公开(公告)号：US20150056221A1

公开(公告)日：2015-02-26

申请号：US14464297

申请日：2014-08-20

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Nicholas J. PAPADOPOULOS ,  Gavin THURSTON ,  Jessica R. KIRSHNER ,  Marcus P. KELLY ,  Thomas NITTOLI ,  Frank J. DELFINO

IPC: A61K47/48 ,  A61K31/537 ,  C07K16/28

CPC classification number: C07K16/2866 ,  A61K31/537 ,  A61K47/6803 ,  A61K47/6849 ,  A61K2039/505 ,  C07K16/2869 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94

Abstract: The present invention provides antibodies that bind to prolactin receptor (PRLR) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PRLR with high affinity. In certain embodiments, the invention includes antibodies that bind PRLR and block prolactin-mediated cell signaling. In other embodiments, the invention includes antibodies that bind PRLR but do not block prolactin-mediated cell signaling. The antibodies of the invention may be fully human antibodies. The invention includes anti-PRLR antibodies conjugated to a cytotoxic agent, radionuclide, or other moiety detrimental to cell growth or proliferation. The antibodies of the invention are useful for the treatment of various cancers as well as other PRLR-related disorders. The present invention also includes antibody drug conjugates comprising an antibody or antigen-binding fragment thereof that specifically binds a class I cytokine receptor, wherein the antibody or antigen-binding fragment thereof is conjugated to a cytotoxic agent.

Abstract translation: 本发明提供了结合催乳素受体（PRLR）的抗体及其使用方法。 根据某些实施方案，本发明的抗体以高亲和力结合人PRLR。 在某些实施方案中，本发明包括结合PRLR并阻断催乳素介导的细胞信号传导的抗体。 在其它实施方案中，本发明包括结合PRLR但不阻断催乳素介导的细胞信号传导的抗体。 本发明的抗体可以是完全人抗体。 本发明包括与细胞毒性剂，放射性核素或对细胞生长或增殖有害的其它部分缀合的抗PRLR抗体。 本发明的抗体可用于治疗各种癌症以及其它PRLR相关疾病。 本发明还包括抗体药物缀合物，其包含特异性结合I类细胞因子受体的抗体或其抗原结合片段，其中所述抗体或其抗原结合片段与细胞毒性剂缀合。

公开(公告)号：US20130078675A1

公开(公告)日：2013-03-28

申请号：US13678650

申请日：2012-11-16

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Joel H. MARTIN ,  Tammy T. HUANG ,  Jeanette L. FAIRHURST ,  Nicholas J. PAPADOPOULOS

IPC: C07K16/28

CPC classification number: C07K16/2866 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/76 ,  C07K2317/92

Abstract: The present invention provides nucleic acid molecules that encode antibodies or antigen-binding fragments thereof, which specifically bind human interleukin-4 receptor (IL-4R). Also provided are expression vectors comprising nucleic acid molecule that encode anti-IL-4R antibodies, host cells comprising the expression vectors, and methods of producing anti-IL-4R antibodies or antigen-binding fragments thereof comprising growing the host cells under conditions permitting production of the antibody or fragment, and recovering the antibody or fragment so produced

Abstract translation: 本发明提供编码特异性结合人白细胞介素-4受体（IL-4R）的抗体或其抗原结合片段的核酸分子。 还提供了包含编码抗IL-4R抗体的核酸分子，包含表达载体的宿主细胞和产生抗IL-4R抗体或其抗原结合片段的方法的表达载体，包括在允许生产的条件下培养宿主细胞 的抗体或片段，并回收如此制备的抗体或片段

公开(公告)号：US20180186883A1

公开(公告)日：2018-07-05

申请号：US15905653

申请日：2018-02-26

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Nicholas J. PAPADOPOULOS ,  Andrew J. MURPHY ,  Gavin THURSTON ,  Ella IOFFE ,  Elena BUROVA

IPC: C07K16/28 ,  C07K16/30 ,  A61K39/395 ,  A61K45/06 ,  C07K16/22 ,  A61K39/00

CPC classification number: C07K16/2827 ,  A61K39/3955 ,  A61K39/39558 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/22 ,  C07K16/30 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/75 ,  C07K2317/76 ,  C07K2317/92 ,  A61K2300/00

Abstract: The present invention provides antibodies that bind to the T-cell co-inhibitor ligand programmed death-ligand1 (PD-L1) protein, and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that bind to PD-L1. In certain embodiments, the present invention provides multi-specific antigen-binding molecules comprising a first binding specificity that binds to PD-L1 and a second binding specificity that binds to a tumor cell antigen, an infected cell-specific antigen, or a T-cell co-inhibitor. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing PD-L1 activity, thus providing a means of treating a disease or disorder such as cancer or viral infection.

