公开(公告)号：US07235648B1

公开(公告)日：2007-06-26

申请号：US09258600

申请日：1999-02-26

申请人： Dana M. Fowlkes ,  Jim Broach ,  John Manfredi ,  Christine Klein ,  Andrew J. Murphy ,  Jeremy Paul ,  Joshua Trueheart

发明人： Dana M. Fowlkes ,  Jim Broach ,  John Manfredi ,  Christine Klein ,  Andrew J. Murphy ,  Jeremy Paul ,  Joshua Trueheart

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12P33/02 ,  C12N1/14 ,  C07K14/00 ,  C12N15/63

CPC分类号： C12N15/1086 ,  C07K14/395

摘要： Yeast cells are engineered to express both a surrogate of a pheromone system protein (e.g., enzymes involved in maturation of α-factor, transporters of a-factor, pheromone receptors, etc.) and a potential peptide modulator of the surrogate, in such a manner that the inhibition or activation of the surrogate affects a screenable or selectable trait of the yeast cells. Various additional features improve the signal-to-noise ratio of the screening/selection system.

摘要翻译： 酵母细胞被设计成表达信息素系统蛋白质的替代物（例如，参与α因子成熟的酶，α-因子的转运蛋白，信息素受体等）和代理的潜在的肽调节剂，在这样的 替代物的抑制或活化影响酵母细胞的可筛选或选择性状的方式。 各种附加功能提高了筛选/选择系统的信噪比。

公开(公告)号：US07122305B2

公开(公告)日：2006-10-17

申请号：US09747774

申请日：2000-12-21

申请人： Christine A. Klein ,  Andrew J. Murphy ,  Dana M. Fowlkes ,  James Broach ,  John Manfredi ,  Jeremy Paul ,  Joshua Trueheart

发明人： Christine A. Klein ,  Andrew J. Murphy ,  Dana M. Fowlkes ,  James Broach ,  John Manfredi ,  Jeremy Paul ,  Joshua Trueheart

IPC分类号： C12Q1/68 ,  G01N33/53 ,  C12N1/20 ,  C12N1/14

CPC分类号： C12N15/81 ,  C07K14/395 ,  C07K2319/02

摘要： The present invention makes available a rapid, effective assay for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assay enables rapid screening of large numbers of polypeptides in a library to identifying those polypeptides which induce or antagonize receptor bioactivity. The subject assay is particularly amenable for identifying surrogate ligands for orphan receptors.

公开(公告)号：US10143186B2

公开(公告)日：2018-12-04

申请号：US13022759

申请日：2011-02-08

申请人： John McWhirter ,  Lynn Macdonald ,  Sean Stevens ,  David R. Buckler ,  Andrew J. Murphy

发明人： John McWhirter ,  Lynn Macdonald ,  Sean Stevens ,  David R. Buckler ,  Andrew J. Murphy

IPC分类号： A01K67/027 ,  C07K16/46 ,  C07K16/00 ,  C07K16/28 ,  C12N15/85 ,  C12N15/90 ,  C07K16/22

摘要： A genetically modified mouse is provided, wherein the mouse is incapable of rearranging and expressing an endogenous mouse immunoglobulin light chain variable sequence, wherein the mouse expresses only one or two human light chain variable domains encoded by human immunoglobulin sequences operably linked to the mouse kappa (κ) constant gene at the endogenous mouse κ locus, wherein the mouse expresses a reverse chimeric antibody having a light chain variable domain derived from one of only two human light chain variable region gene segments and a mouse κ constant domain, and a human heavy chain variable domain and a mouse heavy chain constant domain, from an endogenous mouse heavy chain locus. Bispecific epitope-binding proteins that are fully human are provided, comprising two different heavy chains that associate with an identical light chain that comprises a variable domain derived from one of two different human light chain variable region gene segments.

