Abstract: Methods for preparing synthetic heparins are provided. Synthetic heparin compounds, including ultralow molecular weight heparin compounds are provided. Also provided are methods of chemoenzymatically synthesizing structurally homogeneous ultra-low molecular weight heparins. Heparin compounds provided herein can have anticoagulant activity.

Abstract: Presented is a method for diagnosing and/or grading diastolic dysfunction or at least one structural or functional abnormality associated with diastolic dysfunction. The method involves measuring the level of IGFBP7 (Insulin like growth factor binding protein 7) and, optionally, the level of at least one further marker in a patient suffering from heart failure, and comparing the level to a reference level. Further envisaged is a method of monitoring diastolic function in a patient suffering from heart failure. Also described are kits and devices adapted to carry out the method.

Abstract: Compositions and methods for accurate and sensitive quantitation of T-tau and P-tau are disclosed.

Abstract: The invention describes antibodies having a high affinity for aggregated forms of ?-synuclein and a low affinity for monomeric forms of ?-synuclein. The antibodies are useful in the diagnosis of neurodegenerative diseases.

Abstract: Test kits and methods for diagnosing and monitoring relative risk of joint injury are provided. The apparatus and methods beneficially permit intervention to reduce the risk of joint injury and/or reduce the damage resulting from joint injury. Methods for monitoring recovery from a joint injury are also provided.

Abstract: An in vitro method for the early detection of a potential inflammation, in particular a rejection of a transplant is disclosed, wherein the level of kynurenine in saliva is determined. The test method can be easily performed and allows the early detection of potential problems.

Abstract: The present invention relates to anti-drug vaccines based on conjugates between the drug and a non-immunogenic carrier protein. In preferred embodiments, it provides for anti-cocaine vaccines and their use to diminish the effects and/or use of cocaine in a subject.

Abstract: Methods for treating a cocaine-related disorder in an individual include administering to the individual a therapeutic amount of an antibody comprising a human immunoglobulin gamma heavy chain and a murine lambda light chain. In another embodiment, the light chain includes a human kappa light chain at least partially derived from 1B3. Other embodiments are directed toward the antibodies themselves and methods of binding the antibodies.

Abstract: Improved methods for the production, selection and inhibition of catalytic and covalent antibodies are disclosed.

Abstract: The present invention provides a process for preparing a compound of Formula 5b, as well as intermediates thereof, and novel classes of compounds useful in process for preparing these and similar compounds.

Abstract: A method of producing a metalloprotein inhibitor, the method comprising generating antibodies directed at a composition including a metal ion-bound chelator, wherein the composition is selected having structural and electronic properties similar to a functional domain of the metalloprotein, thereby producing the metalloprotein inhibitor.

Abstract: The present invention relates to CAB molecules, ADEPT constructs directed against CEA, and their use in therapy.

Abstract: A strategy to improve protein stability by domain insertion. TEM 1 beta-lactamase (BLA) and exo-inulinase, as model target enzymes, are inserted into a hyperthermophilic maltose binding protein from Pyrococcus furiosus (PfMBP). Unlike conventional protein stabilization methods that employ mutations and recombinations, the inventive approach does not require any modification on a target protein except for its connection with a hyperthermophilic protein scaffold. For that reason, target protein substrate specificity was largely maintained, which is often modified through conventional protein stabilization methods. The insertion was achieved through gene fusion by recombinant DNA techniques.

Abstract: A number of human beta-glucuronidase variants having higher enzymatic activity at physiological pH as compared with wild-type beta-glucuronidase and uses thereof in prodrug therapy. Also disclosed herein is a method for identifying enzyme variants having elevated enzymatic activity using a mammalian surface display system.

Abstract: The present invention provides antibody targeting compounds in which the specificity of the antibody has been reprogrammed by covalently or noncovalently linking a targeting agent to the combining site of an antibody. By this approach, the covalently modified antibody takes on the binding specificity of the targeting agent. The compound may have biological activity provided by the targeting agent or by a separate biological agent. Various uses of the invention compounds are provided.

Abstract: The present invention provides: a novel antiviral agent containing a human antibody ? light chain, a novel human abzyme containing a human antibody ? light chain; a polynucleotide, a vector, and a transformant, each of which relating to the containing a human antibody ? light chain of the above; a primer set for effectively obtaining a human antibody ? light chain having a function as an antiviral agent or abzyme; and a method for producing a polynucleotide and a method for producing a polypeptide, each of which method utilizes the primer set.

Abstract: The present invention relates to CAB molecules, ADEPT constructs directed against CEA, and their use in therapy.

