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11. 发明申请

US20050215767A1 Fcgamma riib specific antibodies and methods of use thereof 有权
标题翻译： FcγRibib特异性抗体及其使用方法
公开(公告)号：US20050215767A1
公开(公告)日：2005-09-29
申请号：US10524134
申请日：2003-08-14
申请人： Scott Koenig , Maria Veri
发明人： Scott Koenig , Maria Veri
IPC分类号： A61K39/395 , C07K16/28 , C07K16/32 , C07K16/42
CPC分类号： C07K16/32 , A61K2039/505 , C07K16/283 , C07K16/2896 , C07K2317/24 , C07K2317/34 , C07K2317/732
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 invention 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.
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。本发明提供了通过施用本发明的抗体来增强治疗性抗体的效应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施用本发明的抗体来增强疫苗组合物的功效的方法。

12. 发明授权

US08968730B2 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：US08968730B2
公开(公告)日：2015-03-03
申请号：US12167765
申请日：2008-07-03
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon
IPC分类号： A61K39/395 , A61K39/40 , C07K16/28 , C07K16/00 , A61K39/00
CPC分类号： C07K16/283 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C07K2317/41 , C07K2317/54 , C07K2317/71 , C07K2317/732 , C07K2317/76 , C07K2317/92
摘要： The present invention relates to antibodies or fragments thereof that specifically bind the extracellular domain of FcγRIIB, particularly human FcγRIIB, and block the Fc binding site of human FcγRIIB. The invention 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.
摘要翻译：本发明涉及特异性结合FcγRIIB细胞外结构域，特别是人FcγRIIB的抗体或其片段，并阻断人FcγRIIB的Fc结合位点。本发明提供了通过施用本发明的抗体来增强免疫应答来治疗癌症和/或调节免疫复合物介导的细胞活化的方法。本发明还提供了通过施用本发明的抗原 - 抗体复合物和抗体来破坏对抗原的耐受性的方法。

13. 发明授权

US08652466B2 Methods for the treatment of disease using immunoglobulins having Fc regions with altered affinities for FcγRactivating and FcγRinhibiting 有权
标题翻译：使用免疫球蛋白治疗疾病的方法，所述免疫球蛋白具有对Fcγ激活和Fcγ抑制具有改变的亲和力的Fc区
公开(公告)号：US08652466B2
公开(公告)日：2014-02-18
申请号：US11952568
申请日：2007-12-07
申请人： Jeffrey B. Stavenhagen , Scott Koenig
发明人： Jeffrey B. Stavenhagen , Scott Koenig
IPC分类号： A61K39/395 , A61K39/40 , C07K16/00
CPC分类号： C07K16/30 , A61K2039/505 , C07K16/2887 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/734
摘要： The present invention relates to methods of treating or preventing cancer and other diseases using molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds an FcγR that activates a cellular effector (“FcγRActivating,” such as FcγRIIA or FcγRIIIA) and an FcγR that inhibits a cellular effector (“FcγRInhibiting,” such as FcγRIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such FcγR for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcγR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcγR is desired (e.g., inflammation, autoimmune disease).
摘要翻译：本发明涉及使用分子，特别是多肽，特别是包含变体Fc区的免疫球蛋白（例如抗体）治疗或预防癌症和其它疾病的方法，其中所述变体Fc区包含至少一个相对于野生型Fc区，该变体Fc区结合激活细胞效应物（“FcγR激活”，例如FcγRIIA或FcγRIIIA）的FcγR和抑制细胞效应子（FcgammaRIhibiting，例如FcγRIIA）的FcgamR，其具有改变的比例的亲和力相对于野生型免疫球蛋白Fc区的FcFcγR的各自的结合亲和力。本发明的方法特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状，其中需要由FcγR受体介导的效应细胞功能的增强功效（例如癌症，感染性疾病）或由FcgammaR介导的受抑制的效应细胞反应是期望的（例如，炎症，自身免疫性疾病）。

14. 发明申请

US20090092610A1 FcGammaRIIB Specific Antibodies and Methods of Use Thereof 有权
标题翻译： FcGammaRIIB特异性抗体及其使用方法
公开(公告)号：US20090092610A1
公开(公告)日：2009-04-09
申请号：US12167765
申请日：2008-07-03
申请人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon
发明人： Scott Koenig , Maria Concetta Veri , Nadine Tuaillon
IPC分类号： A61K39/395 , C07K16/28 , A61P35/00
CPC分类号： C07K16/283 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C07K2317/41 , C07K2317/54 , C07K2317/71 , C07K2317/732 , C07K2317/76 , C07K2317/92
摘要： The present invention relates to antibodies or fragments thereof that specifically bind the extracellular domain of FcγRIIB, particularly human FcγRIIB, and block the Fc binding site of human FcγRIIB. The invention 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.
摘要翻译：本发明涉及特异性结合FcγRIIB细胞外结构域，特别是人FcγRIIB的抗体或其片段，并阻断人FcγRIIB的Fc结合位点。本发明提供了通过施用本发明的抗体来增强免疫应答来治疗癌症和/或调节免疫复合物介导的细胞活化的方法。本发明还提供了通过施用本发明的抗原 - 抗体复合物和抗体来破坏对抗原的耐受性的方法。

15. 发明申请

US20090053218A1 FcGammaRIIB Specific Antibodies and Methods of Use Thereof 有权
标题翻译： FcGammaRIIB特异性抗体及其使用方法
公开(公告)号：US20090053218A1
公开(公告)日：2009-02-26
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 , A61P31/00
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的用途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。本发明还包括抗FcgammaRIIB抗体或其抗原结合片段与其它癌症治疗组合的用途。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，其量有效预防，治疗，治疗或改善癌症，例如B细胞恶性肿瘤，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。

