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: 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: 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: 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.

Abstract: Nitroaromatic compounds and immunogenic conjugates comprising a novel nitroaromatic compound and a carrier protein are disclosed. The invention further presents monoclonal antibodies highly specific for the claimed nitroaromatic compounds, the compounds' protein conjugates, the compounds' reductive byproducts, and adducts formed between the compounds and mammalian hypoxic cell tissue proteins. The invention is further directed to methods for detecting tissue hypoxia using immunohistological techniques, non-invasive nuclear medicinal methods, or nuclear magnetic resonance. Diagnostic kits useful in practicing the methods of claimed invention are also provided.

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: Methods of generating a conjugate of MHC class I molecule and a compound via a cysteine residue engineered into the &bgr;2-M subunit. Also featured are uses of the conjugates.

Abstract: The present invention provides antibodies useful in assays for mycophenolic acid (MPA). These antibodies bind MPA and are able to distinguish MPA from its esters, such as morpholinoethyl E-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate, and/or its metabolites, such as mycophenolic acid glucuronide. The present invention also provides conjugates of labels and MPA or MPA analogs. The antibodies of the invention are capable of binding these conjugates and are also capable of inhibiting the activity of the label when bound to the conjugates. The present invention also provides methods for the determination of MPA in a sample suspected of containing MPA that use the antibodies and/or conjugates of the invention. The present invention also provides assay reagents as well as packaged kits useful for performing the methods of the invention.

Abstract: Provided by this invention are essentially homogeneous, defined compositions of matter and hetero-polyoximes of defined structure comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention.

Abstract: The present invention provides novel cyclosporine C (CsC) derivatives having improved protein conjugatibility and hydrolytic stability. The present invention further provides a CsC derivative conjugated to a carrier, e.g., a solid support. Preferably, the solid support is a latex or magnetic particle.

Abstract: Novel stem cell factors, oligonucleotides encoding the same, and methods of production, are disclosed. Pharmaceutical compositions and methods of treating disorders involving blood cells are also disclosed.

Abstract: Provided by this invention are essentially homogeneous, defined compositions of matter comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention.

Abstract: The invention provides a vaccine composition in the form of a kit, comprising a first container containing an antigenic preparation comprising influenza antigen or antigens; and a second container containing an effective adjuvant amount of a chitosan which is a deacetylated chitin which is at least 80% deacetylated. The antigenic preparation in the first container preferably comprises haemagglutinin and neuraminidase influenza antigens.

Abstract: Novel baculovirus expression vectors and recombinant antigens for detecting, type-specific herpes simplex virus (HSV) infection have been made. Diagnostic kits and assays for detecting type-specific HSV infection have been described. High level production of foreign proteins in substantially pure form are now made possible by the novel baculoviruses of the present invention.

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 is directed to novel propoxyphene derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to propoxyphene and propoxyphene metabolites. The resulting novel antigens may be used for the production of antibodies or receptors using standard methods. Once generated, the antibodies or receptors and the novel derivatives which are covalently attached to proteins, polypeptides or labels may be used in the immunoassay process.

Abstract: Polyethylene and polypropylene protein conjugates which modulate body weight of animals and humans for the treatment, prevention and control of obesity and associated diseases or conditions, and the recombinant expression of these biologically active proteins in purified and homogeneous forms.

Abstract: Polyethylene and polypropylene protein conjugates which modulate body weight of ani is and humans for the treatment, prevention and control obesity and associated diseases or conditions, and the recombinant expression of these biologically active proteins in purified and homogeneous forms.

Abstract: Provided by this invention are defined compositions of hetero-polyoximes of defined structure comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention.

Abstract: The combination of the capabilities of stimuli-responsive components such as polymers and interactive molecules to form site-specific conjugates which are useful in a variety of assays, separations, processing, and other uses is disclosed. The polymer chain conformation and volume can be manipulated through alteration in pH, temperature, light, or other stimuli. The interactive molecules can be biomolecules like proteins or peptides, such as antibodies, receptors, or enzymes, polysaccharides or glycoproteins which specifically bind to ligands, or nucleic acids such as antisense, ribozymes, and aptamers, or ligands for organic or inorganic molecules in the environment or manufacturing processes.