公开(公告)号：US20180185668A1

公开(公告)日：2018-07-05

申请号：US15905685

申请日：2018-02-26

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Nicholas J. PAPADOPOULOS ,  Andrew J. MURPHY ,  Gavin THURSTON ,  Ella IOFFE ,  Elena BUROVA

IPC: A61N5/10 ,  C07K16/28 ,  A61K45/06 ,  A61K39/395 ,  A61K39/00

Abstract: The present invention provides antibodies that bind to the T-cell co-inhibitor programmed death-1 (PD-1) protein, and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that bind to PD-1. In certain embodiments, the present invention provides multi-specific antigen-binding molecules comprising a first binding specificity that binds to PD-1 and a second binding specificity that binds to an autoimmune tissue antigen, another T-cell co-inhibitor, an Fc receptor, or a T-cell receptor. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing PD-1 activity, thus providing a means of treating a disease or disorder such as cancer or a chronic viral infection. In other embodiments, the antibodies are useful for enhancing or stimulating PD-1 activity, thus providing a means of treating, for example, an autoimmune disease or disorder.

公开(公告)号：US20170247474A1

公开(公告)日：2017-08-31

申请号：US15345161

申请日：2016-11-07

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： George D. YANCOPOULOS ,  Nicholas J. PAPADOPOULOS ,  Neil STAHL ,  Samuel DAVIS ,  Andrew J. MURPHY ,  Lynn MACDONALD

IPC: C07K16/46 ,  C07K16/28

CPC classification number: C07K16/468 ,  C07K16/2803 ,  C07K16/2809 ,  C07K16/2887 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/52 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2317/64

Abstract: Multivalent antigen-binding proteins comprising two or three or four or more immunoglobulin heavy chain variable domain binding domains are provided, as are methods for making them, nucleic acid constructs, and cell lines for making them. Proteins comprising two or three or four or more different heavy chain variable domains that lack an immunoglobulin variable domain are provided. Proteins comprising two or three or four or more different heavy chain variable domains that associate with the same immunoglobulin light chain variable domain are also provided.

公开(公告)号：US20160130320A1

公开(公告)日：2016-05-12

申请号：US14822929

申请日：2015-08-11

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Nicholas J. PAPADOPOULOS ,  Samuel DAVIS ,  George D. YANCOPOULOS

IPC: C07K14/71

CPC classification number: C07K14/71 ,  A61K38/00 ,  C07K16/22 ,  C07K19/00 ,  C07K2319/00 ,  C07K2319/30

Abstract: The present invention provides VEGF antagonists with improved pharmacokinetic properties. According to certain embodiments, a fusion polypeptide capable of antagonizing VEGF activity is provided comprising a modified extracellular ligand binding domain of a VEGF receptor fused to a multimerizing component.

Abstract translation: 本发明提供具有改善的药代动力学性质的VEGF拮抗剂。 根据某些实施方案，提供能够拮抗VEGF活性的融合多肽，其包含与多聚化成分融合的VEGF受体的修饰的细胞外配体结合结构域。

公开(公告)号：US20140088295A1

公开(公告)日：2014-03-27

申请号：US14031075

申请日：2013-09-19

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Eric SMITH ,  Nicholas J. PAPADOPOULOS

IPC: C07K16/28

CPC classification number: C07K16/2809 ,  A61K2039/505 ,  C07K16/2887 ,  C07K2317/21 ,  C07K2317/31 ,  C07K2317/33 ,  C07K2317/35 ,  C07K2317/734 ,  C07K2317/74 ,  C07K2317/92

Abstract: The present invention provides antibodies that bind to CD3 and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with high affinity and induce human T cell proliferation. The invention includes antibodies that bind CD3 and induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human CD20. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell tumors expressing CD20. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders.

