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 90% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 91% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 92% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 93% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 94% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 95% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 96% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 97% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 98% sequence identity to the amino acid sequence of SEQ ID NO: 626. In certain embodiments, the heavy chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 627; and the light chain has at least about or about 99% sequence identity to the amino acid sequence of SEQ ID NO: 626. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 205 and the light chain variable domain has the CDRs of SEQ ID NO: 626.
[0121] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 211; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 212; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 213; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 214; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 215; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 216;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 217; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 218; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 219; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 220; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 221; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 222;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 223; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 224; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 225; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 226; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 227; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 228;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 229; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 230; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 231; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 232; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 233; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 234;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 235; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 236; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 237; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 238; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 239; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 240;
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 241; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 242; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 243; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 244; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 245; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 246;
(vii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 247; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 248; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 249; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 250; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 251; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 252;
(viii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 253; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 254; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 255; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 256; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 257; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 258;
(ix) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 259; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 260; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 261; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 262; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 263; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 264;
(x) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 265; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 266; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 267; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 268; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 269; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 270;
(xi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 271; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 272; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 273; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 274; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 275; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 276;
(xii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 277; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 278; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 279; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 280; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 281; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 282;
(xiii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 283; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 284; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 285; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 286; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 287; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 288;
(xiv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 289; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 290; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 291; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 292; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 293; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 294;
(xv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 295; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 296; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 297; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 298; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 299; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 300;
(xvi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 301; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 302; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 303; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 304; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 305; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 306; or
(xvii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 307; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 308; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 309; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 310; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 311; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 312.
[0122] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 511; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 512. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 511 and the light chain variable domain has the CDRs of SEQ ID NO: 512. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 211- 213, and the light chain variable domain has CDRs of SEQ ID NOS: 214-216.
[0123] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 513; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 514. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 513, and the light chain variable domain has the CDRs of SEQ ID NO: 514. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 217- 219, and the light chain variable domain has CDRs of SEQ ID NOS: 220-222.
[0124] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 515; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 516. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 515, and the light chain variable domain has the CDRs of SEQ ID NO: 516. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 223- 225, and the light chain variable domain has CDRs of SEQ ID NOS: 226-228. [0125] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 517; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 518. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 517, and the light chain variable domain has the CDRs of SEQ ID NO: 518. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 229- 231, and the light chain variable domain has CDRs of SEQ ID NOS: 232-234.
[0126] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 519; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 520. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 519, and the light chain variable domain has the CDRs of SEQ ID NO: 520. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 235- 237, and the light chain variable domain has CDRs of SEQ ID NOS: 238-240.
[0127] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 521; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 522. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 521, and the light chain variable domain has the CDRs of SEQ ID NO: 522. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 241- 243, and the light chain variable domain has CDRs of SEQ ID NOS: 244-246.
[0128] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 523; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 524. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 523, and the light chain variable domain has the CDRs of SEQ ID NO: 524. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 247- 249, and the light chain variable domain has CDRs of SEQ ID NOS: 250-252.
[0129] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 525; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 526. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 525, and the light chain variable domain has the CDRs of SEQ ID NO: 526. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 253- 255, and the light chain variable domain has CDRs of SEQ ID NOS: 256-258.
[0130] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 527; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 528. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 527, and the light chain variable domain has the CDRs of SEQ ID NO: 528. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 259- 261, and the light chain variable domain has CDRs of SEQ ID NOS: 262-264.
[0131] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 529; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 530. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 529, and the light chain variable domain has the CDRs of SEQ ID NO: 530. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 265- 267, and the light chain variable domain has CDRs of SEQ ID NOS: 268-270. [0132] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 531; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 532. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 531, and the light chain variable domain has the CDRs of SEQ ID NO: 532. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 271- 273, and the light chain variable domain has CDRs of SEQ ID NOS: 274-276.
[0133] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 533; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 534. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 533, and the light chain variable domain has the CDRs of SEQ ID NO: 534. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 277- 279, and the light chain variable domain has CDRs of SEQ ID NOS: 280-282.
[0134] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 535; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 536. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 535, and the light chain variable domain has the CDRs of SEQ ID NO: 536. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 283- 285, and the light chain variable domain has CDRs of SEQ ID NOS: 286-288.
[0135] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 537; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 538. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 537, and the light chain variable domain has the CDRs of SEQ ID NO: 538. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 289- 291, and the light chain variable domain has CDRs of SEQ ID NOS: 292-294.
[0136] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 539; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 540. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 539, and the light chain variable domain has the CDRs of SEQ ID NO: 540. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 295- 297, and the light chain variable domain has CDRs of SEQ ID NOS: 298-300.
[0137] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 541; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 542. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 541, and the light chain variable domain has the CDRs of SEQ ID NO: 542. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 301- 303, and the light chain variable domain has CDRs of SEQ ID NOS: 304-306.
[0138] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb and FGFR3-IIIc, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 543; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 544. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 543, and the light chain variable domain has the CDRs of SEQ ID NO: 544. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 307- 309, and the light chain variable domain has CDRs of SEQ ID NOS: 310-312. [0139] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 313; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 314; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 315; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO:
316; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 317; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 318;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 319; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 320; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 321; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 322; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 323; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 324;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 325; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 326; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 327; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 328; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 329; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 330;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 331; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 332; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 333; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 334; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 335; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 336;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 337; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 338; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 339; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 340; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 341; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 342;
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 343; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 344; a CDRH3 comprising the amino acid sequence of DDY; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 346; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 347; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 348;
(vii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 349; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 350; a CDRH3 comprising the amino acid sequence of TTH; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 352; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 353; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 354;
(viii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 355; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 356; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 357; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 358; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 359; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 360;
(ix) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 361; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 362; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 363; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 364; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 365; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 366;
(x) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 367; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 368; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 369; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 370; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 371; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 372;
(xi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 373; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 374; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 375; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 376; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 377; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 378;
(xii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 379; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 380; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 381; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 382; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 383; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 384;
(xiii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 385; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 386; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 387; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 388; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 389; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 390;
(xiv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 391; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 392; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 393; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 394; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 395; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 396;
(xv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 397; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 398; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 399; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 400; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 401; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 402;
(xvi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 403; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 404; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 405; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 406; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 407; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 408;
(xvii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 409; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 410; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 411; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 412; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 413; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 414; (xviii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 415; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 416; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 417; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 418; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 419; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 420;
(xix) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 421; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 422; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 423; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 424; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 425; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 426;
(xx) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 427; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 428; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 429; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 430; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 431; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 432;
(xxi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 433; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 434; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 435; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 436; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 437; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 438;
(xxii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 439; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 440; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 441; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 442; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 443; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 444;
(xxiii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 445; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 446; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 447; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 448; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 449; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 450;
(xxiv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 451; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 452; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 453; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 454; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 455; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 456;
(xxv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 457; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 458; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 459; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 460; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 461; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 462;
(xxvi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 463; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 464; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 465; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 466; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 467; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 468;
(xxvii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 469; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 470; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 471; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 472; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 473; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 474;
(xxviii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 475; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 476; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 477; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 478; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 479; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 480;
(xxix) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 481; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 482; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 483; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 484; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 485; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 486;
(xxx) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 487; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 488; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 489; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 490; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 491; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 492;
(xxxi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 493; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 494; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 495; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 496; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 497; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 498;
(xxxii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 499; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 500; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 501; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 502; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 503; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 504; or
(xxxiii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 505; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 506; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 507; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 508; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 509; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 510.
[0140] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 545; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 546. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 545, and the light chain variable domain has the CDRs of SEQ ID NO: 546. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 313-315, and the light chain variable domain has CDRs of SEQ ID NOS: 316-318.
[0141] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 547; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 548. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 547, and the light chain variable domain has the CDRs of SEQ ID NO: 548. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 319-321, and the light chain variable domain has CDRs of SEQ ID NOS: 322-324.
[0142] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 549; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 550. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 549, and the light chain variable domain has the CDRs of SEQ ID NO: 550. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 325-327, and the light chain variable domain has CDRs of SEQ ID NOS: 328-330.
[0143] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 551; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 552. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 551, and the light chain variable domain has the CDRs of SEQ ID NO: 552. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 331-333, and the light chain variable domain has CDRs of SEQ ID NOS: 334-336.
