Polymer derivatives

• US 9,574,048 B2
• Filed: 07/14/2011
• Issued: 02/21/2017
• Est. Priority Date: 10/09/2003
• Status: Active Grant

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Wilson, Troy E.
• Primary Examiner(s): SELLERS, ROBERT E
• Application Number:
  US13/183,343
• Publication Number:
  US 20110269974A1
• Time in Patent Office: 2,049 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: C08F 216/16 Monomers containing no hetero atoms other than the ether oxygen
• CPC Class Codes: C08F 8/02 Alkylation
• CPC Class Codes: C08F 8/30 Introducing nitrogen atoms or nitrogen-containing groups
• CPC Class Codes: C08G 65/325 containing nitrogen
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08G 65/333 containing nitrogen

Abstract

The invention provides water-soluble compounds that include a polymer and at least one terminal azide or acetylene moiety. Also provided are highly efficient methods for the selective modification of proteins with PEG derivatives, which involves the selective incorporation of non-genetically encoded amino acids, e.g., those amino acids containing an azide or acetylene moiety, into proteins in response to a selector codon and the subsequent modification of those amino acids with a suitably reactive PEG derivative.

Claims

1. A water-soluble polymer containing at least one acetylene moiety, wherein said polymer is selected from the group consisting of poly(oxyethylated polyols) and poly(olefinic alcohols), wherein said polymer comprises at least one arm of a branched molecular structure, and wherein said polymer has a molecular weight of from about 6,000 to 80,000 for each chain of the polymer backbone.

2. The water-soluble compound of claim 1 wherein said polymer is poly(oxyethylated glycerol).

3. The water-soluble compound of claim 1 wherein said polymer is poly(oxyethylated sorbitol).

4. The water-soluble compound of claim 2, wherein said polymer is poly(ethylene glycol)acetylene and wherein the acetylene moiety is covalently linked to a polymer backbone via a linker moiety.

5. The water-soluble compound of claim 2 wherein said polymer is poly(ethylene glycol)acetylene, wherein said acetylene moiety is covalently bound to a polymer backbone via an ether linkage.

6. The water-soluble compound of claim 1 wherein said polymer is a random or block copolymer or terpolymer.

7. The water-soluble compound of claim 1 wherein said compound comprises a dumbbell structure comprising:

a) said acetylene moiety on at least a first end of a polymer backbone; and

b) at least a second functional group on at least a second end of the polymer backbone;

wherein the second functional group can be the same or different from said acetylene moiety.

8. The water-soluble compound of claim 7 wherein said second functional group is an acetylene moiety.

9. The water-soluble compound of claim 1 wherein said polymer is poly(oxyethylated glucose).

10. The water-soluble polymer of claim 1 wherein the molecular weight of each chain of the polymer backbone is about 6,000.

11. The water-soluble polymer of claim 1 wherein the molecular weight of each chain of the polymer backbone is about 80,000.

12. A water-soluble polymer containing at least one acetylene moiety, wherein said polymer is selected from the group consisting of poly(oxyethylated polyols) and poly(olefinic alcohols), wherein said polymer comprises at least one arm of a branched molecular structure, and wherein said polymer has a molecular weight of from about 80,000 to 100,000 for each chain of the polymer backbone.

13. The water-soluble polymer of claim 12 wherein the molecular weight of each chain of the polymer backbone is about 100,000.