发明授权
- 专利标题: Anti-PCSK9 antibodies with pH dependent antigen binding
- 专利标题(中): 具有pH依赖性抗原结合的抗PCSK9抗体
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申请号: US13045345申请日: 2011-03-10
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公开(公告)号: US09029515B2公开(公告)日: 2015-05-12
- 发明人: Jaume Pons , Jeffrey Raymond Chabot , Javier Fernando Chaparro Riggers , Bruce Charles Gomes , Hong Liang , Kapil Mayawala , Jerome Thomas Mettetal, II , Arvind Rajpal , David Louis Shelton
- 申请人: Jaume Pons , Jeffrey Raymond Chabot , Javier Fernando Chaparro Riggers , Bruce Charles Gomes , Hong Liang , Kapil Mayawala , Jerome Thomas Mettetal, II , Arvind Rajpal , David Louis Shelton
- 申请人地址: US CA South San Francisco US NY New York
- 专利权人: Rinat Neuroscience Corp.,Pfizer Inc.
- 当前专利权人: Rinat Neuroscience Corp.,Pfizer Inc.
- 当前专利权人地址: US CA South San Francisco US NY New York
- 代理机构: Pfizer Inc.
- 主分类号: C07K16/00
- IPC分类号: C07K16/00 ; C07K16/40 ; C07K16/42
摘要:
The present invention relates to antibodies with pH dependent binding to its antigen such that the affinity for antigen binding at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6.0 or 5.5). In other words, the KD or koff ratio at pH 5.5/pH 7.4 or at pH 6.0/pH 7.4 is more than, or ranges between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This can increase antibody half life, as compared to antibodies with equivalent KDs at pH 7.4 but with no pH dependent binding, when the antigen is one that undergoes antigen-mediated clearance (e.g., PCSK9). Antibodies with pH dependent binding can decrease total antigen half life when the antigen undergoes reduced clearance when bound to antibody (e.g., IL6). Antibodies with pH dependent binding can also prolong the decrease in antigen which is not antibody-bound. This can be important when antagonizing a target antigen typically present at high levels (e.g., IgE, DKK1, C5 and SOST). In addition, such antibodies can increase antigen half life when the antigen is a receptor and the receptor has increased clearance when bound to antibody (e.g., GMCSF receptor).
公开/授权文献
- US20110229489A1 Antibodies with pH Dependent Antigen Binding 公开/授权日:2011-09-22
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