Abstract: Improved methods for the production, selection and inhibition of catalytic antibodies are disclosed.

Abstract: Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a ?-amyloid epitope. Also disclosed are methods for inhibiting the formation of ?-amyloid plaques in the brain of a human, or promoting the disaggregation of a preformed ?-amyloid plaque. Such methods recite the administration of a bispecific antibody.

Abstract: Nine efficient aldolase antibodies were generated using hapten 2. This hapten combines, in a single molecule, structural components employed for reactive immunization with structural components employed for forming a transition state analog of the aldol reaction. Characterization of two of these antibodies reveals that they are highly proficient (up to 1000-fold better than any other antibody catalyst) and enantioselective catalysts for aldol and retro-aldol reactions and exhibit enantio- and diastereo-selectivities opposite that of antibody 38C2.

Abstract: The present invention relates generally to a growth factor precursor and its use to select production of antigen specific catalytic antibodies. Such catalytic antibodies are produced following B cell activation and proliferation induced by catalytic cleavage products of a target antigen portion of the growth factor precursor of the present invention. A particularly useful form of the growth factor precursor is as a nucleic acid vaccine. The nucleic acid vaccine of the present invention preferably further comprises a molecular adjuvant. Another aspect of the present invention comprises a growth factor precursor in multimeric form. The growth factor precursor of the present invention is useful for generating catalytic antibodies for both therapeutic, diagnostic and industrial purposes.

Abstract: The invention relates to murine monoclonal antibodies (MAbs), A, B, C and D, which are directed against tumor-associated antigens. The nearly complete nucleotide sequences of the V genes of these MAbs are described, so that the relevant variable domains can be put together to give chimeric MAbs, or “humanized” MAbs are obtained by inserting the hypervariable regions (complementarity determining regions=CDR) into a human MAb framework. Antibody constructs of this type can be employed in human therapy and in vivo diagnosis without the disadvantages observed with murine MAbs.

Abstract: Improved methods for the production, selection and inhibition of catalytic antibodies are disclosed.

Abstract: A method is disclosed of determining the presence of catalytic anti-Factor VIII allo-antibodies capable of degrading Factor VIII in a mammal, and of characterising the cleavage sites in said Factor VIII molecule by said catalytic anti-Factor VIII allo-antibodies. It also relates to an anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor; and to a pharmaceutical composition comprising said catalytic anti-Factor VIII allo-antibodies which are capable of degrading Factor VIII and which originate from said method of determination; and further to a pharmaceutical composition comprising said anti-Factor VIII allo-antibody-catalysed Factor VIII degradation inhibitor.

Abstract: In some embodiments, the present invention pertains to a method for conjugating a first compound to a second compound wherein the conjugation involves an electrophilic moiety. The method comprises reacting the first compound with the second compound to form a conjugate. The improvement in embodiments of the present invention comprises adding a nucleophilic reagent to the conjugate wherein the nucleophilic reagent forms a neutral product upon reaction with unreacted electrophilic moieties of the conjugate. In some embodiments, the nucleophilic reagent is substantially non-reactive with disulfide bonds in the event that the conjugate comprises disulfide bonds. The conjugate formed is doubly deactivated because the other moiety for linking to the electrophilic moiety is also deactivated.

Abstract: A fusion protein composition of an antibody Fc region which is useful as a medicament in which effector function is improved is desired. The present invention provides a fusion protein composition comprising a fusion protein molecule of an antibody Fc region having complex type N-glycoside-linked sugar chains in the Fc region, wherein the complex type N-glycoside-linked sugar chains have a structure in which fucose is not bound to N-acetylglucosamine in the reducing end in the sugar chains; a transformant producing the fusion protein composition; a process for producing the fusion protein composition; and a medicament comprising the fusion protein composition.

Abstract: Disclosed are antibodies which catalyze hydrolysis of ?-amyloid. Antibodies generated are characterized by the amide linkage which they hydrolyze. Methods of generating the antibodies by using ?-amyloid peptides which incorporate transition state analogs are also provided. Also disclosed is a vectorized antibody which is characterized by the ability to cross the blood brain barrier, and is further characterized by the ability to catalyze the hydrolysis of ?-amyloid. The vectorized antibody can take the form of bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a taransition state adopted by ?-amyloid hydrolysis.

