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.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: A method of mutagenesis by which a predetermined amino acid is introduced into each and every position of a selected set of positions in a preselected region (or several different regions) of a protein to produce library of mutants. The method is based on the premise that certain amino acids play crucial role in the structure and fuction of proteins. Libraries can be generated which contain a high proportion of the desired mutants and are of reasonable size for screening. This libraries can be used to study the role of specific amino acids in protein structure and function and to develop new or improved proteins and polypeptides such as enzymes, antibodies, single chain antibodies and catalytic antibodies.

Abstract: The invention provided compositions and methods to initiate site-specific thrombosis in tumor vasculature. The present invention also provides methods for using the disclosed compositions and methods to treat tumors.

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 methods and compositions of the present invention are directed to enhancing an immune response and increasing vaccine efficacy through the simultaneous or sequential targeting of specific immune system components. More particularly, specific immune components, such as macrophages, dendritic cells, B cells and T cells, are individually activated by component-specific immunostimulating agents. One such component-specific immunostimulating agent is an antigen-specific, species-specific monoclonal antibody. The invention is also directed to a method for the in vitro production of the antigen-specific, species-specific monoclonal antibodies which relies upon the in vitro conversion of blood-borne immune cells, such as macrophages and lymphocytes. Vaccine efficacy is enhanced by the administration of compositions containing component-specific immunostimulating agents and other elements, such as antigens or carrier particles, such as colloidal methods, such as gold.

Abstract: The present invention relates to the field of glycosylation engineering of proteins. More particularly, the present invention relates to glycosylation engineering to generate proteins with improved therapeutic properties, including antibodies with increased antibody-dependent cellular cytotoxicity.

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 purified and isolated polynucleotides encoding Type I ribosome-inactivating proteins (RIPS) and analogs of the RIPs having a cysteine available for disulfide bonding to targeting molecules. Vectors comprising the polynucleotides and host cells transformed with the vectors are also provided. The RIPs and RIP analogs are particularly suited for use as components of cytotoxic therapeutic agents of the invention which include gene fusion products and immunoconjugates. Cytotoxic therapeutic agents or immunotoxins according to the present invention may be used to selectively eliminate any cell type to which the RIP component is targeted by the specific binding capacity of the second component of the agent, and are suited for treatment of diseases where the elimination of a particular cell type is a goal, such as autoimmune disease, cancer and graft-versus-host disease.

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 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: Catalytic antibodies, including 38C2 and 33F12, are capable of efficiently catalyzing a wide variety of ketone-ketone, ketone-aldehyde, aldehyde-ketone, and aldehyde-aldehyde intermolecular aldol reactions, and in some cases to catalyze their subsequent dehydration to yield aldol condensation products. A number of intramolecular aldol reactions have also been defined. Catalysis of all intramolecular aldol reactions examined yields the corresponding condensation products.

Abstract: This invention provides for new recombinant ribonuclease proteins which are active when expressed by bacteria. This allows the recombinant ribonucleases of this invention to be fused in-frame with ligand binding moieties to form cytotoxic fusion proteins. Furthermore, these proteins are more active than ribonucleases currently available even though the proteins of this invention lack an N-terminal pyroglutamic acid, which has been found to be necessary for ribonucleolytic activity. Because these proteins are recombinant proteins, mutations which increase cytotoxicity can be engineered.

Abstract: Disclosed are antibodies which catalyze hydrolysis of &bgr;-amyloid. Antibodies generated are characterized by the amide linkage which they hydrolyze. Methods of generating the antibodies by using &bgr;-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 &bgr;-amyloid. The vectorized antibody can take the form of a bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a transition state adopted by &bgr;-amyloid during hydrolysis.

Abstract: Disclosed are water soluble compositions of paclitaxel and docetaxel formed by conjugating the paclitaxel or docetaxel to a water soluble polymer such as poly-glutamic acid, poly-aspartic acid or poly-lysine. Also disclosed are methods of using the compositions for treatment of tumors, auto-immune disorders such as rheumatoid arthritis. Other embodiments include the coating of implantable stents for prevention of restenosis.

