Abstract: The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use in PET imaging. In particular embodiments, the labeled molecules may be peptides or proteins, although other types of molecules may be labeled and utilized. Preferably, the F-18 is attached to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety. In other embodiments, the metal may first be attached to the chelating group and subsequently the F-18 bound to the metal. More preferably, the F-18 label moiety may be attached to a targetable conjugate that is used for pretargeting in combination with a bispecific or multispecific antibody. The F-18-metal labeled molecules are stable in human serum at 37° C.

Abstract: Probes comprising one or more selectively cleavable ?-azidoether moieties are provided; and linkers comprising the one or more selectively cleavable ?-azidoether moieties. The ?-azidoether moiety will undergo a Staudinger reaction with a suitable reducing agent, resulting in cleavage. The probes find use in a variety of detection assays, e.g. specific polynucleotide binding assays, polypeptide binding assays, etc. The cleavable linkers are suitable for synthetic reactions, e.g. to prepare probes of the invention; in the synthesis of cleavable peptide conjugates; and the like.

Abstract: Various system and method embodiments of the present invention are directed to separating target molecules from complex solutions by affinity column chromatography using organic-solvent-containing eluants. In one embodiment of the present invention, an eluant containing an organic-solvent is used, at a first pH, to remove non-target solutes and suspended entities from an affinity chromatography column. The pH of the eluant is then changed to a second pH, and the organic-solvent-containing eluant is used to elute target molecules from the affinity column chromatography.

Abstract: Anti-TAT226 antibodies and immunoconjugates thereof are provided. Methods of using anti-TAT226 antibodies and immunoconjugates thereof are provided.

Abstract: The present invention relates to new and improved interleukin-7 polypeptides, as well as compositions comprising the same, their preparation and uses. The invention more particularly relates to hyperglycosylated IL-7 polypeptides having improved properties, as well as their manufacture and therapeutic uses. The invention also discloses novel IL-7 polypeptides having modified amino acid sequences containing artificially created glycosylation site(s), as well as corresponding nucleic acid molecules, vectors and recombinant host cells. The invention also relates to the use of such polypeptides, cells or nucleic acids for curative or preventive treatment of mammalian subjects, including human subjects.

Abstract: The present invention relates to antibody-drug conjugate compounds of Formula I: Ab-(L-D)p??I where one or more maytansinoid drug moieties (D) are covalently linked by L to an antibody (Ab) which binds to an ErbB receptor, or which binds to one or more tumor-associated antigens or cell-surface receptors. These compounds may be used in methods of diagnosis or treatment of cancer, and other diseases and disorders.

Abstract: Enantiomer-pure compounds of general formulas VIIa and VIIb in which A stands for a group —COO—, and Z and R have different meanings, as well as use thereof are described.

Abstract: Disclosed is a method of detecting even a very small amount of a target substance by mixing a linker and a spacer at a suitable ratio and immobilizing the mixture on the surface of carbon nanotubes in a carbon nanotube-based biosensor. This method detects a specific substance at the level of femtomoles and lowers the detection limit of conventional carbon nanotube transistor sensors. Accordingly, the method detects even a very small amount of a target substance, and thus the carbon nanotube-based biosensor is a highly useful sensor which can be used either as a medical sensor for diagnosing diseases or as an environmental sensor.

Abstract: It is intended to provide a novel contrast agent for photoacoustic imaging that is highly capable of binding to a target molecule and generates high photoacoustic signals. The present invention provides a contrast agent for photoacoustic imaging represented by Formula 1: MNP?((L)l?(P)m)n ??(Formula 1) (wherein MNP represents a particle containing an iron oxide particle; L represents a linker molecule; P represents a ligand molecule; l represents 0 or 1; and m and n represent an integer of 1 or larger), the contrast agent for photoacoustic imaging including: a particle containing an iron oxide particle that absorbs light in a near-infrared region; and at least one or more ligand molecule(s) immobilized on the particle containing an iron oxide particle, wherein the immobilization density of the ligand molecule is equal to or higher than the cell surface density of a target molecule.

Abstract: Protease resistant modified interferon-beta polypeptides, and pharmaceutical compositions containing such modified interferon-beta polypeptides are provided. The modified interferon-beta polypeptides contain amino acid substitutions that confer increased resistance to proteolysis over unmodified IFN beta cytokine molecules. The present invention provides for pharmaceutical formulations suitable for oral, nasal and pulmonary administration, and the use of such formulations in the treatment of disease.

