公开(公告)号：US20180312594A1

公开(公告)日：2018-11-01

申请号：US16033477

申请日：2018-07-12

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Jessica R. KIRSHNER ,  Douglas MACDONALD ,  Gavin THURSTON ,  Joel H. MARTIN ,  Frank DELFINO ,  Thomas NITTOLI ,  Marcus KELLY

IPC: C07K16/28 ,  C07K16/30 ,  A61K47/68 ,  A61K39/395 ,  A61K45/06 ,  A61K39/00

Abstract: The present invention provides antibodies that bind to the class III variant of EGFR (EGFRvIII) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human EGFRvIII with high affinity. The antibodies of the invention may be fully human antibodies. The invention includes anti-EGFRvIII 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.

公开(公告)号：US20240207412A1

公开(公告)日：2024-06-27

申请号：US18196863

申请日：2023-05-12

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Thomas NITTOLI

IPC: A61K47/54 ,  A61K31/395 ,  A61K31/5383 ,  A61K31/5517 ,  A61K38/07 ,  A61K38/17 ,  A61K47/55 ,  A61K47/65 ,  A61K47/68 ,  A61K49/00 ,  A61K51/10 ,  A61P31/04 ,  A61P35/00

CPC classification number: A61K47/545 ,  A61K31/395 ,  A61K31/5383 ,  A61K31/5517 ,  A61K38/07 ,  A61K38/1729 ,  A61K47/542 ,  A61K47/55 ,  A61K47/65 ,  A61K47/6849 ,  A61K49/0052 ,  A61K49/0058 ,  A61K51/1093 ,  A61P31/04 ,  A61P35/00

Abstract: Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for producing protein-payload constructs (e.g., antibody-drug conjugates) utilizing a combination of transglutaminase and Diels-Alder techniques. Antibody-drug conjugates and compositions which comprise glutaminyl-modified antibodies, Diels-Alder adducts, and reactive payloads and are provided.

公开(公告)号：US20240100179A1

公开(公告)日：2024-03-28

申请号：US18225567

申请日：2023-07-24

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Alina BAUM ,  Thomas NITTOLI

IPC: A61K47/68 ,  A61K31/506 ,  A61K31/5383

CPC classification number: A61K47/6841 ,  A61K31/506 ,  A61K31/5383 ,  A61K47/6803

Abstract: Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with influenza, including VX-787 and derivatives thereof, baloxavir and derivatives thereof, and baloxavir marboxil and derivatives thereof, and protein (e.g., antibody) drug conjugates thereof.

公开(公告)号：US20230285581A1

公开(公告)日：2023-09-14

申请号：US18090138

申请日：2022-12-28

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Thomas NITTOLI ,  Seungyong Sean CHOI ,  Mrinmoy SAHA

IPC: A61K47/68 ,  C07D498/18

CPC classification number: A61K47/6803 ,  C07D498/18

Abstract: The disclosure relates to rifamycin analog compounds, intermediates and precursors thereof, and pharmaceutical compositions capable of inhibiting bacterial growth (e.g., S. aureus growth) and treating bacterial infections (e.g., S. aureus infections). The disclosure further relates to antibody-drug conjugates of rifamycin analog compounds and antibodies, for example, antibodies specific for infectious disease-related targets such as membrane glycoprotein receptor (MSR1), wall teichoic acids (WTA) or Protein A, and methods of use thereof to inhibit bacterial growth and treat bacterial infections.

公开(公告)号：US20230079407A1

公开(公告)日：2023-03-16

申请号：US17727432

申请日：2022-04-22

Applicant: REGENERON PHARMACEUTICALS, INC.

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

IPC: C07K16/28 ,  A61K47/61 ,  A61K47/68 ,  A61K47/60 ,  A61P9/10 ,  A61P37/06 ,  A61P3/06 ,  A61P19/02 ,  A61P31/04 ,  A61K31/165 ,  A61K31/167 ,  A61K31/417 ,  A61K31/4985 ,  A61K31/5383 ,  A61K31/58 ,  A61K38/14 ,  A61K39/395

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：US20220378918A1

公开(公告)日：2022-12-01

申请号：US17232854

申请日：2021-04-16

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Thomas NITTOLI

IPC: A61K47/54 ,  A61K47/68 ,  A61K38/07 ,  A61K38/17 ,  A61K31/395 ,  A61K49/00 ,  A61K51/10 ,  A61K47/65 ,  A61K31/5517 ,  A61K47/55 ,  A61K31/5383 ,  A61P31/04 ,  A61P35/00

Abstract: Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for producing protein-payload constructs (e.g., antibody-drug conjugates) utilizing a combination of transglutaminase and Diels-Alder techniques. Antibody-drug conjugates and compositions which comprise glutaminyl-modified antibodies, Diels-Alder adducts, and reactive payloads and are provided.

公开(公告)号：US20220332729A1

公开(公告)日：2022-10-20

申请号：US17733974

申请日：2022-04-29

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Thomas NITTOLI

IPC: C07D507/00 ,  A61K47/68 ,  A61K31/5365

Abstract: The present disclosure relates to linker compounds that are useful in covalently linking biologically active molecules with Ligands. The disclosed compounds also relate to biologically active molecules and Ligand conjugates, wherein the biologically active molecule is linked to the Ligand through a linker. The disclosure further provides compositions comprising biologically active molecule-ligand conjugates, methods of modifying abnormal cell growth and methods of treatment using the conjugates or the compositions.

公开(公告)号：US20190151323A1

公开(公告)日：2019-05-23

申请号：US16189925

申请日：2018-11-13

Applicant: REGENERON PHARMACEUTICALS, INC.

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

IPC: A61K31/537 ,  A61K47/68 ,  A61K31/5365 ,  C07D498/18 ,  A61K45/06

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.

公开(公告)号：US20150056222A1

公开(公告)日：2015-02-26

申请号：US14530265

申请日：2014-10-31

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Nicholas J. PAPADOPOULOS ,  Gavin THURSTON ,  Jessica R. KIRSHNER ,  Marcus P. KELLY ,  Thomas NITTOLI ,  Frank J. DELFINO ,  William C. OLSON ,  Yashu LIU

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

CPC classification number: A61K47/48561 ,  A61K39/3955 ,  A61K47/48384 ,  A61K47/6803 ,  A61K47/6849 ,  C07K16/2869 ,  C07K16/30 ,  C07K2317/21 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92

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. According to certain embodiments, the invention includes antibodies that bind to the first fibronectin-like type III domain of the extracellular domain of PRLR. 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。 根据某些实施方案，本发明包括结合PRLR细胞外结构域的第一纤连蛋白样III型结构域的抗体。 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：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。