Abstract: This invention describes processes for producing mature human members of the NGF/BDNF family of neurotrophic proteins that are fully biologically active. In addition, the gene encoding human BDNF and human BDNF are disclosed. A previously-unreported member of the NGF/BDNF family of neurotrophic proteins, NGF-3, has been identified and a portion of the gene encoding for the NGF-3 has been described.

Abstract: A method for preventing the activation of inactive, recombinant Helicobacter pylori apourease is presented. The method comprises contacting the apourease with a compound that modifies a sulfhydryl or lysyl residue of the urease. The covalently modified apourease is prevented from molecular aggregation.

Abstract: .sup.32 P- and .sup.33 P-labeled proteins which are useful for radiotherapy are prepared by stably linking .sup.32 P- or .sup.33 P-containing molecules to targeting proteins in such a way that the targeting protein retains the ability to bind to a cellular target. Methods for preparing the labeled proteins and their use in methods of radiotherapy are described.

Abstract: A conjugate of a synthetic polypeptide containing RGD or (dR) GD and a biodegradable polymer, such as hyaluronic acid or chondroitin sulfate is disclosed. Methods of making the conjugate and using it to aid wound healing by providing a temporary matrix are disclosed.

Abstract: The present invention provides a topiramate immunoassay and reagents for use in the immunoassay. In particular, topiramate is derivatized at the sulfamate moiety or the 9-carbon or 10-carbon methyl group of topiramate to add a label bound directly or through a linking group for use as a tracer (competitive analyte analog) or to add a linking group bound to a carrier for use as an immunogen to induce anti-topiramate antibodies. Immunoassay methods and kits are also provided.

Abstract: The invention relates to a compound of the formula (I) wherein whereinY is the fraction of a solid or soluble support, where Y may include a residue of a functional group having been attached to said support, said functional group having been hydroxy, amino, thio, epoxy or halogen,R.sup.1 is aryl, heteroaryl, alkyl chain or ring or ring system, which may include a heteroatom, or R.sup.1 is nothing, and R.sup.2 is vinyl;CH.sub.2 CH.sub.2 X, where X is halogen; orR.sup.3 C.dbd.CHR or R.sup.3 CH--CH.sub.2 R.sup.4 X, where R.sup.3 and R.sup.4 are the same or different and are alkyl, acyl, carbonyl, cyano or nitro groups and X is halogen.The invention also relates to a method for preparation of compound (I) and to its use as a substrate in the synthesis of tertiary amines. The invention still concerns a group of alpha-2-receptor active tetrahydroisoquinoline derivatives.

Abstract: A poly(ethylene glycol) derivative is disclosed that is activated with a sulfone moiety for selective attachment to thiol moieties on molecules and surfaces. The activated PEG is water soluble, hydrolytically stable for extended periods, and forms hydrolytically stable linkages with thiol moieties. The linkages generally are not reversible in reducing environments. The PEG derivative is useful for modifying the characteristics of substances including modifying biologically active molecules and surfaces for biocompatibility. Methods for synthesizing the active PEG and for preparing conjugates of the active PEG and other substances, including biologically active substances, are also disclosed.

Abstract: Novel oxy- and thio-substituted fatty acid analog substrates of myristoylating enzymes are provided which contain an oxygen or sulfur in place of a methylene group in a carbon position from 4 to 13 in the fatty acid chain of a C.sub.13 -C.sub.14 fatty acid or alkyl ester thereof.

Abstract: The present invention provides a method for sulfurizing a phosphorus-containing compound, such as a trivalent phosphorus compound, using a disulfide-containing five-membered heterocycle.

Abstract: A method for making a preconjugate which includes immunogenic species of a polymorphic analyte. The method is carried out by reacting an activated binding moiety, and a polymorphic analyte at room temperature for between about 10 hours and about 60 hours. The attaching reaction results in an excess of the preconjugate which includes the immunogenic species of the polymorphic analyte. The preconjugate can be used to make an immunoreactive conjugate useful as a developer antigen in a competitive inhibition immunoassay for the polymorphic analyte.

