Abstract: The present invention provides dioxetane-based chemiluminescence probes, more specifically fluorophore-tethered dioxetane-based chemiluminescence probes and compositions thereof. The chemiluminescence probes disclosed are useful for both diagnostics and in vivo imaging.

Abstract: A dual targeting drug carrier is provided. The dual targeting drug carrier comprises a first targeting molecule and a second targeting molecule, wherein the targeting molecule comprises peptide, protein or antibody. The targeting molecule can bind to specific receptors, proteins, or glycoproteins to recognize the specific tumor cells, tissues, or organs. The dual targeting drug carriers are further conjugated with imaging agents, radioactive molecules (radiopharmaceuticals, isotopes, or chemotherapeutic drugs) or nanoparticles to form a conjugate.

Abstract: The present invention provides for methods and materials for diagnosing and treating neuromyelitis optica (NMO).

Abstract: New chemiluminescent compounds, stable in aqueous buffers, for use in biological assaying include acridane-based compounds and 1,2-dioxetanes. Among the new acridane-based compounds are water-soluble acridanes, enhancer coupled acridanes, bis and tris-acridanes as well as acridane-1,2-dioxetanes. Among the new 1,2-dioxetanes are electron deficient group-containing dioxetanes and tethered bis-1,2-dioxetanes. The 1,2-dioxetanes are useful as substrates for various enzymes. The acridanes can be admixed with an oxidizing agent. an aqueous buffer and, optionally, a stabilizer to form a substrate or reagent formulation useful for assaying, inter alia, HRP.

Abstract: The present invention generally relates to methods of functionalizing proteins, particularly antibodies, at oligosaccharide linkages, methods of humanizing antibodies by modifying glycosylation, as well as to novel antibodies linked to modified oligosaccharides. The invention further relates to kits that may be used to produce the antibodies of the invention.

Abstract: Novel withanolide chemical genetic probes identify the in vivo binding target of withaferin A, which is the intermediate filament type III protein vimentin. In addition, a withanolide-based small molecule screening method screens drug candidates that target intermediate filament type III proteins. The method includes introducing a tagged linker covalently bonded to the withanolide molecule to form a withanolide probe. Better or alternative small molecule compounds as potential drug candidates can be generated based on their likely affinity for the determined binding site in vimentin. The affinity labeled withanolide can also be used to find intermediate filament-associated proteins using chemical proteomics by extracting proteins from cells that were exposed to withanolide-biotin analog. The withanolide probes can be used to monitor expression of vimentin, in tumor samples or other diseased tissues.

Abstract: The present invention provides methods of treating a subject diagnosed with, or at risk for developing, pathogenic fibrosis, particularly pulmonary fibrosis. The method of the invention comprises administering to the subject a compound or composition which inhibits semaphorin (SEMA) 7A, SEMA 7A receptors, or downstream effectors. A SEMA 7A inhibitor comprises an antibody, a soluble SEMA 7A receptor, an siRNA, a ribozyme, an antisense, an aptamer, a peptidomimetic, a small molecule, a soluble receptor, or any combinations thereof.

Abstract: The present invention relates to compositions and methods for prevention and treatment of diseases and conditions, particularly ocular diseases and conditions, characterized by aberrant fibrogenesis or scarring, inflammation, and/or aberrant neovascularization or angiogenesis. The compositions and methods of the invention utilize immune-derived moieties that are specifically reactive against the bioactive lipid, sphingosine-1-phosphate, and its variants, which moieties are capable of decreasing the effective concentration of bioactive lipid being targeted. In one embodiment, the immune-derived moiety is a humanized monoclonal antibody that is reactive against sphingosine-1-phosphate.

Abstract: The methods of the disclosure provide fluorescence-based assays for calcineurin activity, especially in isolated T cells. The methods include the stimulation of the T cells with agents that specifically target the TCR with or without influencing co-stimulatory pathways. One TCR agonist is monoclonal antibodies specific for CD3, which more precisely distinguish the inducible activity of calcineurin than does an alternative method targeting the T cell receptor (CD3) combined with CD28 costimulation. This method more accurately distinguishes between the measured level of calcineurin activity of T cells from immunosuppressed transplant recipients and normal individuals, and thus has improved diagnostic accuracy with respect to the response of an individual to immunosuppressant therapy following an organ transplant.