Abstract: Cysteine engineered antibodies comprising a free cysteine amino acid in the heavy chain or light chain are prepared by mutagenizing a nucleic acid sequence of a parent antibody and replacing one or more amino acid residues by cysteine to encode the cysteine engineered antibody; expressing the cysteine engineered antibody; and isolating the cysteine engineered antibody. Certain highly reactive cysteine engineered antibodies were identified by the PHESELECTOR assay. Isolated cysteine engineered antibodies may be covalently attached to a capture label, a detection label, a drug moiety, or a solid support.

Abstract: The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.

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: Described herein are methods, compositions and articles of manufacture involving neutral conjugated polymers including methods for synthesis of neutral conjugated water-soluble polymers with linkers along the polymer main chain structure and terminal end capping units. Such polymers may serve in the fabrication of novel optoelectronic devices and in the development of highly efficient biosensors. The invention further relates to the application of these polymers in assay methods.

Abstract: Described herein are methods, compositions and articles of manufacture involving neutral conjugated polymers including methods for synthesis of neutral conjugated water-soluble polymers with linkers along the polymer main chain structure and terminal end capping units. Such polymers may serve in the fabrication of novel optoelectronic devices and in the development of highly efficient biosensors. The invention further relates to the application of these polymers in assay methods.

Abstract: Certain disclosed embodiments of the present invention concern the synthesis, derivatization, conjugation to immunoglobulins and signal amplification based on discrete, relatively short polymers having plural reactive functional groups that react with plural molecules of interest. Reactive functional groups, such as hydrazides, may be derivatized with a variety of detectable labels, particularly haptens. The remaining reactive functional groups may be conjugated directly to a specific binding molecule, such as to the oxidized carbohydrate of the Fc region of the antibody. Disclosed conjugates display large signal amplification as compared to those based on molecules derivatized with single haptens, and are useful for assay methods, particularly multiplexed assays.

Abstract: Certain disclosed embodiments of the present invention concern the synthesis, derivatization, conjugation to immunoglobulins and signal amplification based on discrete, relatively short polymers having plural reactive functional groups that react with plural molecules of interest. Reactive functional groups, such as hydrazides, may be derivatized with a variety of detectable labels, particularly haptens. The remaining reactive functional groups may be conjugated directly to a specific binding molecule, such as to the oxidized carbohydrate of the Fc region of the antibody. Disclosed conjugates display large signal amplification as compared to those based on molecules derivatized with single haptens, and are useful for assay methods, particularly multiplexed assays.

Abstract: Provided is a fluorescent labeling material, including zinc oxide nanoparticles each surface-modified with an organic compound having an amino group placed at an outer end thereof. Also provided is a fluorescent labeling agent to be used in vivo or in vitro, including the fluorescent labeling material, in which: EDC or the like is bound thereto through the amino group; and a substance capable of selectively binding to a target to be fluorescently labeled, such as an antibody, is linked thereto.

Abstract: Fluorescent, sulfonated 3,7-diamino-[8,9]benzophenoxazine dyes are provided that are especially useful for labelling biopolymers and other substrates. The dye-labelled conjugates can be used in a variety of contexts, including cell surface assays employing intact, live cells and in nucleic acid detection methods. The new dyes are water soluble and can be conjugated to a variety of substrates, such as polynucleotides, nucleosides, nucleotides, peptides, proteins, antibodies, carbohydrates, ligands, particles and surfaces.

Abstract: The present invention relates to a method of revealing a biological process using a FRET measurement, which comprises the following steps: incorporating, into a measurement medium containing a lipid membrane, a biological entity X coupled with a first member of a pair of FRET partners and a second biological entity Y coupled with the second member of the pair of FRET partners, the energy-donating member of the pair of FRET partners having a long lifetime and the members of said pair of FRET partners being located on either side of the lipid membrane; exciting the measurement medium at the excitation wavelength of the energy-donating member; and measuring the FRET signal or the variations in said signal emitted in said culture medium.

Abstract: In order to improve the detection sensitivity of MUSTag, the present invention provides an antibody complex including a nucleic acid chain as a label, an antibody to specifically recognize the antigen and an adaptor moiety linking the nucleic acid chain and the antibody, wherein the adaptor moiety includes an immunoglobulin binding domain of Protein G, Protein A or Protein L for binding with the antibody, and the adaptor moiety and the antibody are chemically cross-linked to form a cross-linked antibody complex.

