APLNR modulators and uses thereof

Patent metadata

Field	Value
Publication number	US-10155811-B2
Application number	US-201415038202-A
Country	US
Kind code	B2
Filing date	Nov 20, 2014
Priority date	Nov 20, 2013
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

The present invention provides apelin receptor (APLNR) modulators that bind to APLNR and methods of using the same. The invention includes APLNR modulators such as antibodies, or antigen-binding fragments thereof, that inhibit or attenuate APLNR-mediated signaling. The invention includes APLNR modulators such as antibodies, or antibody fusion proteins thereof, that activate APLNR-mediated signaling. According to certain embodiments of the invention, the antibodies or antigen-binding fragments or antibody fusion proteins are fully human antibodies that bind to human APLNR with high affinity. The APLNR modulators of the invention are useful for the treatment of diseases and disorders associated with APLNR signaling and/or APLNR cellular expression, such as cardiovascular diseases, angiogenesis diseases, metabolic diseases and fibrotic diseases.

First claim

What is claimed is:

1. An isolated antibody or antigen-binding fragment thereof that binds to apelin receptor (APLNR) and blocks the interaction of APLNR and apelin, wherein the antibody or antigen-binding fragment comprises: (a) the complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) having an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 18, 34, 50, 66, 82, 98, and 130; and (b) the CDRs of a light chain variable region (LCVR) having an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 26, 42, 58, 74, 90, 106, and 138.

2. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 domains, respectively, selected from the group consisting of: SEQ ID NOs: 4-6-8-12-14-16; 20-22-24-28-30-32; 36-38-40-44-46-48; 52-54-56-60-62-64; 68-70-72-76-78-80; 84-86-88-92-94-96; 100-102-104-108-110-112; and 132-134-136-140-142-144.

3. The isolated antibody or antigen-binding fragment of claim 2 , wherein the antibody or antigen-binding fragment comprises: (a) a heavy chain variable region (HCVR) having an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 18, 34, 50, 66, 82, 98, and 130; and (b) a light chain variable region (LCVR) having an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 26, 42, 58, 74, 90, 106, and 138.

4. The isolated antibody or antigen-binding fragment of claim 3 , wherein the antibody or antigen-binding fragment comprises a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 2/10, 18/26, 34/42, 50/58, 66/74, 82/90, 98/106, and 130/138.

5. The isolated antibody or antigen-binding fragment of claim 4 , wherein the antibody or antigen-binding fragment comprises the HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 98/106.

6. The isolated antibody or antigen-binding fragment of claim 4 , wherein the antibody or antigen-binding fragment comprises the HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 2/10.

7. The isolated antibody or antigen-binding fragment of claim 4 , wherein the antibody or antigen-binding fragment comprises the HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 18/26.

8. The isolated antibody or antigen-binding fragment of claim 4 , wherein the antibody or antigen-binding fragment comprises the HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 130/138.

9. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises the CDRs of a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 98/106.

10. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises the CDRs of a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 2/10.

11. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises the CDRs of a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 18/26.

12. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises the CDRs of a HCVR/LCVR amino acid sequence pair of SEQ ID NOs: 130/138.

13. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises the CDRs of a HCVR/LCVR amino acid sequence pair selected from the group consisting of: SEQ ID NOs: 34/42, 50/58, 66/74, and 82/90.

14. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 , and a pharmaceutically acceptable carrier or diluent.

15. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 2 , and a pharmaceutically acceptable carrier or diluent.

16. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 5 , and a pharmaceutically acceptable carrier or diluent.

17. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 6 , and a pharmaceutically acceptable carrier or diluent.

18. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 7 , and a pharmaceutically acceptable carrier or diluent.

19. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 8 , and a pharmaceutically acceptable carrier or diluent.

20. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 19 , and a pharmaceutically acceptable carrier or diluent.

Assignees

• Regeneron Pharma

Inventors

• Stevis Panayiotis
• Gromada Jesper
• Murphy Andrew J
• Ray Yonaton
• Kim Jee H
• Lobov Ivan B

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/08

  Vasodilators for multiple indications · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title