公开(公告)号：US20100298541A1

公开(公告)日：2010-11-25

申请号：US12739149

申请日：2008-10-31

申请人： Herren Wu ,  Manuel Baca ,  Jeffrey Swers ,  Benoy Chacko

发明人： Herren Wu ,  Manuel Baca ,  Jeffrey Swers ,  Benoy Chacko

IPC分类号： C07K14/00

CPC分类号： G01N33/566 ,  C07K14/78 ,  C07K16/2878 ,  C07K2318/20 ,  C07K2319/00 ,  C12N15/1037 ,  C12N15/1044

摘要： The invention provides protein scaffolds and methods of preparing, screening, engineering and using such protein scaffolds.

摘要翻译： 本发明提供蛋白质支架和制备，筛选，工程和使用这种蛋白质支架的方法。

公开(公告)号：US20100266614A1

公开(公告)日：2010-10-21

申请号：US12777814

申请日：2010-05-11

申请人： James F. YOUNG ,  Leslie S. Johnson ,  William D. Huse ,  Herren Wu ,  Jeffry D. Watkins

发明人： James F. YOUNG ,  Leslie S. Johnson ,  William D. Huse ,  Herren Wu ,  Jeffry D. Watkins

IPC分类号： A61K39/42 ,  C07K16/08 ,  A61P31/12

CPC分类号： C07K16/00 ,  A61K2039/505 ,  C07K16/1027 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/00

摘要： Ultra high affinity antibodies with binding affinities in the range of 1010 M−1, and even 1011 M−1 are disclosed. Such antibodies include antibodies having novel high affinity complementarity determining regions (CDRs), especially those with framework and constant regions derived from either humans or mice. Methods of preparing and screening such antibodies, as well as methods of using them to prevent and/or treat disease, especially virus-induced diseases, are also disclosed.

摘要翻译： 公开了具有1010M-1甚至1011M-1范围内的结合亲和力的超高亲和力抗体。 此类抗体包括具有新型高亲和力互补决定区（CDR）的抗体，特别是具有来自人或小鼠的骨架和恒定区的抗体。 还公开了制备和筛选这些抗体的方法，以及使用它们来预防和/或治疗疾病，特别是病毒诱导的疾病的方法。

公开(公告)号：US20080311122A1

公开(公告)日：2008-12-18

申请号：US12094449

申请日：2006-11-27

申请人： Herren Wu ,  Ling-Ling An ,  Peter Kiener ,  Anthony Coyle ,  Jane Tian ,  Changsou Gao

发明人： Herren Wu ,  Ling-Ling An ,  Peter Kiener ,  Anthony Coyle ,  Jane Tian ,  Changsou Gao

IPC分类号： A61K39/395 ,  A61K31/7105 ,  A61P37/02

CPC分类号： C07K16/24 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/32

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, lupus, 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， 败血病，内毒素性休克，囊性纤维化，心内膜炎，狼疮，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：US20080118506A1

公开(公告)日：2008-05-22

申请号：US11931060

申请日：2007-10-31

申请人： Ling-Ling An ,  Sek Chung Fung ,  Robert F. Kelley ,  Henry B. Lowman ,  Sanjaya Singh ,  Herren Wu

发明人： Ling-Ling An ,  Sek Chung Fung ,  Robert F. Kelley ,  Henry B. Lowman ,  Sanjaya Singh ,  Herren Wu

IPC分类号： A61K39/395 ,  C07K16/18 ,  C07K14/00 ,  A61P43/00 ,  C12N15/11 ,  C12N15/00 ,  C12N5/06

CPC分类号： C07K16/18 ,  A61K2039/505 ,  C07K16/40 ,  C07K2317/24 ,  C07K2317/50 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92

摘要： The invention relates to humanized anti-human Factor D monoclonal antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

摘要翻译： 本发明涉及人源化抗人因子D单克隆抗体，其核酸和氨基酸序列，携带这些抗体的细胞和载体及其在制备用于治疗与过度或不受控制的疾病和病症的组合物和药物中的用途 补体激活。 这些抗体可用于疾病的诊断，预防和治疗。

公开(公告)号：US07323172B2

公开(公告)日：2008-01-29

申请号：US10962285

申请日：2004-10-08

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

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

IPC分类号： A61K39/42 ,  A61K39/155

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：US20060234296A1

公开(公告)日：2006-10-19

申请号：US10544057

申请日：2004-02-02

申请人： Sanjaya Singh ,  Catherine Foster ,  Herren Wu

发明人： Sanjaya Singh ,  Catherine Foster ,  Herren Wu

IPC分类号： G01N33/53 ,  C07H21/04 ,  C12P21/06 ,  C40B40/10 ,  C12N5/06

CPC分类号： C07K16/4291 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/92

摘要： The invention relates to high affinity human monoclonal antibodies, particularly those directed against isotypic determinants of immunoglobulin E (IgE), as well as direct equivalents and derivatives of these antibodies. These antibodies bind to their respective target with an affinity at least 100 fold greater than the original parent antibody. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

