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.

Abstract: The invention relates to novel conjugates of CD44 antibodies with cytotoxic compounds, pharmaceutical compositions comprising such compounds, and their use in tumor therapy.

Abstract: The present invention relates to the use in human and animal nutrition (monogastric and polygastric animals) of known chelates of bivalent metal Mg, Ca, Mn, Co, Cu, Zn and Fe with methionine hydroxy analogue. The present invention further relates to a method for preparing new chelates with methionine hydroxy analogue, both in solid form with iron (II), vanadium (iV) and (V) and molybdenum (V) and (VI), and in liquid form in aqueous solution with iron (II) and (III) and chrome (III). Eventually, the present invention relates to the use of said new chelates, both in solid form with iron (II), vanadium (IV) and (V) and molybdenum (V) and (VI), and in liquid form in aqueous solution with iron (II) and (III) and chrome (III), in human and animal nutrition.

Abstract: Described are ortho carboxy phenol derived acetals and compositions containing ortho carboxy phenol derived acetals which are useful for delivering biologically active compounds to cells. The acetals can be used to reversibly link up to three different molecules and have rapid hydrolysis kinetics in conditions which are present in a cell as well as in vivo. Cleavage of the acetal enhances delivery of the biologically active compound.

Abstract: Heterobifunctional polymeric prodrug platforms for delivering biologically active compounds, including proteins, monoclonal antibodies and the like are disclosed. One preferred compound is Methods of making and using the compounds and conjugates described herein are also provided.

Abstract: A novel anti-polyethylene glycol monoclonal antibody and its preparation are disclosed. Such an antibody can be used for determining polyethylene glycol concentration in vitro or accelerating the clearance of a polyethylene glycol containing compound from the blood circulation in the human body thereby reducing the toxicity associated with the polyethylene glycol containing conjugate. The antibody is particularly useful in cancer therapy where the therapeutic agent is selectively delivered to the tumor by increasing the tumor/blood ratio of the polyethylene glycol containing compound.

Abstract: The present invention relates to a method for the preparation of a conjugate comprising a first and a second polypeptide, said method comprising the steps of (a) incubating said first polypeptide in the presence of a heterobifunctional crosslinker comprising an N-hydroxylsuccinimide ester group and a maleimide group linked via a polyethylene oxide spacer; (b) removing excess heterobifunctional crosslinker; and (c) incubating the reaction product of step (b) with said second polypeptide, wherein said second polypeptide comprises at least one sulfhydryl group. Furthermore, the present invention relates to a conjugate obtainable by the method of the present invention. Also described is a pharmaceutical composition comprising the conjugate of the present invention and, optionally, a pharmaceutically acceptable carrier and/or diluent, and the use of the conjugate for the preparation of a pharmaceutical composition for preventing and/or treating an allergic disease or an autoimmune disease.

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: 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: An antibody, or a derivate or a fragment thereof, having a binding structure for a target structure is described. The antibody is displayed in, and on the cell surface of, human gastrointestinal epithelial tumour cells and in a subpopulation of normal human gastrointestinal epithelial cells. Said binding structure comprises the complementarity determining region (CDR) sequences in the light chain comprising essentially the amino acids number 23–33 (CDR1), 49–55 (CDR2), 88–98 (CDR3) of the amino acid sequence shown in SEQ ID NO:2, and the CDR sequences in the heavy chain comprising essentially the amino acids number 158–162 (CDR1), 177–193 (CDR2, 226–238 (CDR3) of the amino acid sequence shown in SEQ ID NO:2, or other binding structures with similar unique binding properties. There is also described a target structure displayed in, or on the surface of tumour cells, vaccine compositions, pharmaceutical compositions as well as methods related to human malignant diseases.

Abstract: The present invention is directed to the use of antibodies or binding portions thereof, probes, ligands, or other biological agents which either recognize an extracellular domain of prostate specific membrane antigen or bind to and are internalized with prostate specific membrane antigen. These biological agents can be labeled and used for detection of cancerous tissues, particularly cancerous tissues proximate to or containing vascular endothelial cells, which express an extracellular domain of prostate specific membrane antigen. The labeled biological agents can also be used to detect normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof. They also can be used alone or bound to a substance effective to ablate or kill such cells as a therapy for prostate or other cancers.

Abstract: Water-dispersible nanoparticles are prepared by applying a coating of a multiply amphipathic dispersant to the surface of a hydrophobic nanoparticle comprised of a semiconductive or metallic material. The multiply amphipathic dispersant has two or more hydrophobic regions and two or more hydrophilic regions, and is typically polymeric. Preferred polymeric dispersants are comprised of (1) a hydrophobic backbone with hydrophilic branches, (2) a hydrophilic backbone with hydrophobic branches, or (3) a backbone that may be either hydrophobic or hydrophilic, and substituted with both hydrophilic and hydrophobic branches. Monodisperse populations of water-dispersible nanoparticles are also provided, as are conjugates of the water-dispersible nanoparticles with affinity molecules such as peptides, oligonucleotides, and the like.

