[go: up one dir, main page]

WO2007120651A2 - Utilisation et compositions pour le traitement de l'arthrite rhumatoïde juvénile - Google Patents

Utilisation et compositions pour le traitement de l'arthrite rhumatoïde juvénile Download PDF

Info

Publication number
WO2007120651A2
WO2007120651A2 PCT/US2007/008826 US2007008826W WO2007120651A2 WO 2007120651 A2 WO2007120651 A2 WO 2007120651A2 US 2007008826 W US2007008826 W US 2007008826W WO 2007120651 A2 WO2007120651 A2 WO 2007120651A2
Authority
WO
WIPO (PCT)
Prior art keywords
antigen
antibody
tnfα
binding portion
jra
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.)
Ceased
Application number
PCT/US2007/008826
Other languages
English (en)
Other versions
WO2007120651A3 (fr
Inventor
John R. Medich
Nicolino Ruperto
Alberto Martini
Daniel J. Lovell
Edward H. Giannini
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.)
AbbVie Biotechnology Ltd
Original Assignee
Abbott Biotech Ltd Bermuda
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 Abbott Biotech Ltd Bermuda filed Critical Abbott Biotech Ltd Bermuda
Priority to EP07755184A priority Critical patent/EP2010213A4/fr
Publication of WO2007120651A2 publication Critical patent/WO2007120651A2/fr
Publication of WO2007120651A3 publication Critical patent/WO2007120651A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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

