Pharmacokinetic and Pharmacodynamic Evaluation of Different PEGylated Human Interleukin-11 Preparations in Animal Models.

Treating thrombocytopenia induced by chemotherapy remains an unmet-medical need. The use of recombinant human interleukin-11 (rhIL-11) requires repeated injections and induces significant fluid retention in some patients. Modification of human interleukin-11 with chemically inert polyethylene glycol polymer (PEG) may extend the peripheral circulation half-life leading to an improved pharmacokinetic and pharmadynamic profile.

Efficient expression and isolation of recombinant human interleukin-11 (rhIL-11) in Pichia pastoris.

Current source of recombinant human interleukin-11 (rhIL-11) is isolated from a fusion protein expressed by E. coli that requires additional enterokinase to remove linked protein, resulting in product heterogeneity of N-terminal sequence. Due to lack of glycosylation, rhIL-11 is suitable to be expressed by yeast cells.

Preclinical evaluation of the mono-PEGylated recombinant human interleukin-11 in cynomolgus monkeys.

The mono-PEGylated recombinant human interleukin-11 (rhIL-11) was evaluated for its pharmacology and toxicology profile in non-human primates. This PEGylated IL-11 (PEG-IL11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-PEGylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhIL-11 in humans (t=6.9h).