Abstract: The present invention relates to a radioimmunoconjugate that binds human CD37. Pharmaceutical compositions and uses thereof for the treatment of cancer and in particular B cell malignancies are aspects of the present invention.

Abstract: The present disclosure provides conjugate structures (e.g., polypeptide conjugates) and hydrazinyl-indole compounds used to produce these conjugates. The disclosure also provides methods of production of such conjugates, as well as methods of using the same.

Abstract: Hydroxamate substituted azaindoline cyanine dyes, conjugates thereof and methods of using the same are provided. The subject cyanine dyes include an azaindoline ring having a hydroxamate substituent. The dyes may further include a reactive group moieties (RGM) and/or a water soluble group. Also provided are conjugates of the subject dyes. Also provided are tandem conjugates including a fluorescent protein capable of energy transfer to the dye. Methods of detecting an analyte in a sample by contacting the sample with a detection reagent are provided. The detection agent may be a dye-conjugate that specifically binds the analyte, or may be a reactive dye which conjugates to the analyte. Also provided are compositions, e.g., kits, etc., incorporating such dyes which facilitate use in such methods.

Abstract: The invention is directed to a releasable conjugate comprising a biotinylated ligand having a biotin moiety, a ligand moiety (Ligand1) and a biotin-binding molecule (bbm) bound to the biotin moiety of the biotinylated ligand. The ligand moiety of the biotinylated ligand may be separated by a spacer group consisting of polyethylene glycol. Furthermore, the invention relates to a method for cleaving the releasable conjugate by providing biotin or streptavidin and an auxiliary release agent in a sufficient concentration to displace the biotin-binding molecule (bbm) from the biotin moiety of the biotinylated ligand and a method for separation of target cells from a cell sample utilizing the conjugate.

Abstract: Described is a pretargeting method, and related kits, for targeted medical imaging and/or therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention involves the use of [4+2] inverse electron demand (retro) Diels-Alder chemistry in providing the coupling between a Pre-targeting Probe and an Effector Probe. To this end one of these probes comprises an electron-deficient tetrazine or other suitable diene, and the other an E-cyclooctene which has a flattened structure as a result of the position of at least two exocyclic bonds.

Abstract: A contrast agent composition and a method of diagnostic imaging are provided. The composition comprises a pharmaceutically acceptable carrier and a metal-complex comprising a ligand having structure (XXX): wherein R1, R2, R3, R7, R8, R?1, R?2, R?3, R7? and R8? are selected form hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group; R4, R?4 are selected from a hydrogen, a hydroxyl, a protected hydroxyl group, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; n is an integer between 0 and 4; R5, R?5 are selected from a hydrogen, a protecting group comprising C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals, m is an integer between 1 and 10; at least one of R7 and R?7 is acidic groups or protected acidic groups; Y comprises a protein or peptide moiety, a particle, a micelle, a liposome, an organic molecule, oligomer, polymer or a hydrophilic moiety.

Abstract: The present invention provides methods of site-specific labeling of antibodies, using proteins having 4?-phosphopantetheinyl transferase activity that catalyze post-translational modification of peptide sequences (“peptide tags”) incorporated into one or more specific sites of an antibody of interest. Enzymatic labeling enables quantitative and irreversible covalent modification of a specific serine residue within the peptide tags incorporated into the antibody, and thus creates desirable antibody conjugates.

Abstract: Provided herein are modified Fc proteins comprising non-natural amino acid residues at site-specific positions, conjugates of the modified Fc proteins for therapy or diagnosis, compositions comprising the modified Fc proteins and conjugates thereof, methods of their production and methods of their use. The modified Fc proteins and conjugates are useful for methods of treatment and prevention, methods of detection and methods of diagnosis.

Abstract: Provided herein are antibodies comprising non-natural amino acid residues at site-specific positions, compositions comprising the antibodies, methods of their production and methods of their use. The antibodies are useful for methods of treatment and prevention, methods of detection and methods of diagnosis.

Abstract: The present invention relates to a radioimmunoconjugate that binds human CD37. Pharmaceutical compositions and uses thereof for the treatment of cancer—and in particular B-cell malignancies—are aspects of the present invention.

Abstract: Biotin derivatives, methods of using the biotin derivatives and kits comprising the biotin derivatives.

