Antibody substituting for function of blood coagulation...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 16/46 (2006.01) A61K 39/395 (2006.01) A61P 7/04 (2006.01) C07K 16/36 (2006.01) C07K 16/40 (2006.01) C12N 15/09 (2006.01)

Patent

CA 2603264

A variety of bispecific antibodies which bind specifically to both F.IX/F.IXa and F.X and substitute for the cofactor function of F.VIIIa, i.e., a function of promoting F.X activation by F.IXa., were prepared Among these antibodies, as for an antibody (A44/B26) with which coagulation time is shortened by 50 seconds or more compared to the case where the antibody is not added, when the L chains of the antibody were commonized with the L chain of A44, it was found that the commonization is possible using A44L although the activity was lowered compared to that of the antibody (A44HL-B26HL) before the commonization. Further, a highly-active multi-specific antibody substituting for the function of blood coagulation factor F.VIII was successfully prepared by appropriately shuffling CDR.

L~invention concerne la préparation d~une variété d~anticorps bispécifiques qui lient spécifiquement F.IX/F.IXa et F.X et substituent la fonction de cofacteur de F.VIIIa, c~est-à-dire, la fonction d~accélération de l~activation F.X par F.IXa. Parmi ces anticorps, de la même manière que pour un anticorps (A44/B26) avec lequel le temps de coagulation est réduit de 50 secondes ou plus comparativement au cas où l~anticorps n~est pas ajouté, lorsque les chaînes L de l~anticorps ont été mises en commun avec la chaîne L de A44, on a observé que la communité est possible en utilisant A44L bien que l~activité ait été réduite comparativement à celle de l~anticorps (A44HL-B26HL) avant communité. En outre, un anticorps multispécifique hautement actif, substitut de la fonction du facteur F.VIII de coagulation sanguine a été préparé de façon satisfaisante par déplacement CDR approprié.

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