Abstract: Compounds of formula (I) or their salts or esters: [wherein R1 is alkyl or haloalkyl; R2 and R3 each represents hydrogen or aliphatic acyl; X is hydroxy, halogen, alkoxy, or a group of formula RaO—, where Ra is aliphatic acyl; Y is a group of formula RbRcN— or RbRcN—O—, where Rb and Rc each is hydrogen or alkyl; and Z is oxygen or sulfur] have excellent sialidase inhibitory activity and are therefore useful for the treatment and prevention of influenza and other viral diseases where the replication of the virus is susceptible to sialidase inhibitors.

Abstract: An antiserum containing an antibody, which when combined with an immunogen having a nonfluorescent dye, confers fluorescent ability to the dye. In particular, an antiserum which confers fluorescent ability on a conjugate of an immunogenic substance and Malachite Green.

Abstract: A method of measuring the amount of cyclosporin in a sample suspected of containing cyclosporin is disclosed. A method of inactivating interfering cross-reactive material in an assay for measuring the amount of cyclosporin in a sample suspected of containing cyclosporin is also disclosed. Compositions wherein cyclosporin is conjugated to an immunogenic carrier or a label, optionally through a linking group, at an alanine nitrogen atom of the cyclic backbone of cyclosporin are also disclosed. Compositions wherein atiocyclosporin is conjugated, optionally through a linking group, to an immunogenic carrier or a label are also disclosed. Where cyclosporin is conjugated to an immunogenic carrier, the conjugates may be used as immunogens for the preparation of antibodies which are capable of recognizing cyclosporin.

Abstract: Novel methods and compositions are provided for modulating homing of leukocytes, particularly lympho-cytes, where the compounds are cross-reactive with Neu5Ac2-3Gal&bgr;1-X[Fuc&agr;1-y]GlcNAc, where one of x and y is three and the other is four. These compounds may be administered to a host associated with inflammation, to avoid the deleterious effects of leukocyte infiltration and for directing molecules to such sites.

Abstract: An anti-cocaine vaccine employs a cocaine hapten conjugated to a carrier protein. The anti-cocaine vaccine elicits an immune response which reduces the psychoactive effects of cocaine consumption by the production of anti-cocaine polyclonal antibodies. The antibodies may be employed in an ELISA test for assaying cocaine. The immune response elicited by the anti-cocaine vaccine produces antibody producing cells which may be isolated and cloned for producing anti-cocaine monoclonal antibodies.

Abstract: Chemiluminescent 1,2-dioxetane compounds capable of producing light energy when decomposed, substantially stable at room temperature, represented by the formulas I or II:

Abstract: The present invention is directed to novel methods for identifying small molecule ligands that are capable of binding with high affinity to a biological target molecule of interest. High affinity binding ligands identified by the described methods find use, for example, as small molecule lead compounds that may they themselves be, or may give rise to, novel therapeutic drugs. More specifically, the subject invention is directed to methods for identifying a ligand that binds to a target biological molecule of interest, wherein a population of small organic compounds are selected and then “pre-screened” to identify those that are capable of binding to the molecular target.

Abstract: Method for identifying a drug lead compound that inhibits binding of target bioogical molecules (TBM) by contacting TBM with members of a library of candidate cross-linked target binding fragments (CXBF), each CXBF having at least two candidate target bindig fragments (CTBF), which are inhibitors of binding, linked to a cross-linker, and selecting CXBF that inhibit the binding of the TBM to a greater extent than either of the individual CTBF linked to said cross-linker, wherein the library of CXBF is produced by: (a) screening a population of CTBF capable of being chemically cross-linked by a cross-linker to identify a subpopulation of the CTBF that inhibit binding of the TBM; and (b) chemically cross-linking members of the subpopulation of CTBF or structurally related analogs thereof with a cross-linker to provide a library of CXBF, wherein at least one linking group comprises an oxime ether linking group.

Abstract: Novel hapten-carrier conjugates are capable of inducing the production of antibodies, in vivo, that specifically bind to nicotine. These conjugates comprise a nicotine hapten conjugated to an immunogenic carrier protein. The novel conjugates preserve the chirality of nicotine in its native (S)-(−) state, and have good stability properties. The conjugates are useful in formulating vaccines for active immunization, that are used to prevent and treat nicotine addiction. The antibodies raised in response to the nicotine hapten-carrier conjugate are used for passive immunization. These antibodies are administered for prevention and treatment of nicotine addiction.

Abstract: The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic noeplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule in combination with administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. “Antigenic molecule” as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual.

