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1. 发明申请

US20140328836A1 HER2/neu-Specific Antibodies and Methods of Using Same 有权
标题翻译： HER2 / neu特异性抗体及其使用方法
公开(公告)号：US20140328836A1
公开(公告)日：2014-11-06
申请号：US14332239
申请日：2014-07-15
申请人： Leslie S. Johnson , Ling Huang , Nadine Tuaillon , Ezio Bonvini
发明人： Leslie S. Johnson , Ling Huang , Nadine Tuaillon , Ezio Bonvini
IPC分类号： C07K16/32 , A61K39/395 , A61K45/06
CPC分类号： C07K16/32 , A61K39/39558 , A61K45/06 , A61K2039/505 , A61K2039/54 , C07K2317/24 , C07K2317/51 , C07K2317/515 , C07K2317/71 , C07K2317/732 , C07K2317/92
摘要： This invention relates to antibodies that specifically bind HER2/neu, and particularly chimeric 4D5 antibodies to HER2/neu, which have reduced glycosylation as compared to known 4D5 antibodies. The invention also relates to methods of using the 4D5 antibodies and compositions comprising them in the diagnosis, prognosis and therapy of diseases such as cancer, autoimmune diseases, inflammatory disorders, and infectious disease.
摘要翻译：本发明涉及与已知的4D5抗体相比具有降低的糖基化的HER2 / neu特异性结合HER2 / neu的嵌合4D5抗体的抗体。本发明还涉及将4D5抗体及其组合物用于诊断，预后和治疗疾病如癌症，自身免疫性疾病，炎症性疾病和感染性疾病的方法。

2. 发明授权

US08802093B2 HER2/neu-specific antibodies and methods of using same 有权
标题翻译： HER2 / neu特异性抗体及其使用方法
公开(公告)号：US08802093B2
公开(公告)日：2014-08-12
申请号：US12933885
申请日：2009-03-25
申请人： Leslie S. Johnson , Ling Huang , Nadine Tuaillon , Ezio Bonvini
发明人： Leslie S. Johnson , Ling Huang , Nadine Tuaillon , Ezio Bonvini
IPC分类号： A61K39/395 , A61P35/04 , C07K16/28
CPC分类号： C07K16/32 , A61K39/39558 , A61K45/06 , A61K2039/505 , A61K2039/54 , C07K2317/24 , C07K2317/51 , C07K2317/515 , C07K2317/71 , C07K2317/732 , C07K2317/92
摘要： This invention relates to antibodies that specifically bind HER2/neu, and particularly chimeric 4D5 antibodies to HER2/neu, which have reduced glycosylation as compared to known 4D5 antibodies. The invention also relates to methods of using the 4D5 antibodies and compositions comprising them in the diagnosis, prognosis and therapy of diseases such as cancer, autoimmune diseases, inflammatory disorders, and infectious disease.
摘要翻译：本发明涉及与已知的4D5抗体相比具有降低的糖基化的HER2 / neu特异性结合HER2 / neu的嵌合4D5抗体的抗体。本发明还涉及将4D5抗体及其组合物用于诊断，预后和治疗疾病如癌症，自身免疫性疾病，炎症性疾病和感染性疾病的方法。