Abstract: Compositions that include an A&bgr; polypeptide linked to a non-A&bgr; polypeptide are described, as well as methods of using such compositions.

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: A hybrid protein contains a protein that binds to a receptor of mastocytes and basophils and is endocyted by them. The protein can be IgE; IgE fragment; IgE Fc fragment; antibody against IgE receptor of mastocytes and basophils; fragment of the antibody against the IgE receptor of mastocytes and basophils; antibody against mastocyte specific potassium channel; and mast cell degranulating peptide. The hybrid protein also contains a protease cleaving proteins of the secretion process of the mastocytes and basophils so as to inhibit the secretion process without killing the mastocytes and basophils.

Abstract: The present invention describes IgE antagonists (including variant anti-IgE antibodies) and their use in diagnosis, therapy or prophylaxis of allergic and other IgE-mediated disorders, including asthma, food allergies, hypersensitivity and anaphylactic reactions.

Abstract: The invention provides methods for detection, diagnosis and monitoring of tumor cells in a sample of mammalian cells. In one aspect, the invention provides methods for detecting the protein, p38.5 expressed at the cell surface, where cell surface expression of p38.5 is indicative of a tumor cell, particularly of hematopoietic origin. In another aspect the invention provides methods of diagnosis of tumor cells by determining the total level of expression of p38.5 or p38.5-specific RNA, a higher than normal level of total p38.5 expression by the cells being diagnostic of tumor cells in a wide range of cell types. Methods of treating tumors expressing cell surface p38.5 are also provided. Also described are screening methods for identifying compounds that inhibit NK mediated cytotoxicity.

Abstract: The structure, formation and use of blocked antibodies, especially those blocked with Protein A, or active fragments of Protein A, are disclosed as well as processes of producing such antibodies. The uses of such blocked antibodies to achieve significant reduction in both specific cross-reaction and non-specific interaction thereby increasing specificity and reactivity with targeted antigenic sites is also described.

Abstract: The present invention is directed generally to catalytic antibodies and, more particularly, to a novel method of producing same. The method of the present invention is predicated in part on the exploitation of the products of catalysis to induce B cell mitogenesis. In a preferred embodiment, a growth factor having an ability to induce B cell mitogenesis is linked to a target antigen to which catalytic antibodies are sought. B cell mitogenesis is then dependent on the catalytic cleavage of the antigen portion of the growth factor by catalytic antibodies on the surface of B cells. The method of the present invention is useful for generating catalytic antibodies for both therapeutic and diagnostic purposes.

Abstract: Antigens capable of eliciting antibodies which can enhance the rate of chemical reactions at peptide bonds are disclosed. In particular, the rate of cleavage or formation of metastable peptide bonds, such as ASN-X, ASP-X, GLN-X, GLU-X, LYS-X, and HIS-Y-X, where X and Y are any amino acid, is enhanced by antibodies elicited by said antigen.

Abstract: A fusion protein for treatment of prostate cancer and other cancers which includes an endopeptidase bound to a monoclonal antibody, or an antigen binding portion thereof, specific for prostate specific membrane antigen (PSMA)expressed either on the tumor cell surface or on the surface of epithelial cells within the tumor. The invention also features pharmaceutical compositions comprising such fusion proteins as well as methods of manufacture and treatment with such fusion proteins.

Abstract: Disclosed are compositions containing antibody conjugates made up of an antibody fragment and a biomolecule. The biomolecule is coupled to the antibody fragment via a reactive chemical group such that the coupling between the biomolecule and the antibody fragment is resistant to reducing agents. Reactive chemical groups include sulfhydryl groups, amino groups, carboxyl groups, and imidazole groups. The reactive chemical group can be in the hinge region of the antibody fragment. This location reduces or eliminates interference between the antibody/antigen interaction and the biomolecule. The biomolecule can be coupled to the antibody fragment via a maleimide group. The antibody fragment preferably is a half antibody or a F(ab′)2. Half antibodies can be produced by reducing an antibody to break disulfide bonds.

