Pharmaceutical preparation and method of treatment of human malignancies with arginine deprivation
View Patent ↗The present invention provides an isolated and substantially purified recombinant human arginase having sufficiently high enzymatic activity and stability to maintain Adequate Arginine Depletion in a patient. The present invention also provides a pharmaceutical composition comprising the modified invention enzyme and method for treatment of diseases using the pharmaceutical composition.
1. A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide having an amino acid sequence encoded by a nucleic acid of SEQ ID NO: 8, which wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule, wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.
2. A method of treatment of human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide having the amino acid sequence of SEQ ID NO: 9, wherein said human arginase I modified by covalent linkage to at least one polyethylene glycol (PEG) molecule, wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.
3. A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide having an amino acid sequence encoded by a nucleic acid of SEQ ID NO: 2, wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule, wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.
4. A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide having the amino acid sequence of SEQ ID NO: 3, wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule, wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.
5. A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide of 80-100% purity as determined by gel chromatography and densitometry having an amino acid sequence encoded by a nucleic acid of SEQ ID NO: 8, wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.
6. A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide of 80-100% purity as determined by gel chromatography and densitometry, having the amino acid sequence of SEQ ID NO: 9, wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule, wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.
7. A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide of 80-100% purity as determined by gel chromatography and densitometry having an amino acid sequence encoded by a nucleic acid of SEQ ID NO: 2, wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.
8. A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide of 80-100% purity as determined by gel chromatography and densitometry having the amino acid sequence of SEQ ID NO: 3, wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.
9. A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide comprising the amino acid sequence of SEQ ID NO: 3, which is of 80-100% purity, wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule, and has an extended half-life of at least 3 days.
10. The method of claim 9 , wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days.