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1. 发明专利

JP2011121954A IDENTIFICATION AND ENGINEERING OF ANTIBODY WITH VARIANT Fc REGION AND METHOD FOR UTILIZING THE SAME 审中-公开
标题翻译：具有变体Fc区的抗体的鉴定和工程及其利用方法
公开(公告)号：JP2011121954A
公开(公告)日：2011-06-23
申请号：JP2010292632
申请日：2010-12-28
申请人： Macrogenics Inc , マクロジェニクス,インコーポレーテッド
发明人： STAVENHAGEN JEFFREY , VIJH SUJATA
IPC分类号： C07K16/00 , A61K39/395 , A61P31/04 , A61P35/00 , C12N15/09
CPC分类号： C07K14/70535 , C07K14/36 , C07K14/405 , C07K16/005 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/76 , C07K2317/92 , C07K2319/70 , G01N33/6857 , G01N2333/70535
摘要： PROBLEM TO BE SOLVED: To provide a molecule, particularly a polypeptide, more particularly immunoglobulin (e.g., an antibody) comprising a variant Fc region. SOLUTION: The variant Fc region includes 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. The molecule is particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecule is particularly useful for treatment or prevention of a disease or disorder where an enhanced efficacy or effector cell function äe.g., antibody-dependent cellular cytotoxicity (ADCC)} mediated by FcγR is desired (e.g., cancer or infectious disease), and in enhancing the therapeutic efficacy of therapeutic antibodies (the effect of which is mediated by the ADCC). COPYRIGHT: (C)2011,JPO&INPIT
摘要翻译：待解决的问题：提供包含变体Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体）。解决方案：变体Fc区包含相对于野生型Fc区的至少一个氨基酸修饰，该变体Fc区以更大的亲和力结合FcγRIIIA和/或FcγRIIA。该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。该分子特别可用于治疗或预防由FcγR介导的增强的功效或效应细胞功能，即抗体依赖性细胞毒性（ADCC）}（例如癌症或感染性疾病）的疾病或病症，并提高治疗性抗体的疗效（其作用由ADCC介导）。版权所有（C）2011，JPO＆INPIT

2. 发明专利

JP2015044817A 変異型Ｆｃ領域を含む抗体の同定および作製ならびにその利用法有权
标题翻译：具有变体Fc区的抗体的鉴定和工程及其利用方法
公开(公告)号：JP2015044817A
公开(公告)日：2015-03-12
申请号：JP2014203774
申请日：2014-10-02
申请人：マクロジェニクス,インコーポレーテッド , Macrogenics Inc
发明人： STAVENHAGEN JEFFREY , VIJH SUJATA
IPC分类号： C07K16/32 , A61K39/002 , A61K39/02 , A61K39/12 , A61K39/395 , A61K45/00 , A61P31/00 , A61P31/04 , A61P31/12 , A61P33/00 , A61P35/00 , A61P37/04 , C07K16/00 , C12N15/09
CPC分类号： C07K14/70535 , C07K14/36 , C07K14/405 , C07K16/005 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/76 , C07K2317/92 , C07K2319/70 , G01N33/6857 , G01N2333/70535
摘要：【課題】変異型Fc領域を含む分子、特にポリペプチド、さらに特定すると免疫グロブリン(例えば、抗体)に関し、該変異型Fc領域は、野生型Fc領域に対して少なくとも1個のアミノ酸の改変を含み、野生型Fc領域を含む対応する分子よりも高い親和性でFcγRIIIA及び/又はFcγRIIAと結合する分子の提供。【解決手段】分子は、疾患、障害又は感染と関連した1以上の症状を予防し、治療し、又は改善するのに特に有用である。分子は、FcγRにより媒介されるエフェクター細胞機能(例えば、ADCC)の増大した効力が望まれる疾患又は障害(例えば、癌、感染症)を治療又は予防するのに、又、治療用抗体(その効果がADCCによって媒介される)の治療効力を高めるのに、特に有用である。【選択図】図1
摘要翻译：要解决的问题：提供包含变体Fc区，特别是多肽的分子，更具体地，其中变体Fc区在野生型Fc区具有至少一个氨基酸修饰的免疫球蛋白（例如抗体），以及分子以比含有野生型Fc区的配对分子更高的亲和力结合FcγRIIIA和/或FcγRIIA。解决方案：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病症。该分子特别可用于治疗或预防由FcγR（例如ADCC）介导的效应细胞功能的增强功效的疾病或病症如癌症和感染性疾病，以及用于增强治疗性抗体的治疗效果其作用由ADCC介导。

3. 发明申请

WO2004063351A2 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT Fc REGIONS AND METHODS OF USING SAME 审中-公开
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：WO2004063351A2
公开(公告)日：2004-07-29
申请号：PCT/US2004000643
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： C07K16/00 , C12N
CPC分类号： C07K14/70535 , C07K14/36 , C07K14/405 , C07K16/005 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/76 , C07K2317/92 , C07K2319/70 , G01N33/6857 , G01N2333/70535
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 FcgammaRIIIA and/or FcgammaRIIA 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 FcgammaR 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Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比较分子，以更大的亲和力结合FcγRIIIA和/或FcγRIIA。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通过FcγAMR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，感染性疾病和增强治疗功效的治疗性抗体，其作用由ADCC介导。

