公开(公告)号：WO2019217591A1

公开(公告)日：2019-11-14

申请号：PCT/US2019/031383

申请日：2019-05-08

Applicant: REGENERON PHARMACEUTICALS, INC. ,  KYRATSOUS, Christos ,  NITTOLI, Thomas ,  ZUMSTEG, Anna

Inventor： KYRATSOUS, Christos ,  NITTOLI, Thomas ,  ZUMSTEG, Anna ,  GROMADA, Jesper ,  GUSAROVA, Viktoria ,  HAN, Amy ,  HAXHINASTO, Sokol ,  MURPHY, Andrew J. ,  OLSON, William ,  SLEEMAN, Matthew

IPC: C07K16/28 ,  A61K47/68

Abstract: Provided herein are antibodies and antigen-binding fragments that bind MSR1 and methods of use thereof. According to certain embodiments, the antibodies bind human MSR1 with high affinity. In certain embodiments, the antibodies bind MSR1 without blocking, or blocking less than 90%, of modified LDL binding to MSR1. In some embodiments, the antibodies bind cell surface expressed-MSR1 and are internalized. The antibodies of the invention may be fully human antibodies. The invention includes anti-MSR1 antibodies, or antigen-binding fragments thereof, conjugated to drugs or therapeutic compounds.

公开(公告)号：WO2018058001A1

公开(公告)日：2018-03-29

申请号：PCT/US2017/053111

申请日：2017-09-22

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： RUDGE, John ,  DELFINO, Frank ,  HABER, Lauric ,  SMITH, Eric ,  KIRSHNER, Jessica R. ,  CRAWFORD, Alison ,  NITTOLI, Thomas

IPC: C07K16/30 ,  C07K16/28 ,  A61K47/68 ,  A61P35/00

Abstract: The protein known as six-transmembrane epithelial antigen of prostate 2 (STEAP2) is highly expressed in prostate cancer and is associated with the expression of other prostate cancer-associated genes. The present invention provides novel full-length human IgG antibodies that bind to human STEAP2 (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both STEAP2 and CD3 and activate T cells via the CD3 complex in the presence of STEAP2 -expressing tumors. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human and monkey CD3, and a second antigen-binding molecule that specifically binds humanSTEAP2. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing STEAP2. The bispecific antigen-binding molecules of the invention are useful for the treatment of prostate diseases and disorders in which an upregulated or induced STEAP2 -targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of prostate cancers, including castrate-resistant prostate cancer. The present invention also includes anti-STEAP2 antibody drug conjugates which inhibit tumor growth in vivo.

Abstract translation: 被称为前列腺2（STEAP2）的六跨膜上皮抗原的蛋白质在前列腺癌中高度表达，并与其他前列腺癌相关基因的表达相关。 本发明提供了与人STEAP2（单特异性抗体）结合的新型全长人IgG抗体。 本发明还提供了新的双特异性抗体（bsAb），其在表达STEAP2的肿瘤存在下通过CD3复合物结合STEAP2和CD3并激活T细胞。 根据某些实施方案，本发明提供了包含特异性结合人和猴CD3的第一抗原结合结构域和特异性结合人STEAP2的第二抗原结合分子的双特异性抗原结合分子。 在某些实施方案中，本发明的双特异性抗原结合分子能够抑制表达STEAP2的肿瘤的生长。 本发明的双特异性抗原结合分子可用于治疗需要上调或诱导的STEAP2靶向的免疫应答和/或治疗有益的前列腺疾病和病症。 例如，本发明的双特异性抗体可用于治疗前列腺癌，包括去势抵抗性前列腺癌。 本发明还包括抑制体内肿瘤生长的抗STEAP2抗体药物缀合物。

公开(公告)号：WO2015031396A1

公开(公告)日：2015-03-05

申请号：PCT/US2014/052757

申请日：2014-08-26

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： NITTOLI, Thomas ,  JAIN, Nareshkumar F. ,  MARKOTAN, Thomas Patrick

IPC: A61K31/5365 ,  C07D413/14 ,  A61K47/48 ,  A61P29/00 ,  A61P37/00 ,  A61P35/00

CPC classification number: A61K47/48384 ,  A61K31/5365 ,  A61K31/537 ,  A61K45/06 ,  A61K47/6803 ,  A61K47/6809 ,  A61K47/6851 ,  C07B2200/07 ,  C07D498/18

Abstract: The disclosure relates to compositions comprising diastereomer of a macrolide exhibiting improved therapeutic profile in the context of inhibiting cell proliferation compared to the corresponding compositions comprising mixture of diastereomers. The disclosure further provides drug-ligand conjugates formed using diastereomer of the macrolide. The disclosure also provides novel method of preparation of diastereomer of the macrolide and their therapeutic uses.

Abstract translation: 本公开涉及包含大环内酯非对映异构体的组合物，其与包含非对映体混合物的相应组合物相比，在抑制细胞增殖的情况下表现出改善的治疗特征。 本公开进一步提供了使用大环内酯非对映异构体形成的药物 - 配体结合物。 本公开还提供了制备大环内酯非对映体及其治疗用途的新方法。