Abstract: A method for simply measuring a 1,2-dicarbonyl derivative in multiple specimens is provided, which comprises converting a 1,2-dicarbonyl derivative to a pyrazine derivative represented by the formula (I): wherein R1 and R2 independently represent a hydrogen atom, a methyl group, a hydroxymethyl group, a hydroxyethyl group, a dihydroxyethyl group, a dihydroxypropyl group, a trihydroxypropyl group, or a trihydroxybutyl group, A represents a group that binds to the pyrazine ring to form a 6-membered aromatic hydrocarbon group, a 5- or 6-membered aromatic heterocyclic group, or a 5- or 6-membered alicyclic hydrocarbon group, and R3 represents a linking residue, wherein said 5-membered ring formed by A may have 1 or 2 substituents and said 6-membered ring may have 1 to 3 substituents, in addition to R3 and measuring the pyrazine derivative by an immunological method using an antibody that recognizes the pyrazine derivative.

Abstract: Disclosed are multibinding compounds which inhibit microsomal triglyceride transferase protein (MTP), a protein which mediates the transfer of lipids during the assembly of lipoproteins and related biomolecules. The multibinding compounds contain from 2 to 10 ligands covalently attached to one or more linkers. The multibinding compounds of this invention are useful for lowering serum lipid, cholesterol and/or triglyceride levels, and for preventing and treating disorders associated with hyperlipemia, hyperlipidemia, hyperlipoproteinemia, hypercholestrolemia, hypertriglyceridemia and the like, such atherosclerosis.

Abstract: The substitution of the L-Pro at the 7-position with D-Phe or D-Tic and substitution of the L-Phe at the 8-position with hydroxyproline ethers and thioethers of the peptide hormone bradykinin and other additional substituted analogs of bradykinin converts bradykinin agonists into bradykinin antagonists. The invention further includes additional modifications at other positions within the novel 7- and 8-position modified bradykinin antagonists, which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.

Abstract: A hybridoma cell line has been produced for secreting a monoclonal antibody that binds ractopamine and is effective to detect ractopamine levels of about 1 ng/mL or lower. This monoclonal antibody may be used for the detection and quantitative determination of trace amounts of ractopamine in samples, especially in animal tissue, body fluids and feed material.

Abstract: The invention relates to the accurate and precise direct molar-mass measurement of low-molar-mass fragments of polysaccharides such as Haemophilus influenzae Type b. The methods for obtaining such determinations for polysaccharides use size-exclusion chromatography (SEC) with detection by multi-angle laser-light-scattering photometry (MALLS) and differential refractometry (RI) and/or (2) determination of polysaccharide fragments and direct measurement of average chain length by quantitative 1H NMR, from which molar masses may be derived. Variation between the molar masses obtained by the two methods ranged from 5 to 7%.

Abstract: A bifunctional molecule consisting of a therapeutic molecule and a ligand which specifically binds a transcytotic receptor can be transported specifically from the basolateral surface of epithelial cells to the apical surface. This approach provides the ability to deliver a therapeutic molecule directly to the apical surface of the epithelium, by targeting the transcytotic receptor with an appropriate ligand. Thus, the highest concentration of the therapeutic molecule will be at the apical surface, where it can have the greatest therapeutic effect.

Abstract: Novel hapten-carrier conjugates are capable of inducing the production of antibodies, in vivo, that specifically bind to nicotine. These conjugates comprise a nicotine hapten conjugated to an immunogenic carrier protein. The novel conjugates preserve the chirality of nicotine in its native (S)-(−) state, and have good stability properties. The conjugates are useful in formulating vaccines for active immunization, that are used to prevent and treat nicotine addiction. The antibodies raised in response to the nicotine hapten-carrier conjugate are used for passive immunization. These antibodies are administered for prevention and treatment of nicotine addiction.

Abstract: The present invention describes a soluble fusion protein composed of a plurality of major histocompatibility complex (MHC) molecules linked together by a stabilizing structure herein referred to as the “linker,” the MHC molecules being loaded with a specific peptide or peptides. Such fusion proteins can be used as a method for stimulating or inhibiting specific T cell clones expressing T cell receptors (TCR) restricted to the specific MHC-peptide combination. Such fusion proteins can thus be used as delivery systems to stimulate T cell immunity and as a treatment for diseases such as transplant rejection or autoimmunity.

