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1. 发明授权

US11072653B2 LAG-3-binding molecules and methods of use thereof 有权
公开(公告)号：US11072653B2
公开(公告)日：2021-07-27
申请号：US15580029
申请日：2016-06-07
申请人： MacroGenics, Inc.
发明人： Ross La Motte-Mohs , Kalpana Shah , Douglas H. Smith , Leslie S. Johnson , Paul A. Moore , Ezio Bonvini , Scott Koenig
IPC分类号： C07K16/28 , A61K47/68 , A61P31/04 , A61K39/00
摘要： The present invention is directed to the anti-LAG-3 antibodies, LAG-3 mAb 1, LAG-3 mAb 2, LAG-3 mAb 4, LAG-3 mAb 5, and LAG-3 mAb 6, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to LAG-3-binding molecules that comprise LAG-3 binding fragments of such anti-LAG-3 antibodies, immunocongugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such LAG-3-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cells. The present invention also pertains to methods of detecting LAG-3, as well as methods of using molecules that bind LAG-3 for stimulating immune responses.

2. 发明授权

US10160806B2 Covalently bonded diabodies having immunoreactivity with PD-1 and LAG-3, and methods of use thereof 有权
公开(公告)号：US10160806B2
公开(公告)日：2018-12-25
申请号：US15321279
申请日：2015-06-19
申请人： MacroGenics, Inc.
发明人： Ezio Bonvini , Leslie S. Johnson , Kalpana Shah , Ross La Motte-Mohs , Paul A. Moore , Scott Koenig
IPC分类号： C07K16/28 , C07K16/46
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×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×LAG-3 bi-specific, tetra-valent diabody”).

3. 发明申请

US20170157251A1 Bi-Specific Monovalent Diabodies That are Capable of Binding CD19 and CD3, and Uses Thereof 审中-公开
公开(公告)号：US20170157251A1
公开(公告)日：2017-06-08
申请号：US15369360
申请日：2016-12-05
申请人： MacroGenics, Inc.
发明人： Ezio Bonvini , Leslie S. Johnson , Scott Koenig , Chia-Ying Kao Lam , Liqin Liu , Paul A. Moore
IPC分类号： A61K39/395 , A61K31/519 , C07K16/30 , C07K16/28
CPC分类号： A61K39/39558 , A61K31/497 , A61K31/505 , A61K31/519 , A61K39/39541 , A61K47/6803 , A61K47/6849 , A61K47/6879 , A61K2039/505 , A61P35/00 , C07K16/2803 , C07K16/2809 , C07K16/3061 , C07K2317/31 , C07K2317/33 , C07K2317/35 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/56 , C07K2317/626 , C07K2317/64 , C07K2317/92 , C07K2317/94 , A61K2300/00
摘要： The present invention is directed to a combination therapy involving the administration of: (1) a bi-specific molecule capable of specifically binding to CD19 and to CD3 (i.e., a CD19×CD3 bi-specific molecule), and (2) a Bruton's Tyrosine Kinase (BTK) inhibitor for the treatment of disease, in particular treatment of a disease associated with or characterized by the expression of CD19. Preferably, such a CD19×CD3 bi-specific molecules are bi-specific monovalent diabodies. The invention is directed to pharmaceutical compositions that contain such a CD19×CD3 bi-specific molecule, a BTK inhibitor, or a combination of such agents. The invention is additionally directed to methods for the use of such pharmaceutical compositions in the treatment of disease, in particular, treatment of a cancer associated with or characterized by the expression of CD19.

4. 发明申请

US20160017038A1 Bispecific Molecules That are Immunoreactive with Immune Effector Cells That Express an Activating Receptor and an Antigen Expressed by a Cell Infected by a Virus and Uses Thereof 有权
标题翻译：表达激活受体和由病毒感染的细胞表达的抗原的免疫效应细胞的免疫反应性的双特异性分子及其用途
公开(公告)号：US20160017038A1
公开(公告)日：2016-01-21
申请号：US14775041
申请日：2014-03-13
申请人： MACROGENICS, INC.
发明人： Scott Koenig
IPC分类号： C07K16/28 , C07K16/10 , C07K16/08
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。

5. 发明授权

US11078279B2 Combination therapy for the treatment of cancer 有权
公开(公告)号：US11078279B2
公开(公告)日：2021-08-03
申请号：US15580969
申请日：2016-06-09
申请人： MacroGenics, Inc.
发明人： Jon Marc Wigginton , Naimish Bharat Pandya , Robert Joseph Lechleider , Scott Koenig , Ezio Bonvini
IPC分类号： C07K16/28 , C07K16/32 , A61P35/00 , A61K39/00
摘要： This invention relates to a pharmaceutical composition that comprises a first molecule that specifically binds HER2/neu and a second molecule that specifically binds a cell-surface receptor (or its ligand) that is involved in regulating an immune checkpoint (or the ligand thereof). The invention particularly relates to the embodiment wherein the second molecule binds to PD-1. The invention also relates to the use of such pharmaceutical compositions to treat cancer and other diseases.

