Abstract: In accordance with the present invention, there is provided a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. Thus, in accordance with the present invention, dithiocarbamates are linked to the surface of a non-immunogenic, non-targeting macromolecule other than an antibody (e.g., albumin protein) either by using cross-linking reagents or by nonspecific binding to produce polydithiocarbamate-macromolecule-containing compositions, which represent a new class of drugs for therapeutic treatment of such indications as cerebral stroke and other ischemia/reperfusion injury. In accordance with another aspect of the present invention, combinational therapeutic methods have been developed for the in vivo inactivation or inhibition of formation (either directly or indirectly) of species which induce the expression of inducible nitric oxide synthase, as well as reducing nitric oxide levels produced as a result of .NO synthase expression.

Abstract: Highly hydrophilic indole and benzoindole derivatives that absorb and fluoresce in the visible region of light are disclosed. These compounds are useful for physiological and organ function monitoring. Particularly, the molecules of the invention are useful for optical diagnosis of renal and cardiac diseases and for estimation of blood volume in vivo.

Abstract: Monoclonal antibodies to rapamycin and to 40-O-alkylated derivatives of rapamycin are provided, together with novel haptens, immunogenic conjugates, and processes for making them and assay kits for using them.

Abstract: A hapten-polymer carrier complex was found to be useful for immunoassay purposes, specifically ELISAs, for the detection of pesticides and their degradation products in hydrosoil and ground water. The degradation products of Casoron G® (also known as dichlorobenzonitrile and dichlorbenil) and Prefix® (also known as chlorthiamid and dichlorobenzthiamide) are analytes detected with high specificity and sensitivity, particularly the degradation product BAM (2,6-dichlorobenzamide). The polymer carrier complex is bound to the hapten via a linker unit, strategically positioned meta to the amide or amide derivative of BAM.

Abstract: The invention relates to (ethylene)-(propylene)-triaminepentaacetic acid derivatives that are substituted on both the ethylene bridge and the propylene bridge, as well as conjugates of these compounds with biomolecules. The compounds and conjugates are suitable as agents for NMR diagnosis and radiodiagnosis as well as for radiotherapy.

Abstract: The present invention relates to a polysaccharide-protein conjugate. The invention also relates to a method of using the conjugate to prevent systemic infections. The invention further relates to a pharmaceutical composition. The invention also relates to a method of producing a polysaccharide-protein conjugate.

Abstract: The invention provides an immunogen comprising a hapten coupled to an antigenicity-conferring carrier material, a conjugate comprising the aforementioned hapten coupled to a labelling agent, as well as, antibodies raised against the aforementioned immunogen and capable of binding with at least one structural epitope of metabolites of fentanyl and of metabolites of fentanyl analogs.

Abstract: Novel haptens, which can be conjugated to form immunogens, are of formula I, II or III 1

Abstract: A method of estimating the average exposure within a population of subjects to a pharmacological substance, administered according to a given protocol, by estimating the area under the concentration curve (AUC), characterised in that the area under the population concentration curve is estimated by the steps of obtaining measurements of the drug concentrations in each of the subjects at any time during the study, independently from the time when measurements of the drug concentration level in the other subjects are being taken; building a hierarchical stochastic model composed of the population and of the individual levels; determining the posterior probability distribution of the average AUC from the sample data and hence the average population AUC. The exposure of an individual and its precision within the sample of individuals can be determined by determining the posterior probability distribution of the individual AUC from the sample data.

Abstract: Synthetic polypeptides from the conserved exposed region of streptococcal M protein are useful to prepare vaccines for oral or intranasal administration which will protect against streptococcal infection.

Abstract: A novel cyanine dye having the formula is useful for labeling biological and nonbiological molecules.

Abstract: A new method for assaying the ability of a compound to block the binding of an &agr;4 integrin to a binding partner thereof provides a useful screening tool.

Abstract: Provided are methods of labeling multiple proteins in protein mixtures to prepare the samples for identification and analysis, and useful in developing a proteomics database.

Abstract: Activated haptens useful for generating immunogens to HIV protease inhibitors, immunogens useful for producing antibodies to HIV protease inhibitors, and antibodies and labeled conjugates useful in immunoassays for HIV protease inhibitors. The novel haptens feature an activated functionality at the central, non-terminal hydroxyl group common to all HIV protease inhibitors, e.g., saquinavir, nelfinavir, indinavir, amprenavir, ritonavir and lopinavir.

