公开(公告)号：US07585504B2

公开(公告)日：2009-09-08

申请号：US11254679

申请日：2005-10-21

申请人： Herren Wu ,  Christian B. Allan ,  Changshou Gao ,  Ling-Ling An ,  Peter Kiener ,  Su-Yau Mao ,  Anthony Coyle

发明人： Herren Wu ,  Christian B. Allan ,  Changshou Gao ,  Ling-Ling An ,  Peter Kiener ,  Su-Yau Mao ,  Anthony Coyle

IPC分类号： A61K39/395

CPC分类号： C07K16/24 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30 ,  Y02A50/412

摘要： Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

摘要翻译： 公开了用于抑制促炎细胞因子从脊椎动物细胞中释放并抑制患者炎性细胞因子级联的组合物和方法。 组合物包含例如特异性结合HMG1的高亲和力抗体及其抗原性片段。 本发明的高亲和力抗体和包含其的药物组合物可用于许多目的，例如作为针对广泛范围的炎性疾病和病症的治疗剂，例如败血症，类风湿性关节炎，腹膜炎，克罗恩病，再灌注损伤，败血症 内毒素性休克，囊性纤维化，心内膜炎，牛皮癣，牛皮癣关节炎，关节炎，过敏性休克，器官缺血，再灌注损伤和同种异体移植排斥。 此外，本发明的高亲和力抗体可用作诊断抗体。

公开(公告)号：US20090130111A1

公开(公告)日：2009-05-21

申请号：US12067396

申请日：2006-09-28

申请人： Herren Wu ,  Peter Kiener ,  Partha S. Chowdhury ,  James F. Young

发明人： Herren Wu ,  Peter Kiener ,  Partha S. Chowdhury ,  James F. Young

IPC分类号： A61K39/395 ,  C07K16/18 ,  C12N15/11 ,  C40B30/04 ,  C12N5/06

CPC分类号： G01N33/56972 ,  A61K2039/505 ,  C07K16/4291 ,  C07K2317/52 ,  C07K2317/55 ,  Y10S424/805 ,  Y10S530/862 ,  Y10S530/868

摘要： The present invention relates to the discovery of antibodies that bind to novel epitopes present on membrane-anchored immunoglobulins and which bind to these novel epitopes on the surface of B cells and plasma cells. In addition, the antibodies of the present invention can mediate ADCC and can be useful to deplete those B cells and plasma cells expressing the novel epitopes of the invention. The antibodies of the present invention can be useful for the treatment of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells. Accordingly the present invention also provides compositions and methods for the prevention, management, treatment or amelioration of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells.

摘要翻译： 本发明涉及结合存在于膜锚定的免疫球蛋白上并与B细胞和浆细胞表面上的这些新表位结合的抗体的发现。 此外，本发明的抗体可以介导ADCC，并且可用于消耗表达本发明的新表位的那些B细胞和浆细胞。 本发明的抗体可用于治疗由B细胞的单克隆扩增引起的B细胞介导的疾病和疾病。 因此，本发明还提供了用于预防，治疗或改善由B细胞的单克隆扩增引起的B细胞介导的疾病和疾病的组合物和方法。

公开(公告)号：US20090023900A1

公开(公告)日：2009-01-22

申请号：US12102818

申请日：2008-04-14

申请人： William D. Huse ,  Herren Wu

发明人： William D. Huse ,  Herren Wu

IPC分类号： C07K16/18

CPC分类号： C07K16/2848 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565

摘要： The invention provides enhanced LM609 grafted antibodies exhibiting selective binding affinity to αvβ3, or a functional fragment thereof. The invention also provides nucleic acid molecules encoding the enhanced LM609 grafted antibodies. Additionally provided are methods of inhibiting a function of αvβ3 by contacting αvβ3 with an enhanced LM609 grafted antibody.

摘要翻译： 本发明提供了增强的显示对α2β3的选择性结合亲和力的LM609接枝抗体或其功能性片段。 本发明还提供编码增强的LM609接枝抗体的核酸分子。 另外提供的方法是通过使α受体结合的LM609接枝抗体接触alphavbeta3来抑制alphavbeta3的功能。

公开(公告)号：US20070196916A1

公开(公告)日：2007-08-23

申请号：US11643982

申请日：2006-12-20

申请人： James Young ,  Scott Koenig ,  Leslie Johnson ,  William Huse ,  Jeffrey Watkins ,  Herren Wu

发明人： James Young ,  Scott Koenig ,  Leslie Johnson ,  William Huse ,  Jeffrey Watkins ,  Herren Wu