4. 发明申请

WO2006088494A2 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT FC REGIONS AND METHODS OF USING THE SAME 审中-公开
标题翻译：具有不同FC区域的抗体的鉴定和工程及其使用方法
公开(公告)号：WO2006088494A2
公开(公告)日：2006-08-24
申请号：PCT/US2005024645
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： G01N33/53 , C07H21/04 , C07K16/00 , C07K16/44 , C12N5/06 , C12P21/04
CPC分类号： A61K39/39558 , A61K2039/505 , C07K16/00 , C07K16/005 , C07K2317/52 , C07K2317/732 , C07K2317/734
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 Fc?RIIIA and/or Fc?RIIA 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 Fc?R 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Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比较分子，以更高的亲和力结合FcγRIIIA和/或FcγRIIA。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。

5. 发明申请

WO2006088494A3 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT FC REGIONS AND METHODS OF USING THE SAME 审中-公开
标题翻译：具有不同FC区域的抗体的鉴定和工程及其使用方法
公开(公告)号：WO2006088494A3
公开(公告)日：2007-08-23
申请号：PCT/US2005024645
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 , C07K16/00 , C07K16/28
CPC分类号： A61K39/39558 , A61K2039/505 , C07K16/00 , C07K16/005 , C07K2317/52 , C07K2317/732 , C07K2317/734
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 Fc?RIIIA and/or Fc?RIIA 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 Fc?R 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Fc区的分子，特别是多肽，更特别是免疫球蛋白（例如，抗体），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，所述变体Fc区相对于包含野生型Fc区的可比较分子，以更高的亲和力结合FcγRIIIA和/或FcγRIIA。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。

6. 发明专利

SG170110A1 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT HEAVY CHAINS AND METHODS OF USING SAME 未知
公开(公告)号：SG170110A1
公开(公告)日：2011-04-29
申请号：SG2011017993
申请日：2007-03-08
申请人： MACROGENICS INC
发明人： STAVENHAGEN JEFFREY
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 Fc?R with an altered affinity relative to a comparable molecule comprising the wild- type heavy chain. 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 Fc?R is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC. Figure No. 17A

7. 发明专利

AU2011265460A1 Identification and engineering of antibodies with variant Fc regions and methods of using same 未知
公开(公告)号：AU2011265460A1
公开(公告)日：2012-01-19
申请号：AU2011265460
申请日：2011-12-22
申请人： MACROGENICS INC
发明人： VIJH SUJATA , STAVENHAGEN JEFFREY
IPC分类号： C07K16/00
摘要： The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fe region, wherein said variant Fe region comprises at least one amino acid modification relative to a wild-type Fe region, which variant Fc region binds FcϝRIIIA 5 and/or FeϝRIIA 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 10 efficacy of effector cell function (e.g., ADCC) mediated by FcϝR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

8. 发明专利

CA2512729A1 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT FCREGIONS AND METHODS OF USING SAME 未知
公开(公告)号：CA2512729A1
公开(公告)日：2004-07-29
申请号：CA2512729
申请日：2004-01-09
申请人： MACROGENICS INC
发明人： VIJH SUJATA , STAVENHAGEN JEFFREY
IPC分类号： C07K16/00 , A61K39/395 , C07K16/28
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 Fc³RIIIA and/or Fc³RIIA 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 Fc³R is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

9. 发明公开

EP1810035A4 ENGINEERING FC ANTIBODY REGIONS TO CONFER EFFECTOR FUNCTION 审中-公开
标题翻译： ERZEUGUNG VON FC-ANTIKÖRPERREGIONENFÜREFFEKTORFUNKTION
公开(公告)号：EP1810035A4
公开(公告)日：2010-03-17
申请号：EP05857976
申请日：2005-11-10
申请人： MACROGENICS INC
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 FcgammaR, such as, but not limited to, ADCC. In one embodiment, the variant Fc region binds FcgammaRIIIA and/or FcgammaRIIA 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区包含相对于野生型Fc区的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介导的增强的效应细胞功能，例如但不限于ADCC。在一个实施方案中，相对于包含野生型Fc区的可比分子，变体Fc区以更高的亲和力结合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靶抗原表达水平低的现有治疗性抗体治疗难治的患者中。

10. 发明申请

WO2007106707A8 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：WO2007106707A8
公开(公告)日：2009-07-23
申请号：PCT/US2007063548
申请日：2007-03-08
申请人： MACROGENICS INC , STAVENHAGEN JEFFREY
发明人： STAVENHAGEN JEFFREY
IPC分类号： G01N33/53 , C07H21/04 , C07K16/44 , C12N5/06
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 Fc?R 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 Fc?R 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较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期望由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。

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