Abstract: The invention relates to murine/human chimeric monoclonal antibodies with high specificity to and affinity for human carcinoembryonic antigen (CEA), derivatives thereof, processes for the preparation of these antibodies and their derivatives, DNAs coding for heavy and light chains of these antibodies, processes for the preparation of said DNAs, mammalian cell lines that produce and secrete the antibodies and processes for the preparation of said cell lines. The chimeric antibodies and their derivatives are used for clinical purposes in vitro and in vivo, especially for the diagnosis of cancer, for localization and in vivo imaging of tumors, for therapy, e.g. site-directed delivery of cytotoxins, and similar purposes. The invention also concerns test kits and pharmaceutical compositions containing said chimeric monoclonal antibodies and/or derivatives thereof.

Abstract: Target cell specificity of delivery vectors is provided by incorporation of a target cell specific binding domain by the use of any binding domain, which binds specifically to a binding site on the target cell. The binding site may be endogenous to the target cell, provided by engineering the target cell, or a suitable binding site may be associated with the target cell. Target cells may also be associated with a CVR polypeptide to provide specificity for the delivery vector. The association of the CVR polypeptide confers target cell specificity for a second virus host cell range, which specificity differs from the viral host cell range of the endogenous target cell or animal host cell viral receptors. The CVR polypeptide may thus comprise a chimeric virus binding site which binds a second virus env binding domain specific for a second virus host cell range, selected from at least one of the group consisting of amphotropic, polytropic, xenotropic, ecotropic and tissue specific.

Abstract: High titre helper-free recombinant retrovirus are produced by (a) growing a transfected host cell, produced by transfecting a eukaryotic host cell with a recombinant vector capable of stable episomal maintenance in the host cell, in a medium under conditions whereby the recombinant vector is stably maintained as an episome in the transfected host cell and transcripts of said vector form, with retroviral gag, pol and env gene products, an infectious retrovirus; and (b) isolating from the medium helper-free infectious retrovirus formed in the transfected host cell. The recombinant vectors comprise (i) a retroviral construct comprising an exogenous gene; (ii) a eukaryotic origin of replication sequence providing a substrate for replicase activity capable of replicating the vector in the host cell; and, (iii) a copy control sequence providing a substrate for a copy control activity capable of maintaining the vector at a stable copy number in the host cell.

Abstract: A purified preparation of a peptide consisting essentially of an amino acid sequence identical to that of a segment of a naturally-occurring human protein, said segment being of 10 to 30 residues in length, inclusive, wherein said peptide binds to a human major histocompatibility complex (MHC) class II allotype.

Abstract: Methods for cryopreserving spermatogonia cells are presented.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g.

Abstract: This invention is directed to a chimeric mouse capable of mounting murine cellular and humoral immune response, said chimeric mouse being tolerant of human tissue implanted therein. The chimeric mouse of this invention is capable of developing murine T cells and producing murine IgG antibodies, which T cells and antibodies are tolerant of the human tissue implanted in said mouse, thereby allowing for the challenge of said vaccinated mouse with human-specific pathogens and determining the capacity of the vaccine to protect the cells in said implanted tissue from infection. This invention is also directed to a method for the development of said chimeric mouse, as well as to the use of said chimeric mouse for the screening of vaccines for human-specific pathogens.

Abstract: A cell population which is composed of cells bearing the stem cell marker CD34 and which are small in size and have little granulation are obtained by separating low density mononuclear hematopoietic cells according to size and then selecting for CD34.sup.+ cells in the smallest size fraction. The size of the cell population corresponds to that obtained at a flow rate of 25-29 ml/min in a counterflow elutriation method using a rotor equivalent to Beckman JE 5.0 spun at 900.times.g. This population of cells consists essentially of very early progenitor cells and the cells are useful in autologous bone marrow transplantation as well as gene therapy.

Abstract: The present invention comprises an endothelial inhibitor and method of use therefor. The endothelial inhibitor is a protein isolated from the blood or urine that is eluted as a single peak from C4-reverse phase high performance liquid chromatography. The endothelial inhibitor is a molecule comprising a protein having a molecular weight of between approximately 38 kilodaltons and 45 kilodaltons as determined by reducing polyacrylamide gel electrophoresis and having an amino acid sequence substantially similar to that of a murine plasminogen fragment beginning at amino acid number 98 of a murine plasminogen molecule.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g.

