Abstract: Active agents such as proteins are covalently immobilized on substrates carrying hydroxyl groups. A silane is bound to the substrate and coupled to a heterobifunctional crosslinker at one functional group leaving a free functional group, different than the first group, to which a protein is bound while retaining high protein functionality. Preferably, the silane has a functional group which reacts with the hydroxyl group of the substrate and a thiol terminal group which reacts with a functional group of a heterobifunctional crosslinking agent which contains a succinimide group that reacts with an amino group of the active agent. Bound active agents such as proteins are useful as biosensors or reactants in a variety of applications including bioassays.

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: Thromboresistant materials are disclosed comprising hirudin or hirudin derivatives covalently linked to support materials such that the resultant composition has substantially the same biological activity as hirudin. Methods for making such compositions are also disclosed.

Abstract: Substantially pure modified .beta..sub.2 -microglobulin (m.beta..sub.2 m) of the formula I ##STR1## wherein R.sub.1 is 24-amino acid residue, with the sequence Ile-Gln-Arg-Thr-Pro-Lys-Ile-Gln-Val-Tyr-Ser-Arg-His-Pro-Ala-Glu-Asn-Gly-Ly s-Ser-Asn-Phe-Leu-Asn, R.sub.2 is a 30-amino acid residue with the sequence Tyr-Val-Ser-Gly-Phe-His-Pro-Ser-Asp-Ile-Glu-Val-Asp-Leu-Leu-Lys-Asn-Gly-Gl u-Arg-Ile-Gly-Lys-Val-Glu-His-Ser-Asp-Leu-Ser, R.sub.3 is a 20-amino acid residue with the sequence Trp-Ser-Phe-Tyr-Leu-Leu-Tyr-Tyr-Glu-Phe-Thr-Pro-Thr-Glu-Lys-Asp-Glu-Tyr-Al a, R.sub.4 is a 19-amino acid residue with the sequence Arg-Val-Asn-His-Val-Thr-Leu-Ser-Gln-Pro-Lys-Ile-Val-Lys-Trp-Asp-Arg-Asp-Me t, X is Phe, Phe-Ser, or Phe-Ser-Lys, and Y is Asp, Lys-Asp, or Ser-Lys-Asp is disclosed. The presence of the protein in body fluids is a diagnostic and/or prognostic marker for the development of a variety of disorders such as different types of cancer and diseases involving the immune system. Also disclosed are specific anti-m.

Abstract: Porous immobilization support materials for use in physical and chemical processes are produced from bird, animal or fish bone by cleaning finely divided bone to remove all external tissue and by dissolving away all internal tissue from internal pores and internal Haversian canals of the bone to result in cleaned bone containing not more than 0.5% by weight of remaining lipid material, preferably containing only trace amounts, i.e. less than 0.1% by weight. The cleaned bone consists of porous finely-divided animal bone containing a collagenous matrix of organic fibrous connective tissue material including osein having uniformaly distributed therethrough mineral hydroxyapatite. The collagenous matrix provides an ideal distributed site for the chemical attachment of bacteria, cells and enzyme catalysts. The attachment may be by absorption, or by charge attraction, or with a cross-linking agent attachable between the bone and the supported material.

Abstract: A polymeric drug comprising an inert synthetic polymeric carrier combined through aminoacid or peptide spacers with a bioactive molecule, a targeting moiety, and an optional cross-linkage, comprises:(a) 5.0 to 99.7 mol % of units derived from N-(2-hydroxypropyl)methacrylamide,(b) 0.2 to 20.0 mol % of units derived from an N-methylacrylcylated peptide, the peptide groups being bound to a bioactive moiety,(c) 0.1 to 94.8 mol % of units derived from N-methacrylamide, N-methacrylic acid or an N-methacrylolated aminoacid or peptide, to which are bound a determinant capable of interacting with specific receptors on cell surfaces,(d) optionally, 0 to 5 mol % of units derived from an N-methacryloylated peptide, the peptide groups being bound to a linking group which is similarly to a similar peptide group attached to another polymer chain, and(e) optionally, as a bioassay label, 0 to 2 mol % units derived from N-methyacryloylated tyrosinamide.

Abstract: Physiologically active substances are immobilized on an inorganic support, by treating the inorganic support with an aminoalkylakoxysilane having the general formula(RO).sub.3 SiCH.sub.2 CH.sub.2 CH.sub.2 NH(CH.sub.2).sub.n NH.sub.2wherein, R is an alkyl group having 1 to 4 carbon atoms, and n is an integer having a value of 5 to 12, and chemically bonding a physiologically active substance by means of an amino group to the support.

