Claims for Patent: 10,493,125

Summary for Patent: 10,493,125

Title:	Co-agonists of the glucagon and GLP-1 receptors
Abstract:	Co-agonists of the glucagon and GLP-1 receptors are described.
Inventor(s):	Palani; Anandan (Bridgewater, NJ), Carrington; Paul E. (San Mateo, CA), Pessi; Antonello (Rome, IT), Lahm; Armin (Rome, IT), Bianchi; Elisabetta (Pomezia, IT), Demartis; Anna (Pomezia, IT)
Assignee:	Merck Sharp & Dohme Corp. (Rahway, NJ)
Application Number:	15/774,622
Patent Claims:	1. A co-agonist peptide comprising a peptide selected from following peptides TABLE-US-00011 SEQ ID NO: Name Sequence 1 PD17 HSVGNFWSDYSKYLDSRRAQDFVQWLMLT-CONH.sub.2 2 PD18 HSQGTFTSDYSKYVEDRRAHDFVQWLMNT-CONH.sub.2 3 PD19 HSQGTFTSDYRKYLDERAAWDFVQWLMNT-CONH.sub.2 4 PD20 HSQGTFTSDYSKYLNSWMTQDFVQWLMNT-CONH.sub.2 5 PD21 HSQGTFTSDYSKYLDIGRAQDFVQWLLNT-CONH.sub.2 6 PD22 HSQGTFTSDYSKYLDSLMAQDFVQWLMST-CONH.sub.2 7 PD23 HSQGTFTSDYSKYLDWRRAQDFVQWLLNT-CONH.sub.2 8 PD24 HSQGTFTSDYIKLLDSRRAQDFVQWLMNT-CONH.sub.2 9 PD25 HSQGTFTSDYSKYLDARRAQDFVQWLIRT-CONH.sub.2 10 PD26 HSQGTFTSDYSKYLDVRRAQDFVQWLMNT-CONH.sub.2 11 PD27 HSQGTFTSDYSKYLDELRAYDFVQWLMNT-CONH.sub.2 12 PD28 HSQGTFTSDYSKYLDYMRAYDFVQWLMNT-CONH.sub.2 13 PD29 HSQGTFTSDYSKYLDSRRAHDFVQWLLNT-CONH.sub.2 14 PD30 HSQGTFTSDYSKYLDSRRAQDFVQWLMNP-CONH.sub.2 15 PD31 HSQGTFTSDYSKYLDSRRAQDFVQWLINY-CONH.sub.2 16 PD32 INHEQWAFTSDYSKYLDSRRAQDFVQWLMNT-CONH.sub.2 17 PD33 ASMFTFFSDYSKYLDSRRAQDFVQWLMLT-CONH.sub.2 18 PD34 HSQGTFLSDYSKLLDSRRAQDFVQWLMQT-CONH.sub.2 19 PD35 HSQGTFLHDYYYYLDSRRAQDFVQWLMDT-CONH.sub.2 20 PD36 HSQGTFTSDYSKYLDSIRAQDFVQWLMDT-CONH.sub.2 21 PD37 HSQGTFTSDYSKYLDNKRAQDFVQWLMQT-CONH.sub.2 22 PD38 HSQGTFTSDYSKYLDSRRAQDFVDWLMNE-CONH.sub.2 23 PD39 HSQGTFTSDYSKYLDSRRAQEFVEWLMDE-CONH.sub.2 24 PD40 HSQGTFTSDYSKYLDSRRAQDFVQWLINT-CONH.sub.2 25 PD41 KALGQFTFTSDYSKYLDSRRAQDFVQWLMNT-CONH.sub.2 26 PD42 HSQGTFFHDYSKYLDSRRAQDFVQWLLNT-CONH.sub.2 27 PD43 HSQGTFFSDYSHWLDSRRAQDFVQWLMNT-CONH.sub.2 28 PD44 HSQGTFTSDYSKYLDWRRAQDFVQWLQNT-CONH.sub.2 29 PD45 HSQGTFTSDYSKYLDSKRAHDFVQWLLNT-CONH.sub.2 30 PD46 HSQGTFTSDYSKYLDSRRAQDFWIDLMNT-CONH.sub.2 31 PD47 HSQGTFTSDYSKYLDSRRAQDFVMTSMNT-CONH.sub.2 32 PD48 HSQGTFTSDYSKYLDSRRAQDFVDWLLNA-CONH.sub.2 33 PD49 HSQGTFTSDYSKYLDSRRAQDFVEWLMNN-CONH.sub.2 34 PD50 HSQGTFTSDYSKYLDSRRAQDFVDWLINS-CONH.sub.2 35 PD51 HSHGTFTSDYSKYLDSRRAQDFVQWLMTT-CONH.sub.2 36 PD52 HSQGIFFSDYSKYLDSRRAQDFVQWLMNT-CONH.sub.2 37 PD53 HSQGTFLSDYSKYLDSRRAQDFVQWLMNT-CONH.sub.2 38 PD54 HSQGTFTSDYSWYLDSRRAQDFVQWLMNT-CONH.sub.2 39 PD55 HSQGTFTSDYSKYLDMQRAHDFVQWLMNT-CONH.sub.2 40 PD56 HSQGTFTSDYSKYLDSRMAYDFVQWLMNT-CONH.sub.2 41 PD57 HSQGTFTSDYSKYLDSRRAQDFVQWLLNQ-CONH.sub.2 42 PD58 HSQGTFFSDYSKYLDSRRAQDFVQWLLET-CONH.sub.2 43 PD59 HSQGTFTSDYSKYLDSRRAQDFVQWLLDS-CONH.sub.2 wherein the L-Serine at position 2 is replaced with Val, Ile, Asp, Glu, Met, Trp, Asn, D-Ala, D-Ser, or .alpha.-aminoisobutyric acid (aib), the Tyrosine at position 10 is replaced with a Lysine residue conjugated to a fatty acid or fatty diacid via a linking moiety, wherein CONH.sub.2 indicates the C-terminal amino acid carboxy group is amidated. 2. The co-agonist peptide of claim 1, wherein the fatty acid or fatty diacid comprises 14 to 20 methylene groups. 3. The co-agonist peptide of claim 1, wherein the fatty acid or fatty diacid comprises 16 carbon atoms. 