公开(公告)号：US20130171149A1

公开(公告)日：2013-07-04

申请号：US13517662

申请日：2012-06-14

申请人： Mark W. Sleeman ,  Viktoria Gusarova ,  Andrew J. Murphy

发明人： Mark W. Sleeman ,  Viktoria Gusarova ,  Andrew J. Murphy

IPC分类号： C07K16/22 ,  A61K45/06 ,  A61K39/395

CPC分类号： C07K16/22 ,  A61K31/455 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/76 ,  C07K2317/92 ,  A61K2300/00

摘要： A fully human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits or interferes with at least one activity of human angiopoietin-like protein 3 (hANGPTL3) is provided. The human anti-hANGPTL3 antibodies are useful in treating diseases or disorders associated with ANGPTL3, such as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including hypertriglyceridemia, hypercholesterolemia, chylomicronemia, and so forth. Furthermore, the anti-hANGPTL3 antibodies can be administered to a subject in need thereof to prevent or treat diseases or disorders, for which abnormal lipid metabolism is a risk factor. Such diseases or disorders include cardiovascular diseases, such as atherosclerosis and coronary artery diseases; acute pancreatitis; nonalcoholic steatohepatitis (NASH); diabetes; obesity; and the like.

公开(公告)号：US08425907B2

公开(公告)日：2013-04-23

申请号：US13325098

申请日：2011-12-14

申请人： Lynn MacDonald ,  Andrew J. Murphy ,  Nicholas J. Papadopoulos ,  Marc R. Morra ,  Robert R. Salzler ,  Michael L. LaCroix-Fralish

发明人： Lynn MacDonald ,  Andrew J. Murphy ,  Nicholas J. Papadopoulos ,  Marc R. Morra ,  Robert R. Salzler ,  Michael L. LaCroix-Fralish

IPC分类号： A61K39/00 ,  A61K39/395

CPC分类号： A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/28 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/76

摘要： The present invention provides methods for treating pruritus by blocking human protease activated receptor-2 (PAR2) activity. The methods of the invention can be used to treat pruritus associated with atopic dermatitis, psoriasis, burn scarring, hypertrophic scarring, keloids, renal failure or hepatic failure. The methods of the invention include administering an antibody or antigen-binding fragment thereof that specifically binds human PAR2.

摘要翻译： 本发明提供了通过阻断人蛋白酶活化的受体-2（PAR2）活性来治疗瘙痒的方法。 本发明的方法可用于治疗与特应性皮炎，银屑病，烧伤瘢痕，肥大性瘢痕形成，瘢痕疙瘩，肾衰竭或肝衰竭相关的瘙痒。 本发明的方法包括施用特异性结合人PAR2的抗体或其抗原结合片段。

公开(公告)号：US20130045492A1

公开(公告)日：2013-02-21

申请号：US13488628

申请日：2012-06-05

申请人： Robert Babb ,  John McWhirter ,  Lynn MacDonald ,  Sean Stevens ,  Samuel Davis ,  David R. Buckler ,  Karolina A. Hosiawa ,  Andrew J. Murphy

发明人： Robert Babb ,  John McWhirter ,  Lynn MacDonald ,  Sean Stevens ,  Samuel Davis ,  David R. Buckler ,  Karolina A. Hosiawa ,  Andrew J. Murphy

IPC分类号： C12P21/00 ,  G01N21/64 ,  G01N33/566

CPC分类号： C07K16/468 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C07K16/00 ,  C07K16/28 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/515 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30 ,  C12N15/8509 ,  C12N2800/204

摘要： A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided. Bispecific antibodies capable of binding first and second antigens are provided, wherein the first and second antigens are separate epitopes of a single protein or separate epitopes on two different proteins are provided.

摘要翻译： 提供遗传修饰的小鼠，其中小鼠表达免疫球蛋白轻链总谱，其特征在于有限数量的轻链可变结构域。 提供的小鼠在其种系中仅来自有限谱系的一个或几个免疫球蛋白轻链可变结构域。 提供了使用如本文所述的小鼠制备具有通用轻链的双特异性抗体的方法，包括人轻链可变区。 提供了适合用于多特异性结合蛋白（例如双特异性抗体）和宿主细胞的人可变区的方法。 提供了能够结合第一和​​第二抗原的双特异性抗体，其中第一和第二抗原是单个蛋白质的分离表位或两种不同蛋白质上的分离表位。

公开(公告)号：US20120260357A1

公开(公告)日：2012-10-11

申请号：US13466225

申请日：2012-05-08

申请人： Lynn Macdonald ,  Naxin Tu ,  Cagan Gurer ,  Sean Stevens ,  Andrew J. Murphy

发明人： Lynn Macdonald ,  Naxin Tu ,  Cagan Gurer ,  Sean Stevens ,  Andrew J. Murphy

IPC分类号： A01K67/027 ,  C12N5/10

CPC分类号： A61K49/0008 ,  A01K67/0276 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0387 ,  C07K14/70535 ,  G01N33/5014

摘要： Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.

