Polymer conjugates of therapeutic peptides

Patent metadata

Field	Value
Publication number	US-9682153-B2
Application number	US-201514664582-A
Country	US
Kind code	B2
Filing date	Mar 20, 2015
Priority date	Sep 19, 2008
Publication date	Jun 20, 2017
Grant date	Jun 20, 2017

Abstract

The invention provides peptides that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the peptide not attached to the water-soluble oligomer.

First claim

What is claimed is:

1. A conjugate having the structure:

where:
mPEG is CH 3 O—(CH 2 CH 2 O) n CH 2 CH 2 —;
n is an integer from 10 to 1800;
R 1 is H or lower alkyl;
R 2 is H or lower alkyl;
X 1 and X 2 are each independently —NH—C(O)—CH 2 —O—, —NH—C(O)—(CH 2 ) q —O—, —NH—C(O)—(CH 2 ) q —CO—NH—, —NH—C(O)—(CH 2 ) q —, or —C(O)—NH—;
q is 2, 3, 4, or 5;
˜NH-ZICO is an amino group of a ziconotide moiety; and
k is 1, 2, or 3.

2. The conjugate of claim 1 , wherein the ziconotide moiety is prepared by chemical synthesis.

3. The conjugate of claim 1 , wherein mPEG has a weight-average molecular weight in a range of from about 2,000 Daltons to about 50,000 Daltons.

4. The conjugate of claim 3 , wherein mPEG has a weight-average molecular weight in a range of from about 5,000 Daltons to about 40,000 Daltons.

5. The conjugate of claim 1 , wherein ˜NH-ZICO is at an amino-terminal amino acid of the ziconotide moiety.

6. The conjugate of claim 1 , wherein ˜NH-ZICO is at an epsilon amino group of an internal lysine amino acid of the ziconotide moiety.

7. The conjugate of claim 1 , prepared using a polymeric reagent selected from the following:

8. The conjugate according to claim 1 , wherein the ziconotide comprises the amino acid sequence of SEQ ID NO: 264.

9. A pharmaceutical composition comprising the conjugate of claim 1 and a pharmaceutically acceptable excipient.

10. A method of treatment comprising administering the conjugate of claim 1 to a subject in need thereof.

11. The conjugate of claim 1 , having a structure selected from:

12. The conjugate of claim 1 , wherein k is 1.

Assignees

• Nektar Therapeutics

Inventors

• Bossard Mary J
• Roczniak Steven O
• Zappe Harold
• Wang Yujun
• Zhang Ping
• Sheng Dawei
• Jude-Fishburn C Simone
• Minamitani Elizabeth Louise
• Liu Xiaofeng
• Moskowitz Haim
• Fry Dennis G
• Ali Cherie F
• Brew Christine Taylor

Classifications

• A61K38/10 Primary

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title

• A61K38/16

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)} · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title