公开(公告)号：US08518404B2

公开(公告)日：2013-08-27

申请号：US13411409

申请日：2012-03-02

申请人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare ,  Jason Sagert

发明人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare ,  Jason Sagert

IPC分类号： A61K39/00 ,  A61K39/395 ,  C07K16/28 ,  C07K16/46

CPC分类号： C07K16/22 ,  C07K16/24 ,  C07K16/2818 ,  C07K16/2836 ,  C07K16/42 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/50 ,  C12N15/1034 ,  C12N15/1044

摘要： Activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM) are provided. Activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM are provided. Furthermore, ABPs which contain a first TBM, a second TBM and a CM are provided. The ABPs exhibit an “activatable” conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. Further provided are libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. Further provided are ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

摘要翻译： 提供了含有靶结合部分（TBM），掩蔽部分（MM）和可切割部分（CM）的可活化结合多肽（ABPs）。 提供含有含有抗原结合结构域（ABD），MM和CM的TBM的可活化抗体组合物。 此外，提供了包含第一TBM，第二TBM和CM的ABP。 ABP表现出“可激活”构象，使得当不能切割CM时，在存在能够切割CM的切割剂的情况下，TBM中的至少一种在未切割时难以接触。 还提供了候选ABP的图书馆，筛选鉴定这种ABP的方法和使用方法。 还提供了具有结合VEGF，CTLA-4或VCAM的TBM的ABP，具有结合VEGF的第一TBM的ABP和结合FGF的第二TBM，以及组合物和使用方法。

公开(公告)号：US20120237977A1

公开(公告)日：2012-09-20

申请号：US13411416

申请日：2012-03-02

申请人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare

发明人： Patrick Daugherty ,  Nancy Stagliano ,  Jerry Thomas ,  Kathryn Kamath ,  James W. West ,  Sanjay Khare

IPC分类号： C07K19/00 ,  C12P21/08 ,  C12P21/00

CPC分类号： C07K16/22 ,  C07K16/24 ,  C07K16/2818 ,  C07K16/2836 ,  C07K16/42 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/50 ,  C12N15/1034 ,  C12N15/1044

摘要： Activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM) are provided. Activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM are provided. Furthermore, ABPs which contain a first TBM, a second TBM and a CM are provided. The ABPs exhibit an “activatable” conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. Further provided are libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. Further provided are ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

公开(公告)号：US20110003973A1

公开(公告)日：2011-01-06

申请号：US11538331

申请日：2006-10-03

申请人： Cindy A. Sprecher ,  Julia E. Novak ,  James W. West ,  Scott R. Presnell ,  Richard D. Holly ,  Andrew J. Nelson

发明人： Cindy A. Sprecher ,  Julia E. Novak ,  James W. West ,  Scott R. Presnell ,  Richard D. Holly ,  Andrew J. Nelson

IPC分类号： C07K16/28

CPC分类号： C07K16/2866 ,  A61K38/00 ,  C07K14/7155 ,  C07K2317/73 ,  C07K2319/00

摘要： Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for soluble zalpha11 receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block zalpha11 Ligand activity in vitro and in vivo, and may be used in conjunction with zalpha11 Ligand and other cytokines to selectively stimulate the immune system. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

摘要翻译： 公开了可用作新型细胞因子拮抗剂的可溶性zalpha11受体的新型多肽组合，编码多肽的多核苷酸以及相关组合物和方法，以及用于检测刺激造血，淋巴和骨髓细胞增殖和/或发育的配体的方法 体外和体内。 配体结合受体多肽也可用于在体外和体内阻断zalpha11配体活性，并可与zalpha11配体和其他细胞因子结合使用以选择性刺激免疫系统。 本发明还包括生产蛋白质的方法，用途及其抗体。

公开(公告)号：US07763713B2

公开(公告)日：2010-07-27

申请号：US11538359

申请日：2006-10-03

申请人： Cindy A. Sprecher ,  Julia E. Novak ,  James W. West ,  Scott R. Presnell ,  Richard D. Holly ,  Andrew J. Nelson

发明人： Cindy A. Sprecher ,  Julia E. Novak ,  James W. West ,  Scott R. Presnell ,  Richard D. Holly ,  Andrew J. Nelson

IPC分类号： C07K14/435 ,  C07K14/52

CPC分类号： C07K16/2866 ,  A61K38/00 ,  C07K14/7155 ,  C07K2317/73 ,  C07K2319/00

摘要： Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for soluble zalpha11 receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block zalpha11 Ligand activity in vitro and in vivo, and may be used in conjunction with zalpha11 Ligand and other cytokines to selectively stimulate the immune system. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

