Abstract: Production of human procollagen or collagen in cells which ordinarily do not produce these molecules is effected by constructing expression systems compatible with mammary glands of non-human mammals. For example, expression systems can be microinjected into fertilized oocytes and reimplanted in foster mothers and carried to term in order to obtain transgenic non-human mammals capable of producing milk containing recombinant human procollagen or collagen. Human procollagen or collagen produced in this manner can be made of a single collagen type uncontaminated by other human or non-human collagens.

Abstract: Transgenes for producing recombinant polypeptides transgenic bovine species are described. A transgene for producing recombinant polypeptides in the milk of transgenic bovine species comprises at least one expression regulation sequence, a secretory DNA sequence encoding a secretory signal sequence which is functional in mammary secretory cells of the bovine species and a recombinant DNA sequence encoding the recombinant polypeptide. Also included are methods for producing transgenic bovine species. The method includes introducing the above transgene into an embryonal target cell of a bovine species, transplanting the transgenic embryonic target cell formed thereby into a recipient bovine parent and identifying at least one female offspring which is capable of producing the recombinant polypeptide in its milk.

Abstract: Transgenes for producing recombinant polypeptides transgenic bovine species. A transgene for producing recombinant polypeptides in the milk of transgenic bovine species comprises at least one expression regulation sequence, a secretory DNA sequence encoding a secretory signal sequence which is functional in mammary secretory cells of the bovine species and a recombinant DNA sequence encoding the recombinant polypeptide. Also included are methods for producing transgenic bovine species. The method includes introducing the above transgene into an embryonal target cell of a bovine species, transplanting the transgenic embryonic target cell formed thereby into a recipient bovine parent and identifying at least one female offspring which is capable of producing the recombinant polypeptide in its milk.

Abstract: Described are methods of targeting specific genes or DNA sequences encoding biologically active proteins to the mammary gland such that the DNA sequence is expressed in the mammary gland and the protein is secreted into the milk of the mammal. Also described is the production of transgenic nonhuman mammals whose germ line comprises a DNA gene complex containing a casein promoter, a casein enhancer, a DNA sequence which encodes a signal peptide and a DNA sequence encoding a biologically active protein. The milk containing the biologically active protein or the biologically active protein itself can be used in the making of diary products.

Abstract: Production of human procollagen or collagen in cells which ordinarily do not produce these molecules is effected by constructing expression systems compatible with mammary glands of non-human mammals. For example, expression systems can be microinjected into fertilized oocytes and reimplanted in foster mothers and carried to term in order to obtain transgenic non-human mammals capable of producing milk containing recombinant human procollagen or collagen. Human procollagen or collagen produced in this manner can be made of a single collagen type uncontaminated by other human or non-human collagens.

Abstract: A process is disclosed for the production of a protein or polypeptide in the milk of a transgenic non-human mammal where the protein or polypeptide is produced as fusion protein with another protein. The fusion protein can then be cleaved to release the protein or polypeptide. This method would reduce or prevent the formation of side effects associated with ectopic expression or leakage of the protein or polypeptide. Such a fusion protein is .beta.-lactoglobulin-EPO, where biologically active EPO is released upon cleavage of the fusion protein.

Abstract: The invention provides methods for purification of human lactoferrin from milk, especially milk of nonhuman species, and for separation of human lactoferrin from undesired macromolecular species present in the milk, including separation from nonhuman lactoferrin species.

Abstract: Production of human procollagen or collagen in cells which ordinarily do not produce these molecules is effected by constructing expression systems compatible with mammary glands of non-human mammals. For example, expression systems can be microinjected into fertilized oocytes and reimplanted in foster mothers and carried to term in order to obtain transgenic non-human mammals capable of producing milk containing recombinant human procollagen or collagen. Human procollagen or collagen produced in this manner can be made of a single collagen type uncontaminated by other human or non-human collagens.

Abstract: The invention provides methods for purification of human lactoferrin from milk, especially milk of nonhuman species, and for separation of human lactoferrin from undesired macromolecular species present in the milk, including separation from nonhuman lactoferrin species.

Abstract: The invention provides methods for purification of human lactoferrin from milk, especially milk of nonhuman species, and for separation of human lactoferrin from undesired macromolecular species present in the milk, including separation from nonhuman lactoferrin species.

Abstract: This invention relates to the production of recombinant proteins, such as coagulation factors VIII and IX, tissue plasminogen activator (TPA), urokinase, growth hormone, insulin, interferons, interleukins, peptide hormones and immunoglobulins, in mammals' milk. Particularly, this invention relates to an expression system which when transgenically incorporated into a mammal permits the female species of that mammal to produce the desired recombinant protein in or along with its milk. This invention also relates to the transgenic mammal that produces the desired recombinant product in its milk.

Abstract: A transgenic bovine is disclosed whose somatic and germ cells contain a transgene, wherein the transgene comprising a mammary gland specific promoter, a mammary gland specific enhancer, a DNA sequence encoding a signal sequence functional in bovine mammary gland secretory cells and a DNA sequence encoding a heterologous polypeptide of interest wherein the transgenic bovine expresses the transgene such that the polypeptide of interest is detectable in milk produced by the transgenic bovine.

Abstract: The invention relates to methods for intracellularly producing DNA segments by homologous recombination of smaller overlapping DNA fragments and transgenic mammalian cells and transgenic non-human mammals produced by such methods.

Abstract: A method is disclosed for the production of a transgenic bovine or a transgenic bovine embryo comprising obtaining an ovum from bovine ovaries, maturing the ovum in vitro, fertilizing the mature ovum or ova in vitro to form a zygote, introducing a transgene into the zygote in vitro and maturing the zygote to a preimplantation stage embryo in vitro. To produce the transgenic bovine, the embryo is transplanted into a recipient female bovine, wherein the female bovine gestates the embryo to produce a transgenic bovine.

Abstract: Described is a method of targeting specific genes to the mammary gland which results in the efficient synthesis and secretion of biologically important molecules. Further, there is described as a composition of matter, a transgenic mammal having the ability to reproduce itself and being suitable for the secretion of biologically active agents into its milk. Additionally there is disclosed as a composition of matter, recombinant DNA gene complexes designed to integrate into a mammalian genome and to synthesize and secrete biological active agents into the milk. Furthermore methods of producing and using altered milk are disclosed.