Abstract: The invention provides a process for preparing a conjugate of a S. aureus type 5 or type 8 capsular polysaccharide and a carrier molecule, comprising the steps of: (a) depolymerizing the capsular polysaccharide, to give a polysaccharide fragment; (b) oxidizing the fragment in order to introduce an aldehyde group into at least one saccharide residue in the fragment, to give an oxidized saccharide residue; and (c) coupling the oxidized saccharide residue to a carrier molecule via the aldehyde group, thereby giving the conjugate. The coupling in step (c) may be direct, or may be via a linker molecule. The invention also provides a conjugate obtained or obtainable by this process.

Abstract: The present application discloses a method for making an immunogenic composition comprising an improved way of conducting saccharide-protein conjugation reactions using carbodiimide condensation chemistry. Depending on the nature of the saccharide or protein carrier involved, the quality of the conjugate may be improved by adding one of the reaction components slowly to the reaction mixture. In addition, the conjugate is mixed with a staphylococcal antigen. Immunogenic compositions are further provided comprising the saccharide-protein conjugates made by the methods disclosed.

Abstract: Nucleoside analogues comprising a citrate group can be used to obtain immunogens designed to produce antibodies having an affinity for triphosphorylated nucleosides. Such antibodies are useful for implementing sensitive immunologic assays for triphosphorylated nucleoside derivatives.

Abstract: Novel conjugates and immunogens derived from imatinib and monoclonal antibodies generated by these immunogens are useful in immunoassays for the quantification and monitoring of imatinib or its pharmacologically active salts in biological fluids.

Abstract: Novel conjugates of doxorubicin and novel doxorubicin immunogens derived from the 13 and 14 positions of doxorubicin and antibodies generated by these doxorubicin linked immunogens all of which are useful in immunoassays for the quantification and monitoring of doxorubicin in biological fluids.

Abstract: The present invention relates to the identification of antigenic and immunogenic peptide-based mimicry of mannose-containing cell-wall compounds characterizing mycobacterial infectious agents, such as Mycobacterium tuberculosis. Amino acid molecules which are mimotopes of mannosylated lipoglycans, such as lipoarabinomannan (ManLAM), including at least one of the following characteristics: (a) being capable of binding to ManLAM binding antibodies; (b) being capable of eliciting production of ManLAM binding antibodies, are provided. Also diagnostic methods for diagnosing mycobacterial infections and methods of vaccinating subjects against such infections. The diagnostic and vaccination methods employ the provided amino acid molecules. Accordingly, a diagnostic kit and a vaccine for executing the aforementioned methods are provided.

Abstract: The invention relates to polypeptide carrier proteins that comprise at least five CD4+ T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines are particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.

Abstract: A method of making a derivatized aminoglycoside includes reacting an aminoglycoside with at least 2 equivalents of a divalent metal ion in an aprotic solvent to complex two neighboring amino group and hydroxyl group pairs; reacting the non-complexed amino groups with a protecting reagent to provide protecting groups; removing the divalent metal ion to provide two unprotected amino groups; reacting one of the unprotected amino groups with a reactive substance containing an linker, a carrier, or a label; and removing the protecting groups. This method can be used to produce novel compounds and regents.

Abstract: A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.

Abstract: A solid-phase immunoassay for 6-keto-Prostaglandin F1?, the stable hydrolysis product of prostacyclin (Prostaglandin I2) is disclosed. Prostacyclin, a potent vasodilator with anti-platelet and anti-proliferative properties is an effective treatment for primary pulmonary hypertension and pulmonary arterial hypertension associated with scleroderma and scleroderma-like syndrome. Levels of 6-keto-Prostaglandin F1? can be directly correlated with levels of prostacyclin. Therefore, 6-keto-Prostaglandin F1? has become the indicator of choice to measure prostacyclin levels. The single step immunoassay for 6-keto-Prostaglandin F1? uses the bioluminescent protein, aequorin as a label. Analyte-label conjugates were constructed by linking the carboxyl group of 6-keto-Prostaglandin F1? and lysine residues of aequorin by chemical conjugation methods. The binding properties of 6-keto-Prostaglandin F1? towards its antibody and the bioluminescent properties of aequorin are retained in the conjugate.

Abstract: Novel conjugates of doxorubicin and novel doxorubicin immunogens derived from the 13 and 14 positions of doxorubicin and antibodies generated by these doxorubicin linked immunogens all of which are useful in immunoassays for the quantification and monitoring of doxorubicin in biological fluids.

