Granulocyte Colony- Stimulating Factor (G-CSF) is a cytokine that stimulates proliferation and differentiation of granulocytes. Recombinant human G-CSF is widely used to stimulate neutrophil production in patients with neutropenia resulting from myelosuppressive chemotherapy and is awaiting FDA approval for treating neutropenia resulting from immunosuppressive diseases such as AIDS. Recombinant human G-CSF had world-wide sales in excess of $1 billion during 1996. The applicant proposes to create modified G-CSF proteins that are equal or superior to natural G-CSF at stimulating granulocyte formation in vivo, but which require less frequent dosing, on the order of once per week or once every other week. During Phase I the applicant will identify sites in G-CSF that can be modified without affecting the protein's in vitro bioactivity. During Phase II, the applicant will manufacture sufficient quantities of the modified G-CSF proteins for testing in animal models of neutropenia. The improved characteristics of the novel G-CSF proteins will reduce the amount of G-CSF required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Information gained from these studies will aid in creating long-acting versions of structurally related cytokines and growth factors for use in treating cancer, infectious disease and hematopoeitic disorders.
Recombinant human G-CSF is used to restore neutrophil production in patients with neutropenia resulting from chemotherapy, chronic neutropenia and immunosuppressive disease such as AIDS. Recombinant G- CSF has world wide sales in excess of $1 billion in 1996. The modified G-CSF proteins under development will require much less frequent dosing, providing significant cost savings to patients and healthcare providers. Additional potential benefits include improved drug efficacy and improved patient quality of life.