Abstract: An immunoassay procedure is provided which exhibits increased specificity over current procedures. The procedure allows the differentiation of animals infected with Brucella abortus from animals vaccinated with Brucella abortus Strain 19. The invention employs unique monospecific monoclonal antibodies having particular affinity, specificity and binding characteristics directed to a B. abortus lipopolysaccharide antigen. The invention also concerns continuous hybrid cell lines for producing the unique monoclonal antibodies.

Abstract: Polyionic derivatives of cyclodextrin polymers and cyclodextrins immobilized on a solid surface are disclosed. Compositions and methods for separating a molecular species, including but not limited to a biologically active protein, from a mixture, for the storage of protein factors and for the therapeutic biodelivery of protein factors which employ the polyionic derivatives of cyclodextrin polymers and cyclodextrins immobilized on a solid surface are also disclosed.

Abstract: An adhesion receptor for laminin is provided. The receptor is isolated from cell or tissue extracts and fractionated on an affinity column composed of cell attachment-promoting fragments of laminin coupled to Sepharose.TM. in the presence of divalent cations. This receptor can be used to prepare specific antibodies for the analysis of the amount of laminin receptor expressed by cells and has other applications in cellular and tumor biology.

Abstract: A peptide being capable of binding to interleukin 6, and an adsorbent for interleukin 6 comprising the peptide immobilized on a carrier.

Abstract: A trifunctional conjugate is provided having three chemical moieties, attached through a spacer moiety. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical mouths sterically inhibits the binding of a different macromolecule to another chemical moiety. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second chemical moiety to a proximate location on the same macromolecule.

Abstract: The invention relates to compounds of formula: ##STR1## in which m, n, p and q are equal to 0 or 1, p being different from q and the sum m+n+p+q being equal to 2, A denotes a nonionic chain arrangement chosen from the groups:C.sub.2 H.sub.4 O.sub.r and/orC.sub.3 H.sub.5 (OH)O.sub.s,in which r denotes a number which can assume all integral values between 0 and 5 or a statistical average value between 0 and 20,s denotes a number which can assume all integral values between 0 and 5 or a statistical average value between 0 and 10,u is equal to 0 or 1, with the restriction that when u=0, s and r are also zero,R denotes(i) a linear or branched hydrocarbon radical which has 1 to 32 carbon atoms and can contain one or more oxygen atoms in the chain or bear one or more OH groups or(ii) a (C.sub.8 -C.sub.18 alkyl)phenyl radical.These compounds can be used for preparing stable chemical compounds, for conveying active substances or for forming vesicles.

Abstract: Methods are provided for the purification of interleukin-2 (IL-2) from a wide variety of sources, including synthetic mixtures, culture medium conditioned by natural IL-2 producing cells, and mammalian and bacterial recombinant IL-2 expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 can be produced in a single step from bacterial extracts or conditioned medium. The IL-2 thus purified is largely free of aggregated forms, which are often present when other purification methods are used.

Abstract: Methods are provided for the purification of interleukin-2 (IL-2) and chimeric proteins containing an IL-2 moiety from a wide variety of sources, including synthetic mixtures, cell culture conditioned medium and mammalian and bacterial recombinant expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 and chimeric proteins containing an IL-2 moiety can be produced in a single step from bacterial extracts or conditioned medium. The proteins thus purified are largely free of aggregated forms, which are often present when other purification methods are used.

Abstract: A process for surface modifying a variety of polymeric support surfaces is disclosed in which a predetermined modifying polymer is irreversibly absorbed onto essentially all the surfaces of the support polymer accessible to the modifying polymer. The modifying polymer is selected to impart the desired surface characteristics to the modified polymeric surface.

Abstract: Undesired immune responses are suppressed by administering a nonimmunogenic material which comprises one or more haptens or epitopes corresponding to the antigen which causes the undesired immune response, the number and spacing of the haptens or epitopes being insufficient to trigger an immune response but sufficient to inhibit it. Also disclosed is an improved vaccine from which low molecular weight suppressive polymer has been removed.

