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

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: 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: The present invention is directed to novel opiate derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to the opiates and opiate 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: A novel coconjugate comprising an immunogenic protein or protein complex having a first set of covalent linkages to low molecular weight moieties, --a.sup.--, which have an anionic or polyanionic character at physiological pH, and a second set of covalent linkages to peptides comprising Human Immunodeficiency Virus (HIV) Principal Neutralizing Determinants (PNDs), or peptides immunologically equivalent therewith, is useful for inducing anti-peptide immune responses in mammals, for inducing HIV-neutralizing antibodies in mammals, for formulating vaccines to prevent HIV infection or disease, including the Acquired Immune Deficiency Syndrome (AIDS), or for treating humans afflicted with HIV infection or disease.

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: A process for the activation of disulphide linked recombinant proteins expressed in prokaryotes is described. The process includes cell digestion, solubilization under denaturing and reducing conditions and activation under oxidizing conditions in the presence of GSH/GSSG and a non-denaturing amount of a denaturing agent.

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: The invention relates to novel aromatic acids, especially to compounds of formula ##STR1## wherein R.sub.1 is lower alkyl, R.sub.2 is lower alkyl, R.sub.3 is hydrogen, carboxy or sulfo, R.sub.4 is carboxy or sulfo, G is an unsubstituted or substituted 1,4-phenylene group or an unsubstituted or substituted 1,4-naphthylene group, and wherein either R.sub.5 and R.sub.6 together are an additional bond and L is an oxygen or sulfur atom or wherein R.sub.5 is hydrogen, R.sub.6 is halomethyl and L is an oxygen atom, and salts thereof, to the use of compounds I and their salts, to a process for the preparation of compounds I and their salts, to starting materials used in that preparation process, and salts thereof, to a process for the preparation of those starting materials and their salts, to a device in which the compounds I and their salts are used, and to a process in which that device is used.

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: Immunoassay methods and reagents for the specific quantification of imipramine or desipramine in a test sample are disclosed. The measurement of imipramine or desipramine is accomplished in a specific immunoassay employing antibodies prepared with imipramine or desipramine derivatives of the Formula III: ##STR1## wherein P is an immunogenic carrier material, X is two heteroatoms, Y is a linking group comprising from 1 to 6 carbon atoms and P is an immunogenic carrier material, and wherein for imipramine, R is CH.sub.3, and for desipramine, R is H.The present invention also describes the synthesis of unique labeled reagents of the structure of the Formula IV: ##STR2## wherein Z is a linking group comprising 1 to 4 carbon atoms and 0 to 2 heteroatoms and Q is a detectable moiety, preferably fluorescein or a fluorescein derivative, and wherein for imipramine, R.sub.1 is CH.sub.3, and for desipramine, R.sub.1 is H.

Abstract: A method for acylating peptides and proteins with the CoA-ester of diheteroatom substituted C.sub.13 to C.sub.14 myristic acid analogs catalyzed by N-myristoyltransferase is presented. In the analogs, two non-adjacent methylene groups, which are normally at positions 3-13, are replaced with oxygen or sulfur atoms.

Abstract: A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen of hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals.

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: 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: Methods for preparing metabolically stable, covalently crosslinked F(ab').sub.2 fragments of antibody molecules for use in labeled form as in vivo diagnostic and therapeutic agents, the stabilized F(ab').sub.2 fragments so produced in free form or conjugated to a chemical moiety, kits containing such fragments, and methods of using these fragments for diagnosis or therapy, are disclosed. In the method, crosslinking is carried out after reduction of inter-heavy chain disulfide bonds, but before cleavage of the crosslinked antibody to produce the F(ab').sub.2 molecules.

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: 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: 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: The invention relates to compounds from biopolymers and effector substances which are linked with the aid of derivatives of optically active amino acids in which the amino group has been converted into a maleimido group and the carboxyl group into an active ester group, processes for the preparation thereof and the use thereof.