摘要翻译： 公开了可用作新型细胞因子拮抗剂的可溶性zalpha11受体的新型多肽组合，编码多肽的多核苷酸以及相关组合物和方法，以及用于检测刺激造血，淋巴和骨髓细胞增殖和/或发育的配体的方法 体外和体内。 配体结合受体多肽也可用于在体外和体内阻断zalpha11配体活性，并可与zalpha11配体和其他细胞因子结合使用以选择性刺激免疫系统。 本发明还包括生产蛋白质的方法，用途及其抗体。

公开(公告)号：US20100167391A1

公开(公告)日：2010-07-01

申请号：US12107571

申请日：2008-04-22

申请人： Zeren Gao ,  Charles E. Hart ,  Christopher S. Piddington ,  Paul O. Sheppard ,  Kimberty E. Shoemaker ,  Debra G. Gilbertson ,  James W. West

发明人： Zeren Gao ,  Charles E. Hart ,  Christopher S. Piddington ,  Paul O. Sheppard ,  Kimberty E. Shoemaker ,  Debra G. Gilbertson ,  James W. West

IPC分类号： C12N5/071

CPC分类号： C07K14/52 ,  A01K2217/05 ,  A61K38/1858 ,  C07K14/475 ,  C12N2799/022

摘要： Polypeptide growth factors, methods of making them, polynucleotides encoding them, antibodies to them, and methods of using them are disclosed. The polypeptides comprise an amino acid segment that is at least 90% identical to residues 46-163 of SEQ ID NO:2 or residues 235-345 of SEQ ID NO:2. Multimers of the polypeptides are also disclosed. The polypeptides, multimeric proteins, and polynucleotides can be used in the study and regulation of cell and tissue development, as components of cell culture media, and as diagnostic agents.

摘要翻译： 公开了多肽生长因子，其制备方法，编码它们的多核苷酸，针对它们的抗体以及使用它们的方法。 多肽包含与SEQ ID NO：2的残基46-163或SEQ ID NO：2的残基235-345至少90％相同的氨基酸区段。 还公开了多肽的多聚体。 多肽，多聚体蛋白和多核苷酸可用于细胞和组织发育的研究和调节，作为细胞培养基的组分和诊断剂。

公开(公告)号：US20090311750A1

公开(公告)日：2009-12-17

申请号：US12139417

申请日：2008-06-13

申请人： James W. West

发明人： James W. West

IPC分类号： C12P21/04

CPC分类号： C07K16/00 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/622

摘要： In various embodiments, the present invention provides methods of converting a Fab molecule to a scFv molecule. The methods include amplifying the polynucleotide sequence of the variable light and variable heavy regions of the Fab molecule from the framework 1 to framework 4 sequences; adding one or more restriction endonuclease sites to the amino or carboxyl terminal of the amplified variable region sequence by PCR or ligation; adding one or more linker sequences to the amino or carboxyl terminal of the amplified variable region sequence by PCR or ligation. Additionally, in various embodiments the variable light chain sequence is either amino terminal or carboxyl terminal to the variable heavy chain sequence.

摘要翻译： 在各种实施方案中，本发明提供了将Fab分子转化成scFv分子的方法。 所述方法包括从框架1到框架4序列扩增Fab分子的可变轻链和可变重区的多核苷酸序列; 通过PCR或连接将一个或多个限制性内切核酸酶位点加入扩增的可变区序列的氨基或羧基末端; 通过PCR或连接将一个或多个接头序列添加到扩增的可变区序列的氨基或羧基末端。 另外，在各种实施方案中，可变轻链序列是可变重链序列的氨基末端或羧基末端。

公开(公告)号：US20090196882A1

公开(公告)日：2009-08-06

申请号：US11538319

申请日：2006-10-03

申请人： Cindy A. Sprecher ,  Julia E. Novak ,  James W. West ,  Scott R. Presnell ,  Richard D. Holly ,  Andrew J. Nelson

发明人： Cindy A. Sprecher ,  Julia E. Novak ,  James W. West ,  Scott R. Presnell ,  Richard D. Holly ,  Andrew J. Nelson

IPC分类号： A61K39/00 ,  C07K16/18

CPC分类号： C07K16/2866 ,  A61K38/00 ,  C07K14/7155 ,  C07K2317/73 ,  C07K2319/00

摘要： Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for soluble zalpha11 receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block zalpha11 Ligand activity in vitro and in vivo, and may be used in conjunction with zalpha11 Ligand and other cytokines to selectively stimulate the immune system. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