IPC分类号： C07H21/04 ,  A61K39/395 ,  C12N5/06 ,  C12N5/16

CPC分类号： C07K16/1027 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/565

摘要： The present invention encompasses novel antibodies and fragments thereof which immunospecifically bind to one or more RSV antigens and compositions comprising said antibodies and antibody fragments. The present invention encompasses methods preventing respiratory syncytial virus (RSV) infection in a human, comprising administering to said human a prophylactically effective amount of one or more antibodies or fragments thereof that immunospecifically bind to one or more RSV antigens, wherein a certain serum titer of said antibodies or antibody fragments is achieved in said human subject. The present invention also encompasses methods for treating or ameliorating symptoms associated with a RSV infection in a human, comprising administering to said human a therapeutically effective amount of one or more antibodies or fragments thereof that immunospecifically bind to one or more RSV antigens, wherein a certain serum titer of said antibodies or antibody fragments is achieved in said human subject. The present invention further encompasses compositions comprising antibodies or fragments thereof that immunospecifically bind to a RSV antigen, and methods using said compositions for detection or diagnosis of a RSV infection.

公开(公告)号：US20060115485A1

公开(公告)日：2006-06-01

申请号：US11263230

申请日：2005-10-31

申请人： Genevieve Losonsky ,  Edward Connor ,  James Young ,  Herren Wu ,  William Dall'Acqua

发明人： Genevieve Losonsky ,  Edward Connor ,  James Young ,  Herren Wu ,  William Dall'Acqua

IPC分类号： A61K39/42

CPC分类号： C07K16/1027 ,  A61K2039/505 ,  A61K2039/543 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/72 ,  C07K2317/92 ,  C07K2317/94

摘要： The present invention provides methods for preventing, managing, treating and/or ameliorating a Respiratory Syncytial Virus (RSV) infection (e.g., acute RSV disease, or a RSV upper respiratory tract infection (URI) and/or lower respiratory tract infection (LRI)), otitis media (preferably, stemming from, caused by or associated with a RSV infection, such as a RSV URI and/or LRI), and/or a symptom or respiratory condition relating thereto (e.g., asthma, wheezing, and/or reactive airway disease (RAD)) in a subject, comprising administering to said human an effective amount of one or more antibodies that immunospecifically bind to one or more RSV antigens with a high affinity and/or high avidity. In some embodiments, one or more antibodies comprise a modified IgG constant domain, or FcRn-binding fragment thereof resulting in longer in vivo serum half-life. In particular embodiments the methods of the invention comprising administering to subject an effective amount of one or more modified antibodies that immunospecifically bind to one or more RSV antigens with an association rate (kon) of at least 2×105 M−1s−1 and a dissociation rate (koff) of less than 5×10−4 s−1.

摘要翻译： 本发明提供了用于预防，治疗和/或改善呼吸道合胞病毒（RSV）感染（例如急性RSV疾病或RSV上呼吸道感染（URI））和/或下呼吸道感染（LRI）的方法， ），中耳炎（优选来源于，由RSV感染引起或与RSV感染相关联，例如RSV URI和/或LRI），和/或与其相关的症状或呼吸病症（例如，哮喘，喘鸣和/或 反应性气道疾病（RAD）），包括向所述人施用有效量的一种或多种以高亲和力和/或高亲合力免疫特异性结合一种或多种RSV抗原的抗体。 在一些实施方案中，一种或多种抗体包含修饰的IgG恒定结构域或其FcRn结合片段，导致更长的体内血清半衰期。 在具体实施方案中，本发明的方法包括施用有效量的一种或多种经免疫特异性结合一种或多种RSV抗原的修饰的抗体，其具有至少2×10 6的结合速率（kNI） 小于5×10-6的解离速率（k >） 4 -1 。

公开(公告)号：US20050147616A1

公开(公告)日：2005-07-07

申请号：US10962285

申请日：2004-10-08

申请人： James Young ,  Scott Koenig ,  Leslie Johnson ,  William Huse ,  Jeffrey Watkins ,  Herren Wu

发明人： James Young ,  Scott Koenig ,  Leslie Johnson ,  William Huse ,  Jeffrey Watkins ,  Herren Wu