Abstract: The present invention relates to an immunogenic conjugate comprising a carrier molecule coupled to an autoinducer of a Gram negative bacteria. The immunogenic conjugate, when combined with a pharmaceutically acceptable carrier, forms a suitable vaccine for mammals to prevent infection by the Grain negative bacteria. The immunogenic conjugate is also used to raise and subsequently isolate antibodies or binding portions thereof which are capable of recognizing and binding to the autoinducer. The antibodies or binding portions thereof are utilized in a method of treating infections, a method of inhibiting autoinducer activity, and in diagnostic assays which detect the presence of autoinducers or autoinducer antagonists in fluid or tissue samples.

Abstract: To improve the detection of LSD, and LSD metabolites in biological samples, antibodies are raised to 2-oxo-3-hydroxy-LSD conjugated to a protein carrier. Selected antibodies are matched with an immunoassay reagent in which the 2-oxo-3-hydroxy-LSD is conjugated in the same position to a labeling or separation means. The set of reagents can be used in immunoassays for detecting or confirming the presence of LSD or LSD metabolites in a sample potentially containing interfering substances.

Abstract: Hapten-carrier conjugates capable of eliciting anti-hapten antibodies in vivo by administering, in a therapeutic composition, are disclosed. Methods of preparing said conjugates and therapeutic compositions are also disclosed. Where the hapten is a drug of abuse, a therapeutic composition containing the hapten-carrier conjugate is particularly useful in the treatment of drug addiction, more particularly, cocaine addiction. Passive immunization using antibodies raised against conjugates of the instant invention is also disclosed. The therapeutic composition is suitable for co-therapy with other conventional drugs.

Abstract: This invention allows the fluorescence analysis of a nonfluorescent dye with high specificity and high sensitivity by virtue of the formation of a complex among an antibody directed against an immunogen having the nonfluorescent dye, an antiserum containing the antibody, and the nonfluorescent dye, which is an IgG fraction of the antibody, as well as, of the manifestation of fluorescent ability of the dye, which would otherwise be nonfluorscent, resulting from the formation of the complex. Also, the invention enables higher sensitivity in fluorescence measurement where the background fluorescence is less, by employing Malachite Green which will turn into a fluorescent dye.

Abstract: Hybridoma cell lines have been generated which produce and secrete monoclonal antibodies which selectively bind to tilmicosin. These hybridomas may be obtained by using as an immunization agent or immunogen, 23-deoxo-23-demycinosyl tilmicosin which has been conjugated to an immunogenic carrier. The antibodies may be used to detect and/or quantify tilmicosin in biological samples. The monoclonal antibodies also may be incorporated into kits.

Abstract: Novel activated peptides and conjugates thereof, useful in diagnostic assays and therapeutics, and processes for the preparation thereof are disclosed.

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: Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides a rapamycin specific monoclonal antibody.

Abstract: Disclosed are novel coumarin based fluorogenic compounds useful in assaying for biological activity. Specifically, these fluorogenic compounds exhibit fluorescence at particular wavelengths when cleaved by target enzymes. Preferred compounds include sugar and peptide derivatives of umbelliferone derivatives bearing a heterocyclic five membered ring at the 3-position. These compounds can be used for rapidly detecting food pathogens and for determining sterilization effectiveness. The compounds may also be used in a form bounded to a polymeric support or to a biomolecule or macromolecule.

Abstract: A method of improving specific immune responses to small immunogens, haptens, has been developed by changing the linkage between the hapten and carrier being used for immunization. High affinity antibodies to the hapten cotinine have been produced using this method. Antibodies to a glycated protein have also been developed, utilizing an immunogen which is composed of a glycated peptide mimic of the glycated peptide sequence which is the target epitope, wherein the peptide mimic is constructed to conformationally mimic the conformation of the peptide in the native protein, the peptide mimic contains no charged groups or other immunodominant group, and the peptide mimic is connected to a spacer sequence equivalent to a peptide spacer of between one and thirty amino acids in length, which serves to position the peptide epitope in a conformation that approximates its conformation in the native protein. In a further embodiment the peptide mimic and spacer are linked to a carrier molecule.

Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: Chemically-defined, non-polymeric valency platform molecules and conjugates comprising chemically-defined valency platform molecules and biological or chemical molecules including polynucleotide duplexes of at least 20 base pairs that have significant binding activity-for human lupus anti-dsDNA autoantibodies.

