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1. 发明申请

WO2008140603A2 METHODS FOR THE TREATMENT OF DISEASE USING IMMUNOGLOBULINS HAVING FC REGIONS WITH ALTERED AFFINITIES FOR FCγR ACTIVATING AND FCγR INHIBITING 审中-公开
标题翻译：使用具有更改功能的FC区域的免疫球蛋白治疗疾病的方法用于FC？R激活和FC？R抑制
公开(公告)号：WO2008140603A2
公开(公告)日：2008-11-20
申请号：PCT/US2007/086793
申请日：2007-12-07
申请人： MACROGENICS, INC. , STAVENHAGEN, Jeffrey, B. , KOENIG, Scott
发明人： STAVENHAGEN, Jeffrey, B. , KOENIG, Scott
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 ("FcγR activating ," such as FcγRIIA or FcγRIIIA) and an FcγR that inhibits a cellular effector ("FcγR inhibiting " 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, autoimmunde 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（“FcγRIIA活化”，例如FcγRIIA或FcγRIIIA）的FcγR和FcγR 其具有相对于野生型Fc区的Fc区的这种FcγR的各自结合亲和力的改变的亲和力比例抑制细胞效应子（“FcαRα抑制”如FcγRIIA）型免疫球蛋白。本发明的方法特别可用于预防，治疗或改善与需要由FcγR介导的效应细胞功能的增强功效的疾病，病症或感染相关的一种或多种症状（例如，癌症，感染性疾病）或由FcγR介导的受抑制的效应细胞应答是期望的（例如炎症，自身免疫疾病）。

2. 发明申请

WO2008118324A3 COMPOSITION AND METHOD OF TREATING CANCER WITH AN ANTI-UROPLAKIN IB ANTIBODY 审中-公开
标题翻译：抗UROPLAKIN抗体治疗癌症的组合物和方法
公开(公告)号：WO2008118324A3
公开(公告)日：2008-10-02
申请号：PCT/US2008/003635
申请日：2008-03-20
申请人： MACROGENICS, INC. , FERGUSON, Stacy , KOENIG, Scott , TUAILLON, Nadine , JOHNSON, Leslie, S. , HUANG, Ling , RANKIN, Christopher
发明人： FERGUSON, Stacy , KOENIG, Scott , TUAILLON, Nadine , JOHNSON, Leslie, S. , HUANG, Ling , RANKIN, Christopher
IPC分类号： C07K16/28
摘要： This invention provides antibodies that specifically recognize and bind to UPK-Ib. Also included are diagnostic and therapeutic assays directed to diseases associated with unregulated levels of UPK-Ib using said antibodies. The antibodies and derivatives thereof can also be useful in the diagnisic and/or treatment of cancer associated with abnormal expression of UPK-Ib.
摘要翻译：本发明提供了特异性识别并结合UPK-1b的抗体。还包括使用所述抗体针对与未调节水平的UPK-Ib相关的疾病的诊断和治疗测定。所述抗体及其衍生物还可用于诊断和/或治疗与UPK-Ib异常表达相关的癌症。

3. 发明申请

WO2008079713A2 METHODS FOR THE TREATMENT OF LADA AND OTHER ADULT-ONSET AUTOIMMUNE DIABETES USING IMMUNOSUPPRESSIVE MONOCLONAL ANTIBODIES WITH REDUCED TOXICITY 审中-公开
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LADA和其他成年人自身免疫性糖尿病的方法
公开(公告)号：WO2008079713A2
公开(公告)日：2008-07-03
申请号：PCT/US2007/087394
申请日：2007-12-13
申请人： MACROGENICS INC. , KOENIG, Scott
发明人： KOENIG, Scott
IPC分类号： A61K39/395
CPC分类号： C07K16/2809 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/71
摘要： The present invention provides methods of treating, preventing or ameliorating the symptoms of Latent Autoimmune Diabetes in Adults (LADA) and adult-onset type 1 diabetes through the use of anti-human CD3 antibodies. In particular, in invention provides methods of preventing or delaying insulin requirement in patients diagnosed with LADA. 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-human CD3 antibodies 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：本发明提供了通过使用抗人CD3抗体来治疗，预防或改善成人潜伏性自身免疫性糖尿病（LADA）和成人发病1型糖尿病的症状的方法。特别地，本发明提供了在诊断为LADA的患者中预防或延迟胰岛素需求的方法。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，本发明提供抗人CD3抗体的修饰，使得它们与未修饰的抗人CD3抗体相比表现出降低或消除的效应子功能和T细胞活化。

4. 发明申请

WO2005018669A1 FCγRIIB-SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译： FCgammaRIIB特异性抗体及其使用方法
公开(公告)号：WO2005018669A1
公开(公告)日：2005-03-03
申请号：PCT/US2003/026071
申请日：2003-08-18
申请人： MACROGENICS, INC. , KOENIG, Scott , VERI, Maria-Concetta
发明人： KOENIG, Scott , VERI, Maria-Concetta
IPC分类号： A61K39/395
CPC分类号： C07H21/02 , A61K2039/505 , C07K16/283 , C07K2317/34 , C07K2317/732 , C07K2317/76
摘要： The present invention relates to antibodies or fragments thereof that specifically bind Fc,γRIIB, 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Fc，γRIIB，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。

