Variant forms of urate oxidase and use thereof
View Patent ↗Genetically modified proteins with uricolytic activity are described. Proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidase are described.
1. A polypeptide comprising the amino acid sequence of SEQ ID NO: 8.
2. The polypeptide of claim 1 conjugated to polyethylene glycol (PEG).
3. The polypeptide of claim 1 , wherein the PEG is monomethoxy PEG (mPEG).
4. The polypeptide of claim 3 , wherein the mPEG has a molecular weight between 5 kDa and 20 kDa.
5. The polypeptide of claim 4 , wherein the mPEG has a molecular weight of about 10 kDa.
6. The polypeptide of claim 5 , wherein the mPEG is covalently, linked to a lysine residue of the polypeptide.
7. The polypeptide of claim 5 , comprising 2-12 mPEG molecules attached to said polypeptide.
8. A conjugate comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 8 linked to polyethylene glycol (PEG).
9. The conjugate of claim 8 , wherein the PEG is monomethoxy PEG (mPEG).
10. The conjugate of claim 9 , wherein the mPEG has a molecular weight between 5 kDa and 20 kDa.
11. The conjugate of claim 10 , wherein the mPEG has a molecular weight of about 10 kDa.
12. The conjugate of claim 11 , wherein 2-12 mPEG molecules are linked to the polypeptide.
13. A pharmaceutical composition comprising i) a conjugate comprising a polypeptide having the amino acid sequence of SEQ ID NO: 8 linked to polyethylene glycol (PEG); and ii) phosphate buffered saline.
14. The pharmaceutical composition of claim 13 , wherein the PEG is monomethoxy PEG (mPEG).
15. The pharmaceutical composition of claim 14 , wherein the mPEG has a molecular weight between 5 kDa and 20 kDa.
16. The pharmaceutical composition of claim 15 , wherein the mPEG has a molecular weight of about 10 kDa.
17. The pharmaceutical composition of claim 16 , wherein 2-12 mPEG molecules are linked to the polypeptide.
18. The pharmaceutical composition of claim 17 , comprising 8 mg of the polypeptide.
19. The pharmaceutical composition of claim 18 , wherein said conjugate consists of the amino acid sequence of SEQ ID NO: 8 linked to PEG.
20. A uricase comprising the amino acid sequence of SEQ ID NO: 8.
21. The uricase of claim 20 , wherein the uricase comprises a tetramer.
22. The uricase of claim 20 , conjugated to polyethylene glycol (PEG).
23. The uricase of claim 22 , wherein the PEG is monomethoxy PEG (mPEG).
24. The uricase of claim 23 , wherein the mPEG has a molecular weight between 5 kDa and 20 kDa.
25. The uricase of claim 24 , wherein the mPEG has a molecular weight of about 10 kDa.
26. The unease of claim 25 , wherein the mPEG is covalently attached to a lysine residue of the unease.
27. The unease of claim 23 , comprising 2-12 mPEG molecules per unease monomer.
28. The unease of claim 22 , wherein the unease is formulated in a pharmaceutical composition comprising phosphate buffered saline.
29. The uricase of claim 28 , wherein the pharmaceutical composition comprises 8 mg of the uricase.