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Single-gene bispecific antibody capable of targeting CTLA4 and PD-1 and application thereof

A bispecific antibody, PD-1 technology, applied in applications, antibodies, genetic engineering, etc., can solve problems such as high treatment costs, and achieve the effects of simple structure, improved maintenance time, and short antibody sequences

Inactive Publication Date: 2019-05-17
Y CLONE MEDICAL SCI CO LTD
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0007] However, the combination therapy of the two antibodies leads to high treatment costs, but currently no bispecific antibody with good anti-CTLA4 and anti-PD-1 has been constructed in the field

Method used

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  • Single-gene bispecific antibody capable of targeting CTLA4 and PD-1 and application thereof
  • Single-gene bispecific antibody capable of targeting CTLA4 and PD-1 and application thereof
  • Single-gene bispecific antibody capable of targeting CTLA4 and PD-1 and application thereof

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Embodiment Construction

[0029] The principles and features of the present invention are described below in conjunction with the accompanying drawings, and examples are only used to explain the present invention, and are not intended to limit the scope of the present invention.

[0030] 1. Construction and expression of monogenic tetravalent bispecific antibody

[0031] We obtained three antibodies during the study, one targeting PD-1 and the other two targeting CTLA4. Through the structure and sequence analysis of these three antibodies, we designed a protein domain AC (amino acid sequence SEQ ID NO: 1, nucleotide sequence SEQ ID NO: 9) targeting CTLA4, and two targeting PD The protein domains of -1 were named AP1 (sequence not given) and AP2 (SEQ ID NO: 2, nucleotide sequence SEQ ID NO: 10), respectively.

[0032] After these three structural domains are combined and linked with a linker, they are then linked with the IgG Fc4 constant region (SEQ ID NO: 3) (such as figure 1 Shown), six new antibod...

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Abstract

The invention relates to a single-gene bispecific antibody capable of targeting CTLA4 and PD-1. The single-gene bispecific antibody comprises a first target binding region, a second target binding region and an Fc region from an N end to a C end in sequence, wherein the first target binding region is connected with the second target binding region through a connecting fragment, and the first target binding region targets one of the CTLA4 and PD-1, the second target binding region targets the other of the CTLA4 and PD-1. The invention also relates to application of the single-gene bispecific antibody in preparation of antitumor drugs. The invention also relates to an AAV bispecific antibody expression vector. The single-gene bispecific antibody can effectively target the PD1 and CTLA4, is short in sequence and simple in structure, is suitable for construction of an AAV virus-based antibody expression vector, the antibody expression vector can be directly injected, and the maintenance time of the antibody in the body is prolonged.

Description

technical field [0001] The present invention relates to the field of tumor treatment drugs, more particularly, to a monogene bispecific antibody targeting CTLA4 and PD-1 and its application, and an AAV antibody comprising the DNA coding sequence of the above monogene bispecific antibody Expression vector. [0002] priority [0003] This application claims the priority of the invention patent application with application number 201810903651X submitted by the applicant on August 9, 2018, the entire contents of which are incorporated herein by reference. Background technique [0004] Bispecific antibodies first appeared in the 1990s. At that time, some scholars began to study antibodies with two antigen-binding sites. According to the structure of bispecific antibodies, they can be divided into IgG subtypes and non-IgG subtypes. There are two types, and there are many different forms under each category. Among them, the IgG subtype trifunctional antibody (Triomab) and the no...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/46C12N15/864A61K39/395A61P35/00
Inventor 吴稚伟吴喜林李彦磊黄碧莲马晓花
Owner Y CLONE MEDICAL SCI CO LTD
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