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1. 发明申请

WO2021167885A CD137 BINDING MOLECULES AND USES THEREOF 审中-公开
公开(公告)号：WO2021167885A
公开(公告)日：2021-08-26
申请号：PCT/US2021/018177
申请日：2021-02-16
申请人： MACROGENICS, INC. [US]/[US]
发明人： BEREZHNOY, Alexey Yevgenyevich , DIEDRICH, Gundo , MOORE, Paul A. , BONVINI, Ezio , SHAH, Kalpana
IPC分类号： A61K39/395 , C07K14/715 , C07K16/28 , C12P21/08
摘要： The present invention is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137, including antibodies, and molecules comprising epitope-binding fragments thereof The invention is further directed to multispecific binding molecules comprising one or more epitope-binding sites specific for an epitope of CD137 and one or more epitope-binding sites specific for an epitope of a tumor antigen ("TA") (e.g, a "CD137 x TA Binding Molecule").

2. 发明申请

WO2019160904A1 VARIANT CD3-BINDING DOMAINS AND THEIR USE IN COMBINATION THERAPIES FOR THE TREATMENT OF DISEASE 审中-公开
公开(公告)号：WO2019160904A1
公开(公告)日：2019-08-22
申请号：PCT/US2019/017772
申请日：2019-02-13
申请人： MACROGENICS, INC.
发明人： BONVINI, Ezio , HUANG, Ling , LAM, Chia-Ying, Kao , CHICHILI, Gurunadh, Reddy , ALDERSON, Ralph, Froman , MOORE, Paul, A. , JOHNSON, Leslie, S.
IPC分类号： A61K39/395 , C07K16/28 , C07K16/30 , C07K16/32 , C07K16/44
摘要： The present invention is directed to DA x CD3 Binding Molecules comprising a vCD3- Binding Domain, which comprises a CDRHI Domain, a CDRH2 Domain, a CDRH3 Domain, a CDRL I Domain, a CDRL2 Domain, and a CDRL3 Domain, at least one of which differs in amino acid sequence from the amino acid sequence of the corresponding CDR of a rCD3- Binding Domain, wherein the DA x CD3 Binding Molecule comprising such vCD3-Binding Domain exhibits an altered affinity for CD3, relative to a DA x CD3 Binding Molecule comprising such rCD3-Binding Domain. The invention particularly concerns to such DA x CD3 Binding Molecules comprising a vCD3-Binding Domain which exhibit reduced affinity for CD3 and are capable of mediating redirected killing of target cells expressing a DA and exhibit lower levels of cytokine release relative to a DA x CD3 Binding Molecule comprising a rCD3-Binding Domain. The invention particularly concerns the use of DA x CD3 Binding Molecules comprising a vCD3 -Binding Domain in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s).

3. 发明申请

WO2018119196A1 IMMUNOCONJUGATES TARGETING ADAM9 AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：WO2018119196A1
公开(公告)日：2018-06-28
申请号：PCT/US2017/067823
申请日：2017-12-21
申请人： IMMUNOGEN, INC. , MACROGENICS, INC.
发明人： HICKS, Stuart William , YODER, Nicholas C. , BARAT, Bhaswati , BONVINI, Ezio , DIEDRICH, Gundo , JOHNSON, Leslie S. , LOO, Deryk , SCRIBNER, Juniper A.
IPC分类号： A61K47/68 , A61P35/00 , C07K16/40 , C07K16/28 , C07K16/30
摘要： The present invention is directed to immunoconjugates comprising an antibody or fragment thereof capable of specifically binding to "Disintegrin and Metalloproteinase Domain-containing Protein 9" ("ADAM9") conjugated to at least one pharmacological agent. The invention particularly concerns such immunoconjugates that are cross -reactive with human ADAM9 and the ADAM9 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to all such immunoconjugates that comprise a Light Chain Variable (VL) Domain and/or a Heavy Chain Variable (VH) Domain that has been humanized and/or deimmunized so as to exhibit reduced immunogenicity upon administration of such immunoconjugate to a recipient subject. The invention is also directed to pharmaceutical compositions that contain any of such immunoconjugates, and to methods involving the use of any of such immunoconjugates in the treatment of cancer and other diseases and conditions.

