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81. 发明申请

WO2015200119A8 COVALENTLY BONDED DIABODIES HAVING IMMUNOREACTIVITY WITH PD-1 AND LAG-3, AND METHODS OF USE THEREOF 审中-公开
标题翻译：具有PD-1和LAG-3的具有免疫反应性的双重结合的双歧杆菌及其使用方法
公开(公告)号：WO2015200119A8
公开(公告)日：2017-03-30
申请号：PCT/US2015036634
申请日：2015-06-19
申请人： MACROGENICS INC
发明人： BONVINI EZIO , JOHNSON LESLIE S , SHAH KALPANA , LA MOTTE-MOHS ROSS , MOORE PAUL A , KOENIG SCOTT
IPC分类号： C07K16/28
CPC分类号： C07K16/2803 , C07K16/2818 , C07K16/468 , C07K2317/31 , C07K2317/626 , C07K2317/74
摘要： The present invention is directed to bi-specific diabodies that comprise two or more polypeptide chains and which possess at least one Epitope-Binding Site that is immunospecific for an epitope of PD-1 and at least one Epitope-Binding Site that is immunospecific for an epitope of LAG-3 (i.e., a "PD-I x LAG-3 bi-specific diabody"). More preferably, the present invention is directed to bi-specific diabodies that comprise four polypeptide chains and which possess two Epitope-Binding Sites that are immunospecific for one (or two) epitope(s) of PD-1 and two Epitope-Binding Site that are immunospecific for one (or two) epitope(s) of LAG-3 (i.e., a "PD-1 x LAG-3 bi-specific, tetra-valent diabody").
摘要翻译：本发明涉及包含两个或多个多肽链并且具有至少一个针对PD-1的表位具有免疫特异性的表位结合位点和至少一个对于一个或多个具有免疫特异性的表位结合位点的表位的双抗体 LAG-3表位（即，“PD-1×LAG-3双特异性双抗体”）。更优选地，本发明涉及包含四个多肽链并且具有对PD-1的一个或两个表位和两个表位结合位点具有免疫特异性的两个表位结合位点的双特异性双抗体，对于一个（或两个）LAG-3表位（即，“PD-1×LAG-3双特异性四价双抗体”）是免疫特异性的。

82. 发明申请

WO2016122702A1 MULTIVALENT MOLECULES COMPRISING DR5-BINDING DOMAINS 审中-公开
标题翻译：包含DR5结合域的多重分子
公开(公告)号：WO2016122702A1
公开(公告)日：2016-08-04
申请号：PCT/US2015/033099
申请日：2015-05-29
申请人： MACROGENICS, INC.
发明人： MOORE, Paul, A. , JOHNSON, Leslie, S. , LI, Jonathan, C. , SHAH, Kalpana
IPC分类号： C07K16/28
CPC分类号： C07K16/2878 , A61K2039/505 , C07K16/30 , C07K2317/24 , C07K2317/35 , C07K2317/622 , C07K2317/73 , C07K2317/92
摘要： The present invention is directed to multivalent DR5 -Binding Molecules that comprise Binding Domain(s) of anti-DR5 antibodies, and particularly Binding Domain(s) of anti-human DR5 antibodies. The DR5 -Binding Molecules of the present invention include bivalent and tetravalent molecules having two, three or four DR5-Binding Domains each capable of binding human DR5. In particular, the present invention is directed to multivalent DR5 -Binding Molecules that comprise diabodies, and more particularly, diabodies that comprise a covalently bonded complex of two or more polypeptide chains. The invention particularly pertains to such multivalent DR5 -Binding Molecules that comprise fragments of the anti-DR5 antibodies DR5 mAb 1 and/or DR5 mAb 2, and/or humanized and chimeric versions of such antibodies.
摘要翻译：本发明涉及包含抗DR5抗体的结合域，特别是抗人DR5抗体的结合结构域的多价DR5-结合分子。本发明的DR5-结合分子包括具有两个，三个或四个能结合人DR5的DR5结合结构域的二价和四价分子。特别地，本发明涉及包含双抗体的多价DR5-结合分子，更具体地，涉及包含两个或多个多肽链的共价键合复合物的双抗体。本发明特别涉及包含抗DR5抗体DR5mAb1和/或DR5mAb2的片段，和/或这种抗体的人源化和嵌合形式的多价DR5-结合分子。

