Abstract: The invention provides, among other things, activatable prothrombin, compositions comprising prothrombin, transgenic organisms for making prothrombin, methods for making the transgenic organisms, methods for making prothrombin-comprising compositions and for further purifying prothrombin from the compositions. Illustrative embodiments of the invention particularly provide transgenic mammals that express an exogenous gene for prothrombin and excrete the prothrombin encoded by the gene into their milk. In a highly particular illustrative embodiment in this regard the invention provides transgenic female pigs that express prothrombin in their milk. In this regard, the invention relates particularly to female pigs having stably incorporated in their genomes a DNA comprising a region that encodes prothrombin operably linked to a mammary gland-specific promoter. Further in this regard the invention relates to the milk containing the prothrombin and to prothrombin-containing compositions derived from the milk.

Abstract: A non-human transgenic mammalian animal, as described above, contains an exogenous double stranded DNA sequence stably integrated into the genome of the animal, which comprises cis-acting regulatory units operably linked to a DNA sequence encoding human FIX protein without the benefit of the presence of a complete milk gene sequence for gene rescue, and a signal sequence is active in directing newly expressed Factor IX into the milk of the animal at levels in an unactivated form that is suitable for subsequent processing for therapeutic applications in treating Hemophilia B. The transgenic mammals are preferably pigs, cows, sheep, goats and rabbits. The applications include milk derivatives for oral delivery and oral tolerization in the treatment of Hemophilia B.

Abstract: Disclosed herein is a simple method for the treatment of antigen-deficiency diseases, by orally administering to a subject a therapeutically effective amount of the deficient antigen, wherein the antigen is not present in a liposome. In one embodiment, the method increases hemostasis in a subject having hemophilia A or B, by orally administering to the hemophiliac a therapeutically effective amount of the appropriate clotting factor other than in a liposome, sufficient to induce oral tolerance and supply exogenous clotting factor to the subject.

Abstract: A non-human trangenic mammalian animal, as described above, contains an exogenous double stranded DNA sequence stably integrated into the genome of the animal, which comprises cis-acting regulatory units operably linked to a DNA sequence encoding human FIX protein without the benefit of the presence of a complete milk gene sequence for gene rescue, and a signal sequence is active in directing newly expressed Factor IX into the milk of the animal at levels in an unactivated form that is suitable for subsequent processing for therapeutic applications in treating Hemophilia B. The transgenic mammals are preferably pigs, cows, sheep, goats and rabbits. The applications include milk derivatives for oral delivery and oral tolerization in the treatment of Hemophilia B.

Abstract: Disclosed herein is a simple method for the treatment of antigen-deficiency diseases, by orally administering to a subject a therapeutically effective amount of the deficient antigen, wherein the antigen is not present in a liposome. In one embodiment, the method increases hemostasis in a subject having hemophilia A or B, by orally administering to the hemophiliac a therapeutically effective amount of the appropriate clotting factor other than in a liposome, sufficient to induce oral tolerance and supply exogenous clotting factor to the subject.

Abstract: Disclosed herein is a simple method for the treatment of antigen-deficiency diseases, by orally administering to a subject a therapeutically effective amount of the deficient antigen, wherein the antigen is not present in a liposome. In one embodiment, the method increases hemostasis in a subject having hemophilia A or B, by orally administering to the hemophiliac a therapeutically effective amount of the appropriate clotting factor other than in a liposome, sufficient to induce oral tolerance and supply exogenous clotting factor to the subject.

Abstract: A non-human transgenic mammalian animal, as described above, contains an exogenous double stranded DNA sequence stably integrated into the genome of the animal, which comprises cis-acting regulatory units operably linked to a DNA sequence encoding human FIX protein without the benefit of the presence of a complete milk gene sequence for gene rescue, and a signal sequence is active in directing newly expressed Factor IX into the milk of the animal at levels in an unactivated form that is suitable for subsequent processing for therapeutic applications in treating Hemophilia B. The transgenic mammals are preferably pigs, cows, sheep, goats and rebbits. The application include milk derivatives for oral delivery and oral tolerization in the treatment of Hemophilia B.

Abstract: A non-human trangenic mammalian animal, as described above, contains an exogenous double stranded DNA sequence stably integratedintot he gemone of the animal, which comprises cis-acting regulatory untis operably linked to a DNA sequence encoding a modifed or variant human FVIII protein, and a signal sequence and secretion motif that is active in directing newly expressed Factor VIII into the milk of the animal at levels an in an unactivated, nondegraded and otherwise stable form that is suitable for subsequent processing for therapeutic applications in treating Hemophilia A. The transgenic mammals are preferably pigs, cows, sheep, goats and rabbits. The applications include milk derivatives used for oral delivery and oral tolerization in the treatment of Hemophilia A.