Pegylated OXM variants

• US 10,537,646 B2
• Filed: 06/04/2013
• Issued: 01/21/2020
• Est. Priority Date: 06/04/2012
• Status: Active Grant

• Current Assignee: Opko Biologics Ltd. (Opko Health, Inc.)
• Original Assignee: Opko Biologics Ltd. (Opko Health, Inc.)
• Inventors: Fima, Udi Eyal, Hershkovitz, Oren
• Primary Examiner(s): Kemmerer, Elizabeth C.
• Assistant Examiner(s): DeBerry, Regina M
• Application Number:
  US14/405,597
• Publication Number:
  US 20150148289A1
• Time in Patent Office: 2,422 Days
• Field of Search: None
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• 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: C07K 1/00 General methods for the preparation of peptides , i.e. processes for the organic chemical preparation of peptides or proteins of any length
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

A composition which includes oxyntomodulin and polyethylene glycol polymer (PEG polymer) linked via a reversible linker such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS) is disclosed. Pharmaceutical compositions comprising the reverse pegylated oxyntomodulin and methods of using same are also disclosed.

Claims

1. A conjugate consisting of an oxyntomodulin, a polyethylene glycol polymer (PEG polymer) and 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS), wherein said PEG polymer is attached to the amino terminus of said oxyntomodulin or to a lysine residue on position number twelve (Lys₁₂) of said oxyntomodulin, via Fmoc or FMS.

2. The conjugate of claim 1, wherein said oxyntomodulin consists of the amino acid sequence set forth in SEQ ID NO:

1.

3. The conjugate of claim 1, wherein said PEG polymer is a PEG polymer with a sulfhydryl moiety.

4. The conjugate of claim 1, wherein said PEG polymer is PEG30.

5. A pharmaceutical composition comprising the conjugate of claim 1 and a pharmaceutical acceptable carrier.

6. A method of inducing glucose tolerance in a subject in need thereof, or increasing insulin sensitivity in a subject in need thereof, or inducing glycemic control in a subject in need thereof, or reducing insulin resistance in a subject in need thereof, the method comprising administering the pharmaceutical composition of claim 5.

7. A method of reducing food intake in a subject in need thereof, or reducing body weight in a subject in need thereof, or for increasing energy expenditure in a subject in need thereof, or improving the cholesterol levels in a subject in need thereof, the method comprising administering the pharmaceutical composition of claim 5.