83. 发明申请

WO2016048938A1 BI-SPECIFIC MONOVALENT DIABODIES THAT ARE CAPABLE OF BINDING CD19 AND CD3, AND USES THEREOF 审中-公开
标题翻译：具有结合CD19和CD3的双特异性单价糖尿病及其用途
公开(公告)号：WO2016048938A1
公开(公告)日：2016-03-31
申请号：PCT/US2015/051314
申请日：2015-09-22
申请人： MACROGENICS, INC.
发明人： JOHNSON, Leslie, S. , BONVINI, Ezio , LAM, Chia-ying, Kao , MOORE, Paul, A. , LIU, Liqin , KOENIG, Scott
IPC分类号： C07K16/28
CPC分类号： C07K16/2803 , A61K39/39558 , A61K2039/505 , C07K16/2809 , C07K16/2896 , C07K16/3061 , C07K16/468 , C07K2317/31 , C07K2317/33 , C07K2317/35 , C07K2317/524 , C07K2317/526 , C07K2317/56 , C07K2317/569 , C07K2317/626 , C07K2317/73 , C07K2317/90 , C07K2317/92 , C07K2317/94
摘要： CD 19 x CD3 bi-specific monovalent diabodies, and particularly, CD 19 x CD3 bi- specific monovalent Fc diabodies, are capable of simultaneous binding to CD 19 and CD3, and are used in the treatment of hematologic malignancies.
摘要翻译： CD 19 x CD3双特异性单价双抗体，特别是CD 19 x CD3双特异性单价Fc双抗体能够同时结合CD19和CD3，并用于血液恶性肿瘤的治疗。

84. 发明申请

WO2008019199A8 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：WO2008019199A8
公开(公告)日：2015-10-29
申请号：PCT/US2007072153
申请日：2007-06-26
申请人： MACROGENICS INC , JOHNSON LESLIE S , HUANG LING , GERENA ROBYN
发明人： JOHNSON LESLIE S , HUANG LING , GERENA ROBYN
IPC分类号： A61K39/395 , C07K16/00
CPC分类号： C07K16/283 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2317/34 , C07K2317/52 , C07K2317/565 , 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 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。

85. 发明申请

WO2014159940A1 BISPECIFIC MOLECULES THAT ARE IMMUNOREACTIVE WITH IMMUNE EFFECTOR CELLS THAT EXPRESS AN ACTIVATING RECEPTOR 审中-公开
标题翻译：具有表达活化受体的免疫效应细胞的免疫分子
公开(公告)号：WO2014159940A1
公开(公告)日：2014-10-02
申请号：PCT/US2014/025491
申请日：2014-03-13
申请人： MACROGENICS, INC.
发明人： KOENIG, Scott
IPC分类号： A61K39/12 , A61K45/00 , A61K39/00 , A61K39/38 , A01N65/00 , C12N7/00 , C12N7/01 , C12N5/07 , C12N5/16
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/084 , C07K16/085 , C07K16/1027 , C07K16/1063 , C07K16/2809 , C07K2317/31 , C07K2317/626 , C07K2317/73 , C07K2317/92 , C12N5/0638 , C12N2510/00 , C12N2710/16211 , C12N2710/20011 , C12N2740/16111 , C12N2760/18511
摘要： The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections.
摘要翻译：本发明涉及能够定位表达病毒感染细胞的激活受体的免疫效应细胞的双特异性分子，从而有助于杀死病毒感染的细胞。在优选的实施方案中，使用与免疫效应细胞的活化受体免疫反应的双特异性分子和由病毒感染的细胞表达的抗原来实现这种定位，其中抗原可检测地存在于感染病毒的细胞上比通过双特异性分子在病毒上检测抗原的水平高的水平，以及这种双特异性分子在潜伏性病毒感染的治疗中的用途。