4. The co-agonist peptide of claim 1, wherein the linking moiety comprises a PEG.sub.2 (8-amino-3,6-dioxaoctanoic acid) Gamma-Glutamic acid (.gamma.Glu), a .gamma.Glu, a .gamma.Glu.gamma.Glu, or a PEG.sub.2PEG.sub.2 .gamma.Glu. 5. A co-agonist peptide comprising a peptide selected from the following peptides TABLE-US-00012 SEQ ID NO: Name Sequence 44 TP534 HsQGTFTSDK(.gamma.E.gamma.EC16)SKYLDNKRAQDFVQWLMQT- CONH.sub.2 45 TP535 HsQGTFTSDK(.gamma.E.gamma.EC16)SKYLDSRRAHDFVQWLLNT- CONH.sub.2 46 TP536 HsQGTFLSDK(.gamma.E.gamma.EC16)SKLLDSRRAQDFVQWLMQT- CONH.sub.2 47 TP552 HsQGTFLSDYSKLLDSRAAQDFVQWLLQT-CONH.sub.2 48 TP559 HsQGTFTSDK(.gamma.E.gamma.EC16)SKYLDARAAHDFVQWLLNT- CONH.sub.2 49 TP572 HUQGTFTSDK(.gamma.E.gamma.EC16) SKYLDSRRAHDFVQWLLNTK.gamma.E-CONH.sub.2 50 TP573 HUQGTFTSDK(.gamma.E.gamma.EC16) SKYLDARAAHDFVQWLLNTK.gamma.E-CONH.sub.2 51 TP574 HUQGTFTSDK(.gamma.E.gamma.EC16) SKYLDNKRAQDFVQWLMQTK.gamma.E-CONH.sub.2 wherein U is aminoisobutyric acid, s is D-Ser, .gamma.E=.gamma.-glutamic acid, and C16=--CO--(CH.sub.2).sub.14--CH.sub.3, and wherein CONH.sub.2 indicates the C-terminal amino acid carboxy group is amidated. 6. A composition comprising one or more co-agonist peptides of claim 1 and a pharmaceutically acceptable carrier and/or pharmaceutically acceptable salt. 7. A method for treating a patient for a metabolic disease or disorder comprising administering the patient an effective amount of any one or more of the co-agonist peptides of claim 1 to treat the metabolic disease or disorder in the patient. 8. The method of claim 7, wherein the metabolic disease or disorder comprises diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or obesity. 9. The method of claim 8, wherein the diabetes comprises Type I diabetes, Type II diabetes, or gestational diabetes. 10. The method of claim 7, wherein the patient has more than one metabolic disease or disorder. 11. The method of claim 10, wherein the metabolic disease or disorder comprises, diabetes and NASH, NAFLD, or obesity; obesity and NASH or NAFLD; diabetes, NASH, and obesity; diabetes, NAFLD, and obesity; or diabetes and obesity. 12. A method for treating a patient for a metabolic disease or disorder comprising administering the patient an effective amount of the composition of claim 6 to treat the metabolic disease or disorder in the patient. 13. The method of claim 12, wherein the metabolic disease or disorder comprises diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or obesity. 14. The method of claim 12, wherein the patient has more than one metabolic disease or disorder. 15. The method of claim 14, wherein the metabolic disease or disorder comprises, diabetes and NASH, NAFLD, or obesity; obesity and NASH or NAFLD; diabetes, NASH, and obesity; diabetes, NAFLD, and obesity; or diabetes and obesity. 16. A method for treating a metabolic disease or disorder in a patient or individual comprising: administering to the patient or individual an effective amount of the composition of claim 6 and administering to the patient or individual an effective amount of a composition comprising an insulin or insulin analog to treat the metabolic disease or disorder in the patient or individual. 17. The method of claim 16, wherein the insulin analog comprises insulin detemir, insulin glargine, insulin levemir, insulin glulisine, insulin degludec, or insulin lispro. 18. The method of claim 17, wherein the metabolic disease or disorder comprises diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or obesity. 19. The method of claim 18, wherein the diabetes comprises Type I diabetes, Type II diabetes, or gestational diabetes. 20. The method of claim 16, wherein the patient has more than one metabolic disease or disorder selected from diabetes and NASH, NAFLD, or obesity; obesity and NASH or NAFLD; diabetes, NASH, and obesity; diabetes, NAFLD, and obesity; or diabetes and obesity.

Details for Patent 10,493,125

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	June 14, 1996	10,493,125	2036-12-05
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	August 06, 1998	10,493,125	2036-12-05
Eli Lilly And Company	HUMALOG	insulin lispro	Injection	020563	September 06, 2007	10,493,125	2036-12-05