Conjugates of an IL-2 moiety and a polymer

Inventors

Bossard, Mary J. • Ali, Cherie F. • Liu, Xiaofeng • Charych, Deborah H. • Wang, Yujun

Assignees

Nektar Therapeutics

Abstract

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.

Core Innovation

The invention provides a composition comprising a conjugate of an interleukin-2 (IL-2) moiety, wherein the IL-2 moiety is aldesleukin. The conjugate comprises from three to seven branched poly(ethylene glycol) polymers that are covalently attached via a releasable linkage to an amino group of the IL-2 moiety, and each branched poly(ethylene glycol) has a weight average molecular weight from about 20,000 daltons to about 85,000 daltons.

The composition possesses no IL-2 activity prior to in vivo release of the branched poly(ethylene glycol) polymer(s) from the conjugate. The releasable linkage chemistry includes attachment to amino groups of the IL-2 moiety, including attachment to an amino group of a lysine, and includes PEG-linker reagents and branched or forked mPEG polymers with linker and spacer moieties.

The disclosed chemistry includes succinimidyl reagents, aldehyde-derived secondary amine linkages, amide linkages, carbamate linkages, thiol-based attachment, cysteine thiols, disulfide linkage, thioether linkage, hydrazone linkage, ester, thioester, and PEG derivatized groups including mPEG acetal, mPEG piperidone, mPEG methylketone, mPEG maleimide, tosylate, epoxide, and forked or branched maleimide.

Claims Coverage

The consolidated claim coverage identifies three main inventive features centered on an aldesleukin conjugate with branched poly(ethylene glycol) polymers attached via a releasable linkage and having no IL-2 activity prior to in vivo release.

The claim coverage is focused on an aldesleukin conjugate bearing three to seven branched poly(ethylene glycol) polymers covalently attached via releasable linkages to amino groups of the IL-2 moiety, with branched PEG molecular weights of about 20,000 to about 85,000 daltons and with no IL-2 activity prior to in vivo release.

Stated Advantages

Documented Applications