公开(公告)号：US20170058045A1

公开(公告)日：2017-03-02

申请号：US15119986

申请日：2015-02-20

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Jesper GROMADA ,  Eric SMITH ,  Andrew MURPHY ,  Nicholas PAPADOPOULOS ,  Joel MARTIN ,  George YANCOPOULOS ,  Douglas MACDONALD ,  David BUCKLER

IPC: C07K16/32 ,  A61K39/395 ,  C07K16/28

CPC classification number: C07K16/32 ,  A61K39/39558 ,  A61K2039/507 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2818 ,  C07K16/283 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/2869 ,  C07K16/3069 ,  C07K2317/31 ,  C07K2317/622 ,  C07K2317/75

Abstract: The present invention provides, inter alia, a method for cell-specific modulation of a target antigen. The method comprises contacting a target cell having the target antigen on the surface of the target cell with: (a) first multi-specific antigen-binding polypeptide comprising: (i) a cell-specific antigen binding domain (C1), (ii) a target antigen binding domain (T1); and (b) a second multi-specific antigen-binding polypeptide comprising: (i) a cell-specific antigen binding domain (C2), (ii) a target antigen binding domain (T2); wherein C1 and C2 interact with the same cell-specific antigen, and the cell-specific antigen and the target antigen are on the same target cell. Pharmaceutical compositions and kits thereof are also included in the present invention.

Abstract translation: 本发明尤其提供了靶抗原的细胞特异性调节方法。 该方法包括使靶细胞表面上具有靶抗原的靶细胞与（a）第一多特异性抗原结合多肽包含：（i）细胞特异性抗原结合结构域（C1），（ii） 靶抗原结合结构域（T1）; （b）第二多特异性抗原结合多肽，其包含：（i）细胞特异性抗原结合结构域（C2），（ii）靶抗原结合结构域（T2）; 其中C1和C2与相同的细胞特异性抗原相互作用，细胞特异性抗原和靶抗原位于相同的靶细胞上。 药物组合物及其试剂盒也包括在本发明中。

公开(公告)号：US20150330998A1

公开(公告)日：2015-11-19

申请号：US14811056

申请日：2015-07-28

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Nicholas PAPADOPOULOS ,  Anthony DORE ,  Douglas MACDONALD

IPC: G01N33/74 ,  C07K14/71 ,  C07K16/22

CPC classification number: G01N33/74 ,  C07K14/71 ,  C07K16/22 ,  C07K2319/30 ,  G01N2333/515 ,  G01N2800/52

Abstract: The invention provides a method for enriching the level of VEGF-A121 isoform in a sample by selectively removing the VEGF-A165 isoform from the sample using a neuropilin-1 pull-down procedure, then determining the total amount of VEGF-A remaining afterward. The invention provides methods of treating a patient suffering from a disease which may benefit from the administration of a VEGF antagonist by determining the level or ratio of VEGF-A121 in the patient's circulation. Methods of diagnosis, prognosis, monitoring, and patient stratification are also provided.

Abstract translation: 本发明提供了通过使用神经丝氨酸-1下拉法从样品中选择性除去VEGF-A165同种型，然后确定其后剩余的VEGF-A的总量，从而提高样品中VEGF-A121同种型水平的方法。 本发明提供了通过确定患者循环中VEGF-A121的水平或比例来治疗患有可能受益于VEGF拮抗剂的患者的患者的方法。 还提供了诊断，预后，监测和患者分层的方法。

公开(公告)号：US20130315907A1

公开(公告)日：2013-11-28

申请号：US13900129

申请日：2013-05-22

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Nicholas PAPADOPOULOS ,  Anthony DORE ,  Douglas MACDONALD

IPC: G01N33/74

CPC classification number: G01N33/74 ,  C07K14/71 ,  C07K16/22 ,  C07K2319/30 ,  G01N2333/515 ,  G01N2800/52

Abstract: The invention provides a method for determining the level of VEGF-A121 isoform in a sample by selectively removing the VEGF-A165 isoform from the sample using a neuropilin-1 pull-down procedure, then determining the total amount of VEGF-A remaining afterward. The invention provides methods of treating a patient suffering from a disease which may benefit from the administration of a VEGF antagonist by determining the level of VEGF-A121 in the patient's circulation. Methods of diagnosis, prognosis, monitoring, and patient stratification are also provided.

Abstract translation: 本发明提供了一种通过使用神经丝氨酸-1下拉法从样品中选择性除去VEGF-A165同种型，然后测定其后剩余的VEGF-A总量来确定样品中VEGF-A121同种型水平的方法。 本发明提供了通过测定患者血液循环中VEGF-A121的水平来治疗患有可能受益于VEGF拮抗剂的疾病的患者的方法。 还提供了诊断，预后，监测和患者分层的方法。

公开(公告)号：US20170007715A1

公开(公告)日：2017-01-12

申请号：US15202822

申请日：2016-07-06

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Julian ANDREEV ,  Nithya THAMBI ,  Frank DELFINO ,  Joel MARTIN ,  Gavin THURSTON ,  Katherine CYGNAR ,  Nicholas PAPADOPOULOS

IPC: A61K47/48 ,  C07K16/30 ,  C07K16/22 ,  C07K16/32 ,  C07K16/28

CPC classification number: A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6879 ,  A61K2039/507 ,  A61K2039/572 ,  A61P35/00 ,  C07K14/4702 ,  C07K16/1203 ,  C07K16/18 ,  C07K16/22 ,  C07K16/28 ,  C07K16/2833 ,  C07K16/2866 ,  C07K16/2869 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/32 ,  C07K16/468 ,  C07K2317/21 ,  C07K2317/31 ,  C07K2317/35 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2319/00 ,  C07K2319/30 ,  C12N9/6454

Abstract: The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the invention, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention causes or facilitates the targeted killing of tumor cells.

Abstract translation: 本发明提供多特异性抗原结合分子及其用途。 多特异性抗原结合分子包含特异性结合靶分子的第一抗原结合结构域和特异性结合内在效应蛋白的第二抗原结合结构域。 在一些实施方案中，本发明的多特异性抗原结合分子可以是能够结合靶分子和内化效应蛋白的双特异性抗体。 在本发明的某些实施方案中，通过本发明的多特异性抗原结合分子同时结合靶分子和内化效应蛋白导致目标分子的活性比所述靶分子的结合更大程度地减弱 靶分子单独。 在本发明的其它实施方案中，靶分子是肿瘤相关抗原，并且通过本发明的多特异性抗原结合分子同时结合肿瘤相关抗原和内在效应蛋白导致或促进靶向杀伤肿瘤细胞 。

公开(公告)号：US20150330999A1

公开(公告)日：2015-11-19

申请号：US14811074

申请日：2015-07-28

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Nicholas PAPADOPOULOS ,  Anthony DORE ,  Douglas MACDONALD

IPC: G01N33/74

CPC classification number: G01N33/74 ,  C07K14/71 ,  C07K16/22 ,  C07K2319/30 ,  G01N2333/515 ,  G01N2800/52

Abstract: The invention provides a method for enriching the level of VEGF-A121 isoform in a sample by selectively removing the VEGF-A165 isoform from the sample using a neuropilin-1 pull-down procedure, then determining the total amount of VEGF-A remaining afterward. The invention provides methods of treating a patient suffering from a disease which may benefit from the administration of a VEGF antagonist by determining the level or ratio of VEGF-A121 in the patient's circulation. Methods of diagnosis, prognosis, monitoring, and patient stratification are also provided.