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AssigneeCenteon L.L.C.
InventorsDavid L. Farb, Michael E. Hrinda, Ted C. K. Lee, Christopher P. Prior, David Weber
Estimating the term…
Processes for preparing aqueous solutions of cysteine-altered von Willebrand Factor fragment which are substantially free of aggregate and capable of therapeutic use for treating thrombosis are provided. The claimed process comprises providing an aqueous solution of vWF fragment and denaturant and containing undesired contaminants, said solution having an acidic pH; separating said contaminants from said solution by contacting said solution with an affinity chromatography medium to which said vWF fragments adhere; eluting said vWF fragment from said affinity chromatography medium in the presence of the denaturant; and separating the eluted fragment from said denaturant while maintaining the aqueous solution of the fragment at a pH of about 2.5 to less than about 5.5 to increase monomerization of, and decrease aggregation of, said fragment, thereby forming an aqueous solution of vWF fragment which is substantially free of aggregate.
A process for preparing an aqueous solution of recombinantly prepared von Willebrand factor (vWF) fragment having an amino terminal residue at about amino acid residue 445 and a carboxy terminal residue at about amino acid 733 which is substantially free of aggregate comprising:
A process for limiting the dimerization of monomeric cysteine-altered von Willebrand factor (vWF) fragment isolated by heparin affinity chromatography performed at pH below about 6.0 wherein said fragment has an amino terminal residue at about amino acid residue 445 and a carboxy terminal residue at about amino acid 733, said dimerization involving one or more of ionic, hydrophobic or hydrogen bonds which facilitate in vivo the association of two or more mature vWF subunits, said process comprising forming an aqueous solution of monomeric cysteine-altered vWF fragment which has a pH of about 2.5 to less than about 5.5 and which includes therein up to about 10 mg/ml of said fragment and wherein the total concentration in the solution of additional species of ions (if any) is less than about 75 mM.
A process for preparing an aqueous solution of cysteine-altered von Willebrand factor (vWF) fragment having an amino terminal residue at about amino acid residue 445 and a carboxy terminal residue at about amino acid 733 which is substantially free of aggregate comprising:
An aqueous solution of cysteine-altered vWF fragment having an amino terminal residue at about amino acid residue 445 and a carboxy terminal residue at about amino acid 733 which is substantially free of aggregate and wherein the concentration of said vWF fragment is about 1 to about 30 mg/ml.
An aqueous therapeutic solution of cysteine-altered vWF fragment having an amino terminal residue at about amino acid residue 445 and a carboxy terminal residue at about amino acid 733 in a form capable of being administered to humans, having a pH of about 2.5 to less than about 5.5 and consisting essentially of:
A pharmaceutical composition comprising cysteine-altered vWF fragment having an amino terminal residue at about amino acid residue 445 and a carboxy terminal residue at about amino acid 733 at a concentration of from about 1 to about 30 mg/ml, about 0.5 to 10 mM citric acid, about 0.5 to 15 mM lysine hydrochloride, about 0.5 to 10 mM sodium chloride, mannitol, and having a pH of from about 2.5 to about 5.5.
A method of treating thrombosis in a patient comprising administering to said patient an aqueous solution of cysteine-altered vWF fragment having an amino terminal residue at about amino acid residue 445 and a carboxy terminal residue at about amino acid 733 which is substantially free of aggregate.
A method of treating thrombosis in a patient comprising administering to said patient an aqueous solution of cysteine-altered vWF fragment having an amino terminal residue at about amino acid residue 445 and a carboxy terminal residue at about amino acid 733 which is substantially free of aggregate wherein said cysteine residues are alkylated.
Dependencies are inferred from the claim text.