Abstract: Antigens, immunogens, inocula, antibodies, and particularly diagnostic methods and systems relating to Epstein-Barr virus nuclear antigen (EBNA) are disclosed. The diagnostic methods and systems utilize a synthetic, random copolymer polypeptide containing about 8 to about 40 amino acid residues that includes the overlapping five and six amino acid residue sequences--Gly--R.sup.1 --Gly--R.sup.2 --Gly-- (i)wherein R.sup.1 and R.sup.2 are amino acid residues selected from Ala, Asn, Arg, Gly, Leu, Pro, Ser, and Thr with the provision that R.sup.1 and R.sup.2 are not both Gly; and--Gly--Ala--Gly--Gly--Ala--Gly--. (ii)The polypeptide contains at least 50 mole percent Gly residues. The diagnostic method and system are particularly useful for assaying for the stage of mononucleois disease, and the presence of nasopharynegeal carcinoma.

Abstract: Antigens, immunogens, inocula, antibodies, and particularly diagnostic methods and systems relating to Epstein-Barr virus nuclear antigen (EBNA) are disclosed. The diagnostic methods and systems utilize a synthetic, random copolymer polypeptide containing about 8 to about 40 amino acid residues that includes the overlapping five and six amino acid residue sequences(i) --Gly--R.sup.1 --Gly--R.sup.2 --Gly--wherein R.sup.1 and R.sup.2 are amino acid residues selected from Ala, Asn, Arg, Gly, Leu, Pro, Ser, and Thr with the provision that R.sup.1 and R.sup.2 are not both Gly; and(ii) --Gly--Ala--Gly--Gly--Ala--Gly--.The polypeptide contains at least 50 mole percent Gly residues. The diagnostic method and system are particularly useful for assaying for the stage of mononucleois disease, and the presence of nasopharynegeal carcinoma.

Abstract: Disclosed is a soluble, biocompatible, pharmacological agent for inhibiting thrombin generation and thrombus formation, and methods for producing the same. The pharmacological agent or conjugate includes a soluble, biocompatible carrier and a thrombogenesis inhibitor immobilized thereto via the carrier which binds the inhibitor. The thrombogenesis inhibitor is hirudin, or an active analog or active fragment thereof. The thrombogenesis inhibitor may be bound to the carrier via a bifunctional cross-linking reagent.

Abstract: Human tumor associated Thomsen-Friedenreich (TF) antigen is purified from adenocarcinoma conditioned media, adenocarcinoma cell detergent extracts or plural effusion fluid by affinity chromatography using an insolubilized TF-specific monoclonal antibody, MAb 49H.8. The TF antigen is a glycoprotein characterized by a non-cryptic Gal .beta.(1.fwdarw.3) GalNAc epitope, a molecular weight in excess of 1,000,000 daltons, and extractability with perchloric acid, the epitope being sensitive to alkali and periodate but resistant to acid. A heterologous sandwich immunoassay has been developed for human TF antigen using a monoclonal antibody as the catcher and labelled peanut agglutinin as the probe. Since human TF antigen is shed by tumor cells, a positive determination of the TF antigen in a patient sample indicates the presence of cancer.

Abstract: A new homogeneous cytosolic binding (HCB) protein, having a specific binding activity of about 26 .mu.g FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506 but not cyclosporine A (CSA). The protein is stable to heating at 56 degrees C. for 30 minutes retaining its FK-506 binding affinity, and has the (partial) amino terminal amino acid sequence: H.sub.2 N-Gly-Val-Gln-Val-Glu-Thr-Ile-Ser-Pro- Gly-Asp-Gly-Arg-Thr-Phe-Pro-Lys- Ar g-Gly-Gln-Thr-X-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp-Gly-Lys-Lys-Phe-As p (wherein X is undefined). The HCB protein is isolated from the cytosol of mammalian tissues, preferably human neoplastic T-cell lines, e.g., Jurkat, and can be used in diagnostic and purification procedures involving FK-506 macrolide type immunosuppressants. The HCB protein also catalyzes the cis-trans isomerization of proline-containing peptide bonds.

