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1. 发明申请

WO2006088494A9 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT FC REGIONS AND METHODS OF USING THE SAME 审中-公开
公开(公告)号：WO2006088494A9
公开(公告)日：2006-08-24
申请号：PCT/US2005/024645
申请日：2005-07-12
申请人： MACROGENICS, INC. , STAVENHAGEN, Jeffrey , VIJH, Sujata , RANKIN, Christopher , GORLATOV, Sergey , HUANG, Ling
发明人： STAVENHAGEN, Jeffrey , VIJH, Sujata , RANKIN, Christopher , GORLATOV, Sergey , HUANG, Ling
IPC分类号： A61K39/395 , C07K16/28
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobins ( 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 FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function ( e.g ., ADCC) mediated by FcγR is desired, e.g ., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

2. 发明申请

WO2004063351A3 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT Fc REGIONS AND METHODS OF USING SAME 审中-公开
公开(公告)号：WO2004063351A3
公开(公告)日：2004-07-29
申请号：PCT/US2004/000643
申请日：2004-01-09
申请人： MACROGENICS, INC. , STAVENHAGEN, Jeffrey , VIJH, Sujata
发明人： STAVENHAGEN, Jeffrey , VIJH, Sujata
IPC分类号： A61K39/395
摘要： The present invention relates to 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 FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g ., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

3. 发明申请

WO2007106707A2 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT HEAVY CHAINS AND METHODS OF USING SAME 审中-公开
标题翻译：具有不同重要链条的抗体的鉴定和工程及其使用方法
公开(公告)号：WO2007106707A2
公开(公告)日：2007-09-20
申请号：PCT/US2007/063548
申请日：2007-03-08
申请人： MACROGENICS, INC. , STAVENHAGEN, Jeffrey
发明人： STAVENHAGEN, Jeffrey
IPC分类号： G06F19/00
CPC分类号： C07K16/44 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K2317/24 , C07K2317/72 , C07K2317/732 , C07K2317/734 , Y02A90/26
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant heavy chain, which variant heavy chain comprises constant domains from more than one IgG isotype. The variant heavy chain of the invention may further comprise at least one amino acid modification relative to the parental heavy chain, such that the Fc region of said variant heavy chain binds an FcγR with an altered affinity relative to a comparable molecule comprising the wild-type heavy cahin. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
摘要翻译：本发明涉及包括变体重链的分子，特别是多肽，更特别是包含变体重链的免疫球蛋白（例如抗体），该变体重链包含来自多于一种IgG同种型的恒定结构域。本发明的变体重链可以进一步包含相对于亲本重链的至少一个氨基酸修饰，使得所述变体重链的Fc区相对于包含野生型的可比分子具有改变的亲和力结合FcγR 型重胡萝卜素。本发明的分子特别可用于预防，治疗或改善与疾病，病症或感染相关的一种或多种症状。本发明的分子特别可用于治疗或预防需要由FcγR介导的效应细胞功能增强的功效（例如ADCC）的疾病或病症，例如癌症，感染性疾病，以及在增强治疗性抗体的治疗功效，其作用由ADCC介导。

4. 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。

5. 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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