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1. 发明申请

US20070184523A1 Method for Making Multispecific Antibodies Having Heteromultimeric and Common Components 审中-公开
标题翻译：制备具有异源多聚体和共同成分的多特异性抗体的方法
公开(公告)号：US20070184523A1
公开(公告)日：2007-08-09
申请号：US11536439
申请日：2006-09-28
申请人： William Arathoon , Paul Carter , Anne Merchant , Leonard Presta
发明人： William Arathoon , Paul Carter , Anne Merchant , Leonard Presta
IPC分类号： C12P21/08 , C07K16/44 , C07H21/04
CPC分类号： C07K16/2809 , A61K38/00 , C07K16/2869 , C07K16/32 , C07K16/46 , C07K16/468 , C07K2317/24 , C07K2317/31 , C07K2317/52 , C07K2319/00
摘要： The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method further involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide. The method allows for the enhanced formation of the desired heteromultimer relative to undesired heteromultimers and homomultimers.
摘要翻译：本发明涉及制备异源多聚体多肽如双特异性抗体，双特异性免疫粘附素和抗体免疫粘附素嵌合体的方法。本发明还涉及使用该方法制备的异源多聚体。通常，该方法提供具有与具有抗体结合结构域的每个异聚多肽相关联的共同轻链的多特异性抗体。另外，该方法还包括将多特异性抗体引入第一多肽的界面处的第二多肽的界面上的特异性和互补相互作用，以促进异源多聚体形成并阻碍同源多聚体形成; 和/或在第二多肽的界面处的第一多肽和相应的游离含硫醇残基的界面处的游离含硫醇残基，使得在第一和第二多肽之间形成非天然存在的二硫键。该方法允许相对于不想要的异多元反应物和同源多聚体增强所需异源多聚体的形成。

2. 发明申请

US20070178552A1 Method for Making Multispecific Antibodies Having Heteromultimeric and Common Components 有权
公开(公告)号：US20070178552A1
公开(公告)日：2007-08-02
申请号：US11608673
申请日：2006-12-08
申请人： W. Arathoon , Paul Carter , Anne Merchant , Leonard Presta
发明人： W. Arathoon , Paul Carter , Anne Merchant , Leonard Presta
IPC分类号： C07K16/44 , C07H21/04 , C12P21/06 , C12N5/06
CPC分类号： C07K16/2863 , A61K38/00 , C07K1/22 , C07K16/2809 , C07K16/2812 , C07K16/46 , C07K16/468 , C07K2317/732 , Y10S435/972
摘要： The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method further involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide. The method allows for the enhanced formation of the desired heteromultimer relative to undesired heteromultimers and homomultimers.

3. 发明申请

US20070098712A1 Method for making multispecific antibodies having heteromultimeric and common components 有权
标题翻译：制备具有异源多聚体和共同成分的多特异性抗体的方法
公开(公告)号：US20070098712A1
公开(公告)日：2007-05-03
申请号：US11536951
申请日：2006-09-29
申请人： W. Arathoon , Paul Carter , Anne Merchant , Leonard Presta
发明人： W. Arathoon , Paul Carter , Anne Merchant , Leonard Presta
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C12N5/06 , C07K16/44
CPC分类号： C07K16/00 , C07K16/46 , C07K16/468 , C07K2317/732
摘要： The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method further involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide. The method allows for the enhanced formation of the desired heteromultimer relative to undesired heteromultimers and homomultimers.
摘要翻译：本发明涉及制备异源多聚体多肽如双特异性抗体，双特异性免疫粘附素和抗体免疫粘附素嵌合体的方法。本发明还涉及使用该方法制备的异源多聚体。通常，该方法提供具有与具有抗体结合结构域的每个异聚多肽相关联的共同轻链的多特异性抗体。另外，该方法还包括将多特异性抗体引入第一多肽的界面处的第二多肽的界面上的特异性和互补相互作用，以促进异源多聚体形成并阻碍同源多聚体形成; 和/或在第二多肽的界面处的第一多肽和相应的游离含硫醇残基的界面处的游离含硫醇残基，使得在第一和第二多肽之间形成非天然存在的二硫键。该方法允许相对于不想要的异多元反应物和同源多聚体增强所需异源多聚体的形成。

4. 发明申请

US20070196363A1 Method for Making Multispecific Antibodies Having Heteromultimeric and Common Components 审中-公开
公开(公告)号：US20070196363A1
公开(公告)日：2007-08-23
申请号：US11537195
申请日：2006-09-29
申请人： W. Arathoon , Paul Carter , Anne Merchant , Leonard Presta
发明人： W. Arathoon , Paul Carter , Anne Merchant , Leonard Presta
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C12P21/04 , C07K16/18 , C12N5/06
CPC分类号： C07K16/2809 , C07K16/00 , C07K16/2812 , C07K16/2869 , C07K16/32 , C07K2317/24 , C07K2317/31 , C07K2317/52 , C07K2317/622 , C07K2317/624 , C07K2319/00
摘要： The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method further involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide. The method allows for the enhanced formation of the desired heteromultimer relative to undesired heteromultimers and homomultimers.

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