6. 发明申请

US20210206851A1 LAG-3-Binding Molecules and Methods of Use Thereof 有权
公开(公告)号：US20210206851A1
公开(公告)日：2021-07-08
申请号：US17147279
申请日：2021-01-12
申请人： MacroGenics, Inc.
发明人： Ross La Motte-Mohs , Kalpana Shah , Douglas H. Smith , Leslie S. Johnson , Paul A. Moore , Ezio Bonvini , Scott Koenig
IPC分类号： C07K16/28 , A61P31/04
摘要： The present invention is directed to the anti-LAG-3 antibodies: LAG-3 mAb 1, LAG-3 mAb 2, LAG-3 mAb 4, LAG-3 mAb 5, and LAG-3 mAb 6, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to LAG-3-binding molecules that comprise LAG-3 binding fragments of such anti-LAG-3 antibodies, immunoconjugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such LAG-3-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cell. The present invention also pertains to methods of detecting LAG-3, as well as methods of using molecules that bind LAG-3 for stimulating immune responses.

7. 发明申请

US20180009902A1 Methods for the Treatment of Disease Using Immunoglobulins Having Fc Regions with Altered Affinities for FcgammaRactivating and FcgammaRinhibiting 审中-公开
公开(公告)号：US20180009902A1
公开(公告)日：2018-01-11
申请号：US15621710
申请日：2017-06-13
申请人： MacroGenics, Inc.
发明人： Jeffrey B. Stavenhagen , Scott Koenig
IPC分类号： C07K16/30 , C07K16/28 , A61K39/00
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).

8. 发明申请

US20160046714A1 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：US20160046714A1
公开(公告)日：2016-02-18
申请号：US14668036
申请日：2015-03-25
申请人： MacroGenics, Inc.
发明人： Scott Koenig , Ronald Wilder , Ezio Bonvini , Leslie S. Johnson
IPC分类号： C07K16/28 , A61K45/06 , 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。

9. 发明授权

US11639386B2 Bi-specific monovalent diabodies that are capable of binding CD19 and CD3, and uses thereof 有权
公开(公告)号：US11639386B2
公开(公告)日：2023-05-02
申请号：US16807514
申请日：2020-03-03
申请人： MacroGenics, Inc.
发明人： Leslie S. Johnson , Ezio Bonvini , Chia-Ying Kao Lam , Paul A. Moore , Liqin Liu , Scott Koenig
IPC分类号： C07K16/28 , C07K16/46 , C07K16/30 , A61K39/395 , A61K39/00
摘要： CD19×CD3 bi-specific monovalent diabodies, and particularly, CD19×CD3 bi-specific monovalent Fc diabodies, are capable of simultaneous binding to CD19 and CD3, and are used in the treatment of hematologic malignancies.

10. 发明申请

US20200231675A1 PD-1-BINDING MOLECULES AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：US20200231675A1
公开(公告)日：2020-07-23
申请号：US16752464
申请日：2020-01-24
申请人： MACROGENICS, INC
发明人： Kalpana Shah , Douglas H. Smith , Ross La Motte-Mohs , Leslie S. Johnson , Paul A. Moore , Ezio Bonvini , Scott Koenig
IPC分类号： C07K16/28
摘要： The present invention is directed to selected anti-PD-1 antibodies capable of binding to both cynomolgus monkey PD-1 and to human PD-1: PD-1 mAb 1, PD-1 mAb 2, PD-1 mAb 3, PD-1 mAb 4, PD-1 mAb 5, PD-1 mAb 6, PD-1 mAb 7, PD-1 mAb 8, PD-1 mAb 9, PD-1 mAb 10, PD-1 mAb 11, PD-1 mAb 12, PD-1 mAb 13, PD-1 mAb 14, or PD-1 mAb 15, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to PD-1-binding molecules that comprise PD-1 binding fragments of such anti-PD-1 antibodies, immunocongugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such PD-1-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cells. The present invention also pertains to methods of using molecules that bind PD-1 for stimulating immune responses, as well as methods of detecting PD-1.

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