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WO2023011650A1 - Anticorps multispécifique et son utilisation - Google Patents

Anticorps multispécifique et son utilisation Download PDF

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Publication number
WO2023011650A1
WO2023011650A1 PCT/CN2022/110659 CN2022110659W WO2023011650A1 WO 2023011650 A1 WO2023011650 A1 WO 2023011650A1 CN 2022110659 W CN2022110659 W CN 2022110659W WO 2023011650 A1 WO2023011650 A1 WO 2023011650A1
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WO
WIPO (PCT)
Prior art keywords
domain
terminus
light chain
heavy chain
chain variable
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/CN2022/110659
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English (en)
Chinese (zh)
Inventor
乔晶
焦娇
王娇
王瑞雪
孙宇
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.)
Gan and Lee Pharmaceuticals Co Ltd
Original Assignee
Gan and Lee Pharmaceuticals Co Ltd
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 Gan and Lee Pharmaceuticals Co Ltd filed Critical Gan and Lee Pharmaceuticals Co Ltd
Priority to CN202280052925.3A priority Critical patent/CN117915950A/zh
Publication of WO2023011650A1 publication Critical patent/WO2023011650A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • 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

Definitions

  • X1 contains the Jun domain and X2 contains the Fos domain
  • the Jun domain is a sequence as shown in SEQ ID NO:9, or a sequence with at least 80%, 85%, 90%, 95%, or 99% identity to SEQ ID NO:9; and/or
  • a first light chain comprising a first light chain variable domain (VL1) operably linked to a first pairing domain (X1), and
  • VL2 the C-terminal of VL2 is operably linked to the N-terminal of the second CL
  • the first light chain comprises a first light chain variable domain (VL1) and a first pairing domain (X1) from the N-terminus to the C-terminus, and the first heavy chain comprises from the N-terminus to the C-terminus A first heavy chain variable domain (VH1), a second pairing domain (X2), and a first dimerization domain; and
  • the second light chain comprises a Fos domain, L3, and a second light chain variable domain (VL2) from N-terminus to C-terminus
  • the second heavy chain comprises a Jun domain, L4 from N-terminus to C-terminus , a second heavy chain variable domain (VH2), and a second dimerization domain; or
  • the second light chain comprises a second light chain variable domain (VL2), L3 and Fos domain from N-terminus to C-terminus
  • the second heavy chain comprises a second heavy chain variable domain from N-terminus to C-terminus domain (VH2), L4, Jun domain, second dimerization domain, L6, and Myc domain; or
  • the second light chain comprises a Fos domain, L3, restriction site peptide, and a second light chain variable domain (VL2) from the N-terminus to the C-terminus, and the second heavy chain is from the N-terminus to the C-terminus comprising a Jun domain, L4, a cleavage site peptide, a second heavy chain variable domain (VH2), a second dimerization domain, a cleavage site peptide, L6, and a WinzipB1 domain; or
  • the second light chain comprises Myc domain, L3, enzyme cleavage site peptide, and the second light chain variable domain (VL2) from N-terminus to C-terminus, and the second heavy chain is from N-terminus to C-terminus Contains Max domain, L4, cleavage site peptide, second heavy chain variable domain (VH2), second dimerization domain, cleavage site peptide, L6, and WinzipB1 domain.
  • the cells are selected from one of CHO cells, COS cells, and yeast cells.
  • antibodies of the present invention also include antibodies with incomplete constant regions, such as only including CH1, including CH1 and CH2, including CH1 and CH3, including CH2 and CH3, etc.
  • hydrophobic interaction refers to the phenomenon that hydrophobic groups gather close to each other to avoid water.
  • interface refers to specific regions on the polypeptides that interact/associate with each other.
  • An interface comprises one or more amino acid residues that interact with corresponding amino acid residues that are in contact or associate when the interaction occurs.
  • the amino acid residues in the interface may or may not be in contiguous sequence. For example, when the interface is three-dimensional, the amino acid residues within the interface may be located separately at different positions on the linear sequence.
  • FIG. 1-3 Schematic diagram of the structure of antibody AmF3
  • FIG. 1-4 Schematic diagram of the structure of antibody AmF4
  • TROP2 is rarely expressed or not expressed in adult normal tissues (Cubas et al. (2009) Biochimica et Biophysica Acta.1796:309–314; Zhang et al. (1997)
  • the present invention is directed at the variable region sequence of PRLR as follows:
  • Protein A affinity chromatography column buffer (equilibrium buffer: 9.5mM sodium dihydrogen phosphate, 40.5mM disodium hydrogen phosphate, 200mM sodium chloride, pH 7.0; elution buffer: 100mM glycine, 100mM chloride Sodium, adjust the pH value to 3.0; neutralization buffer: 1M Tris, adjust the pH value to 8.0), the buffer solution is filtered through a 0.45 ⁇ m filter membrane; after the sample is centrifuged, take the supernatant and filter through a 0.45 ⁇ m filter membrane; wash and prepare Pipeline; install the Protein A column, after the column is equilibrated, prepare to load the sample, and adjust the UV to zero; during the sample loading, ensure that no air bubbles enter the pipeline; then wash the breakthrough peak with the equilibration buffer until the UV value drops to the baseline level; Adjust the flow rate to 5.0 mL/min, use the elution buffer to elute the protein from the column and collect it; finally use the neutralization buffer
  • Example 12 Purity detection of bispecific antibody BmF and monoclonal antibody mAb-T
  • Example 13 Affinity of bispecific antibody BmF and monoclonal antibody mAb-T to antigen

