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 Factor VIII protein and a signal peptide, where the cis-acting regulatory units are active in mammary gland cells and the signal peptide is active in directing newly expressed Factor VIII into the milk of the animal. The promoter may be a milk protein promoter such as for whey acidic protein, casein, lactalbumin, or beta-lactoglobulin promoter. The transgenic mammals are preferably farm animals, for example, cows, goats, sheep, rabbits and pigs. Concurrent expression of a gene for human von Willebrand's Factor into milk may be used to stabilize newly-secreted Factor VIII.

Abstract: Recombinant Factor IX characterized by a high percentage of active protein can be obtained in the milk of transgenic animals that incorporate chimeric DNA molecules according to the present invention. Transgenic animals of the present invention are produced by introducing into developing embryos DNA that encodes Factor IX, such that the foreign DNA is stably incorporated in the DNA of germ line cells of the mature animal. Particularly efficient expression was accomplished using a chimeric construct comprising a mammary gland specific promoter, Factor IX cDNA that lacked the complete or any portion of the 5′-untranslated and 3′-untranslated region, which is substituted with a 5′- and 3′-end of the mouse whey acidic protein gene. In vitro cell cultures of cells explanted from the transgenic mammal of the invention and methods of producing Factor IX from such said culture and methods of treating hemophilia B are also described.

Abstract: The present invention relates to the preparation and use of liquid formulations of plasma proteins, particularly blood coagulation factors. More specifically, the present invention relates to stable liquid formulations of Factor VIII and Factor IX that can be administered by injection or infusion to provide a constant level of the coagulation factor in the blood.

Abstract: An isolated DNA sequence which regulates the expression of a heterologous gene composed of a mouse whey acidic protein promoter having a length of greater than about 2.4 kb extending upstream from the unique KpnI site in the mouse whey acidic protein gene is disclosed. Specifically a mouse whey acidic protein promoter of about 4.1-4.2 kb in length extending upstream from the unique KpnI site is preferred. This mouse whey acid protein promoter is operably linked to a DNA sequence encoding a heterologous polypeptide and used to prepare transgenic non-human mammals expressing the heterologous polypeptide in their milk. Particularly efficient expression of both cDNAs and genomic DNAs encoding heterologous polypeptides was obtained in transgenic non-human mammals using this promoter, known as the long whey acidic protein promoter.

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 Factor VIII protein and a signal peptide, where the cis-acting regulatory units are active in mammary gland cells and the signal peptide is active in directing newly expressed Factor VIII into the milk of the animal. The promoter may be a milk protein promoter such as for whey acidic protein, casein, lactalbumin, or beta-lactoglobulin promoter. The transgenic mammals are preferably farm animals, for example, cows, goats, sheep, rabbits and pigs. Concurrent expression of a gene for human von Willebrand's Factor into milk may be used to stabilize newly-secreted Factor VIII.

Abstract: A method for the production of thrombin from pure prothrombin is provided by converting pure prothrombin by treating pure prothrombin with sodium citrate in the absence of additional coagulation factors. Preferrably, a solution is used containing about 30% to about 40% sodium citrate.

Abstract: The present invention pertains to improved methods for the selective separation of organic components from biological fluids. More particularly, the present invention pertains to methods for the selective separation of organic components from biological fluids which comprise the step of contacting the biological fluid with a synthetic hydrated alkaline earth silicate (i.e., SHAES), such as synthetic hydrated calcium silicate (i.e., SHCS) or synthetic hydrated magnesium silicate (i.e., SHMS). In a preferred embodiment, the present invention pertains to such methods where the biological fluid is a mammalian blood fluid (e.g., whole blood, blood plasma, blood serum, blood fraction, plasma fraction, serum fraction).

Abstract: This invention is directed to the preparation and utilization of supplemented chitin hydrogels, such as chitosan hydrogels. Further provided are biomaterials comprising same. The particular supplement delivered by the chitin hydrogel is selected as a function of its intended use. In one embodiment, this invention provides a composition of matter, comprising a chitin hydrogel or chitin-derived hydrogel, wherein the hydrogel does not inhibit full-thickness skin wound healing.

