Composition for long-acting peptide analogs
First Claim
1. A composition comprising a peptide analog having a general formula:
- A-(Cm)x-peptide, wherein;
a. Cm is independently selected from(i) Gly,(ii) Ala,(iii) Arg,(iv) Lys,(v) (N)q-Lys, wherein N is any amino acid, q is 0 or 1, and(vi) (N)q-Arg, wherein N is any amino acid, q is 0 or 1;
b. x is an integer from 3-6;
c. A is an alkyl group with 6 to 36 carbon units with a linker group selected from carbonyl and amino; and
d. the peptide comprises 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, luteinizing-hormone-releasing-hormone, or vasoactive intestinal peptide (VIP).
0 Assignments
0 Petitions
Accused Products
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)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 imidiodacetic acid group, or 4) a moiety of formula (ZyHisw)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.
-
Citations
23 Claims
-
1. A composition comprising a peptide analog having a general formula:
- A-(Cm)x-peptide, wherein;
a. Cm is independently selected from (i) Gly, (ii) Ala, (iii) Arg, (iv) Lys, (v) (N)q-Lys, wherein N is any amino acid, q is 0 or 1, and (vi) (N)q-Arg, wherein N is any amino acid, q is 0 or 1; b. x is an integer from 3-6; c. A is an alkyl group with 6 to 36 carbon units with a linker group selected from carbonyl and amino; and d. the peptide comprises 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, luteinizing-hormone-releasing-hormone, or vasoactive intestinal peptide (VIP). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 20, 21)
- A-(Cm)x-peptide, wherein;
-
18. A composition comprising a peptide analog having a general formula:
- A-(Cm)x-peptide, wherein;
a. Cm is independently selected from (i) Gly, (ii) Ala, (iii) Arg, (iv) Lys, (v) (N)q-Lys, wherein N is any amino acid, q is 0 or 1, and (vi) (N)q-Arg, wherein N is any amino acid, q is 0 or 1; b. x is an integer from 3-6; c. A is an alkyl group with 6 to 36 carbon units with a linker group selected from carbonyl, amino, and —
OCH(CH3)CO—
;wherein Cm has at least one Gly or one Ala linked directly to the peptide, wherein the A-(Cm)x-(peptide) has lower biological activity in cell culture than a corresponding peptide lacking the A-(Cm)x in the absence of serum, and wherein the peptide comprises 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, luteinizing-hormone releasing-hormone, or vasoactive intestinal peptide (VIP). - View Dependent Claims (22, 23)
- A-(Cm)x-peptide, wherein;
-
19. A method of making a peptide analog having a general formula:
- A-(Cm)x-peptide, wherein;
a. Cm is independently selected from (i) Gly, (ii) Ala, (iii) Arg, (iv) Lys, (v) (N)q-Lys, wherein N is any amino acid, q is 0 or 1, and (vi) (N)q-Arg, wherein N is any amino acid, q is 0 or 1; b. x is an integer from 3-6; c. A is an alkyl group with 6 to 36 carbon units with a linker group selected from carbonyl and amino; and d. the peptide comprises 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, luteinizing-hormone releasing-hormone, or vasoactive intestinal peptide (VIP), the method comprising; step (i);
forming a covalent bond between a resin and a reactive group on a first amino acid to provide a resin comprising a covalently bonded amino acid;step (ii);
forming a covalent bond between the resin comprising the covalently bonded amino acid and a reactive group on a second amino acid;step (iii);
repeating step (ii) to provide a (Cm)x-peptide; andforming a carbonyl or amino bond between the (Cm)x-peptide and an alkyl group with 6 to 36 carbon units to provide the peptide analog.
- A-(Cm)x-peptide, wherein;
Specification