[0144] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 553; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 554. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 553, and the light chain variable domain has the CDRs of SEQ ID NO: 554. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 337-339, and the light chain variable domain has CDRs of SEQ ID NOS: 340-342.
[0145] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 555; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 556. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 555, and the light chain variable domain has the CDRs of SEQ ID NO: 556. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 343-344 and the amino acid sequence DDY, and the light chain variable domain has CDRs of SEQ ID NOS: 346- 348.
[0146] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 557; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 558. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 557, and the light chain variable domain has the CDRs of SEQ ID NO: 558. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 349-350 and the amino acid sequence TTH, and the light chain variable domain has CDRs of SEQ ID NOS: 352- 354.
[0147] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 559; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 560. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 559, and the light chain variable domain has the CDRs of SEQ ID NO: 560. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 355-357, and the light chain variable domain has CDRs of SEQ ID NOS: 358-360.
[0148] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 561; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 562. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 561, and the light chain variable domain has the CDRs of SEQ ID NO: 562. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 361-363, and the light chain variable domain has CDRs of SEQ ID NOS: 364-366.
[0149] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 563; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 564. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 563, and the light chain variable domain has the CDRs of SEQ ID NO: 564. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 367-369, and the light chain variable domain has CDRs of SEQ ID NOS: 370-372.
[0150] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 565; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 566. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 565, and the light chain variable domain has the CDRs of SEQ ID NO: 566. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 373-375, and the light chain variable domain has CDRs of SEQ ID NOS: 376-378. [0151] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 567; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 568. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 567, and the light chain variable domain has the CDRs of SEQ ID NO: 568. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 379-381, and the light chain variable domain has CDRs of SEQ ID NOS: 382-384.
[0152] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 569; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 570. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 569, and the light chain variable domain has the CDRs of SEQ ID NO: 570. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 385-387, and the light chain variable domain has CDRs of SEQ ID NOS: 388-390.
[0153] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 571; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 572. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 571, and the light chain variable domain has the CDRs of SEQ ID NO: 572. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 391-393, and the light chain variable domain has CDRs of SEQ ID NOS: 394-396.
[0154] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 573; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 574. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 573, and the light chain variable domain has the CDRs of SEQ ID NO: 574. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 397-399, and the light chain variable domain has CDRs of SEQ ID NOS: 400-402.
[0155] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 575; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 576. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 575, and the light chain variable domain has the CDRs of SEQ ID NO: 576. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 403-405, and the light chain variable domain has CDRs of SEQ ID NOS: 406-408.
[0156] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 577; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 578. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 577, and the light chain variable domain has the CDRs of SEQ ID NO: 578. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 409-411, and the light chain variable domain has CDRs of SEQ ID NOS: 412-414.
[0157] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 579; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 580. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 579, and the light chain variable domain has the CDRs of SEQ ID NO: 580. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 415-417, and the light chain variable domain has CDRs of SEQ ID NOS: 418-420. [0158] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 581; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 582. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 581, and the light chain variable domain has the CDRs of SEQ ID NO: 582. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 421-423, and the light chain variable domain has CDRs of SEQ ID NOS: 424-426.
[0159] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 583; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 584. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 583, and the light chain variable domain has the CDRs of SEQ ID NO: 584. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 427-429, and the light chain variable domain has CDRs of SEQ ID NOS: 430-432.
[0160] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 585; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 586. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 585, and the light chain variable domain has the CDRs of SEQ ID NO: 586. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 433-435, and the light chain variable domain has CDRs of SEQ ID NOS: 436-438.
[0161] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 587; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 588. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 587, and the light chain variable domain has the CDRs of SEQ ID NO: 588. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 439-441, and the light chain variable domain has CDRs of SEQ ID NOS: 442-444.
[0162] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 589; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 590. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 589, and the light chain variable domain has the CDRs of SEQ ID NO: 590. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 445-447, and the light chain variable domain has CDRs of SEQ ID NOS: 448-450.
[0163] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 591; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 592. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 591, and the light chain variable domain has the CDRs of SEQ ID NO: 592. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 451-453, and the light chain variable domain has CDRs of SEQ ID NOS: 454-456.
[0164] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 593; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 594. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 593, and the light chain variable domain has the CDRs of SEQ ID NO: 594. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 457-459, and the light chain variable domain has CDRs of SEQ ID NOS: 460-462. [0165] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 595; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 596. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 595, and the light chain variable domain has the CDRs of SEQ ID NO: 596. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 463-465, and the light chain variable domain has CDRs of SEQ ID NOS: 466-468.
[0166] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 597; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 598. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 597, and the light chain variable domain has the CDRs of SEQ ID NO: 598. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 469-471, and the light chain variable domain has CDRs of SEQ ID NOS: 472-474.
[0167] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 599; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 600. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 599, and the light chain variable domain has the CDRs of SEQ ID NO: 600. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 475-477, and the light chain variable domain has CDRs of SEQ ID NOS: 478-480.
[0168] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 601; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,
- I l l - 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 602. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 601, and the light chain variable domain has the CDRs of SEQ ID NO: 602. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 481-483, and the light chain variable domain has CDRs of SEQ ID NOS: 484-486.
[0169] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 603; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 604. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 603, and the light chain variable domain has the CDRs of SEQ ID NO: 604. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 487-489, and the light chain variable domain has CDRs of SEQ ID NOS: 490-492.
[0170] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 605; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 606. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 605, and the light chain variable domain has the CDRs of SEQ ID NO: 606. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 493-495, and the light chain variable domain has CDRs of SEQ ID NOS: 496-498.
[0171] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 607; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 608. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 607, and the light chain variable domain has the CDRs of SEQ ID NO: 608. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 499-501, and the light chain variable domain has CDRs of SEQ ID NOS: 502-504. [0172] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb, wherein the heavy chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 609; and the light chain variable domain has 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 610. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 609, and the light chain variable domain has the CDRs of SEQ ID NO: 610. In some embodiments, the heavy chain variable domain has CDRs of SEQ ID NOS: 505-507, and the light chain variable domain has CDRs of SEQ ID NOS: 508-510.
[0173] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 632; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 633. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 632 and the light chain variable domain has the CDRs of SEQ ID NO: 633.
[0174] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 634; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 635. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 634 and the light chain variable domain has the CDRs of SEQ ID NO: 635.
[0175] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 636; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 637. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 636 and the light chain variable domain has the CDRs of SEQ ID NO: 637.
[0176] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 638; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 633. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 632 and the light chain variable domain has the CDRs of SEQ ID NO: 639.
[0177] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 632; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 640. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 641 and the light chain variable domain has the CDRs of SEQ ID NO: 633.
[0178] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 680; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 681. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 680 and the light chain variable domain has the CDRs of SEQ ID NO: 681.
[0179] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 683; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 682. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 683 and the light chain variable domain has the CDRs of SEQ ID NO: 682.
[0180] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the heavy chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 684; and the light chain variable domain has at least about or about 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 682. In some embodiments, the heavy chain variable domain has the CDRs of SEQ ID NO: 684 and the light chain variable domain has the CDRs of SEQ ID NO: 682.
[0181] Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the antibodies and/or antibody fragments comprise a constant region having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 611-613. Provided and exemplified herein are antibodies and/or antibody fragments that bind FGFR3-IIIb or FGFR3-IIIc, wherein the antibodies and/or antibody fragments comprise a constant region having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 685-688.
[0182] Pharmaceutical compositions
[0183] In some embodiments, provided herein are pharmaceutical compositions and/or formulations comprising an antibody or antibody fragment described herein. Pharmaceutical compositions include and/or refers a preparation that is in such form as to permit biological activity of the antibody or antibody fragment (e.g., binding to FGFR3-IIIb), and that contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. In certain embodiments, the pharmaceutical composition comprises a pharmaceutically acceptable carrier (e.g., an ingredient in a pharmaceutical formulation, other than an active ingredient, which is nontoxic to an individual). A pharmaceutically acceptable carrier includes, but is not limited to, a buffer, excipient, stabilizer, and preservative.