Abstract: A single-step procedure for the immobilization of antibodies, comprising reacting a purified antibody with buffered periodate in an amount sufficient to produce aldehyde groups in the presence of a polymer carrier material which has been modified with adipic acid dihydrazide is disclosed. The present invention provides dramatic improvements in activity. and yield of immobilized antibody over the prior multi-step procedure employing separate oxidation and immobilization steps.

Abstract: Acetylated low density lipoproteins are combined with active and effective lipophilic peptide or other lipophilic immunomodulators, antigens or vaccines to carry the same to macrophage specific targeted receptor mediated endocytosis sites in a living system for treatment of cancer, infection hyperimmune related diseases or deficiences, or to enhance vaccine induction of immunity. Such receptor mediated endocytosis sites are found on macrophages, monocytes and endothelial cells in organs and tissues of the body.The combination of acetyl-LDL and a lipophilic peptide or related lipophilic immunomodulators, antigens, polynucleotides or vaccines enables delivery of such to be made across vascular barriers by transcytosis. The penetration of endothelial blood-brain, eye or testicular barriers is included in this concept.

Abstract: A cell-specific toxin molecule is prepared containing an enzymatically active toxin moiety coupled to a cell-specific binding ligand. The toxin moiety may be a diphtheria toxin, and has a non-naturally occurring cysteine residue encoded by a DNA sequence including a non-naturally occurring cysteine codon. The ligand may be a peptide hormone, proteinaceous growth factor, antibody of steroid hormone, and is derivatized with a sulfhydryl group reactive with the cysteine residue of the toxin moiety to couple the ligand to the toxin moiety via a disulfide bond. Derivatization of the ligand may be by providing the ligand with a non-naturally occurrring cysteine residue encoded by a DNA sequence including a non-naturally occurring cysteine codon. The toxin moiety exhibits cytotoxic activity but fails to exhibit generalized eukaryotic cell binding, and may be used to treat medical disorders.

Abstract: A recombinant peptide antigen is provided which is derived from HTLV-I envelope protein gp46 and immunoreactive with anti-HTLV-I antibody present in a individuals with HTLV-I related T-cell leukemia. The antigen is useful as a diagnostic tool in determining whether an individual has been or is infected with HTLV-I, and is also useful in a method of immunizing individuals against such infection.

Abstract: A bridging molecule carrying a drug, or a label such as a fluorophore, which adds across disulfide bonds of molecules, particularly proteins, and methods of manufacturing and using the bridging molecules, are disclosed. The bridging molecule is reactive with sulfhydryl groups formed by the reduction of disulfide bonds of the protein. The functional groups of the bridging molecules are typically --SH groups.

Abstract: A method of forming an amino acid thiohydantoin from an N-protected amino acid or the C-terminal amino acid of an N-protected peptide. The amino acid is activated by reaction with a ketenimine, and the activated ester is converted to the thiohydantoin by reaction with silyl or pyridine isothiocyanate. The ketenimine is generated by treating an N-substituted isoxazolium compound, such as Woodwards Reagent K with a base, preferably in the presence of the amino acid. Also disclosed is a solid phase support having a derivatized N-substituted isoxazolium or ketenimine group for use in the method.

Abstract: Homogeneous cyclophilin, a soluble binding protein, having a specific binding activity of above 50 ug cyclosporin A per mg protein and a molecular weight of about 17,600 daltons, reversibly binds immunosuppressants or antibodies thereto such as cyclosporin or anti-cyclophilin. It is isolated from the cytosol of several different mammalian tissues and can be used in various diagnostic and purifications procedures.

