Abstract: The present disclosure relates to selected antigenic proteins obtained from the outer membranes of Moraxella catarrhalis, that have been found by the inventors to have a variety of useful properties. These proteins, termed OMPs ("Outer Membrane Proteins"), are characterized as having molecular weights of 30, 80 and 100 kD, respectively. Studies set forth herein demonstrate that monoclonal antibodies directed against these proteins confer a protective effect against infection by Moraxella catarrhalis organisms in animal models, demonstrating the potential usefulness of such antibodies in conferring passive immunity as well as the potential usefulness of these OMPs, or variants thereof, in the preparation of vaccines. Also disclosed are DNA segments encoding these OMPs, methods for preparing the antigens, or variants, through the application of recombinant DNA techniques, as well as diagnostic methods and embodiments.

Abstract: A method of detecting or determining a sequence of amino acids which is antigenically active within a known amino acid sequence of a protein or portion thereof comprises the steps of: synthesising a plurality of peptides, each of said peptides comprising a sequence of a plurality of amino acids which corresponds to a sequence within the known amino acid sequence, and the said peptides having overlapping amino acid sequences; contacting each of said peptides with antibody against the protein or portion of interest; and detecting or determining the presence or absence of an antigen-antibody reaction between each of said peptides and said antibody to indicate whether or not said peptide has antigenic activity.

Abstract: Methods for preventing or treating vascular hemorrhaging such as that incident to thrombolytic therapy, or characteristic of Alzheimer's and related diseases are provided. Such methods provide improved thrombolytic therapy to individuals who receive such therapy, and permit the diagnosis and treatment of diseases, such as Alzheimer's disease, that are characterized by the deposition of amyloid deposits.

Abstract: Disclosed is a highly sensitive anti-HIV antibody detection assay. The assay detects the presence of anti-HIV antibodies through the use of a non-denatured HIV antigenic determinant which immunoreactivity binds anti-HIV antibodies in a biological sample. The non-denatured HIV antigenic determinant has provided a means for detecting anti-HIV antibodies in serum samples testing seronegative for the presence of HIV antibodies directed against denatured HIV antigens p17, p19, p24, p27, p39, gp41, p55, gp120 and gp160. The antigenic determinant may take the form of a cross-immunoreactive live HIV-infected cell line or a biologically engineered peptide possessing conserved or shared HIV surface antigenic determinants. Methods of preparing HIV target antigens are also disclosed, as well as methods for determining the presence of anti-HIV antibodies through the use of these non-denatured HIV target antigens. A test kit for detecting anti-HIV antibodies is also disclosed.

Abstract: A medium and method for blotting macromolecules is disclosed. The method begins with the separation of macromolecules on a slab gel. Next, a sheet of cellulosic paper is dipped into an alcohol bath. The dipped paper is placed against the slab gel. The paper and the gel are exposed to a means for transferring the macromolecules from the gel onto the paper. In a particularly advantageous embodiment of the method, the paper is dipped into a methanol bath, the transferring means includes an electric field, and the paper is either xerographic paper or cotton bond paper. The present invention is also a medium for blotting macromolecules comprising a piece of cellulosic paper that has been dipped in alcohol.

Abstract: Peptides which bind to selected ligands are identified by screening peptide libraries which encode a random or controlled collection of amino acid sequences. A rapid and convenient iterative strategy is employed to determine the peptide sequences which bind to the ligand of interest. The peptides so identified can be used as diagnostic or therapeutic agents, or in the design of lead compounds for such uses.

Abstract: Compounds having detergent properties are disclosed. When a modifying reagent is brought into contact with these compounds, the detergent properties are decreased. These compounds are useful, for example, as solubilizing agents for microbial antigens and/or antibodies and for reversibly wetting hydrophobic surfaces. Accordingly, methods are disclosed for increasing the hydrophilic properties of a material, such as a microbial antigen and/or antibody, the methods generally comprising the steps of contacting the material with the compound having detergent properties and a modifiable group, and modifying the compound with a modifying reagent. Kits are also disclosed for use in accordance with this methodology.