Abstract: Methods and compositions are provided for determining ADP in the presence of ATP. These comprise including among the assay reagents at least one of the correcting components creatine phosphokinase and phosphocreatine, pyruvate kinase and phosphoenolpyruvate, peroxidase and a non-interfering peroxidase substrate, and catalase. One aspect of the method employs formation of hydrogen peroxide from the ADP by pyruvate kinase, phosphoenolpyruvate and pyruvate oxidase. The hydrogen peroxide is then determined. A combined reagent having all of the reagents may optionally include a peroxidase when the hydrogen peroxide is to be enzymatically determined. A peroxidase substrate is added to the sample in conjunction with the peroxidase substrate reagent, the mixture incubated and depending on whether the peroxidase substrate is a fluorescer or chemiluminescer, the mixture may be illuminated with excitation light and the emitted light determined as a measure of the ADP in the sample.

Abstract: Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.

Abstract: The in vitro polymerization of silica, silicone, non-silicon metalloid-oxane and metallo-oxane polymer networks, by combining a catalyst and a substrate to polymerize the substrate to form silica, polysiloxanes, polymetalloid-oxanes polymetallo-oxanes (metal oxides), polyorganometalloid oxanes, polyorganometallo oxanes, and the polyhydrido derivatives thereof, at about neutral pH.

Abstract: A method for increasing the rate of chemical reactions involving the conversion of at least one reactant to at least one product involves contacting the reactant with an appropriate monoclonal antibody under conditions permitting the formation of a complex between the antibody and the reactant. The complexed reactant is converted to the product which is then released from the complex. The monoclonal antibody may employ a cofactor and may be directed to a known substrate of an enzyme. Methods for preparing such monoclonal antibodies are also disclosed.

Abstract: The present invention relates to the identification of lipid oxidising antibodies as a key pathogenic factor in atherosclerotic disorders. The presence of such antibodies is a important marker for the diagnosis and prognosis of such disorders and methods and means for the assessment of athersclerotic conditions are provided herein.

Abstract: Antigens capable of eliciting antibodies which can catalyze chemical reactions, in particular, the cleavage or formation of a peptide linkage, comprising a hapten or a hapten and a suitable carrier molecule are disclosed. Haptens include, among others, silicon and boron containing compounds. Antibodies which are catalytically active for chemical reactions, in particular, the cleavage or formation of a selected peptide linkage or an ester bond, and which are elicited by such antigens are disclosed as well as methods for producing the antibodies and methods for catalyzing the cleavage or formation of a peptide linkage or in ester bond in a molecule.

Abstract: Disclosed are catalytic antibodies and polypeptides capable of degrading cocaine. Said catalytic antibodies and polypeptides are characterized by the amino acid sequence of their complementary determining regions and framework regions. The present invention also discloses a pharmaceutical composition and a method for decreasing the concentration and a method for decreasing the concentration of cocaine of a subject. Finally, the invention discloses pharmaceutical compositions and methods for treating cocaine overdose and addiction in subjects.

Abstract: In as assay, an analyte is specifically associated with a reporter adenylate kinase, ADP is added and then formation of ATP is monitored. Prior to addition of ADP, adenylate kinase other than reporter adenylate kinase is removed. Assay apparatus comprises a solid phase on which is immobilised the analyte or an antibody specific for the analyte, a reporter composition comprising a thermostable adenylate kinase coupled to an antibody specific for the analyte, and ADP plus associated reagents for conversion of ADP into ATP by thermostable adenylate kinase.

Abstract: Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a ?-amyloid epitope. Also disclosed are methods for inhibiting the formation of ?-amyloid plaques in the brain of a human, of promoting the disaggregation of a preformed ?-amyloid plaque. Such methods recite the administration of a bispecific antibody.

Abstract: A sample solution treating instrument is provided for facilitating rapid and simplified adjustment of the condition of a sample solution proper for analysis with a biosensor before supplying the solution to the biosensor. The sample solution treating instrument includes, for example, a catalyst or an adsorbent which can remove any interfering substance in order to adjust the sample solution for measurement with a biosensor.

Abstract: Covalently reactive antigen analogs are disclosed herein. The antigens of the invention may be used to stimulate production of catalytic antibodies specific for predetermined antigens assocated with particular medical disorders. The antigen analogs may also be used to permanently inactivate endogenously produced catalytic antibodies produced in certain autoimmune diseases as well as in certain lymphoproliferative disorders.

Abstract: Improved methods for the production, selection and inhibition of catalytic antibodies are disclosed.

Abstract: A system for detecting physical or chemical changes in an environment is disclosed. The system comprises means for conducting a chemical reaction; an active biological molecule whose physiological function is noncatalytic which is capable of catalyzing a chemical reaction wherein at least one reactant is converted to one product; and means for sensing and processing information relating to changes in said environment. A method for detecting physical or chemical changes in an environment is also disclosed.

