Patent ID: 6255554
Filing Date: 2001-07-03
Classification: A01K,C07K,C12N

Abstract:
A non-human transgenic mammal that produces in its mammary gland cells and secretes into its milk at detectable levels human Factor VIII or fragment thereof which retains physiological activity of human Factor VIII and human von Willebrand Factor or fragment thereof which retains physiological activity of human von Willebrand Factor, wherein said transgenic mammal has stably integrated into its genome a first exogenous gene construct and a second exogenous gene construct, wherein said first exogenous gene construct comprises:(A) 5' expression regulating sequences, including a mammary gland-specific promoter;(B) DNA encoding said Factor VIII or fragment thereof, and a signal sequence effective in directing secretion of said Factor VIII or fragment thereof into the milk of said transgenic mammal; and(C) 3' regulatory sequences, including a polyadenylation signal, that result in the expression of said DNA encoding said Factor VIII or fragment thereof, in said mammary gland cells,wherein (A), (B) and (C) are operably linked in said first exogenous gene construct to obtain production of said Factor VIII or fragment thereof in said mammary gland cells and secretion thereof into the milk of said transgenic mammal; and said second exogenous gene construct comprises:(D) 5' expression regulating sequences, including a mammary gland-specific promoter;(E) DNA encoding said von Willebrand Factor or fragment thereof, and a signal sequence effective in directing secretion of said von Willebrand Factor or fragment thereof into the milk of said transgenic mammal; and(F) 3' regulatory sequences, including a polyadenylation signal, that result in the expression of said DNA encoding said von Willebrand Factor or fragment thereof, in said mammary gland cells,wherein (D), (E) and (F) are operably linked in said second exogenous gene construct to obtain production of said von Willebrand Factor or fragment thereof in said mammary gland cells and secretion thereof into the milk of said transgenic mammal.