Abstract: A novel heterogenous purification method is disclosed. The method removes a macromolecule from a liquid by allowing the macromolecule to undergo a specific binding affinity reaction with a bidentate conjugate. The method is carried out by immobilizing the bidentate conjugate on a solid phase, contacting the bidentate conjugate with the liquid comprising the macromolecule, and separating the immobilized bidentate conjugate from contact with the liquid, thereby removing the macromolecule from the liquid to obtain either purified macromolecule or a purified liquid.

Abstract: A method is provided for detecting an analyte of interest in a sample. The method involves binding the analyte to the surface of a substrate through a biotin-biotin binding protein interaction, contacting the surface-bound analyte with a quantitatively detectable analyte-binding moiety that binds thereto, measuring the quantity of detectable moiety bound to the substrate surface and deriving therefrom the quantity of analyte in solution. A preferred use for the present method is in conjunction with a piezoelectric surface transverse wave device. Novel reagents useful for carrying out the inventive method are provided as well.

Abstract: The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the .alpha. anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate .alpha. (2-3) and .alpha. (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.

Abstract: Antibodies raised against derivatives of inositol are used to assay for specific isomers of inositol in a sample by first converting any inositol present in the sample to the derivative that was used to raise the antibody and then conducting an immunoassay for the inositol derivative in a conventional manner.

Abstract: New acridinium compounds are provided which comply with formula 1, whereinA is a divalent organic moiety, such as an alkylene chain,X is a group which can be transformed together with C-9 of the acridine into a dioxetane by reaction with hydrogen peroxide, such as an aryloxy group,Y is a counter ion, andZ is a functional group, such as a carboxyl derivative.These acridinium compounds are useful as chemiluminogenic labels for both heterogeneous and homogeneous immunoassays.

Abstract: The invention involves an immunological method of separating specifically-targeted cells or molecular structures from a mixed population under conditions which minimize damage to the cellular structure or the molecular integrity. The method is based upon the specific interaction of a label and an antibody directed against the label and the ability of a competitor to inhibit the interaction between the label and the antibody.

Abstract: An improved device is provided which may be used, e.g. for immunoassay of lipopolysaccharides or for removing LPS pyrogens from aqueous solutions, or for removing LPS endotoxins from wounds. Such device comprises, in combination, a substrate, e.g. plastic, i.e. polystyrene, polycarbonate, polymethylmethacrylate or polyvinyl chloride, or a woven cloth, i.e. a rayon/polyester cloth or a polyester cloth, or a non-woven cloth, i.e. a rayon/polyester cloth, or a polyester cloth, or paper, which is adapted to receive a sample to be tested, and an oligopeptide, or a hydrophobic polypeptide or a polymyxin, e.g. polymyxin B, polymyxin B.sub.1, polymyxin B.sub.2, polymyxin D.sub.1, polymyxin D.sub.2, or polymyxin E, adhered to the substrate.

Abstract: The invention is directed to monoclonal antibodies which immunoreact with bare small moieties such as metallic cations and small organic molecules, the hybridomas for production of the monoclonal antibodies, immunogen compounds for developing the hybridomas, and methods for use of the monoclonal antibodies.

Abstract: New purified mite allergens useful as pharmaceutical and diagnostic compositions for the treatment and diagnosis of mite allergic diseases are provided. Both allergens are contained in fecal extracts of mites in culture. The high molecular weight allergen has a weight average molecular weight of 70,000 to 80,000 as determined by sedimentation equilibrium. This is a glycoprotein containing more than about 70% sugar, and possesses allergen activity. The low molecular weight antigen has a molecular weight of 1,500 to 5,000 as determined by Sephadex G25 gel filtration. This is a glycoprotein containing more than about 40% sugar, and also possesses allergen activity.

Abstract: A method for the treatment of the symptoms of fescue toxicosis in mammals comprising injecting a subject mammal with a vaccine which includes from about 5 .mu.g to about 1 mg of a protein-alkaloid conjugate per mL of a physiologically acceptable carrier. There is also provided a vaccine for the treatment of the symptoms of fescue toxicosis and a compound for preparing that vaccine.

