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31. 发明授权

US07186805B2 IL-21 antagonists 有权
标题翻译： IL-21拮抗剂
公开(公告)号：US07186805B2
公开(公告)日：2007-03-06
申请号：US11174398
申请日：2005-07-01
申请人： Scott R. Presnell , James W. West , Julia E. Novak
发明人： Scott R. Presnell , James W. West , Julia E. Novak
IPC分类号： C07K14/47 , C07K14/475
CPC分类号： C07K14/54 , A61K38/00 , C07K14/7155 , C07K2319/00 , C12N2799/026
摘要： The polypeptides, and the polynucleotides encoding for them, described herein are IL-21 antagonists that bind with specificity and exhibit an EC50 that is not detectable in receptor binding studies. These molecules have mutations in the D helix of the IL-21 molecule, and can be used to inhibit the activity of IL-21 with its cognate receptor.
摘要翻译：本文所述的多肽和编码它们的多核苷酸是与特异性结合并显示在受体结合研究中不可检测的EC 50的IL-21拮抗剂。这些分子在IL-21分子的D螺旋中具有突变，并且可用于以其同源受体抑制IL-21的活性。

32. 发明授权

US5756511A Method for treating symptoms of a neurodegenerative condition 失效
标题翻译：治疗神经退行性疾病症状的方法
公开(公告)号：US5756511A
公开(公告)日：1998-05-26
申请号：US416270
申请日：1995-04-03
申请人： James W. West , David W. Leung , J. Peter Klein , Gail E. Underiner , Anil M. Kumar
发明人： James W. West , David W. Leung , J. Peter Klein , Gail E. Underiner , Anil M. Kumar
IPC分类号： A61K31/522 , A01N43/90
CPC分类号： A61K31/522
摘要： A method for treating symptoms of Alzheimer's Disease by administering an effective amount of a compound, racemate, isolated R or S enantionmer, solvate, hydrate or salt having the formula: X--terminal heterocyclic moiety. In the above formula, the terminal heterocyclic moiety is a 3,7-dimethylxanthinyl, 3-methylxanthinyyl or xanthinyl moiety and X is: ##STR1## n is zero or an integer from one to four; and m is an integer from seven to fourteen. For compounds useful in the inventive method, R.sub.1 and R.sub.2 are hydrogen, a straight or branched chain alkyl, alkenyl or alkynyl of up to twenty carbon atoms in length or --(CH.sub.2).sub.w R.sub.5. w may be an integer from one to twenty and R.sub.5 is preferably an hydroxyl, halo C.sub.1-8 alkoxyl group or a substituted or unsubstituted carbocycle or heterocycle. R.sub.3 in compounds useful in the inventive method may be either an hydroxyl group, an oxygen atom, the single bond represented being instead a double bond, or --O--R.sub.4, R.sub.4 being a C.sub.1-6 oxoalkyl.
摘要翻译：通过施用有效量的具有下式的化合物，外消旋物，分离的R或S对映体，溶剂合物，水合物或盐，来治疗阿尔茨海默病症状的方法：在上式中，末端杂环部分为 3,7-二甲基黄烷基，3-甲基黄嘌呤基或xanthinyl部分，X为：n为0或1至4的整数; m为7〜14的整数。对于可用于本发明方法的化合物，R 1和R 2是氢，直链或支链烷基，链烯基或炔基，其长度为至多20个碳原子或 - （CH 2）w R 5。 w可以是从一到二十的整数，R 5优选为羟基，卤代C 1-8烷氧基或取代或未取代的碳环或杂环。可用于本发明方法的化合物中的R 3可以是羟基，氧原子，所表示的单键代替双键，或-O-R4，R4是C1-6氧代烷基。

33. 发明授权

US08563269B2 Modified antibody compositions, methods of making and using thereof 有权
标题翻译：改良的抗体组合物，其制备和使用方法
公开(公告)号：US08563269B2
公开(公告)日：2013-10-22
申请号：US13315623
申请日：2011-12-09
申请人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Frederick W. Gluck , Jason Sagert , Patrick Daugherty
发明人： Nancy E. Stagliano , James W. West , Kathryn Kamath , Paul H. Bessette , Frederick W. Gluck , Jason Sagert , Patrick Daugherty
IPC分类号： C12P21/08 , C12N15/74 , C12N9/00 , C12N15/62 , C07H21/04 , C07K16/28 , C07K16/46 , C07K14/00
CPC分类号： C07K16/22 , A61K39/3955 , A61K47/6845 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K7/06 , C07K7/08 , C07K14/001 , C07K16/00 , C07K16/18 , C07K16/241 , C07K16/28 , C07K16/2818 , C07K16/2845 , C07K16/2863 , C07K16/2866 , C07K16/2875 , C07K16/2896 , C07K16/30 , C07K2317/20 , C07K2317/21 , C07K2317/34 , C07K2317/40 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/92 , C07K2317/94 , C07K2319/30 , C07K2319/31 , C07K2319/50 , G01N33/6845 , G01N33/6854
摘要： The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.
摘要翻译：本公开提供了修饰的抗体，其含有用掩蔽部分（MM）修饰的抗体或抗体片段（AB）。这样的修饰抗体可以进一步与可切割部分（CM）偶联，产生可激活抗体（AAs），其中CM能够被切割，还原，光解或以其它方式修饰。 AAs可以表现出可激活的构象，使得AB在例如通过在能够切割，还原或光解所述蛋白质的试剂存在下，通过CM的切割，还原或光解来除去MM来更容易地进行靶标厘米。本公开进一步提供了制备和使用这些修饰抗体和可激活抗体的方法。

34. 发明授权

US08518404B2 Activatable binding polypeptides and methods of identification and use thereof 有权
标题翻译：可活化的结合多肽及其鉴定和使用的方法
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。

35. 发明申请

US20120237977A1 Activatable Binding Polypeptides and Methods of Identification and Use Thereof 有权
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.

36. 发明申请

US20110003973A1 ANTIBODIES TO ZALPHA11 CYTOKINE RECEPTORS 审中-公开
标题翻译： ZALPHA11细胞因子受体的抗体
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。

37. 发明授权

US07763713B2 Zalpha11 cytokine receptors 有权
标题翻译： Zalpha11细胞因子受体
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。

38. 发明申请

US20090311750A1 METHODS OF CONVERTING FAB SEQUENCES INTO SINGLE CHAIN ANTIBODY SEQUENCES 审中-公开
标题翻译：将FAB序列转化为单链抗体序列的方法
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。

39. 发明申请

US20090196882A1 METHODS OF PRODUCING ANTIBODIES TO ZALPHA11 CYTOKINE RECEPTORS 审中-公开
标题翻译：向ZALPHA11细胞因子受体生产抗体的方法
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。

40. 发明授权

US06777539B2 Soluble zalpha11 cytokine receptors 有权
标题翻译：可溶性zalpha11细胞因子受体
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。

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