Abstract: The present invention relates to stable compositions useful as primary standards and calibrators and controls comprising a cardiac troponin I (cTnI) such as native, recombinant, addition and deletion forms thereof, whether or not complexed with other troponin subunits such as TnC and/or TnT, in an inactivated human serum. The compositions are obtained by incubating troponin complexes with human serum. The compositions are characterized by an immunodetectability ratio of epitopes on the N-terminal segment to epitopes on the C-terminal segment substantially equivalent to that of pooled, fresh serum from acute myocardial infarction patients.

Abstract: The present invention provides hapten derivatives that are useful for the preparation of antigens, antibodies and reagents having superior performance characteristics for use in immunoassays for the detection of LSD and nor-LSD. In the present invention the LSD nucleus is derivatized out of the indole nitrogen to form an aminoalkyl derivative. Derivatives have also been synthesized out of the piperidine nitrogen of the LSD nucleus. The resulting haptens can then be further modified at these functionalized positions for linking to appropriate antigenic or labelling groups to provide reagents for LSD immunoassays having excellent sensitivity and selectivity for both LSD and nor-LSD.

Abstract: A method of measuring the amount of cyclosporin in a sample suspected of containing cyclosporin is disclosed. A method of inactivating interfering cross-reactive material in an assay for measuring the amount of cyclosporin in a sample suspected of containing cyclosporin is also disclosed. Compositions wherein cyclosporin is conjugated to an immunogenic carrier or a label, optionally through a linking group, at an alanine nitrogen atom of the cyclic backbone of cyclosporin are also disclosed. Compositions wherein atiocyclosporin is conjugated, optionally through a linking group, to an immunogenic carrier or a label are also disclosed. Where cyclosporin is conjugated to an immunogenic carrier, the conjugates may be used as immunogens for the preparation of antibodies which are capable of recognizing cyclosporin.

Abstract: The present invention provides hapten derivatives that are useful for the preparation of antigenic, antibody and label reagents having superior performance characteristics for use in immunoassays for the detection of d-propoxyphene and d-nor-propoxyphene. In the present invention the propoxyphene nucleus is derivatized out of the nitrogen center to form an aminoalkyl -carboxyl, or -hydroxyl haptenic derivative. The resulting hapten can then be further modified at the now functionalized position off the nitrogen for linking to an appropriate antigenic or labeling group to provide reagents for propoxyphene immunoassays having excellent sensitivity and selectivity for both d-propoxyphene and d-nor-propoxyphene.

Abstract: The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

Abstract: An immunogen comprising a residue of a histamine-releasing peptide comprising a cationic N-terminal head and a hydrophobic C-terminal tail, together with a residue capable of eliciting antibodies against said peptide whilst inhibiting histamine release by said peptide is useful in anti-allergy treatment. Preferably the histamine-releasing peptide is of formula:Lys-Thr-Lys-Gly-Ser-Gly-Phe-Phe-Val-Phe,optionally amidated at the C terminal.Antibodies to the histamine-releasing peptide are useful for passive immunisation.

Abstract: The invention addresses new photo-activatable biotin derivatives having the formula I ##STR1## wherein R=?(CH.sub.2).sub.n --O.sub.m !.sub.q --?(CH.sub.2).sub.r --O.sub.s !.sub.t --(CH.sub.2).sub.pwith n,r=2,3; m,s=0,1; q+t=1-4; p=1-4,wherein the sum of all CH.sub.2 groups does not exceed 10and wherein R1 as a single or multiple substituent is hydrogen, C.sub.1 -C.sub.5 alkyl, NH.sub.2, COOH, F, Cl, or Br.and their preparation, their use to inactivate streptavidin, the use of the inactivated streptavidin to reduce interference in immunoassays.

Abstract: A conjugate consisting of a sequence of the analyte and an antibody against one of the antibodies used in the test can be employed, in aqueous solution and in precisely known quantity, as a stable calibrator in a sandwich immunoassay for detecting the analyte.

Abstract: Linker compounds for formation of stably-linked conjugates are disclosed. Such linker compounds are aminooxy-containing linker compounds useful in forming conjugates having stable oxime linkages. The stably-linked conjugates have utility in a variety of immunodiagnostic and separation techniques.

Abstract: The present invention provides an immunogenic compound comprising the formula: ##STR1## wherein X is selected from the group consisting of methyl and hydrogen; wherein R.sub.1 is a suitable functional group of the lysergic ring;wherein R.sub.2 is an immunogenic protein; andwherein Y is a bridge to link R.sub.1 to R.sub.2.The present invention also provides purified polyclonal and monoclonal antibodies specifically reactive with the immunogenic compound and reactive with the lysergic ring of ergopeptine and clavine alkaloids. The present invention further provides an antibody which is an anti-idiotype of the monoclonal antibody. Also provided are methods of prevention and treatment of fescue toxicosis utilizing the immunogenic compounds and antibodies of the present invention.