Abstract: An antigen capture method, and an antigen capture assay diagnostic kit, for detecting the presence or concentration of HIV in a biological sample without interference from antigen-antibody immune complexes is provided. The lysate of a biological sample obtained from an animal is contacted with a detectable amount of an antibody specifically reactive with the nucleocapsid p7 antigen or an immunoreactive fragment of the p7 antigen for a time and under conditions sufficient for p7 antigen contained in the lysate to form a p7-antibody complex. The presence or concentration of this p7-antibody complex is determined to detect or quantitate the presence of HIV in the biological sample. Uses of this assay and method include detecting the presence of HIV infection in an infant born to an HIV-infected mother, monitoring the progression of HIV infection, and evaluating the effectiveness of an anti-HIV treatment administered to an animal, such as a human.

Abstract: A diagnostic test for detection of antinuclear antibody anti-La in a serum sample, comprises contacting the serum sample with a support having immobilised thereon a synthetic polypeptide displaying the antigenicity of all or a portion of the human autoantigen La, or an antigenically active fragment thereof, and detecting the presence of anti-La antibody bound to the synthetic polypeptide or fragment.

Abstract: A Raman label which, upon radiation, produces a detectable Raman scattering signal in a ligand-binding assay for an analyte in a test sample. A conjugate containing a Raman label attached to a specific binding member.

Abstract: The present invention concerns an improved method for the determination of fibrin in body fluids in which before the actual determination the sample solution containing fibrin is incubated in the presence of thiocyanate, iodide, magnesium or/and guanidinium ions.

Abstract: A method for making a valproic acid derivative comprising a functionalized spacer arm attached to a .delta. carbon atom of a valproic acid molecule is disclosed. The method proceeds by attaching a spacer arm joined to an inorganic moiety to a valproic acid precursor to make an alkylated compound, derivatizing the alkylated compound in a liquid medium to make the valproic acid derivative, and then separating the valproic acid derivative from the liquid medium. The valproic acid derivative can be used to make an immunoreactive valproic acid conjugate.

Abstract: Method for the immunological determination of a ligand in which the ligand to be determined is reacted witha) at least 2 molecules of a specifically bindable substance P2 of which at least one of these molecules carries a label andb) a receptor R which consists of a binding partner P1 which is capable of monovalent binding to P2 and a binding site R.sub.1 for the ligand to be determined and then the label is determined,as well as a reagent for the immunological determination of a ligand which contains a specifically bindable substance P2 which is present at least partially in labelled form and a receptor R which consists of a binding partner P1 which is capable of monovalent binding to P2 and a binding site R.sub.1 for the ligand to be determined.

Abstract: The invention relates to a novel process for preparing immunoconjugates consisting of haptens which are sparingly soluble or insoluble in aqueous solution and proteins/polypeptides using special solvents, in particular diethylene glycol monoalkyl ethers.

Abstract: A method is described for diagnosing rheumatoid arthritis by providing a recombinant IgM-specific rheumatoid arthritis-associated antigen and detecting antibodies against the antigen in patient sera. Preliminary steps of making a cDNA library from polyadenylated RNA purified from human cells, selecting recombinants that express the antigen, recloning cDNA containing the antigen gene in a high level expression vector, expressing the antigen in transformed cells, and purifying the antigen are also described.

Abstract: This invention is directed to an adjuvant composition in the form of an emulsion which is comprised of an emulsion-forming amount of a non-toxic tetra-polyol or of a POP-POE block polymer and an immunopotentiating amount of a muramyldipeptide of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, where R and R.sub.1 are each independently H or acyl of 1 to 22 carbon atoms, R.sub.2 is optionally substituted alkyl or optionally substituted aryl, R.sub.3 is H, alkyl, or aryl, R.sub.4 is H or lower alkyl, X is L-alanyl, L-.alpha.-aminobutyryl, L-arginyl, L-asparginyl, L-aspartyl, L-cysteinyl, L-glutaminyl, L-glutamyl, glycyl, L-histidyl, L-hydroxyprolyl, L-isoleucyl, L-leucyl, L-lysyl, L-methionyl, L-ornithinyl, L-phenylalanyl, L-prolyl, L-seryl, L-threonyl, L-tyrosyl, L-tryptophanyl, or L-valyl, and Y is D-glutamine, D-isoglutamine or D-isoasparagine. This invention is also directed to a vaccine containing an antigen and an adjuvant composition of the invention.

