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1. WO2020108611 - ANTI-CD40 ANTIBODY, ANTIGEN BINDING FRAGMENT AND PHARMACEUTICAL USE THEREOF

Publication Number WO/2020/108611
Publication Date 04.06.2020
International Application No. PCT/CN2019/121941
International Filing Date 29.11.2019
IPC
C07K 16/28 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins, e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
A61P 35/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
A61K 39/395 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 37/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37Drugs for immunological or allergic disorders
C12N 15/13 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
11DNA or RNA fragments; Modified forms thereof
12Genes encoding animal proteins
13Immunoglobulins
C12N 15/63 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
CPC
A61K 39/395
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
395Antibodies
A61P 29/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29Non-central analgesic, antipyretic or anti-inflammatory agents, e.g antirheumatic agents; Non-steroidal anti-inflammatory drugs (NSAIDs)
A61P 35/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
A61P 37/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37Drugs for immunological or allergic disorders
C07K 16/28
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
16Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
18against material from animals or humans
28against receptors, cell surface antigens or cell surface determinants
C12N 15/63
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
Applicants
  • 江苏恒瑞医药股份有限公司 JIANGSU HENGRUI MEDICINE CO., LTD. [CN]/[CN]
  • 上海恒瑞医药有限公司 SHANGHAI HENGRUI PHARMACEUTICAL CO., LTD. [CN]/[CN]
Inventors
  • 廖成 LIAO, Cheng
  • 蒋家骅 JIANG, Jiahua
  • 徐祖朋 XU, Zupeng
  • 张连山 ZHANG, Lianshan
  • 林源 LIN, Yuan
  • 林侃 LIN, Kan
  • 钱雪明 QIAN, Xueming
  • 滕菲 TENG, Fei
Agents
  • 北京戈程知识产权代理有限公司 GE CHENG & CO., LTD.
Priority Data
201811448228.130.11.2018CN
Publication Language Chinese (ZH)
Filing Language Chinese (ZH)
Designated States
Title
(EN) ANTI-CD40 ANTIBODY, ANTIGEN BINDING FRAGMENT AND PHARMACEUTICAL USE THEREOF
(FR) ANTICORPS ANTI-CD40, FRAGMENT DE LIAISON À L'ANTIGÈNE DE CELUI-CI ET UTILISATION PHARMACEUTIQUE ASSOCIÉE
(ZH) 抗CD40抗体、其抗原结合片段及其医药用途
Abstract
(EN)
The present invention relates to an anti-CD40 antibody, an antigen binding fragment and a pharmaceutical use thereof. Heavy-chain constant regions of the anti-CD40 antibody and the antigen binding fragment thereof contain mutations. Due to the mutations, the anti-CD40 antibody loses the binding activity to FcγRIII, and the binding of the anti-CD40 antibody and FcγRIII is enhanced, thereby losing the antibody-dependent cytotoxicity (ADCC) but improving FcγRIII-mediated antibody crosslinking. The mutations in the heavy-chain constant regions enhance the activation of CD40, and enhance the presentation of dendritic cells to antigens. The anti-CD40 antibody and the antigen binding fragment thereof can be used as anti-cancer drugs to treat CD40-mediated diseases or symptoms.
(FR)
La présente invention concerne un anticorps anti-CD40, un fragment de liaison à l'antigène de celui-ci et une utilisation pharmaceutique associée. L'anticorps anti-CD40 et le fragment de liaison à l'antigène de celui-ci comprend des régions constantes de chaîne lourde qui contiennent des mutations. Les mutations causent la perte de la liaison de l'anticorps anti-CD40 à FcγRIII, et améliorent la liaison de l'anticorps anti-CD40 et FcγRIII, ce qui permet de perdre la cytotoxicité dépendante de l'anticorps (ADCC) et d'améliorer la réticulation de l'anticorps à médiation par FcγRIII. Les mutations dans les régions constantes de chaîne lourde améliorent l'activation de CD40 ainsi que la présentation de cellules dendritiques à des antigènes. L'anticorps anti-CD40 et le fragment de liaison à l'antigène de celui-ci peuvent être utilisés en tant que médicaments anticancéreux pour traiter des maladies ou des symptômes à médiation par CD40.
(ZH)
本公开涉及抗CD40抗体、其抗原结合片段及其医药用途。所述抗CD40抗体、其抗原结合片段的重链恒定区含有突变,所述突变使得抗CD40抗体丧失了其与FcγRIII结合的活性,同时增强了抗CD40抗体与FcγRIIB的结合,从而丧失了抗体依赖的细胞毒性(ADCC),但是增强了FcγRIIB介导的抗体交联。重链恒定区中的突变导致增强了对CD40的激活,以及增强了树突细胞对抗原的递呈。本公开的抗CD40抗体及其抗原结合片段作为抗癌药物具有治疗CD40介导的疾病或病症的用途。
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