Abstract: Methods and compositions are provided for producing monoclonal antibodies capable of distinguishing between antigenic aggregates, which are differentiated by one or a small number of antigenic determinants. The method involves immunization of a mammal to produce spleen cells which are fused with a cell line which is stable in vitro. The hybridized cells are then dispensed into culture wells at a density level which encourages the production of one colony per well. Autologous antigenic aggregates are employed for screening to distinguish the antibodies which discriminate between the antigenic aggregates. Particularly, mice are hyperimmunized with a homogeneous population of T-cells, the immunized mice killed and the spleens removed. The spleen cells are fused with mouse myeloma cells and the resulting hybrids plated at a relatively low density in culture wells. Plates containing fewer than 30% hybrid positive wells are found to have primarily one colony per well.

Abstract: A method for obtaining fetal cells for diagnostic examination comprises removing detached cells from the uterine cavity and outer surface of the amnionic sac. The cells are then incubated in the presence of a separation antibody which binds preferentially to either fetal cell antigens or maternal cell antigens for a time sufficient to permit antibody-antigen binding to occur. Cells having said separation antibody bound thereto are separated for the mixture. The separation antibody can be an anitbody binding preferentially to fetal cell antigens and not significantly to maternal cell antigens or it can be an antibody binding preferentially to maternal cell antigens and not significantly to fetal cell antigens. The antibody can be bound to an insoluble support prior to the incubation, and separation can be effected by separating the insoluble support from the cell mixture following the incubation.

Abstract: A non-human, mammalian monoclonal receptor produced and secreted by a hybridoma having the ATCC accession number HB 8568 and methods of preparing and using same, as well as diagnostics utilizing the receptor are disclosed. The monoclonal receptor reacts with cells such as human neuroectodermal tumors having ganglioside GD.sub.2 antigen expressed on their cellular membrane surfaces.

Abstract: Bifunctional derivatives of a 3-carboxhydrazide of an antineoplastic dimeric indole-dihydroindole alkaloids, useful both in forming conjugates with immunoglobulins and as anti-tumor agents.

Abstract: A hybrid cell formed by the fusion of a mouse spleen cell with a mouse myeloma cell secretes an IgM class antibody. The antibody is useful as a preparative reagent in the isolation of three proteins, molecular weights 45,000, 49,000 and 53,000, from the parasite Trichinella spiralis and is also useful as a direct diagnostic reagent is a competitive serodiagnostic test.

Abstract: Mouse monoclonal antibodies to several cell antigens of human ovarian, cervical and endometrial carcinomas have been produced and characterized. The distribution of the antigens was determined by mixed hemagglutination assays on 153 normal and malignant cell cultures of various types, and by immunoperoxidase staining of frozen sections of 27 normal adult and 24 fetal tissues. five monoclonal antibodies representative of five classes of mAb raised to restricted ovarian, cervical and endometrial cells were tested extensively producing mAb reactive with cancer but not normal cells. One such mAb, MF116 was readily detected in the spent culture medium of metabolically radiolabeled cells. These antibodies, reacting with relatively restricted cell surface antigens, are useful in the analysis of epithelial cell differentiation, in cancer diagnosis and therapy and in tissue typing of normal or abnormal cells.

Abstract: Chromatographic procedures are individually and jointly applied to the rapid and efficient isolation of biologically active proteins and especially glycoproteins such as recombinant erythropoietin present in the medium of growth of genetically transformed mammalian host cells. Illustratively, recombinant EPO is isolated from culture fluids by reverse phase chromatography employing a C.sub.4 or C.sub.6 column and elution with ethanol. Recombinant erythropoietin may also be purified by anion exchange chromatography employing, e.g., a DEAE resin, with preliminary selective elution of contaminant materials having a lower pKa than erythropoietin from the resin under conditions mitigating against acid activated protease degradation. Practiced serially, the two chromatographic procedures allow for high yields of biologically active recombinant erythropoietin from mammalian cell culture media.

Abstract: A novel non-allelic human growth hormone variant protein is disclosed. The structure of the protein is determined and the protein product is produced by recombinant DNA methods.

Abstract: Binding of a particular protein by an antibody reagent involving denaturation of the protein and use of an antibody reagent specific for binding a linear peptide epitope therein. Denaturation by chemical or physical means effectively exposes or enhances the exposure of the linear peptide epitope for binding by the antibody reagent which is preferably raised against a synthetic peptide immunogen. The technique is particularly useful in performing immunoassays for protein analytes, such as a glycosylated protein, in aqueous test samples.

Abstract: Monoclonal antibodies specific for a protein associated with a lung surfactant complex, decreased levels of which are related to respiratory distress syndrome, are disclosed. The antibodies are useful for prediction and diagnosis of respiratory problems in newborns.

Abstract: The supernatant of engineered yeast cells having produced hepatitis B surface antigaen and disrupted in the presence of a polysorbate non-ionic detergent is clarified by addition of urea and adsorbed on colloidal silica from which the purified antigen is desorbed with a low ionic strength buffer supplemented with urea and a polysorbate non-ionic detergent.

Abstract: Proteinaceous binding compositions are prepared employing hybrid DNA techogy, where the variable region polypeptides of immunoglobulins are substantially reproduced to provide relatively small protein molecules having binding specificity and lacking the undesirable aspects of the heavy regions of immunoglobulins. The compositions find a wide range of use, particularly for physiological purposes for diagnosis and therapy. The binding compositions may be modified by labeling with radioisotopes, fluorescers, and toxins for specific applications in diagnosis or therapy.

Abstract: A photo-cleavable compound for delivery and release of a biologically active substance to selected target cells; the compound includes a binding partner for a specific cell-surface receptor of those target cells, the biologically active substance to be delivered, and a photo-cleavable bridge between the binding partner and the biologically active substance. When the compound is exposed to a heterogeneous population of target and non-target cells, it binds selectively to the receptors on the surface of the target cells. Exposing the compound to light of selected wave length cleaves it, yielding the active substance.

Abstract: This specification describes a process for separating impurities from an impure mixture containing proinsulin-like material with substantially complete recovery of said proinsulin-like material, which comprises:(1) applying said mixture to a reverse phase macroporous acrylate ester copolymer resin support at a pH of from about 7 to about 10; and(2) eluting said proinsulin-like material from said support with an aqueous eluant having a pH of from about 8 to about 11 and containing from about 10% to about 30% by volume of an organic diluent selected from the group consisting of acetone, acetonitrile, and a combination of acetone and acetonitrile.

Abstract: This specification describes a process for separating impurities from an impure mixture containing growth hormone-like material with substantially complete recovery of said growth hormone-like material, which comprises:(1) applying said mixture to a reverse phase macroporous acrylate ester copolymer resin support at a pH of from about 7 to about 9; and(2) eluting said growth hormone-like material from said support with an aqueous eluant having a pH of from about 7 to about 9 and containing from about 20% to about 80% by volume of an organic diluent selected from the group consisting of acetone, acetonitrile, and a combination of acetone and acetonitrile.

Abstract: Recombinant plasmids are described that carry the structural gene for human proinsulin in expressible form. The human proinsulin structural gene is fused to a functional transport sequence. Host organisms transformed by the recombinant plasmids express a preproinsulin in vivo, and is transported across the host organism's cell wall. Following its recovery, in vitro methods are used to convert the human proinsulin to human insulin.