Abstract: The present invention is directed to a fluorescence polarization immunoassay for determining the 3-methoxy-4-hydroxyphenylglycol content in body fluids, to the various components needed for preparing and carrying out such an assay, and to methods of making these components. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for preparing them. The assay is conducted by measuring the degree of polarization of plane polarized light that has been passed through a sample containing antiserum and tracer.

Abstract: The present invention provides for a method for preparing antibodies that specifically detect the type IV collagen .alpha.5 chain that is defective in various basement membrane disorders such as in X chromosome-linked Alport's syndrome. The invention further provides for the use of such antibodies to detect the .alpha.5(IV) collagen chain in solutions and other human tissue specimens using immunological methods comprised of antibodies specific for said protein. Along this line, the invention relates to the use of the specific antibodies to examine the presence or absence of the .alpha.5(IV) collagen chain in the tissues, e.g. skin or kidneys, etc. of patients with renal failure, possibly due to Alport's syndrome.

Abstract: The present invention is directed to a method and a kit for diagnosing active human neurocysticercosis utilizing an immunoblot assay which comprises:detecting the presence of antibodies in the serum or cerebrospinal fluid of a human to be diagnosed, wherein the antibodies are reacted with Taenia solium larval antigens which have been isolated by lentil lectin affinity. The larval antigens are designated GP50, GP42, GP24, GP21, GP18, GP14, and GP13, wherein GP indicates that said antigen is a glycoprotein and the number indicates the molecular weight in K daltons, as determined by SDS-PAGE.

Abstract: Nonmetallic tetrapyrrole molecules are shown to catalyze the production of light by chemiluminescence in the presence of a signal solution at a pH from about 10.0 to about 14.0, having an appropriate oxidant or combination of oxidants and a luminescent reactant. The addition of an electron transport facilitator, a surfactant, a carbohydrate, and a chelating agent to the signal solution increases the output of light. These tetrapyrrole molecules are used alone or attached to haptens or macromolecules and are utilized as labels in the preparation of chemiluminescent, homogeneous or heterogeneous assays. They are also used in conjunction with other chemiluminescent label molecules to produce multiple analyte chemiluminescent assays. A chemiluminescent signal solution which comprises at a pH ranging from about 10.0 to about 14.

Abstract: The present invention is directed to novel PCP derivatives which are synthesized for the covalent attachment to antigens or receptors (proteins or polypeptides) for the preparation of antibodies or receptors to PCP and PCP analogue metabolites. The resulting novel antigens may be used for the production of antibodies or receptors using standard methods. Once generated, the antibodies and the novel derivatives which are covalently attached to proteins, polypeptides or labels may be used in the immunoassay process.

Abstract: A method for the direct analysis of analyte in keratinized structures, e.g., hair, fingernails and toenails, which comprises preparing a mixture containing a low redox potential compound such as dithiothreitol or dithioerythritol, an enzyme suitable for the degradation of the keratin structure and a sample of the keratin structure; permitting the enzyme to at least substantially degrade the sample of keratin structure, and subjecting the mixture to analysis to determine the identity and amount of analyte in the keratin substance sample. To accelerate the method, cupric sulfate or sodium arsenite may be added to the mixture after degradation of the keratin sample. The enzyme may be a peptidase, endopeptidase or proteinase, with papain, chymopapain, and proteinase K being preferred for use in the invention.

