Claims for Patent: 10,253,102

Summary for Patent: 10,253,102

Title:	Antigen-binding proteins that activate the leptin receptor
Abstract:	The present invention provides antibodies and antigen-binding fragments of antibodies that bind to leptin receptor (LEPR), and methods of using the same. According to certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR and activate LEPR signaling. In other embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind to LEPR and enhance sensitization of LEPR to an antigen. In certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR in the presence and absence of leptin. In certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that induce signaling in cells expressing LEPR mutants that otherwise exhibit defective or impaired signaling in the presence of leptin. The antibodies and antigen-binding fragments of the present invention are useful for the treatment of lipodystrophies and other diseases and disorders associated with or caused by leptin deficiency or leptin resistance.
Inventor(s):	Gromada; Jesper (Scarsdale, NY), Stevis; Panayiotis (West Orange, NJ), Altarejos; Judith (Chappaqua, NY)
Assignee:	REGENERON PHARMACEUTICALS, INC. (Tarrytown, NY)
Application Number:	16/007,848
Patent Claims:	1. An isolated antibody or antigen-binding fragment thereof that binds human leptin receptor (LEPR) which comprises: the light chain complementarity determining regions (CDRs) of a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 10; and the heavy chain CDRs of a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 2, SEQ ID NO: 26 or SEQ ID NO: 34. 2. An isolated antibody or antigen-binding fragment thereof that binds human leptin receptor (LEPR) which comprises: a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 10; and a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 2, SEQ ID NO: 26 or SEQ ID NO: 34. 3. An isolated antibody or antigen-binding fragment thereof that binds human leptin receptor (LEPR) which comprises a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 10; and a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 2. 4. The antibody or antigen-binding fragment of claim 3 which is an antibody. 5. The antibody of claim 4 wherein the heavy chain variable region is linked to a human IgG1 heavy chain constant domain and the light chain variable region is linked to a human kappa light chain constant domain. 6. The antibody of claim 4 wherein the heavy chain variable region is linked to a human IgG4 heavy chain constant domain and the light chain variable region is linked to a human kappa light chain constant domain. 7. An isolated antibody or antigen-binding fragment thereof that binds human leptin receptor (LEPR) which comprises a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 10; and a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 26. 8. The antibody or antigen-binding fragment of claim 7 which is an antibody. 9. The antibody of claim 8 which wherein the heavy chain variable region is linked to a human IgG1 heavy chain constant domain and the light chain variable region is linked to a human kappa light chain constant domain. 10. The antibody of claim 8 which wherein the heavy chain variable region is linked to a human IgG4 heavy chain constant domain and the light chain variable region is linked to a human kappa light chain constant domain. 11. An isolated antibody or antigen-binding fragment thereof that binds human leptin receptor (LEPR) which comprises a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 10; and a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 34. 12. The antibody or antigen-binding fragment of claim 11 which is an antibody. 13. The antibody of claim 12 which wherein the heavy chain variable region is linked to a human IgG1 heavy chain constant domain and the light chain variable region is linked to a human kappa light chain constant domain. 14. The antibody of claim 12 which wherein the heavy chain variable region is linked to a human IgG4 heavy chain constant domain and the light chain variable region is linked to a human kappa light chain constant domain. 15. A pharmaceutical composition comprising the antibody of claim 4 and a pharmaceutically acceptable carrier or diluent. 16. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier or diluent. 17. A pharmaceutical composition comprising the antibody of claim 12 and a pharmaceutically acceptable carrier or diluent. 18. The antibody of claim 4 in combination with one or more additional therapeutically active components. 19. The antibody of claim 8 in combination with one or more additional therapeutically active components. 20. The antibody of claim 12 in combination with one or more additional therapeutically active components. 21. A pen delivery device comprising the pharmaceutical composition of claim 15. 22. A pen delivery device comprising the pharmaceutical composition of claim 16. 23. A pen delivery device comprising the pharmaceutical composition of claim 17. 24. The antibody of claim 4 in combination with recombinant human leptin, alirocumab, evolocumab, bococizumab, lodelcizumab, ralpancizumab, atorvastatin, rosuvastatin, cerivastatin, pitavastatin, fluvastatin, simvastatin, lovastatin, pravastatin, ezetimibe, insulin, metformin, dapaglifozin, canaglifozin, empagliflozin, extendin-4, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, an anti-GCG antibody, an anti-GCGR antibody, an anti-ANGPTL3 antibody, an anti-ANGPTL4 antibody, anti-ANGPTL8 antibody, phentermine, orlistat, topiramate, bupropion, topiramate and phentermine, bupropion and naltrexone, bupropion and zonisamide, pramlintide and metrelepin, lorcaserin, cetilistat, tesofensine or velneperit. 25. The antibody of claim 8 in combination with recombinant human leptin, alirocumab, evolocumab, bococizumab, lodelcizumab, ralpancizumab, atorvastatin, rosuvastatin, cerivastatin, pitavastatin, fluvastatin, simvastatin, lovastatin, pravastatin, ezetimibe, insulin, metformin, dapaglifozin, canaglifozin, empagliflozin, extendin-4, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, an anti-GCG antibody, an anti-GCGR antibody, an anti-ANGPTL3 antibody, an anti-ANGPTL4 antibody, anti-ANGPTL8 antibody, phentermine, orlistat, topiramate, bupropion, topiramate and phentermine, bupropion and naltrexone, bupropion and zonisamide, pramlintide and metrelepin, lorcaserin, cetilistat, tesofensine or velneperit. 26. The antibody of claim 12 in combination with recombinant human leptin, alirocumab, evolocumab, bococizumab, lodelcizumab, ralpancizumab, atorvastatin, rosuvastatin, cerivastatin, pitavastatin, fluvastatin, simvastatin, lovastatin, pravastatin, ezetimibe, insulin, metformin, dapaglifozin, canaglifozin, empagliflozin, extendin-4, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, an anti-GCG antibody, an anti-GCGR antibody, an anti-ANGPTL3 antibody, an anti-ANGPTL4 antibody, anti-ANGPTL8 antibody, phentermine, orlistat, topiramate, bupropion, topiramate and phentermine, bupropion and naltrexone, bupropion and zonisamide, pramlintide and metrelepin, lorcaserin, cetilistat, tesofensine or velneperit. 27. The antibody of claim 4 which is bispecific. 28. The antibody of claim 8 which is bispecific. 29. The antibody of claim 12 which is bispecific.

Details for Patent 10,253,102

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Glaxosmithkline Llc	TANZEUM	albiglutide	For Injection	125431	04/15/2014		2035-10-12
Eli Lilly And Company	TRULICITY	dulaglutide	Injection	125469	09/18/2014		2035-10-12
Eli Lilly And Company	TRULICITY	dulaglutide	Injection	125469	09/04/2020		2035-10-12
Amgen, Inc.	REPATHA	evolocumab	Injection	125522	08/27/2015		2035-10-12
Amgen, Inc.	REPATHA	evolocumab	Injection	125522	07/08/2016		2035-10-12
Regeneron Pharmaceuticals, Inc.	PRALUENT	alirocumab	Injection	125559	07/24/2015		2035-10-12
Sanofi-aventis U.s. Llc	ADLYXIN	lixisenatide	Injection	208471	07/27/2016		2035-10-12