Abstract: Immunoassay methods and reagents for the specific quantification of thyroxine in a test sample are disclosed employing antibodies prepared with thyroxine derivatives of the formula: ##STR1## wherein P is an immunogenic carrier material and X is a linking moiety. The present invention also describes the synthesis of unique labelled reagent of the formula: ##STR2## wherein Q is a detectable moiety and W is a linking moiety, preferably fluorescein or a fluorescein derivative.

Abstract: Immunoassay methods and reagents for the specific quantification of thyroxine in a test sample are disclosed employing antibodies prepared with thyroxine derivatives of the formula: ##STR1## wherein P is an immunogenic carrier material and X is a linking moiety. The present invention also describes the synthesis of unique labelled reagent of the formula: ##STR2## wherein Q is a detectable moiety and W is a linking moiety, preferably fluorescein or a fluorescein derivative.

Abstract: Neisseria meningitidis group B polysaccharide (GBMP) modified by having sialic acid residue N-acetyl groups replaced by N-acyl groups exhibits enhanced immuno response thereto. In addition, induction of antibodies which cross-react with unmodified group B meningococcal and E. coli K1 capsular polysaccharide and other tissue cells having a common epitope is minimized. Conjugation of the modified polysaccharides with a physiologically acceptable protein such as tetanus toxoid induces the production of specific protective antibodies with negligible levels of GBMP-cross reactive antibodies, to thereby afford protection against infections caused by group B meningococci and E. coli K1.

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: 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: 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 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: Several poly(ethylene glycol) mixed carbonates and their preparation are closed. These carbonates are synthesized by conversion of polyethylene glycol first to the chloroformate then by reaction with the hydroxyl group of N-hydroxybenzotriazole or 2-hydroxypyrimidine or N-hydroxy-2-pyrrolidinone. These mixed carbonate analogs smoothly react with amino groups in aminoglycans and protein and amino containing surfaces to form stable, hydrolysis resistant carbamate linkages.

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: An assay to confirm the presence of antibodies to T. cruzi in a test sample. The assay comprises detecting the presence of antibody to three T. cruzi antigens, Gp90, Gp 60/50 and LPPG in a test sample. The presence of antibody in the test sample to at least two of three T. cruzi antibodies is indicative of a confirmed reactive sample. Also provided are diagnostic reagents for detection of T. cruzi, a process for purifying GP 60/50, a process for linking a protein and LPPG, and diagnostic test kits for use when assaying for antibodies to T. cruzi.

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.

Abstract: Peptides substantially corresponding to the 148-162 region of type A influenza M protein and additionally containing at least one amino acid in the 163-166 region are disclosed to have high activity as influenza transcription inhibitors and thus as antiviral agents against influenza virus and other RNA viruses. The modification of these peptides by incorporation into liposomes or by addition of long-chain alkylamino acids is also shown as in the use of all such materials in antiviral drug formulations.

Abstract: Novel tethered hapten intermediates and related conjugates based on 3-phenyl-1-adamantaneacetic acid, as well as methods for making and using such conjugates. Haptens based on the above core structure may be substituted at any position on the phenyl ring, especially at the para position. Using tethered intermediates, immunogens, tracers, solid supports and labeled oligonucleotides are all described; as are methods for using the intermediates to prepare the conjugates, methods of using the conjugates to make and purify anitbodies, as assay tracers, and in nucleic acid hybridization assays. Kits containing haptenated oligonucleotides and anti-hapten conjugates are also described.

Abstract: Immunoassay methods and reagents for the specific quantification of amitriptyline or nortriptyline in a test sample are disclosed employing antibodies prepared with amitriptyline or nortriptyline derivatives of the Formula III: ##STR1## wherein for amitriptyline, R is CH.sub.3, and for nortriptyline, R is H. The present invention also describes the synthesis of unique fluorescein tracers of the structure of Formula IV and Formula V: ##STR2## wherein for a specific amitriptyline immunoassay, W.sub.1 is a heteroatom linked to the aromatic ring at the 2 or 3 position, and for a specific nortriptyline immunoassay, W.sub.2 is two heteroatoms linked together and attached to the aromatic ring at the 2 or 3 position, and wherein Q is a detectable moiety, preferably fluorescein or a fluorescein derivative.

Abstract: Anchimeric chelates are disclosed which are capable of rapidly forming stable chelates with radionuclide metals at or below physiological temperature. Bifunctional anchimeric chelates having these same properties are also disclosed which are useful for radiolabeling target specific molecules such as monoclonal antibodies and fragments thereof.

