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1. 发明申请

WO2017214096A1 METHODS FOR THE USE OF CD32B X CD79B-BINDING MOLECULES IN THE TREATMENT OF INFLAMMATORY DISEASES AND DISORDERS 审中-公开
标题翻译：使用CD32B X CD79B结合分子治疗炎性疾病和病症的方法
公开(公告)号：WO2017214096A1
公开(公告)日：2017-12-14
申请号：PCT/US2017/036079
申请日：2017-06-06
申请人： MACROGENICS, INC.
发明人： CHEN, Wei , MOORE, Paul, A. , PANDYA, Naimish, Bharat , BONVINI, Ezio
IPC分类号： C07K16/28 , C07K16/46
摘要： The present invention is directed to methods for using bispecific binding molecules that possess a binding site specific for an epitope of CD32B and a binding site specific for an epitope of CD79B, and are thus capable of simultaneous binding to CD32B and CD79B. The invention particularly concerns such molecules that are bispecific antibodies or bispecific diabodies (and especially such diabodies that additionally comprise an Fc Domain). The invention is directed to the use of such molecules, and to the use of pharmaceutical compositions that contain such molecules in the treatment of inflammatory diseases or conditions.
摘要翻译：本发明涉及使用具有对CD32B的表位特异的结合位点和对CD79B的表位特异性的结合位点的双特异性结合分子的方法，并且因此能够同时结合 CD32B和CD79B。本发明特别涉及这样的分子，其是双特异性抗体或双特异性双抗体（并且尤其是另外包含Fc结构域的此类双抗体）。本发明涉及这种分子的用途，以及含有这种分子的药物组合物在治疗炎性疾病或病症中的用途。

2. 发明申请

WO2015200119A1 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：WO2015200119A1
公开(公告)日：2015-12-30
申请号：PCT/US2015/036634
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。

3. 发明申请

WO2017096368A1 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能力的双特异性双价糖尿病及其用途
公开(公告)号：WO2017096368A1
公开(公告)日：2017-06-08
申请号：PCT/US2016/064958
申请日：2016-12-05
申请人： MACROGENICS, INC.
发明人： BONVINI, Ezio , JOHNSON, Leslie, S. , KOENIG, Scott , LAM, Chia-Ying, Kao , LIU, Liqin , MOORE, Paul, A.
IPC分类号： A61K39/00 , A61K39/395 , C07K16/00 , C07K16/18 , 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 x 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 CD 19. Preferably, such a CD 19 x CD3 bi-specific molecules are bi-specific monovalent diabodies. The invention is directed to pharmaceutical compositions that contain such a CD19 x 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 CD 19.
摘要翻译：本发明涉及一种联合疗法，其涉及施用以下物质：（1）能够特异性结合CD19和CD3（即α CD19×CD3双特异性分子）和（2）布鲁顿氏酪氨酸激酶（BTK）抑制剂，用于治疗疾病，特别是治疗与CD19表达相关或以CD19表达为特征的疾病。优选地，这种CD19 x CD3双特异性分子是双特异性单价双抗体。本发明涉及含有这种CD19xCD3双特异性分子，BTK抑制剂或这些试剂的组合的药物组合物。本发明另外涉及使用此类药物组合物治疗疾病，特别是治疗与CD 19表达相关或以其为特征的癌症的方法。

4. 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。

5. 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。

6. 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).

7. 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。

8. 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。

9. 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。

10. 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。

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