Abstract: In order to detect analytes with an immunological method by incubation with receptors and analysis of the complexes formed, a mixture of at least two monoclonal antibodies which are specifically bindable to the analyte and whose cross-reactivities are different are used for at least one of the receptors.

Abstract: The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the a anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate .alpha. (2-3) and .alpha. (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.

Abstract: A detecting reagent for an antiplatelet antibody, comprises a carrier particle, and a platelet antigen component immobilized on a surface of the carrier particle. The reagent particles do not agglutinate with each other, contrary to the platelets subjected to natural agglutination, probably because the platelet membrane antigen component immobilized on the carrier particle is solubilized in advance.

Abstract: This invention provides a quantitative assay for determining the amount of a biologically active ligand selected from the group consisting of human chorionic gonadotropin and luetinizing hormone present in a sample comprising contacting the sample with both the receptor to which the ligand naturally binds in order to effect its biologicaly activity and a monoclonal antibody directed to the ligand or to a complex of the ligand and the receptor so as to form a complex of the ligand bound to both the receptor, at the site to which the ligand naturally binds to the receptor, and the monoclonal antibody. In the complex so formed, either the receptor or the monoclonal antibody is labeled with a detectable marker and a determination is made of the amount of labeled receptor or of labeled monoclonal antibody bound to the ligand or the amount of labeled receptor or of labeled monoclonal antibody not bound to the ligand, or both such amounts.

Abstract: This invention relates to methods, reagents and kits for detection of normal or ectopic pregnancy, the termination of pregnancy, or increased risk of preterm labor and rupture of membranes. Each embodiment involves sampling from the vaginal cavity, and determining the presence or absence of a specific analyte in the test sample. Sandwich or competition assay procedures can be used. Reagents and reagent kits for the above assays are included. The kit contains anti-(fetal fibronectin) antibody and an anti-fibronectin antibody.

Abstract: Disclosed is a protein that specifically binds carcinoembryonic actigen (CEA) in the presence of divalent cation in vitro. This protein has a molecular weight of about 20 kD as determined by SDS-polyacrylamide gel electrophoresis, is glycosylated, and includes the amino acid sequence set forth in the Sequence Listing as SEQ ID NO:4. Also disclosed are antibodies that recognize the CEA binding protein, methods of detecting carcinoma, methods of treating carcinoma, and a kit for screening a patient for carcinoma.

Abstract: Disclosed is a protein that specifically binds carcinoembryonic actigen (CEA) in the presence of divalent cation in vitro. This protein has a molecular weight of about 21 kD as determined by SDS-polyacrylamide gel electrophoresis, is glycosylated, and includes the amino acid sequence set forth in the Sequence Listing as SEQ ID NO: 2. Also disclosed are antibodies that recognize the CEA binding protein, methods of detecting carcinoma, methods of treating carcinoma, and a kit for screening a patient for carcinoma.

Abstract: N-substituted azetidinones are a class of inhibitors of human leukocytes elastase which are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the radioimmune assay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured. The assays are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.

Abstract: A method for preparing phycobiliprotein/amine-reactive dye conjugates is disclosed in which the conjugates so prepared overcome the energy transfer/fluorescent quenching dilemma encountered in the use of prior art conjugates. A phycobiliprotein, for example, phycoerythrin or allophycocyanin, is conjugated with an amine-reactive dye, for example, Texas Red or carboxyfluorescein succinimidyl ester, in the presence of a selective salt which causes a hydrophobic intramolecular rearrangement of the phycobiliprotein thereby exposing more hydrophobic sites for binding to the amine-reactive dye. The conjugates prepared according to the invention are useful in multiple color fluorescence assays without requiring the use of multiple exciting sources.

Abstract: A radioimmunoassay for pyridostigmine in biological fluids. The method disclosed can detect 250 pg of pyridostigmine per ml of biological fluid using 0.1 ml of biological fluid. The antibody used in this method is raised from an antigen produced by diazotizing para-aminobenzoic acid and reacting the diazotized material with pyridostigmine to form a pyridostigmine-hapten solution, which is then reacted with bovine serum albumen. The antibody used in the disclosed method has a cross-reactivity with the major metabolites of pyridostigmine of less than 2%.

