Claims for Patent: 8,518,876

Summary for Patent: 8,518,876

Title:	Composition for long-acting peptide analogs
Abstract:	The invention describes compositions of peptide analogs that are active in blood or cleavable in blood to release an active peptide. The peptide analogs have a general formula: A-(Cm).sub.x-Peptide (SEQ ID NO: 76), wherein A is hydrophobic moiety or a metal binding moiety, e.g., a chemical group or moiety containing 1) an alkyl group having 6 to 36 carbon units, 2) a nitrilotriacetic acid group, 3) an imidodiacetic acid group, or 4) a moiety of formula (Z.sub.yHis.sub.w).sub.p (SEQ ID NO: 50), wherein Z is any amino acid residue other than histidine, His is histidine, y is an integer from 0-6; w is an integer from 1-6; and p is an integer from 1-6; wherein if A has alkyl group with 6 to 36 carbon units x is greater than 0; and Cm is a cleavable moiety consisting of glycine or alanine or lysine or arginine or N-Arginine or N-lysine, wherein x is an integer between 0-6 and N may be any amino acid or none. The peptide analogs are complexed with polymeric carrier to provide enhanced half-life.
Inventor(s):	Castillo; Gerardo M. (Bothell, WA), Bolotin; Elijah M. (Bothell, WA)
Assignee:	Pharmaln Corporation (Bothell, WA)
Application Number:	13/095,753
Patent Claims:	1. A composition comprising a peptide analog having a general formula: A-(Cm).sub.x-peptide, wherein: a. Cm is any one of glycine, alanine, lysine, and arginine; b. x is an integer from 3-6; c. A is a chemical group or moiety comprising an alkyl group with 6 to 36 carbon units with a --OCH(CH.sub.3)CO-- linker attached to -(Cm).sub.x-peptide; and d. the A-(Cm).sub.x-peptide has lower biological activity in cell culture than the parent peptide in the absence of serum, wherein the peptide has at least 8 amino acids and is not SEQ ID NO: 53, or wherein the peptide is auristatin. 2. The composition of claim 1, further comprising a polymeric carrier with a plurality of hydrophobic groups of 8-36 carbons each, wherein group A of the peptide analog is non-covalently bound to the plurality of hydrophobic groups of the polymeric carrier by hydrophobic interaction. 3. The composition of claim 2, wherein the peptide is selected from vasopressin, glucagon like peptide (GLP), leptin fragment, gastric inhibitory polypeptide (GIP), epidermal growth factor (EGF) receptor ligand, EGF, transforming growth factor alpha (TGF-alpha), gastrin cholecystokinin receptor ligand, gastrin, cholecystokinin, auristatin, nisin, insulin, insulin-like growth factor, parathyroid hormone (PTH), atrial natriuretic factor, somatostatin, gonadotropin releasing hormone, leutinizing-hormone-releasing-hormone, and vasoactive intestinal peptide (VIP). 4. The composition of claim 2, wherein the peptide is GLP-1 and A-(Cm).sub.x- is attached to the C terminus of the peptide or a side chain. 5. The composition of claim 2, wherein A is a linear alkyl. 6. The composition of claim 3, wherein A is a linear alkyl. 7. The composition of claim 4, wherein A is a linear alkyl. 8. The composition of claim 2, wherein A is a branched alkyl. 9. The composition of claim 3, wherein A is a branched alkyl. 10. The composition of claim 4, wherein A is a branched alkyl. 11. The composition of claim 1, wherein the peptide is selected from glucagon like peptide (GLP), leptin fragment, gastric inhibitory polypeptide (GIP), epidermal growth factor (EGF) receptor ligand, EGF, transforming growth factor alpha (TGF-alpha), gastrin cholecystokinin receptor ligand, gastrin, cholecystokinin, auristatin, nisin, insulin, insulin-like growth factor, parathyroid hormone (PTH), atrial natriuretic factor, somatostatin, gonadotropin releasing hormone, leutinizing-hormone-releasing-hormone, and vasoactive intestinal peptide (VIP). 12. The composition of claim 1, wherein the peptide is GLP-1 and A-(Cm).sub.x- is not attached to the N terminus of the peptide. 13. The composition of claim 1, wherein A is a linear alkyl. 14. The composition of claim 11, wherein A is a linear alkyl. 15. The composition of claim 12, wherein A is a linear alkyl. 16. The composition of claim 1, wherein A is a branched alkyl. 17. The composition of claim 12, wherein A is a branched alkyl. 18. The composition of claim 12, wherein A is a branched alkyl. 19. A method of making a composition comprising a peptide analog comprising: forming a covalent bond between a parent peptide and a group A-(Cm).sub.x- (reactive group) to form a composition comprising peptide analog according to claim 1, where said peptide analog has lower biological activity in cell culture than the parent peptide in the absence of serum. 20. A method for treatment of diabetes in a subject comprising administering the composition of claim 4 or the composition of claim 12 to a patient in need thereof.

Details for Patent 8,518,876

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2027-08-03