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1. 发明申请

US20130089553A1 METHOD FOR MAKING HETEROMULTIMERIC POLYPEPTIDES 失效
标题翻译：制备异构多糖的方法
公开(公告)号：US20130089553A1
公开(公告)日：2013-04-11
申请号：US13494870
申请日：2012-06-12
申请人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
发明人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
IPC分类号： C07K16/46
CPC分类号： C07K16/468 , A61K38/00 , C07K14/70514 , C07K16/2809 , C07K16/46 , C07K19/00 , C07K2317/526 , C07K2319/00 , C07K2319/30
摘要： The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins, heteromultimers and antibody-immunoadhesin chimeras. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.
摘要翻译：本发明涉及制备异源多聚体多肽的方法，例如双特异性抗体，双特异性免疫粘附素，异源多聚体和抗体免疫粘附素嵌合体。通常，该方法包括在第二多肽的界面中的第一多肽和相应空腔的界面处引入突起，使得突起可以位于空腔中，以促进异源多聚体形成并阻止同源多聚体形成。突起和空腔可以通过合成方式制备，例如改变编码多肽的核酸或通过肽合成。

2. 发明授权

US5807706A Method for making heteromultimeric polypeptides 失效
公开(公告)号：US5807706A
公开(公告)日：1998-09-15
申请号：US433105
申请日：1995-05-03
申请人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
发明人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61P31/04 , A61P31/12 , C07K14/73 , C07K16/28 , C07K16/46 , C07K19/00 , C12N5/10 , C12N15/13 , C12P21/08 , C12R1/91 , C12P21/06
CPC分类号： C07K16/468 , C07K14/70514 , C07K16/2809 , C07K16/46 , C07K19/00 , A61K38/00 , C07K2317/526 , C07K2319/00 , C07K2319/30
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 involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. "Protuberances" are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.

3. 发明授权

US08679785B2 Knobs and holes heteromeric polypeptides 失效
标题翻译：旋钮和孔异聚多肽
公开(公告)号：US08679785B2
公开(公告)日：2014-03-25
申请号：US13494870
申请日：2012-06-12
申请人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
发明人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
IPC分类号： A61K39/395 , C07K14/00 , C07K16/00 , C07K16/46 , C07K19/00 , C12N5/10
CPC分类号： C07K16/468 , A61K38/00 , C07K14/70514 , C07K16/2809 , C07K16/46 , C07K19/00 , C07K2317/526 , C07K2319/00 , C07K2319/30
摘要： The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins, heteromultimers and antibody-immunoadhesin chimeras. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.
摘要翻译：本发明涉及制备异源多聚体多肽的方法，例如双特异性抗体，双特异性免疫粘附素，异源多聚体和抗体免疫粘附素嵌合体。通常，该方法包括在第二多肽的界面中的第一多肽和相应空腔的界面处引入突起，使得突起可以位于空腔中，以促进异源多聚体形成并阻止同源多聚体形成。突起和空腔可以通过合成方式制备，例如改变编码多肽的核酸或通过肽合成。

4. 发明授权

US5821333A Method for making heteromultimeric polypeptides 失效
公开(公告)号：US5821333A
公开(公告)日：1998-10-13
申请号：US434869
申请日：1995-05-03
申请人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
发明人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61P31/04 , A61P31/12 , C07K14/73 , C07K16/28 , C07K16/46 , C07K19/00 , C12N5/10 , C12N15/13 , C12P21/08 , C12R1/91 , C07K1/00
CPC分类号： C07K16/468 , C07K14/70514 , C07K16/2809 , C07K16/46 , C07K19/00 , A61K38/00 , C07K2317/526 , C07K2319/00 , C07K2319/30
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 involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. "Protuberances" are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.

5. 发明授权

US08216805B2 Knobs and holes heteromeric polypeptides 失效
标题翻译：旋钮和孔异聚多肽
公开(公告)号：US08216805B2
公开(公告)日：2012-07-10
申请号：US12700618
申请日：2010-02-04
申请人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
发明人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
IPC分类号： A61K39/395 , C07K14/00 , C07K16/00 , C07K16/46 , C07K19/00 , C12N5/10
CPC分类号： C07K16/468 , A61K38/00 , C07K14/70514 , C07K16/2809 , C07K16/46 , C07K19/00 , C07K2317/526 , C07K2319/00 , C07K2319/30
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 involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. “Protuberances” are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.
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，该方法包括在第二多肽的界面中的第一多肽和相应空腔的界面处引入突起，使得突起可以位于空腔中，以促进异源多聚体形成并阻止同源多聚体形成。通过用较大侧链（例如酪氨酸或色氨酸）从第一多肽的界面替代小的氨基酸侧链构建“突起”。通过用较小的（例如丙氨酸或苏氨酸）代替大的氨基酸侧链，在第二多肽的界面中产生与突起相同或相似大小的补偿性“空腔”。突起和空腔可以通过合成方式制备，例如改变编码多肽的核酸或通过肽合成。