Abstract: Stable cross-linked complexes of transition-metal tetracarboxylates and proteins are formed. The preferred transition-metal is rhodium. The protein may be collagen or an enzyme such as a proteolytic enzyme.

Abstract: An active material and method of making same are disclosed comprising a metal oxide/hydroxide surface having chemically bonded to reactive sites thereon, a layer of a perfluorinated organic material formed by reacting with the metal oxide/hydroxide a perfluorinated organic acid comprised of an acid group and a perfluorinated carbon-containing group. The bond to the metal oxide/hydroxide surface is formed by reaction of the acid group with the metal oxide/hydroxide surface, so that the perfluorinated carbon-containing group is oriented away from the metal oxide/hydroxide surface. The perfluorinated organic acid may be a perfluorinated phosphonic acid, a perfluorinated phosphinic acid, a perfluorinated carboxylic acid, or a mixture of two or more of the acids.

Abstract: Immobilized IgG binding proteins and the use thereof to effect affinity chromatography and separate the subclasses of IgG. Disclosed are cysteine-containing IgG binding proteins which have high binding capacity for human IgG and mouse monoclonal IgG.

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: A cloned gene encoding Protein G, or functionally active portions thereof, vectors containing the cloned gene, and microorganisms transformed by those vectors are disclosed.

Abstract: A regenerable support matrix useful for immobilization of biologically active materials is prepared by coating a core support with a cellulose ester, removing ester groups by hydrolysis to produce hydroxyl groups and converting the hydroxyl groups to dialkylaminoalkyl ether groups. The support matrix can immobilize biologically active proteinaceous materials with a net negative charge by adsorption. The support matrix is readily regenerated when an immobilized biologically active material becomes inactive by washing the support with a base or salt solution and adsorbing additional biologically active material to the support. Multiple cycles of immobilization and regeneration are possible without significant deleterious affects.

Abstract: Methods and materials are described for the preparation of novel immobilized membrane compositions. The described compositions are useful for evaluating membrane association charcteristics of chemical compounds, and as a chromatographic support material for separation/purification of biomolecules and particularly those expressed by genetically transformed cells as novel hybrid proteins having covalently bound membrane-binding peptides. Novel phospholipid carboxylates are useful intermediates for the preparation of chromatography supports having surfaces formed as covalently bound artificial membranes which simulate natural cellular membranes. The immobilized membrane compositions are adapted for use in chromatographic systems to study interactions of biologically active substances with membranes in vitro.

Abstract: A membrane mimetic structure having a hydrophilic outer portion and a hydrophobic inner portion is covalently bound to a surface having reactive functional groups. The membrane mimetic structure consists essentially of adjacent amphiphilic molecules independently covalently bound to the surface. The structures can be applied to surfaces and should find application in a wide variety of disciplines requiring surfaces exhibiting properties of biological membranes.

Abstract: Peptide-containing compounds such as enzymes, antibodies and antigens are immobilized on metal hydroxy gels formed by hydrolysis of metal alkoxides in an aqueous solvent while evaporating off the solvent. Preferably, hydrogen fluoride is present in the solvent during hydrolysis to provide a fluoride-substituted metal hydroxy gel. Water containing lower alcohol is a preferred solvent. The gel is treated with a coupling agent and a peptide-containing compound is chemically bonded to the gel.

Abstract: Contact lens comprising an eye-compatible surface on which monoclonal antibodies or fragments of antibodies are immobilized, the N-terminal ends of which are directed against mucous substances of the human ocular tear film.

Abstract: A component for the rapid detection of anti-Treponema pallidum antibodies adapted for use as a selective foundation material in standard immunoassays is provided. The component comprises a quantity of fibronectin insolubilized to a solid matrix. The fibronectin component provides a foundation material for the selective binding of antigenic outer membrane proteins extracted from Treponema pallidum. Incorporation of the insolubilized fibronectin component bound to the antigenic outer membrane proteins extracted from Treponema pallidum into a standard immunoassay test pack provides an immunological assay for the presence of respective complementary anti-Treponema pallidum antibody in a biological sample.

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 hybrid protein which comprises plasmin A-chain linked to urokinase B-chain, the catalytic site of which is blocked by a removable blocking group.

