US6284727B1
Expired / Lapsed
US
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Prolonged delivery of peptides
Assignee: Scios LLC
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Filing: 1995-06-07
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Granted: 2001-09-04
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Expires: 2015-06-07
Abstract
Abstract There are disclosed methods for the treatment of non-insulin dependent diabetes mellitus in a mammal comprising the prolonged administration of GLP-1 (7-37), and related peptides. Also disclosed are compositions to prolong the administration of the peptides.
Inventors
- 👤 Yesook Kim
- 👤 William J. Lambert
- 👤 Hong Qi
- 👤 Robert A Gelfand
- 👤 Kieran F. Geoghegan
- 👤 Dennis E. Danley
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 10:14
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/41; A61K31/425; A61K31/426; A61K31/435; A61K31/44; A61K31/4427; A61K31/4439; A61K38/00; A61K38/16; A61K38/17; A61K38/22; A61K38/26; C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/605
Claims Analysis
Total Claims: 47
Claim 1
Independent Claim
356 words
A composition of matter comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (E) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Trp-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a polymer selected from the group consisting of polyvinylalcohol, polyoxyethylene-polyoxypropylene copolymers, polysaccharides selected from the group consisting of cellulose, chitosan, acacia gum, karaya gum, guar gum, xanthan gum, tragacanth, alginic acid, carrageenan, agarose, and furcellarans, dextran, starch, starch derivatives, hyaluronic acid, polyamides, polyanhydrides, and polyortho esters; wherein said composition of matter is in an injectable formulation and comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions; and wherein said composition of matter is capable of providing, in a patient who has been administered said composition by injection, plasma concentrations of said compound that are sufficient to enhance insulin action for the length of time necessary to achieve sustained glycemic control.
Claim 2
Dependent Claim
356 words
A composition of matter comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (E) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Trp-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a polymer selected from the group consisting of polyvinylalcohol, polyoxyethylene-polyoxypropylene copolymers, polysaccharides selected from the group consisting of cellulose, chitosan, acacia gum, karaya gum, guar gum, xanthan gum, tragacanth, alginic acid, carrageenan, agarose, and furcellarans, dextran, starch, starch derivatives, hyaluronic acid, polyamides, polyanhydrides, and polyortho esters; wherein said composition of matter is in an injectable formulation and comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions; and wherein said composition of matter is capable of providing, in a patient who has been administered said composition by injection, plasma concentrations of said compound that are sufficient to enhance insulin action for the length of time necessary to achieve sustained glycemic control.
Claim 3
Dependent Claim
29 words
A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising the administration of a composition according to claim 1 .
Claim 4
Dependent Claim
317 words
A composition of matter comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a pharmaceutically acceptable water-immiscible oil suspension; wherein said composition of matter is in an injectable formulation and comprises said compound of part (i) in particulate form having a solubility equal to or less than 500 μg/ml under physiological conditions; and wherein said composition of matter is capable of providing, in a patient who has been administered said composition by injection, plasma concentrations of said compound that are sufficient to enhance insulin action for the length of time necessary to achieve sustained glycemic control.
Claim 5
Dependent Claim
317 words
A composition of matter comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a pharmaceutically acceptable water-immiscible oil suspension; wherein said composition of matter is in an injectable formulation and comprises said compound of part (i) in particulate form having a solubility equal to or less than 500 μg/ml under physiological conditions; and wherein said composition of matter is capable of providing, in a patient who has been administered said composition by injection, plasma concentrations of said compound that are sufficient to enhance insulin action for the length of time necessary to achieve sustained glycemic control.
Claim 6
Dependent Claim
48 words
A composition according to claim 3 wherein said oil is selected from the group consisting of peanut oil, sesame oil, almond oil, castor oil, camellia oil, cotton seed oil, olive oil, corn oil, soy oil, safflower oil, coconut oil, and esters of fatty acids, esters of fatty alcohols.
Claim 7
Dependent Claim
11 words
A composition according to claim 3 further comprising a wetting agent.
Claim 8
Dependent Claim
14 words
A composition according to claim 5 wherein said wetting agent is a nonionic surfactant.
Claim 9
Dependent Claim
11 words
A composition according to claim 3 further comprising a suspending agent.
Claim 10
Dependent Claim
30 words
A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 3 .
Claim 11
Dependent Claim
270 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) zinc (II) wherein said injectable composition of matter comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 12
Dependent Claim
270 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) zinc (II) wherein said injectable composition of matter comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 13
Dependent Claim
12 words
A composition according to claim 9 capable of achieving sustained glycemic control.
Claim 14
Dependent Claim
11 words
A composition according to claim 9 which is an aqueous suspension.
Claim 15
Dependent Claim
30 words
A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 9 .
Claim 16
Dependent Claim
287 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a metal selected from the group consisting of Ni (II), Co (II), Mn (II), Fe (II), and Cu (II); wherein said injectable composition of matter comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 17
Dependent Claim
287 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a metal selected from the group consisting of Ni (II), Co (II), Mn (II), Fe (II), and Cu (II); wherein said injectable composition of matter comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 18
Dependent Claim
12 words
A composition according to claim 13 capable of achieving sustained glycemic control.
Claim 19
Dependent Claim
30 words
A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 13 .
Claim 20
Dependent Claim
283 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a phenolic compound; wherein said injectable composition of matter comprises said compound of part (i) in precipitate or aggregate form having a solubility equal to or less than 500 μg/ml under physiological conditions, and wherein said composition of matter is capable of sustained glycemic control.
Claim 21
Dependent Claim
283 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a phenolic compound; wherein said injectable composition of matter comprises said compound of part (i) in precipitate or aggregate form having a solubility equal to or less than 500 μg/ml under physiological conditions, and wherein said composition of matter is capable of sustained glycemic control.