Abstract: The present invention provides for methods and materials for diagnosing and treating neuromyelitis optica (NMO).

Abstract: This invention pertains to methods, mixtures, kits and/or compositions for the determination of analytes by mass analysis using unique labeling reagents or sets of unique labeling reagents. The labeling reagents can be isomeric or isobaric and can be used to produce mixtures suitable for multiplex analysis of the labeled analytes.

Abstract: Monoclonal antibodies, synthetic and biotechnological derivatives thereof (ScFv or others) are able to recognise the NGF high affinity receptor, TrkA, and act as NGF-antagonist molecules. Pharmacological compositions for therapy, gene therapy, diagnostics of neurological pathologies are also described. Transgenic animal models to study such pathologies are also described.

Abstract: Methods and reagents are disclosed for pretreating a sample suspected of containing a hydrophobic drug for conducting an assay method for detecting the hydrophobic drug. A combination is provided in a medium that includes the sample, a releasing agent for releasing the hydrophobic drug and the metabolites from endogenous binding moieties, and a selective solubility agent that provides for substantially equal solubility of the hydrophobic drug and the metabolites in the medium. The selective solubility agent includes a water miscible, non-volatile organic solvent and is present in the medium in a concentration sufficient to provide for substantially equal solubility of the hydrophobic drug and the metabolites in the medium. The medium, which may further include a hemolytic agent, is incubated under conditions for releasing the hydrophobic drug and the metabolites from endogenous binding moieties. The pretreated sample may be subjected to an assay for determining the hydrophobic drug.

Abstract: The invention relates to the use a BD16 and/or BB18 anti-CD100 antibody or of a chimeric or humanized or human form thereof, or a fragment thereof, for the therapy or diagnosis of a central nervous system disorder, more particularly a myelin disorder or a disease that affects oligodendrocytes, such as multiple sclerosis or HTLV-1 associated myelopathy or peripheral myelinating cells.

Abstract: Described is a method for identifying and quantifying of tumour-associated peptides, wherein first at least two different sources for obtaining the peptide are provided (tumourous and healthy tissue), and, separately of one another, the peptides from the different sources are chemically modified in an identical manner by using at least two different stable isotopes of the same element. Subsequently, the peptides are isolated by a chromatographic method, and the amino acid sequences of the peptides are determined, wherein the determination of the relative amount ratios of peptides having the identical sequence from different samples one to the other occurs by using a stable isotope in the chemical modification. Furthermore, the invention relates to a tumour-associated peptide having an amino acid sequence that is selected from the group consisting of SEQ-ID No.

Abstract: New chemiluminescent compounds, stable in aqueous buffers, for use in biological assaying include acridanebased compounds and (1,2)-dioxetanes. Among the new acridanebased compounds are water-soluble acridanes, enhancer coupled acridanes, bis and trisacridanes as well as acridane-(1,2)-dioxetanes. Among the new (1,2)-dioxetanes are electron deficient group-containing dioxetanes and tethered bis-1,2-dioxetanes. The (1,2)-dioxetanes are useful as substrates for various enzymes. The acridanes can be admixed with an oxidizing agent. An aqueous buffer and, optionally, a stabilizer to form a substrate or reagent formulation useful for assaying, inter alia, HRP.

Abstract: The present invention is directed to a novel method for quantifying antigen, such as the amount expressed on a cell. The method comprises formulating an equation of correlation between the amount expressed of expressed antigen and the intensity of fluorescence from fluorescent labelled antibody.

Abstract: Provided are compounds capable of covalently binding to a protein tyrosine phosphatase (PTP). The compounds comprise Formula A: Also provided are compositions comprising one of the above compounds covalently bound to a member of the PTP superfamily, methods of labeling a PTP using the compounds, methods of isolating a PTP from a mixture of proteins using the compounds, methods of evaluating whether a substance is an inhibitor of a PTP using the compounds, methods of evaluating the specificity of an inhibitor of a PTP using the compounds, methods of identifying a PTP involved in a disease in a mammal using the compounds, and methods of diagnosing a disease in a mammal using the compounds.

Abstract: Disclosed are improved methods and apparatus for radiolabeling, particularly methods and apparatus for large scale in-line radiolabeling of products, such as proteins and antibodies.

Abstract: A method of imaging apoptosis in vivo, using radiolabeled annexin, is described.

