Conjugates of an IL-2 moiety and a polymer
Conjugates of an interleukin-2 (“IL-2”) moiety and one or more nonpeptidic, water-soluble polymers are provided. Typically, the non-peptidic, 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.
1. A method comprising administering to an individual a conjugate of an interleukin-2 moiety, the conjugate comprising from one to seven branched poly(ethylene glycol) polymers each covalently attached via a releasable linkage to an amino group of an interleukin-2 moiety having the amino acid sequence of SEQ ID NO:1, wherein each branched poly(ethylene glycol) molecule has a weight average molecular weight from about 20,000 daltons to about 85,000 daltons.
2. The method of claim 1 , wherein each branched poly(ethylene glycol) polymer is terminally capped with C1-C5 alkoxy end-capping groups.
3. The method of claim 2 , wherein the alkoxy end-capping groups are methoxy groups.
4. The method of claim 1 , wherein each branched poly(ethylene glycol) polymer comprises two poly(ethylene glycol) chains.
5. The method of claim 1 , wherein the releasable linkage is a releasable carbamate linkage.
6. The method of claim 1 , wherein each branched poly(ethylene glycol) polymer has a weight average molecular weight of about 20,000 daltons.
7. The method of claim 1 , wherein upon release of the branched poly(ethylene glycol) polymer in vivo, the polymer detaches from the interleukin-2 moiety without leaving a fragment thereof attached to the interleukin-2 moiety.
8. The method of claim 1 , wherein the conjugate has one, two, three or four branched poly(ethylene glycol) polymers each covalently attached via a releasable linkage to an amino group of the interleukin-2 moiety.
9. The method of claim 8 , wherein the conjugate has one, two, or three branched poly(ethylene glycol) polymers each covalently attached via a releasable linkage to an amino group of the interleukin-2 moiety.
10. The method of claim 1 , wherein the conjugate has four, five, six, or seven branched poly(ethylene glycol) polymers each covalently attached via a releasable linkage to an amino group of the interleukin-2 moiety.
11. The method of claim 10 , wherein the conjugate possesses no interleukin-2 activity prior to release of the branched poly(ethylene glycol) polymer(s) from the conjugate in vivo following the administering.
12. The method of claim 1 , wherein the conjugate is comprised in a composition comprising a plurality of the conjugates.
13. The method of claim 12 , wherein the plurality of conjugates is a mixture of conjugates selected from the group consisting of conjugates having four, five, six and seven of the branched poly(ethylene glycol) polymers each covalently attached via a releasable linkage to an amino group of the interleukin-2 moiety.
14. The method of claim 12 , wherein the plurality of conjugates is a mixture of conjugates having an average of six branched poly(ethylene glycol) polymers per interleukin-2 moiety.
15. The method of claim 1 , wherein the conjugate is comprised in a composition suitable for injection.
16. The method of claim 15 , wherein the conjugate is administered parenterally.
17. The method of claim 16 , wherein the conjugate is administered intravenously.
18. The method of claim 17 , wherein the conjugate is administered to an individual having cancer.
19. The method of claim 18 , wherein the cancer is selected from renal cell carcinoma, metastatic melanoma, acute myeloid leukemia, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, breast cancer and bladder cancer.
20. The method of claim 1 , wherein the conjugate is administered in combination with another active agent.