4. 发明申请

WO2017214092A1 COMBINATION THERAPY 审中-公开
标题翻译：联合治疗
公开(公告)号：WO2017214092A1
公开(公告)日：2017-12-14
申请号：PCT/US2017/036075
申请日：2017-06-06
申请人： MACROGENICS, INC.
发明人： BONVINI, Ezio , KOENIG, Scott , JOHNSON, Leslie, S. , MOORE, Paul, A. , ALDERSON, Ralph, F.
IPC分类号： A61K39/395 , C07K16/28 , A61P35/00 , A61P31/00
摘要： The present invention is directed to a combination therapy for the treatment of cancer and pathogen-associated diseases, that comprises the administration of: (I) a molecule (e.g., a diabody, an scFv, an antibody, a TandAb, etc.) capable of binding PD-I or a natural ligand of PD-I, and (2) a molecule (e.g., a diabody, a BiTe, a bispecific antibody, a CAR, etc.) capable of mediating the redirected killing of a target cell (e.g., a cancer cell or a pathogeninfected cell, etc.) expressing a Disease Antigen. The invention particularly concerns the embodiment in which the molecule capable of mediating the redirected killing of the target cell is a bispecific binding molecule that comprises a first epitope-binding site capable of immunospecifically binding an epitope of a cell surface molecule of an effector cell and a second epitope-binding site that is capable of immunospecifically binding an epitope of such target cells.
摘要翻译：本发明涉及用于治疗癌症和病原体相关疾病的组合疗法，其包括施用以下物质：（I）分子（例如双抗体，scFv，抗体，TandAb等），和（2）能够介导PD-1或PD-1的天然配体的分子（例如双抗体，BiTe，双特异性抗体，CAR等）表达疾病抗原的靶细胞（例如，癌细胞或病原体感染的细胞等）的重定向杀死。本发明特别涉及其中能够介导重定向杀死靶细胞的分子的双特异性结合分子的实施方案，其包含能够免疫特异性结合效应细胞的细胞表面分子的表位的第一表位结合位点和第二表位结合位点，其能够免疫特异性地结合此类靶细胞的表位。

5. 发明申请

WO2017062619A3 COMBINATION THERAPY FOR THE TREATMENT OF CANCER 审中-公开
标题翻译：治疗癌症的组合治疗
公开(公告)号：WO2017062619A3
公开(公告)日：2017-05-18
申请号：PCT/US2016055750
申请日：2016-10-06
申请人： MACROGENICS INC
发明人： VASSELLI JAMES , WIGGINTON JON MARC , BONVINI EZIO , KOENIG SCOTT
IPC分类号： A61K39/395 , A61K35/04 , C07K16/18 , C07K16/28
CPC分类号： A61K45/06 , A61K2039/507 , A61K2039/545 , C07K16/2818 , C07K16/2827
摘要： The present invention is directed to a combination therapy involving the administration of a first molecule that specifically binds to human B7-H3 and a second molecule that that specifically binds to human PD-1 to a subject for the treatment of cancer and/or inflammation. The invention also concerns pharmaceutical compositions that comprise a first molecule that specifically binds to human B7-H3 and a second molecule that specifically binds to human PD-1 that are capable of mediating, and more preferably enhancing, the activation of the immune system against cancer cells that are associated with any of a variety of human cancers. The invention also relates to the use of such pharmaceutical compositions to treat cancer and other diseases in recipient subjects.
摘要翻译：本发明涉及组合疗法，其涉及将特异性结合人B7-H3的第一分子和特异性结合人PD-1的第二分子施用于受试者以治疗癌症和/或炎症。本发明还涉及药物组合物，其包含特异性结合人B7-H3的第一分子和特异性结合人PD-1的第二分子，所述第二分子能够介导并且更优选增强免疫系统对癌症的激活与任何各种人类癌症相关的细胞。本发明还涉及这种药物组合物在受体受试者中治疗癌症和其他疾病的用途。