Abstract: Methods are described for conjugating radioiodinated peptides or carbohydrate structures to proteins with improved yields and qualities of conjugates. In one method, specially designed radioiodinated bifunctional peptides containing nonmetabolizable amide bonds are coupled to antibodies. In a second method, radioiodinated nonmetabolizable bifunctional peptides, which also contain aminopolycarboxylates, are coupled to antibodies. In a third method, radioiodinated bifunctional aminopolycarboxylates are coupled to antibodies. In a fourth method, a hydrazide-appended antibody is coupled to a radioiodinated carbohydrate or a thiolated antibody is coupled to a hydrazide-appended and radioiodinated carbohydrate. In a fifth method a monoderivatized cyanuric chloride is used to conjugate thiolated antibody. Radioiodinated residualizing antibody conjugates made by these methods are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.

Abstract: Protein and polypeptid 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: 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: The present invention provides a mutant antibody comprising a reactive site not present in the wild-type of the antibody and a complementarity-determining region that specifically binds to a metal chelate, wherein the reactive site is in a position proximate to or within the complementarity-determining region.

Abstract: Water-dispersible nanoparticles are prepared by applying a coating of a multiply amphipathic dispersant to the surface of a hydrophobic nanoparticle comprised of a semiconductive or metallic material. The multiply amphipathic dispersant has two or more hydrophobic regions and two or more hydrophilic regions, and is typically polymeric. Preferred polymeric dispersants are comprised of (1) a hydrophobic backbone with hydrophilic branches, (2) a hydrophilic backbone with hydrophobic branches, or (3) a backbone that may be either hydrophobic or hydrophilic, and substituted with both hydrophilic and hydrophobic branches. Monodisperse populations of water-dispersible nanoparticles are also provided, as are conjugates of the water-dispersible nanoparticles with affinity molecules such as peptides, oligonucleotides, and the like.

Abstract: Hybrid proteins are described which comprise one or more antigen-binding antibody fragments covalently linked to one or more serum carrier proteins. The hybrid proteins can bind antigens, have a long half-life in vivo and can be used in medicine for therapy and diagnosis.

Abstract: The present invention provides immunoselective targeting agents that bind to transporters that are transiently accessible on the surface of neuronal cells, and that deliver compounds selectively to such cells. The invention provides methods of selectively killing, as well as methods of selectively promoting survival of, a neuronal cell.

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: Polyacetals comprising a recurring units represented by a formula selected from the group consisting of formula (I) and (II): wherein A comprises at least one acetal group; B is selected from the group consisting of —CH—, —CH(CH3)—, CH2CH—, —CH2C(CH3)—, —CH(CH3)CH—, and —CHCH(CH3)CH(CH3)—; Z is selected from the group consisting of C(O)OR1, C(O)SR1, C(O)NR1R2, and VU; V is a linker group; U is selected from the group consisting of poly(ethyleneimine), poly(propyleneimine), poly(lysine), PAMAM dendrimer, octaamine dendrimer, hexadecaamine dendrimer, enhancer, and targeting receptor; R1 and R2 are each individually selected from the group consisting of hydrogen, C1 to C10 alkyl, and C6 to C10 aryl; D is a linkage selected from the group consisting of carboxylic amide, carboxylic ester, urea, and urethane; and G is selected from the group consisting of C4 to C20 alkyl, C6-C10 aryl, and —(OCH2CH2)n—, where n is in the range of 1 to about 250, are useful in nucleic acid delivery applications.

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: 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: Methods to introduce highly phosphorylated mannopyranosyl oligosaccharide derivatives containing mannose 6-phosphate (M6P), or other oligosaccharides bearing other terminal hexoses, to carbonyl groups on oxidized glycans of glycoproteins while retaining their biological activity are described. The methods are useful for modifying glycoproteins, including those produced by recombinant protein expression systems, to increase uptake by cell surface receptor-mediated mechanisms, thus improving their therapeutic efficacy in a variety of applications.

Abstract: Antibodies to cell surface ligands such as EGFRvIII can be used to therapeutically or diagnostically deliver a radiolabel to tumor cells with high selectivity. The utility of radioconjugated internalizing antibodies is limited, however, by release of the label and its reuptake into normal cells. The invention provides new technology for radioconjugation of internalizing antibodies which reduces the release of label and improves retention of radioconjugated antibodies in lysosomes, where radiation is more effectively and selectively delivered to the nucleus of tumor cells.

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: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that is reactive against a targeted tissue and at least one other arm that is reactive against a linker moiety. The linker moiety encompasses a hapten to which antibodies have been prepared. The antigenic linker is conjugated to one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bispecific antibodies or antibody fragments, as well as methods for using them.

