G-CSF analog compositions and methods
AssigneeMassachusetts Institute of Technology
InventorsCasim A. Sarkar, Douglas A. Lauffenburger, Bruce Tidor
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Abstract
The present invention relates to granulocyte colony stimulating factor (“G-CSF”) analog polypeptide compositions, related nucleic acids, expression constructs, host cells, and processes for recombinant production of the present G-CSF analogs. The concept detailed herein involves novel mutants of G-CSF, using single substitutions to amino acids, which were rationally chosen to affect the cellular trafficking of G-CSF and/or G-CSFR. In addition, pharmaceutical compositions, and methods of use are provided.
Claims15
A human Granulocyte Colony Stimulating Factor (G-CSF) analog polypeptide which comprises an amino acid substitution in the sequence of SEQ ID NO:
- 2 selected from the group consisting of:
- a) a substitution of aspartic acid with histidine at position number 109, [His109]G-CSF;
- b) a substitution of aspartic acid with histidine at position number 112, [His112]G-CSF;
- c) a substitution of glutamine with histidine at position number 119, [His119]G-CSF;
- and
- d) any of the said analogs of subparts (a-c) optionally including an N-terminal methionyl residue.
A polynucleotide encoding a human G-CSF analog polypeptide which comprises an amino acid substitution in the sequence of SEQ ID NO:
- 2 selected from the group consisting of:
- a) a substitution of aspartic acid with histidine at position number 109, [His109]G-CSF;
- b) a substitution of aspartic acid with histidine at position number 112, [His112]G-CSF;
- c) a substitution of glutamine with histidine at position number 119, [His119]G-CSF;
- and
- d) any of the said analogs of subparts (a-c) optionally including an N-terminal methionyl residue.
Dependencies are inferred from the claim text.