Definitions

  • the invention provides a method of preventing a flare up in a subject having JRA comprising administering an effective TNF ⁇ antibody, or antigen-binding portion thereof, to a subject such that the flare-up is prevented, wherein the effective TNF ⁇ antibody, or antigen-binding portion thereof, was previously identified as preventing a flare-up in about 43% or less of a patient population having JRA.
  • the TNF ⁇ antibody is an isolated human antibody, or antigen-binding portion thereof, with the following characteristics: a) dissociates from human TNF ⁇ with a K o ff rate constant of 1 x 10" 3 s" 1 or less, as determined by surface plasmon resonance; b) has a light chain CDR.3 domain comprising the amino acid sequence of SEQ ID NO: 3, or modified from SEQ ID NO: 3 by a single alanine substitution at position 1, 4, 5, 7 or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9; c) has a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, or modified from SEQ ID NO: 4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 1 1 and/or 12.
  • Figure 2 shows the patient disposition
  • TNF ⁇ inhibitor includes agents which interfere with TNF ⁇ activity.
  • the term also includes each of the anti-TNF ⁇ human antibodies and antibody portions described herein as well as those described in U.S. Patent Nos. 6,090,382; 6,258,562; 6,509,015, and in U.S. Patent Application Serial Nos. 09/801 185 and 10/302356.
  • the TNF ⁇ inhibitor used in the invention is an anti-TNF ⁇ antibody, or a fragment thereof, including infliximab (Remicade , Johnson and Johnson; described in U.S. Patent No.
  • multivalent antibody refers to an antibody comprising more than one antigen recognition site.
  • a “bivalent” antibody has two antigen recognition sites, whereas a “tetravalent” antibody has four antigen recognition sites.
  • the terms “monospecific”, “bispecif ⁇ c”, “trispeciflc”, “tetraspecific”, etc. refer to the number of different antigen recognition site specificities (as opposed to the number of antigen recognition sites) present in a multivalent antibody.
  • a "monospecific” antibody's antigen recognition sites all bind the same epitope.
  • the TNF ⁇ inhibitor used in the invention is an TNF ⁇ antibody (also referred to herein as a TNF ⁇ antibody), or an antigen-binding fragment thereof, including chimeric, humanized, and human antibodies.
  • TNF ⁇ antibodies which may be used in the invention include, but not limited to, infliximab
  • the invention features uses and composition for treating or determining the efficacy of a TNF ⁇ inhibitor for the treatment of juvenile rheumatoid arthritis, wherein the TNF ⁇ antibody is an isolated human antibody, or antigen-binding portion thereof, that binds to human TNF ⁇ with high affinity and a low off rate, and also has a high neutralizing capacity.
  • the human antibodies used in the invention are recombinant, neutralizing human anti-hTNF ⁇ antibodies.
  • the methods of the invention may also be performed using chimeric and humanized murine anti-hTNF ⁇ antibodies which have undergone clinical testing for treatment of rheumatoid arthritis (see e.g., Elliott, MJ. , el at. (1994) Lancet 344: 1 125-1 127; Elliot, MJ., et al. (1994) Lancet 344:1105-1110; Rankin, E.C., et al. (1995) Br. J. Rheumatol. 34:334-342).
  • PCR primers suitable for use in amplifying the DP-31 germline VH and A20 germline VL sequences can be designed based on the nucleotide sequences disclosed in the references cited supra, using standard methods. Once the germline VH and VL fragments are obtained, these sequences can be mutated to encode the D2E7 or D2E7-related amino acid sequences disclosed herein. The amino acid sequences encoded by the germline VH and VL DNA sequences are first compared to the D2E7 or D2E7-reIated VH and VL amino acid sequences to identify amino acid residues in the D2E7 or D2E7-related sequence that differ from germline.
  • the heavy chain constant region can be an IgGl, IgG2, IgG3, IgG4, IgA, IgE, IgM or IgD constant region, but most preferably is an IgGl or IgG4 constant region.
  • the VH-encoding DNA can be operatively linked to another DNA molecule encoding only the heavy chain CHl constant region.
  • the isolated DNA encoding the VL region can be converted to a full-length light chain gene (as well as a Fab light chain gene) by operatively linking the VL-encoding DNA to another DNA molecule encoding the light chain constant region, CL.
  • the sequences of human light chain constant region genes are known in the art (see e.g. , Kabat, E.A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth
  • Preferred mammalian host cells for expressing the recombinant antibodies of the invention include Chinese Hamster Ovary (CHO cells) (including dhfr- CHO cells, described in Urlaub and Chasin, (1980) Proc. Natl. Acad. Sci. USA 77:4216-4220, used with a DHFR selectable marker, e.g., as described in RJ. Kaufman and P. A. Sharp (1982) MoI. Biol. 159:601-621), NSO myeloma cells, COS cells and SP2 cells.
  • Chinese Hamster Ovary CHO cells
  • dhfr- CHO cells described in Urlaub and Chasin, (1980) Proc. Natl. Acad. Sci. USA 77:4216-4220, used with a DHFR selectable marker, e.g., as described in RJ. Kaufman and P. A. Sharp (1982) MoI. Biol. 159:601-621
  • NSO myeloma cells
  • a recombinant expression vector encoding both the antibody heavy chain and the antibody light chain is introduced into dhfr-CHO cells by calcium phosphate-mediated transfection.
  • the antibody heavy and light chain genes are each operatively linked to CMV enhancer/ AdMLP promoter regulatory elements to drive high levels of transcription of the genes.
  • the recombinant expression vector also carries a DHFR gene, which allows for selection of CHO cells that have been transfected with the vector using methotrexate selection/amplification.
  • nucleotide sequence encoding the D2E7 heavy chain variable region is shown in SEQ ID NO: 37.
  • the CDRl domain of the HCVR encompasses nucleotides 91-105
  • the CDR2 domain encompasses nucleotides 148-198
  • the CDR3 domain encompasses nucleotides 295- 330.
  • nucleotide sequences encoding D2E7 -related antibodies, or portions thereof ⁇ e.g., a CDR domain, such as a CDR3 domain can be derived from the nucleotide sequences encoding the D2E7 LCVR and HCVR using the genetic code and standard molecular biology techniques.
  • compositions suitable for administration to a subject can be incorporated into pharmaceutical compositions suitable for administration to a subject.
  • the pharmaceutical composition comprises an antibody, antibody portion, or other TNF ⁇ inhibitor, and a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable carrier includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible.
  • compositions for use in the methods and compositions of the invention may be in a variety of forms. These include, for example, liquid, semi-solid and solid dosage forms, such as liquid solutions ⁇ e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes and suppositories.
  • liquid solutions ⁇ e.g., injectable and infusible solutions
  • dispersions or suspensions tablets, pills, powders, liposomes and suppositories.
  • Typical preferred compositions are in the form of injectable or infusible solutions, such as compositions similar to those used for passive immunization of humans with other antibodies or other TNF ⁇ inhibitors.
  • the preferred mode of administration is parenteral (e.g., intravenous, subcutaneous, intraperitoneal, intramuscular).
  • the antibody or other TNF ⁇ inhibitor is administered by intravenous infusion or injection.
  • the antibody or other TNF ⁇ inhibitor is administered by intramuscular or subcutaneous injection.
  • biweekly dosing includes a dosing regimen where doses of a TNF ⁇ inhibitor are administered to a subject every other week consecutively for a given time period, e.g., 4 weeks, 8 weeks, 16, weeks, 24 weeks, 26 weeks, 32 weeks, 36 weeks, 42 weeks, 48 weeks, 52 weeks, 56 weeks, etc.
  • MTX had flared compared with placebo.
  • placebo + MTX or ada + mtx 65 percent of the patients receiving placebo flared while only 37% of the patients receiving adalimumab flared.
  • 71% of the placebo patients flared versus only 43% receiving adalimumab.
  • the ACR response rates by MTX use at week 48 of non-responders (patients who flared) are shown in Table 3. The table reveals a reduction in ACR for those patients switched to the placebo in the double blind phase.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des méthodes, des utilisations et des compositions pour le traitement de l'arthrite rhumatoïde juvénile (ARJ). L'invention décrit des méthodes et des utilisations pour le traitement de l'ARJ, dans lesquelles un inhibiteur de TNFα, tel qu'un anticorps TNFα humain, ou une partie de celui-ci se liant à l'antigène, est utilisé pour prévenir les poussées actives associées à l'ARJ. L'invention concerne également des méthodes permettant de déterminer l'efficacité d'un inhibiteur de TNFα pour le traitement de l'ARJ chez un sujet.
PCT/US2007/008826 2006-04-10 2007-04-10 Utilisation et compositions pour le traitement de l'arthrite rhumatoïde juvénile Ceased WO2007120651A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP07755184A EP2010213A4 (fr) 2006-04-10 2007-04-10 Utilisation et compositions pour le traitement de l'arthrite rhumatoïde juvénile

