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Polypeptide linker for preparing multispecific antibodies

A multi-specific antibody, multi-specific technology, applied in specific peptides, medical preparations with inactive ingredients, anti-animal/human immunoglobulins, etc., can solve problems such as complexity and laborious manufacturing batches

Pending Publication Date: 2019-11-29
BIOMUNEX PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, the characterization of such formulations can be quite complicated, which can make comparisons between different manufacturing batches laborious.

Method used

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  • Polypeptide linker for preparing multispecific antibodies
  • Polypeptide linker for preparing multispecific antibodies
  • Polypeptide linker for preparing multispecific antibodies

Examples

Experimental program
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Embodiment

[0150] design

[0151] The first bispecific antibody of the invention is the antibody called BiXAb2a having the following structure:

[0152] i) a continuous heavy chain comprising

[0153] Trastuzumab heavy chain variable region (VH) corresponding to SEQ ID NO:7

[0154] The wild-type CH1 constant domain from human IgG1 corresponding to SEQ ID NO: 8 (residue 192 of Kabat is threonine)

[0155] A polypeptide linker connecting the two Fab heavy chains consisting of

[0156] Composed of EPKSCDKTHTSPPAPAPELLGGPGGPPGPGPGGG (SEQ ID NO: 2);

[0157] Cetuximab heavy chain variable region (VH) corresponding to SEQ ID NO: 9

[0158] Mutated CH1 constant domain from human IgG1 corresponding to SEQ ID NO: 10 (Kabat residue 192 has been mutated from threonine to glutamic acid)

[0159] The wild-type hinge region from human IgG1 corresponding to SEQ ID NO: 11

[0160] - Wild-type CH2 domain from human IgG1 corresponding to SEQ ID NO: 12

[0161] · Wild-type CH3 domain from human I...

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Abstract

The present invention relates to a mutant polypeptide linker for preparing multispecific antibodies, the multispecific antibodies, and methods for producing the multispecific antibodies.

Description

[0001] The present invention relates to multispecific antibodies with improved properties that can be used in the medical field. [0002] Background of the invention [0003] Therapeutic fusion proteins have become an important modality in drug development. Typically, peptide linkers are used to construct multidomain proteins from different functional protein modules. The resulting multi-domain proteins are designed to bind targets associated with individual modules (or to simultaneously exert the biological functions of individual modules) to enhance biological effects associated with isolated single domains or to generate novel domains not available from isolated single domains. biological activity. There are many examples of molecules that utilize peptide linkers: single chain variable domains of antibodies (scFv), immunocytokines (cytokine-antibody fusions), bispecific antibodies (BsAbs), etc. The choice of linker for a particular fusion protein is determined by considera...

Claims

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Application Information

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IPC IPC(8): C07K16/46A61K47/68C07K16/28C07K16/32
CPCC07K16/2827C07K16/2863C07K16/2896C07K16/32C07K16/468C07K2317/31C07K2317/41C07K2317/55C07K2317/60A61P35/00C07K2317/14C07K2317/24C07K2317/522C07K2317/524C07K2317/526C07K2317/53
Inventor E.朱科夫斯基O.莱格
Owner BIOMUNEX PHARMA