Abstract: Titanium oxide-antibody conjugated particles are disclosed, which are provided with selective binding ability without loss of dispersibility and catalytic activity by modifying titanium oxide conjugated particles, dispersed in a water-based solvent by a water-soluble polymer, with an antibody via a linker molecule bound without changing the nature of the water-soluble polymer. The present invention is an antitumor agent, comprising titanium oxide-antibody conjugated particles, wherein a linker molecule is bound to the titanium oxide surface of the titanium oxide conjugated particles, dispersed in a water-based solvent by a water-soluble polymer, via at least one functional group selected from a group consisting of a carboxyl group, an amino group, a diol group, a salicylic acid group, and a phosphoric acid group, and wherein the titanium oxide conjugated particles are further modified with an antibody via the linker molecule.

Abstract: The invention relates to therapeutic conjugates with improved ability to target various cancer cells containing a targeting moiety and a therapeutic moiety. The targeting and therapeutic moieties are linked via an acid cleavable linkage that increases therapeutic efficacy of the immunoconjugate.

Abstract: Methods and kits for radiolabeling proteins, peptides and ligands with radiolytic isotopes, particularly yttrium-90, are disclosed, whereby sufficient purity, specific activity and binding affinity are achieved such that the radiolabeled protein may be directly administered to a patient without further column purification. Such kits and methods will be particularly useful in bringing radioimmunotherapy to the hospital and outpatient setting for the treatment of cancer.

Abstract: Anti-STEAP-1 antibodies and immunoconjugates thereof are provided. Methods of using anti-STEAP-1 antibodies and immunoconjugates thereof are provided.

Abstract: An agent for use in medicine, which agent comprises a plurality of ligands covalently co-linked so as to form a complex with a plurality of C-reactive protein (CRP) molecules in the presence thereof, wherein (i) at least two of the ligands are the same or different and are capable of being bound by ligand binding sites present on the CRP molecules; or (ii) at least one of the ligands is capable of being bound by a ligand binding site present on a CRP molecule, and at least one other of the ligands is capable of being bound by a ligand binding site present on a serum amyloid P component (SAP) molecule.

Abstract: The present invention relates generally to receptor-selective variants of the low-density lipoprotein receptor-associated protein (RAP) and compositions thereof, methods of generating such variants and methods of using such receptor-selective RAP variant compositions for therapeutic purposes. The invention also relates to antibodies that bind to one or a small subset of CR-containing proteins.

Abstract: Antibody binding assays and radiolabeling kits are disclosed for radiolabeling and testing therapeutic antibodies in the commercial setting. In particular, the kits are designed for making and evaluating radiolabeled anti-CD20 conjugates to be used for the treatment and imaging of B cell lymphoma tumors. All kit reagents are sterile and are designed to achieve a high level of antibody radiolabeling and product stability with results which are highly reproducible.

Abstract: An alternative HER-2/neu product, herstatin, consists of subdomains I and II from the ectodomain of p185HER-2 and a unique 79 amino acid C-terminus encoded by intron 8. Recombinant herstatin added to cells was found to bind to and inhibit p185HER-2. The effects of ectopic expression of herstatin in combination with either p185HER-2 or with its homolog, the EGF receptor, in several cell lines was studied. Cotransfection of herstatin with HER-2 inhibited p185HER-2 levels and caused an approximate 8-fold reduction in p185 tyrosine phosphorylation. Inhibition of p185HER-2 tyrosine phosphorylation corresponded to a dramatic decline in colony formation by cells that coexpressed p185HER-2 and herstatin. Herstatin also interferred with EGF activation of the EGF receptor in cotransfected cells as demonstrated by impaired receptor tyrosine phosphorylation, reduced receptor down-regulation, and growth suppression.