[0184] Methods
[0185] The antibodies and antibody fragments that bind (e.g., specifically) FGFR3-IIIb can be useful in methods that include and/or require specific recognition of FGFR3-IIIb and/or internalization of antibodies and antibody fragments that FGFR3-IIIb. [0186] Accordingly, in some embodiments, provided herein are methods inhibiting proliferation of a cell expressing FGFR3-IIIb, the method comprising: contacting a cell with the antibody or antibody fragment that binds FGFR3-IIIb (as those described herein). In certain embodiments, the antibody or antibody fragment is internalized by the cell. In certain embodiments, the cell is a Ba/F3 cell expressing FGFR3-IIIb. In some embodiments, cell proliferation is measured by the assay described in Example 6.
[0187] Definitions
[0188] As described herein, the term “percent (%) sequence identity,” and terms related thereto, in the context of amino acid sequences or nucleic acid sequences, is the percentage of amino acid residues or nucleic acid residues in a candidate sequence that are identical with the amino acid residues or nucleic acid residues, respectively, in a selected sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity or percent nucleic acid identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as Clustal Omega, BLAST, BLAST-2, ALIGN, ALIGN-2 or Megalign (DNASTAR) software, with BLAST being the alignment algorithm of preference. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full-length of the sequences being compared, although for simplicity it maybe preferred to use default parameters.
[0189] As used herein, the term “individual” is synonymous with patient and/or subject and includes and/or refers to a human and may be a human that has been diagnosed as needing to treat a disease or condition as disclosed herein. However, examples are not limited to humans and include, chimpanzees, marmosets, cows, horses, sheep, goats, pigs, rabbits, dogs, cats, rats, mice, guinea pigs, and the like. The term individual includes vertebrates. The individual is typically a human and may be a human that has been diagnosed as needing to treat a disease or condition as disclosed herein.
[0190] As used herein, treating or treatment of includes and/or refers to ameliorating the disease or disorder or symptoms thereof (e.g., slowing or arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In certain embodiments, treating or treatment also includes and/or refers to alleviating or ameliorating at least one physical and/or biological parameters including those which may not be discernible by the patient. In certain embodiments, treating or treatment includes and/or refers to modulating a disease, disorder, or biological process either physically, (e.g., stabilization of a discernible symptom), physiologically, e.g., stabilization of a physical and/or biological parameter), or both. In certain embodiments, treating or treatment includes and/or refers to preventing or delaying the onset or development or progression of the disease or disorder. In certain embodiments, treating or treatment includes and/or refers to preventing or delaying or inhibiting the deterioration of (i) a healthy physiological state or (ii) a baseline physiological state (e.g., the progression of a disease or disorder).
[0191] As used herein, in any instance or embodiment described herein, “comprising” may be replaced with “consisting essentially of’ and/or “consisting of,” unless context clearly connotes otherwise. Similarly, as used herein, in any instance or embodiment described herein, “comprises” may be replaced with “consists essentially of’ and/or “consists of,” unless context clearly connotes otherwise.
[0192] As used herein, the term “about,” “approximately”, or “approximate”, when used in connection with a numerical value, means that a collection or range of values is included. For example, “about X” may include a range of values that are ±10%, ±5%, ±2%, ±1%, ±0.5%, ±0.2%, or ±0.1% of X, where X is a numerical value.
[0193] As used herein, the term “and/or” is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example, “A and/or B” is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each were set out individually herein.
EXAMPLES
Example 1: Mouse immunization and production of mouse antibodies against human FGFR3
[0194] To generate antibodies against the human FGFR3, domain 2-3 of FGFR3-IIIb (SEQ ID NO: 193) and FGFR3-IIIc (SEQ ID NO: 194) were produced and used as antigens. DNA encoding domain 2-3 of FGFR3-IIIb fused with histidine Tag (hFGFR3-IIIb-HisTag, SEQ ID NO: 195; and hFGFR3-IIIc-HisTag, SEQ ID NO: 196), or human Fc tag (hFGFR3-IIIb-hFc, SEQ ID NO: 197; and hFGFR3-IIIc-hFc, SEQ ID NO: 198) were obtained by PCR and subcloned into expression vector pcDNA3.1 (Invitrogen, Cat. No: V-790), respectively. After transient expression in freestyle 293 cells, hFGFR3-IIIb-HisTag and hFGFR3-IIIc-HisTag was purified with NTA column (BIOLINK, Cat. No: 1021-1131); hFGFR3-IIIb-hFc and hFGFR3- IIIc-hFc was purified with MabSelect PrismA (Cytiva, Cat. No: 17549802).
[0195] BALB/c mice were immunized subcutaneously every 2 weeks for 6 weeks with hFGFR3-IIIb-HisTag and hFGFR3-IIIc-HisTag (100 pg/mouse) emulsified with an equal volume of Freund's complete/incomplete adjuvant. Three days before fusion, mice were boosted by intravenous injection of the antigen without adjuvant. Spleen cells (1 * 108) from immunized mouse were fused with SP2/0 myeloma cells (1.5>< 107) with PEG Hybri-Max (Sigma Inc., Cat. No: 7181). After fusion, the cells were distributed into 96-well plates at 0.1 ml per well and incubated at 37°C, 5% CO2 incubator. On day 1, an additional 0.1 ml media containing serum and HAT plus 2* methotrexate was added to each well. On day 3 and day 7, 0.1 ml of media from each well was replaced with 0.1 ml of fresh HT media. The screening typically occurred between days 8-9, and the culture supernatant from each well was tested for hFGFR3-IIIb- HisTag and hFGFR3-IIIc-HisTag binding by ELISA and cell binding analysis. Cell binding analysis of FGFR3-IIIb antibody was performed using 293T cell line stably expressing FGFR3- Illb (SEQ ID NO: 191, FGFR3-IIIb-293T) and FGFR3-IIIc (SEQ ID NO: 192; FGFR3-IIIc- 293 T). Subcloning was conducted to obtain individual hybridoma clones. Each of the hybridomas was subjected to multiple rounds (2-3 rounds) of limiting dilution. For each round of subcloning, the clones were tested by ELISA binding and cell binding analysis
Example 2: hFGFR3 hybridoma antibody screening based on ELISA binding assay
[0196] The binding specificity of hybridoma antibody with hFGFR3-IIIb-hFc and hFGFR3-IIIc- hFc was measured by ELISA. 96-well plate (Costar, Cat. No: 9018) was coated with 100 pL of 1 pg/mL Goat anti -Human IgG or Fc fragment specific antibody (Jackson, Cat. No: 109-005-008) in PBS buffer (Hyclone, Cat. No: SH30256.01B) overnight at 4 °C. The wells were aspirated, and non-specific binding sites were blocked by adding 200 pL of blocking buffer containing 1% (w/v) of bovine serum albumin (Sigma, Cat. No: V900933) and incubating for 1 hour at 37 °C. After the plate was washed three times with PBS buffer containing 0.05%(v/v) Tween 20 (Sigma, Cat. No: P1379), 100 pL 1 pg/mL hFGFR3-IIIb-hFc or hFGFR3-IIIc-hFc diluted in blocking buffer was added to each well and incubated at room temperature for 1 hour. After washing three times with PBS buffer, 100 pL of 10 pg/mL purified hybridoma antibody diluted in the blocking buffer was added to each well and incubated at room temperature for 1 hour. The plate was washed and incubated with 100 pL/well of Goat anti -Mouse IgG (Thermo, Cat. No: 31432) in blocking buffer for 60 min. After the plate was washed, 100 pL/well of substrate solution TMB (eBioscience, Cat. No: 00-4201-56) was added, and the plate was incubated for 2 min at room temperature before 100 pL/well of 2N H2SO4 was added to stop the reaction. The colorimetric signal was measured at 450 nm using a SpectraMax Plus microplate reader (Molecular Devices). Table 3 shows ELISA binding data for FGFR3-IIIb antibodies against FGFR3-IIIb or FGFR3-IIIc. Reference mAb 1 was also used as a comparison and control. Table 3: FGFR3-IIIb and -IIIc binding by FGFR3-IIIb antibodies
[0197] To measure the binding EC50 of each monoclonal antibody by ELISA, a serial concentration of hybridoma antibody (starting from 30,000 ng/mL, five-fold serial dilution) in the blocking buffer was added to each well of the 96-well plate and incubated at room temperature for 1 hour. After washing, the 96-well plate was incubated with 100 pL/well of Goat anti-Mouse IgG (Thermo, Cat. No: 31432) for 60 min. The plate was washed and incubated with 100 pL/well of substrate solution TMB (eBioscience, Cat. No: 00-4201-56) for 2 min at room temperature before 100 pL/well of 2N H2SO4 was added. The colorimetric signals were monitored at 450 nm using a microplate reader, and the binding EC50 was calculated using GraphPad Prism 5 Software. Table 4 and FIGS. 1A and IB shows ELISA EC50 data for FGFR3-IIIb antibodies against FGFR3-IIIb (FIG. 1A) or FGFR3-IIIc (FIG. IB). Antibodies 33E2 (SEQ ID NOS: 680, 681) and 456 (SEQ ID NOS: 543, 544) were tested and identified as binding to FGFR3-IIIb and FGFR3-IIIc.
