Interleukin-11 PEGylation reaction intermediate composition
AssigneeNansha Biologies (Hong Kong) Limited
InventorsKuo-Ming Yu, Qui-Lim Choo, Manson Fok, Johnson Yiu-Nam Lau
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Abstract
Compositions are presented that include a recombinant IL-11 PEGylated at equimolar to low molar excess of PEG to achieve a highly pure monoconjugate preparation, which provides improved half-life in serum while having desirable therapeutic activity and presenting fewer side-effects. Most preferably, the IL-11 is an N-terminally truncated human or humanized IL-11 and has a 20 Kd or 40 Kd branched PEG moiety, Y- or comb-shaped in particular, coupled to the N-terminal amino group. Such compounds are characterized by substantially increased stability in serum and sustained biological activity while exhibiting significantly reduced plasma expansion.
Claims7
An interleukin 11 (IL-11) conjugation reaction intermediate of an IL-11 PEG conjugation process, comprising:
- an IL-11 PEG conjugate comprising an IL-11 polypeptide chain coupled to a bound PEG moiety, wherein the IL-11 PEG process selectively couples an amine-reactive PEG moiety to the N-terminus of the IL-11 polypeptide chain, and wherein the amine reactive PEG moiety has an average molecular weight of between 10-50 Kd and has at least two branches;
- and
- residual PEG moiety derived from the amine-reactive PEG moiety that did not couple to the IL-11 polypeptide chain during coupling, wherein a total PEG moiety represents a summation of the bound PEG moiety and the residual PEG moiety, and where the total PEG moiety of the IL-11 conjugation reaction intermediate is equimolar to 2-fold molar excess relative to IL-11 polypeptide chain provided to the IL-11 PEG conjugation process;
- wherein the amine reactive PEG moiety and the IL-11 polypeptide chain are selected such that the IL-11 conjugation reaction intermediate comprises a monosubstituted IL-11 PEG conjugate at a purity of greater than 93%;
- and
- wherein the IL-11 polypeptide chain is a human IL-11 or truncated human IL-11 polypeptide chain.
Dependencies are inferred from the claim text.