Abstract: The present invention is based on the discovery that the administration of at least one immunoconjugate and at least one chemotherapeutic agent provides an unexpectedly superior treatment for cancer. The present invention is directed to compositions comprising at least one immunoconjugate and at least one chemotherapeutic agent and to methods of treating cancer using at least one immunoconjugate and at least one chemotherapeutic agent. The present invention also provides methods of modulating the growth of selected cell populations, such as cancer cells, by administering a therapeutically effective amount of at least one chemotherapeutic agent and at least one immunoconjugate.

Abstract: The invention provides isolated nucleic acid molecules and polypeptide molecules that encode glycoprotein VI, a platelet membrane glycoprotein that is involved platelet-collagen interactions. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The present invention relates to an insulinotropic peptide conjugate having improved in-vivo duration of efficacy and stability, comprising an insulinotropic peptide, a non-peptide polymer and a carrier substance, which are covalently linked to each other, and a use of the same. The insulinotropic peptide conjugate of the present invention has the in-vivo activity which is maintained relatively high, and has remarkably increased blood half-life, and thus it can be desirably employed in the development of long acting formulations of various peptide drugs.

Abstract: The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

Abstract: The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: Provided is an immunotoxin including (a) an anti-CD19 antibody lacking an Fc fragment, (b) a modified exotoxin A protein having both Domains II and III, but lacking Domain I, and (c) a peptide linker joining the C-terminal end of the antibody to the N-terminal end of the modified exotoxin A protein. The linker is substantially resistant to extracellular cleavage. The modified exotoxin A protein may be further modified to include a C-terminal KDEL sequence (SEQ ID NO: 6) that promotes transport of the protein to the endoplasmic reticulum of cells that have taken up the immunotoxin. Also provided is an anti-CD19 antibody having enhanced binding activity, antibody-dependent cellular cytotoxicity (ADCC) and methods for using the antibody to treat a disease state associated with B-lineage cells that express CD19. The antibody variable light and variable heavy chains have unique sequences in their J region relative to known anti-CD19 antibody sequences.

Abstract: This invention relates to the field of antibody-drug conjugates, and more particularly antibody-drug conjugates that are intended for the treatment and/or diagnosis of diseases such as tumors and/or inflammatory reactions.

Abstract: The invention relates to molecules for treatment and diagnosis of tumors and malignancies, comprising a tumor seeking biomolecule, which is coupled to an intercalating moiety, which is capable of complexing a metal, which metal is preferably a radioactive metal, to the use of these molecules and to therapeutic and diagnostic compositions containing them.

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody.

Abstract: The present invention provides polymeric conjugates containing positively charged moieties. Methods of making the polymeric delivery systems and methods of treating mammals using the same are also disclosed.

Abstract: The present invention provides a monoclonal antibody or a fragment thereof binding to the extracellular I-domain of integrin alpha10beta1 and a hybridoma cell line deposited at the Deutsche Sammlung von Microorganismen und Zellkulturen GmbH under the accession number DSM ACC2583. Furthermore, the present invention also provides a monoclonal antibody or a fragment thereof binding to the extracellular I-domain of integrin alpha10beta1 produced by the hybridoma cell line deposited. Methods and uses of said antibody or a fragment thereof in identifying and selecting cells of a chondrogenic nature for treatment purposes, in particular for the identification and isolation of chondrocytes, mesenchymal progenitor cells and embryonic stem cells for tissue engineering of cartilage, or for identifying diagnostic and therapeutic tools in studying the biological role and the structural/functional relationships of the integrin alpha10beta1 with its various extracellular matrix ligands are also included.

Abstract: The present invention provides analogues of duocarmycins that are potent cytotoxins. Also provided are peptidyl and disulfide linkers that are cleaved in vivo. The linkers are of use in forming prodrugs and conjugates of the cytotoxins of the invention as well as other diagnostic and therapeutic moieties. The invention provides prodrugs and conjugates of the duocarmycin analogues with the linker arms of the invention.