Abstract: The present invention provides a process for the production of a polysaccharide matrix to which haptens are covalently bound, wherein polysaccharide-containing material is rendered alkaline, dried to a water content of less than 5% and then reacted in an anhydrous medium with a hapten containing at least one activated functional group.The present invention also provides a device for carrying out this process, which comprises a winding core (3) in a container (1) for a reaction solution which has a tube (11), provided on its wall with a plurality of openings (7) and closed on one end (9), for the reception of a winding (13) of the material to be treated and two axial end walls (15, 17) for sealing off the axial ends of the winding (13) and feeds the reaction solution from the container (1) into the other end (21) of the tube (11) by means of a circulating pump cycle (19).

Abstract: Superior pharmaceutical compositions which comprise carriers coupled to epitope-bearing moieties are described. The carriers are crystalline or paracrystalline glycoproteins, especially those derived from S-layers of microbial cell walls. These conjugates are capable of eliciting the formation of antibodies as well as a T-cell response.

Abstract: Molecular binding partners such as antibodies and haptens are immobilized to support materials that have the property of contact activation of blood protein coagulation. A binding partner is attached to a surface-active protein carrier and the resulting conjugate non-covalently adsorbs onto the surface of the support. The method provides for diagnostic assays of greater sensitivity and convenience.

Abstract: A device for the determination of amino acid sequence of a polypeptide comprises two new features offering great advantages in the cost and efficiency of operation of amino acid sequencers. The sequencer is provided with the capability for the bidirectional flow of sequencing reagents and contains a sample chamber having a bicompositional adsorbent for the polypeptide.

Abstract: Novel pH-sensitive immunoconjugates which dissociate in low-pH tumor tissue, comprising a chemotherapeutic agent and an antibody reactive with a tumor-associated antigen are described. The chemotherapeutic agent is coupled to the antibody by a link which is unstable in low pH. The link may comprise a spacer consisting of a polyamino acid. Representative antibodies for use in these immunoconjugates include monoclonal antibodies which are not internalized by tumor cells.

Abstract: Several distinct peptide regions of the secreted form of purified human interleukin-1 species pI 6.8 have been found to exhibit characteristics associated with highly immunogenic protein moieties and are used to produce specific anti-peptide antibodies. The antibodies raised against the individual peptides are specific for the peptide used for their production and for IL-1, pI 6.8. The individual antibodies bind to both the precursor of IL-1, pI 6.8 and the mature or extracellular IL-1, pI 6.8.

Abstract: An assay for an analyte wherein sample is applied to a support capable of binding proteins by essentially only hydrogen bonding and fixed on the support. Analyte may be determined on the support by use of a suitable tracer. A preferred support is amphiphilic cellulose acetate. In an immunoassay, it is possible to determine analyte without use of a supported ("capture") antibody.

Abstract: Synthetic polypeptides having influenza virus antigenic properties are disclosed. These polypeptides correspond substantially to particular regions in the matrix protein of influenza virus. Salts, derivatives, and conjugates of these polypeptides are disclosed as well as methods for using these materials for diagnostic and medical/veterinary purposes.

Abstract: An improved heterogeneous immunoassay is provided which includes the utilization of support materials capable of reversible immobilization of proteinaceous binding partners of biological material of interest and the removal of labeled complexes from these supports through the use of release reagents permitting the subsequent solution phase determination of the amount of label.

Abstract: A solution of an active protein substance and an inactive protein substance is reacted with a cross-linking agent, optionally in the presence of an inert carrier, under cross-linking conditions to produce articles comprising both active and inactive protein substances. The active protein substance comprises up to about 20 percent, e.g. from 1 to 20 percent by weight, based on the final weight of the total protein substance, whereas the cross-linking agent comprises from 0.5 to 8 percent by weight, based on the weight of the total treated mixture. The obtained articles are in the form of a solution or a suspension in aqueous medium, in the form of a film, in the form of a membrane, in the form of a fabric, in the form of a porous material, or in the form of a mass, such as granules, pills or tablets.