IPC分类号： C07K16/10 ,  C12P21/08 ,  A61K39/42 ,  C07H21/04 ,  C07K16/08 ,  C12N5/06 ,  C12Q1/70

CPC分类号： C07K16/1027 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/565

摘要： The present invention encompasses novel antibodies and fragments thereof which immunospecifically bind to one or more RSV antigens and compositions comprising said antibodies and antibody fragments. The present invention encompasses methods preventing respiratory syncytial virus (RSV) infection in a human, comprising administering to said human a prophylactically effective amount of one or more antibodies or fragments thereof that immunospecifically bind to one or more RSV antigens, wherein a certain serum titer of said antibodies or antibody fragments is achieved in said human subject. The present invention also encompasses methods for treating or ameliorating symptoms associated with a RSV infection in a human, comprising administering to said human a therapeutically effective amount of one or more antibodies or fragments thereof that immunospecifically bind to one or more RSV antigens, wherein a certain serum titer of said antibodies or antibody fragments is achieved in said human subject. The present invention further encompasses compositions comprising antibodies or fragments thereof that immunospecifically bind to a RSV antigen, and methods using said compositions for detection or diagnosis a RSV infection

摘要翻译： 本发明包括免疫特异性结合一种或多种RSV抗原的新型抗体及其片段，以及包含所述抗体和抗体片段的组合物。 本发明包括预防人类呼吸道合胞病毒（RSV）感染的方法，包括向所述人施用预防有效量的一种或多种免疫特异性结合一种或多种RSV抗原的抗体或其片段，其中一定的血清滴度为 所述抗体或抗体片段在所述人受试者中实现。 本发明还包括用于治疗或改善与人类RSV感染有关的症状的方法，包括向所述人施用治疗有效量的一种或多种免疫特异性结合一种或多种RSV抗原的抗体或其片段，其中一定 所述抗体或抗体片段的血清滴度在所述人受试者中实现。 本发明还包括包含免疫特异性结合RSV抗原的抗体或其片段的组合物，以及使用所述组合物检测或诊断RSV感染的方法

公开(公告)号：US20050064438A1

公开(公告)日：2005-03-24

申请号：US10697400

申请日：2003-10-30

申请人： William Huse ,  Jeffry Watkins ,  Herren Wu

发明人： William Huse ,  Jeffry Watkins ,  Herren Wu

IPC分类号： C07K16/28 ,  C07K16/36 ,  C07K16/46 ,  C12Q1/68 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00

CPC分类号： C07K16/465 ,  C07K16/00 ,  C07K16/2878 ,  C07K16/36 ,  C07K16/464 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/92

摘要： The invention provides a method of conferring donor CDR binding affinity onto an antibody acceptor variable region framework. The method consists of: (a) constructing a population of altered antibody variable region encoding nucleic acids, said population comprising encoding nucleic acids for an acceptor variable region framework containing a plurality of different amino acids at one or more acceptor framework region amino acid positions and donor CDRs containing a plurality of different amino acids at one or more donor CDR amino acid positions; (b) expressing said population of altered variable region encoding nucleic acids, and (c) identifying one or more altered variable regions having binding affinity substantially the same or greater than the donor CDR variable region. The acceptor variable region framework can be a heavy or light chain variable region framework and the populations of heavy and light chain altered variable regions can be expressed alone to identify heavy or light chains having binding affinity substantially the same or greater than the donor CDR variable region. The populations of heavy and light chains additionally can be coexpressed to identify heteromeric altered variable region binding fragments. The invention also provides a method of simultaneously grafting and optimizing the binding affinity of a variable region binding fragment. The method consists of: (a) constructing a population of altered heavy chain variable region encoding nucleic acids comprising an acceptor variable region framework containing donor CDRs and a plurality of different amino acids at one or more framework region and CDR amino acid positions; (b) constructing a population of altered light chain variable region encoding nucleic acids comprising an acceptor variable region framework containing donor CDRs and a plurality of different amino acids at one or more framework regions and CDR amino acid positions; (c) coexpressing said populations of heavy and light chain variable region encoding nucleic acids to produce diverse combinations of heteromeric variable region binding fragments, and (d) identifying one or more heteromeric variable region binding fragments having affinity substantially the same or greater than the donor CDR heteromeric variable region binding fragment. A method of optimizing the binding affinity of an antibody variable region is also provided. The method consists of: (a) constructing a population of antibody variable region encoding nucleic acids, said population comprising two or more CDRs containing a plurality of different amino acids at one or more CDR amino acid positions; (b) expressing said population of variable region encoding nucleic acids, and (c) identifying one or more variable regions having binding affinity substantially the same or greater than the donor CDR variable region. The variable region populations can be heavy or light chains and can be expressed as individual populations or they can be coexpressed to produce heteromeric variable region binding fragments.