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US79090906P 2006-04-10 2006-04-10
US60/790,909 2006-04-10
US80977006P 2006-05-30 2006-05-30
US60/809,770 2006-05-30
US81548906P 2006-06-20 2006-06-20
US60/815,489 2006-06-20
US85837606P 2006-11-10 2006-11-10
US60/858,376 2006-11-10

Publications (2)

Publication Number Publication Date
WO2007120651A2 true WO2007120651A2 (fr) 2007-10-25
WO2007120651A3 WO2007120651A3 (fr) 2008-07-31

Family

ID=38610129

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/008826 Ceased WO2007120651A2 (fr) 2006-04-10 2007-04-10 Utilisation et compositions pour le traitement de l'arthrite rhumatoïde juvénile

Country Status (2)

Country Link
EP (1) EP2010213A4 (fr)
WO (1) WO2007120651A2 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2297209A4 (fr) * 2008-06-03 2012-08-01 Abbott Lab Immunoglobulines à deux domaines variables et leurs utilisations
US8716450B2 (en) 2009-10-15 2014-05-06 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US8722855B2 (en) 2009-10-28 2014-05-13 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US8735546B2 (en) 2010-08-03 2014-05-27 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US8822645B2 (en) 2008-07-08 2014-09-02 Abbvie Inc. Prostaglandin E2 dual variable domain immunoglobulins and uses thereof
US8987418B2 (en) 2013-03-15 2015-03-24 Abbvie Inc. Dual specific binding proteins directed against IL-1β and/or IL-17
US9029508B2 (en) 2008-04-29 2015-05-12 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US9046513B2 (en) 2010-08-26 2015-06-02 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US9045551B2 (en) 2012-11-01 2015-06-02 Abbvie Inc. Anti-DLL4/VEGF dual variable domain immunoglobulin and uses thereof
US9109026B2 (en) 2008-06-03 2015-08-18 Abbvie, Inc. Dual variable domain immunoglobulins and uses thereof
US9120870B2 (en) 2011-12-30 2015-09-01 Abbvie Inc. Dual specific binding proteins directed against IL-13 and IL-17
US9840554B2 (en) 2015-06-15 2017-12-12 Abbvie Inc. Antibodies against platelet-derived growth factor (PDGF)
US10093733B2 (en) 2014-12-11 2018-10-09 Abbvie Inc. LRP-8 binding dual variable domain immunoglobulin proteins