Abstract: 1,2-dioxetane compounds bearing a proteolytic enzyme specific amino acid or peptide are provided, which amino acid or peptide can be removed by action of the corresponding protease. When the amino acid or peptide is removed, the 1,2-dioxetane decomposes with chemiluminescence, the generation of light providing a rapid, ultra-sensitive and convenient means for detecting the presence of the protease in the sample being inspected. The amount of light generated, or degree of chemiluminescence, can be correlated with the amount of protease present. Immunoassays, as well as DNA hybridization and DNA probe assays are provided.

Abstract: 1, 2-dioxetane compounds bearing a proteolytic enzyme specific amino acid or peptide are provided, which amino acid or peptide can be removed by action of the corresponding protease. When the amino acid or peptide is removed, the 1,2-dioxetane decomposes with chemiluminescence, the generation of light providing a rapid, ultra-sensitive and convenient means for detecting the presence of the protease in the sample being inspected. The amount of light generated, or degree of chemiluminescence, can be correlated with the amount of protease present. Immunoassays, as well as DNA hybridization and DNA probe assays are provided.

Abstract: Methods for diagnosing pre-hypertension, hypertension, congestive cardiomyopathy, renal failure, salt-sensitivity and adenomas and endocrine cell hyperplasias are disclosed. Also disclosed are methods for monitoring hypertension therapy, congestive cardiomyopathy therapy, renal failure therapy and adenoma and endocrine cell hyperplasia therapy. These methods involve using an antibody having binding specificity to ouabain to immunologically measure the level of human ouabain in body fluid or tissue of a subject. Additionally, methods for treating a hypertensive subject by inducing passive or active immunity to human ouabain in the subject are disclosed, along with an antibody having binding specificity for ouabain.

Abstract: The present invention relates to pharmaceutically effective heterodimers comprising a bradykinin antagonist component covalently linked to a mu-opioid agonist component.

Abstract: There are disclosed hapten tracer complexes which, on the one hand, contain a hapten which is linked to an indicator component and, on the other hand, an antibody which can bind specifically to the indicator component. These hapten tracer complexes can be employed advantageously in immunoassays.

Abstract: The present invention relates to lipopolysaccharides from Brucella abortus and their use as carriers in vaccines for humans and animals. In particular, the present invention relates to conjugate molecules having a carrier molecule of purified lipopolysaccharide from B. abortus coupled to an antigenic component of an infectious organism.

Abstract: A new method for immobilization of small molecules on solid supports via a macromolecular spacer has been developed. A protein or another macromolecule is first immobilized in an aqueous medium, and the solid support is than washed with an organic solvent. The small molecule is coupled in an organic medium, followed by organic medium washes. The new solid phases are useful for affinity purifications, immunoassays and other binding assays, and for selection of binders by panning procedures.

Abstract: The present invention provides hapten derivatives that are useful for the preparation of antigenic, antibody and label reagents having superior performance characteristics for use in immunoassays for the detection of d-propoxyphene and d-nor-propoxyphene. In the present invention the propoxyphene nucleus is derivatized out of the nitrogen center to form an aminoalkyl -carboxyl, -amino, -thiol or -hydroxyl haptenic derivative. The resulting hapten can then be further modified at the now functionalized position off the nitrogen for linking to an appropriate antigenic or labelling group to provide reagents for propoxyphene immunoassays having excellent sensitivity and selectivity for both d-propoxyphene and d-nor-propoxyphene.

Abstract: The present invention provides devices and methods for the detection of creatinine in biological fluids using lateral flow methodologies. The invention is particularly useful in providing one step creatinine assays for correcting urinary steroid hormone assays.

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: The present invention relates to P5 outer membrane protein of the non-typable Haemophilus influenzae bacterial strain and antibodies directed to P5 protein. The invention also relates to a method of isolating P5 protein and a vaccine composition for use in the treatment of non-typable Haemophilus influenzae infection.

Abstract: Novel quinidine derivatives are provided which can be used in an improved immunoasssay for the detection of quinidine and quinidine metabolites.

Abstract: An immunogenic compound comprising the formula: ##STR1## wherein X is selected from the group consisting of methyl and hydrogen; wherein R.sub.1 is a suitable functional group of the lysergic ring;wherein R.sub.2 is an immunogenic protein; andwherein Y is a bridge to link R.sub.1 to R.sub.2.Purified polyclonal and monoclonal antibodies specifically reactive with the immunogenic compound and reactive with the lysergic ring of ergopeptine and clavine alkaloids are described. An antibody which is an anti-idiotype of the monoclonal antibody is provided. Methods of prevention and treatment of fescue toxicosis utilizing the immunogenic compounds and antibodies of the present invention are provided.

