Nav1.9 target polypeptide, antibody and antibody fragment combined with same and related pharmaceutical composition

文档序号:1602383 发布日期:2020-01-07 浏览:27次 中文

阅读说明:本技术 Nav1.9的靶点多肽、与其结合的抗体及抗体片段和相关药物组合物 (Nav1.9 target polypeptide, antibody and antibody fragment combined with same and related pharmaceutical composition ) 是由 杨代常 于 2018-02-07 设计创作,主要内容包括:本发明提供了一种靶向细胞膜电压门控钠离子通道α亚基Nav1.9的抗体或其抗体片段,其特异结合的靶点为电压门控钠离子通道α亚基的第II结构域的电压传感器桨的S3-4环。所述抗体或其抗体片段能失活电压传感器阀门,使得钠离子不能正常进入神经细胞,从而达到治疗和缓解疼痛的效果。(The invention provides an antibody or an antibody fragment thereof targeting a cell membrane voltage-gated sodium ion channel alpha subunit Nav1.9, wherein a specific combined target point is an S3-4 loop of a voltage sensor paddle of a II structural domain of the voltage-gated sodium ion channel alpha subunit. The antibody or the antibody fragment can inactivate the voltage sensor valve, so that sodium ions can not normally enter nerve cells, thereby achieving the effects of treating and relieving pain.)

an antibody or antibody fragment thereof that specifically binds to cell membrane voltage-gated sodium ion channel alpha subunit Nav1.9.

The antibody or antibody fragment thereof of claim 1, wherein the target specifically bound by said antibody or antibody fragment is the S3-4 loop of a voltage sensor paddle of domain II of the α subunit of a voltage-gated sodium channel.

The antibody or antibody fragment thereof according to claim 1, characterized in that: the heavy chain variable region of the antibody or the antibody fragment thereof comprises CDR sequences of CDRH1 shown in SEQ ID NO.4, CDRH2 shown in SEQ ID NO.5 and CDRH3 shown in SEQ ID NO. 6; and/or

The light chain variable region of the antibody or the antibody fragment thereof comprises CDR sequences of CDRL1 shown in SEQ ID NO.7, CDRL2 shown in SEQ ID NO.8 and CDRL3 shown in SEQ ID NO. 9.

The antibody or antibody fragment thereof according to claim 3, characterized in that said antibody or antibody fragment comprises the heavy chain variable region as shown in SEQ ID No.2 and/or the light chain variable region as shown in SEQ ID No. 3.

The antibody or antibody fragment thereof according to claim 1, characterized in that the antibody further comprises an antibody constant region.

The antibody or antibody fragment thereof according to claim 1, characterized in that said antibody or antibody fragment is selected from the following structural forms: whole antibody, Fab, F (ab')2dsFv, scFv, diabodies, minibodies, diabodies, multispecific antibodies, chimeric antibodies and CDR-grafted antibodies.

The antibody or antibody fragment thereof according to claim 1, characterized in that the antibody is a monoclonal antibody.

A polypeptide which specifically binds to the antibody or antibody fragment thereof of claim 1, characterized in that said polypeptide has the amino acid sequence shown in SEQ ID No. 1.

A pharmaceutical composition comprising the antibody or antibody fragment thereof of claim 1.

Use of the antibody or antibody fragment thereof of claim 1 in the manufacture of a medicament for the treatment of a pain-related disorder.

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