Table 4: ELISA EC50 values for FGFR3-IIIb antibodies
Example 3: hFGFR3 hybridoma antibody screening based on FACS binding assay
[0198] The binding specificity of hybridoma antibody with hFGFR3-IIIb and hFGFR3-IIIc was further measured by FACS using 293T cell line stably expressing FGFR3-IIIb. l * 10A5 FGFR3- IIIb-293T cells were added to each well of 96-well plate and incubated with 10 pg/mL hybridoma antibody at 4 °C for 1 hr. After the cells were washed three times with FACS buffer (PBS + 3% FBS (ExCell Bio, Cat. No: FND500) (v/v)), the secondary antibody (APC Goat antimouse (BioLegend, Cat. No: 405308) 1 :200 dilution) was added to each cell at 100 pL/well and incubated at 4 °C for 40 min. Cells were washed three times with FACS buffer and analyzed by FACS Array. Table 5 shows cell binding data of FGFR3-IIIb antibodies with the cells expressing FGFR3-IIIb or FGFR3-IIIc.
Table 5: Binding of FGFR3-IIIb antibodies to cells expressing FGFR3-IIIb or FGFR3-IIIc
[0199] To measure the binding ECso of each monoclonal antibody by FACS, a serial concentration of hybridoma antibody (starting from 30,000 ng/mL, five-fold serial dilution) in the FACS buffer was incubated with l * 10A5 FGFR3-IIIb-293T cells at 4 °C for 1 hr. The cells were then washed three times, and 100 pl/well of the secondary antibody (APC Goat antimouse: 1 :200) was added and incubated at 4 °C for 40 min. After washing, the cells were analyzed by FACS Array, and the binding ECso of each antibody was calculated using GraphPad Prism 5 Software. Table 6 and FIGS. 2A and 2B shows binding profiles and ECso data for binding of FGFR3-IIIb antibodies to cells expressing FGFR3-IIIb (FIG. 2A) or FGFR3-IIIc (FIG. 2B)
Table 6: ELISA EC50 values for binding of FGFR3-IIIb antibodies to cells expressing FGFR3-IIIb or -IIIc Example 4: Internalization of hFGFR3-IIIb antibody
[0200] 50 pL FGFR3-293T cells (2* 10A5 cells/well) were added to a 96-well U bottom plate and mixed with 50 pL FGFR3-IIIb antibody, which was 3-fold serial diluted at a final concentration from 30 pg/mL to 4.57 ng/mL. After the plate was incubated at 4 °C for 1 hour, the mixture of cells and antibody in each well was washed twice with 200 pL/well FACS buffer (PBS with 3% FBS). 100 pL of 2 pg/mL of 2nd antibody (CypHer5E (Cytiva, Cat. No: PA15401) labeled Goat anti-mlgG Fc, Jackson ImmunoResearch, Cat. No: 115-006-071) was then added to each well and incubate at 4 °C for 40 mins in the dark. The supernatant in each well was discarded after centrifuging the plate at 1500 rpm for 3 mins at room temperature, and the cells were washed twice with 200 pL/well FACS buffer. After the cells were incubated with 200 pL warm growth medium at 37 °C for 0-4 hours in the dark, the culture medium was removed by centrifuging the plate at 1500 rpm for 3 mins, and the cell pellets were resuspended with 200 pL of Cell Suspension Buffer (PBS, pH 9.0) and analyze on a flow cytometer. Table 7 shows internalization of FGFR3-IIIb antibodies 8511, 287, 1012, 295, and 547.
Table 7: Internalization of FGFR3-IIIb antibodies by cells expressing FGFR3-IIIb
Example 5: hFGFR3 hybridoma antibody gene cloning, chimeric antibody generation and characterization
[0201] The total RNA of each hFGFR3 hybridoma clone was isolated by RNeasy Mini Kit (Qiagen, Cat. No: 74104) and used as the template to synthesize first-strand cDNA with SuperScript® II Reverse Transcriptase (Life Technology, Cat. No: 18064-14) according to the manufacturer's instructions. The cDNA product was then subjected to PCR in a 50 pL volume reaction mixture using degenerate mouse IgG primers (Kettleborough et al., (1993) European Journal of Immunology 23:206; Strebe et al., (2010) Antibody Engineering 1 :3). The reaction was carried out in a S1000TM Thermal Cycler (Bio-Rad, Cat. No: 184-2000) with 30 cycles of: 94 °C, 1.5 minutes for denaturation; 50 °C, 1 minute for annealing; and 72 °C, 1 minute for synthesis. At the end of the 30th cycle, the reaction mixture was incubated for an additional 7 minutes at 72° C for extension. The PCR mixture was subjected to electrophoresis in a 1% agarose/Tris-Borate gel containing 0.5 pg/mL ethidium bromide. DNA fragments with the expected sizes (approximately 450 bp for the heavy chain and the light chain) were excised from the gel and purified. 3 pL of purified PCR product were cloned into the pMD-18T vector (Takara, Cat. No: D101A) and transformed into One Shot® TOPIO chemically competent E. coli (Invitrogen, CAT. NO:C4040-03). Clones were screened by colony PCR using universal M13 forward and reverse primers, and 5 positive clones from each reaction were picked for DNA sequencing in both directions using Ml 3 forward and Ml 3 reverse primers.
[0202] The light chain of chimeric antibody was constructed by inserting the cDNA encoding mouse light chain various region (VL) to the upstream of human kappa chain constant region (SEQ ID NO: 199), and the heavy chain of chimeric antibody was constructed by linking the cDNA encoding mouse heavy chain various region (VH) to the upstream of human IgGl constant region (SEQ ID NO: 200). The 5'-ends of the mouse cDNA sequences were modified using PCR primers designed to add a leader sequence to both light chain and heavy chain, and the DNAs encoding the light chain and heavy chain of each chimeric antibody were subcloned into expression vector pcDNA3.1 (Invitrogen Cat. No: V-790), respectively.
[0203] 200 mL Freestyle 293 cells (l >< 10A6/mL) were co-transfected with 100 pg each of the chimeric heavy and light chain expression plasmid and cultured for 5 days at 37° C. The chimeric antibody in the supernatant was then purified with Protein-A column (GE healthcare, Cat. No: 17-5498-02).
[0204] Binding of the chimeric antibody with hFGFR3 was also measured by FACS using the same methods described above in Example 3. Binding of FGFR3-IIIb chimeric antibodies chi8511, chi287, chil012, chi295, and chi547 was also tested against FGFR3-IIIb mutants R248C and S249C. Table 8 shows binding data to FGFR3-IIIb to cells expressing FGFR3-IIIb mutants R248C and S249C.
[0205] Binding of chimeric antibodies with hFGFR3-IIIb and FGFR3-IIIc was also measured by ELISA (FIG. 4) using the same methods described above in Example 2. Binding of FGFR3-IIIb antibodies chi8511, chi287, chil012, chi295, and chi547 was also tested against FGFR3-IIIb, FGFR1, FGFR2, and FGFR4 (FIG. 6). The results demonstrate the specificity of the antibodies for hFGFR3-IIIb or hFGFR3-IIIb and FGFR3-IIIc and inability to bind FGFR1, FGFR2, and FGFR4.