Abstract: The invention is directed to monoclonal antibodies, their fragments, single chains and polypeptide mimics of their hypervariable regions which immunoreact with bare small moieties such as metallic cations and small organic molecules, the hybridomas for production of the monoclonal antibodies, immunogen compounds for developing the hybridomas, and methods for use of the monoclonal antibodies.

Abstract: A method for the immobilization of an organic thiol compound, HS--R, in which R is an organic residue, to a water-insoluble polymer of non-polypeptide structure exhibiting a disulfide (--S--S--) group directly bound to a saturated carbon atom at each of its sulphur atoms, which comprising contacting the polymer with an oxidation agent in such an amount and of such a kind that it is capable of transforming the disulfide group (--S--S--) to an oxidized disulfide group capable of reacting with thiol groups, whereupon the polymer obtained exhibiting one or more oxidized disulfide groups is contacted with the organic thiol compound HS--R under conditions allowing reaction to the formation of one --S--S--R group and one --SO.sub.n (H) group per disulfide oxide group that undergoes the reaction, where n is 1 or 2.

Abstract: Oligonucleotide signalling conjugates including a nucleic acid sequence, an amino-group containing linker group, a sulphur (thio) containing group and a non-isotopic label or marker and thiolated oligonucleotide derivative intermediates reactive with activated non-isotopic label or marker are described. The non-isotopic label is especially an enzyme such as alkaline phosphatase or horse radish peroxidase. The conjugates have application in the detection or characterisation of nucleic acid sequences and in particular in genetic characterisation.

Abstract: The invention describes reactive dyes having an alkyl spacer attached via a sulfonamide bond to a sulforhodamine 101 fluorophore, and a variety of useful conjugates prepared therefrom. The increased length of the covalent linkage due to the alkyl spacer results in dye-conjugates having a number of surprisingly advantageous properties relative to previous sulforhodamine 101-labeled conjugates, including enhanced solubility and increased fluorescence. The reactive dyes of the present invention are more stable than the known compound sulforhodamine 101 sulfonyl chloride. Novel reactive dyes are described for selective modification of groups other than amines, including thiols and photoreactive derivatives.

Abstract: A method for preparing phycobiliprotein/amine-reactive dye conjugates is disclosed in which the conjugates so prepared overcome the energy transfer/fluorescent quenching dilemma encountered in the use of prior art conjugates. A phycobiliprotein, for example, phycoerythrin or allophycocyanin, is conjugated with an amine-reactive dye, for example, Texas Red or carboxyfluorescein succinimidyl ester, in the presence of a selective salt which causes a hydrophobic intramolecular rearrangement of the phycobiliprotein thereby exposing more hydrophobic sites for binding to the amine-reactive dye. The conjugates prepared according to the invention are useful in multiple color fluorescence assays without requiring the use of multiple exciting sources.

Abstract: A pyridinoline composition in which pyridinoline is derivatized specifically at its aliphatic hydroxyl group by a selected chemical group is disclosed. In various embodiments, the composition may be used as a standard for HPLC or immunoassay of pyridinoline, a pyridinoline immunogen for producing anti-pyridinoline antibodies, and a solid-phase reagent for use in an immunoassay kit. Also disclosed are methods for making and using the composition.

Abstract: A poly(ethylene glycol) derivative is disclosed that is activated with a sulfone moiety for selective attachment to thiol moieties on molecules and surfaces. The activated PEG is water soluble, hydrolytically stable for extended periods, and forms hydrolytically stable linkages with thiol moieties. The linkages generally are not reversible in reducing environments. The PEG derivative is useful for modifying the characteristics of substances including modifying biologically active molecules and surfaces for biocompatibility. Methods for synthesizing the active PEG and for preparing conjugates of the active PEG and other substances, including biologically active substances, are also disclosed.

Abstract: .sup.32 P- and .sup.33 P-labeled proteins which are useful for radiotherapy are prepared by stably linking .sup.32 P- or .sup.33 P- containing molecules to targeting proteins in such a way that the targeting protein retains the ability to bind to a cellular target. Methods for preparing the labeled proteins and their use in methods of radiotherapy are described.

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: Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy.