Abstract: The invention concerns a peptide having the biological activity of an inhibitor of amyloid formation and its diagnostic and medical use.

Abstract: The invention provides methods and compositions for the rapid and sensitive detection of post-translationally modified proteins, and particularly of those with post-translational glycosylations. The methods can be used to detect O-GlcNAc post-translational modifications on proteins on which such modifications were undetectable using other techniques. In one embodiment, the method exploits the ability of an engineered mutant of ?-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling detection of the modified protein. The approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Further, the preferred embodiments can be used for detection of certain disease states, such as cancer, Alzheimer's disease, neurodegeneration, cardiovascular disease, and diabetes.

Abstract: The invention provides isolated nucleic acid molecules and polypeptide molecules that encode glycoprotein VI, a platelet membrane glycoprotein that is involved platelet-collagen interactions. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: A post-translational modification of a predetermined protein expressed by a cell is detected by specifically detecting an O-acetylation of a serine, threonine or tyrosine residue of the protein as an indication of the post-translational modification. The detection may employ antibodies that specifically bind an O-acetylated protein expressed by the cell, wherein the specific binding is dependent on the presence of an O-acetylated serine, threonine or tyrosine residue in the protein.

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: The present invention is directed antibodies specific to multiple beta blockers, as well as immunogens used to produce the antibodies and immunoassay kits and methods for using the antibodies.

Abstract: Artificial antibodies or antibody mimics are described. They consist of polymers that carry specific binding sites mimicking the properties of antibodies. There is also described a method for producing artificial antibodies, in which polymerisable monomers carrying functional groups and crosslinking monomers are polymerised in the presence of a print molecule and subsequently the print molecule is removed leaving specific binding sites complementary to the print molecules. There are also described methods for determination and isolation of organic molecules using the artificial antibodies as well as therapeutic and diagnostic methods using these antibodies.

Abstract: The present invention relates to monoclonal antibodies that specifically bind buprenorphine and/or at least one metabolic product thereof. The present invention further relates to buprenorphine metabolite conjugates for the production of monoclonal antibodies that specifically bind buprenorphine and/or at least one metabolic product thereof and hybridoma cells that produce the monoclonal antibodies. The invention also relates to immunoassay methods for determining buprenorphine and/or one or more buprenorphine metabolites in a sample using the novel antibodies and conjugates of the present invention.

Abstract: New derivatives of FK 506 are disclosed. These new derivatives and other derivatives that are useful for determining the levels of FK 506 in a sample are also provided as are assay procedures and kits for use in determining the levels of FK 506 or other macrophilin binding substances in blood, particularly un-extracted blood in the presence of specific binding proteins for FK 506.

Abstract: Compounds including haptens, intermediates, and immunogens that are useful in the production of antibodies specific for the methylenedioxy class of amphetamine derivatives are described. Antibodies specific for the methylenedioxy class of amphetamine derivatives, reagent kits containing antibodies specific for the methylenedioxy class of amphetamine derivatives, methods of producing antibodies specific for the methylenedioxy class of amphetamine derivatives, and methods of detecting analytes including members of the methylenedioxy class of amphetamine derivatives are also described.

Abstract: The present invention concerns coupling agents having the following general formula: activated intermediates consisting of a coupling agent such as defined above with either a molecule having on its surface at least one aldehyde and/or ketone function before conjugation, or with one to eight molecules having on their surface at least one free thiol function before conjugation, conjugates consisting of a coupling agent such as defined above, of a molecule having on its surface at least one aldehyde and/or ketone function and of one to eight molecules having on their surface at least one free thiol function, and the use of said conjugates for in vitro diagnostic methods of diseases involving recognition of a ligand-anti-ligand pair.

Abstract: The invention concerns a ligand comprising wherein n is an integer from 1 to 5, X represents —NO2, —NH2, —NCS, —NHCOCH2-Z. NHCO—W—COCNHS, —NH-Q, —NHCS-Q, —NHCOCH2-Q, or —NHCO(CH2)m ?-Q where Q is an hapten chosen from the group consisting of steroids, enzymes, proteins, monoclonal antibodies, chimeric antibodies, or fragments thereof or any activated linker ready for coupling reaction, Y is CO2H or PO3H2 W is —(CH2)m— m is an integer from 1 to 10.