Abstract: Novel tandem dyes comprising a conjugate of a Cy7 dye and allophycocyanin are provided. Also provided are probes comprising the subject dyes conjugated to a member of a specific binding pair. Probes comprising the subject tandem dyes find use as labels in variety of fluorescence detection assays.

Abstract: The present invention is directed to immunoassay reagents including specific antibodies to quinoline carboxylic acids, such as brequinar; novel quinoline carboxylic acid haptens useful as standards in immunoassays or for conjugating to large molecular weight carriers as immunogens or conjugating to detectable fluorescent moieties as tracer compounds. The present invention also relates to immunoassays for detecting quinoline carboxylic acids in clinical samples, and finally to kits containing said reagents.

Abstract: Immunoassay methods and reagents for the specific quantification of thyroxine in a test sample are disclosed employing antibodies prepared with thyroxine derivatives of the formula: ##STR1## wherein P is an immunogenic carrier material and X is a linking moiety. The present invention also describes the synthesis of unique labelled reagent of the formula: ##STR2## wherein Q is a detectable moiety and W is a linking moiety, preferably fluorescein or a fluorescein derivative.

Abstract: Immunoassay methods and reagents for the specific quantification of thyroxine in a test sample are disclosed employing antibodies prepared with thyroxine derivatives of the formula: ##STR1## wherein P is an immunogenic carrier material and X is a linking moiety. The present invention also describes the synthesis of unique labelled reagent of the formula: ##STR2## wherein Q is a detectable moiety and W is a linking moiety, preferably fluorescein or a fluorescein derivative.

Abstract: A compound useful for forming immunoconjugates used in the detection of organophosphate pesticides is provided. The compound has the formula ##STR1## wherein X is selected from the group consisting of R--O--, R--S-- and R--NH--, where R is an optionally substituted aromatic or heterocyclic group, or an optionally substituted alkyl or alkenyl group;Y is O or S;R.sup.1 is H or alkyl; andR.sup.2 is a group of the formula --(CH.sub.2).sub.n -- wherein n is an integer of from 1 to 10, or branched chain alkylene, or a group of the formula R.sup.3 --O--R.sup.4 wherein R.sup.3 and R.sup.4 are both or straight or branched chain alkylene;or a salt or ester thereof.

Abstract: A coupling agent which is an activated ester such as N-maleimido-6-aminocaproyl-HNSA (mal-sac-HNSA) is formed by reacting 4-hydroxyl-3-nitrobenzene sulfonic acid sodium salt (HNSA) with a carboxylic acid moiety of a compound such as N-maleimido-6-aminocaproic acid. The coupling agent is reacted with an amino group of an amine-containing biological material such as a protein at a pH of about 5.5 to 10.0 and HNSA is released. The released HNSA is spectroscopically measured at a wavelength of from about 350 nm to about 500 nm to precisely monitor and control conjugating of the coupling agent to the biological material. The resulting product is coupled to a sulfhydryl group or other group of another material to provide cross-linking between the two. This enables joining the biological material to one another, to a support matrix, to a label, to a hapten, and to other materials.

Abstract: A brandykinin antagonist of the formula:X(BKA).sub.nwherein BKA is the peptide chain of a bradykinin antagonist peptide, X is a linking group and n is a whole number greater than 1. The BKA substituents may be the same or different. Monomeric antagonists of the formula X(BKA) are also disclosed. Also disclosed are bradykinin antagonists of the formula:(Y)(X)(BKA)where X and BKA have the meanings indicated above and Y is the peptide chain of an antagonist or agonist for a non-bradykinin receptor.

Abstract: A bradykinin antagonist of the formula:X(BKA).sub.nwherein BKA is the peptide chain of a bradykinin antagonist peptide, X is a linking group and n is a whole number greater than 1. The BKA substituents may be the same or different. Monomeric antagonists of the formula X(BKA) are also disclosed. Also disclosed are bradykinin antagonists of the formula:(Y)(X)(BKA)where X and BKA have the meanings indicated above and Y is the peptide chain of an antagonist or agonist for a non-bradykinin receptor.

Abstract: The present invention relates to P5 outer membrane protein of the non-typable Haemophilus influenzae bacterial strain and antibodies directed to P5 protein. The invention also relates to a method of isolating P5 protein and a vaccine composition for use in the treatment of non-typable Haemophilus influenzae infection.