6. 发明申请

WO2017019846A1 PD-1-BINDING MOLECULES AND METHODS USE THEREOF 审中-公开
标题翻译： PD-1结合分子及其使用方法
公开(公告)号：WO2017019846A1
公开(公告)日：2017-02-02
申请号：PCT/US2016/044430
申请日：2016-07-28
申请人： MACROGENICS, INC.
发明人： SHAH, Kalpana , SMITH, Douglas, H. , LA MOTTE-MOHS, Ross , JOHNSON, Leslie, S. , MOORE, Paul, A. , BONVINI, Ezio , KOENIG, Scott
IPC分类号： A61K39/00 , A61K39/395 , C07K16/00
CPC分类号： A61K39/00 , A61K39/395 , C07K16/2803 , C07K16/2818 , C07K2317/24 , C07K2317/31 , C07K2317/33 , C07K2317/76
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.
摘要翻译：本发明涉及能够结合食蟹猴PD-1和人PD-1的选择的抗PD-1抗体：PD-1mAb 1，PD-1mAb 2，PD-1mAb 3，PD- 1mAb 4，PD-1mAb 5，PD-1mAb 6，PD-1mAb 7，PD-1mAb 8，PD-1mAb 9，PD-1mAb 10，PD-1mAb 11，PD-1mAb 12，PD-1mAb 13，PD-1mAb 14或PD-1mAb 15，以及这些抗体的人源化和嵌合形式。本发明还涉及包含PD-1结合片段的PD-1结合分子，所述PD-1结合片段包含抗PD-1抗体，免疫接种物以及双特异性分子，包括双抗体，BiTE，双特异性抗体等，其包含（i）这样的PD-1结合片段，和（ii）能够结合涉及调节免疫细胞表面上存在的免疫检测点的分子表位的结构域。本发明还涉及使用结合PD-1的分子刺激免疫应答的方法，以及检测PD-1的方法。

7. 发明申请

WO2016054101A1 BISPECIFIC MOLECULES COMPRISING AN HIV-1 ENVELOPE TARGETING ARM 审中-公开
标题翻译：包含HIV-1环境目标对象的双向分子
公开(公告)号：WO2016054101A1
公开(公告)日：2016-04-07
申请号：PCT/US2015/053027
申请日：2015-09-29
申请人： DUKE UNIVERSITY , MACROGENICS, INC. , UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
发明人： HAYNES, Barton, F. , FERRARI, Guido , KOENIG, Scott , JOHNSON, Leslie, S. , LAM, Chia-Ying, Kao , SUNG, Julia, A. , MARGOLIS, David, M.
IPC分类号： C07K16/10
CPC分类号： C07K16/1063 , A61K39/39541 , A61K39/42 , A61K45/06 , A61K2039/505 , C07K16/2803 , C07K16/2809 , C07K16/2812 , C07K16/283 , C07K16/44 , C07K16/468 , C07K2317/31 , C07K2317/52 , C07K2317/626 , C07K2317/72 , C07K2317/73 , C07K2317/732 , C07K2317/76
摘要： The invention is directed to bispecific molecules comprising an HIV-1 envelope targeting arm and an arm targeting an effector cell, compositions comprising these bispecific molecules and methods of use. In certain aspects, the bispecific molecules of the present invention can bind to two different targets or epitopes on two different cells wherein the first epitope is expressed on a different cell type than the second epitope, such that the bispecific molecules can bring the two cells together. In certain aspects, the bispecific molecules of the present invention can bind to two different cells, wherein the bispecific molecules comprises an arm with the binding specificity of A32, 7B2, CH27, CH28 or CH44.
摘要翻译：本发明涉及包含HIV-1包膜靶向臂和靶向效应细胞的臂的双特异性分子，包含这些双特异性分子的组合物和使用方法。在某些方面，本发明的双特异性分子可以结合两个不同细胞上的两个不同靶或表位，其中第一表位在不同于第二表位的细胞类型上表达，使得双特异性分子可以使两个细胞在一起。在某些方面，本发明的双特异性分子可以结合两种不同的细胞，其中双特异性分子包含具有A32，7B2，CH27，CH28或CH44的结合特异性的臂。