Abstract: This patent application describes the use of molecular imprinting as a means for preparation of anti-idiotypic imprint matrices. With this technique, imprints of artificial or natural molecules including their recognition sites, such as of molecularly imprinted polymers or biological receptors, antibodies or enzymes, can be prepared. In the former case, using the original imprints as casts or molds in a subsequent polymerisation step, utilising preferentially functionally complementary monomers, the formation of imprint materials containing recognition sites complementary in shape and functionality with the original imprint can be obtained but being of different composition. Alternatively, imprints or images of the artificial or biological species can be obtained directly. The so formed preparations can be used in a vast variety of applications, e.g. as new drugs, inhibitors or new affinity materials.

Abstract: A method for screening a cDNA library by identifying the expressed protein target, comprising:

Abstract: Described and claimed are compounds of the formula wherein: Y is a polypeptide, R1 is bonded to the N-terminus of Y and is hydrogen or a branched or linear, substituted or unsubstituted, C1-21 alkyl, alkene, or alkyne group, R2 is a side chain of a naturally occuring amino acid, and X is Such compounds are useful as haptens and immunogens for the elicitation of antibodies which catalytically enhance the rate of formation or hydrolysis of primary amide bonds. Also described and claimed are methods employing the compounds and antibodies.

Abstract: The present invention relates to novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: An immunoassay method including reacting a sample from a patient with a bispecific antibody, wherein the bispecific antibody includes one antibody specific for a compound to be detected and a second antibody specific for a compound foreign to said patient sample, and subsequently reacting the patient sample with a polymer probe, wherein the polymer probe includes a compound recognized by the second antibody in the bispecific antibody complex and further includes at least two detectable signals; the bispecific antibody; and the polymer probe of the immunoassay method are disclosed.

Abstract: Methods are provided for deuteration, tritiation, dedeuteration or detritiation of a carbonyl compound. A catalytic antibody that catalyzes an aldol addition reaction is contacted with a carbonyl compound to exchange at least one hydrogen atom of the carbonyl compound with a deterium or tritium atom of an isotopically enriched water molecule, or to exchange at least one deuterium or tritium atom of the carbonyl compound with a hydrogen atom. The aldol addition reaction may be between an aliphatic ketone donor and an aldehyde acceptor. Isotopically enriched water molecules include deuterium hydrogen oxide, dideuterium oxide, tritium hydrogen oxide, ditritium oxide and deuterium tritium oxide. The catalytic antibody may be that secreted by hybridoma 38C2 (ATCC HB 12005) or 33F12 (ATCC HB 12004).

Abstract: A conjugate compound comprises a cell-specific portion, such as an antibody specific to tumour cell antigens, and an enzymatically active portion which will cleave a cyanogenic compound to release cyanide. Enzymes such as &bgr;-glucosidases are suitable. The cyanogenic compound, e.g. amygdalin or some other plant-derived saccharide, is administered after the conjugate. Intravesical (intra-bladder) administration is preferred (for bladder cancers) and forms a further aspect of the invention, whether the compound is cyanide-liberating (as above) or suitable for therapy or imaging in any other way.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: Catalytic monoclonal antibodies (abzymes) with selective protease activity in the pathologies characterized by the presence of plaques and fibrillar aggregates with protein component; methods for the preparation thereof and the use thereof as medicaments in the treatment of pathologies such as Alzheimer's disease, amyloidosis, atherosclerosis, prions diseases.

Abstract: Described and claimed are compounds of the formula 1

Abstract: Antibodies that catalyze the aldol reaction are generated by immunization with a reactive compound that covalently traps a Lysine (Lys) residue in the binding pocket of the antibody by formation of a stable vinylogous amide, i.e., a covalent antibody/hapten complex. The resultant catalytic antibodies employ a catalytic mechanism which mimics the catalytic mechanism employed by natural class I aldolase enzymes.

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: The present invention is directed generally to catalytic antibodies and, more particularly, to a novel method of producing same. The method of the present invention is predicated in part on the exploitation of the products of catalysis to induce B cell mitogenesis. In a preferred embodiment, a growth factor having an ability to induce B cell mitogenesis is linked to a target antigen to which catalytic antibodies are sought. B cell mitogenesis is then dependent on the catalytic cleavage of the antigen portion of the growth factor by catalytic antibodies on the surface of B cells. The method of the present invention is useful for generating catalytic antibodies for both therapeutic and diagnostic purposes.