Abstract: A process for the detection of antibodies to HTLV III/LAV comprising:(A) mixing an unknown serum sample with a crude HTLV III/LAV viral antigen selected from the group consisting of(1) an antigen comprising P24 core protein and Penv protein;(2) a P24 antigen and(3) a Penv antigen,(B) incubating the resultant mixture from step (A);(C) contacting the mixture of step (B) with a solid substrate coated with antibody to HTLV III/LAV;(D) incubating the mass from step (C);(E) washing the mass from step (D);(F) contacting the mass from step (E) with a labeled antibody to HTLV III/LAV;(G) incubating the mass from step (F);(H) washing the mass from step (G);(I) assaying the label in the mass from step (H);(J) as a negative control, mixing a serum sample known to be negative to HTLV III/LAV antibody with a diluent;(K) subjecting the mass from step (J) to steps (B) to (I);(L) as a positive control, mixing a predetermined amount of the crude HTLV III/LAV viral antigen and the diluent;(M) subjecting the mass from step (L) t

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: An immunoadsorbent material for removing IgM and IgM-complexes from biological fluids is prepared by covalently binding anti-IgM antibodies to a solid-phase silica matrix. It has been found that reacting hydroxy-derivatized silica in the presence of cyanogen bromide with the anti-IgM antibodies provides a particularly stable, high-capacity immunoadsorbent. The immunoadsorbent material may be employed in a column for therapeutic treatment of various disorders, such as primary biliary cirrhosis.

Abstract: A radioactive diagnostic or therapeutic agent, which comprises a metallic element-labeled high molecular compound which comprises one unit of (1) a polyamine compound having at least three amino groups in the side chains per molecule, at least two units of (2) a chelate-forming compound having a carboxyl group, at least one unit of (3) a physiologically active substance and (4) at least two radioactive metallic elements, each unit of the chelate-forming compound (2) and the physiologically active substance (3) being combined to any of the amino groups in the side chains of the polyamine compound (1) and each of the radioactive metallic element (4) being chelate-bonded to the chelate-forming compound (2).

Abstract: The peptide X-Arg-Gly-Asp-R-Y wherein X is H or at least one amino acid and Y is OH or at least one amino acid, and R is an amino acid selected from Thr or Cys, or other amino acid, having the same cell-attachent activity as fibronectin and the peptide X-Arg-Gly-Asp-Ser-Y, wherein X and Y, having said activity are disclosed.

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: A two-step process of immobilization of biologically efficient compounds is disclosed, in which the biologically efficient compounds are bonded from an aqueous solution by a hydrolytically stable linkage to a macroporous polymeric carrier containing reactive functional groups. In the first step, a hydrophobic adsorption occurs of the biologically efficient compounds on a macroporous matrix of the carrier, and an increase of their concentration on the solid surface. In the second step, the reaction takes place with the reactive functional groups of the carrier, and a covalent linkage is formed. The hydrophobic adsorption of compounds determined for immobilization is achieved by the addition of inorganic salts in a concentration from 0.5 to 3.0 mol/l. The invention can be utilized in the preparation of enzymatic catalysts for transformations of compounds and in the preparation of specific sorbents for both analytical and preparative affinity chromatography.

Abstract: The use of immunologically non-specific peptide linked amino acids containing compounds that are capable of immobilizing circulating immune complexes for the purpose of detection or removal from serum or blood, such compounds including oligopeptides, modified oligopeptides, polypeptides, modified polypeptides, proteins, modified proteins, and in particular glycosylated polypeptides and proteins.

Abstract: A composite article is prepared comprising in sequence a fibrous polymeric support which has been subjected to a surface treatment to provide binding sites thereon, a layer of a protein immobilizer compound, and a biologically active protein. The surface treatment comprises coating the support with a 2 to 500 nm thick layer of inorganic oxide or subjecting the support to a plasma treatment. The protein immobilizer can be a polymer or silane-functional compound. The biologically active protein can be the enzyme, catalase, which has use in decomposing hydrogen peroxide when disinfecting contact lenses.

Abstract: A matrix useful for immobilizing organic ligands, such as biologically active materials, is prepared by reacting a hydroxyl group containing polymer with polyethyleneimine.