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5888511A (en) * 1993-02-26 1999-03-30 Advanced Biotherapy Concepts, Inc. Treatment of autoimmune diseases, including AIDS
UA81743C2 (uk) * 2000-08-07 2008-02-11 Центокор, Инк. МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ
CA2868614A1 (fr) * 2001-06-08 2002-12-08 Abbott Laboratories (Bermuda) Ltd. Methodes pour administrer des anticorps anti-tnf.alpha.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of EP2010213A4 *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9029508B2 (en) 2008-04-29 2015-05-12 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US9109026B2 (en) 2008-06-03 2015-08-18 Abbvie, Inc. Dual variable domain immunoglobulins and uses thereof
US9035027B2 (en) 2008-06-03 2015-05-19 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
EP2297209A4 (fr) * 2008-06-03 2012-08-01 Abbott Lab Immunoglobulines à deux domaines variables et leurs utilisations
US8822645B2 (en) 2008-07-08 2014-09-02 Abbvie Inc. Prostaglandin E2 dual variable domain immunoglobulins and uses thereof
US8716450B2 (en) 2009-10-15 2014-05-06 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US8722855B2 (en) 2009-10-28 2014-05-13 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US8735546B2 (en) 2010-08-03 2014-05-27 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US9493560B2 (en) 2010-08-03 2016-11-15 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US9046513B2 (en) 2010-08-26 2015-06-02 Abbvie Inc. Dual variable domain immunoglobulins and uses thereof
US9120870B2 (en) 2011-12-30 2015-09-01 Abbvie Inc. Dual specific binding proteins directed against IL-13 and IL-17
US9045551B2 (en) 2012-11-01 2015-06-02 Abbvie Inc. Anti-DLL4/VEGF dual variable domain immunoglobulin and uses thereof
US9163093B2 (en) 2012-11-01 2015-10-20 Abbvie Inc. Anti-DLL4/VEGF dual variable domain immunoglobulin and uses thereof
US9944720B2 (en) 2012-11-01 2018-04-17 Abbvie Inc. Anti-DLL4/VEGF dual variable domain immunoglobulin and uses thereof
US9062108B2 (en) 2013-03-15 2015-06-23 Abbvie Inc. Dual specific binding proteins directed against IL-1 and/or IL-17
US8987418B2 (en) 2013-03-15 2015-03-24 Abbvie Inc. Dual specific binding proteins directed against IL-1β and/or IL-17
US10093733B2 (en) 2014-12-11 2018-10-09 Abbvie Inc. LRP-8 binding dual variable domain immunoglobulin proteins
US9840554B2 (en) 2015-06-15 2017-12-12 Abbvie Inc. Antibodies against platelet-derived growth factor (PDGF)

Also Published As

Publication number Publication date
EP2010213A2 (fr) 2009-01-07
EP2010213A4 (fr) 2010-08-11
WO2007120651A3 (fr) 2008-07-31

Similar Documents

Publication Publication Date Title
US9669093B2 (en) Methods for treating juvenile idiopathic arthritis
US20160280776A1 (en) Uses and Compositions for Treatment of Juvenile Rheumatoid Arthritis
CA2898009C (fr) Utilisation d'un inhibiteur du tnf alpha pour le traitement de la polyarthrite erosive
US20100040630A1 (en) Methods and compositions for treating bone loss
US8926975B2 (en) Method of treating ankylosing spondylitis
EP2010213A2 (fr) Utilisation et compositions pour le traitement de l'arthrite rhumatoïde juvénile
US20080131374A1 (en) Uses and compositions for treatment of rheumatoid arthritis
EP2666479A2 (fr) Utilisations et compositions pour le traitement de l'arthrite rhumatoïde juvénile
HK1191232A (en) Uses and compositions for treatment of juvenile rheumatoid arthritis
AU2012254978C1 (en) Use of TNF inhibitor for treatment of erosive polyarthritis
AU2016256831A1 (en) Use of TNF inhibitor for treatment of erosive polyarthritis
HK1175714A (en) Use of tnf alpha inhibitor for treatment of erosive polyarthritis
HK1133397B (en) Use of tnf inhibitor for treatment of erosive polyarthritis

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07755184

Country of ref document: EP

Kind code of ref document: A2

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
NENP Non-entry into the national phase in:

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2007755184

Country of ref document: EP