Abstract: Disclosed are immunoconjugates having specificity for CD138 that diminish adhesion of CD138 expressing tumor cells to stroma cells and methods of using the same. This diminished adhesion renders the tumor cells not only susceptible to the immunoconjugate, but also to other agents, in particular cytotoxic agents.

Abstract: This invention, inter alia, relates to CD19 binding agents and methods of using such CD19 binding agents for treating disease.

Abstract: Protein and polypeptide derivatives and their salts are claimed characterized in that a protein or polypeptide is conjugated via an intermediate grouping containing at least one radical of the formula —C(R)?N— (or —N?C(R)—) or —CH(R)—NH— (or —NH—CH(R)—), wherein R is hydrogen or a hydrocarbon residue which may be substituted, with the same or a different protein or polypeptide, with a reporter group or a cytotoxic agent as well as a process for their preparation and the novel intermediates therefor.

Abstract: The present invention relates to therapeutic agents with reduced toxicity comprising a serum albumin binding peptide (SABP), a targeting agent and a cytotoxic agent. The present invention also relates to methods for reducing the toxicity of therapeutic agents and methods of treatment using the therapeutic agents with reduced toxicity.

Abstract: The invention pertains to conjugates of the capsular polysaccharide of Vibrio cholerae O139, or a structurally and/or immunologically related oligo- or poly-saccharide, and a carrier. These conjugates are useful as pharmaceutical compositions and/or vaccines to induce serum antibodies which have bactericidal (vibriocidal) activity against V. cholerae, in particular V. cholerae O139, and are useful to prevent, treat and/or reduce the severity of disease caused by V. cholerae infection, such as cholera. The present invention also relates to diagnostic tests for V. cholerae infection, and/or cholera caused by V. cholerae infection, using one or more of the oligo- or poly-saccharide-carrier conjugates or antibodies described above.

Abstract: Modified antibodies, or antigen-binding fragments thereof, to the extracellular domain of human prostate specific membrane antigen (PSMA) are provided. The modified anti-PSMA antibodies, or antigen-binding fragments thereof, have been rendered less immunogenic compared to their unmodified counterparts to a given species, e.g., a human. Pharmaceutical compositions including the aforesaid antibodies, nucleic acids, recombinant expression vectors and host cells for making such antibodies and fragments are also disclosed. Methods of using the antibodies of the invention to detect human PSMA, or to ablate or kill a PSMA-expressing cell, e.g., a PSMA-expressing cancer or prostatic cell, either in vitro or in vivo, are also provided.

Abstract: The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: The present invention provides heterocyclic linker compounds useful for linking drug moieties to ligands. The compounds also include drug-ligand conjugates comprising a ligand capable of targeting a selected cell population, and a drug connected to the ligand by a heterocyclic linker moiety. The linker moiety comprises a peptide sequence that is a substrate for an intracellular enzyme, for example a cathepsin, that cleaves the peptide at an amide bond. The peptide further contains a self-immolating moiety which connects the drug and the protein peptide sequence. Upon cleavage of the peptide sequence by an intracellular enzyme the self-immolating moiety cleaves itself from the drug moiety such that the drug moiety is in an underivatized and active form.

Abstract: The present invention relates generally to the prevention and treatment of disease states, and more particularly to the treatment and prevention of plasma cell disorders and plasma cell dyscrasias and other malignancies, amyloidosis and amyloid-associated diseases. In particular, the present invention relates to methods and compositions comprising immunogenic peptides for the treatment and prevention of diseases and malignancies, for example plasma cell disorders, plasma cell dyscrasias and amyloidosis or amyloid-associated diseases. The present invention also provides methods for an assay to screen for therapeutic vaccines for plasma cell disorders, plasma cell dyscrasias and amyloidosis or amyloid-associated diseases.

