Conjugates of an IL-2 Moiety and a Polymer

• US 20140328791A1
• Filed: 11/11/2011
• Published: 11/06/2014
• Est. Priority Date: 11/12/2010
• Status: Active Grant

• Current Assignee: Nektar Therapeutics Incorporated
• Original Assignee: Nektar Therapeutics Incorporated
• Inventors: Bossard, Mary J., Ali, Cherie F., Liu, Xiaofeng, Charych, Deborah H., Zappe, Harold, Wang, Yujun, Huang, Jicai
• Granted Patent: US 9,861,705 B2
• Time in Patent Office: Days
• US Class Current: 424/85.2
• CPC Class Codes: A61K 38/2013 IL-2
• 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 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 14/55 IL-2
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Conjugates of an IL-2 moiety and one or more nonpeptidic, water-soluble polymers are provided. Typically, the nonpeptidic, water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided, among other things, are compositions comprising conjugates, methods of making conjugates, methods of administering compositions to an individual, nucleic acid sequences, expression systems, host cells, and methods for preparing IL-moieties.

Claims

1. A conjugate comprising a residue of an IL-2 moiety covalently attached to a water-soluble polymer.

2. The conjugate of claim 1, wherein the IL-2 moiety covalently attached to the water-soluble polymer is covalently attached via a releaseable linkage.

3. The conjugate of claim 1, wherein the IL-2 moiety covalently attached to the water-soluble polymer is covalently attached via a stable linkage.

4. The conjugate of claim 1, wherein the water-soluble polymer is a branched water-soluble polymer.

5. The conjugate of claim 1, wherein the water-soluble polymer is a polymer selected from the group consisting of poly(alkylene oxide), poly(vinyl pyrrolidone), poly(vinyl alcohol), polyoxazoline, and poly(acryloylmorpholine).

6. The conjugate of claim 5, wherein the water-soluble polymer is a poly(alkylene oxide).

7. The conjugate of claim 6, wherein the poly(alkylene oxide) is a poly(ethylene glycol).

8. The conjugate of claim 7, wherein the poly(ethylene glycol) is terminally capped with an end-capping moiety selected from the group consisting of hydroxy, alkoxy, substituted alkoxy, alkenoxy, substituted alkenoxy, alkynoxy, substituted alkynoxy, aryloxy and substituted aryloxy.

9. The conjugate of claim 1, wherein the water-soluble polymer has a weight-average molecular weight in a range of from about 500 Daltons to about 100,000 Daltons.

10. The conjugate of claim 1, wherein the conjugate is covalently attached at an amine group of the residue of the IL-2 moiety.

11. The conjugate of claim 1, wherein one, two, three or four water-soluble polymers are attached to the residue of the IL-2 moiety.

12. The conjugate of claim 1, wherein one, two or three water-soluble polymers are attached to the residue of the IL-2 moiety.

13. The conjugate of claim 1, wherein one or water-soluble polymers are attached to the residue of the IL-2 moiety.

14. The conjugate of claim 1, wherein one water-soluble polymer is attached to the residue of the IL-2 moiety.

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

17. A method comprising administering to an individual a pharmaceutical composition of claim 16.

15. A conjugate comprising a residue of an IL-2 moiety covalently attached to a water-soluble polymer, wherein the water-soluble polymer, prior to being covalently attached, is a polymeric reagent bearing an N-hydroxysuccinimidyl group.

18. A method for making a conjugate comprising contacting, under conjugation conditions, an IL-2 moiety with a polymeric reagent.

19. An isolated nucleic acid molecule encoding an IL-2 moiety, wherein said nucleic acid molecule includes a sequence having at least 95% sequence identify to the sequence set forth in SEQ ID NO:

5.

20. The nucleic acid molecule of claim 19, wherein the nucleic acid molecule is DNA.

21. An expression vector comprising the nucleic acid molecule of claim 19.

22. The expression vector of claim 21, wherein the expression vector is a plasmid.

23. An in vitro host cell comprising the vector of claim 22.

24. A method comprising placing a protein within a dialysis bag having a pore size smaller than the size of the protein to form a protein-containing dialysis bag, and subjecting the protein-containing dialysis bag to a protein denaturant-free solution.

25. A composition comprising an IL-2 moiety, 5-15 mM sodium acetate and 2-7% trehalose.