Abstract: Compositions and methods for the therapy and diagnosis of cancer, particularly ovarian cancer, are disclosed. Illustrative compositions comprise one or more ovarian tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly ovarian cancer.

Abstract: The invention concerns a method for determining at least one target molecule map in a tissue section, using at east one (A-X)n-B conjugate, wherein A is a tag molecule of known molecular weight, X is a linker that is cleaved during sample desorption/ionization, n is an integer of at least 1, and B is a binding molecule that binds specifically to said target molecule. When using MALDI mass spectrometry, said linker molecule X may be cleaved by photodissociation during sample laser irradiation if photocleavable at the wavelength of said MALDI laser. Alternatively, when using UV-MALDI, IR-MALDI, SIMS or DESI mass spectrometry, said linker molecule X may be cleaved by fragmentation during sample desorption/ionization.

Abstract: Anti-CD22 antibodies and immunoconjugates thereof are provided. Methods of using anti-CD22 antibodies and immunoconjugates thereof are 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: It is intended to provide a novel contrast agent for photoacoustic imaging that is highly capable of binding to a target molecule and generates high photoacoustic signals. The present invention provides a contrast agent for photoacoustic imaging represented by Formula 1: MNP-((L)l-(P)m)n??(Formula 1) (wherein MNP represents a particle containing an iron oxide particle; L represents a linker molecule; P represents a ligand molecule; l represents 0 or 1; and m and n represent an integer of 1 or larger), the contrast agent for photoacoustic imaging including: a particle containing an iron oxide particle that absorbs light in a near-infrared region; and at least one or more ligand molecule(s) immobilized on the particle containing an iron oxide particle, wherein the immobilization density of the ligand molecule is equal to or higher than the cell surface density of a target molecule.

Abstract: The present invention relates to fluorescent pyrene dyes in general. The present invention provides a wide range of fluorescent dyes and kits containing the same, which are applicable for labeling a variety of biomolecules, cells and microorganisms. The present invention also provides various methods of using the fluorescent dyes for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions.

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 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 invention provides anti-Robo4 antibodies, and compositions comprising the antibodies and methods of using these antibodies, including diagnostic and therapeutic methods.

Abstract: The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a the substitution of serine for phenylalanine at Kabat residue 91 in the human framework region in the hA19 VH sequence.

Abstract: Cysteine engineered antibodies useful for the site-specific conjugation to a variety of agents are provided. Methods for the design, preparation, screening, selection and use of such antibodies are also provided.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc.

Abstract: Assay methods are disclosed involving specific binding reactions which are simplified compared to known methods. A compound capable of producing chemiluminescence is immobilized on a solid support as is a member of a specific binding pair for capturing an analyte from a sample. An activator compound that activates the chemiluminescent compound and is conjugated to a specific binding pair member is added in excess along with the sample to the solid support. Addition of a trigger solution causes a chemiluminescent reaction at the sites where the activator conjugate has been specifically bound. The assay methods are termed non-separation assays because they do not require removal or separation of excess detection label (activator conjugate) prior to the detection step. The methods are applicable to various types of assays including immunoassays, receptor-ligand assays and nucleic acid hybridization assays.

Abstract: A protein containing one or more activatable groups, e.g., an antibody, is subjected to partial or complete reduction of one or more such bonds to form reactive groups; the resulting protein is reacted with a drug which is reactive with some of the reactive groups, such as certain radiometals, chelating agents, and toxins, so as to form a conjugate useful in, e.g., in vitro diagnosis, in vivo imaging, and therapy.

Abstract: The invention provides anti-Robo4 antibodies, and compositions comprising the antibodies and methods of using these antibodies, including diagnostic and therapeutic methods.

Abstract: Compositions, methods and kits for labeling proteins and uses in reporter systems for detecting, quantifying and/or characterizing analytes.

Abstract: The invention relates to recombinant polypeptides, in particular antibodies or antibody fragments that bind Ed-B-isoforms of fibronectin and can block their function. In addition, the diagnostic and pharmaceutical application of the polypeptides according to the invention is disclosed.

Abstract: The present invention relates to the use of radioimmunoconjugates for the treatment of haematological malignancies, particularly multiple myeloma.