Abstract: The invention provides a hapten derivatized with a crosslinker at the nitrogen of the 8?-carboxamide of 2-oxo-3-hydroxy LSD. The invention also 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 the 3-hydroxy-2-pyrrolidone structural epitope of 2-oxo-3-hydroxy LSD.

Abstract: Methods and reagents for obtaining simplified mixtures of peptides from a sample containing a number of peptides are disclosed. The simplified sample can be easier to analyze than the original peptide sample yet it is representative of all or nearly all of the proteins present in the mixed protein sample from which the original and more complex peptide sample was derived. The methods entail the use of tagging moieties that include an amino-acid-specific reactive group (R). The tagging moieties “tag” peptides or proteins at specific amino acids (e.g., by reacting with an amino acid to form a covalent bond), ultimately allowing the isolation of peptides that contain those specific amino acids. Other methods entail the used of a reactive moiety (RP) that comprises a reagent that selectively interacts with selected proteins, either covalently or noncovalently. For example, RP can be a natural ligand for a receptor that is to be tagged or a protein that interacts with a second protein that is to be tagged.

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: Disclosed is a method for the measurement of a cellular process, or for the measurement of the effect of a test compound on a cellular process, in one or more different populations of cells. The method comprises providing separate samples of one or more different populations of cells adhering to support particles, the support particles comprising a scintillant substance and being adapted for cell growth. In one embodiment, different samples of cells are introduced into separate reaction vessels in a fluid medium, together with a reagent labelled with a radioisotope, in the presence or the absence of the test compound, under conditions so as to cause a portion of said radiolabelled reagent to become associated with the cells. In another embodiment, multiparameter analysis may be performed to determine the effect of a test compound on a cellular process using two or more different cell populations present in the same well.

Abstract: The invention provides isolated nucleic acid molecules and polypeptide molecules that encode glycoprotein VI, a platelet membrane glycoprotein that is involved platelet-collagen interactions. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: Compounds including haptens, intermediates, and immunogens that are useful in the production of antibodies specific for the methylenedioxy class of amphetamine derivatives are described. Antibodies specific for the methylenedioxy class of amphetamine derivatives, reagent kits containing antibodies specific for the methylenedioxy class of amphetamine derivatives, methods of producing antibodies specific for the methylenedioxy class of amphetamine derivatives, and methods of detecting analytes including members of the methylenedioxy class of amphetamine derivatives are also described.

Abstract: An IgG1 ? monoclonal antibody to the immunosuppressive drug tacrolimus has improved properties. In particular, this monoclonal antibody, designated 1H6, has reduced cross-reactivity to several tacrolimus metabolites. This antibody is suitable for performance of immunoassays such as homogeneous immunoassays to detect or determine the presence or concentration of tacrolimus in samples such as blood samples. The invention further includes derivatives of tacrolimus derivatized at a non-binding portion of the molecule useful in immunizing antibody-producing animals and in producing such monoclonal antibodies, as well as labeled derivatives of tacrolimus useful as tacrolimus analogues in such assays. The invention further includes immunoassay methods for the detection of tacrolimus and test kits useful in performing such immunoassays.

Abstract: The invention provides methods and compositions for azide tagging of biomolecules. In one embodiment of the invention, proteins are tagged by metabolic incorporation of prenylated azido-analog substrates. Examples of such analogs are azido farnesyl diphosphate and azido farnesyl alcohol. The azido moiety in the resulting modified proteins provides an affinity tag, which can be chemoselectively captured by an azide-specific conjugation reaction, such as the Staudinger reaction, using a phosphine capture reagent. When the capture agent is biotinylated, the resulting conjugates can be detected and affinity-purified by streptavidin-linked- HRP and streptavidin-conjugated agarose beads, respectively. The invention allows detection and isolation of proteins with high yield, high specificity, and low contamination without harsh treatment of proteins.

Abstract: A method for selective labeling of phosphate groups in natural and synthetic oligomers and polymers in the presence of chemically related groups such as carboxylic acid groups. The method is specifically applicable to biological oligomers and polymers, including phosphopeptides, phosphoproteins and phospholipids. In a specific embodiment, selective labeling of phosphate groups in proteins and peptides, for example, facilitates separation, isolation and detection of phosphoproteins and phosphopeptides in complex mixtures of proteins. Selective labeling can be employed to selectively introduce phosphate labels at phosphate groups in an oligomer or polymer, e.g., in a peptide or protein. Detection of the presence of the label, is used to detect the presence of the phosphate group in the oligomer or polymer. The method is useful for the detection of phosphoproteins or phosphopeptides.