Abstract: This invention relates generally to the generation of antibodies, e.g., monoclonal antibodies including fully human monoclonal antibodies, that recognize Jagged 1 and/or Jagged 2, to antibodies, e.g., monoclonal antibodies including fully human antibodies that recognize Jagged 1 and/or Jagged 2, and nucleic acid molecules that encode antibodies, e.g., nucleic acid molecules that encode monoclonal antibodies including fully human cross-reactive antibodies that recognize both Jagged 1 and Jagged 2, and to methods of making the anti-Jagged antibodies and methods of using the anti-Jagged antibodies as therapeutics, prophylactics, and diagnostics. The invention also relates generally to activatable antibodies that include a masking moiety (MM), a cleavable moiety (CM), and an antibody (AB) that specifically bind to Jagged 1 and Jagged 2, and to methods of making and using these activatable anti-Jagged antibodies in a variety of therapeutic, diagnostic and prophylactic indications.

Abstract: A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.

Abstract: The invention provides a novel class of reactive fluorescent agents that are based on a pyrene sulfonic acid nucleus. The agents are readily incorporated into conjugates with other species by reacting the reactive group with a group of complementary reactivity on the other species of the conjugate. Also provided are methods of using the compounds of the invention to detect and/or quantify an analyte in a sample. In an exemplary embodiment, the invention provides multi-color assays incorporating the compounds of the invention.

Abstract: The invention relates to conjugates of anti-integrin specific antibodies with cytotoxic compounds, the synthesis, selection, and use of such conjugates for use in cancer therapy or other diseases mediated by cell proliferation, cell migration, or inflammation and which pathology involves angiogenesis or neovascularization of new tissue. In addition the invention relates to combination therapy of such diseases wherein the treatment comprises use of said conjugates in combination with one or more other treatment modalities including but not limited to: chemotherapy, surgery or radiation therapy. The preferred conjugates contain maytansinoid compounds linked to the antibody by a disulfide linkage, and preferred chemotherapeutic agents are doxorubicin, a taxane, a camptothecin, a podophyllotoxin, a nucleoside analog, or a pyrimidine analog.

Abstract: The present invention relates to linker molecules that readily conjugate cellular recognition ligand at one end and drug payload at the other, and are useful in treating or preventing cancer, an autoimmune disease, an inflammatory condition, a central nervous system disorder or an infection.

Abstract: Described are Galectin-1/Ig fusion constructs and methods of use thereof, e.g., in diagnostic and biomedical assays, and as therapeutic agents for the treatment of conditions associated with immune dysfunction, e.g., autoimmune diseases, and cancers.

Abstract: The present application discloses compositions and methods of synthesis and use of 18F- or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may then be directly or indirectly attached to the targeting molecule. In other embodiments, the 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the bifunctional chelating agent bound to 18F- or 19F-metal complex may be conjugated to the molecule to be labeled at a reduced temperature, e.g. room temperature.

Abstract: Provided is a composition for detecting a protein, containing a tyrosine oxide-coupled biomaterial. Various diseases may be easily and rapidly diagnosed by easily detecting the composition containing a tyrosine oxide-coupled biomaterial according to the present invention, by identifying a color of the protein bound with a tyrosine oxide-coupled biomaterial prepared by binding tyrosine oxide, which is a natural pigment present in a living body, with the biomaterial. Accordingly, the composition of the present invention may be used to easily and rapidly diagnose various diseases in real time in an operating room, and may usefully replace conventional histological analysis without a secondary antibody reaction and a final operation of color expression.

Abstract: Compounds and methods are disclosed that are useful for noninvasive imaging in the near-infrared spectral range. The cyanine compounds of Formula I are presented: wherein Q is a portion of a polymethine bridge: Also included are bioconjugates of the compounds of Formula I, methods of labeling biomolecules with the compounds, and methods of imaging.

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 herein are modified anti-EGFR antibodies and nucleic acid molecules encoding modified anti-EGFR antibodies. Also provided are methods of treatment and uses using modified anti-EGFR antibodies.

Abstract: Multifunctional probes are synthesized in a single step using peptide scaffold-based multifunctional single-attachment-point reagents. To obtain multifunctional probes using the methods of the invention, a substrate (e.g., a nanoparticle, polymer, antibody, protein, low molecular weight compound, drug, etc.) is reacted with a multifunctional single-attachment-point (MSAP) reagent. The MSAP reagents can include three components: (i) a peptide scaffold, (ii) a single chemically reactive group on the peptide scaffold for reaction of the MSAP with a substrate having a complementary reactive group, and (iii) multiple functional groups on the peptide scaffold. The peptide scaffold can include any number of residues; however, for ease of synthesis and reproducibility in clinical trials, it is preferred to limit the residues in the peptide to 20 or less.