Abstract: Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Abstract: Analogs of 6-monoacetyl morphine (6-MAM) are described. These include analogs derivatized at either the C-3 position, the C-6 position, or the nor position of the molecule. These analogs allow for elaboration with linkers terminated by a functional group such as an activated ester, the functional groups being useful for attaching the molecule to other entities such as proteins, polysaccharides, and reporter groups.

Abstract: Novel conjugates of busulfan and novel busulfan immunogens derived from ?-substituted derivatives of busulfan and antibodies generated by these busulfan linked immunogens are useful in immunoassays for the quantification and monitoring of busulfan in biological fluids.

Abstract: The invention relates to an adjuvant product which is intended to improve the activity of a molecule when administered to a host, characterized in that it comprises at least one part of the P40 protein of Klebsiella pneumoniae or a protein having at least 80% homology with the P40 protein of Klebsiella pneumoniae. The invention also relates to nucleotide sequences which encode these peptides or proteins and to the use of these sequences as a medicament. More particularly, such DNA sequences can be used in compositions which are intended for immunization by the intramuscular or intradermal route.

Abstract: The invention provides haptens, immunogens comprising such haptens coupled to an antigenicity-conferring carrier material, conjugates comprising such haptens bonded to a labelling agent as well as, antibodies raised against such immunogens and capable of binding with ketamine and its primary metabolite, norketamine.

Abstract: The present invention provides ligand-detection reagents, ligand analogs and methods for determining the presence of a ligand in a sample. The ligand-detection reagent comprises a ligand-binding antibody and a ligand analog to form an antibody-ligand analog complex wherein the ligand analog is covalently bonded to a reporter molecule. This complex may additionally comprise a labeling protein non-covalently bonded to the antibody to form a ternary complex wherein the labeling protein comprises a monovalent antibody fragment or a non-antibody protein that is covalently bonded to a label moiety. The reporter molecule is either quenched by the ligand-binding antibody or by the label moiety of the labeling protein, depending on the reporter molecule and the ligand-binding antibody, wherein the amount of quenching is directly related to the amount of ligand present in the sample.

Abstract: Analogs of 6-monoacetyl morphine (6-MAM) are described. These include analogs derivatized at either the C-3 position, the C-6 position, or the nor position of the molecule. These analogs allow for elaboration with linkers terminated by a functional group such as an activated ester, the functional groups being useful for attaching the molecule to other entities such as proteins, polysaccharides, and reporter groups.

Abstract: A method of making a derivatized aminoglycoside includes reacting an aminoglycoside with at least 2 equivalents of a divalent metal ion in an aprotic solvent to complex two neighboring amino group and hydroxyl group pairs; reacting the non-complexed amino groups with a protecting reagent to provide protecting groups; removing the divalent metal ion to provide two unprotected amino groups; reacting one of the unprotected amino groups with a reactive substance containing an linker, a carrier, or a label; and removing the protecting groups. This method can be used to produce novel compounds and reagents.

Abstract: Immunoassays for the detection of everolimus are provided. Compounds for producing antibodies for everolimus, as well as antibodies produced therefrom, are also provided.

Abstract: A process for detecting the forms of the prion pathogens responsible for subacute, transmissible, spongiform encephalopathies, including a macrocyclic adjuvant ligand (AML), free or bound to a support, that is added to a biological sample capable of containing PrPsc, the resulting suspension then being reacted with an anti-PrPsc antibody, and the presence of PrP is then detected.

Abstract: The invention provides a hapten, an immunogen comprising the hapten coupled to an antigenicity-conferring carrier material, a conjugate comprising the hapten coupled to a labelling agent, as well as, antibodies raised against the aforementioned immunogen and capable of binding with MDMA.

Abstract: Compounds are disclosed comprising a moiety, such as a poly(amino acid), a non-poly(amino acid) label moiety, or a non-poly(amino acid) immunogenic carrier, linked to a sirolimus compound at position 26 or at position 32. Such sirolimus compounds comprising an immunogenic carrier can be employed to raise both polyclonal and monoclonal antibodies to the sirolimus compound. Polyclonal antibodies are also disclosed, which are raised against a compound wherein a moiety, such as a poly(amino acid), a non-poly(amino acid) label moiety, or a non-poly(amino acid) immunogenic carrier, is linked to a sirolimus compound at position 32. The above antibodies and sirolimus compounds comprising a label can be used in assays for the detection of sirolimus compounds.

Abstract: Outer-membrane vesicles, Class 1 outer membrane proteins of Neisseria meningitidis, fragments or oligopeptides containing epitopes of the Class I OMP can be used to immunize against meningococcal disease.