Abstract: The present invention relates to 9-substituted adenine derivatives represented by formula (I) wherein W is selected from the group consisting of H, halogen, azido and amino group; X is selected from the group consisting of O, S, N(H), CH2, CH and C; Y is selected from the group consisting of H, hydroxy, C1-4 alkyl, C1-4 alkoxy and halogen; R is selected from the group consisting of H, hydroxymethyl, C1-4 alkyl, and C1-4 alkoxy; R1is selected from the group consisting of O, NH and CH2; R2represents a radical selected from the group consisting of —(CH2)n—S—C(O)—R4 and —(CH2)n—S—S—R4, where n=1-4 and R4is a C1-4-alkyl or aryl group and R4 is optionally substituted with a halogen, amino, N-alkylamino, N, N-dialkylamino or C1-4 alkoxy group and wherein each of the R2radicals may be the same or different; and R3is O or S. The derivatives are useful as prodrugs for inhibiting adenylyl cyclase and lowering 3?:5?-cAMP in cells, thereby inhibiting adenylyl cyclase dependent effects within cells.

Abstract: Novel bipyridyl-osmium complex conjugates and their use in electrochemical assays are described. The redox reversible-osmium complexes can be prepared to exhibit unique reversible redox potentials and can thus be used in combination with other electroactive redox reversible species having redox potentials differing by at least 50 millivolts in electrochemical assays designed for use of multiple electroactive species in the same cell and in the same sample without interference between the two or more redox coupled conjugate systems.

Abstract: The invention concerns a ligand comprising (I) wherein n is an integer from 1 to 5 Y is CO2H or PO3H2T represents —X or -phenyl-X, wherein X represents NO2, NH2, NCS, NHCOCH2-Z, NHCO—W—COCNHS, —NH-Q, —NHCS-Q, —NHCOCH2-Q, or NHCO(CH2)m-Q where Q is a hapten chosen from the group consisting of steroids, enzymes, proteins, monoclonal antibodies, chimeric antibodies, or fragments thereof or any activated linker ready for coupling reaction, W is —(CH2)m- m is an integer from 1 to 10 Z is chloride, bromide or iodine

Abstract: An antibody is provided which specifically recognizes and binds to INGAP protein. The antibody is used in competitive binding assays for quantitation of INGAP in biological samples. The assay can be performed on a solid support or in a suspension.

Abstract: When insoluble magnetic carrier particles are used in immunoassay, a method is provided which is suitable for saving labor and for treating a large number of samples within a short time while avoiding problems including difficulties in the stability of sensitized insoluble magnetic particles and in their preparation. In assaying an antigenic substance in test samples, no use is made of insoluble magnetic particles carrying an antibody specific to the said antigenic substance but insoluble magnetic carrier particles are provided in a state free from adsorbing said antibody, etc. Then the antigenic substance per se to be assayed is adsorbed on the insoluble magnetic carrier particles followed by reaction with a labeled antibody specific to the said adsorbed antigenic substance. Thus, the antigenic substance in the test sample can be efficiently assayed in a mode suitable for automation.

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 a system for the improved detection of ecstasy-class compounds in biological samples. New ecstasy-class analogs are provided for detection of such ecstasy-class drugs. These analogs are compounds, or salts thereof, of a 2-amino-methylenedioxyphenyl (MDP) derivative attached to Z, where Z is a moiety capable of bonding, either directly or indirectly, with an immunogenic carrier, a detectable label, or a solid capture vehicle. Such analogs may be used to construct immunogens, enzyme or enzyme-donor conjugates, and other conjugates. The immunogens reproducibly generate antibodies with an exquisite ability to distinguish various ecstasy-class drugs in biological samples from potentially interfering substances. The specific antibodies and the conjugates may be used to distinguish and measure various ecstasy-class compounds in biological samples, such as those obtained from an individual suspected of substance abuse.

Abstract: The present invention relates to a linker system for activating surfaces for bioconjugation, and particularly to a linker system having a novel hydrophilic spacer group. The inventive linker system may be used for the construction of sensor chips or biochips for the detection of sample biomolecules.

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.