3. 发明授权

US08663634B2 Methods for the treatment of autoimmune disorders using immunosuppressive monoclonal antibodies with reduced toxicity 有权
标题翻译：使用免疫抑制性单克隆抗体治疗自身免疫性疾病的方法，毒性降低
公开(公告)号：US08663634B2
公开(公告)日：2014-03-04
申请号：US11485557
申请日：2006-07-11
申请人： Scott Koenig , Ronald Wilder , Ezio Bonvini , Leslie S. Johnson
发明人： Scott Koenig , Ronald Wilder , Ezio Bonvini , Leslie S. Johnson
IPC分类号： A61K39/395 , A61K39/40 , C07K16/00
CPC分类号： C07K16/2809 , A61K38/28 , A61K2039/505 , C07K2317/24 , C07K2317/524 , C07K2317/53 , C07K2317/71 , A61K2300/00
摘要： The present invention provides methods of treating, preventing or ameliorating the symptoms of T cell-mediated immunological diseases, particularly autoimmune diseases, through the use of anti-CD3 antibodies. In particular, the methods of the invention provide for administration of antibodies that specifically bind the epsilon subunit within the human CD3 complex. Such antibodies modulate the T cell receptor/alloantigen interaction and, thus, regulate the T cell mediated cytotoxicity associated with autoimmune disorders. Additionally, the invention provides for modification of the anti-CD3 antibodies such that they exhibit reduced or eliminated effector function and T cell activation as compared to non-modified anti-CD3 antibodies.
摘要翻译：本发明提供了通过使用抗CD3抗体来治疗，预防或改善T细胞介导的免疫疾病，特别是自身免疫性疾病的症状的方法。特别地，本发明的方法提供了特异性结合人CD3复合物内的ε亚基的抗体的施用。这种抗体调节T细胞受体/同种异体抗原相互作用，因此调节与自身免疫疾病相关的T细胞介导的细胞毒性。另外，本发明提供抗CD3抗体的修饰，使得与未修饰的抗CD3抗体相比，它们表现出降低或消除的效应子功能和T细胞活化。

4. 发明授权

US08187593B2 FcγRIIB specific antibodies and methods of use thereof 有权
标题翻译： FcγRIIB特异性抗体及其使用方法
公开(公告)号：US08187593B2
公开(公告)日：2012-05-29
申请号：US12167760
申请日：2008-07-03
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
IPC分类号： A61K39/395 , A61K39/40 , A61K39/00 , C07K16/00
CPC分类号： C07K16/283 , A01K2267/0331 , A61K2039/505 , C07K16/2896 , C07K16/32 , C07K2317/24 , C07K2317/34 , C07K2317/732 , C07K2317/92
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention with a vaccine composition.
摘要翻译：本发明涉及以比所述抗体或其片段更大的亲和力结合FcγRIIA，特别是人FcγRIIA的FcγRIIB特别是人FcγRIIB特异性结合的抗体或其片段。本发明还包括使用抗FcγRIIB抗体或其抗原结合片段作为治疗，预防，治疗或改善癌症，优选B细胞恶性肿瘤，特别是B细胞恶性肿瘤的单一药物治疗细胞性慢性淋巴细胞白血病或非霍奇金淋巴瘤，自身免疫性疾病，炎症性疾病，IgE介导的过敏性疾病或其一种或多种症状。本发明还包括与其他癌症疗法组合的抗FcγRIIB抗体或其抗原结合片段的用途。本发明提供了包含抗FcγRIIB抗体或其抗原结合片段的药物组合物，其量有效地预防，治疗，治疗或改善诸如B细胞恶性肿瘤，自身免疫病症，炎症性疾病，IgE介导的过敏性疾病或其一种或多种症状。本发明还提供了通过施用本发明的抗体来增强治疗性抗体的效应子功能来增强治疗性抗体的治疗效果的方法。本发明还提供了通过用疫苗组合物施用本发明的抗体来增强疫苗组合物的功效的方法。

5. 发明申请

US20090076251A1 FcGammaRIIB Specific Antibodies and Methods of Use Thereof 有权
公开(公告)号：US20090076251A1
公开(公告)日：2009-03-19
申请号：US12186058
申请日：2008-08-05
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
IPC分类号： C07K16/28
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/2896 , C07K16/32 , C07K2317/24 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/72 , C07K2317/732
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, more particularly the extracellular domain of FcγRIIB with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA, and block the Fc binding site of FcγRIIB. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention with a vaccine composition. The invention further provides methods of treating cancer and/or regulating immune complex-mediated cell activation by administering the antibodies of the invention to enhance an immune response. The invention also provides methods of breaking tolerance to an antigen by administering an antigen-antibody complex and an antibody of the invention.

6. 发明申请

US20090074771A1 FcGammaRIIB Specific Antibodies and Methods of Use Thereof 有权
公开(公告)号：US20090074771A1
公开(公告)日：2009-03-19
申请号：US12186065
申请日：2008-08-05
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
IPC分类号： A61K39/395 , G01N33/53 , A61P37/02
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/32 , C07K2317/34 , C07K2317/41 , C07K2317/71 , C07K2317/732 , C07K2317/76
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, more particularly the extracellular domain of FcγRIIB with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA, and block the Fc binding site of FcγRIIB. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention with a vaccine composition. The invention further provides methods of treating cancer and/or regulating immune complex-mediated cell activation by administering the antibodies of the invention to enhance an immune response. The invention also provides methods of breaking tolerance to an antigen by administering an antigen-antibody complex and an antibody of the invention.

