Patent ID: 6022953
Filing Date: 2000-02-08
Classification: C07K

Abstract:
A multifunctional fusion protein having an M-CSF protein component and second bioactive protein component, wherein said M-CSF protein is capable of stimulating the formation of primarily macrophage colonies in the in vitro colony-stimulating assay, and the second bioactive protein is selected from the group consisting of IL-1, IL-2, IFN-.gamma., and G-CSF,said M-CSF protein having amino acids 1 to 522 of SEQ ID NO: 2 or amino acids 1 to 224 of SEQ ID NO: 4 or being a biologically active fragment thereof, said fragment thereof having M-CSF activity and an N-terminus that begins with an amino acid residue at a position that is a member of the group consisting of positions 1, 2, 3 and 4 of SEQ ID NOS: 2 and 4, and having a C-terminus that ends with an amino acid residue at a position that is a member of the group consisting of positions 150, 158, 190, 221 and 224 of SEQ ID NOS: 2 or 4, or 522 of SEQ ID NO: 2;said second bioactive protein having the provisions: said IL-1 protein comprises amino acid residues 127 through 271 of human IL-1.alpha. or amino acids residues 1 through 147 of human IL-1.beta. as shown in SEQ ID NO: 8;when said second bioactive protein is IL-2, said IL-2 protein comprises amino acid residues 12 through 127 of SEQ ID NOS: 5 or 6, said fusion protein being capable of stimulating the proliferation of T-lymphocytes;when said second bioactive protein is IFN-.gamma., said IFN-.gamma. protein comprises amino acid residues 6 through 127 of human IFN-.gamma. as shown in SEQ ID NO: 9, said fusion protein having IFN-.gamma. activity; andwhen said second bioactive protein is G-CSF, said G-CSF protein comprises amino acid residues 1 through 163 of recombinant G-CSF as shown in SEQ ID NO: 7, said fusion protein capable of stimulating the production of primarily neutrophil colonies of neutrophil-macrophage colonies in a colony forming assay using bone marrow progenitor cells of a species in which stimulation is to be effected.