Table 8: Binding of FGFR3-IIIb chimeric antibodies to cells expressing FGFR3- Illb or -IIIc
[0206] The internalization capability of FGFR3-IIIb chimeric antibody was measured using Incucyte. Briefly, 1.6* 104 FGFR3-IIIb-293T cells were seeded in 96-well plate (Coming, Cat. No:3610) and incubate overnight at 37 °C. After mixing FGFR3-IIIb antibody with Incucyte Human Fabfluor-pH Red (Statorius, Cat. No: 4722), the mixture was incubated at room temperature for 5 min before being added to the cells. The 96-well plate was loaded to Incucyte S3 Live Cell Analysis System and incubated at 37°C for 24 hrs. The real-time image of the cells in each well of the 96-well plate was continuously monitored by the Incucyte system. Changes in fluorescence intensity indicate internalization, and analysis of these images provides quantitative data on internalization kinetics and extent (FIG. 3).
[0207] The binding kinetics of FGFR3-IIIb antibody with hFGFR3-IIIb-HisTag were measured by a Biacore T200 instrument at 25 °C. Protein A (Sino Biology, Cat. No: 10600-P07E) was diluted with lOmM pH 5.0 sodium acetate and immobilized onto reference and experiment flow cells of a CM5 biosensor chip to around 15,000 RU using an amine coupling kit (Cytiva, Cat. No: BRI 0050). At the beginning of each cycle, diluted test antibody (1.5 pg/mL) was injected to the experiment flow cell for 1 minute to get captured. hFGFR3-IIIb-HisTag analyte series were prepared by diluting the stocks with running buffer to 100 nM followed by 2-fold serial dilution in the same buffer down to 0.78 nM. Analytes were injected in series over the reference and experiment flow cells for 3 minutes at a flow rate of 30 pL/minute. Running buffer (PBS with 0.05% P20) was allowed to flow over for 10 minutes at a flow rate of 30 pL/minute. At the end of each cycle, the biosensor surface was regenerated via 30-second injection of Glycine pH 2.0 (Cytiva, Cat. No: BR100355) buffer at a flow rate of 10 pL/minute. For each analyte sample injection (i.e., each cycle), binding responses obtained from the experimental biosensor surface were double referenced by subtracting simultaneously recorded responses from the reference surface followed by additional subtraction of responses from a single referenced running buffer sample. The association and dissociation rate constants (ka and kd) were determined simultaneously by fitting double-referenced sensorgrams of the entire titration series to Langmuir model (1 :1) using Biaevaluation software. The dissociation constant (KD) was calculated from the determined rate constants by the equation KD = kd/ka. The binding affinity of chimeric FGFR3-IIIb antibodies with hFGFR3-IIIb-HisTag are summarized in Table 9.
Table 9: Binding kinetics of FGFR3-IIIb chimeric antibodies to FGFR3-IIIb
Example 6: Generation of FGFR3-IIIb/BaF3 stable cell lines and cell proliferation assay [0208] cDNA encoding full length FGFR3-IIIb was subcloned into pLVX vector (YouBio, Cat. No: VT4005) to generate pLVX-FGFR3-IIIb plasmid, which was used to generate Ba/F3 cell lines by co-transfecting with psPAX2 (Qualit Yard, Cat. No: QYV0052) and pMD2.G (Qualit Yard, Cat. No: QYV0053). After drug selection with 1 ug/mL puromycin for 2 weeks, the surviving cells were subcloned to generate cell lines stably expressing FGFR3-IIIb (FGFR3- IIIb/BaF3). FGFR3-IIIb/BaF3 cells (l x lOA4/mL) were seeded in RPMI 1640 medium supplemented with 10% fetal bovine serum, 10 ng/mL FGF1 and 10 ug/mL heparin (Stemcell, Cat. No: 07980). FGFR3-IIIb antibodies were added at a final concentration from 30,000 ng/mL to 4.6 ng/mL (three-fold serial dilution). After incubation for 72 hours at 37 °C, cell viability was measured with CellTiter-Glo (Promega, Cat. No: G7572). The effect of FGFR3-IIIb antibodies on the proliferation of FGFR3-IIIb/BaF3 cells is shown in FIG. 5. FGFR3-IIIb antibodies 8511, 287, 1012, 295, and 547 reduced proliferation of FGFR3-IIIb/BaF3 cells.
Example 7: Humanization design for h547, h8511, h287, h295 and h!012 antibodies [0209] Antibodies 547, 8511, 287, 295 and 1012 were humanized using a CDR grafting approach. The light chain and heavy chain variable chain sequences of the murine antibody 547, 8511, 287, 295 and 1012 (see Table 3) were compared to those available in the Research Collaboratory for Structural Bioinformatics (RCSB) protein databank by searching the NCBI database. The structural models of murine antibody 547, 8511, 287, 295 and 1012 were generated respectively based on the VH and VL structure with the highest sequence homology. [0210] Human antibody germlines which have high sequence homology with mouse antibody 547, 8511, 287, 295 and 1012 were selected by searching the IMGT/Domain Gap Align 3D structure database (http://www.imgt.org/3Dstructure-DB/cgi/DomainGapAlign.cgi). The frameworks of human germline antibodies were used as templates for grafting the complementary determining regions (CDRs) from the heavy chain and light chain variable regions of the mouse antibodies. In addition, some amino acids in the frameworks of the human germline templates were back mutated to the corresponding mouse sequences to give a functional humanized antibody.
[0211] For mouse antibody 547, a combination of human germline IGHV1-2*O6 and IGHJ4*01 was selected as the template for heavy chain humanization, and a combination of IGKV1-9*O3 and IGKJ4*01 was chosen as the template for light chain humanization. Several sites in the frameworks of the human germline templates were back mutated to the corresponding amino acid sequences in mouse antibody. For the humanization of h547 antibody light chain variable region, the amino acid at position 1 was mutated from Ala (A) to Asp (D), the amino acid at position 43 was mutated from Ala (A) to Thr (T), the amino acid at position 44 was mutated from Pro (P) to Asn (N); and for the humanization of h547 antibody heavy chain variable region, the amino acid at position 38 was mutated from Arg (R) to Lys (K), the amino acid at position 48 was mutated from Met (M) to He (I), the amino acid at position 67 was mutated from Arg (R) to Lys (K), the amino acid at position 70 was mutated from Met (M) to Leu (L), the amino acid at position 72 was mutated from Arg (R) to Vai (V), the amino acid at position 74 was mutated from Thr (T) to Lys (K), the amino acid at position 84 was mutated from Ser (S) to His (H), the amino acid at position 85 was mutated from Arg (R) to Ser (S).
[0212] For mouse antibody 8511, a combination of human germline IGHV1-2*O6 and IGHJ6*01 was selected as the template for heavy chain humanization, and a combination of IGKVl-33*01 and IGKJ2*01 was chosen as the template for light chain humanization. For the humanization of h8511 antibody light chain variable region, the amino acid at position 3 was mutated from Gin (Q) to Vai (V), the amino acid at position 49 was mutated from Tyr (Y) to Asn (N); and for the h8511 antibody heavy chain variable region humanization, the amino acid at position 48 was mutated from Met (M) to He (I), the amino acid at position 67 was mutated from Arg (R) to Lys (K), the amino acid at position 70 was mutated from Ser (S) to Leu (L), the amino acid at position 72 was mutated from Arg (R) to Vai (V), the amino acid at position 74 was mutated from Thr (T) to Lys (K), the amino acid at position 84 was mutated from Ser (S) to Arg (R), the amino acid at position 85 was mutated from Arg (R) to Ser (S).
[0213] For mouse antibody 287, a combination of human germline IGHV1-2*O6 and IGHJ4*01 was selected as the template for heavy chain humanization, and a combination of IGKV6-21*02 and IGKJ4*01 was chosen as the template for light chain humanization. For the humanization of h287 antibody light chain variable region, the amino acid at position 45 was mutated from Leu (L) to Arg (R), the amino acid at position 46 was mutated from Leu (L) to Trp (W), the amino acid at position 48 was mutated from Lys (K) to Tyr (Y), the amino acid at position 69 was mutated from Asp (D) to Ser (S), the amino acid at position 70 was mutated from Phe (F) to Tyr (Y); and for the h287 antibody heavy chain variable region humanization, the amino acid at position 48 was mutated from Met (M) to He (I), the amino acid at position 66 was mutated from Arg (R) to Lys (K), the amino acid at position 70 was mutated from Met (M) to Leu (L), the amino acid at position 72 was mutated from Arg (R) to Vai (V), the amino acid at position 74 was mutated from Thr (T) to Lys (K), the amino acid at position 84 was mutated from Ser (S) to His (H).