8. 发明申请

WO2015026894A2 BI-SPECIFIC MONOVALENT DIABODIES THAT ARE CAPABLE OF BINDING TO GPA33 AND CD3, AND USES THEREOF 审中-公开
标题翻译：可与GPA33和CD3结合的双特异性双价糖尿病及其应用
公开(公告)号：WO2015026894A2
公开(公告)日：2015-02-26
申请号：PCT/US2014/051793
申请日：2014-08-20
申请人： MACROGENICS, INC.
发明人： MOORE, Paul, A. , LI, Jonathan , CHEN, Francine, Zhifen , JOHNSON, Leslie, S. , SHAH, Kalpana , BONVINI, Ezio
IPC分类号： B60Q1/00 , G06F7/00
CPC分类号： C07K16/28 , A61K2039/505 , A61K2039/545 , C07K16/2803 , C07K16/2809 , C07K16/3046 , C07K2317/24 , C07K2317/31 , C07K2317/33 , C07K2317/35 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/56 , C07K2317/624 , C07K2317/626 , C07K2317/64 , C07K2317/73 , C07K2317/732 , C07K2317/92 , C07K2317/94 , C07K2319/31
摘要： The present invention is directed to bi-specific monovalent diabodies that comprise two polypeptide chains and which possess at least one binding site specific for an epitope of CD3 and one binding site specific for an epitope of gpA33 (i.e., a "gpA33 x CD3 bi-specific monovalent diabody"). The present invention also is directed to bi-specific monovalent diabodies that comprise an immunoglobulin Fc Domain ("bi- specific monovalent Fc diabodies") and are composed of three polypeptide chains and which possess at least one binding site specific for an epitope of gpA33 and one binding site specific for an epitope of CD3 (i.e ., a "gpA33 x CD3 bi-specific monovalent Fc diabody"). The bi-specific monovalent diabodies and bi-specific monovalent Fc diabodies of the present invention are capable of simultaneous binding to gpA33 and CD3. The invention is directed to pharmaceutical compositions that contain such bi-specific monovalent diabodies or such bi-specific monovalent Fc diabodies. The invention is additionally directed to methods for the use of such diabodies in the treatment of cancer and other diseases and conditions.
摘要翻译：本发明涉及双特异性单价双抗体，其包含两条多肽链并且具有至少一个对CD3表位特异的结合位点和对gpA33表位特异的一个结合位点（即，“gpA33xCD3双特异性单价双抗体”）。本发明还涉及包含免疫球蛋白Fc结构域的双特异性单价双抗体（“双特异性单价Fc双抗体”）并且由三条多肽链组成并且具有对gpA33的表位特异的至少一个结合位点和一个对CD3表位特异的结合位点（即“gpA33xCD3双特异性单价Fc双抗体”）。本发明的双特异性单价双抗体和双特异性单价Fc双抗体能够同时结合gpA33和CD3。本发明涉及含有此类双特异性单价双抗体或此类双特异性单价Fc双抗体的药物组合物。本发明另外涉及使用这种双抗体治疗癌症和其他疾病和病症的方法。

9. 发明申请

WO2015026892A1 BI-SPECIFIC MONOVALENT DIABODIES THAT ARE CAPABLE OF BINDING CD123 AND CD3, AND USES THEROF 审中-公开
标题翻译：具有结合CD123和CD3的双特异性单价糖尿病及其用途
公开(公告)号：WO2015026892A1
公开(公告)日：2015-02-26
申请号：PCT/US2014/051790
申请日：2014-08-20
申请人： MACROGENICS, INC.
发明人： BONVINI, Ezio , JOHNSON, Leslie, S. , HUANG, Ling , MOORE, Paul, A. , CHICHILI, Gurunadh, Reddy , ALDERSON, Ralph, Froman
IPC分类号： A61K39/395 , C07K16/28 , C07K17/14
CPC分类号： C07K16/2896 , A61K2039/505 , C07K16/2809 , C07K16/2866 , C07K2317/31 , C07K2317/33 , C07K2317/56 , C07K2317/626 , C07K2317/73 , C07K2317/92 , C07K2319/30 , C07K2319/31
摘要： The present invention is directed to sequence-optimized CD 123 x CD3 bi-specific monovalent diabodies that are capable of simultaneous binding to CD 123 and CD3, and to the uses of such diabodies in the treatment of hematologic malignancies.
摘要翻译：本发明涉及能够同时结合CD123和CD3的序列优化的CD123×CD3双特异性一抗双抗体，以及这种双抗体在治疗血液恶性肿瘤中的用途。

10. 发明申请

WO2009117030A2 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：WO2009117030A2
公开(公告)日：2009-09-24
申请号：PCT/US2008/087390
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： A61K39/395
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。

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