Abstract: The present invention provides a process for the determination of a bindable analyte according to the principle of heterogeneous immunoassay by incubation of a sample solution which contains the analyte with a labelled first receptor specifically bindable with the analyte and present in dissolved phase and a second receptor present in a solid phase which does not cross-react with the first receptor and can fix a complex which contains the analyte and first receptor, separation of the phases after incubation and quantitative measurement of the labelling bound to the solid phase, wherein there is determined the back dissociation velocity of the labelling bound to the solid phase into the dissolved phase and the quotients of the back dissociation velocity and measurement value are used as a measure for the correctness of the test result of the first measurement.

Abstract: Gas containing granules of a resiliently compressible material having a density variable with pressure are used as a solid phase support in liquid phase reactions such in immunological reactions. Varying pressure causes the density of the granules to change and is used for mixing and separating the granules in liquid phase. In an immunological reaction, the granules having an attached antibody are combined with a solution containing an antigen, then varying pressure is applied to the solution to mix the granules in the solution to fix the antigen to the antibody and then pressure on the solution is varied to force the granules to the top or bottom of the solution whereby the solution can be separated from the granules.

Abstract: New Amines and amides of carboxylated polysaccharides having the nitrogen of the amido and amino groups directly attached to the polysaccharides and method of making same, based on reacting in solution a material having carboxyl-containing polysaccharides, such as carboxymethyl cellulose, with ammonium donors having the general formula >NH such as primary and secondary amine reagents and with or without a reducing agent to obtain amides or amines. These products may be used for instance in biological separations, for the immobilization of proteins, for the removal of metal ions, a thickeners, and as suspension agents.

Abstract: Methods and materials for preparing specific binding reagents with a multiplicity of relatively noninterfering label moieties are described. By spacing the labels at the surface of a specific reagent with bulking agent, increased sensitivity can be achieved without interference between individual labeling entities.

Abstract: The present invention involves a method for producing a substrate useful in a system for the detection of antibodies directed against platelet antigens. This method comprises several steps. A platelet sample of interest is initially treated with an aqueous solution comprising a dialyzable nonionic detergent. This initial treatment is under conditions to solubilize platelet components and produce a platelet lysate. Such conditions may involve treatment of a platelet sample with an aqueous solution comprising nonionic detergent at a concentration between about 0.2% and about 0.5%. Platelet antigens are most preferably solubilized for about 30 min and at about 0.degree. C. in an aqueous solution comprising about 1 mg dialyzable nonionic detergent per mg platelet protein.The partially purified platelet antigens resulting from these manipulations are then preferably affixed to a solid matrix.

Abstract: A process for preserving the phosphorylating activity of brewer's yeast by means of the intracellular immobilization of the glycolytic enzymes by glutaraldehyde. The process provides the following steps:permeabilization of the cell wall by the combined effect of temperature and the osmotic shock caused by the addition of a concentrated solution of dextrose and phosphates;immobilization of the glycolytic enzymes by cross-linking with intracellular proteins;protection of the SH groups against possible oxidation by the addition of deproteinized yeast extract.

Abstract: The present invention relates to a 40 kilodalton subunit of serous cystadinocarcinoma ovarian tumor associated antigen CA125, useful in the diagnosis and monitoring of ovarian cancer. It also relates to an immunoassay method for detection of the antigen in serum for diagnosis and monitoring purposes.

Abstract: Proteinaceous, antigenic factor derived from a group C Streptococcus which is receptor for the Fc region of IgG, a method for its preparation and immunoassay and antigen detection methods employing the receptor.

Abstract: An immunogenicity increasing carrier substance for immunogenic determinants is composed of particles derived from gram-negative cells substantially devoid or depleted of their natural immunogenic determinants, more particularly prepared by stripping the O-antigen and core region off the lipid A by chemical cleavage (acid hydrolysis). These socalled "naked bacteria" are chemically treated with a linking reagent to provide covalently bonded intermediate linking moieties while preserving the adjuvant effect of the particles. The linking moieties have functional groups. These serve for the covalent bonding of selected haptens or antigens comprising the desired immunogenic determinants against which antibodies are to be elicited in living antibody-producing cells.