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 an immunoassay for phthalic acid esters, which comprises measuring the phthalic acid esters contained in a sample using an antibody produced with a conjugate of a carrier protein and a phthalic acid ester derivative represented by the formula wherein R1 and R2 may be the same or different and are hydrogen, alkyl, cycloalkyl or phenylalkyl, with the proviso that both of R1 and R2 are not hydrogen; m is an integer from 1 to 5; and Y is amino or carboxyl.

Abstract: Polyamide conjugates comprising either (a) a xenoantigenic group; or (b) a biologically active group and a macromolecular, macro- or microscopic entity, bound to a polyamide backbone, processes for their preparation and the use of these conjugates in therapeutic compositions.

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: The present invention relates to compositions comprising novel reduced cortisol conjugates, methods for their preparation and use in immunoassays for cortisol. In another aspect, it relates to conjugates of reduced cortisol as immunogens or haptens for eliciting anti-cortisol or anti-reduced cortisol antibodies.

Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Abstract: The present invention is directed to novel tricyclic antidepressant drug derivatives synthesized for covalent attachment to proteins or polypeptide antigens for use in the preparation of antibodies or receptors to tricyclic antidepressant drugs and tricyclic antidepressant metabolites. The new derivatives are characterized by a saturated double bond on the amitriptyline portion of the molecule and are represented by the structure where R1 is a saturated or unsaturated, substituted or unsubstituted, straight or branched chain of 0-10 carbon or heteroatoms, X is a linker group consisting of 0-2 substituted or unsubstituted aromatic rings, and Y is an activated ester or NH—Z, where Z is a poly(amino acid).

Abstract: Hapten-carrier conjugates capable of eliciting anti-hapten antibodies in vivo by administering, in a therapeutic composition, are disclosed. Methods of preparing said conjugates and therapeutic compositions are also disclosed. Where the hapten is a drug of abuse, a therapeutic composition containing the hapten-carrier conjugate is particularly useful in the treatment of drug addiction, more particularly, cocaine addiction. Passive immunization using antibodies raised against conjugates of the instant invention is also disclosed. The therapeutic composition is suitable for co-therapy with other conventional drugs.

Abstract: This application relates to long-wavelength acridinium compounds having electron-donating groups, which may either be: (a) Part of an extended conjugation system attached by appropriate functional groups to the acridinium nucleus, with coplanarity of the attached functional group and the acridone moiety during light emission (geometry requirement), said functional group consisting of at least one aromatic ring and one electron-donating atom or group with an extra pair of electrons which can readily delocalize into the extended &pgr; system to which the heteroatom is directly attached or built into, and establish stable extended resonance with the electron-withdrawing carbonyl moiety of the light emitting acridone.

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: There can be provided a fungal antigen which is an insoluble fraction obtainable from fungal cells of which cell wall has been substantially removed or at least partially removed; a process for producing the same; a nucleic acid encoding the fungal antigen; a biologic product containing the fungal antigen; a method of stimulating immunological responses by using the biologic product; a method of suppressing allergic reaction to fungi in a vertebrate; and a method for diagnosing a disease caused by fungi in a vertebrate.

Abstract: Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin or a derivative thereof, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides monoclonal antibodies specific for rapamycin or a ring opened derivative of rapamycin.

Abstract: A method of modifying protein solubility employs polyionic polymers. These facilitate the solubilization, formulation, purification and refolding of proteins especially incorrectly folded proteins and aggregated proteins. Compositions are described that are suitable for formulating TFPI. The compositions allow preparation of pharmaceutically acceptable compositions of TFPI at concentrations above 0.2 mg/mL and above 10 mg/mL.

Abstract: A protein having a labeling compound attached to its C-terminal, in which the compound comprises a label portion comprising a label substance and an acceptor portion comprising a compound having an ability of binding to a C-terminal of a synthesized protein when protein synthesis is carried out in a cell-free protein synthesis system or in a living cell is provided. Also, a method for producing the protein comprising the step of performing synthesis of a protein in a cell-free protein synthesis system or in a living cell in the presence of a labeling compound comprising a label portion comprising a label substance and an acceptor portion comprising a compound having an ability of binding to a C-terminal of a synthesized protein when protein synthesis is carried out in the cell-free protein synthesis system or in the living cell, the labeling compound being present at a concentration effective for the labeling compound to bind to the C-terminal of the synthesized protein is provided.