5. 发明申请

WO2004016750A2 FcγRIIB-SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译： FcγRIIB特异性抗体及其使用方法
公开(公告)号：WO2004016750A2
公开(公告)日：2004-02-26
申请号：PCT/US2003/025399
申请日：2003-08-14
申请人： MACROGENICS, INC. , KOENIG, Scott , VERI, Maria-Concetta
发明人： KOENIG, Scott , VERI, Maria-Concetta
IPC分类号： C12N
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。

6. 发明申请

WO2007147090A2 METHODS FOR THE TREATMENT OF AUTOIMMUNE DISORDERS USING MONOCLONAL ANTIBODIES WITH REDUCED TOXICITY 审中-公开
标题翻译：使用具有降低毒性的单克隆抗体治疗自身免疫性疾病的方法
公开(公告)号：WO2007147090A2
公开(公告)日：2007-12-21
申请号：PCT/US2007/071275
申请日：2007-06-14
申请人： MACROGENICS, INC. , KOENIG, Scott , WILDER, Ronald , BONVINI, Ezio , JOHNSON, Leslie, S. , PILLEMER, Stanley
发明人： KOENIG, Scott , WILDER, Ronald , BONVINI, Ezio , JOHNSON, Leslie, S. , PILLEMER, Stanley
IPC分类号： A61K39/395
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。

7. 发明申请

WO2007024249A2 ENGINEERING FC ANTIBODY REGIONS TO CONFER EFFECTOR FUNCTION 审中-公开
标题翻译：工程FC抗体区域协调执行器功能
公开(公告)号：WO2007024249A2
公开(公告)日：2007-03-01
申请号：PCT/US2005/040962
申请日：2005-11-10
申请人： MACROGENICS, INC. , STAVENHAGEN, Jeffrey , KOENIG, Scott
发明人： STAVENHAGEN, Jeffrey , KOENIG, Scott
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效应子功能，其中母体分子不可检测地表现出该效应子功能。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。本发明的分子在治疗预防或管理疾病或病症例如癌症的患者亚群中特别有用，其中靶标抗原在靶细胞群体中以低水平表达，特别是在由于癌症或相关细胞上的靶抗原表达水平低，用现有治疗性抗体治疗难治的患者。

8. 发明申请

WO2007009064A2 METHODS FOR THE TREATMENT OF AUTOIMMUNE DISORDERS USING IMMUNOSUPPRESSIVE MONOCLONAL ANTIBODIES WITH REDUCED TOXICITY 审中-公开
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：WO2007009064A2
公开(公告)日：2007-01-18
申请号：PCT/US2006/027386
申请日：2006-07-11
申请人： MACROGENICS, INC. , KOENIG, Scott , WILDER, Ronald , BONVINI, Ezio , JOHNSON, Leslie, S.
发明人： KOENIG, Scott , WILDER, Ronald , BONVINI, Ezio , JOHNSON, Leslie, S.
IPC分类号： A61K39/395 , A61K48/00
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，使得它们与非修饰抗CD3抗体相比表现出降低或消除的效应子功能和T细胞活化。

9. 发明申请

WO2007117600A2 COMBINATION THERAPY FOR TREATING AUTOIMMUNE DISEASES 审中-公开
标题翻译：治疗自身免疫性疾病的组合疗法
公开(公告)号：WO2007117600A2
公开(公告)日：2007-10-18
申请号：PCT/US2007/008579
申请日：2007-04-06
申请人： MACROGENICS, INC. , KOENIG, Scott
发明人： KOENIG, Scott
IPC分类号： A61K39/395
CPC分类号： C07K16/2809 , A61K2039/507 , C07K16/2887
摘要： A combination therapy comprising administering to a subject in need of an effective therapeutic treatment for an autoimmune disease, a T cell antibody that is capable of modulating the activation of a T cell response to an antigen presenting cell in combination with a B cell antibody. The combination therapy may provide improved clinical benefits to a subject in need of treatment by reducing the circulating and tissue levels of B cells while providing immunosuppression of T cell activation, thus modulating the immune response to self antigens.
摘要翻译：一种联合疗法，其包括对需要对自身免疫性疾病进行有效治疗的受治疗者，能够调节与B细胞抗体组合的抗原呈递细胞的T细胞应答活化的T细胞抗体。联合治疗可以通过减少B细胞的循环和组织水平来提供需要治疗的受试者的改善的临床益处，同时提供T细胞活化的免疫抑制，从而调节对自身抗原的免疫应答。

10. 发明申请

WO2005115452A2 FCγRIIB-SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译： FCgammaRIIB特异性抗体及其使用方法
公开(公告)号：WO2005115452A2
公开(公告)日：2005-12-08
申请号：PCT/US2005/012798
申请日：2005-04-15
申请人： MACROGENICS, INC. , KOENIG, Scott , VERI, Maria, Concetta , TUAILLON, Nadine , BONVINI, Ezio , STAVENHAGEN, Jeffrey , RANKIN, Christopher
发明人： KOENIG, Scott , VERI, Maria, Concetta , TUAILLON, Nadine , BONVINI, Ezio , STAVENHAGEN, Jeffrey , RANKIN, Christopher
IPC分类号： A61K39/395
CPC分类号： C07K16/283 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C07K2317/41 , C07K2317/71 , C07K2317/732 , C07K2317/76 , 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 provides 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 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。本发明还提供抗FcγRIIB抗体或其抗原结合片段作为单一药物治疗用于治疗，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。

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