Abstract: The present invention relates to the general field of recombinant protein expression, purification of recombinant proteins, diagnosis of HCV infection, prophylactic treatment against HCV infection and to the prognosing/monitoring of the clinical efficiency of treatment of an individual with chronic hepatitis, or the prognosing/monitoring of the natural disease. In particular, the present invention relates to the use of yeast, i.e. Hansenula or Saccharomyces glycosylation minus strains, for the efficient expression of HCV envelope proteins that are core-glycosylated, purification methods for these proteins, and the use in various applications, such as the use in diagnosis, prophylaxis or therapy of HCV envelope proteins purified according to the present invention.

Abstract: Novel haptens, which can be conjugated to form immunogens, are of formula I, II or III wherein R is a divalent alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, and X is a functional group.

Abstract: The invention relates to a synthetic, biologically active molecule for fixing an active ingredient to the virus protein 1 (VP1) of the polyoma virus. According to the invention, an amino acid sequence A1 which is derived from the C-terminal end of virus protein 2 (VP2) or 3 (VP3) of the polyoma virus is bonded to an active ingredient at one of its ends.

Abstract: A heparin-binding protein functionalized by covalently bonding thereto a sugar chain, a method for producing the protein and a pharmaceutical composition containing the protein as an active ingredient, as well as a method for functionalizing a natural protein having no sugar chain by covalently bonding thereto a sugar chain.

Abstract: The invention provides compositions and processes for the production of ordered and repetitive antigen or antigenic determinant arrays. The compositions of the invention are useful for the production of vaccines for the prevention of infectious diseases, the treatment of allergies and the treatment of cancers. Various embodiments of the invention provide for a core particle that is coated with any desired antigen in a highly ordered and repetitive fashion as the result of specific interactions.

Abstract: The invention provides a hapten comprising a 6-[D-?-aminoacetamido] penicillin derivative crosslinked at the ?-amino group with a substituted or unsubstituted phenyldicarbaldehyde. In addition, the invention provides an immunogen comprising the aforementioned 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 an intact ?-lactam ring.

Abstract: The present invention provides compositions comprising a conjugate of a hapten with a carrier in an ordered and repetitive array, and methods of making such compositions. The conjugates and compositions of the invention may comprise a variety of haptens, including hormones, toxins and drugs, especially drugs of addiction such as nicotine. Compositions and conjugates of the invention are useful for inducing immune responses against haptens, which can use useful in a variety of therapeutic, prophylactic and diagnostic regimens. In certain embodiments, immune responses generated using the conjugates, compositions and methods of the present invention are useful to prevent or treat addiction to drugs of abuse and the resultant diseases associated with drug addiction.

Abstract: A novel compound comprising an immunologically invisible polyethylene glycol copolymer is used to carry one or more immunologically reactive substances. The novel compounds may be used as part of kits for immunological assays.

Abstract: This invention relates to conjugates of the O-specific polysaccharide of E. coli O157 with a carrier, and compositions thereof, and to methods of using of these conjugates and/or compositions thereof for eliciting an immunogenic response in mammals, including responses which provide protection against, or reduce the severity of, bacterial infections. More particularly it relates to the use of polysaccharides containing the tetrasaccharide repeat unit: (?3)-?-D-GalpNAc-(1?2)-?-D-PerpNAc-(1?3)-?-L-Fucp-(1?4)-?-D-Glcp-(1?), and conjugates thereof, to induce serum antibodies having bactericidal (killing) activity against hemolytic-uremic syndrome (HUS) causing E. coli, in particular E. coli O157. The conjugates, and compositions thereof, are useful as vaccines to induce serum antibodies which have bactericidal or bacteriostatic activity against against E. coli, in particular E. coli O157, and are useful to prevent and/or treat illnesses caused by E. coli O157.

Abstract: The invention relates to adjuvants that contain a lecithin, an oil and an amphiphilic surfactant and that are capable of forming a stable oil-in-water emulsion vaccine so as to minimize local reactions to the vaccine in the injected animal.

Abstract: The present invention provides novel clustered multi-antigenic constructs having the structure: 1

Abstract: The present invention relates to the construction of synthetic peptide immunogens to induce the production of anitbodies specific to a designated B epitope, usually a self molecule. The peptide immunogens are synthesized in branched forms with artificial Th epitopes conjugated, directly or through a spacer, to a B epitope in a specific orientation. The novel peptide immunogens are designed to elicit high level of antibodies for immunotherapy or immunomodulation of the body regulatory processes.