Abstract: The invention concerns new aminoalkylmaleimides of the general formula I ##STR1## in which R.sub.1 and R.sub.2 are the same or different and represent hydrogen or a C.sub.1 -C.sub.4 alkyl group and A represents a straight-chain or branched, saturated or unsaturated alkylene group with 2 to 6 carbon atoms which is interrupted, if desired, by an oxygen or sulphur atom or a carbonyl group, as well as their corresponding acid addition salts.The present invention also concerns amidoalkylmaleimide derivatives formed from compounds of the general formula I and immunological binding partners. In addition, the invention concerns immunological conjugates which can be produced by reaction of the amidoalkylmaleimide derivatives with peptides or proteins.The subject matter of the present invention are also the corresponding processes of production of the compounds according to the present invention as well as the use of these conjugates in diagnostic methods of determination, in particular in immunoassays.

Abstract: The present invention is a physiologically active, substantially non-immunogenic water soluble polyethylene glycol protein conjugate having the same utility as the protein which forms the conjugate, without having the same properties of producing an immunogenic response possessed by the protein which forms this conjugate.

Abstract: Acridinium compounds represented by the general formula (I) where A is an intervening group which does not have activity for binding with a specific binding substance, Z is a labelling active group which has activity for binding with a specific binding substance, R.sup.1 is a halogen atom, an alkyl group or an aryl group; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, a nitro group, a halogen atom or a carbonyl group, and Y is a counter ion. The acridinium compounds may form conjugates with specific binding substances. The acridinium compounds have high emission efficiency and stability and, hence, are useful as chemiluminescence labelling agents.

Abstract: Complex of a drug, hormone, bio-active peptide, or immunogen with the carrier molecule vitamin B12 and a method for delivering the complex to the intestine of a host vertebrate in order to deliver the complex to the circulation of the host and thereby elicit a pharmacological response to the drug, hormone, bio-active molecule or to elicit a systemic immune response to the immunogen. The invention also provides a method for the production of the complex. Further, the invention provides medicaments containing the complex.

Abstract: Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O.sub.2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

Abstract: A detoxified B. pertussis toxin or antigenic preparation is described, which is characterized by stability to reversion to toxicity upon storage at 4.degree.-8.degree. C. and at temperatures above 23.degree. C. Also provided are methods for producing detoxified pertussis toxin and vaccines containing same.

Abstract: Neisseria meningitidis group B polysaccharide (GBMP) modified by having sialic acid residue N-acetyl groups replaced by N-acyl groups exhibits enhanced immuno response thereto. In addition, induction of antibodies which cross-react with unmodified group B meningococcal and E. coli K1 capsular polysaccharide and other tissue cells having a common epitope is minimized. Conjugation of the modified polysaccharides with a physiologically acceptable protein such as tetanus toxoid induces the production of specific protective antibodies with negligible levels of GBMP-cross reactive antibodies, to thereby afford protection against infections caused by group B meningococci and E. coli K1.

Abstract: A class of predominantly hydrophobic non-azo N-substituted 1,8-naphthalimide compounds, each bearing, at its 3-position, a nucleofuge and, at its 4-position, a heteroatomic electron-releasing group. The heteroatomic electron-releasing group is being characterized as having a heteroatom directly linked to the 4-position of the ring, and having at least one hydrogen directly attached to the heteroatom. Upon activation by an activating agent in an environment independent of the presence or absence of oxygen, these compounds generate activated species. The activated species initiate chemical changes in lipid bilayer membranes of viruses and other target cells. These changes can eradicate viruses and other target cells. The activated species can also cause structural changes in lipid and any associated proteins and polypeptides at a level beneath the surface of the membrane, leading to polymerization and crosslinking.

Abstract: The invention is directed to a method of incorporating expanded porphyrins, and particularly of incorporating a sapphyrin or a texaphyrin, before, during, or after chemical synthesis of an oligomer to form an expanded porphyrin-oligonucleotide conjugate, and particularly a sapphyrin- or texaphyrin-oligonucleotide conjugate. This method includes reacting derivatized nucleotides and a sapphyrin or a texaphyrin in a desired order in an automated or manual DNA synthesizer having a solid support to form a sapphyrin- or a texaphyrin-oligonucleotide conjugate.