Abstract: A monoclonal antibody, and a cell line capable of producing the same, has been produced with the ability to detect the primary metabolites generated from the pyrolysis of smokeable, or “crack”, cocaine. This monoclonal antibody, while being highly specific for anhydroecgonine methyl ester (AEME) and ecgonidine (ECD), does not cross-react at a significant level with the primary cocaine metabolites of powdered or injected cocaine. Also, crack cocaine conjugates capable of evoking an immune response in animals have been produced.

Abstract: Recombinant hybrid streptococcal M protein antigens are provided which elicit protective antibodies against Group A streptococci and prevent rheumatic fever. Recombinant hybrid genes which encode the antigen are provided. Vaccine compositions and methods of administering the compositions are provided to elicit immunity against Group A streptococci.

Abstract: The present invention generally relates to compositions and methods for preventing and treating human diseases including, but not limited to, pathogens such as bacteria, yeast, parasites, fungus, viruses, and cancer. More specifically, embodiments described herein concern the manufacture and use of ligand/receptor specificity exchangers, which redirect existing antibodies in a subject to receptors present on pathogens.

Abstract: Multivalent immunogenic molecules comprise a carrier molecule containing at least one functional T-cell epitope and multiple different carbohydrate fragments each linker to the carrier molecule and each containing at least one functional B-cell epitope. The carrier molecule inputs enhanced immunogenicity to the multiple carbohydrate fragments. The carbohydrate fragments may be capsular oligosaccharide fragments from Streptococcus pneumoniae, which may be serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F or 23F, or Neisseria meningitidis, which may be serotype A, B, C, W-135 or Y. Such oligosaccharide fragments may be sized from 2 to 5 kDa. Alternatively, the carbohydrate fragments may be fragments of carbohydrate-based tumor antigens, such as Globo H, LeY or STn. The multivalent molecules may be produced by random conjugation or site-directed conjugation of the carbohydrate fragments to the carrier molecule.

Abstract: The present invention provides an immunogenic conjugate comprising biologically deacylated gram-negative bacterial moieties linked to D. discoideum proteinase 1, as well as novel subunits thereof, and methods of making and using the conjugates in vaccines to treat sepsis and other infectious complications.

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: This invention provides materials and methods for the site specific attachment of virtually any moiety to a layered silicate surface. The methods involve covalently attaching the moiety to an arginine tag; and contacting the arginine tag with the layered silicate (e.g., mica) surface.

Abstract: A monoclonal antibody which reacts strongly with uracil and thymine but scarcely with N-carbamyl-?-alanine; a hybridoma producing this monoclonal antibody; a method of immunochemically assaying uracil or thymine characterized by using the above-described monoclonal antibody; and diagnostics for DPD deficiency containing the above monoclonal antibody. Because of high sensitivity and specific reaction with uracil and thymine, the above-described monoclonal antibody enables convenient, quick, and selective assaying of uracil and thymine in a sample. The antibody is useful in screening patients with DPD deficient cancer with contraindication to the administration of pyrimidine fluoride-based antitumor agents.

Abstract: Biotinylated pharmacologically active agents and complexes containing same are disclosed. In particular, biotinylated-chemokines are described. The complexes further include an anti-biotin antibody that selectively binds to biotin. The complex can be dissociated by contact with free biotin. The complexes are particularly useful for enhancing an immune response to tumor cells and virus-infected cells, in vivo or in vitro.

Abstract: The invention relates to polyepitope carrier proteins that comprise at least five CD4+ T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are use useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines arm particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.

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: The invention relates to an adjuvant product which is intended to improve the activity of a molecule when administered to a host, characterized in that it comprises at least one part of the P40 protein of Klebsiella pneumoniae or a protein having at least 80% homology with the P40 protein of Klebsiella pneumoniae. The invention also relates to nucleotide sequences which encode these peptides or proteins and to the use of these sequences as a medicament. More particularly, such DNA sequences can be used in compositions which are intended for immunization by the intramuscular or intradermal route.

Abstract: The invention provides a novel human Mab Fab, cloned by phage display, and its use in diagnostic and therapeutic methods. In particular the invention provides a method for analyzing the OxLDL components of atherosclerotic plaques in vivo and a means to determine their relative pathology. As the method is based on a human Fab rather than a mouse Mab, the progress or regression of the disease may be monitored over time. The antibody may also be used for the analysis of surgical or serum samples ex vivo for the presence of OxLDL. The antibody may also be used to target therapeutic agents to the site of atherosclerotic plaques or may have use as a therapeutic agent itself.