Abstract: The invention relates to biotechnology, immunology, gene engineering, and the microbiological and medical industries. The aim of the invention is to develop a method for producing catalytic antibodies to proteins and peptides, in particular to gp120, using animals having spontaneous and induced autoimmune pathologies. Various methods for producing catalytic antibodies are also disclosed. The inventive methods make it possible to create a catalytic vaccine which can when injected to a patient to exhibits adhesive properties in relation to antigen simultaneously with a destructive function, there by suspending the progression of disease. Said invention discloses the inventive method for the autoimmunisation of animal lines SJL by fused proteins containing classical peptide epitope which develops pathology of an animal by protein fragments gp120 accompanied with an interest target catalytic antibody.

Abstract: Disclosed is a pO157 plasmid-specified polypeptide found in E. coli EDL933 and other E. coli that binds to and cleaves C1-esterase inhibitor, and antibodies specific for the polypeptide. Also disclosed are methods employing the polypeptide for diagnosing enterohemorrhagic E. coli infection, identifying potential inhibitors of its activity, and reducing viscosity of material containing glycosylated polypeptides.

Abstract: Described herein are methods for purifying a protein of interest from a mixture of proteins wherein the mixture comprises the protein of interest and a fusion analog thereof. The method begins with a recovery in which filtration is used to remove cells and concentrate the protein of interest. Liquid chromatography is then used to remove fusion analogs and other contaminants resulting in a composition substantially free of contaminants. Substantially pure compositions of the protein of interest find use in therapeutic preparations.

Abstract: Conjugates of the enzyme alliinase with a protein carrier that targets the alliinase to specific cells are used in combination with alliin to produce allicin at a desired target site. The enzyme converts alliin to allicin at the target site to kill cancer cells or pathogens.

Abstract: A process for preparing arrays of two or more heterogeneous catalysts, heterogeneous catalyst precursors, or combinations thereof in a body having preferably parallel through-channels. In this process, a solution, emulsion or dispersion of elements present in the catalyst, catalyst precursor, or combination thereof, is first prepared, and is used to simultaneously or successively coat the channels of the body to produce freshly impregnated moist channels. These channels are then treated and reacted with one or more reactive gases, and the coated body is optionally heated in the presence or absence of inert or reactive gases.

Abstract: The present invention is based on the discovery of a composition that provides targeted ubiquitination. Specifically the composition contains a ubiquitin pathway protein binding moiety which recognizes a ubiquitin pathway protein and a targeting moiety which recognizes a target protein. In addition, the present invention provides libraries of compositions, where each composition contains a ubiquitin pathway protein binding moiety and a member of a molecular library. The libraries of the present invention can be used to identify proteins involved in a predetermined function of cells.

Abstract: Tubedown-1 (tbdn-1), a protein associated with acetyltransferase activity has been characterized and its cDNA isolated. Tbdn-1 regulates endothelial differentiation through protein acetylation, DNA-binding or by interacting with and/or acetylating other protein targets important for endothelial differentiation. In normal adult eyes, tbdn-1 is expressed highly in the corneal endothelium proper and in the vascular endothelium of the limbus and retina. Tbdn-1 is absent or downregulated in the vascular endothelia of diseased and injured eyes, including eyes from patients with proliferative retinopathies involving neovascularization. Inhibition of tbdn-1 expression in endothelial cells in vitro indicates tbdn-1 acts as an inhibitor of angiogenesis. Thus, high levels of tbdn-1 expression present in normal ocular endothelial cells is associated with suppression of abnormal neovascularization in the eye demonstrating the therapeutic usefulness of tbdn-1 as a regulator of retinal angiogenesis.

Abstract: Described herein are methods for the production of monoclonal antibodies in filamentous fungi host cells. The monoclonal antibodies are expressed as full-length fusion proteins that retain functional antigen binding and antibody-dependent cellular cytotoxicity capabilities. Improvements in the cleavage of the glucoamylase-light chain fusion protein to yield a mature antibody are also provided. The antibodies produced in filamentous fungi show equivalent pharmacokinetic disposition to antibodies produced in mammalian cells.

Abstract: The invention provides methods of discovering nitroreductases and biocatalytic methods for reducing compounds comprising a nitro group.

Abstract: This invention relates to methods and compositions for monitoring the interaction of binding partners as a function of the addition or subtraction of a phosphate group to or from one of the binding partners by a protein kinase or phosphatase.