Abstract: A radioimmunoassay for physostigmine in biological fluids. The method disclosed can detect 100 pg of physostigmine per ml of biological fluid using 0.1 ml of biological fluid. The antibody used in this method can be raised from an antigen produced by either or two methods--diazotizing para-aminobenzoic acid and reacting the diazotized material with physostigmine to form a physostigmine-hapten solution, which is then reacted with bovine serum albumin or by using a Mannich reaction to directly conjugate physostigmine to bovine serum albumin. The antibody used in the disclosed method has a cross-reactivity with the major metabolites of physostigmine of less than 1%.

Abstract: An immunofluorescent assay method, characterized in using an immunodetective reagent, which is an antigen-like substance comprising a fluorescent substance and an antigen chemically bonded thereto with or without intervention of an additional chemical bond, said fluorescent substance being changed in the wavelength or intensity of the fluorescence when an antibody comes close thereto, and said antigen being specific to said antibody.

Abstract: Antiserum which can recognize all subtypes of human leukocyte interferon is prepared from the blood of an animal immunized with partially purified human leukocyte interferon obtained from a culture of human leukocyte stimulated with Sendai virus.The antiserum is added to a column whereon concentrated culture broth of human leukocyte has been immobilized to adsorb impurities, the effluent is added to a column whereon partially purified human leukocyte interferon has been immobilized to adsorb anti-human leukocyte interferon antibody and then the antibody is eluted from the column.The antibody thus obtained recognizes all subtypes of human leukocyte interferon and can be separated by a chromatography to each monoclonal antibody which recognizes a single subtype.Employing these antibodies, the subtypes of human leukocyte interferon or their antibodies in a sample can be analized or assayed.

Abstract: A chemical moiety is disclosed which comprises a chemical, biochemical, or biological substance attached to one or more electrochemiluminescent organometallic compounds. In a preferred embodiment of the invention the substance is attached to one or more ruthenium-containing or osmium-containing luminescent organometallic compounds. Methods are disclosed for detecting very small amounts of the chemical moiety using chemiluminescent, electrochemiluminescent, and photoluminescent means. Compounds are disclosed which are useful for labelling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labelled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labelled substances are of particular use in homogeneous binding assays.

Abstract: The invention relates to an assay for determining an analyte in a fluid sample. Three receptors are used, with formation of a quaternary or four member complex. One of the receptors is bound to a solid phase, and binds to complexes of another receptor and the analyte. A third receptor is labelled, and it, too, binds analyte. The invention also involves the use of a displacement solution to wash fluid sample from solid phase after the first portion of the quaternary complex forms, i.e., prior to binding with the labelled receptor.

Abstract: A monoclonal antibody specifically reactive to hamster immunoglobulins, a hybridoma producing said monoclonal antibody, and an immunoassay utilizing said monoclonal antibody are provided. The monoclonal antibody is useful in an immunoassay as a secondary antibody to a hamster-derived primary antibody or antiserum raised against various antigens.

Abstract: The invention concerns peptides which react immunochemically with antibodies directed against NANBH. A method for the detection of NANBH or anti-NANBH in a test fluid, an immunochemical reagent and a testkit to be used when applying said detection methods belong to the invention.

Abstract: A chemical moiety is disclosed which comprises a chemical biochemical, or biological substance attached to one or more electrochemiluminescent organometallic compounds. In a preferred embodiment of the invention the substance is attached to one or more ruthenium-containing or osmiumcontaining luminescent organometallic compounds. Methods are disclosed for detecting very small amounts of the chemical moiety using chemiluminescent, electrochemiluminescent, and photoluminescent means. Compounds are disclosed which are useful for labelling substances of interest with ruthenium-containing and osmium-containing labels or other electrochemiluminescent labels. These labelled substances are useful in methods provided for detecting and quantifying analytes of interest in binding assays and competitive binding assays. The labelled substances are of particular use in homogeneous binding assays.