Claim 22
Dependent Claim
23 words
A composition according to claim 16 wherein said phenolic compound is selected from the group consisting of phenol, cresol, resorcinol, and methyl paraben.
Claim 23
Dependent Claim
30 words
A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 16 .
Claim 24
Dependent Claim
286 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a Moypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Glu-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Ser-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a basic polypeptide and a phenolic compound, wherein said composition of matter comprises said compound of part (i) in precipitate or aggregate form having a solubility equal to or less than 500 μg/ml under physiological conditions; and wherein said composition of matter is capable of sustained glycemic control.
Claim 25
Dependent Claim
286 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a Moypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Glu-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Ser-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a basic polypeptide and a phenolic compound, wherein said composition of matter comprises said compound of part (i) in precipitate or aggregate form having a solubility equal to or less than 500 μg/ml under physiological conditions; and wherein said composition of matter is capable of sustained glycemic control.
Claim 26
Dependent Claim
30 words
A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 19 .
Claim 27
Dependent Claim
290 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Thr-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a basic polypeptide, a phenolic compound, and a metal ion; wherein said injectable composition of matter comprises said compound of part (i) in precipitate or aggregate form having a solubility equal to or less than 500 μg/ml under physiological conditions; and wherein said composition of matter is capable of sustained glycemic control.
Claim 28
Dependent Claim
290 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Thr-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a basic polypeptide, a phenolic compound, and a metal ion; wherein said injectable composition of matter comprises said compound of part (i) in precipitate or aggregate form having a solubility equal to or less than 500 μg/ml under physiological conditions; and wherein said composition of matter is capable of sustained glycemic control.
Claim 29
Dependent Claim
12 words
A composition according to claim 21 wherein said basic polypeptide is protamine.
Claim 30
Dependent Claim
12 words
A composition according to claim 21 wherein said metal ion is zinc.
Claim 31
Dependent Claim
30 words
A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 21 .
Claim 32
Dependent Claim
291 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a pharmaceutically acceptable medium; wherein said peptides and derivatives thereof have been subjected to conditions resulting in amorphous or crystalline material formation, and wherein said injectable composition of matter comprises said compound of part (i) in amorphous or crystalline form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 33
Dependent Claim
291 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) a pharmaceutically acceptable medium; wherein said peptides and derivatives thereof have been subjected to conditions resulting in amorphous or crystalline material formation, and wherein said injectable composition of matter comprises said compound of part (i) in amorphous or crystalline form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 34
Dependent Claim
18 words
A composition according to claim 25 wherein said conditions are high shear, exposure to salts; or combinations thereof.
Claim 35
Dependent Claim
54 words
A composition according to claim 26 wherein said salt is selected from the group consisting of ammonium sulfate, sodium sulfate, lithium sulfate, lithium chloride, sodium citrate, ammonium citrate, sodium phosphate, potassium phosphate, sodium chloride, potassium chloride, ammonium chloride, sodium acetate, ammonium acetate, magnesium sulfate, calcium chloride, ammonium nitrate, and sodium formate; and combinations thereof.
Claim 36
Dependent Claim
30 words
A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 25 .
Claim 37
Dependent Claim
273 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) lays, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:4) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) zinc (II) and a phenolic compound; wherein said injectable composition of matter comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 38
Dependent Claim
273 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) lays, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:4) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) zinc (II) and a phenolic compound; wherein said injectable composition of matter comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 39
Dependent Claim
12 words
A composition according to claim 29 capable of achieving sustained glycemic control.
Claim 40
Dependent Claim
11 words
A composition according to claim 29 which is an aqueous suspension.
Claim 41
Dependent Claim
274 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) zinc (II) and a basic polypeptide; wherein said injectable composition of matter comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 42
Dependent Claim
274 words
A composition of matter in an injectable formulation comprising: (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQUENCE ID NO: 2) (b) a peptide having the amino acid sequence: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO: 7) wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a polypeptide comprising the primary structure H 2 N—W—COOH wherein W is an amino acid sequence selected from the group consisting of His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly (SEQUENCE ID NO: 1) and His-Asp-Glu-Phe-Glu-Arg-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg (SEQUENCE ID NO: 6) which polypeptide when processed in a mammal results in a peptide having insulinotropic activity; (d) a peptide comprising the primary structure H 2 N—R—COOH wherein R is an amino acid sequence selected from the group consisting of His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly; (SEQ ID NO:2) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg; (SEQ ID NO:3) His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly; (SEQ ID NO:4) and His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys; (SEQ ID NO:5) and (e) a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide; and (ii) zinc (II) and a basic polypeptide; wherein said injectable composition of matter comprises said compound of part (i) in crystalline or amorphous form having a solubility equal to or less than 500 μg/ml under physiological conditions.
Claim 43
Dependent Claim
12 words
A composition according to claim 32 capable of achieving sustained glycemic control.
Claim 44
Dependent Claim
11 words
A composition according to claim 32 which is an aqueous suspension.
Claim 45
Dependent Claim
12 words
A composition according to claim 32 wherein the basic polypeptide is protamine.
Claim 46
Independent Claim
26 words
The method of any one of claims 2 , 8 , 12 , 15 or 18 , 20 , 24 or wherein said administration is subcutaneous.
Claim 47
Independent Claim
27 words
The method of any one of claims 2 , 8 , 12 , 15 or 18 , 20 , 24 or 28 wherein said administration is intramuscular.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 2004-09-03 | 2005-03-05 | 2005-09-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2008-09-03 | 2009-03-05 | 2009-09-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2012-09-03 | 2013-03-05 | 2013-09-04 | $7700.00 | Window Closed / Lapsed |