Abstract: The present invention provides a method of transcriptionally modulating the expression of a gene of interest, the expression of which is associated with a defined physiological or pathological effect within a multicellular organism. The method comprises contacting a cell which is capable of expressing the gene with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell. Molecules useful in the practice of the invention are characterized as follows (a) do not naturally occur in the cell, (b) specifically transcriptionally modulate expression of the gene of interest, and (c) bind to DNA or RNA or bind to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell, the binding of a ligand to which ligand binding domain is normally associated with the defined physiological or pathological effect.

Abstract: The present invention relates, in general, to methods of stimulating phagocytosis and thereby combating infection and/or modulating immune complex disease, in particular, to methods of modulating the number and type of Fc receptors present on cells that normally possess such receptors, including monocytes and macrophages, as well as on cells that normally do not possess Fc receptors, such as fibroblasts, and to compounds and compositions suitable for use in such methods.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: Human protein C molecules are modified to provide increased resistance to inactivation by human plasma factors while retaining substantially the biological activity of human protein C. The modifications are generally to the heavy chain of protein C, which chain may be substituted with a protein C heavy chain of non-human origin, such as bovine, yielding a chimeric protein C molecule. The human protein C heavy chain may also be modified to be human-like, in that at least one amino acid from a non-human sequence may be substituted for the corresponding residue(s) of the human sequence, thereby allowing the molecule to retain substantially human characteristics yet having increased resistance to inactivation. Also included are methods for producing the modified protein C molecules and pharmaceutical compositions thereof.

Abstract: Disclosed are methods, compositions and devices for use in transferring nucleic acids into bone cells in situ. The transfer of an osteotropic gene into bone progenitor cells is described, which event is shown to stimulate the progenitor cells and to promote bone growth, repair and regeneration in vivo. These gene transfer protocols are suitable for use in transferring various nucleic acid materials into bone, and have many uses, for example, in treating various bone-related diseases and defects, such as, in promoting fracture repair, use in connection with implants, and in treating osteoporosis and osteogenesis imperfecta.

Abstract: Avian diseases, particularly those which threaten birds early in life, are controlled by embryonal vaccination using oil emulsion vaccines. The site of inoculation is the albumin end of the egg via entry through the air cell end of the egg.

Abstract: The present invention provides novel antisense oligodeoxynucleotides which are useful in inhibiting lymphoma or leukemia cells. The subject oligodeoxynucleotides are complementary to a strategic site in the mRNA sense strand to the human bcl-2 gene. Such oligodeoxynucleotide are provided either in their native state or as a derivative such as the phosphorothioate. In the preferred embodiments, these antisense oligodeoxynucleotide straddle the predicted translation-initiation site of the mRNA coding strand, the splice donor region, the splice acceptor region of the mRNA coding strand, or the 5'-cap region for the human bcl-2 gene.

Abstract: This invention relates to the use of genetically modified, non-pathogenic bacteria on the mucosal surfaces of a host to inhibit infection by specific viruses at mucosal surfaces. Specifically, non-pathogenic bacteria are modified to acquire the capacity to bind and functionally inactivate specific viruses. Further manipulations are devised to ensure the persistent colonization of said bacteria on the desired mucosal surface of a host. The capacity to bind a pathogen by said bacteria may be accomplished through the expression on the bacterial surface of a molecule, either a polypeptide or carbohydrate moiety, which binds specifically to a molecule on the target virus. Such a capacity may be conferred upon said bacteria via genetic manipulations.

Abstract: The present invention relates to transgenic rats in the genome of which at least one human gene is integrated the gene product of which participates in blood pressure control. More specifically, the invention relates to transgenic rats and their offspring exhibiting increased blood pressure (>90/>140 mm Hg) or high blood pressure (>95/>160 mm Hg). Finally, the invention relates to processes for the production of the transgenic rats of the present invention and their offspring and their use for pharmacological tests.

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.