Abstract: Biochemically active material is immobilized on porous silica-rich glass fibers having a diameter of about 3 to 150 microns, a length of about 0.03 inch to continuous fiber length, a mean pore diameter in the range of about 10 to 3000 angstroms, a pore volume of about 0.5 to 1.5 cc/gm and a surface area of about 10 to 600 m.sup.2 /gm. The porous glass fibers are preferably formed from a composition containing greater than 35 up to 60 weight percent B.sub.2 O.sub.3, about 1 to 10 weight percent alkali metal oxides, about 30 to 65 weight percent SiO.sub.2, up to about 5 weight percent ZrO.sub.2, and up to about 4 weight percent Al.sub.2 O.sub.3. Fibers having the composition are heated to cause phase separation into a boron-rich phase and a silica-rich phase, and are then treated by water and acid leaching to produce the porous glass fibers. A biochemically active material is attached to the fibers by absorption or by covalent bonding with a linking agent.

Abstract: Disclosed are antibody substances displaying unique, multi-specific immunoreactivities with respect to glycoprotein D of Herpes Simplex Virus types 1 and 2 (HSV gD-1 and gD-2) and structurally related compounds. Illustratively, an IgG Type 2 monoclonal antibody material produced by mouse-mouse hybridoma cell line A.T.C.C. No. HB8606 is capable of in vitro neutralization of HSV-1 and HSV-2 infectivity and of specific immunological reactivity and reversible immunobinding with natrually-occuring and recombinant gD-1 and gD-2 in both native and denatured conformations as well as with proteinaceous materials (produced, e.g., by proteolytic digestion of naturally-occurring materials, by recombinant methods, or by polymerization of amino acids) which comprise a primary structural conformation substantially duplicating part or all of that which is predicted to be extant at residues 266 through 287 of gD-1 and gD-2 [i.e., PELA(or V)PEDPEDSALLEDPV(or A)GTVA(or S)].

Abstract: Biocatalyst such as enzymes or cells are immobilized in hollow porous microspheres for use as bioreactors in biochemical processes. The microspheres are of substantially uniform diameter of 200 to 10,000 microns and of substantially uniform wall thickness of 1 to 1000 microns. Walls of the microspheres are formed of sintered together particles such as inorganic particles. The walls have interconnecting voids that are continuous and extend from outer wall surface to the inner wall surface. The biocatalyst is introduced into the microspheres through macropores in the walls, and then immobilized. Immobilization may be performed by introducing a gel forming material with the biocatalyst and forming a semipermeable gel in situ within the microspheres.

Abstract: The process for the separation of antiVIII:C antibodies present in a liquid consists of contacting said liquid with a solid support constituted by a polymer or a copolymer having in its chain substitutable groups, whereof at least part is substituted by groups having an affinity for antiVIII:C antibodies and a selectivity for antiVIII:C antibodies compared with other immunoglobulins and then separating the liquid from the support on which have been adsorbed the antiVIII:C antibodies.Preferably use is made of polystyrene, to which have been fixed groups --SO.sub.3 Na and --SO.sub.2 Glu, --SO.sub.2 Threo, --SO.sub.2 OHPro or SO.sub.2 Lys. These supports can be used for ex-vivo purification in the column of the blood plasma of a type A hemophiliac.

Abstract: A naturally occuring protein is chemically modified to provide the protein with activity of a selected enzyme. The protein does not contain activity of the selected enzyme before modification. Modification is preferably carried out by partially denaturing the protein in the presence of an inhibitor for the selected enzyme to form a partially denatured protein-enzyme inhibitor complex, adsorbing the complex to a solid support and crosslinking the adsorbed complex to form an immobilized modified protein having activity of the selected enzyme. Alternatively, the protein may be adsorbed onto the support, partially denatured and crosslinked in the presence of the inhibitor or the protein may be partially denatured, adsorbed on the support and crosslinked in the presence the inhibitor. In another embodiment, the protein has at least three disulphide groups.

Abstract: A method for detecting or removing a substance in a medium is presented. Magnetic material, particularly magnetic bacteria or magnetic particles contained therein, are treated to render them receptive to binding or attachment to the substance sought to be detected or removed. Following binding or attachment to the treated magnetic material, the medium is subjected to a magnetic field, which results in removal of the magnetic material and the substance bound or attached thereto.

Abstract: Recombinant vaccines for immunizing horses against equine influenza virus (EIV) are disclosed. The DNA sequences encoding the hemagluttinin (HA) and neuraminidase (NA) glycoproteins from the two strains of EIV currently infective in horses are used to construct vaccinia carried vaccines, to design synthetic peptides for primer and booster administration, and to permit recombinant synthesis of HA and/or NA protein based vaccines. These DNA sequences also provide probes useful for preparing similar vaccines from fresh isolates of new strains generated by genetic drift.