7. 发明申请

US20150175697A1 Deimmunized Serum-Binding Domains and Their Use in Extending Serum Half-Life 有权
标题翻译：去免疫的血清结合域及其在延长血清半衰期中的应用
公开(公告)号：US20150175697A1
公开(公告)日：2015-06-25
申请号：US14118516
申请日：2012-05-16
申请人： Ezio Bonvini , Bhaswati Barat , Ling Huang , Leslie S. Johnson
发明人： Ezio Bonvini , Bhaswati Barat , Ling Huang , Leslie S. Johnson
IPC分类号： C07K16/28 , C07K16/32
CPC分类号： C07K16/32 , C07K14/315 , C07K16/2803 , C07K16/2809 , C07K16/283 , C07K16/2851 , C07K16/44 , C07K2317/24 , C07K2317/31 , C07K2317/567 , C07K2317/62 , C07K2317/624 , C07K2317/626 , C07K2317/73 , C07K2317/76 , C07K2317/90 , C07K2317/92 , C07K2319/31 , C07K2319/32 , C07K2319/73
摘要： The present invention is directed to a polypeptide (for example, an antigen-binding molecule) that comprises a polypeptide portion of a deimmunized serum-binding protein capable of binding to said serum protein. The presence of the serum-binding protein extends the serum half-life of the polypeptide, relative to the serum half-life of the polypeptide if lacking the polypeptide portion of the deimmunized serum-binding protein. The invention also pertains to methods and uses that employ such molecules.
摘要翻译：本发明涉及包含能够结合所述血清蛋白的解除免疫的血清结合蛋白的多肽部分的多肽（例如，抗原结合分子）。如果缺乏去免疫的血清结合蛋白的多肽部分，则血清结合蛋白的存在相对于多肽的血清半衰期延长了多肽的血清半衰期。本发明还涉及使用这种分子的方法和用途。

8. 发明授权

US09056906B2 Methods for the treatment of autoimmune disorders using immunosuppressive monoclonal antibodies with reduced toxicity 有权
标题翻译：使用免疫抑制性单克隆抗体治疗自身免疫性疾病的方法，毒性降低
公开(公告)号：US09056906B2
公开(公告)日：2015-06-16
申请号：US11763434
申请日：2007-06-14
申请人： Scott Koenig , Ronald L. Wilder , Ezio Bonvini , Leslie S. Johnson
发明人： Scott Koenig , Ronald L. Wilder , Ezio Bonvini , Leslie S. Johnson
IPC分类号： A61K39/395 , A61K39/40 , C07K16/28 , C07K16/00 , A61K39/00
CPC分类号： C07K16/2809 , A61K39/3955 , A61K45/06 , A61K2039/505 , A61K2039/545 , C07K2317/24 , C07K2317/41 , C07K2317/71
摘要： The present invention provides methods of treating, preventing, slowing the progression of, or ameliorating the symptoms of T cell mediated immunological diseases, particularly autoimmune diseases (e.g., autoimmune diabetes (i.e. type 1 diabetes or insulin-dependent diabetes mellitus (IDDM)) and multiple sclerosis) through the use of anti-human CD3 antibodies. The antibodies of the invention of the invention are preferably used in low dose dosing regimens, chronic dosing regimens or regimens that involve redosing after a certain period of time. The methods of the invention provide for administration of antibodies that specifically bind the epsilon subunit within the human CD3 complex. Such antibodies modulate the T cell receptor/alloantigen interaction and, thus, regulate the T cell mediated cytotoxicity associated with autoimmune disorders. Additionally, the methods of the invention provide for use of anti-human CD3 antibodies modified such that they exhibit reduced or eliminated effector function and T cell activation as compared to non-modified anti-human CD3 antibodies.
摘要翻译：本发明提供治疗，预防，减缓T细胞介导的免疫疾病，特别是自身免疫疾病（例如，自身免疫性糖尿病（即1型糖尿病或胰岛素依赖型糖尿病（IDDM））的症状的进展或改善的方法，以及多发性硬化）通过使用抗人CD3抗体。本发明的本发明的抗体优选用于低剂量给药方案，慢性给药方案或方案，其涉及经过一段时间后的再次给药。本发明的方法提供了特异性结合人CD3复合物内的ε亚基的抗体的施用。这种抗体调节T细胞受体/同种异体抗原相互作用，因此调节与自身免疫疾病相关的T细胞介导的细胞毒性。此外，本发明的方法提供使用经修饰的抗人CD3抗体，使得与未修饰的抗人CD3抗体相比，它们表现出降低或消除的效应子功能和T细胞活化。