6. 发明授权

US07695936B2 Knobs and holes heteromeric polypeptides 失效
标题翻译：旋钮和孔异聚多肽
公开(公告)号：US07695936B2
公开(公告)日：2010-04-13
申请号：US11533709
申请日：2006-09-20
申请人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
发明人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
IPC分类号： C07K16/00 , C07K16/46 , C07K19/00 , C07K14/00 , A61K39/395 , C12N5/10
CPC分类号： C07K16/468 , A61K38/00 , C07K14/70514 , C07K16/2809 , C07K16/46 , C07K19/00 , C07K2317/526 , C07K2319/00 , C07K2319/30
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 involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. “Protuberances” are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.
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，该方法包括在第二多肽的界面中的第一多肽和相应空腔的界面处引入突起，使得突起可以位于空腔中，以促进异源多聚体形成并阻止同源多聚体形成。通过用较大侧链（例如酪氨酸或色氨酸）从第一多肽的界面替代小的氨基酸侧链构建“突起”。通过用较小的（例如丙氨酸或苏氨酸）代替大的氨基酸侧链，在第二多肽的界面中产生与突起相同或相似大小的补偿性“空腔”。突起和空腔可以通过合成方式制备，例如改变编码多肽的核酸或通过肽合成。

7. 发明授权

US07642228B2 Method for making heteromultimeric polypeptides 失效
标题翻译：异源多聚体多肽的制备方法
公开(公告)号：US07642228B2
公开(公告)日：2010-01-05
申请号：US10010245
申请日：2001-12-07
申请人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
发明人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
IPC分类号： A61K39/395 , A61K38/16 , C07K14/00 , C07K16/00 , C07K16/46 , C07K19/00
CPC分类号： C07K16/468 , A61K38/00 , C07K14/70514 , C07K16/2809 , C07K16/46 , C07K19/00 , C07K2317/526 , C07K2319/00 , C07K2319/30
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 involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. “Protuberances” are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.
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，该方法包括在第二多肽的界面中的第一多肽和相应空腔的界面处引入突起，使得突起可以位于空腔中，以促进异源多聚体形成并阻止同源多聚体形成。通过用较大侧链（例如酪氨酸或色氨酸）从第一多肽的界面替代小的氨基酸侧链构建“突起”。通过用较小的（例如丙氨酸或苏氨酸）代替大的氨基酸侧链，在第二多肽的界面中产生与突起相同或相似大小的补偿性“空腔”。突起和空腔可以通过合成方式制备，例如改变编码多肽的核酸或通过肽合成。

8. 发明授权

US5731168A Method for making heteromultimeric polypeptides 失效
公开(公告)号：US5731168A
公开(公告)日：1998-03-24
申请号：US399106
申请日：1995-03-01
申请人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
发明人： Paul J. Carter , Leonard G. Presta , John B. Ridgway
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61P31/04 , A61P31/12 , C07K14/73 , C07K16/28 , C07K16/46 , C07K19/00 , C12N5/10 , C12N15/13 , C12P21/08 , C12R1/91 , C12P21/06
CPC分类号： C07K16/468 , C07K14/70514 , C07K16/2809 , C07K16/46 , C07K19/00 , A61K38/00 , C07K2317/526 , C07K2319/00 , C07K2319/30
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 involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. "Protuberances" are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.

9. 发明授权

US07951917B1 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：US07951917B1
公开(公告)日：2011-05-31
申请号：US09520130
申请日：2000-03-07
申请人： W. Robert Arathoon , Paul J. Carter , Anne M. Merchant , Leonard G. Presta
发明人： W. Robert Arathoon , Paul J. Carter , Anne M. Merchant , Leonard G. Presta
IPC分类号： C07K16/00 , A61K39/395 , C12P21/08 , C12N15/13
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。

10. 发明授权

US06407213B1 Method for making humanized antibodies 失效
标题翻译：人源化抗体的制备方法
公开(公告)号：US06407213B1
公开(公告)日：2002-06-18
申请号：US08146206
申请日：1993-11-17
申请人： Paul J. Carter , Leonard G. Presta
发明人： Paul J. Carter , Leonard G. Presta
IPC分类号： C07K1600
CPC分类号： G06F15/00 , A61K38/00 , C07K16/28 , C07K16/2809 , C07K16/32 , C07K16/465 , C07K2317/24 , C07K2317/31 , C07K2317/54 , C07K2317/55 , C07K2317/732 , C07K2319/00
摘要： Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.
摘要翻译：提供了变体免疫球蛋白，特别是人源化抗体多肽，以及其制备和使用方法。还提供了共同的免疫球蛋白序列和结构模型。

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