Pegylated variant of human granulocyte-colony stimulating factor (G-CSF)

Humans and other mammals

The product is a pegylated variant of human granulocyte-colony stimulating factor (G-CSF). This variant contains multiple non-naturally occurring lysines that have been introduced into alpha helixes of wild type human G-CSF as PEGylation sites, and from which multiple undesired, naturally occurring lysines have been removed as compared to wild type human G-CSF to avoid PEGylation of such sites. Specifically, the amino acid sequence of the product differs from that of human wild type G-CSF at residues 16, 34, 40, 105 and 159. This was accomplished by removing the three lysine residues at positions 16, 34 and 40, and replacing them with arginine, and substituting two new lysine residues at positions 105 and 159. The product is pegylated with 5 kd mPEG SPA (succinimidyl propionate) groups at 3 amino acid residues, including PEG groups attached at the amino terminal end of the protein and at two internal lysine residues, while Neulasta has a single 20 Kd PEG group attached at the N terminal end of the wild type G-CSF protein.

Neutropenia is a severe decrease in neutrophil cell counts in the blood. Neutropenia is a common side effect of chemotherapeutic treatments for many forms of cancer, including breast cancer, lung cancer, lymphomas and leukemias. Neutropenic patients contract bacterial infections more easily and often, some of which can be life threatening. Further, and most importantly, neutropenic patients may receive reduced or delayed chemotherapy treatment, which can result in cancer progression. Maxy-G34, like natural G-CSF is a protein that stimulates the body's bone marrow to produce neutrophils, a specific type of white blood cell that plays an important role in the defense against bacterial infections.

The product is a PEGylated proprietary G-CSF variant designed to be administered as a single subcutaneous injection once per chemotherapy cycle. Maxygen has made changes in the G-CSF gene sequence that code for novel PEGylation sites in the resulting protein. In contrast to the currently marketed PEGylated G-CSF, the product has multiple PEG groups attached at specifically selected sites on the molecule. In several in vivo models, the product has demonstratedimproved pharmacokinetics and pharmacodynamics compared to the currently marketed PEGylated G-CSF.