[0214] For mouse antibody 295, a combination of human germline IGHV3-21*01 and IGHJ4*01 was selected as the template for heavy chain humanization, and a combination of IGKVl-33*01 and IGKJ2*01 was chosen as the template for light chain humanization. For the humanization of h295 antibody light chain variable region, the amino acid at position 3 was mutated from Gin (Q) to Lys (K), the amino acid at position 36 was mutated from Tyr (Y) to Phe (F), the amino acid at position 46 was mutated from Leu (L) to Thr (T), the amino acid at position 69 was mutated from Thr (T) to Gin (Q), the amino acid at position 71 was mutated from Phe (F) to Tyr (Y), the amino acid at position 73 was mutated from Phe (F) to Leu (L), the amino acid at position 100 was mutated from Gin (Q) to Gly (G); and for the h295 antibody heavy chain variable region humanization, the amino acid at position 44 was mutated from Gly (G) to Arg (R), the amino acid at position 49 was mutated from Ser (S) to Ala (A), the amino acid at position 72 was mutated from Arg (R) to Thr (T), the amino acid at position 84 was mutated from Asn (N) to Arg (R).
[0215] For mouse antibody 1012, a combination of human germline IGHV3-21*01 and IGHJ5*01 was selected as the template for heavy chain humanization, and a combination of IGKV1-9*O3 and IGKJ2*01 was chosen as the template for light chain humanization. For the humanization of hl 012 antibody light chain variable region, the amino acid at position 3 was mutated from Gin (Q) to Vai (V), the amino acid at position 45 was mutated from Leu (L) to Pro (P), the amino acid at position 46 was mutated from Leu (L) to Trp (W), the amino acid at position 70 was mutated from Phe (F) to Tyr (Y); and for the hl012 antibody heavy chain variable region humanization, the amino acid at position 49 was mutated from Ser (S) to Ala (A), the amino acid at position 76 was mutated from Lys (K) to Arg (R), the amino acid at position 84 was mutated from Asn (N) to Ser (S), the amino acid at position 97 was mutated from Ala (A) to Thr (T).
[0216] For humanized antibody hl 012, the CDR2 of heavy chain and the CDR3 of light chain were further modified at the sites which may cause fragmentation, isomerization, and deamidation. The amino acid at position 60 of heavy chain CDR2 was mutated from Asp (D) to Ser (S) and Tyr (Y); the amino acid at position 62 of heavy chain CDR2 was mutated from Asp (D) to Glu (E); The amino acid at position 91 of light chain CDR3 was mutated from Asn (N) to Gin (Q); the amino acid at position 92 of light chain CDR3 was mutated from Ser (S) to Thr (T). Four antibodies, including hlO12/S92T (SEQ ID NO: 618 and SEQ ID NO: 624), hl012/D60Y/N91Q (SEQ ID NO: 625 and SEQ ID NO: 626), hl012/D60S62E/S92T (SEQ ID NO: 627 and SEQ ID NO: 624), hl012/D60S62E/N91Q (SEQ ID NO: 627 and SEQ ID NO: 626) were generated and showed binding to FGFR3-IIIb (FIG. 10).
Table 10. Non-Limiting Example Humanized Antibodies
Example 8: FACS analysis of antibodies generated from hybridoma clones
[0217] In this example, binding experiments using FGFR3-IIIb antibodies were performed using bladder tumor cells (e.g., RT112/84 and SW780 cell lines) as well as 293T cells over-expressing FGFR3-IIIb, FGFR3-IIIb with S249C mutation, and FGFR3-IIIc. FACS analysis was performed to calculate EC50 of these antibodies.
[0218] RT11/84 cells, SW780 cells, and 293T cells over-expressing FGFR3-IIIb, FGFR3-IIIb with S249C mutation, and FGFR3-IIIc were prepared as described in Example 3. Bindings of antibodies generated from clones (see Table 3) to bladder cancer cell lines, RT112/84 and SW780, are shown in FIG. 7A and FIG. 7B. Further, bindings of antibodies were tested in 293T cells over-expressing FGFR3-IIIb, FGFR3-IIIb with S249C mutation, and FGFR3-IIIc, which were shown in FIG. 7C, FIG. 7D, and FIG. 7E, respectively.
[0219] The EC50 of antibodies binding to 293T cells over-expressing FGFR3-IIIb was calculated and results are shown in FIG. 7F and Table 11.
Table 11. EC50 of binding determined from binding experiments using 293T over expressing FGFR3-IIIb cells.
[0220] FACS analysis was also performed to determine binding of hybridoma antibodies to different isoforms of FGFR3, FGFR3-IIIb and FGFR3-IIIc, and results are shown in FIG. 7G. Example 9: FACS analysis of chimeric antibodies
[0221] In this example, binding experiments of chimeric antibodies as described in example 5 were performed using 293T cells over-expressing FGFR3. FACS analysis was performed to analyze binding affinity and specificity as described in Example 3. FACS results of binding of chimeric antibodies to 293T cells over-expressing FGFR3-IIIb (first column), FGFR3-IIIc (second column 2), FGFR3-IIIb with R248C mutation (third column), or FGFR3-IIIb with S249C mutation (fourth column), are shown in Table 12 and FIG. 8A (for each grouping from left to right: 85B11 (non-blocking), 54H7, 28A7, 10C12, 29E5, hlgGl, 309-hIgGl (nonblocking), and FAYA hlgGl). As shown in Table 13 and FIG. 8A, chimeric 1012 and chimeric 295 antibodies bind to wildtype FGFR3-IIIb or mutant R248C or R249C FGFR3-IIIb, but not FGFR3-IIIc, while chimeric 8511, chimeric 547, and chimeric 287 antibodies bind to both FGFR3-IIIb and FGFR3-IIIc.
Table 12. Binding affinity and specificity of chimeric antibodies calculated from
FACS results.
[0222] The EC50 of chimeric antibody binding determined by FACS is shown in FIG. 8B and
Table 13. EC50 of chimeric antibody binding determined by ELISA is shown in FIG. 8C and
Table 14
[0223] Further, additional binding experiments were performed using RT4 cell line (isolated from urinary bladder tissue), NCI-H1781 cell line (isolated from lung tissue with stage 3B bronchoalveolar carcinoma), and FaDu cell line (head and neck squamous cell carcinoma (HNSCC)), and results are shown in FIG. 8D, FIG. 8E, and FIG. 8F, respectively.
Example 10: FACS analysis of humanized antibodies
[0224] In this example, binding experiments of humanized antibodies as described in Example 7 and Table 10 were performed using 293T cells over-expressing FGFR3-IIIb or FGFR3-IIIc, as well as cancer cell lines, e.g., RT112/84 and RT4, as described in Example 3. Results of binding experiments of humanized antibodies tested in 293T cells over-expressing FGFR3-IIIb, 293T cells over-expressing FGFR3-IIIc, RT112/84 cell line, and RT4 cell line are shown in FIG. 9A, FIG. 9B, FIG. 9C, and FIG. 9D, respectively
Example 11: Analysis of humanized antibodies derived from hl012
[0225] In this example, binding experiments of humanized antibodies: hl012 (SEQ ID NOS: 618, 619), heavy chain mutants hl012/D60S62E (SEQ ID NOS: 627, 619), hl012/D60Y (SEQ ID NOS: 625, 619), hl012/D60S (SEQ ID NO: 690, 619), light chain mutants hlO12/N91Q (SEQ ID NO: 618, 626), hlO12/S92T (SEQ ID NOS: 618, 624), and chimeric 1012 (SEQ ID NOS: 636, 637) antibodies, were performed using 293T cells over-expressing FGFR3-IIIb to determined EC50, as described in Example 3. The EC50 of antibodies binding to 293T cells over-expressing FGFR3-IIIb is shown in FIG. 10 and Table 15.
Table 15. EC50 of binding assay of h!012 antibodies. [0226] In addition, stability experiments were performed using LC/MS/MS. Briefly, humanized hl012 antibody and hl012/D60S62E were incubated in PBS at 4°C and 37°C for 30 days. The modification of these antibodies were analyzed using LC/MS/MS after digestion with trypsin. [0227] Result indicated that N91 in light chain had deamination occur after the antibodies were stored at 37°C for 30 days. Several mutations were performed to eliminate deamidation by mutating N91 to Q, S, T, and S92 to Q and T. The activity of the mutant antibodies were measured by FACS, Biacore binding assay, and internalization assay. Results showed reduction in deamination at residue 91 after mutation without affecting activity of the hl 012 mutant antibodies. Binding kinetics of humanized hl012 and mutant humanized hl012 antibodies were performed. Results are shown in Table 16.
