Method of Administering Porcine B-domainless fVIII
OwnerJohn S. Lollar, Garrett E. Bergmaninventors
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OwnerJohn S. Lollar, Garrett E. Bergmaninventors
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The present invention provides a method of administering porcine B-domainless factor VIII (OBI-1) to a patient having factor VIII deficiency to provide more rapid and effective protection against bleeding episodes, compared to formerly available methods, or to provide more effective protection to such patients during non-bleeding periods. This invention is based on the discovery that the recombinant B-domainless porcine fVIII, termed OBI-1, has greater bioavailability compared to the natural porcine fVIII partially purified from porcine plasma, termed HYATE:C. Therefore, the inventive method employs lower unit doses of OBI-1, including, alternatively, omission of antibody-neutralizing dosage, or has longer intervals between the administration, compared to HYATE:C, to provide equivalent protection in patients having fVIII deficiency. The invention further provides pharmaceutical compositions and kits containing OBI-1 in combination with a pharmaceutically acceptable carrier, that are useful for treating patients in need of fVIII more effectively.
A solid pharmaceutical composition obtainable by lyophilization of a solution comprising OBI-1, wherein the OBI-1 is a product of expression of a nucleic acid molecule encoding SEQ ID NO:2, a surfactant, calcium chloride, sucrose, sodium chloride and trisodium citrate, wherein the solution is maintained at a pH of 6-8 using a buffering agent prior to lyophilization and after reconstitution in water for injection, and wherein the solution is devoid of amino acids.
A pharmaceutical composition for administration to a patient having factor VIII deficiency to achieve and maintain a therapeutically effective level of factor VIII in said patient, wherein the composition comprises OBI-1 at a concentration from 50 to 10,000 Units/mL and a physiologically acceptable carrier, wherein the OBI-1 is a product of expression of a nucleic acid molecule encoding SEQ ID NO:2.
A method of reducing blood clotting time in a patient having factor VIII deficiency, comprising administering a composition comprising a porcine partially B-domainless factor VIII (OBI-1) and a physiologically acceptable carrier to the patient in need thereof in an amount sufficient to reduce the patient's blood clotting time to a desired value wherein the amount of OBI-1 sufficient to reduce the patient's blood clotting time is ½ to 1/10 of the amount of plasma-derived porcine factor VIII sufficient to achieve the same reduction of blood clotting time obtained upon administering the partially B-domainless porcine fVIII (OBI-1), and wherein said OBI-1 is the expression product of SEQ ID NO:1, and wherein the OBI-1 is administered at a rate of 1000-10,000 Units/minute.
A method of administering a porcine partially B-domainless factor VIII (OBI-1) to a patient having factor VIII deficiency, said patient having factor VIII-inhibiting antibodies, wherein the porcine B-domainless factor VIII is administered intravenously to said patient in combination with a physiologically acceptable carrier at a dose about 10-150 Units/kg of body weight and at a rate of 1000-10,000 Units/minute, and wherein said OBI-1 is the expression product of DNA encoding SEQ ID NO:2.
A method of reducing blood clotting time in a patient having factor VIII deficiency, comprising administering a composition comprising a porcine partially B-domainless factor VIII (OBI-1) and a physiologically acceptable carrier to the patient in an amount sufficient to reduce the patient's blood clotting time wherein the amount of OBI-1 sufficient to reduce the patient's blood clotting time is ½ to 1/10 of the amount of plasma-derived porcine factor VIII sufficient to achieve the same reduction of blood clotting time obtained upon administering a B-domainless porcine fVIII (OBI-1), wherein said OBI-1 is administered at a rate of 1000-10,000 Units/minute and wherein said OBI-1 is the expression product of SEQ ID NO:1.
A method of administering a porcine B-domainless fVIII (OBI-1) to control a bleeding episode in a hemophilia A patient in need of such control comprising the steps of
Dependencies are inferred from the claim text.