Abstract: Catalytic antibodies, including 38C2 and 33F12, are capable of efficiently catalyzing a wide variety of ketone-ketone, ketone-aldehyde, aldehyde-ketone, and aldehyde-aldehyde intermolecular aldol reactions, and in some cases to catalyze their subsequent dehydration to yield aldol condensation products. A number of intramolecular aldol reactions have also been defined. Catalysis of all intramolecular aldol reactions examined yields the corresponding condensation products.

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: Three monoclonal aldolase antibodies, generated against a &bgr;-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions providing ent-9a-k by kinetic resolution. Compounds 9a, 9g and 9k were resolved in multi-gram quantities using 0.005-0.0004 mol % antibody catalyst. Enantiomerically pure starting materials, 9a-k, are useful synthons for the construction of epothilones A-E (2-6) and their analogs including 13-alkyl derivatives. Previously, the use of compound 9a as a synthon was reported in the preparation of epothilones A-D, 2-5. To further expand this synthon-based strategy, syntheses of epothilone E, 6, 13-methyl epothilone C, 7, and their trans-isomers have been achieved starting from enantiomerically pure thiazole aldols 9g and 9a, respectively, prepared by large-scale antibody catalyzed resolutions.

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: This invention provides a polypeptide comprising a light chain domain which comprises a complementarity determining region 1 having the amino acid sequence RSSXGTITXXNYAN (Seq ID No: 73), a complementarity determining region 2 having the amino acid sequence XNNYRPP (Seq ID No: 74) and a complementarity determining region 3 having the amino acid sequence ALWYSNHWV (Seq ID No: 75), interposed between appropriate framework regions, and linked to said light chain domain a heavy chain domain which comprises a complementarity determining region 1 having the amino acid sequence DYNMY (Seq ID No: 76), a complementarity determining region 2 having the amino acid sequence YIDPXNGXIFYNQKFXG (Seq ID No: 77) and a complementarity determining region 3 having the amino acid sequence GGGLFAX (Seq ID No: 78) interposed between appropriate framework regions, said polypeptide having a conformation suitable for degrading cocaine.

Abstract: Hapten and antigen designed for eliciting catalytic antibodies effective in inhibiting the ethylene production pathway in plants by deactivating a precursor thereof either by decomposition or derivatization. Catalytic antibodies effective in inhibiting the ethylene production pathway in plants by deactivating a precursor thereof. Genes encoding for such catalytic antibodies and plants and cells expressing these genes and producing the catalytic antibodies for controlling the ripening of fruits and vegetables, as well as for controlling senescence of plant tissue.

Abstract: Prodrugs that are activated by and conjugated to a catalytic antibody conjugated to a moiety that binds to a tumor cell population are provided.

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: This invention provides compounds which are analogs to the hydrolysis transition-state of a cocaine benzoyl ester group. This invention also provides such analogs linked to carrier proteins, and antibodies thereto. This invention further provides pharmaceutical composition for decreasing concentration in a subject using the antibodies produced.

Abstract: Disclosed and claimed are methods for selecting a recombinant virus, phage or cell expressing a catalytic antibody or catalytic portion thereof, or for selecting catalytic activity by a moiety. The method employs reaction-based selection for catalytic activity. The method can also be used to concentrate (increase the proportion of catalytic to non-catalytic moieties) a sample containing a catalytic moiety or viruses, phages or cells expressing a catalytic moiety. The selection or concentrating can be by employing a mechanism-based inhibitor, catalysis-accelerated movement, surface binding, changes in enthalpic component of binding as a function of temperature, or changes in binding by competition, or combinations thereof. The invention also comprehends a method for producing a recombinant virus or a cell-line expressing a catalytic moiety such as a catalytic antibody or catalytic portion thereof; and, this method can include infecting a suitable host with viruses which are screened for the expression.