Abstract: Endothelial protein C receptor (EPCR) is found primarily on endothelial cells of large vessels. EPCR translocates from the plasma membrane surface to the nucleus. Molecules which bind to EPCR can be carried from the plasma membrane surface to the nucleus. These molecules include antibodies to EPCR and activated protein C. Protein C, which also binds to EPCR, can be internalized by endothelial cells, but does not enter the nucleus. Thus, EPCR translocation from the plasma membrane to the nucleus provides a means of delivering nucleic acid such as DNA, proteins such as transcription factors, diagnostic agents or other types of drugs to the nucleus of endothelial cells, particularly those on large blood vessels. Conjugates of the materials to be delivered to the nucleus can be formed by ionic or covalent coupling. For example, proteins, including fusion proteins, can be directly conjugated to an anti-EPCR monoclonal antibody.

Abstract: The present invention is directed to betulinol derivatives and betulinol-antibody conjugates having the formulae: and HO-antibody-spacer-(A2)n and, in particular, betulinol dimethyl ether. Methods for making and using these derivatives and conjugates, as well as a method for making and using betulonic aldehyde, are also disclosed.

Abstract: A polymer comprising recurring units represented by formula (I): wherein X is selected from the group consisting of C(O)OR1, C(O)SR1, C(O)NR1R2, and VZ, where R1 and R2 are each individually selected from the group consisting of hydrogen, C1 to C10 alkyl, and C6 to C10 aryl, where V is a labile linker group, and where Z is selected from the group consisting of poly(ethyleneimine), poly(propyleneimine), poly(lysine), PAMAM dendrimer, octaamine dendrimer, and hexadecaamine dendrimer; and wherein Y is selected from the group consisting of —(CH2)2—, —(CH2)2—O—(CH2)2—, —(CH2)2—O—(CH2)2—, and —(CH2)3—NHC(O)—(CH2)6—C(O)NH—(CH2)3— is useful in nucleic acid delivery applications. Polyacetals of the formula (I) are preferably made by reacting appropriate diols and divinyl ethers. In preferred embodiments, complexes formed between polyacetals of the formula (I) and polynucleotides are useful as transfection reagents.

Abstract: The present invention provides methods for reducing or inhibiting angiogenesis in a tissue, by contacting ?5?1 integrin in the tissue with an agent that interferes with specific binding of the ?5?1 integrin to a ligand expressed in the tissue; and methods of identifying angiogenesis in a tissue, by contacting the tissue with an agent that specifically binds ?5?1 integrin, and detecting specific binding of the agent to ?5?1 integrin associated with a blood vessel in the tissue. Also provided are methods of diagnosing a pathological condition characterized by angiogenesis in a tissue in an individual.

Abstract: A supramolecule has a first supramolecular component including a first effector molecule covalently joined to a first nucleic acid, and a second supramolecular component including a second effector molecule covalently joined to a second nucleic acid, wherein the second nucleic acid has a region of at least partial complementarity to the first nucleic acid, wherein the first nucleic acid is in a base pairing relationship with the second nucleic acid and the first or second effector molecules are proteins, polypeptides, lipids or sugars. The supramolecule may further have a third supramolecule component which includes a third effector molecule covalently joined to a third nucleic acid, wherein the third nucleic acid has a region of at least partial complementary to the first nucleic acid or the second nucleic acid and wherein the third nucleic acid is in a base pairing relationship with the second nucleic acid or the first nucleic acid.

Abstract: The present invention provides a novel surface engineering strategy that uses biomolecular interactions to immobilize surface modifying ligands on biomaterial architectures. The surface modified compositions resulting from the inventive method are useful in many contexts, including, but not limited to, scaffolds for tissue engineering and as vehicles for site specific drug delivery. In one preferred embodiment, the biomolecular interaction is achieved by using an “anchor-adapter-tag” system, in which an adapter which can interact specifically and with high selectivity with an anchor molecule (present on the biodegradable surface) and a tag (bound to the ligand to be immobilized) simultaneously is used in attaching the ligand to the surface in a manner which is stable in vitro or in vivo.

Abstract: Conjugates containing a targeting ligand, such as an antibody, a therapeutically active drug and a branched peptide linker. The branched peptide linker contains two or more amino acid moieties that provide an enzyme cleavage site. The number of drugs capable of being bonded to the branched linkers varies by a factor of two for each generation of branching.

Abstract: The present invention is directed to polymer conjugates of biologically active agents and methods of preparing the same. In preferred aspects of the invention, the conjugates are of the formula wherein G is a linear or branched polymer residue such as a polyethylene glycol and B is a residue of an amine-containing or a hydroxyl-containing biologically active moiety such as Ara-C.

