Novel antibody molecule, preparation method thereof and use thereof

Active Publication Date: 2019-10-08
INNOVENT BIOLOGICS (SUZHOU) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The multispecific antibody formats in the prior art have their own advantages and disadvantages in preparation and application. For example, although Blinatumomab can be produced in large-scale culture by recombinant Chinese hamster ovary (CHO) cells, it is easy to form aggregates and has a short half-life in vivo In actual use, an additional continuous infusion device is required; the production process of Catumaxomab is complex and mouse heterologous antibodies are more likely to cause immunogenicity problems in humans

Method used

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  • Novel antibody molecule, preparation method thereof and use thereof
  • Novel antibody molecule, preparation method thereof and use thereof
  • Novel antibody molecule, preparation method thereof and use thereof

Examples

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Embodiment 1

[0249] Example 1. Construction, expression, purification and characterization of anti-OX40 / PD-L1 bispecific antibody

Embodiment 11

[0250] Example 1.1. Construction of anti-OX40 / PD-L1 bispecific antibody

[0251] In this example, four anti-OX40 / PD-L1 bispecific antibodies with different structures were constructed, named respectively (1) bispecific antibody Bi-110-112HC, and its structural schematic diagram is as follows Figure 1A Shown; (2) bispecific antibody Bi-113-112HC, its structural schematic diagram is shown in Figure 1BShown; (3) bispecific antibody Bi-119-112LC, the schematic diagram of its structure is shown in Figure 1C shown; and (4) bispecific antibody Bi-122-112LC, its structural schematic diagram is shown in Figure 1D shown. The four anti-OX40 / PD-L1 bispecific antibodies are described below.

[0252] (1) from Figure 1A It can be seen from the schematic diagram of the structure that the bispecific antibody Bi-110-112HC is composed of four symmetrical polypeptide chains, of which the two polypeptide chains (ie, peptide chain #1 and peptide chain #2) in the left half are from N-terminal...

Embodiment 12

[0256] Example 1.2. Expression, purification and analysis of anti-OX40 / PD-L1 bispecific antibody

[0257] In this example, the nucleotide sequences encoding the peptide chain #1 and peptide chain #2 of the anti-OX40 / PD-L1 bispecific antibody constructed in Example 1.1 were linked into commercially available real The nuclear expression vector pTT5 was expressed and purified in eukaryotic cells to obtain anti-OX40 / PD-L1 bispecific antibodies Bi-110-112HC, Bi-113-112HC, Bi-119-112LC and Bi-122-112LC . The specific operation is as follows.

[0258] Entrusted Suzhou Genewiz Biotechnology Co., Ltd. (Genewiz) to synthesize the coding nucleotides of the above-mentioned peptide chains of bispecific antibodies Bi-110-112HC, Bi-113-112HC, Bi-119-112LC and Bi-122-112LC sequence. The synthesized nucleotide sequences encoding peptide chains were respectively ligated into vector pTT5 by using appropriate restriction enzymes and ligases to obtain recombinant vectors respectively containing...

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Abstract

The present invention provides a novel artificially designed antibody molecule, which comprises (i) a single domain antigen binding site; (ii) an antigen binding Fab fragment; wherein (i) is located at the N-terminus of a light chain variable domain (VL) of (ii) or the C-terminus of a light-chain constant region (CL), or the (i) is located at the N-terminus of a heavy chain variable domain (VH) ofthe (ii) or the C-terminus of an immunoglobulin CH1 domain, (i) and (ii) respectively bind the same or different antigens, and a linking peptide is existed or does not exist in between (i) and (ii),and an (iii) immunoglobulin Fc domain is positioned at the C-terminus of (i) and (ii). The invention also provides the use of the polynucleotide encoding the antibody molecule, a vector comprising thepolynucleotide, a host cell comprising the polynucleotide or the vector, an immunoconjugate comprising the antibody molecule, and a pharmaceutical composition, and the antibody molecule for immunotherapy, prevention and / or diagnosis of a disease.

Description

[0001] field of invention [0002] The present invention relates generally to the fields of immunology and antibody engineering. Specifically, the present invention relates to various novel artificially designed antibody molecules, polynucleotides encoding said antibody molecules, vectors comprising said polynucleotides, host cells comprising said polynucleotides or vectors, comprising Immunoconjugates and pharmaceutical compositions of the antibody molecules, and uses of the antibody molecules in immunotherapy, prevention and / or diagnosis of diseases. [0003] Background of the invention [0004] Antibody molecules can specifically bind to their corresponding antigens, and are increasingly becoming important therapeutic, preventive and therapeutic agents for various diseases (such as cancer, autoimmune diseases, inflammatory diseases, infectious diseases, etc. and / or diagnostic agents. However, monospecific antibodies against only one target have some limitations in clinical...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/22C07K16/28C12N15/13C12N15/85C12N15/70G01N33/574G01N33/569A61K39/395A61K47/68A61K45/00A61P35/00A61P37/02A61P29/00A61P31/00
CPCC07K16/2878C07K16/2896C07K16/2818C07K16/2827C07K16/2803C07K16/22G01N33/569A61K39/395A61K47/6803A61K45/00A61P35/00A61P37/02A61P29/00A61P31/00C07K2317/56C07K2317/569G01N2800/24G01N2800/22A61K2039/505A61P37/00A61K45/06C07K16/2875C07K2317/31C07K2317/76C07K2317/24C07K2317/94C07K2317/92C07K2317/64C07K2317/22C07K2317/75C07K2317/35C07K2317/53C07K2317/55C07K2317/565
Inventor 刘军建缪小牛匡智慧
Owner INNOVENT BIOLOGICS (SUZHOU) CO LTD
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