CONJUGATES OF AN IL-15 MOIETY AND A POLYMER
Conjugates of an IL-15 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, and methods of administering compositions to an individual.
1 . A conjugate comprising a residue of an IL-15 moiety covalently attached to a water-soluble polymer.
2 . The conjugate of claim 1 , wherein the IL-15 moiety covalently attached to the water-soluble polymer is covalently attached via a releaseable linkage.
3 . The conjugate of claim 1 , wherein the IL-15 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 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 7 , wherein the conjugate is covalently attached at an amine group of the residue of the IL-15 moiety.
11 . The conjugate of claim 10 , wherein one, two, three or four water-soluble polymers are attached to the residue of the IL-15 moiety.
12 . The conjugate of claim 11 , wherein one, two or three water-soluble polymers are attached to the residue of the IL-15 moiety.
13 . The conjugate of claim 12 , wherein one or two water-soluble polymers are attached to the residue of the IL-15 moiety.
14 . The conjugate of claim 13 , wherein one water-soluble polymer is attached to the residue of the IL-15 moiety.
15 . A conjugate comprising a residue of an IL-15 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.
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 .
18 . A method for making a conjugate comprising contacting, under conjugation conditions, an IL-15 moiety with a polymeric reagent.