Abstract: A new radioconjugate NP has been developed using recombinant antibody fragments, di-scFv-c (111 In-DOTA-di-scFv-NP) for imaging and therapy of anti MUC-1 10 expressing cancers since aberrant MUC-1 Is abundantly expressed on the majority of human epithelial cancers. Selection and engineering of anti-MUC-1 di-scFv-c (50 kDa) was generated to link NP-M (maleimide). DOTA chelate was conjugated with di-scFv-c for the radiometal chelation to trace the RINP at in vivo. This RINP preparation can provide uniquely high tumor cell binding NP for AMF driven tumor hyperthermia.

Abstract: The present invention comprises novel “one-step” methods for the production of gold sol and gold sol conjugates. The methods disclosed herein produce gold sol and colloidal gold conjugates with product with yields on the order of about 20 ODs. Since current methods in the art yield conjugates at concentrations on the order of about 2 ODs, the present invention represents an approximately 10-fold increase in production over conventional methods. The novel method provided herein also does not result in the production of undesired aggregate by-products that, in conventional methods, must be removed via centrifugation, filtration or other means. The new method is therefore less labor intensive and requires less time to complete than standard methods in the art for synthesizing pure colloidal gold conjugates.

Abstract: A method is disclosed for making a conjugate of two molecules using a hydrazide thiol linker. In a particular working embodiment, an Fc-specific antibody-enzyme conjugate is made using the method and demonstrated to provide exceptional staining sensitivity and specificity in immunohistochemical and in situ hybridization assays.

Abstract: This invention relates to novel reagent conjugates and a novel multi-step process for delivering active compounds to target analytes of interest in a patient for diagnostic and therapeutic purposes. According to the process, two novel reagents are bound to each other by linkage of the sequence-specific components they contain. The first reagent, which is comprised of a target recognition component and a first sequence-specific component, is introduced into the patient and allowed to achieve maximal localization on the target cells. The second reagent, which is comprised of an active compound component and a second sequence-specific component is then introduced into the patient, thereby forming a complex with the first reagent via the recognition and binding of the sequence-specific components of the two reagents to form the reagent conjugate of the invention. The active compound component is thereby efficiently and specifically delivered to the target analyte.

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 a methods and compositions for receptor mediated drug delivery, particularly across the blood-brain barrier.

Abstract: The present invention provides antibody conjugates comprising a targeting agent covalently attached to an antibody or fragment thereof. The antibody conjugates of the present invention are particularly useful for imaging a tumor, organ, or tissue and for treating diseases and disorders such as cancer, inflammatory diseases, autoimmune diseases, infectious diseases, and neurological disorders. Kits containing the antibody conjugates described herein find utility in a wide range of applications including, for example, in vivo imaging and immunotherapy.

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: 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: This invention pertains to a method for detecting a compound in the presence of other compounds that are substantially similar in structure and metabolically related to the analyte. The invention is particularly suited for the detection of S-adenosylmethionine in the presence of S-adenosylhomocysteine, other nucleosides and derivatives in a biological sample. The methods of this invention involve an antibody produced specifically against S-adenosylmethionine; particularly, analogs modified strategically at the sulfonium position. An assay protocol comprises chemically modified analyte analog linked to an enzymatic reporter and the aforementioned antibody was used to demonstrate the assay specificity and sensitivity. Additional assay method with immobilized immunogen, the specific antibody, and an enzyme labeled secondary antibody was also described for illustration. The invention also features hapten design and novel compounds used as haptens to prepare immunogen and for the specific antibody production.

Abstract: A method for the fluorescent detection of a substance, the method comprising providing particles comprising a metal or a metal oxide core, wherein one or more optionally fluorescently tagged antibodies or human specific peptide nucleic acid (PNA) oligomers for binding to a substance is/are bound, directly or indirectly, to the surface of the metal or metal oxide; contacting a substrate, which may or may not have the substance on its surface, with the particles for a time sufficient to allow the antibody/PNA oligomer to bind with the substance; removing those particles which have not bound to the substrate; if the antibodies or PNA oligomers are not fluorescently tagged, contacting the substrate with one or more fluorophores that selectively bind with the antibody and/or substance, then optionally washing the substrate to remove unbound fluorophores; and illuminating the substrate with appropriate radiation to show the fluorophores on the substrate.