Abstract: The present invention is a physiologically active, substantially non-immunogenic water soluble polyethylene glycol protein conjugate having the same utility as the protein which forms the conjugate, without having the same properties of producing an immunogenic response possessed by the protein which forms this conjugate.

Abstract: The invention includes methods for inhibiting retroviral infections such as HIV. The methods of this invention involve the use of certain fragments of fibronectin and such fragments conjugated to carrier molecules such as ovalbumin to inhibit retroviral infections. The invention also includes novel proteins which comprise fibronectin fragments covalently linked to carrier proteins.

Abstract: Novel 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: To easily detect an amino acid derivative with high sensitivity in carrying out amino acid sequence analysis of a protein from an amino terminal, 2-anilino-5-thiazolinone amino acid derivative is reacted with a volatile primary amine represented by the general formula X-NH.sub.2, wherein X denotes a hydrocarbon containing a halogen to form a phenylthiocarbamyl amino acid derivative, and the phenylthiocarbamyl amino acid derivative is detected by using a gas chromatograph provided with an ECD. Accordingly, amino acid sequencing may be performed with high sensitivity without the need to use harmful radioisotope labeled or fluorescent amino compounds.

Abstract: Novel derivatives of procainamide and N-acetylprocainamide (NAPA) are disclosed having the following formula: ##STR1## wherein: X=hydrogen or acetyl;n=1 to p where p=MW of Z/1000;Z=a poly(amino acid) or polysaccharide; andR3=a bond or ##STR2## wherein R2=an alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms. The derivatives include maleimide conjugates of proteins or poly(amino acids), enzymes, enzyme donor polypeptides and labeling substances. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and derivatives are also disclosed.

Abstract: New acridinium compounds are provided which comply with formula 1, whereinA is a divalent organic moiety, such as an alkylene chain,X is a group which can be transformed together with C-9 of the acridine into a dioxetane by reaction with hydrogen peroxide, such as an aryloxy group,Y is a counter ion, andZ is a functional group, such as a carboxyl derivative.These acridinium compounds are useful as chemiluminogenic labels for both heterogeneous and homogeneous immunoassays.

Abstract: Pro-cytotoxic drug conjugates for anticancer therapy comprising a homing agent first moiety, a spacer molecule second moiety covalently linked to the homing agent, and a third moiety covalently linked to the second moiety consisting of a pro-cytotoxic drug that is non-toxic extracellularly but that, after internalization of the conjugate by proliferating tumor cells, is metabolized by one or more endogenous intracellular enzymes to a cytotoxic metabolic product, so that cell growth is arrested or the cells killed. Preferred procytotoxic drugs are carboxyphosphamide or carboxyisophosphamide.

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: The subject of the present invention is a peptide structure comprising at leastthe sequence 106-116 of a .beta.-CG or a .beta.-LHa sequence of at least 5 amino acids containing at least one lysine residue.These structures may be used for the preparation of vaccines intended to control fertility.

Abstract: This invention relates to novel quaternary ammonium immunogenic conjugates and reporter reagents useful for eliciting antibodies and in immunoassays. Processes for preparing such quaternary ammonium immunogenic conjugates and their use in immunoassays and in eliciting antibodies are also disclosed.

Abstract: Disclosed is a novel photo-activatable derivative of ryanodine 9-hydroxy-21-(4-azidobenzoyloxy)-9-epiryanodine. This novel ryanodine derivative has been conjugated to keyhole limpet hemocyanin (KLH) and used for the production of antibodies with high affinity and specificity to ryanodine. A radioimmunoassay specific for ryanodine was developed using the anti-ryanodine antibodies, and a dissociation constant for ryanodine of 1 nM was determined. Also disclosed is the binding of a labeled, photoactivatable derivative of ryanodine (ABRy) with the ryanodine receptor of skeletal, cardiac and brain membranes. Digestion of the labeled ryanodine receptor revealed a labeled 76 kDa tryptic fragment which is critical for the formation of the high affinity ryanodine binding site.

Abstract: An immunoassay method that integrates a sample processing component that enables the testing of samples for the presence of an immunologically non-remarkable compound, such as benzene, by the use of a monoclonal antibody having specific reactivity for an immunologically remarkable compound, such as nitrobenzene, which has been prepared by reacting the immunologically non-remarkable compound with derivatizing agent, and the components for performing the method, wherein one example of the immunoassay utilizes a monoclonal anti-nitrobenzene antibody to detect the presence or absence of benzene contamination in an aqueous sample when tested in a field or laboratory location.