86. 发明申请

WO2010080538A1 COVALENT DIABODIES AND USES THEREOF 审中-公开
标题翻译：同性双胞胎及其用途
公开(公告)号：WO2010080538A1
公开(公告)日：2010-07-15
申请号：PCT/US2009/068577
申请日：2009-12-17
申请人： MACROGENICS, INC. , JOHNSON, Leslie, S. , HUANG, Ling
发明人： JOHNSON, Leslie, S. , HUANG, Ling
IPC分类号： A61K39/00
CPC分类号： C07K16/283 , A61K2039/505 , C07K16/2803 , C07K16/2809 , C07K16/32 , C07K16/44 , C07K2317/34 , C07K2317/52 , C07K2317/56 , C07K2317/626 , C07K2317/64 , C07K2317/73 , C07K2317/92 , C07K2319/00
摘要： The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody- like functionality to engineered into the molecule.
摘要翻译：本发明涉及双抗体分子及其在治疗各种疾病和病症（包括免疫学疾病，感染性疾病，中毒和癌症）中的用途。本发明的双抗体分子包含两个缔合以形成至少两个表位结合位点的多肽链，其可识别相同或不同抗原上相同或不同的表位。另外，抗原可以来自相同或不同的分子。双抗体分子的单个多肽链可以通过非肽键共价键共价结合，例如但不限于位于每个多肽链内的半胱氨酸残基的二硫键。在具体实施方案中，本发明的双抗体分子还包含Fc区，其允许类似抗体的功能改造成分子。

87. 发明申请

WO2010033279A2 ANTIBODIES WITH ALTERED BINDING TO FCRN AND METHODS OF USING SAME 审中-公开
标题翻译：抗体与FCRN结合的抗体及其使用方法
公开(公告)号：WO2010033279A2
公开(公告)日：2010-03-25
申请号：PCT/US2009/046214
申请日：2009-06-04
申请人： MACROGENICS, INC. , GORLATOV, Sergey
发明人： GORLATOV, Sergey
IPC分类号： A61K39/395
CPC分类号： C07K16/30 , A61K39/395 , A61K39/39558 , A61K45/06 , C07K16/00 , C07K16/18 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/72 , C07K2317/94
摘要： This invention relates to antibodies with altered binding to FcRn, and particularly antibodies having enhanced binding to FcRn and/or enhanced serum half-lives. The invention also relates to methods of using the 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：本发明涉及具有改变的与FcRn的结合的抗体，特别是具有增强的与FcRn的结合和/或增加的血清半衰期的抗体。本发明还涉及使用抗体和包含它们的组合物在诊断，预后和治疗诸如癌症，自身免疫性疾病，炎性病症和传染病等疾病中的方法。

88. 发明申请

WO2009117030A3 IMPROVED COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF SMALLPOX 审中-公开
标题翻译：改进的预防和治疗小型组合物
公开(公告)号：WO2009117030A3
公开(公告)日：2010-01-14
申请号：PCT/US2008087390
申请日：2008-12-18
申请人： MACROGENICS INC , JOHNSON LESLIE S , HUANG LING
发明人： JOHNSON LESLIE S , HUANG LING
IPC分类号： A61K39/00
CPC分类号： C07K16/081 , A61K2039/505 , A61K2039/507 , C07K2317/21 , C07K2317/31 , C07K2317/55 , C07K2317/76
摘要： The present invention relates to improved compositions for the prevention and treatment of smallpox, and in particular to the use of compositions containing an antibody that binds to an epitope found on the MV form of the smallpox virus and an antibody that binds to an epitope found on the EV form of the smallpox virus. The invention relates to such compositions, especially to non-blood derived antibody compositions, such as chimeric or humanized antibodies, and to methods for their use in imparting passive immunity against smallpox infection to individuals at risk of smallpox virus infection or who exhibit smallpox.
摘要翻译：本发明涉及用于预防和治疗天花的改进的组合物，特别是涉及使用含有抗体的组合物，所述组合物含有与在天花病毒MV形式上发现的表位结合的抗体，以及结合表位上发现的表位的抗体 EV形式的天花病毒。本发明涉及这样的组合物，特别是涉及非血液衍生的抗体组合物，例如嵌合或人源化抗体，以及它们用于在天花病毒感染风险或出现天花的个体赋予对天花感染的被动免疫的方法。