Abstract: The present invention provides hapten derivatives useful for the preparation of antigens, antibodies and reagents for use in immunoassays for the detection of LSD and 2-oxo-3-hydroxy LSD. In the present invention, the 2-oxy LSD nucleus is derivatized out of the indole nitrogen to form an aminoalkyl derivative. The resulting haptens can then be further modified at this functionalized position for linking to appropriate immunogenic or labeling groups to provide reagents for immunoassays having substantially equal specificity for both LSD and 2-oxo-3-hydroxy-LSD.

Abstract: A process for preparing a protein-polysaccharide conjugate includes reacting a protein with a polysaccharide to produce a mixture including a protein-polysaccharide conjugate and free protein. At least one unreacted reagent or low molecular weight component is removed from this mixture, without removing all of the free protein, to provide a purified mixture that contains the protein-polysaccharide conjugate and free protein. This purified mixture can be used as a conjugate vaccine, immunogen, or immunological reagent. Keeping the free protein in the purified mixture with the conjugate saves time and money in the conjugate production process. In another aspect of the invention, the purified mixture of the protein-polysaccharide conjugate and free protein is reacted with a hapten to produce a conjugate mixture including a hapten-protein conjugate and a hapten-protein-polysaccharide conjugate.

Abstract: A method of determining a binding capacity of a surface, the method including providing the surface containing a reactive moiety; providing a fluorophore including a fluorescent moiety adapted to emit a detectable signal; reacting the fluorophore with the reactive moiety to form a linking bond between the fluorophore and the reactive moiety; cleaving a cleavable bond to liberate the fluorescent moiety; and detecting the detectable signal to determine the binding capacity of the surface.

Abstract: The present invention provides novel methods for ligand discovery. The inventive methods rely on a process termed “tethering” where potential ligands are covalently bonded or “tethered” to a target and subsequently identified.

Abstract: The present invention relates to a novel chemical process for the covalent conjugation of disulphide bridge cyclised peptides to immunogenic carrier molecules by thio-ether linkages to form vaccine immunogens. In particular, the novel chemistry involves reacting a thiolated carrier with a cyclic peptide containing a disulphide bridge, which cylcic peptide (herein a disulphide bridge cyclised peptide) has attached to it, usually via a linker, a reactive group capable for forming thio-ether bonds with the carrier. The invention further related to activated peptide intermediates of the process, medicaments produced by the process, pharmaceutical compositions containing the medicaments, and the use of the pharmaceutical compositions in medicine. The process of the present invention is particularly useful for the preparation of highly pure immunogens for vaccines, comprising disulphide bridge cyclised peptides.

Abstract: The invention concerns fluorescein isothiocyanate-sinistrin (FITC-sinistrin), a method for its production, its use as a marker substance in a diagnostic agent and a corresponding diagnostic agent.

Abstract: The present invention provides biologically active linear polypeptides that possess a plurality of biologically active groups, methods employing such peptides to target molecules to cells, and methods employing such peptides for inhibiting the binding of cells to each other.

Abstract: A homogeneous polyoxime composition is provided, in which the polyoxime molecules present comprise a first organic baseplate molecule, which is a polypeptide, wherein the baseplate molecule is linked to at least two second organic molecules, which may be the same or different from one another. In the compositions, the linkages between the baseplate and said organic molecules are oxime linkages formed by reaction of an orthogonal reactive group on each the organic molecules with a complementary orthogonal reactive group on the baseplate.

Abstract: Methods for incorporating a stable isotope into a protein or peptide fragment are disclosed. The methods include providing isolated isotope-labeled protein or peptide fragments and analyzing the isolated labeld fragments. In another aspect of the invention, methods for quantitatively comparing peptides in two protein or peptide fragment mixtures are provided. In these methods, protein levels are measured using stable-isotope coded protein or peptide fragments.

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: 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 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: 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: The invention provides a hapten comprising a 6-[D-&agr;-aminoacetamido]penicillin derivative crosslinked at the &agr;-amino group with a substituted or unsubstituted phenyldicarbaldehyde. In addition, the invention provides an immunogen comprising the aforementioned 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 an intact &bgr;-lactam ring.

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

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: A method of producing a diagnostic or therapeutic conjugate of a protein, polypeptide or peptide containing at least one disulfide bond which is necessary to maintain its biological activity, and bearing at least one thiol-containing moiety linked thereto through a hydrazone or hydrazine linkage, is effected by contacting said protein, polypeptide or peptide with a thiol-reactive diagnostic or therapeutic agent, either preformed or generated in situ, to form a stable diagnostic or therapeutic conjugate of the protein, polypeptide or peptide without substantial cleavage of the disulfide bond. Diagnostic and therapeutic conjugates produced using the foregoing method, as well as kits for carrying out the method are provided.

