Composition and Methods for Treatment of Congestive Heart Failure

• US 20100029554A1
• Filed: 05/25/2007
• Published: 02/04/2010
• Est. Priority Date: 05/26/2006
• Status: Abandoned Application

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Soares, Christopher J., Lewis, Diana Y., Janssen, Samuel, Jodka, Carolyn M., Lin, Qing, Liu, Que, Ghosh, Soumitra S., Srivastava, Ved
• Application Number:
  US12/301,199
• Publication Number:
  US 20100029554A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

Provided herein is the use of GLP-1 molecules or agonists and analogs thereof, and the use of exendin molecules or agonists and analogs thereof, including their derivatives and active fragments, for the prevention or treatment of congestive heart failure. Pharmaceutical compositions for use in the methods described herein are also disclosed. Further provided are compositions and methods for the treatment and/or prevention of diabetes mellitus, hyperglycemia, insulin resistance and obesity, and for the reduction of food intake and suppression of appetite of subjects.

Claims

1-119. -119. (canceled)

120. A polypeptide comprising the amino acid sequence of any one of SEQ ID NOs. 4-106.

121. The polypeptide of claim 120, comprising the amino acid sequence of any one of SEQ ID NOs. 4-28, 30-41, 46-54, 56-60, 62-64, 66-70, 80-93, and 96-106.

122. The polypeptide of claim 120, comprising the amino acid sequence of SEQ ID NO. 27 or 44.

123. The polypeptide of claim 120, comprising the amino acid sequence of SEQ ID NO. 60.

124. The polypeptide of claim 120, further comprising a polyamino acid, a fatty acid, a polyethylene glycol polymer, albumin, gelatin, or an immunoglobulin.

125. The polypeptide of claim 120, further comprising a polyethylene glycol polymer having a molecular weight from 500 to 20,000.

126. The polypeptide of claim 120, further comprising a monoclonal antibody or a catalytic antibody.

127. The polypeptide of claim 120, further comprising a C₁-C₂₀ alkyl side chain.

128. A pharmaceutical composition comprising the polypeptide of claim 120 and a pharmaceutically acceptable carrier.

129. The pharmaceutical composition of claim 128, wherein the pharmaceutical composition is a sustained release pharmaceutical composition.

130. A method for treating diabetes mellitus in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the polypeptide of claim 120.

131. The method of claim 130, wherein the diabetes mellitus is Type 1 diabetes mellitus.

132. The method of claim 130, wherein the diabetes mellitus is Type 2 diabetes mellitus.

133. A method for treating diabetes mellitus in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 128.

134. The method of claim 133, wherein the diabetes mellitus is Type 1 diabetes mellitus.

135. The method of claim 133, wherein the diabetes mellitus is Type 2 diabetes mellitus.

136. A method for treating dyslipidemia, insulin resistance, postprandial hyperglycemia, congestive heart failure, obesity, or hypertriglyceridemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the polypeptide of claim 120.

137. A method for treating dyslipidemia, insulin resistance, postprandial hyperglycemia, congestive heart failure, obesity, or hypertriglyceridemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 128.

138. A method for improving cardiac function;

attenuating cardiac remodeling;

limiting infarct size;

attenuating insulin resistance;

improving exercise capacity;

lowering blood glucose;

stimulating an insulin response;

reducing food intake;

or reducing appetite in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the polypeptide of claim 120.

139. A method for improving cardiac function;

attenuating cardiac remodeling;

limiting infarct size;

attenuating insulin resistance;

improving exercise capacity;

lowering blood glucose;

stimulating an insulin response;

reducing food intake;

or reducing appetite in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 128.

140. A polypeptide having at least 90% sequence identity to a polypeptide comprising the amino acid sequence of SEQ ID NO. 60.

141. The polypeptide of claim 140, having at least 94% sequence identity to the polypeptide comprising the amino acid sequence of SEQ ID NO. 60.

142. The polypeptide of claim 140, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO. 52, 56, 59, 60, 76, 77, or 78.

143. The polypeptide of claim 140, further comprising a polyamino acid, a fatty acid, a polyethylene glycol polymer, albumin, gelatin, or an immunoglobulin.

144. A method of treating diabetes mellitus in a human in need thereof comprising administering to the human a therapeutically effective amount of the polypeptide of claim 140.

145. A pharmaceutical composition comprising the polypeptide of claim 140 and a pharmaceutically acceptable carrier.

146. A method of treating diabetes mellitus in a human in need thereof comprising administering to the human a therapeutically effective amount of the pharmaceutical composition of claim 145.

147. A method for treating dyslipidemia, insulin resistance, postprandial hyperglycemia, congestive heart failure, obesity, or hypertriglyceridemia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the polypeptide of claim 140.

148. A method for improving cardiac function;

attenuating cardiac remodeling;

limiting infarct size;

attenuating insulin resistance;

improving exercise capacity;

lowering blood glucose;

stimulating an insulin response;

reducing food intake;

or reducing appetite in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the polypeptide of claim 140.