Hybrid human/porcine factor VIII

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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435 696, 4351723, 530383, 930100, C07K 14755, C12N 1511, C12N 1512

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055832091

ABSTRACT:
A hybrid human/porcine coagulation factor VIII is produced by isolation and recombination of human and porcine factor VIII subunits, or by genetic engineering of the human and porcine factor VIII genes. Subunits of factor VIII that have been purified from human or porcine plasma are isolated, and hybrid human/porcine factor VIII is produced by mixing either porcine heavy chain subunits with human light chain subunits or by mixing human heavy chain subunits with porcine light chain subunits, thereby producing human light chain/porcine heavy chain and human heavy chain/porcine light chain hybrid molecules. These hybrid molecules are isolated by ion exchange chromatography. Alternatively, recombinant DNA methods are used to swap elements of porcine factor VIII for the corresponding elements of human factor VIII to produce hybrid human/porcine factor VIII.

REFERENCES:
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patent: 5246850 (1993-09-01), Bennett et al.
Scandella, D., et al., "Localization of Epitopes for Human Factor VIII Inhibitor Antibodies by Immunoblotting and Antibody Neutralization," 111 (25) Chem. Abst. 570, Abst. 230240 (Dec. 18, 1989).
Scandella, D., et al., "Localization of Epitopes for Human Factor VIII Inhibitor Antibodies by Immunoblotting and Antibody Neutralization," 82 (6) Blood 1767-1775 (1993).
Scandella, D. et al., "A Recombinant Factor VIII A2 Domain Polypeptide Quantitatively Neutralizes Human Inhibitor Antibodies that Bind to A2," 121 (19) Chem. Abst. 782, Abst. 268801 (Dec. 20, 1993).
Scandella, D. et al., "A Recombinant Factor VIII A2 Domain Polypeptide Quantitatively Neutralizes Human Inhibitor Antibodies that Bind to A2," 74 (5) Blood 1618-1626 (1989).
Lollar, P. et al., Biochemistry 26:666-674 (1989).
Toole, J. J. et al., Nature 312:342-347 (1984).
Toole, J. J. et al., PNAS 83:5939-5942 (1986).
Lollar, P. et al. J. Biol. Chem. 266:12481-12486 (1991).

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