Abstract: This invention relates to a method for the active or passive immunization of a vertebrate against ectoparasites and endoparasites, and a method of treating a vertebrate host infected by ectoparasites or endoparasites, comprising administering to the vertebrate an immunogen comprising one or more endocrine products of ectoparasites and endoparasites, coupled with an immunogenic carrier, or administering to the vertebrate, monoclonal antibodies capable of binding to the native form of the endocrine product.

Abstract: A carrier material usable as such in chromatographic separations or as a starting material which, upon linkage to it of compounds containing ionic groups, ligands or bio-active materials can be used as ion exchanger, as a clinical selective adsorbent, as a medium in affinity chromatography or in enzymatic reactions and consists of a core material obtained by addition polymerization of monomers of which at least 50 mole % consists of (meth)acrylic acid or an ester forming equivalent thereof and a hydrophilic coating material, which is covalently bonded to the core by complete or partial conversion of the carboxyl function with a compound containing at least three carbon atoms and an epoxy group, the epoxy groups that are still present having been converted by etherification and/or hydrolysis to form an ester of a compound containing a hydroxyl group or an oligomer thereof having a molecular weight not higher than 1000, as well as a process for preparing the same.

Abstract: A biological composition comprises a solid phase support matrix or marker molecule bound to protein, typically a glycoprotein such as an immunoglobulin through a linking group, spacer arm, and hydrazone group. The linking group is conveniently an ether linkage, while the spacer arm is a linear chain including six atoms, where at least one of the atoms is a tertiary amine which is protonated at a pH below about 8. The hydrazone is formed by reacting the solid phase or marker molecule having the linking arm and the spacer arm including a terminal hydrazide group with a glycoprotein oxidized to include a terminal aldehyde group. Immunological reagents prepared by linking an immunoglobulin (IgG) through a carbohydrate on the Fc or hinge regions have been found to provide very high binding capacity approaching the theoretical bivalent limit of two moles of bound antigen for every mole of bound immunoglobulin.

Abstract: The activity of growth-associated receptors is modulated in vivo in a controlled and reproducible fashion by immunizing animals against target growth-associated receptors. This is accomplished by the use of immunogens predetermined to induce primarily agonist or antagonist responses. The immunogens include anti-ligand antibodies and receptor derivatives.

Abstract: A new cell line has been made which is capable of producing an antibody that reacts with melanoma associated tumors cells. Antigens capable of reacting with the new antibody have been isolated and characterized. Methods are disclosed for the utilizing the antibody and antigen of the present invention and diagnostic procedures for determining the identity and extent of melanoma associated disease. The compositions of the present invention are disclosed to be useful in other immunological procedures.

Abstract: A method of linking primary aromatic amine- or nitro-compounds to carrier proteins by photochemical reactions in order to produce antibodies against the haptens.

Abstract: A novel process for the isolation and purification of vancomycin class antibiotics which utilized affinity chromatography by the formation of a sorption complex between the antibiotic and an immobilizing ligand selected from -D-alanyl-D-alanine or -X-D-alanyl-D-alanine, wherein X is an amino acid radical and the novel affinity chromatography sorbent employed therein are disclosed.

Abstract: Several distinct peptide regions of the secreted form of purified human interleukin-1 species pI 6.8 have been found to exhibit characteristics associated with highly immunogenic protein moieties and are used to produce specific anti-peptide antibodies. The antibodies raised against the individual peptides are specific for the peptide used for their production and for IL-1, pI 6.8. The individual antibodies bind to both the precursor of IL-1, pI 6.8 and the mature or extracellular IL-1, pI 6.8.

Abstract: Polypeptides displaying the antigenicity of hepatitis B virus e antigens, DNA sequences coding for those polypeptides, antibodies to those polypeptides and methods of producing and using those polypeptides, antibodies and DNA sequences. The polypeptides and antibodies of this invention are characterized by their use in compositions and methods for detecting hepatitis B virus infective carriers and in evaluating the course of HBV-related active liver disease.