Methods of treating diseases associated with elevated uric acid
A method of treating a disease or disorder associated with excessive uric acid levels is disclosed herein. The method comprises administering to the subject by i.v. infusion an amount of a recombinant homotetrameric uricase enzyme comprising four uricase polypeptides having the amino acid sequence as set forth in SEQ ID NO: 2, wherein the polypeptides are crosslinked by polyethylene glycol (PEG) bis-aldehyde having a molecular weight of 2-3.5 kDa.
1 . A method of treating gout in a subject in need thereof, comprising administering to the subject by i.v. infusion an amount of a recombinant homotetrameric uricase enzyme comprising four uricase polypeptides having the amino acid sequence as set forth in SEQ ID NO: 2, wherein said polypeptides are crosslinked by polyethylene glycol (PEG) bis-aldehyde having a molecular weight of 2-3.5 kDa, wherein said administering is no more than once every four weeks, wherein said amount is 36 mg per subject.
2 . The method of claim 1 , wherein said polypeptides are crosslinked by polyethylene glycol (PEG) bis-aldehyde having a molecular weight of 3.5 kDa.
3 . The method of claim 1 , wherein said administering is effected over a period of about 1 hour, or about 1.5 hours, or about 2 hours or about 3 hours.
4 . The method of claim 1 , wherein said administering is effected once every four weeks.
5 . The method of claim 1 , wherein said administering is effected once every six weeks.
6 . The method of claim 1 , wherein said administering is effected once every eight weeks.
7 . The method of claim 1 , wherein said administering is effected once every ten weeks.
8 . The method of claim 1 , wherein said administering is effected once every twelve weeks.
9 . The method of claim 1 , wherein:
i) said recombinant homotetrameric uricase enzyme is formulated in a buffer comprising 10 mM sodium phosphate, 140 mM sodium chloride and 0.1 mM ethylenediaminetetraacetic acid (EDTA), and/or
ii) said recombinant homotetrameric uricase enzyme is at a concentration of 2 mg/ml in said buffer, and/or
iii) said recombinant homotetrameric uricase enzyme is a plant recombinant homotetrameric uricase enzyme.
10 . The method of claim 1 , wherein said treating further comprises administration of methotrexate to said subject.
11 . The method of claim 1 , wherein:
i) said gout is severe gout or refractory gout, and/or
ii) the gout is erosive gout or tophaceous gout.
12 . The method of claim 1 , wherein:
i) the subject has a serum urate level ≥6 mg/dL, or
ii) the subject has a serum urate level ≥7 mg/dL.
13 . The method of claim 1 , wherein:
i) the subject has had more than two gout flares over the last year, and/or
ii) the subject has persistent joint inflammation.