METHODS AND TREATMENT WITH GLP-1 RECEPTOR AGONISTS

• US 20150111816A1
• Filed: 01/23/2014
• Published: 04/23/2015
• Est. Priority Date: 06/27/2011
• Status: Abandoned Application

• Current Assignee: PhaseBio Pharmaceuticals, Inc.
• Original Assignee: PhaseBio Pharmaceuticals, Inc.
• Inventors: GEORGOPOULOS, Lynne M., Sue, Sue
• Application Number:
  US14/162,509
• Publication Number:
  US 20150111816A1
• Time in Patent Office: Days
• US Class Current: 514/5.3
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The invention provides methods for treating diabetes or obesity, as well as methods for inducing weight loss, preventing weight gain, or controlling weight in a patient in need thereof. The methods comprise administering to the patient at least one effective dose of a GLP-1 receptor agonist, or a regimen of GLP-1 receptor agonist comprising a plurality of substantially evenly spaced doses. The effective dose or regimen does not induce substantial nausea or appetite suppression in the patient.

Claims

1-109. -109. (canceled)

110. A method of inducing weight loss, preventing weight gain, or controlling weight in a patient in need thereof, comprising administering at least one effective dose of a therapeutic agent comprising a GLP-1 receptor agonist and an elastin-like peptide (ELP) component, wherein the effective dose does not induce substantial appetite suppression in the patient.

111. The method of claim 110, wherein the regimen maintains therapeutic serum levels of said GLP-1 receptor agonist below a nausea-inducing threshold level, and/or avoid a nausea-inducing rise in GLP-1 levels.

112. The method of claim 110, wherein the patient is overweight, obese, or has a metabolic disease.

113. The method of claim 112, wherein the patient is diabetic or pre-diabetic.

114. The method of claim 110, wherein the patient has at least two of:

(1) triglycerides;

>

150 mg/dL (1.7 mmol/L);

(2) HDL cholesterol <

40 mg/dL (1.03 mmol/L) in males, <

50 mg/dL (1.29 mmol/L) in females;

(3) systolic BP >

130 or diastolic BP >

85 mm Hg, or the patient is being treated for hypertension;

(4) fasting plasma glucose (FPG)>

100 mg/dL (5.6 mmol/L) or the patient is being treated for hyperglycemia; and

/or

(5) an elevated waist circumference equal to or greater than 40 inches (102 cm) for men, or equal to or greater than 35 inches (88 cm) for women.

115. The method of claim 110, wherein the GLP-1 receptor agonist is GLP-1 7-36, GLP-1 7-37, exendin, or a derivative or homolog thereof.

116. The method of claim 110, wherein the ELP comprises repeats of an ELP1 amino acid sequence.

117. The method of claim 110, wherein the ELP comprises repeats of the amino acid sequence VPGXG, where each X is selected from V, G, or A.

118. The method of claim 117, wherein the ELP comprises repeats of the amino acid sequence VPGXG, where each X is selected from V, G, or A at a ratio of 5:

3;

2.

119. The method of claim 117, wherein the ELP comprises at least 100 repeats.

120. The method of claim 117, wherein the ELP comprises at least 120 repeats.

121. The method of claim 110, wherein the therapeutic agent is administered about weekly.

122. The method of claim 110, wherein the therapeutic agent is administered two or three times per week.

123. The method of claim 110, wherein the therapeutic agent is administered about daily.

124. The method of claim 110, wherein the therapeutic agent is administered subcutaneously.

125. The method of claim 110, wherein the therapeutic agent has the amino acid sequence of SEQ ID NO:

13 or is a functional equivalent thereof.

126. The method of claim 110, wherein the therapeutic agent is administered at a dose equivalent of from about 0.1 to about 2.0 mg/kg of SEQ ID NO:

13.

127. The method of claim 125, wherein the therapeutic agent is administered at a dose of from about 0.1 to about 2.0 mg/kg.

128. The method of claim 110, wherein the regimen has a substantially neutral impact on the first phase insulin response in the patient.

129. The method of claim 110, wherein the regimen has a substantially enhanced effect on the second phase insulin response in the patient.