Abstract: The invention provides a drug-oligomer conjugate having the following general formula: wherein D is a therapeutic drug moiety; H and H′ are each a hydrophilic moiety, independently selected from the group consisting of straight or branched PEG polymers having from 2 to 130 PEG subunits, and sugars; L is a lipophilic moiety selected from the group consisting of alkyl groups having 2-26 carbon atoms, cholesterol, adamantane and fatty acids; o is a number from 1 to the maximum number of covalent bonding sites on H; m+n+p together have a value of at least one and not exceeding the total number of covalent bonding sites on D for the —H′, —L and —H—L substituents; the H—L bond(s) are hydrolyzable and the D—L′ bond(s), when present, are hydrolyzable; the conjugate being further characterized by one of the following: (i) m is 0 and p is at least 1; (ii) n is 0 and p is at least 1; (iii) m and n are each 0 and p is at least 1; (iv) p is

Abstract: The present invention provides a dye-labeled protein conjugate in which a protein conjugate is labeled with a large number of dye molecules. In the dye-labeled protein conjugate, a protein conjugate that includes a protein and an antibody bound thereto via a disulfide bond is labeled with a cyanine dye represented by the formula (1) or the formula (2) given below: where R1 and R2 denote hydrogen or an alkyl group, X denotes a halogen, M denotes hydrogen or an alkali metal, and n represents an integer in a range of 1 to 4.

Abstract: A high-sensitive indirect polymerized and labelled antibody is disclosed. The antibody facilitates detection of a low concentration of antigen as an analyte in a sample solution. The indirect polymerized and labelled antibody of the present invention is prepared by polymerizing an antibody using a multi-functional reagent, binding the polymerized antibody with a protein via a disulfide bond of the antibody to form a polymerized antibody conjugate, and labelling the conjugate with a cyanine dye represented by the following formula: where R1 and R2 represent hydrogen or an alkyl group, X represents a halogen, M represents hydrogen or an alkali metal, and n represents an integer of 1 to 4.

Abstract: A method for producing a conjugate vaccine includes mixing a uronium salt reagent with a first moiety (e.g., a polysaccharide). According to the invention, the uronium salt reagent has a chemical structure corresponding to formula I: wherein R1 is defined as wherein R6 represents the carbon, hydrogen, and optionally one or more heteroatoms which, together with the nitrogen atom to which they are attached, constitute a 5 to 10 membered heterocyclic ring, which may be substituted or unsubstituted. R2, R3, R4, and R5, each independently represents a hydrogen atom, a substituted or unsubstituted alkyl having 1 to 6 carbon atoms, a substituted or unsubstituted alkenyl having 2 to 6 carbon atoms, or an alkynyl having 2 to 6 carbon atoms. Alternatively, R2 and R3, when taken together, can represent the carbon, hydrogen, sulfur, nitrogen, or oxygen atoms necessary to complete a 5 to 7 membered heterocyclic ring with the nitrogen atom to which they are attached.

Abstract: The present invention provides a dye-labeled protein conjugate in which a protein conjugate is labeled with a large number of dye molecules. In the dye-labeled protein conjugate, a protein conjugate that includes a protein and an antibody bound thereto via a disulfide bond is labeled with a cyanine dye represented by the formula (1) given below. where R1 and R2 denote hydrogen or an alkyl group, X denotes a halogen, M denotes hydrogen or an alkali metal, and n represents an integer in a rage of 1 to 4.

Abstract: The invention concerns a complex comprising at least a lipid and at least a therapeutically active substance useful for transferring said substance into a target cell, characterised in that said lipid is of formula (I): in which: n1, n2, identical or different are whole numbers between 0 and 1; R1, R2, identical or different are: a) selected among the group consisting of a hydrogen atom and alkyl radicals with 1 to 6 carbon atoms optionally substituted, independently of one another, by a hydroxyl radical; or b) in one particular case for which n1=n2=1, R1 and R2 can form together a divalent alkylene chain of 2 to 3 carbon atoms (C2-C3); R3, R4, identical or different are alkyl radicals of 1 to 6 carbon atoms or can together form a divalent alkylene chain of 2 to 3 carbon atoms (C2-C3); m, p, identical or different are whole numbers between 1 and 10; R5, R6, identical or different are selected in the group consisting of radicals of formula: 1) R7 C(═O)—X— in which: X=NH, O

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: The present invention provides an imidazolinone hapten having the structural formula 1

Abstract: Fluorescent monomethine cyanine complexes rigidized a two-carbon alkyl group between the nitrogen's of the cyanine's heterocycles are provided and having the structure wherein R1 through R7 represent various selected groups or ring structures that may be chosen to provide desired solubility, reactive, or spectral properties.