VARIANT FORMS OF URATE OXIDASE AND USE THEREOF
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 - 37 . (canceled)
38 . A uricase comprising the amino acid sequence of SEQ ID NO: 8.
39 . The uricase of claim 38 conjugated to polyethylene glycol (PEG).
40 . The uricase of claim 39 , wherein the PEG is monomethoxy PEG (mPEG).
41 . The uricase of claim 40 , wherein the mPEG has a molecular weight between 5 kDa and 20 kDa.
42 . The uricase of claim 41 , wherein the mPEG has a molecular weight of about 10 kDa.
43 . The uricase of claim 41 , wherein the mPEG is covalently attached to a lysine residue of the uricase.
44 . The uricase of claim 41 , comprising 2-12 mPEG molecules per uricase monomer.
45 . A conjugate comprising a uricase comprising the amino acid sequence of SEQ ID NO: 8 linked to polyethylene glycol (PEG).
46 . The conjugate of claim 45 , wherein the PEG is monomethoxy PEG (mPEG).
47 . The conjugate of claim 46 , wherein the mPEG has a molecular weight between 5 kDa and 20 kDa.
48 . The conjugate of claim 47 , wherein the mPEG has a molecular weight of about 10 kDa.
49 . The conjugate of claim 48 , comprising 2-12 mPEG molecules per uricase monomer.
50 . The conjugate of claim 49 , wherein the uricase comprises a homotetramer.
51 . A pharmaceutical composition comprising i) a conjugate comprising a uricase having the amino acid sequence of SEQ ID NO: 8 linked to polyethylene glycol (PEG); and ii) phosphate buffered saline.
52 . The pharmaceutical composition of claim 51 , wherein the PEG is monomethoxyPEG (mPEG).
53 . The pharmaceutical composition of claim 52 , wherein the mPEG has a molecular weight between 5 kDa and 20 kDa.
54 . The pharmaceutical composition of claim 53 , wherein the mPEG has a molecular weight of about 10 kDa.
55 . The pharmaceutical composition of claim 54 , comprising 2-12 mPEG molecules per uricase monomer.
56 . The pharmaceutical composition of claim 55 , wherein the uricase comprises a homotetramer.
57 . The pharmaceutical composition of claim 56 , comprising 8 mg of the uricase.
58 . The pharmaceutical composition of claim 57 , comprising 8 mg of the uricase per mL of solution.
59 . The pharmaceutical composition of claim 58 , wherein said conjugate consists of the amino acid sequence of SEQ ID NO: 8 linked to PEG.