Table 16 Binding kinetics results of h!012 antibodies.
Example 12: Internalization assays
[0228] In this example, an internalization study of antibodies targeting FGFR3-IIIb was performed, as described in Example 4. The study was performed using hlOC12 N91Q, hlOC12 S92Q, hlOC12 N91T, hlOC12 S92T, hlOC12 N91S, Chi 10C12, hlOC12 D60S62E/N91Q(SEQ ID NOS: 627, 626) secondary antibody only (“2nd only”), and cell only. Results are shown in FIG. HA and FIG. 11B Example 13: Antibody effector function assays
[0229] Antibody Dependent Cellular Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP) Assays were performed using RT112/84 cell line and Jurkat cells. Antibody dependent cell-mediated cytotoxicity (ADCC) is one of the main mechanisms of antibody drugs eliminating tumor cells. Jurkat-NFAT-Luc2-CD16a-V158 cells were used as effector cells. CD16a transmitted the activation signal and activated the NFAT-luc2 luciferase reporter gene, giving rise to chemiluminescence after substrate addition. The ADCC activity of the test articles was determined by measuring the signal of luminescence using luciferase Assay System Kit. Luciferase is an enzyme catalyzed luminescence reaction. In this system, the transcriptional activation of target gene was directly proportional to the expression of luciferase. In the luciferase reaction, the cells were dissolved by the luciferase substrate containing D- luciferin. The ATP and Mg2+ were as co substrates, catalyzes the conversion of D-luciferase extracted from reporter cells to oxidized luciferase. The amount of light emitted was proportional to the amount of luciferase. Therefore, gene activation can be detected by using one-step TM luciferase Assay System Kit.
[0230] Cells were grown in cell culture and harvested during the logarithmic growth period. Cells were counted using a blood counting chamber. The cell viability was found to be >90% as determined by a trypan blue assay. Cells were centrifuged at 1000 RPM for 5 minutes and supernatant discarded. Cell concentration was adjusted with the culture medium. 45 pl cell suspension of effector cells (Jurkat) and target cells (RT112/84) was added to each well in a 96- well plate at 25,000 cells/well each. The plate was incubated in a humidified incubator at 37°C with 5% CO2 while preparing samples. lOx dilution of test antibodies was prepared, the initial concentration is 10000 ng/ml, with 5-fold dilution for 9 gradients. Add 10 pL of lOx dilutions to each well (triplicate for each concentration). The plates were incubated in the humidified incubator at 37°C with 5% CO2 for 6 hours. The plates were then read for luminescence signal. Plates are equilibrated to room temperature and 100 pL/well Bright-Glo reagent was added to each well and incubated for 15 minutes on a shaker to lyse the cells. The plates were then read for luminescence signal. Chi8511, Chi287, Chi295, Chil012, Chi547, Reference mAb 2, and Reference mAb 3, isotype hlgGl, and IgGl were tested as described above. Results are shown in FIG. 11C and FIG. 11G. No ADCC nor ADCP effects on RT112/84 cells were observed.
[0231] ADCC assays were also performed using 293T cells over-expressing FGFR3-IIIb. Protocol was used as described above for Chi8511, Chi287, Chi295, Chil012, Chi547, Reference mAb 2, and Reference mAb 3, isotype hlgGl, and IgGl. Results are shown in FIG. HE and Table 17 Limited ADCC effect on 293T cells over-expressing FGFR3-IIIb of chi295 and chil012 antibodies were observed.
Example 14: Cytotoxicity assays
[0232] Binding, internalization, and cytotoxicity assays of antibody drug conjugates (ADCs) were performed using bladder cancer cell line RT112/84 by FACS, as described by Example 17. Monomethyl auristatin E (MMAE) was used as payload for ADC conjugation. Drug-to-antibody ratio of 4 (DAR4) was used for ADC in this experiment. Results of antibody internalization rate of chi295 and chil012 antibody drug conjugates are shown in FIG. HF, respectively. Results of cytotoxicity assays of chi295 and chil012 antibody drug conjugates arewere shown in FIG.
11G. ADCs of chi295 and chil012 conjugated with MMAE show similar cytotoxicity as Reference mAb 2 conjugated with MMAE.
[0233] Overall, results suggest that chi8511 antibody show lower binding affinity compared to chi295 and chil012 antibodies. Using 293T cells over-expressing FGFR3-IIIb, chi8511 antibody show slightly better internalization than chi295 and chi 1012 antibodies determined by Incucyte; however, chi295 and chil012 antibodies show better internalization determined by FACS. These three antibodies show quick internalization rate.
Example 15: Cytotoxicity of antibodies
[0234] In a further experiment, cytotoxicity of additional chimeric antibodies was tested. As above, Briefly, RT112/84 cell lines were used and were cultured in 2D. Chimeric antibodies were added at a range of concentrations from 0.01 nM to 1,000 nM. After incubation for a set period of time at 37 °C, cell viability was measured with CellTiter-Glo (Promega, Cat. No: G7572). The effect of FGFR3-IIIb chimeric antibody drug conjugates on the proliferation of cells was measured (chi8511, chi287, chi295, chi547, and chil012, each conjugated to MMAE). Cytotoxicity of chimeric antibodies was shown in FIG. 12A. Further, in vitro cytotoxicity tests were performed using 3D cell culture of RT112/84 cell line. A similar cytotoxicity protocol was used as described above. The cytotoxicity of chimeric antibodies was shown in FIG. 12B. Additionally, experiments were performed after 5 days using 293T cells over-expressing FGFR3-IIIb using the cytotoxicity protocol as described above. The cytotoxicity of antibodies was as shown in FIG. 12C.
[0235] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the instant disclosure. It should be understood that various alternatives to the embodiments described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the embodiments disclosed herein, and that methods and structures within the scope of these claims and their equivalents be covered thereby.
Table 18. Example Sequences

Claims

CLAIMS What is claimed is:
1. An antibody or antibody fragment that binds FGFR-IIIb comprising:
(i) a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 67; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 673; a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 661; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 662; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 663;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 689; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666;
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669;
(vii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672;
(viii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 64; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 65; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 66;
(ix) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 68; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 70; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 71; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 72;
(x) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 76; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 77; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 78;
(xi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 82; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 83; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 84;
(xii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 88; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 89; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 90;
(xiii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 163; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 164; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 165; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 166; a CDRL2 comprising the amino acid sequence of EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 168; a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 91; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 92; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 93; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 94; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 96;
(xiv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 97; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 98; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 99; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 100; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 102;
(xv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 103; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 104; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 105; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 106; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 108;
(xvi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 109; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 110; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 111; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 112; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 113; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 114;
(xvii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 115; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 116; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 117; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 118; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 119; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 120; or
(xviii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of NY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 170; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 171; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1 comprising the amino acid sequence of NSY; a CDRL2 comprising the amino acid sequence of RAN; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 174.
2. An antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 4; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 6;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 7; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 8; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 9; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 10; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 12;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 13; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 14; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 15; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 16; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 17; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 18;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 19; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 20; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 21; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 22; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 23; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 24;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 25; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 26; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 27; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 28; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 29; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 30; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 152; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 153; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of STE; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 155; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 156.
3. An antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 31; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 32; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 33; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 34; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 36;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 37; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 38; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 39; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 40; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 41; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 42;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 43; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 44; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 45; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 46; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 47; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 48;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 49; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 50; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 51; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 52; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 53; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 54;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 55; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 56; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 57; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 58; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 59; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 60; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of GY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 158; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 159; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 161; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 162.
4. An antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 121; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 122; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 123; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 124; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 125; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 126;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 127; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 128; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 129; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 130; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 131; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 132;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 133; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 134; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 135; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 136; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 137; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 138;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 139; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 140; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 141; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 142; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 143; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 144;
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 145; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 146; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 147; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 148; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 149; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 150; or
(vi) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of DY; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 176; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 177; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SKY; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 179; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 180.
