Implantable pump for protein delivery for obesity control by drug infusion into the brain

• US 7,790,671 B2
• Filed: 10/07/2005
• Issued: 09/07/2010
• Est. Priority Date: 10/07/2005
• Status: Expired due to Fees

• Current Assignee: Codman & Shurtleff Incorporated (Johnson & Johnson)
• Original Assignee: Codman & Shurtleff Incorporated (Johnson & Johnson)
• Inventors: Stojanovic-Susulic, Vedrana, Cunningham, Mark, Venugopalan, Ramakrishna
• Primary Examiner(s): Kosar; Andrew D
• Application Number:
  US11/245,653
• Publication Number:
  US 20070082843A1
• Time in Patent Office: 1,796 Days
• Field of Search: None
• US Class Current: 514/5.2
• CPC Class Codes: A61K 38/34 Melanocyte stimulating hormone [MSH], e.g. alpha- or beta-melanotropin
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents

Abstract

Methods and compositions are provided for suppressing appetite by surgically implanting a drug infusion pump into a site in a subject, and delivering a stable suspension of an appetite suppressing agent a region in a central nervous system of the subject. The appetite suppressing agent binds to a target receptor on a neural cell in the central nervous system and modifies the receptor function to suppress appetite.

Claims

1. A method of suppressing appetite comprising:

implanting a drug infusion pump into a site in a subject; and

delivering a stable suspension of an effective dosage of an appetite suppressing agent to a site in a central nervous system of the subject, the appetite suppressing agent comprising a polypeptide having the general formula;

(Mp-Lk-V2—

Hg—

C_H2—

C_H3)_(t)

wherein Mp is an alpha melanocyte-stimulating hormone (α

-MSH) peptide, LK is a polypeptide or chemical linkage, V2 is a portion of a C-terminus of an immunoglobulin variable region, Hg is at least a portion of an immunoglobulin variable hinge region, C_H2 is an immunoglobulin heavy chain C_H2 constant region, C_H3 is an immunoglobulin heavy chain C_H3 constant region, and t is an integer of 1 to 10, wherein the appetite suppressing agent binds to a target receptor on a neural cell in the central nervous system and modifies the receptor function to suppress appetite.

2. The method of claim 1, wherein the target receptor is a melanocortin receptor selected from the group consisting of melanocortin-1 receptor (MC1R), melanocortin-2 receptor (MC2R), melanocortin-3 receptor (MC3R), melanocortin-4 receptor (MC4R), and melanocortin-5 receptor (MC5R).

3. The method of claim 1, wherein the target receptor is melanocortin-4 receptor (MC4R).

4. The method of claim 1, wherein the target is melanocortin-3 receptor (MC3R).

5. The method of claim 1, wherein the site in the central nervous system is the brain.

6. The method of claim 1, further comprising delivering a second appetite suppressing agent selected from the group consisting of leptin, NPY peptide, antagonist, PYY 3-36 peptide agonist or its analog, GLP-1 peptide or its analog and MCH receptor antagonist.

7. A method for ameliorating obesity in a subject, comprising:

implanting a drug infusion pump into a site in a subject; and

delivering a stable suspension of an appetite suppressing agent to a region in a central nervous system of the subject, appetite suppressing agent comprising a polypeptide having the general formula;

(Mp-Lk-V2—

Hg—

C_H2—

C_H3)_(t)

wherein Mp is an alpha melanocyte-stimulating hormone (α

-MSH) peptide, LK is a polypeptide or chemical linkage, V2is a portion of a C-terminus of an immunoglobulin variable region, Hg is at least a portion of an immunoglobulin variable hinge region, C_H2 is an immunoglobulin heavy chain C_H2 constant region C_H3 is an immunoglobulin heavy chain C_H3 constant region, and t is an integer of 1 to 10, wherein the appetite suppressing agent binds to a melanocortin receptor on a neural cell in the central nervous system and modifies the melanocortin receptor function to suppress appetite, thereby ameliorating obesity.

8. The method of claim 7, wherein the target receptor is a melanocortin receptor selected from the group consisting of melanocortin-1 receptor (MC1R), melanocortin-2 receptor (MC2R), melanocortin-3 receptor (MC3R), melanocortin-4 receptor (MC4R), and melanocortin-5 receptor (MC5R).

9. The method of claim 7, wherein the target receptor is melanocortin-4 receptor (MC4R).

10. The method of claim 7, wherein the target receptor is melanocortin-3 receptor (MC3R).

11. The method of claim 7, wherein the region in the central nervous system is the brain.

12. The method of claim 7, further comprising delivering a second appetite suppressing agent selected from the group consisting of leptin, NY peptide antagonist, PYY 3-36 peptide agonist or its analog, GLP-1 peptide or its analog, and MCH receptor antagonist.