4 results about "Blood coagulation factor VIII" patented technology

The present application belongs to the technical field of blood product preparation, and particularly relates to a method for separating blood coagulation factor VIII and vWF factor from blood plasma. The method comprises the following steps in sequence: after cellulose is balanced, the cellulose is mixed with raw material blood plasma, filtered after stirring, and cellulose precipitate is obtained; after the cellulose precipitate is eluted, the cellulose precipitate is soaked in precipitate dissolving solution, and filtrate is obtained by filtering; the filtrate is subjected to three times of ion exchange chromatography, and factor VIII and / or vWF factor product is obtained. The technical scheme solves the technical problems of the prior art, such as complicated process steps for purifying and enriching human blood coagulation factor VIII and vWF from blood plasma cold precipitate, and unsatisfactory production efficiency and product quality. The cold precipitate protein solution prepared by the method can separate factor VIII, vWF factor and fibrinogen product at the same time through chromatography, improve the utilization rate of plasma protein, and has an ideal application prospect.

The present inventors examined the procoagulant activity of a multispecific antigen-binding molecule that functionally substitutes for FVIII using blood and plasma derived from FIX disorder patients. The result showed that multispecific antigen-binding molecules that functionally substitute for FVIII can be used not only as methods for preventing and / or treating bleeding in hemophilia A, acquired hemophilia A, von Willebrand disease, and hemophilia C, which are caused by FVIII dysfunction, but also as methods for preventing and / or treating bleeding in FIX disorders, because of their procoagulant activity. Furthermore, the effect of a FIX formulation could be enhanced by using it in combination with a multispecific antigen-binding molecule that functionally substitutes for FVIII, and it was shown that the combined use is promising as a combination therapy that shows stable hemostatic effects.

The invention discloses a preparation of a recombinant blood coagulation factor VIII, such as a pharmaceutical preparation and a freeze-drying preparation, particularly, the recombinant blood coagulation factor VIII is preferably a long-acting blood coagulation factor VIII, and the preparation has good stability and is suitable for long-term storage and clinical application.

The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX / F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44 / B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.