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Mycology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un anticorps multispécifique comprenant une première partie de liaison à l'antigène et une seconde partie de liaison à l'antigène. La chaîne légère et la chaîne lourde de la première partie de liaison à l'antigène et/ou de la seconde partie de liaison à l'antigène comprennent une séquence capable de former une paire de structures de glissière à leucine. La chaîne légère et la chaîne lourde forment un dimère au moyen de la paire de structures de glissière à leucine, réduisant ainsi efficacement le mésappariement entre la chaîne légère et la chaîne lourde. En outre, la chaîne lourde de la première partie de liaison à l'antigène et la chaîne lourde de la seconde partie de liaison à l'antigène peuvent réduire le mésappariement entre les chaînes lourdes au moyen d'une structure nœud dans la cavité (KIH), d'une interaction hydrophobe, d'une interaction électrostatique, d'une interaction hydrophile, ou d'une flexibilité accrue. La présente invention concerne également une méthode de traitement d'une pluralité de maladies à l'aide dudit anticorps multispécifique.
PCT/CN2022/110659 2021-08-06 2022-08-05 Anticorps multispécifique et son utilisation Ceased WO2023011650A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202280052925.3A CN117915950A (zh) 2021-08-06 2022-08-05 一种多特异性抗体及其用途

Applications Claiming Priority (2)

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CN202110903516 2021-08-06
CN202110903516.7 2021-08-06

Publications (1)

Publication Number Publication Date
WO2023011650A1 true WO2023011650A1 (fr) 2023-02-09

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CN (1) CN117915950A (fr)
WO (1) WO2023011650A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20070052920A (ko) * 2005-11-18 2007-05-23 주식회사 아이지세라피 기능성 Ｆｖ 항체 절편 제조 방법
CN101365486A (zh) * 2006-01-04 2009-02-11 默克专利有限公司 使用抗egfr和抗her2抗体的联合治疗
CN102741423A (zh) * 2009-10-23 2012-10-17 雅培制药有限公司 双重可变结构域免疫球蛋白及其用途
CN102946906A (zh) * 2010-04-23 2013-02-27 弗·哈夫曼-拉罗切有限公司 生产异源多聚体蛋白质
CN104628851A (zh) * 2015-02-12 2015-05-20 长春百克生物科技股份公司 一种抗狂犬病毒的基因工程抗体、其制备方法和应用
CN110913902A (zh) * 2017-02-10 2020-03-24 蜻蜓疗法股份有限公司 结合psma、nkg2d和cd16的蛋白质
CN112930186A (zh) * 2018-08-16 2021-06-08 纪念斯隆-凯特琳癌症中心 基于亮氨酸拉链的组合物和使用方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20070052920A (ko) * 2005-11-18 2007-05-23 주식회사 아이지세라피 기능성 Ｆｖ 항체 절편 제조 방법
CN101365486A (zh) * 2006-01-04 2009-02-11 默克专利有限公司 使用抗egfr和抗her2抗体的联合治疗
CN102741423A (zh) * 2009-10-23 2012-10-17 雅培制药有限公司 双重可变结构域免疫球蛋白及其用途
CN102946906A (zh) * 2010-04-23 2013-02-27 弗·哈夫曼-拉罗切有限公司 生产异源多聚体蛋白质
CN104628851A (zh) * 2015-02-12 2015-05-20 长春百克生物科技股份公司 一种抗狂犬病毒的基因工程抗体、其制备方法和应用
CN110913902A (zh) * 2017-02-10 2020-03-24 蜻蜓疗法股份有限公司 结合psma、nkg2d和cd16的蛋白质
CN112930186A (zh) * 2018-08-16 2021-06-08 纪念斯隆-凯特琳癌症中心 基于亮氨酸拉链的组合物和使用方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
B. J. WRANIK, E. L. CHRISTENSEN, G. SCHAEFER, J. K. JACKMAN, A. C. VENDEL, D. EATON: "LUZ-Y, a Novel Platform for the Mammalian Cell Production of Full-length IgG-bispecific Antibodies", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, vol. 287, no. 52, 21 December 2012 (2012-12-21), pages 43331 - 43339, XP055204058, ISSN: 00219258, DOI: 10.1074/jbc.M112.397869 *
FU-XIANG ZHU, SHU-DE YANG, LIU ZE-LONG, JING MIAO, HUI-GE QU, XIAO-YAN CHI: "Leucine zippers improves protein splicing-mediated coagulation factor VIII gene delivery by dual-vector system", ACTA PHARMACEUTICA SINICA, YAOXUE XUEBAO, CN, vol. 47, no. 1, 31 January 2012 (2012-01-31), CN , pages 39 - 44, XP093031516, ISSN: 0513-4870, DOI: 10.16438/j.0513-4870.2012.01.001 *

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