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: The invention is directed to improved immunopotentiating systems for preparation of immunogenic materials. More particularly, the invention is directed to immunogenic compositions containing a protein, polypeptide, or peptide, a hydrophobic anchor, and a proteosome. The immunogenic compositions are suitable for use as therapeutic agents and vaccines.

Abstract: The present invention relates to a chemically modified mutant protein including a cysteine residue substituted for a residue other than cysteine in a precursor protein, the substituted cysteine residue being subsequently modified by reacting the cysteine residue with a glycosylated thiosulfonate. Also, a method of producing the chemically modified mutant protein is provided. The present invention also relates to a glycosylated methanethiosulfonate. Another aspect of the present invention is a method of modifying the functional characteristics of a protein including providing a protein and reacting the protein with a glycosylated methanethiosulfonate reagent under conditions effective to produce a glycoprotein with altered functional characteristics as compared to the protein. In addition, the present invention relates to methods of determining the structure-function relationships of chemically modified mutant proteins.

Abstract: In one aspect, the present invention provides a method for incorporating a stable isotope into a protein or peptide fragment. In the method, a modified protein or peptide fragment is reacted with an agent that includes one or more stable isotopes to provide an isotope-labeled protein or peptide fragment. In another aspect of the invention, methods for measuring protein levels in two protein or peptide fragment mixtures are provided. In these methods, protein levels are measured using stable isotope-coded protein or peptide fragments.

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: 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: The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis.

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: Streptavidin-metallothionein chimeric proteins with biological recognition specificity in which the streptavidin moiety provides high affinity biotin binding and the metallothionein moiety provides a high affinity metal binding. The binding affinity of the streptavidin-metallothionein chimeric protein both for biotin and heavy metal ions allows specific incorporation into, conjugation with, or labelling of any biological material containing biotin with various heavy metal ions.

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: There is disclosed a stable, virus-safe, pharmaceutical preparation comprising thiol-group-containing proteins which are heat-treated and processed such that at least 40% of the thiol groups are capable of being nitrosated, a method of preparing such preparations as well as the use of these preparations.

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: The invention relates to a method for forming a mixed disulfide of recombinant proteins, by solubilizing with a denaturing agent in the presence of a disulphide component, and then adding a disulphide component plus a denaturing agent, at a concentration sufficient to form a mixed disulfide.

Abstract: In our research, 3-phenyl-1,2,4-dithiazoline-5-one is found to be a potential sulfur-transfer reagent. The efficiency and optimization of this new sulfur-transfer reagent was investigated by solid-phase syntheses of dinucleotide phosphorothioate and 25 mer oligonucleotide phosphorothioates at 1 &mgr;mol and 200 &mgr;mol scales. The results show that 3-phenyl-1,2,4-dithiazoline-5-one is a highly efficient sulfurizing reagent, and greater than 99.8% sulfur transfer efficiency can be achieved. In contrast to EDITH or Beaucage reagent, this novel sulfur-transfer reagent is highly stable in storage and in solution, highly soluble in CH3CN solvent, and can be synthesized at a low cost because of the single step reaction. Due to these advantages, 3-phenyl-1,2,4-dithiazoline-5-one can be considered as a better alternative to EDITH or Beaucage reagent, especially in large-scale preparation of oligonucleotide phosphorothioates.

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 process produces a water-soluble, naturally folded eukaryotic polypeptide containing two or several cysteines linked by disulfide bridges. This process involves culturing prokaryotic cells, a) in which the prokaryotic cells contain an expression vector which encodes the polypeptide which contains a prokaryotic signal sequence at the N-terminus, b) under conditions under which the polypeptide is secreted into the periplasm or the medium, c) cleaving the signal sequence and isolating the polypeptide from the periplasm or the medium. In this process, the culturing is carried out in the presence of arginine or a compound of the formula I R2—CO—NR1 (I) in which R and R1 represent hydrogen or a saturated or unsaturated branched or unbranched C1-C4 alkyl chain and R2 represents hydrogen, NHR1 or a saturated or unsaturated branched or unbranched C1-C3 alkyl chain, is suitable for the recombinant production of polypeptides in prokaryotes in a high yield.

Abstract: A method for peptide synthesis is disclosed that requires neither protecting groups nor activation of the C-&agr; carboxyl groups. The method comprises ligating a first molecule to a second molecule by promoting the orthogonal coupling of the molecules to each other. In an aspect of this method, an acyl-type reaction occurs between the molecules. The method contemplates the joining of molecules of variant size to each other, as well as the coupling of multiple identical molecules. The invention also covers the ligation of unprotected peptide, proteins or nonpeptide segments to prepare therapeutic products and synthetic vaccines with linear, circularized, or branched backbone structures, as well as the site-specific modification of peptides or proteins by lipidation and pegylation.

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.