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 composition comprising a conjugate of an interleukin-2 (IL-2) moiety, the conjugate comprising from three to seven branched poly(ethylene glycol) polymers, each covalently attached via a releasable linkage to an amino group of the IL-2 moiety, wherein the IL-2 moiety is aldesleukin, each branched poly(ethylene glycol) has a weight average molecular weight from about 20,000 daltons to about 85,000 daltons, and the composition possesses no IL-2 activity prior to in vivo release of the branched poly(ethylene glycol) polymer(s) from the conjugate.
2. The composition of claim 1 , wherein each branched poly(ethylene glycol) polymer is terminally capped with an alkoxy end-capping moiety.
3. The composition of claim 1 , wherein each branched poly(ethylene glycol) polymer is covalently attached at an amino group of a lysine of the IL-2 moiety.
4. The composition of claim 1 , wherein three or four branched poly(ethylene glycol) polymers are attached to the IL-2 moiety.
5. The composition of claim 1 , wherein each branched poly(ethylene glycol) polymer has a weight average molecular weight of about 20,000 daltons.
6. The composition of claim 5 , wherein each branched poly(ethylene glycol) polymer comprises two poly(ethylene glycol) chains.
7. The composition of claim 1 , wherein the composition comprises a plurality of the conjugates comprising from three to seven branched poly(ethylene glycol) polymers covalently attached to the IL-2 moiety, and the composition possesses no IL-2 activity prior to in vivo release of the branched poly(ethylene glycol) polymer(s) from the conjugates comprised in the composition.
8. The composition of claim 6 , wherein the composition comprises a plurality of the conjugates comprising from three to seven branched poly(ethylene glycol) polymers covalently attached to the IL-2 moiety, and the composition possesses no IL-2 activity prior to in vivo release of the branched poly(ethylene glycol) polymer(s) from the conjugates comprised in the composition.
9. The composition of claim 8 , wherein the plurality of conjugates is a mixture of conjugates selected from the group of conjugates having four, five, six and seven branched poly(ethylene glycol) polymers covalently attached to the IL-2 moiety.
10. The composition of claim 9 , wherein the plurality of conjugates is a mixture of conjugates having an average of six branched poly(ethylene glycol) polymers per interleukin-2 moiety.
11. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable excipient.
12. The composition of claim 11 , in a form suitable for injection.
13. The composition of claim 11 , in the form of a lyophilate for reconstitution with a pharmaceutically acceptable diluent.
14. The composition of claim 11 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of carbohydrates, inorganic salts, buffers, acids, bases, and combinations thereof.
15. A method of treating a patient with cancer, the method comprising administering to the patient a pharmaceutical composition of claim 11 .