Abstract: A water-soluble protein conjugate modified by saccharides is covalently bound to a carbohydrate backbone via a saccharide group. Such protein conjugates modified by saccharides can be produced in a simple way by polymerizing a vinylsaccharide and conjugating in a known way the poly(vinylsaccharide) obtained in this way with the protein, which is preferably an enzyme. The protein conjugates according to the present invention are stable over long time periods at a high enzymatic activity and also in aqueous solution and are thus particularly suitable for use in test kits.

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: A method for the treatment of the symptoms of fescue toxicosis in mammals comprising injecting a subject mammal with a vaccine which includes from about 5 .mu.g to about 1 mg of a protein-alkaloid conjugate per mL of a physiologically acceptable carrier. There is also provided a vaccine for the treatment of the symptoms of fescue toxicosis and a compound for preparing that vaccine.

Abstract: Immunoassay methods and reagents for the quantification of total doxepins (i.e., E-doxepin, Z-doxepin, E-desmethyldoxepin, and Z-desmethyldoxepin) in a test sample are disclosed. The quantification of total doxepins is accomplished in an immunoassay employing antibodies and labeled reagents prepared with doxepin derivatives of the Formula II: ##STR1## wherein Y-Z can be C=CH or N-CH.sub.2, R.sub.1 is a linking group, R.sub.2 can be H or CH.sub.3, and Q can be a detectable moiety or an immunogenic carrier material. The antibody reagent comprises antibodies which are capable of binding to total doxepins and which are produced with one or more immunogens prepared from the doxepin derivative of Formula II, and the labeled reagent is also prepared from the doxepin derivative of Formula II.

Abstract: This invention provides a compound comprising a methyl ecgonine group chemically attached to a phenylphosphonic group which is an analog to an intermediate of the hydrolysis transition-state of a cocaine benzoyl ester group. This invention also provides such analogs linked to carrier proteins, and antibodies thereto.

Abstract: A method of using texaphyrins as radiosensitizers. Advantageous properties of texaphyrins for use as a radiosensitizer include i) a low redox potential which allows radiation induced solvated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing the hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical which, nevertheless, reacts readily to covalently modify neighboring molecules causing further cellular damage, and iii) intrinsic biolocalization and indifference to the presence of O.sub.2 which allow texaphyrin to be particularly effective for treating the hypoxic areas of solid tumors. Sensitizer enhancement ratios of 1.62 and 2.2 were achieved at 20 .mu.M and 80 .mu.M gadolinium-texaphyrin, respectively, with a mouse leukemia cell line.

Abstract: This invention relates to compositions useful for inducing immunoprotection against infections by pathogenic organisms containing phosphocholine antigens, including Streptococcus pneumoniae and other microorganisms that have a phosphocholine antigen component of their membranes or capsids. This invention also relates to vaccines and methods for inducing immunoprotection against infection by these pathogenic organisms.

Abstract: This invention relates to derivatives of dipyrrometheneboron difluoride fluorescent dyes that have an absorption maximum at wavelengths longer than about 525 nm, and are chemically reactive with nucleic acids, proteins, carbohydrates, and other biologically derived or synthetic chemical materials to form dye-conjugates. The dye-conjugates generally have the structure: ##STR1## wherein at least one of the substituents R.sub.1 -R.sub.7, covalently bonds to a specific binding pair member, and further where at least one of the substituents R.sub.1 -R.sub.7 contains a bathochromic moiety that is heteroaryl or alkenyl. The remaining substituents, which may be the same or different, are hydrogen, halogen, alkyl (containing 1-5 carbon atoms), aryl, arylalkyl, or sulfo.

Abstract: Pre-activated stable protein reagents are provided. The reagents can be made by reaction of the protein and a heterobifunctional linker and have extended stability especially after lyophilisation. The reagents can be used in assay kits to form conjugates with proteins e.g. antibodies or polynucleotides e.g. oligonucleotides probes.

Abstract: A method for making a valproic acid derivative comprising a functionalized spacer arm attached to a .delta. carbon atom of a valproic acid molecule is disclosed. The method proceeds by attaching a spacer arm joined to an inorganic moiety to a valproic acid precursor to make an alkylated compound, derivatizing the alkylated compound in a liquid medium to make the valproic acid derivative, and then separating the valproic acid derivative from the liquid medium. The valproic acid derivative can be used to make an immunoreactive valproic acid conjugate.