Modified leptin polypeptides and their uses

• US 9,938,333 B2
• Filed: 02/05/2009
• Issued: 04/10/2018
• Est. Priority Date: 02/08/2008
• Status: Expired due to Fees

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Kraynov, Vadim, Hays Putnam, Anna-Maria A., Knudsen, Nick, Pinkstaff, Jason, Myler, Heather, Sullivan, Lorraine
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US12/863,947
• Publication Number:
  US 20120149636A1
• Time in Patent Office: 3,351 Days
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/5759 Products of obesity genes, e.g. leptin, obese (OB), tub, fat

Abstract

Modified human leptin polypeptides and uses thereof are provided.

Claims

1. A leptin polypeptide comprising one or more non-naturally encoded amino acids substituted at positions selected from:

46, 66, 67, 100, 105, 108, 111 of SEQ ID NO;

4 or the corresponding amino acid encoded by SEQ ID NO;

3 or positions 45, 65, 66, 99, 104, 107, 110 of SEQ ID NO;

2, wherein the non-naturally encoded amino acid in the leptin polypeptide is linked to a water soluble polymer;

wherein the non-naturally encoded amino acid to which the water soluble polymer is linked has the structure;

2. The leptin polypeptide of claim 1, wherein the water soluble polymer comprises a poly(ethylene glycol) moiety.

3. The leptin polypeptide of claim 1, wherein the leptin polypeptide comprises one or more post-translational modifications.

4. The leptin polypeptide of claim 1, wherein said water soluble polymer is linked to a non-naturally encoded amino acid present in said leptin polypeptide.

5. The leptin polypeptide of claim 1, wherein the non-naturally encoded amino acid comprises a carbonyl group, an aminooxy group, a hydrazine group, a hydrazide group, a semi carbazide group, an azide group, or an alkyne group.

6. The leptin polypeptide of claim 1, wherein the non-naturally encoded amino acid comprises a carbonyl group.

7. The leptin polypeptide of claim 1, wherein the water soluble polymer has a molecular weight of between about 0.1 kDa and about 100 kDa.

8. The leptin polypeptide of claim 1, which is made by reacting a water soluble polymer comprising a carbonyl group with a polypeptide comprising a non-naturally encoded amino acid that comprises an aminooxy, a hydrazine, a hydrazide or a semicarbazide group.

9. A composition comprising the leptin polypeptide of claim 1, and a pharmaceutically acceptable carrier.