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: 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: The present invention is directed to novel amphetamine derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to amphetamine and amphetamine 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: 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 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: A process for the activation of t-PA or IgG after expression in prokaryotes is described. The process includes cell digestion, solubilization under denaturing and reducing conditions and activation under oxidizing conditions in the presence of GSH/GSSG.

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: 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: Novel derivatives of procainamide and N-acetylprocainamide (NAPA) are disclosed having the following formula: ##STR1## wherein: X=hydrogen or acetyl;R.sub.1 =an alkyl group having 1 to 3 carbon atoms;m=an integer from 2 to 10;R.sub.2 =an alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms;Z=a poly(amino acid); andn=1 to p where p=MW of Z/1000.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: Peptides immunoreactive with antibodies to native proteins, and which have at least two cysteine residues that contribute to mimicking an epitope of the protein, are prepared with the cysteine thiol groups protected. When deprotected, the peptides have enhanced immunoreactivity. The peptides are particularly useful for detecting antibodies or antigens associated with retroviruses, including the clinically important lymphotropic retroviruses HIV-1, HIV-2, HTLV-I, and HTLV-II.

Abstract: N-substituted azetidinones are a class of inhibitors of human leukocytes elastase which are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the assay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured. The assays are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.

Abstract: There is provided a standard for use in testing for captan in immunoassays. This standard has the structure THPD--(CH.sub.2).sub.x --(R.sup.3).sub.y --R.sup.1 wherein THPD is cis-1,2,3,6-tetrahydrophthalimido, x is an integer from 1 to 10, R.sup.1 selected from the group consisting of --COOH, --NH.sub.2, --NO.sub.2, --SH and --OH, R.sup.3 is an aryl moiety and y is 0 or 1. Compounds of this general structure are known, they mimic the immunological reaction of captan and related compounds which are not stable in water and thus cannot be satisfactorily used as standards in testing for the presence and level of presence of captan and related compounds. There is also provided a method of carrying out such testing, utilizing such standards in which the standard (I) is coupled to a protein that is large enough to elicit an immune response in warm blooded animals, to yield compound (II). THPD--(CH.sub.2).sub.x --(R.sup.3).sub.y --R.sup.

Abstract: The invention relates to a novel process for preparing immunoconjugates consisting of haptens which are sparingly soluble or insoluble in aqueous solution and proteins/polypeptides using special solvents, in particular diethylene glycol monoalkyl ethers.

Abstract: This invention relates to a method for the immunoassay of AZT (3'-azido-3'-deoxythymidine), also known as zidovudine, in biological fluids such as serum, semen, plasma and urine, as well as other body fluids. The invention also includes (1) various novel analogs of AZT useful in preparing immunogens for antibodies to AZT and in preparing labeled AZT, (2) immunogens for antibodies to AZT, (3) monoclonal and polyclonal antibodies to AZT, (4) labeled AZT analogs and (5) diagnostic test kits for the immunoassay.

Abstract: meso-DTA and method for its use in reducing disulfide bonds.

Abstract: A process is disclosed for treating cancer by the process of indirect targeted immunocytolysis, which comprises conjugating an immunogenic sensitizing agent to a targeting agent which is capable of binding to aberrant cells, such as cancer cells in a human or animal host. The conjugate is then introduced into the body of an animal or human which has previously been actively immunized against the sensitizing agent or concomitantly treated with the appropriate antibody (passive immunization). Binding of the conjugate to the object cells occurs and is accompanied by the binding of antibodies produced against the sensitizing agent. This results in triggering of a complement cascade and/or an antibody-dependent T-cell-mediated response leading to cell destruction. Also disclosed are the novel targeting agent/sensitizing agent conjugates for use in the process. Agents comprise autocrine differentiation-inhibiting factor/toxoid conjugates.