9. 发明授权

US08946387B2 FcγRIIB specific antibodies and methods of use thereof 有权
公开(公告)号：US08946387B2
公开(公告)日：2015-02-03
申请号：US12186065
申请日：2008-08-05
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon , Ezio Bonvini
IPC分类号： C07K16/00 , C12P21/08 , A61K39/395 , A61K39/40 , C07K16/28 , C07K16/32 , A61K39/00
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/32 , C07K2317/34 , C07K2317/41 , C07K2317/71 , C07K2317/732 , C07K2317/76
摘要： The present invention relates to antibodies or fragments thereof that specifically bind FcγRIIB, particularly human FcγRIIB, more particularly the extracellular domain of FcγRIIB with greater affinity than said antibodies or fragments thereof bind FcγRIIA, particularly human FcγRIIA, and block the Fc binding site of FcγRIIB. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The present invention provides pharmaceutical compositions comprising an anti-FcγRIIB antibody or an antigen-binding fragment thereof, in amounts effective to prevent, treat, manage, or ameliorate a cancer, such as a B-cell malignancy, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention further provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention with a vaccine composition. The invention further provides methods of treating cancer and/or regulating immune complex-mediated cell activation by administering the antibodies of the invention to enhance an immune response. The invention also provides methods of breaking tolerance to an antigen by administering an antigen-antibody complex and an antibody of the invention.

10. 发明申请

US20120034221A1 T-Cell Receptor Antibodies And Methods of Use Thereof 审中-公开
标题翻译： T细胞受体抗体及其使用方法
公开(公告)号：US20120034221A1
公开(公告)日：2012-02-09
申请号：US13273282
申请日：2011-10-14
申请人： Ezio Bonvini , Leslie S. Johnson , Nadine Tuaillon , Ling Huang
发明人： Ezio Bonvini , Leslie S. Johnson , Nadine Tuaillon , Ling Huang
IPC分类号： A61K39/395 , C12N15/13 , C12N15/63 , C12P21/02 , C12N1/21 , C12N5/10 , C12N1/19 , A61P37/06 , A61P35/00 , A61P29/00 , A61P3/10 , A61P17/06 , A61P1/00 , A61P25/00 , C07K16/28
CPC分类号： C07K16/2809 , A61K2039/505 , C07K2317/52 , C07K2317/56 , C07K2317/71
摘要： The present invention is directed to the production and use of monoclonal antibodies, or antigen binding fragments thereof, that specifically bind the T cell antigen receptor (TCR) and their use for immunomodulation. In preferred embodiments, the antibody or antigen binding fragment of the invention specifically binds the constant region of the α chain of the TCR, or otherwise specifically binds the α chain regardless of TCR clonal origin (i.e., is pan specific for TCR). The antibodies of the invention may be used, for example, in immunosuppressive therapies for transplant maintenance and the treatment of autoimmune diseases, and/or as targeting molecules for use in the treatment of T-cell malignancies.
摘要翻译：本发明涉及特异性结合T细胞抗原受体（TCR）及其用于免疫调节的单克隆抗体或其抗原结合片段的生产和使用。在优选的实施方案中，本发明的抗体或抗原结合片段特异性结合TCR的α链的恒定区，或以其他方式特异性结合α链，而不管TCR克隆来源（即TCR的泛特异性）。本发明的抗体可用于例如用于移植维持的免疫抑制疗法和治疗自身免疫性疾病，和/或用作治疗T细胞恶性肿瘤的靶向分子。

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