89. 发明申请

WO2007021841A3 IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT FC REGIONS AND METHODS OF USING 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：WO2007021841A3
公开(公告)日：2009-06-18
申请号：PCT/US2006031201
申请日：2006-08-10
申请人： MACROGENICS INC , STAVENHAGEN JEFFERY , GORLATOV SERGEY , RANKIN CHRISTOPHER , TUAILLON NADINE
发明人： STAVENHAGEN JEFFERY , GORLATOV SERGEY , RANKIN CHRISTOPHER , TUAILLON NADINE
IPC分类号： C07K16/00 , A61K39/395 , C07H21/04 , C07K17/00 , C12N5/06 , C12N15/00 , C12Q1/68
CPC分类号： G01N33/574 , A61K2039/505 , C07K16/283 , C07K16/2887 , C07K16/32 , C07K16/44 , C07K2317/24 , C07K2317/52 , C07K2317/72 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C07K2317/92 , C07K2319/30
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 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通过FcγR介导的效应细胞功能（例如ADCC）增强功效的疾病或病症，例如，，癌症，感染性疾病，以及提高其作用由ADCC介导的治疗性抗体的治疗功效。

90. 发明申请

WO2008105886A3 HUMANIZED FC?RIIB-SPECIFIC ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译：人类FC？RIIB特异性抗体及其使用方法
公开(公告)号：WO2008105886A3
公开(公告)日：2009-03-05
申请号：PCT/US2007069767
申请日：2007-05-25
申请人： MACROGENICS INC , JOHNSON LESLIE S , HUANG LING
发明人： JOHNSON LESLIE S , HUANG LING
IPC分类号： A61K39/00 , C07K16/00
CPC分类号： A61K39/39 , A61K2039/505 , A61K2039/55516 , C07K16/283 , C07K2317/24 , C07K2317/34 , C07K2317/52 , G01N33/564 , G01N33/6893 , G01N2800/24
摘要： The present invention relates to humanized Fc?RIIB antibodies, fragments, and variants thereof that bind human Fc?RIIB with a greater affinity than said antibody binds Fc?RIIA. The invention encompasses the use of the humanized antibodies of the invention for the treatment of any disease related to loss of balance of Fc receptor mediated signaling, such as cancer, autoimmune and inflammatory disease. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the humanized antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing the efficacy of a vaccine composition by administering the humanized antibodies of the invention. The invention encompasses methods for treating an autoimmune disease and methods for elimination of cancer cells that express Fc?RIIB.
摘要翻译：本发明涉及以比所述抗体更大的亲和力结合FcγRIIA的结合人FcγRIIB的人源化FcγRIIB抗体，其片段和变体。本发明包括本发明的人源化抗体用于治疗与Fc受体介导的信号传导的平衡丧失有关的任何疾病（例如癌症，自身免疫性和炎症性疾病）的用途。本发明提供了通过施用本发明的人源化抗体来增强治疗性抗体的治疗效果以增强治疗性抗体的效应子功能的方法。本发明还提供了通过施用本发明的人源化抗体来增强疫苗组合物的功效的方法。本发明包括治疗自身免疫疾病的方法和消除表达FcγRIIB的癌细胞的方法。

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