Abstract: A conjugate immunogen, having polysaccharide moieties derived from bacterial sources, provides a multivalent vaccine with a low protein to polysaccharide ratio. The vaccine reduces complications associated with injection of protein immunogens due to pyrogenic responses, such as swelling and pain, and is particularly suitable for administration to infants.

Abstract: The present invention relates to a method of producing an E. coli vaccine and to the vaccine produced thereby. The method involves purifying lipopolysaccharide from E. coli expressing complete O-polysaccharide sidechains;isolating the O-polysaccharide region of the lipopolysaccharide molecule by hydrolysis in dilute acetic acid and purifying it essentially free of lipid A; and covalently coupling lipid A-free O-polysaccharide via at least one hydroxyl or carboxyl group of the polysaccharide to a carrier protein. Polyvalent vaccines are prepared by combining two or more monovalent vaccines for different serotypes prepared according to the present invention. The present also relates to conjugates used in the vaccines. The conjugates of the present invention are the O-polysaccharide region of an E. coli lipoplysaccharide molecule covalently coupled to a carrier protein.

Abstract: Chemically modified allergens, whose allergenic activity is reduced with respect to that of the corresponding native allergenic material, which are capable of inducing specific antibodies addressed towards said native allergenic material, wherein a portion of the primary amino groups of the protein molecule of the native allergen are chemically modified so as to give simple or substituted carbamylic amino groups, or substituted thiocarbamylic amino groups, or possibly substituted guanidino groups, and process for the production thereof. The allergens so modified are not polymerized with each other, they are soluble in water media, they are resistent to tryptic hydrolysis and they show particularly suitable for being administered in hyposensitizing therapeutic treatments.

Abstract: This invention provides enzyme conjugates, antigens, antibodies and diagnostic test kits used in an enzyme-linked immunosorbent assay method for determining the presence and concentration of imidazolinone compounds.

Abstract: The efficacy of immunotoxins having an antibody that recognises a tumour associated antigen linked to a cytotoxin through a heterobifunctional agent of the disulphide type is improved by providing in the heterobifunctional agent a molecular grouping creating steric hindrance in relation to the disulphide link. This steric hindrance can be provided by a methyl substituted methylene group located in the heterobifunctional link adjacent to the disulphide bond.

Abstract: This invention pertains to immunogenic conjugates comprising a carbohydrate containing antigen or other antigen bound to or genetically fused with a cytokine, lymphokine, hormone or growth factor having immunomodulating activity, wherein the cytokine, lymphokine, hormone or growth factor is capable of modifying immunogenicity of the carbohydrate containing antigen. The cytokine or lymphokine can be an interleukin or an interferon. The immunogenic conjugate can be used in vaccine and co-vaccine formulations.

Abstract: A method for radiolabeling a monovalent Fab or Fab' antibody fragment which comprises the steps of cleaving a divalent F(ab).sub.2 or F(ab').sub.2 antibody fragment using sulfite or meta-bisulfite ions to produce a monovalent fragment having a free sulfhydryl group, and contacting the monovalent fragment with a cation of a metallic radionuclide which binds to sulfhydryl groups, without removing excess sulfite or metabisulfite.

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

Abstract: The present prevention provides an effective, fast acting method of vaccination useful in suppressing gonadotropic hormone release. The vaccine utilizes LHRH conjugated at its amino terminus to a protein carrier and can be mixed with either adjuvants or detergents in order to provide an effect vaccine.

Abstract: The LTD.sub.4 receptor has been defined by radioligand binding studies as a member of the family of G-protein coupled receptors. A photoactivable azido derivative of LTD.sub.4 ([.sup.125 I]Azido-LTD.sub.4) has been synthesized for use as a photoaffinity probe. Photoactivation of ([.sup.125 I]Azido-LTD.sub.4 under equilibrium binding conditions revealed the selective radiolabeling of a 45 kDa protein in guinea-pig lung membranes, as visualized by SDS-PAGE and autoradiography.