Mutant of granulocyte-colony stimulating factor (G-CSF) and chemically conjugated polypeptide thereof
First Claim
1. A mutant of an isolated human granulocyte-colony stimulating factor (G-CSF), the mutant comprising the amino acid sequence of SEQ ID NO:
- 5.
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Accused Products
Abstract
Provided are mutants of human granulocyte-colony stimulating factor (G-CSF) designed for specific chemical conjugation, and chemical conjugates thereof for use as an adjuvant in the treatment of cancer. The present invention provides a mutant of a G-CSF in which a threonine (Thr) residue at position 133 of G-CSF comprising the amino acid sequence identified in SEQ ID NO: 1 is substituted with a cysteine (Cys) residue. In addition, the invention provides a mutant of a G-CSF in which a cysteine (Cys) residue is inserted between a glycine (GIy) residue at position 135 and an alanine (Ala) residue at position 136 of G-CSF. Further, the invention provides a chemically conjugated mutant G-CSF to which biocompatible polymer such as polyethylene glycol (PEG) was attached at the cysteine residue, which was introduced by the substitution or insertion mutation, increasing its in vivo retention time without reducing in vivo biological activity due to the conjugation with the biocompatible polymer, thereby ultimately extending the in vivo biological activity.
20 Citations
6 Claims
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1. A mutant of an isolated human granulocyte-colony stimulating factor (G-CSF), the mutant comprising the amino acid sequence of SEQ ID NO:
- 5.
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2. A conjugated mutant of an isolated human granulocyte-colony stimulating factor (G-CSF) comprising a mutant of a human G-CSF and a nonprotein chemical compound, wherein the mutant comprises the amino acid sequence of SEQ ID NO:
- 5, and wherein the nonprotein chemical compound is attached to the cysteine residue at position 136 of SEQ ID NO;
5. - View Dependent Claims (3, 4, 5, 6)
- 5, and wherein the nonprotein chemical compound is attached to the cysteine residue at position 136 of SEQ ID NO;
Specification