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

Abstract: Active esters of PEG acids and related polymers are provided that have a single propionic or butanoic acid moiety and no other ester linkages. These polymer acids have a half life in water of from about 10 to 25 minutes. For example, alpha-methoxy, omega-propionic acid succinimidyl ester of PEG ("methoxy-PEG-SPA") has a nearly ideal reactivity with amino groups on proteins and other biologically active substances. The half life of methoxy-PEG-SPA is about 16.5 minutes in water. The invention also provides conjugates with proteins, enzymes, polypeptides, drugs, dyes, nucleosides, oligonucleotides, lipids, phospholipids, liposomes, and surfaces of solid materials that are compatible with living organisms, tissue, or fluid.

Abstract: The invention relates to magnetic protein conjugates of the formula I ##STR1## in which M represents a dispersible magnetically reacting material or particle which carries aminogroups, Ig represents a protein which carries one or more mercapto groups, and X represents an organic chemical structure which links the two ligands by chemical means, to a process for the preparation of protein conjugates of the formula I, and to the use of conjugates of this type for removing cells or soluble bioorganic molecules or components from aqueous salt solutions or body fluids, and to the use thereof within the framework of a diagnostic method or as a diagnostic aid.

Abstract: The present invention relates to the field of immunoassays for metal ions. The invention presents: metal ion-ligand coordination complexes ("MLC"), novel ligands, antibodies specific for MLC, immunoassays utiliizing the foregoing, and methods for selecting said antibodies.

Abstract: This invention is directed to novel nucleophilic polysubstituted aryl acridinium conjugates and the methods for preparation thereof. The novel nucleophilic polysubstituted aryl acridinium conjugates are useful in biological assays, including novel assays for the determination of Vitamin B.sub.12, folate, cortisol, estradiol, and thromboxane B.sub.2.

Abstract: This invention relates to a method of producing peracetyloxazolines from peracetyl saccharides. The method involves reacting the starting material, a peracetyl saccharide, with a reagent combination, to directly produce the peracetyl oxazoline. This method may be used for the activation of oligosaccharides, wherein an oligosaccharide containing a reducing GlcNAc terminus is activated by the formation of an oxazolide at the terminal GlcNAc, and then coupled with a bifunctional spacer to provide an oligosaccharide-spacer conjugate. The activated oligosaccharide-spacer conjugate is then coupled to a protein, such as granulocyte colony stimulating factor or .gamma.-interferon, providing a neoglycoprotein conjugate. The invention provides a method for forming neoglycoprotein conjugates which may improve biological and physiochemical properties of the protein. For example, serum lifetime or efficiency of drug delivery of the peptide to a target organ or cell may be improved.

Abstract: The invention is directed to monoclonal antibodies, their fragments, single chains and polypeptide mimics of their hypervariable regions which immunoreact with bare small moieties such as metallic cations the hybridomas for production of the monoclonal antibodies, immunogen compounds for developing the hybridomas, and methods for use of the monoclonal antibodies.

Abstract: A novel conjugate vaccine comprising partially hydrolyzed, highly purified, capsular polysaccharide (Ps) from Streptococcus pneumoniae bacteria (pneumococci, Pn) linked to an immunogenic carrier protein, is produced by a new process. The conjugate is useful in the prevention of pneumococcal infections. Vaccines comprising a mixture of from one to ten different pneumococcal polysaccharide-immunogenic protein (Pn-Ps-PRO) conjugates induce broadly protective recipient immune responses against the cognate pathogens from which the polysaccharide components are derived. Young children and infants younger than 2 years old, normally unable to mount a protective immune response to the Pn-Ps alone, exhibit protective immune responses upon vaccination with these Pn-Ps-PRO conjugates.

Abstract: The invention concerns a process for the reactivation of denatured protein, in which the protein is incubated with a solution of Tris base or/and a salt of Tris at a concentration of at least 400 mmol/l and at a pH at which the protein to be treated can take up its native conformation.

Abstract: Novel reagents for the detection by immunoassay of drugs in body fluids, their preparation and use are disclosed. The reagents of the present invention correspond to the formulaP--[A--D].sub.nwhere:D is a drug derivative suitably selective for the determination of the presence of the target drug or drug metabolite,A is an activating linker-spacer group having an N-hydroxysuccinimide or isothiocyanate derived linking moiety,P is a poly(amino acid) or polymer capable of covalently bonding with A, andn is less than l.