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1. 发明申请

WO2019050521A1 DOSING REGIMENS OF BI-SPECIFIC CD123 X CD3 DIABODIES IN THE TREATMENT OF HEMATOLOGIC MALIGNANCIES 审中-公开
公开(公告)号：WO2019050521A1
公开(公告)日：2019-03-14
申请号：PCT/US2017/050471
申请日：2017-09-07
申请人： MACROGENICS, INC.
发明人： WIGGINTON, Jon, Marc , ALDERSON, Ralph, Froman , LECHLEIDER, Robert, Joseph
IPC分类号： A01N65/00
CPC分类号： C07K16/2866 , A61K38/00 , A61K2039/505 , A61K2039/545 , A61P35/00 , C07K16/2809 , C07K2317/31 , C07K2317/33 , C07K2317/73 , C07K2317/92
摘要： The present invention is directed to a dosing regimen for administering a CD123 x CD3 bi-specific monovalent diabody to patients with a hematologic malignancy such as acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The invention particularly concerns the use of such a regimen for the sequence-optimized CD 123 x CD3 bi-specific monovalent diabody "DART-A," that is capable of simultaneous binding to CD 123 and CD3.

2. 发明申请

WO2017142928A1 ROR1-BINDING MOLECULES, AND METHODS OF USE THEREOF 审中-公开
标题翻译： ROR1结合分子及其使用方法
公开(公告)号：WO2017142928A1
公开(公告)日：2017-08-24
申请号：PCT/US2017/017939
申请日：2017-02-15
申请人： MACROGENICS, INC.
发明人： BARAT, Bhaswati , JOHNSON, Leslie, S. , MOORE, Paul, A. , ALDERSON, Ralph, Froman , BONVINI, Ezio
IPC分类号： C07K16/28
CPC分类号： C07K16/28 , C07K16/2803 , C07K16/2809 , C07K16/2815 , C07K2317/31 , C07K2317/56 , C07K2317/92
摘要： The present invention is directed to optimized ROR1-binding molecules having enhanced affinity and superior ability to mediate redirected cytotoxicity of tumor cells relative to prior ROR1-binding molecules. More specifically, the invention relates to optimized ROR1-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been optimized for binding to an epitope present on the human ROR1 polypeptide so as to exhibit enhanced binding affinity for human ROR1 and/or a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific ROR1-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such optimized ROR1-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such ROR1-binding molecules, and to methods involving the use of any of such ROR1-binding molecules in the treatment of cancer and other diseases and conditions.
摘要翻译：本发明涉及与先前的ROR1结合分子相比具有增强的亲和力和优异的介导肿瘤细胞的重定向细胞毒性的能力的优化的ROR1结合分子。更具体地说，本发明涉及包含可变轻链和/或可变重链（VH）结构域的优化的ROR1结合分子，所述可变轻链和/或可变重链（VH）结构域已经被优化用于结合存在于人ROR1多肽上的表位，人类ROR1和/或在给予受体对象时降低的免疫原性。本发明尤其涉及双特异性，三特异性或多特异性ROR1结合分子，包括双特异性双抗体，BiTE，双特异性抗体，三价结合分子等，其包含：（i）此类优化的ROR1结合可变结构域和（ii）与存在于效应细胞表面上的分子的表位结合。本发明还涉及含有任何此类ROR1结合分子的药物组合物，并且涉及涉及使用任何此类ROR1结合分子治疗癌症和其他疾病和病症的方法。

3. 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).

4. 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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