摘要翻译： 本发明涉及高亲和力的人单克隆抗体，特别是针对免疫球蛋白E（IgE）的同种型决定簇的那些，以及这些抗体的直接等同物和衍生物。 这些抗体以比原始亲本抗体大至少100倍的亲和力结合到它们各自的靶。 这些抗体可用于疾病的诊断，预防和治疗。

公开(公告)号：US20060228350A1

公开(公告)日：2006-10-12

申请号：US11377148

申请日：2006-03-17

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

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

IPC分类号： A61K39/395 ,  C07H21/04 ,  C12P21/06 ,  C07K16/44 ,  C12N5/06

CPC分类号： C07K16/005 ,  C07H21/04 ,  C07K16/2863 ,  C07K16/40 ,  C07K16/464 ,  C07K2317/55 ,  C07K2317/92 ,  C12N15/1027

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 invention also provides method of producing improved humanized antibodies. 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。 本发明还提供了生产改良的人源化抗体的方法。 本发明还提供通过本发明的方法制备的抗体。

公开(公告)号：US20060094062A1

公开(公告)日：2006-05-04

申请号：US11261630

申请日：2005-10-31

申请人： Herren Wu ,  Changshou Gao

发明人： Herren Wu ,  Changshou Gao

IPC分类号： C40B40/10

CPC分类号： C12N15/1037 ,  C12N15/1058 ,  C12N15/1086 ,  C40B30/04

摘要： The present invention relates to a method for identification and isolation of binding molecules having a selective affinity for a ligand. More specifically, this invention provides a process for the ultra high throughput screening of binding molecules from expression libraries containing billions of independent clones without the biases and limitations of other high throughput screening methods such as panning. Additionally, the present invention provides a method for the production of expression libraries essentially free of clones encoding non-functional molecules.

摘要翻译： 本发明涉及用于鉴定和分离对配体具有选择性亲和性的结合分子的方法。 更具体地，本发明提供了一种从含有数十亿独立克隆的表达文库中超结合分子的超高通量筛选方法，而没有其他高通量筛选方法（如平移）的偏差和限制。 另外，本发明提供了生产基本上不含编码非功能性分子的克隆的表达文库的方法。

公开(公告)号：US20060040325A1

公开(公告)日：2006-02-23

申请号：US11203253

申请日：2005-08-15

申请人： Herren Wu ,  Changshou Gao

发明人： Herren Wu ,  Changshou Gao

IPC分类号： C07K16/28 ,  G01N33/53 ,  C12P21/06 ,  C12N5/06

CPC分类号： G01N33/566 ,  C07K16/00 ,  C07K16/2848 ,  C07K16/2866 ,  C07K2317/52 ,  C07K2317/622 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/92 ,  C07K2319/30 ,  G01N33/574 ,  G01N2500/00

摘要： The present invention relates to novel Fc variants of antibodies that immunospecifically binds to Integrin αvβ3. The Fc variants comprise a variable region that immunospecifically binds to Integrin αvβ3 and a Fc region that further comprises at least one novel amino acid residue which may provide for enhanced effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or C1q. Additionally, the Fc variants have altered antibody dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants of an antibody that immunospecifically binds to Integrin αvβ3, particularly for therapeutic purposes.

摘要翻译： 本发明涉及免疫特异性结合整联蛋白α3β3的抗体的新型Fc变体。 Fc变体包含免疫特异性结合整联蛋白α3β3的可变区和还包含至少一个新的氨基酸残基的Fc区，其可以提供增强的效应子 功能。 更具体地，本发明提供了对一种或多种FcγR和/或C1q具有修饰的结合亲和力的Fc变体。 另外，Fc变体具有改变的抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）活性。 本发明进一步提供了用于免疫特异性结合整联蛋白α3β3的抗体的所述Fc变体的应用的方法和方案，特别是出于治疗目的。

公开(公告)号：US06656467B2

公开(公告)日：2003-12-02

申请号：US09771415

申请日：2001-01-26

申请人： James F. Young ,  Leslie S. Johnson ,  William D. Huse ,  Herren Wu ,  Jeffry D. Watkins

发明人： James F. Young ,  Leslie S. Johnson ,  William D. Huse ,  Herren Wu ,  Jeffry D. Watkins

IPC分类号： A61K3942

CPC分类号： C07K16/00 ,  A61K2039/505 ,  C07K16/1027 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/00

摘要： Ultra high affinity antibodies with binding affinities in the range of 1010 M−1, and even 1011 M−1 are disclosed. Such antibodies include antibodies having novel high affinity complementarity determining regions (CDRs), especially those with framework and constant regions derived from either humans or mice. Methods of preparing and screening such antibodies, as well as methods of using them to prevent and/or treat disease, especially virus-induced diseases, are also disclosed.

摘要翻译： 公开了具有10 10 M -1，甚至10 11 M -1范围内的结合亲和力的超高亲和力抗体。 此类抗体包括具有新型高亲和力互补决定区（CDR）的抗体，特别是具有来自人或小鼠的骨架和恒定区的抗体。 还公开了制备和筛选这些抗体的方法，以及使用它们来预防和/或治疗疾病，特别是病毒诱导的疾病的方法。