Nansha Biologics (hong Kong) Limited

Nansha Biologies (hong Kong) Limited

Nansha Biologies (hk) Limited

Manson Fok

Qui-Lim Choo

Johnson Yiu-Nam Lau

Kuo-Ming Yu

Methods are provided for producing a PEGylated interleukin 11 (IL-11) by treating a recombinant IL-11 PEGylated with an equimolar to low molar excess of PEG carrying an amine-reactive group 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.

Methods of preparing a pegylated human IL-11 composition

Recombinant interleukin-11 (rhIL-11) is expressed in yeast, then isolated from aerobic fermentation media by precipitation, solubilization of the precipitate in the presence of a denaturant, and renaturation of the solubilized protein. Renatured rhIL-11 is further purified by cation exchange and hydrophobic interaction chromatography to provide a highly purified rhIL-11 with high biological activity and low rhIL-11 dimer and oxidized rhIL-11 content.

Systems and methods for production of recombinant IL-11 in yeast

Methods are provided for treating an individual with a pharmaceutical preparation that includes 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.

Methods of treatment using a branched amino terminal pegylated Il-11 composition

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.

Interleukin-11 PEGylation reaction intermediate composition

Compositions and methods are presented in which recombinant IL-11 is PEGylated to achieve improved half-life in serum while having desirable therapeutic activity and presenting less 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.

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Hong Kong, China

Manson Fok