5. An antibody or antibody fragment that binds FGFR3-IIIb comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
6. An antibody or antibody fragment that binds FGFR3-IIIb comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 658; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 660;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 657; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 661; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 662; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 663;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 664; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 665; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 666;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 667; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 668; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 669; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 670; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 671; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 672.
7. An antibody or antibody fragment that binds FGFR3-IIIb comprising:
(i) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 61; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 62; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 63; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 642; a CDRL2 comprising the amino acid sequence EIS; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 644;
(ii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 67; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 673; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 69; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 645; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 646; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 647;
(iii) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 73; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 74; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 75; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 648; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 649; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 650;
(iv) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 79; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 80; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 81; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 651; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 652; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 653; or
(v) a heavy chain variable domain comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 85; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 86; a CDRH3 comprising the amino acid sequence of SEQ ID NO: 87; and a light chain variable domain comprising: a CDRL1 comprising the amino acid sequence of SEQ ID NO: 654; a CDRL2 comprising the amino acid sequence of SEQ ID NO: 655; and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 656.
8. An antibody or antibody fragment that binds FGFR3-IIIb comprising a heavy chain variable region and a light chain variable region, wherein: the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 677, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 676; the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 683, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 206; the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 677, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 206; or the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 684, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 682.
9. An antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprising a heavy chain variable region and a light chain variable region, wherein: the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 209, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 210; or the CDRs of the heavy chain variable region are the CDRs of SEQ ID NO: 201, and the CDRs of the light chain variable region are the CDRs of SEQ ID NO: 202.
10. An antibody or antibody fragment that binds FGFR3-IIIb comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19-21, 22-24; 25-27, 28-30; 31-33, 34-36; 37-39, 40- 42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 61-63, 64-66; 67-69, 70-72; 73-75, 76-78; 79-81, 82-84; 85-87, 88-90; 91-93, 94-96; 97-99, 100-102; 103-105, 106-108; 109-111, 112-114; 115-117, 118-120; 121-123, 124-126; 127-129, 130-132; 133-135, 136-138; 139-141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; GY, 158-159, SY, 161-162; 163-165, 166, EIS, 168; NY, 170-171, NSY, RAN, 174; DY, 176-177, SKY, 179-180; 211-213, 214-216; 217-219, 220-222; 223-225, 226-228; 229-231, 232-234; 235-237, 238-240; 241-243, 244-246; 247-249, 250-252; 253-255, 256-258; 259-261, 262-264; 265-267, 268-270; 271-273, 274-276; 277-279, 280-282; 283-285, 286-288; 289-291, 292, 294; 295-297, 298-300; 301-303, 304-306; 307-309, 310-312; 313-315, 316-318; 319-321, 322-324; 325-327, 328-330; 331-333, 334-336; 337-339, 340-342; 343-344, DDY, 346-348; 349-350, TTH, 352-354; 355-357, 358-360; 361-363, 364-366; 367-369, 370-372; 373-375, 376-378; 379-381, 382-384; 385-387, 388-390; 391-393, 394-396; 397-399, 400-402; 403-405, 406-408; 409-411, 412-414; 415-417, 418-420; 421-423, 424-426; 427-429, 430-432; 433-435, 436-438; 439-441, 442-444; 445-447, 448-450; 451-453, 454-456; 457-459, 460-462; 463-465, 466-468; 469-471, 472-474; 475-477, 478-480; 481-483, 484-486; 487-489, 490-492; 493-495, 496-498; 499-501, 502-504; or 505-507, 508-510; respectively.
11. An antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprising a heavy chain variable region and a light chain variable region, wherein the CDRs of the heavy chain variable region and the CDRs of the light chain variable region comprise SEQ ID NOS: 1-3, 4-6; 7-9, 10-12; 13-15, 16-18; 19-21, 22-24; 25-27, 28-30; 31-33, 34- 36; 37-39, 40-42; 43-45, 46-48; 49-51, 52-54; 55-57, 58-60; 121-123, 124-126; 127-129, 130-132; 133-135, 136-138; 139-141, 142-144; 145-147, 148-150; DY, 152-153, STE, 155-156; DY, 158-159, SY, 161-162; DY, 176-177, SKY, 179-180; 211-213, 214-216; 217-219, 220-222; 223-225, 226-228; 229-231, 232-234; 235-237, 238-240; 241-243, 244-246; 247-249, 250-252; 253-255, 256-258; 259-261, 262-264; 265-267, 268-270; 271-273, 274-276; 277-279, 280-282; 283-285, 286-288; 289-291, 292, 294; 295-297, 298-300; 301-303, 304-306; 307-309, or 310-312; respectively.
12. The antibody or antibody fragment of any one of claims 1-11, wherein the antibody or antibody fragment comprises:
(i) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676;
(ii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206;
(iii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206;
(iv) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 684 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 682;
(v) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202;
(vi) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 203 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 204;
(vii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206;
(viii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 207 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 208; or
(ix) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
13. An antibody or antibody fragment that binds FGFR3-IIIb comprising:
(i) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 676;
(ii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 683 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206; (iii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 677 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206;
(iv) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 684 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 682;
(v) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202;
(vi) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 203 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 204;
(vii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206;
(viii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 207 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 208; or
(ix) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
14. An antibody or antibody fragment that binds FGFR3-IIIb and FGFR3-IIIc comprising:
(i) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 201 and a light chain variable region (VL) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 202;
(ii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 205 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 206;
(iii) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 207 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 208; or
(iv) a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 209 and a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 210.
15. The antibody or antibody fragment of any one of claims 1-14, wherein the antibody or antibody fragment comprises an Fc domain.
16. The antibody or antibody fragment of any one of claims 1-14, wherein the antibody or antibody fragment that binds FGFR3-IIIb comprises:
(i) a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 614 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 615;
(ii) a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 616 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 617;
(iii)a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 618 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 619;
(iv)a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 620 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 621; or
(v) a heavy chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 622 and a light chain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ NO: 623.
17. The antibody or antibody fragment of any one of claims 1-16, wherein the antibody or antibody fragment does not bind with an affinity of about or less than about 10 X 10'8 M to FGFR1, FGFR2, or FGFR4.
18. The antibody or antibody fragment of any one of claims 1-17, wherein the antibody or antibody fragment binds to a FGFR3-IIIb protein with an equilibrium dissociation constant (KD) equal to or less than 10 x 10'8 M.
19. The antibody or antibody fragment of claim 18, wherein the FGFR3-IIIb protein comprises the amino acid sequence of SEQ ID NO: 191, 195, or 197.
20. The antibody or antibody fragment of any one of claims 1-19, wherein the antibody is internalized by a cell expressing FGFR3-IIIb.
21. The antibody or antibody fragment of claim 20, wherein the cell is a HEK-293 cell expressing FGFR3-IIIb.
22. A pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb; and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding FGFR3-IIIb and internalizing into a cell expressing FGFR3-IIIb; and a pharmaceutically acceptable carrier.
24. A method of inhibiting proliferation of a cell expressing FGFR3-IIIb, the method comprising: contacting a cell with the antibody or antibody fragment of any one of claims 1-21 or the pharmaceutical composition of any one of claims 22-23.
25. The method of claim 24, wherein the antibody or antibody fragment is internalized by the cell.
26. The method of any one of claims 24-25, wherein the cell is a Ba/F3 cell expressing FGFR3-IIIb.
PCT/US2025/021849 2024-03-29 2025-03-27 Fgfr3-iiib-binding antibodies Pending WO2025207944A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110052582A1 (en) * 2009-08-28 2011-03-03 Roche Glycart Ag Humanized Anti-CDCP1 Antibodies
US20220056142A1 (en) * 2020-08-21 2022-02-24 Genzyme Corporation Fgfr3 antibodies and methods of use
US20230365706A1 (en) * 2020-10-07 2023-11-16 National University Corporation Chiba University Novel anti-glycan antibody and use thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110052582A1 (en) * 2009-08-28 2011-03-03 Roche Glycart Ag Humanized Anti-CDCP1 Antibodies
US20220056142A1 (en) * 2020-08-21 2022-02-24 Genzyme Corporation Fgfr3 antibodies and methods of use
US20230365706A1 (en) * 2020-10-07 2023-11-16 National University Corporation Chiba University Novel anti-glycan antibody and use thereof

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