Abstract: This invention provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention also provides an immunoconjugate which comprises 1) a gamma radiation-emitting radionuclide of low to moderate cytotoxicity and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention further provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a heterotetramer comprising two heavy chains and two light chains, both heavy chains being either a) IgG2 heavy chains or b) chimeric CD4-IgG2 heavy chains, and both light chains being either a) kappa light chains or b) chimeric CD4-kappa light chains.

Abstract: The invention provides a novel human Mab Fab, cloned by phage display, and its use in diagnostic and therapeutic methods. In particular the invention provides a method for analyzing the OxLDL components of atherosclerotic plaques in vivo and a means to determine their relative pathology. As the method is based on a human Fab rather than a mouse Mab, the progress or regression of the disease may be monitored over time. The antibody may also be used for the analysis of surgical or serum samples ex vivo for the presence of OxLDL. The antibody may also be used to target therapeutic agents to the site of atherosclerotic plaques or may have use as a therapeutic agent itself.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.

Abstract: The subject invention relates to the use of ascorbic acid and derivatives thereof in stabilizing radiolabeled proteins and peptides against oxidation loss of radiolabel and autoradiolysis. Ascorbic acid is added after radiolabeling, including any required incubation period, but prior to patient administration.

Abstract: The present invention provides biologically active linear polypeptides that possess a plurality of biologically active groups, methods employing such peptides to target molecules to cells, and methods employing such peptides for inhibiting the binding of cells to each other.

Abstract: Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions and methods using the new VEGF-specific antibodies are also provided.

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: A method for raising antibodies against molecules, particularly molecules with low immunogenicity, by coupling the molecule to a carrier containing a balanced charge mixture of proteins is provided. Also provided are antibodies and immunoassays containing antibodies raised in accordance with these methods. Pharmaceutical compositions containing these antibodies or a part thereof and methods of using these compositions to treat various diseases and infections are also provided. In addition, vaccines containing an antibody or an immunogenically stimulatory amount of a molecule coupled to the carrier of a balanced charge mixture of proteins and methods of inducing an immune response in an animal against the molecule by administration of these vaccines are provided.

Abstract: Methods are described for conjugating radioiodinated peptides to non-metabolizable carbohydrates with improved yields and qualities of conjugates. Radioiodinated residualizing antibody conjugates comprising a carbohydrate-appended peptide are also provided. The instant radioiodinated residualizing antibody conjugates are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.

Abstract: Compositions and methods are described for preventing and treating sepsis in humans and animals. Surgical patients, low birth weight infants, and burn and trauma victims can be treated prophylactically. Methods for treating acute infections are provided with advantages over current therapeutic approaches.

Abstract: A storage stable composition comprising a carrier usable for the immobilization of compounds containing an amine group, for instance biomolecules and/or affinity ligands. The carrier has been activated to exhibit a squaric acid derivative linked to the carrier and is placed in contact with an aqueous medium. A kit comprising the storage stable composition is also disclosed.

Abstract: The present invention relates to immunotoxins that effectively kill malignant cells having a given marker. The immunotoxins are reagents that comprise internalizing antibodies conjugated to cytotoxic ribonucleases or fragments thereof. The internalizing antibodies are capable of binding with a chosen tumor cell, and thereby confer little non-specific toxicity to the immunotoxin in a host. The immunotoxins exhibit up to 2000-fold higher toxicity against malignant B cells than did the ribonuclease counterparts alone.

Abstract: The isolation, cloning and characterization of a human gene related to but distinct from the EGF receptor gene has been described. Nucleotide sequence of the gene and amino acid sequence of the polypeptide encoded by the gene have been determined. The use of the nucleic acid probes and antibodies having specific binding affinity with said polypeptide for diagnostic and therapeutic purposes has also been described.

Abstract: An immunotoxin molecule is described which comprises an antibody specific for human CD40L antigen located on the surface of a human cell, coupled to a toxin molecule or active fragment thereof, wherein the binding of the immunotoxin to the CD40L molecule results in the killing of the CD40L expressing cell. The toxin molecule is especially a type-1 ribosome inactivating protein, or an active fragment thereof. The immunotoxin can be used for the treatment of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus, or T-cell malignancies.

Abstract: This invention is related to an adhesive composition which may be used to bond or seal tissue in vivo. The adhesive composition is readily formed from a two component mixture which includes a first part of a protein, preferably a serum albumin protein, in an aqueous buffer having a pH in the range of about 8.0-11.0 and a second part of a water-compatible or water-soluble bifunctional crosslinking agent. When the two parts of the mixture are combined, the mixture is initially a liquid which cures in vivo on the surface of tissue in less than about one minute to give a strong, flexible, pliant substantive composition which bonds to the tissue and is absorbed in about four to sixty days. The adhesive composition may be used either to bond tissue, to seal tissue or to prevent tissue adhesions caused by surgery.