Abstract: Nucleic acid-immunoliposome compositions useful as therapeutic agents are disclosed. These compositions preferably comprise (i) cationic liposomes, (ii) a single chain antibody fragment which binds to a transferrin receptor, and (iii) a nucleic acid encoding a wild type p53. These compositions target cells which express transferrin receptors, e.g., cancer cells. These compositions can be used therapeutically to treat persons or animals who have cancer, e.g., head and neck cancer, breast cancer or prostate cancer.

Abstract: The present disclosure relates to compositions and methods for the treatment of a disease, e.g., cancer or pathogenic infection, using a bioconjugated nanoparticle comprising a biocompatible quantum dot conjugated to a targeting moiety. The targeting moiety allows for the nanopaticle to bind to a cancer cell or pathogenic organism. The quantum dot, upon excitation by soft x-rays, emits electromagnetic radiation at a frequency of ultraviolet light, thereby allowing for the disruption of the DNA found in the cancer cell or pathogenic organism.

Abstract: The present invention relates to a compound comprising a tripartite structure in the format C-B-A or C?-B?-A? wherein moiety A and moiety A? is a raftophile, moiety B and moiety B? is a linker, moiety C and moiety C? is a pharmacophore; and wherein moiety B and B? is a linker which has a backbone of at least 8 carbon atoms and wherein one or more of said carbon atoms may be replaced by nitrogen, oxygen or sulfur. Furthermore, specific medical and pharmaceutical uses of the compounds of the invention are disclosed.

Abstract: This invention relates to compounds comprising one or more therapeutic and/or diagnostic moieties and one or more functional moieties linked together via one or more triazole-containing linkers and to their intermediates and methods of their preparation. The triazole-containing linker may optionally contain one or more conditionally-cleavable or conditionally-transformable moieties and one or more spacer systems in between said moiety/moieties and the one or more therapeutic and/or diagnostic moieties.

Abstract: A conjugate comprising a) a trifunctional cross-linking moiety, to which is coupled b) an affinity ligand via a linker 1, c) a cytotoxic agent, optionally via a linker 2, and d) an anti Erb antibody or variants thereof having the ability to bind to Erb antigens expressed on mammalian tumour surfaces with an affinity-binding constant of at least 5×106 M?1, wherein the affinity ligand is biotin, or a biotin derivative having essentially the same binding function to avidin or streptavidin as biotin, wherein stability towards enzymatic cleavage of the biotinamide bond has been introduced in linker 1.

Abstract: Drug compositions, fusions and conjugates are provided. The drug fusions and conjugates contain a therapeutic or diagnostic agent that is fused or conjugated to an antigen-binding fragment of an antibody that binds serum albumin. The drug compositions, fusions and conjugates have a longer in vivo half-life in comparison with the unconjugated or unfused therapeutic or diagnostic agent.

Abstract: A composition for treating a subject is provided. The composition includes antigen specific dimeric secretory IgA and pentameric IgM therapeutic. A process for manufacturing a medicament for the treatment of C. difficile associated disease in a human is also provided that the modification of antigen specific dimeric secretory IgA and pentameric IgM with secretory component to form a antigen specific dimeric secretory IgA and pentameric secretory IgM therapeutic. The antigen specific dimeric secretory IgA and the pentameric secretory IgM therapeutic is then mixed with formulating agents to create a capsule, tablet, liquid or suppository dosing form. The therapeutic is amenable to enrobement directly through microencapsulation or the dosing form is coated with an enteric coating. A method of C. difficile treatment with the therapeutic is also provided that is amenable to supplementation with concurrent or prior antibiotic administration.

Abstract: Methods using internal image antibodies for photodiagnosis and/or phototherapy. The internal image antibodies are conjugated with a photoactive molecule such as a dye or photosensitizer, to target specific regions, such as biological receptors. The photoactive molecules are then activated for diagnosis or therapy. Advantageously, the internal image antibody is specific for a biological receptor, but does not require isolation of the receptor to prepare the antibody, and provides the desired specificity and selectivity for targeted diagnosis or therapy.