Abstract translation: 本发明提供了结合CD3的抗体及其使用方法。 根据某些实施方案，本发明的抗体以高亲和力结合人CD3，并诱导人T细胞增殖。 本发明包括结合CD3并诱导T细胞介导的杀伤肿瘤细胞的抗体。 根据某些实施方案，本发明提供包含特异性结合人CD3的第一抗原结合结构域和特异性结合人CD20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CD20的B细胞肿瘤的生长。 本发明的抗体和双特异性抗原结合分子可用于治疗其中期望和/或治疗有益的上调或诱导的靶向免疫应答的疾病和病症。 例如，本发明的抗体可用于治疗各种癌症以及其它与CD20相关的疾病和病症。

公开(公告)号：US20140044730A1

公开(公告)日：2014-02-13

申请号：US13964159

申请日：2013-08-12

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： George D. YANCOPOULOS ,  Nicholas J. PAPADOPOULOS ,  Andrew J. MURPHY ,  Neil STAHL

IPC: C07K16/40

CPC classification number: C07K16/40 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2317/94

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind proprotein convertase subtilisin/kexin-9 (PCSK9) with greater affinity at neutral pH than at acidic pH. The antibodies of the invention may possess one or more amino acid changes as compared to antibodies that do not exhibit pH-dependent binding properties. For example, the present invention includes anti-PCSK9 antibodies which possess one or more histidine substitutions in one or more complementarity determining regions. The antibodies of the invention, with pH-dependent binding properties, remain in circulation and exhibit cholesterol lowering activity for prolonged periods of time in animal subjects as compared to anti-PCSK9 antibodies that do not exhibit pH-dependent binding properties. The antibodies of the invention are therefore useful for treating diseases and disorders related to elevated HDL cholesterol, wherein the antibodies of the invention can be administered to a patient at a lower dose and/or with less frequent dosing as compared to antibodies that do not exhibit pH-dependent binding properties.

Abstract translation: 本发明提供了在中性pH下比在酸性pH下具有更高亲和力特异性结合前蛋白转化酶枯草杆菌蛋白酶/ kexin-9（PCSK9）的抗体及其抗原结合片段。 与不显示pH依赖性结合特性的抗体相比，本发明的抗体可具有一个或多个氨基酸变化。 例如，本发明包括在一个或多个互补决定区具有一个或多个组氨酸取代的抗PCSK9抗体。 与不具有pH依赖性结合性质的抗PCSK9抗体相比，具有pH依赖性结合特性的本发明的抗体在动物受试者中保持循环并显示长时间的胆固醇降低活性。 因此，本发明的抗体可用于治疗与升高的HDL胆固醇相关的疾病和病症，其中与不显示的抗体相比，本发明的抗体可以较低剂量和/或以较不频繁的给药方式施用于患者 pH依赖性结合性质。

公开(公告)号：US20130084635A1

公开(公告)日：2013-04-04

申请号：US13683216

申请日：2012-11-21

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Nicholas J. PAPADOPOULOS ,  Samuel DAVIS ,  George D. YANCOPOULOS

IPC: C07K14/71

CPC classification number: C07K14/71 ,  A61K38/00 ,  C07H21/04 ,  C07K16/22 ,  C07K19/00 ,  C07K2319/00 ,  C07K2319/30 ,  C12N15/09 ,  C12N15/10

Abstract: The present invention provides cell culture compositions capable of producing fusion polypeptides that bind vascular endothelial growth factor (VEGF). The cell culture compositions of the invention comprise cells which contain an expression vector comprising a nucleic acid molecule encoding a fusion polypeptide that binds VEGF. The fusion polypeptides may comprise a VEGF receptor component having an immunoglobulin-like (Ig) domain 2 of a first VEGF receptor, an Ig domain 3 of a second VEGF receptor, and a multimerizing component.

Abstract translation: 本发明提供能够产生结合血管内皮生长因子（VEGF）的融合多肽的细胞培养组合物。 本发明的细胞培养组合物包含含有包含编码结合VEGF的融合多肽的核酸分子的表达载体的细胞。 融合多肽可以包含具有第一VEGF受体的免疫球蛋白样（Ig）结构域2，第二VEGF受体的Ig结构域3和多聚化成分的VEGF受体组分。