G-CSF hybrid compositions suitable for treating disorders requiring the recruitment of neutrophils

摘要

A G-CSF hybrid molecule comprised of a G-CSF analog moiety and a biologically active protein moiety characterised by: a) Having amino acids 2-175 of Sequence ID 2 optionally with an N-terminal methionyl residue; b) Having an overall three-dimensional conformation as set forth in Figure 4 comprising: i) An anti-parallel 4-alpha helical bundle with a left hand twist; ii) An overall dimension of 45å x 30å x 24å; and iii) A helix crossing angles ranging from -167.5o to -159.4o; and c) Having a biologically active protein attached to an amino acid selected from among amino acids 119-145 of the CD loop of Sequence ID No. 2. G-CSF hybrids are useful for selectively stimulating neutrophil production to compensate for hematopoietic deficits resulting from chemotherapy or radiation therapy.