Abstract: The invention relates in part to novel methods of rapidly determining the ratio of biological molecules. The invention also relates in part to a kit for rapidly determining the ratio of biological molecules.

Abstract: The present invention generally relates to compositions and methods for preventing and treating human diseases including, but not limited to, pathogens such as bacteria, yeast, parasites, fungus, viruses, and cancer. More specifically, embodiments described herein concern the manufacture and use of ligand/receptor specificity exchangers, which redirect existing antibodies in a subject to receptors present on pathogens.

Abstract: A method of identifying a ligand for a second binding site (5) on a biological substrate (1) is disclosed. The method comprises determining the effect of a candidate compound (9) on the binding of a probe compound (2) which binds to a first binding site (3) on the biological substrate in the presence of a first multibinding compound (4) which binds to the first (3) and second (5) binding sites on the biological substrate (1).

Abstract: Multivalent immunogenic molecules comprise a carrier molecule containing at least one functional T-cell epitope and multiple different carbonhydrate fragments each linked to the carrier molecule and each containing at least one functional B-cell epitope. The carrier molecule inparts enhanced immunogenicity to the multiple carbohydrate fragments. The carbohydrate fragments may be capsular oligosaccharide fragments from Streptococcus pneumoniae which may be serotypes (1, 4, 5, 6B, 9V, 14, 18C, 19F or 23F), or Neisseria meningitidis, which may be serotype (A, B, C) W-135 or Y. Such oligosaccharide fragments may be sized from about 2 to about 5 kDa. Alternatively, the carbohydrate fragments may be fragments of carbohydrate-based tumor antigens, such as Globo H, LeY or STn. The multivalent molecules may be produced by random conjugation or site-directed conjugation of the carbohydrate fragments to the carrier molecule.

Abstract: Novel bactericidal antibodies against Neisseria meningitidis serogroup B (“MenB”) are disclosed. The antibodies either do not cross-react or minimally cross-react with host tissue polysialic acid and hence pose minimal risk of autoimmune activity. The antibodies are used to identify molecular mimetics of unique epitopes found on MenB or E. coli K1. Examples of such peptide mimetics are described that elicit serum antibody capable of activating complement-mediated bacteriolysis of MenB. Vaccine compositions containing such mimetics can be used to prevent MenB or E. coli K1 disease without the risk of evoking autoantibody.

Abstract: Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Abstract: This invention provides a hybridoma produced by the fusion of a mouse antibody-producing cell and a mouse myeloma which is designated 1-10F-8A and deposited with the ATCC under Accession Number PTA-279, said hybridoma producing a monoclonal antibody which binds to fullerene C60. This invention provides a mouse monoclonal antibody specific for a fullerene-C60 and produced by the mouse monoclonal antibody-producing hybridoma designated 1-10F-8A. The invention provides the amino acid and encoding nucleic acid sequences of the heavy and light chains of the 1-10F-8A monoclonal antibody. This invention also provides methods of determining a serum concentration of a fullerene in a subject and of purifying a fullerene from a sample.

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: A C-terminal pilin peptide vaccine for immunizing or treating a patient for infection by a Pseudomonas aeruginosa (PA) infection is disclosed. The peptide comprises the peptide identified as SEQ ID NOS. 3-6; and a carrier protein conjugated to the peptide. Also disclosed is a pilin peptide C-terminal PA pilin peptide having the amino acid sequence identified as SEQ ID NO:3, and analogs thereof having one of residues T, K, or A at position 130, D, T, or N at position 132, Q, A, or V at position 133, E, P, N, or A at position 135, Q, M, or K at position 136, and I, T, L, or R at position 138, excluding SEQ ID NOS: 1, 2, 9, 10, and 11, and the ability to cross-react with antibodies against the corresponding C-terminal peptides from PA strains PAK and PAO.

Abstract: The invention concerns a method for the determination of an analyte in which rheumatoid factors or rheumatoid-factor-like substances are added as an interference reducing reagent to reduce of avoid a hook effect. The invention in addition concerns suitable reagent kits for carrying out the method.

Abstract: The present invention relates to methods for the production of a stable troponin preparation and its use as a calibrator and/or control in immunoassays. The formulation is prepared from mammalian, preferably bovine, heart tissue which provides a calibrator/control composition which remains stable over a long period of time.

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 substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with an isoquinoline derivative which converts bradykinin agonists into bradykinin antagonists. The invention further includes the novel 7-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.