16. 发明申请

US20080138349A1 Identification and engineering of antibodies with variant Fc regions and methods of using same 有权
标题翻译：具有变体Fc区的抗体的鉴定和工程及其使用方法
公开(公告)号：US20080138349A1
公开(公告)日：2008-06-12
申请号：US11952568
申请日：2007-12-07
申请人： Jeffrey B. Stavenhagen , Scott Koenig
发明人： Jeffrey B. Stavenhagen , Scott Koenig
IPC分类号： A61K39/395 , C07K16/28 , C07K16/24
CPC分类号： C07K16/30 , A61K2039/505 , C07K16/2887 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/734
摘要： The present invention relates to methods of treating or preventing cancer and other diseases using molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds an FcγR that activates a cellular effector (“FcγRActivating,” such as FcγRIIA or FcγRIIIA) and an FcγR that inhibits a cellular effector (“FcγRInhibiting,” such as FcγRIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such FcγR for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcγR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcγR is desired (e.g., inflammation, autoimmune disease).
摘要翻译：本发明涉及使用分子，特别是多肽，特别是包含变体Fc区的免疫球蛋白（例如抗体）治疗或预防癌症和其它疾病的方法，其中所述变体Fc区包含至少一个相对于野生型Fc区，该变体Fc区结合激活细胞效应子（“FcγAM激活”，例如FcγRIIA或FcγRIIIA）的FcγR，以及抑制细胞效应子的FcγR（“FcgammaR _{抑制，例如FcgammaRIIA），相对于野生型免疫球蛋白Fc区的这种FcγRR的相应结合亲和力具有改变的亲和力比。本发明的方法特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状，其中需要由FcγR受体介导的效应细胞功能的增强功效（例如癌症，感染性疾病）或由FcgammaR介导的受抑制的效应细胞反应是期望的（例如，炎症，自身免疫性疾病）。}

17. 发明申请

US20080095766A1 Methods for the Treatment of Autoimmune Disorders Using Immunosuppressive Monoclonal Antibodies with Reduced Toxicity 有权
标题翻译：使用具有降低毒性的免疫抑制性单克隆抗体治疗自身免疫性疾病的方法
公开(公告)号：US20080095766A1
公开(公告)日：2008-04-24
申请号：US11763434
申请日：2007-06-14
申请人： Scott Koenig , Ronald Wilder , Ezio Bonvini , Leslie Johnson , Stanley Pillemer
发明人： Scott Koenig , Ronald Wilder , Ezio Bonvini , Leslie Johnson , Stanley Pillemer
IPC分类号： A61K39/395 , A61P1/00 , A61P17/06 , A61P19/02 , A61P25/00 , A61P3/10 , A61P35/00 , A61P37/06
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性糖尿病（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。

18. 发明授权

US07229619B1 Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment 有权
标题翻译：给予/给予抗RSV抗体进行预防和治疗的方法
公开(公告)号：US07229619B1
公开(公告)日：2007-06-12
申请号：US09724531
申请日：2000-11-28
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
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。

19. 发明授权

US07179900B2 Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment 失效
标题翻译：给予/给予抗RSV抗体进行预防和治疗的方法
公开(公告)号：US07179900B2
公开(公告)日：2007-02-20
申请号：US10403180
申请日：2003-03-31
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 of 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。

20. 发明申请

US20060134709A1 Engineering Fc antibody regions to confer effector function 有权
标题翻译：工程化Fc抗体区域以产生效应子功能
公开(公告)号：US20060134709A1
公开(公告)日：2006-06-22
申请号：US11271140
申请日：2005-11-10
申请人： Jeffery Stavenhagen , Scott Koenig
发明人： Jeffery Stavenhagen , Scott Koenig
IPC分类号： G01N33/574 , C07K16/08 , C07K16/30
CPC分类号： C07K16/30 , C07K16/00 , C07K16/283 , C07K16/2887 , C07K16/2896 , C07K16/32 , C07K2317/41 , C07K2317/52 , C07K2317/72 , C07K2317/732 , C07K2317/734 , C07K2319/30 , G01N33/574
摘要： The present invention relates to molecules having a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region. These modified molecules confer an effector function to a molecule, where the parent molecule does not detectably exhibit this effector function. In particular, the molecules of the invention have an increased effector cell function mediated by a FcγR, such as, but not limited to, ADCC. In one embodiment, the variant Fc region binds FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention have particular utility in treatment, prevention or management of a disease or disorder, such as cancer, in a sub-population of patients, wherein the target antigen is expressed at low levels in the target cell population, in particular, in patients refractory to treatment with an existing therapeutic antibody due to the low level of target antigen expression on the cancer or associated cells.
摘要翻译：本发明涉及具有变体Fc区的分子，其中所述变体Fc区相对于野生型Fc区包含至少一个氨基酸修饰。这些修饰的分子赋予分子的效应子功能，其中母体分子不可检测地显示出该效应子功能。特别地，本发明的分子具有由FcγR介导的增加的效应细胞功能，例如但不限于ADCC。在一个实施方案中，相对于包含野生型Fc区的可比较分子，变体Fc区以更大的亲和力结合FcγRIIIA和/或FcγRIIA。本发明的分子在患者的亚群中治疗，预防或治疗疾病或病症（例如癌症）具有特别的用途，其中目标抗原在靶细胞群体中以低水平表达，特别是，在由于癌细胞或相关细胞上的靶抗原表达水平低的现有治疗性抗体治疗难治的患者中。

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