Abstract: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.

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: Activated polymeric bicine derivatives such as, as well as conjugates made therewith are disclosed. Methods of making and using the bicine derivatives are also disclosed.

Abstract: Polypeptides and multimeric polypeptides capable of binding interleukin-4 (IL-4) and interluekin-13 (IL-13) which are useful therapeutically in methods of treating IL-4 and IL-13-related conditions or diseases.

Abstract: There is disclosed antibody molecules containing at least one CDR derived from a mouse monoclonal antibody having specificity for human TNF?. There is also disclosed a CDR grafted antibody wherein at least one of the CDRs is a hybrid CDR. Further disclosed are DNA sequences encoding the chains of the antibody molecules, vectors, transformed host cells and uses of the antibody molecules in the treatment of diseases mediated by TNF?.

Abstract: The present invention provides AA targeting compounds which comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody. Various uses of the compounds are provided, including methods to treat disorders connected to abnormal angiogenesis.

Abstract: Compositions containing soluble B7-H4 (sH4) antagonists in an amount effective to reduce, inhibit, or mitigate an inflammatory response in an individual and methods for the treatment or prophylaxis of inflammatory disorders and autoimmune diseases or disorders are provided. Soluble H4 has been discovered to interfere with B7-H4 activity including B7-H4's activity as an inhibitor of T cell immunity. Thus, interference of sH4 biological activity is an effective method to restore B7-H4 activity and thereby provide an effective method for treating inflammatory diseases or disorders including autoimmune diseases or disorders.

Abstract: The present invention relates to at least one novel human EPO mimetic hinge core mimetibody or specified portion or variant, including isolated nucleic acids that encode at least one EPO mimetic hinge core mimetibody or specified portion or variant, EPO mimetic hinge core mimetibody or specified portion or variants, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: The present invention is directed to methods of producing conjugates of A? peptide immunogens with protein/polypeptide carrier molecules, which are useful as immunogens, wherein peptide immunogens are conjugated to protein carriers via activated functional groups on amino acid residues of the carrier or of the optionally attached linker molecule, and wherein any unconjugated reactive functional groups on amino acid residues are inactivated via capping, thus retaining the immunological functionality of the carrier molecule, but reducing the propensity for undesirable reactions that could render the conjugate less safe or effective. Furthermore, the invention also relates to such immunogenic products and immunogenic compositions containing such immunogenic products made by such methods.

Abstract: The present invention provides humanized, chimeric and human anti-CSAp antibodies and anti-CSAp antibody fusion proteins that are useful for the treatment and diagnosis of various cancers, including colon cancer.

Abstract: The present invention relates to monoclonal antibodies that bind to the extracellular domain of prostate-specific membrane antigen (PSMA), hybridoma cell lines producing the antibodies, and methods of using such antibodies for diagnosis and treatment of cancer. In particular, thirty-five monoclonal antibodies reactive with PSMA expressed on the cell surface are exemplified. Additionally, the present invention relates to a novel protein variant (PSM?) of PSMA detected by a number of the antibodies of the invention. The hydrolase activity of PSMA and PSM? allows the use of an immunoenzymatic assay for their detection.

Abstract: The present invention relates to an insulinotropic peptide conjugate having improved in-vivo duration of efficacy and stability, comprising an insulinotropic peptide, a non-peptide polymer and a carrier substance, which are covalently linked to each other, and a use of the same. The insulinotropic peptide conjugate of the present invention has the in-vivo activity which is maintained relatively high, and has remarkably increased blood half-life, and thus it can be desirably employed in the development of long acting formulations of various peptide drugs.

Abstract: A carrier system in the form of protein-based nanoparticles for the cell-specific, intracellular enrichment of at least one pharmacologically active substance. The system has structures that are coupled by reactive groups. The structures enable a cell-specific attachment and cellular absorption of the nanoparticles.