公开(公告)号：US20050048617A1

公开(公告)日：2005-03-03

申请号：US10920899

申请日：2004-08-18

申请人： Herren Wu ,  William Dall-Acqua ,  Melissa Damschroder

发明人： Herren Wu ,  William Dall-Acqua ,  Melissa Damschroder

IPC分类号： C07H21/04 ,  C07K16/00 ,  C07K16/40 ,  C12N15/13 ,  A61K39/395 ,  C07K16/18

CPC分类号： C07K16/005 ,  C07H21/04 ,  C07K16/40 ,  C12N15/1037 ,  C12Q2563/131

摘要： The present invention relates to methods of reengineering or reshaping antibodies to reduce the immunogenicity of the antibodies, while maintaining the immunospecificity of the antibodies for an antigen. In particular, the present invention provides methods of producing antibodies immunospecific for an antigen by synthesizing a combinatorial library comprising complementarity determining regions (CDRs) from a donor antibody fused in frame to framework regions from a sub-bank of framework regions. The present invention also provides antibodies produced by the methods of the invention.

摘要翻译： 本发明涉及重新设计或重塑抗体以降低抗体免疫原性的方法，同时保持针对抗原的抗体的免疫特异性。 特别地，本发明提供了通过合成包含来自框架区域的子库的框架区域融合的供体抗体的互补决定区（CDR）的组合文库的组合文库来产生针对抗原免疫特异性的抗体的方法。 本发明还提供通过本发明的方法制备的抗体。

公开(公告)号：US20120141463A1

公开(公告)日：2012-06-07

申请号：US13372170

申请日：2012-02-13

申请人： Herren Wu ,  Peter Kiener ,  Partha S. Chowdhury ,  James F. Young

发明人： Herren Wu ,  Peter Kiener ,  Partha S. Chowdhury ,  James F. Young

IPC分类号： A61K39/395 ,  C07K16/42 ,  A61P37/00 ,  A61P11/06 ,  A61P37/08 ,  C40B30/04 ,  C07K16/46

CPC分类号： G01N33/56972 ,  A61K2039/505 ,  C07K16/4291 ,  C07K2317/52 ,  C07K2317/55 ,  Y10S424/805 ,  Y10S530/862 ,  Y10S530/868

摘要： The present invention relates to the discovery of antibodies that bind to novel epitopes present on membrane-anchored immunoglobulins and which bind to these novel epitopes on the surface of B cells and plasma cells. In addition, the antibodies of the present invention can mediate ADCC and can be useful to deplete those B cells and plasma cells expressing the novel epitopes of the invention. The antibodies of the present invention can be useful for the treatment of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells. Accordingly the present invention also provides compositions and methods for the prevention, management, treatment or amelioration of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells.

摘要翻译： 本发明涉及结合存在于膜锚定的免疫球蛋白上并与B细胞和浆细胞表面上的这些新表位结合的抗体的发现。 此外，本发明的抗体可以介导ADCC，并且可用于消耗表达本发明的新表位的那些B细胞和浆细胞。 本发明的抗体可用于治疗由B细胞的单克隆扩增引起的B细胞介导的疾病和疾病。 因此，本发明还提供了用于预防，治疗或改善由B细胞的单克隆扩增引起的B细胞介导的疾病和疾病的组合物和方法。

公开(公告)号：US08153131B2

公开(公告)日：2012-04-10

申请号：US12534217

申请日：2009-08-03

申请人： Herren Wu ,  Christian Allan ,  Changshou Gao ,  Ling-Ling An ,  Peter Kiener ,  Su-Yau Mao ,  Anthony Coyle

发明人： Herren Wu ,  Christian Allan ,  Changshou Gao ,  Ling-Ling An ,  Peter Kiener ,  Su-Yau Mao ,  Anthony Coyle

IPC分类号： A61K39/395

CPC分类号： C07K16/24 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30 ,  Y02A50/412

摘要： Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

摘要翻译： 公开了用于抑制促炎细胞因子从脊椎动物细胞中释放并抑制患者炎性细胞因子级联的组合物和方法。 组合物包含例如特异性结合HMG1的高亲和力抗体及其抗原性片段。 本发明的高亲和力抗体和包含其的药物组合物可用于许多目的，例如作为针对广泛范围的炎性疾病和病症的治疗剂，例如败血症，类风湿性关节炎，腹膜炎，克罗恩病，再灌注损伤，败血症 内毒素性休克，囊性纤维化，心内膜炎，牛皮癣，牛皮癣关节炎，关节炎，过敏性休克，器官缺血，再灌注损伤和同种异体移植排斥。 此外，本发明的高亲和力抗体可用作诊断抗体。