摘要翻译： 提供了遗传修饰的非人动物以及用于制备和使用它们的方法和组合物，其中所述遗传修饰包括内源性低亲和力FcγR基因座的缺失，并且其中所述小鼠能够表达功能性FcRγ-链。 描述了转基因小鼠，包括从内源性FcγR基因座表达低亲和性人FcγR基因的小鼠，其中小鼠包含功能性FcRγ-链。 提供了在宿主免疫系统的辅助细胞上表达多达五个低亲和力的人FcγR基因的转基因小鼠。

公开(公告)号：US20120021409A1

公开(公告)日：2012-01-26

申请号：US13093156

申请日：2011-04-25

申请人： John McWhirter ,  Lynn MacDonald ,  Sean Stevens ,  Samuel Davis ,  David R. Buckler ,  Karolina A. Hosiawa ,  Andrew J. Murphy

发明人： John McWhirter ,  Lynn MacDonald ,  Sean Stevens ,  Samuel Davis ,  David R. Buckler ,  Karolina A. Hosiawa ,  Andrew J. Murphy

IPC分类号： C12Q1/68 ,  G01N33/566 ,  A01K67/027

摘要： A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making light chain variable regions in mice, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, are provided.

公开(公告)号：US20110154512A1

公开(公告)日：2011-06-23

申请号：US12971080

申请日：2010-12-17

申请人： Lynn MACDONALD ,  Naxin Tu ,  Cagan Gurer ,  Sean Stevens ,  Andrew J. Murphy

发明人： Lynn MACDONALD ,  Naxin Tu ,  Cagan Gurer ,  Sean Stevens ,  Andrew J. Murphy

IPC分类号： A01K67/027 ,  G01N33/00 ,  C12Q1/18 ,  G01N33/53

CPC分类号： A61K49/0008 ,  A01K67/0276 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0387 ,  C07K14/70535 ,  G01N33/5014

摘要： Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.

摘要翻译： 提供了遗传修饰的非人动物以及用于制备和使用它们的方法和组合物，其中所述遗传修饰包括内源性低亲和力FcγR基因座的缺失，并且其中所述小鼠能够表达功能性FcRγ-链。 描述了转基因小鼠，包括从内源性FcγR基因座表达低亲和性人FcγR基因的小鼠，其中小鼠包含功能性FcRγ-链。 提供了在宿主免疫系统的辅助细胞上表达多达五个低亲和力的人FcγR基因的转基因小鼠。

公开(公告)号：US20110059095A1

公开(公告)日：2011-03-10

申请号：US12877133

申请日：2010-09-08

申请人： Lynn MacDonald ,  Andrew J. Murphy ,  Nicholas J. Papadopoulos ,  Marc R. Morra ,  Robert R. Salzler ,  Michael L. LaCroix-Fralish

发明人： Lynn MacDonald ,  Andrew J. Murphy ,  Nicholas J. Papadopoulos ,  Marc R. Morra ,  Robert R. Salzler ,  Michael L. LaCroix-Fralish

IPC分类号： A61K39/395 ,  C07K16/28 ,  A61P29/00 ,  A61P17/04 ,  A61P11/06 ,  A61P19/02 ,  A61P1/00 ,  A61P1/04 ,  A61P1/18 ,  A61P35/00

CPC分类号： A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/28 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/76

摘要： The present invention provides antibodies that bind to protease-activated receptor-2 (PAR-2) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PAR-2. The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more PAR-2 biological activities, including the treatment of pain conditions, inflammatory conditions and gastrointestinal conditions.

摘要翻译： 本发明提供了结合蛋白酶激活的受体-2（PAR-2）的抗体及其使用方法。 根据本发明的某些实施方案，抗体是与人类PAR-2结合的完全人抗体。 本发明的抗体尤其用于治疗与一种或多种PAR-2生物活性相关的疾病和病症，包括治疗疼痛病症，炎性病症和胃肠病症。