Abstract: The present invention is directed to pathogen inactivating compositions that can be used to disinfect various biological fluids, such as blood, blood fractions, and the like. The compositions are suitable for disinfecting biological fluids containing valuable, but labile, components such as proteins without destroying the desired properties of such components. The pathogen inactivating compositions of the present invention are produced by contacting water or an aqueous solution with iodinated matrix material. The compositions can be pre-formulated and stored for subsequent use in disinfecting a wide range of biological fluids.

Abstract: The present invention provides media for inactivating pathogens found within protein-containing biological fluids. The media of the present invention preserve the structural integrity and biological activity of labile proteins while simultaneously exhibiting potent disinfectant activity. The media of the present invention comprise iodinated chromatographic media, particularly ion exchange media. The invention further provides methods for disinfecting biological fluids.

Abstract: The invention relates to transgenic non-human multicellular organisms that contain polynucleotides for expressing proteins that alter posttranslational modification. In particular, the invention provides multiply-transgenic animals in which a first transgene encodes a first protein, a second transgene encodes a second protein, and expression of the second protein affects the posttranlational modification of the first protein in cells of said organism. Expression in preferred embodiments is in specific cells and the modified protein is secreted into a bodily fluid. The invention provides related methods, proteins and products. An example provides transgenic animals that express human Protein C and the processing protease PACE/furin in mammary glands and secrete both proteins into milk.

Abstract: The present invention relates to the preparation and use of liquid formulations of plasma proteins, particularly blood coagulation factors. More specifically, the present invention relates to stable liquid formulations of Factor VIII and Factor IX that can be administered by injection or infusion to provide a constant level of the coagulation factor in the blood.

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 Factor VIII protein and a signal peptide, where the cis-acting regulatory units are active in mammary gland cells and the signal peptide is active in directing newly expressed Factor VIII into the milk of the animal. The promoter may be a milk protein promoter such as for whey acidic protein, casein, lactalbumin, or beta-lactoglobulin promoter. The transgenic mammals are preferably farm animals, for example, cows, goats, sheep, rabbits and pigs. Concurrent expression of a gene for human von Willebrand's Factor into milk may be used to stabilize newly-secreted Factor VIII.

Abstract: The present invention is directed to DNA encoding human endothelial cell growth factors, and to plasmids comprising said DNA. In particular, the invention relates to DNA encoding a cleavable signal peptide and an endothelial cell growth factor, wherein removal of said signal peptide yields a mature form of the growth factor.

Abstract: Heterologous polypeptides are produced in the milk of transgenic non-human mammals by the expression of a stably integrated DNA sequence containing the long whey acidic protein promoter operably linked to a DNA sequence encoding a heterologous polypeptide and a signal sequence. The transgenic non-human mammals of the present invention are produced by introducing this DNA sequence such that the DNA sequence is stably integrated into the DNA of germ line cells of the mature mammal and inherited in normal Mendelian fashion. A representative heterologous polypeptide is protein C.

Abstract: The present invention is directed to compositions comprising endothelial cell growth factor, an acceptable carrier and, optionally, an extracellular matrix protein, a glycosaminoglycan or serum albumin. The compositions are useful for wound repair.

Abstract: Recombinant protein C characterized by a high percentage of active protein can be obtained in the milk of transgenic mammals that incorporate DNAs according to the present invention. Transgenic mammals of the present invention are produced by introducing into developing embryos DNA that encodes protein C, such that the DNA is stably incorporated in the DNA of germ line cells of the mature mammals and inherited in normal, mendelian fashion.

Abstract: Endothelial cell growth factor is achieved through the application of recombinant DNA technology to prepare cloning vehicles encoding the ECGF protein and procedures are disclosed for recovering ECGF protein essentially free of other proteins of human origin. The product is useful for, among other purposes, diagnostic applications and as potential in the treatment of damaged blood vessels or other endothelial cell-lined structures.

Abstract: New fragments of the Factor VIII procoagulant protein (Factor VIIIC) are disclosed. These fragments have an Mr value of 88,000 d or 49,000 d or extend from amino acid residues 1974 to 2332 or 2052 to 2332. These fragments have use in the treatment of patients who have developed antibodies which inhibit Factor VIII.

Abstract: New fragments of the Factor VIII procoagulant protein (Factor VIIIC) are disclosed. These fragments have an Mr value of 88,000 d or 49,000 d or extend from amino acid residues 1974 to 2332 or 2052 to 2332. These fragments have use in the treatment of patients who have developed antibodies which inhibit Factor VIII.