N-maleimidyl polymer derivatives

• US 10,385,165 B2
• Filed: 10/31/2017
• Issued: 08/20/2019
• Est. Priority Date: 02/22/2000
• Status: Expired due to Term

• Current Assignee: Nektar Therapeutics Incorporated
• Original Assignee: Nektar Therapeutics Incorporated
• Inventors: Shen, Xiaoming
• Primary Examiner(s): Fubara, Blessing M
• Application Number:
  US15/799,754
• Publication Number:
  US 20180051135A1
• Time in Patent Office: 658 Days
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• 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: A61K 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: C08G 65/00 Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
• CPC Class Codes: C08G 65/33337 cyclic
• CPC Class Codes: C08G 65/33396 having oxygen in addition to nitrogen
• CPC Class Codes: C08G 65/48 Polymers modified by chemical after-treatment

Abstract

The invention is directed to multi-functional N-maleimidyl polymer derivatives comprising a water soluble and non-peptidic polymer backbone having a terminal carbon, such as a poly(alkylene glycol), the terminal carbon of the polymer backbone being directly bonded to the nitrogen atom of a N-maleimidyl moiety without a linking group therebetween. The invention also provides two methods of preparing such linkerless N-maleimidyl polymer derivatives.

Claims

1. A homobifunctional N-maleimidyl polymer having a formula:

2. The homobifunctional N-maleimidyl polymer of claim 1, wherein the polyethylene glycol backbone has an average molecular weight of from about 800 daltons to about 100,000 daltons.

3. A method of forming a homobifunctional N-maleimidyl polyethylene glycol polymer, the method comprising:

(i) reacting a N-maleimidyl polyethylene glycol amine,

4. The method of claim 3, wherein the acetate salt in step (ii) is sodium acetate.

5. The method of claim 3, wherein the acetate salt in step (ii) is potassium acetate.

6. The method of claim 3, wherein the heating in step (ii) is at a temperature from about 50°

C. to about 140°

C.

7. The method of claim 3, wherein the heating in step (ii) is carried out for about 0.2 hours to about 5 hours.

8. The method of claim 3, further comprising purifying the homobifunctional N-maleimidyl polyethylene glycol polymer formed in step (ii).

9. The method of claim 8, wherein the purifying comprises precipitation.

10. The method of claim 8, wherein the purifying comprises ion exchange chromatography.