摘要翻译： 公开了可用作新型细胞因子拮抗剂的可溶性zalpha11受体的新型多肽组合，编码多肽的多核苷酸以及相关组合物和方法，以及用于检测刺激造血，淋巴和骨髓细胞增殖和/或发育的配体的方法 体外和体内。 配体结合受体多肽也可用于在体外和体内阻断zalpha11配体活性，并可与zalpha11配体和其他细胞因子结合使用以选择性刺激免疫系统。 本发明还包括生产蛋白质的方法，用途及其抗体。

公开(公告)号：US07387885B2

公开(公告)日：2008-06-17

申请号：US11021088

申请日：2004-12-22

申请人： Zeren Gao ,  Charles E. Hart ,  Christopher S. Piddington ,  Paul O. Sheppard ,  Kimberly E. Shoemaker ,  Debra G. Gilbertson ,  James W. West

发明人： Zeren Gao ,  Charles E. Hart ,  Christopher S. Piddington ,  Paul O. Sheppard ,  Kimberly E. Shoemaker ,  Debra G. Gilbertson ,  James W. West

IPC分类号： C12N15/12

CPC分类号： C07K14/52 ,  A01K2217/05 ,  A61K38/1858 ,  C07K14/475 ,  C12N2799/022

摘要： Polypeptide growth factors, methods of making them, polynucleotides encoding them, antibodies to them, and methods of using them are disclosed. The polypeptides comprise an amino acid segment that is at least 90% identical to residues 46-163 of SEQ ID NO:2 or residues 235-345 of SEQ ID NO:2. Multimers of the polypeptides are also disclosed. The polypeptides, multimeric proteins, and polynucleotides can be used in the study and regulation of cell and tissue development, as components of cell culture media, and as diagnostic agents.

摘要翻译： 公开了多肽生长因子，其制备方法，编码它们的多核苷酸，针对它们的抗体以及使用它们的方法。 多肽包含与SEQ ID NO：2的残基46-163或SEQ ID NO：2的残基235-345至少90％相同的氨基酸区段。 还公开了多肽的多聚体。 多肽，多聚体蛋白和多核苷酸可用于细胞和组织发育的研究和调节，作为细胞培养基的组分和诊断剂。

公开(公告)号：US06777539B2

公开(公告)日：2004-08-17

申请号：US09825561

申请日：2001-04-03

申请人： Cindy A. Sprecher ,  Julia E. Novak ,  James W. West ,  Scott R. Presnell ,  Richard D. Holly ,  Andrew J. Nelson

发明人： Cindy A. Sprecher ,  Julia E. Novak ,  James W. West ,  Scott R. Presnell ,  Richard D. Holly ,  Andrew J. Nelson

IPC分类号： C07K14435

CPC分类号： C07K16/2866 ,  A61K38/00 ,  C07K14/7155 ,  C07K2317/73 ,  C07K2319/00

摘要： Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for soluble zalpha11 receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block zlapha11 Ligand activity in vitro and in vivo, and may be used in conjunction with zalpha11 Ligand and other cytokines to selectively stimulate the immune system. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

摘要翻译： 公开了可用作新型细胞因子拮抗剂的可溶性zalpha11受体的新型多肽组合，编码多肽的多核苷酸以及相关组合物和方法，以及用于检测刺激造血，淋巴和骨髓细胞增殖和/或发育的配体的方法 体外和体内。 配体结合受体多肽也可用于在体外和体内阻断zlapha11配体活性，并可与zalpha11配体和其他细胞因子结合使用以选择性刺激免疫系统。 本发明还包括生产蛋白质的方法，用途及其抗体。

公开(公告)号：US6136964A

公开(公告)日：2000-10-24

申请号：US618651

申请日：1996-03-19

申请人： David W. Leung ,  James W. West ,  Christopher K. Tompkins

发明人： David W. Leung ,  James W. West ,  Christopher K. Tompkins

IPC分类号： C12N9/10 ,  C12N15/54 ,  C07H21/04 ,  C12N9/12

CPC分类号： C12N9/1029

摘要： There is disclosed cDNA sequences and polypeptides having the enzyme lysophosphatidic acid acyltransferase (LPAAT) activity. LPAAT is also known as 1-acyl sn-glycerol-3-phosphate acyltransferase.

摘要翻译： 公开了具有酶溶血磷脂酸酰基转移酶（LPAAT）活性的cDNA序列和多肽。 LPAAT也称为1-酰基sn-甘油-3-磷酸酰基转移酶。