Abstract: The present invention is directed to compositions of matter comprising immunoconjugates comprising an anti-CD79b antibody comprising: (i) an HVR-L1 sequence of KASQSVDYEGDSFLN (SEQ ID NO: 194), (ii) an HVR-L2 sequence of AASNLES (SEQ ID NO: 195), (iii) an HVR-L3 sequence of QQSNEDPLT (SEQ ID NO: 196), (iv) an HVR-H1 sequence of GYTFSSYWIE (SEQ ID NO: 202), (v) an HVR-H2 sequence of GEILPGGGDTNYNEIFKG (SEQ ID NO: 203), and (vi) an HVR-H3 sequence of TRRVPIRLDY (SEQ ID NO: 204) and to methods of using those compositions of matter for the treatment of hematopoietic tumor in mammals.

Abstract: Biosensor comprising an activatable acceptor fluorogen linked via a linker to a donor which transfers energy to the fluorogen on detecting an analyte wherein the fluorogen component reacts and a 100 fold increase in intensity results when the fluorogen interacts non-covalently with an activator e.g. fluorogen activator peptide.

Abstract: The purpose is to produce, with high reproducibility, a complex of labeled probes and a carrier, said complex being to be used for detecting and measuring a target substance to be measured with high sensitivity and high stability. The means for accomplishing the purpose is that a label is bound to a probe-water soluble carrier conjugate using specific binding of an avidin compound such as avidin, streptavidin, etc. to biotin, and the binding of the avidin compound to the probe is performed before the binding to the carrier. Namely, after conjugating the avidin compound to a substance which is capable of binding to the target substance, the conjugate is bound to a high-molecule water-soluble carrier to produce a complex of the avidinized probes and the water-soluble carrier. Then the complex of the avidinized probes and the water-soluble carrier is mixed with a biotinylated label.

Abstract: A modular platform is provided for rapid preparation of various water-soluble prosthetic groups capable to efficiently introduce 18F into proteins with 18F labelling reagents.

Abstract: The invention provides a method detecting free light chains (FLCs) comprising: (i)providing a sample from a subject; (ii)mixing the sample with an anti-FLC specific antibody, or fragments thereof capable of specifically binding the FLC, to form a mixture; (iii)passing the mixture through a capillary tube by capillary zone electrophoresis (CZE); and (iv)detecting the presence of the antibody or fragment thereof after passage through at least a portion of the capillary tube. Capillary tubes for use in CZE and kits comprising capilliary tubes and at least one anti-FLC antibody are also provided.

Abstract: Described is a pretargeting method, and related kits, for targeted medical imaging and/or therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention involves the use of [4+2] inverse electron demand (retro) Diels-Alder chemistry in providing the coupling between a Pre-targeting Probe and an Effector Probe. To this end one of these probes comprises an electron-deficient tetrazine or other suitable diene, and the other an E-cyclooctene which has one or more axial substituents.

Abstract: The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs.

Abstract: The present invention provides a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand and the ion of an alpha-emitting thorium radionuclide. The invention additionally provides therapeutic methods employing such complexes, methods of their production and use, and kits and pharmaceutical compositions comprising such complexes.

Abstract: Compounds and methods are disclosed that are useful for noninvasive imaging in the near-infrared spectral range. The cyanine compounds of Formula I are presented: wherein Q is a portion of a polymethine bridge selected from the group consisting of: Also included are bioconjugates of the compounds of Formula I, methods of labeling biomolecules with the compounds, and methods of imaging.

Abstract: The present invention includes compositions and methods for increasing the effectiveness of antigen presentation using a DCIR-specific antibody or fragment thereof to which an antigen is attached that forms an antibody-antigen complex, wherein the antigen is processed and presented by a dendritic cell that has been contacted with the antibody-antigen complex.

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

Abstract: The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins and nucleic acids. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified by the addition of charged and polar groups to provide beneficial properties.

Abstract: The invention provides methods, kits, devices and compositions for detecting one or more target analytes. In some embodiments, the invention provides binding elements and labeling elements capable of being joined through a plurality of joining elements.

Abstract: The invention provides a novel class of reactive fluorescent agents that are based on a pyrene sulfonic acid nucleus. The agents are readily incorporated into conjugates with other species by reacting the reactive group with a group of complementary reactivity on the other species of the conjugate. Also provided are methods of using the compounds of the invention to detect and/or quantify an analyte in a sample. In an exemplary embodiment, the invention provides multi-color assays incorporating the compounds of the invention.

Abstract: Methods, compositions and kits are provided for treating a subject exposed to or at risk for exposure to a disease agent using a pharmaceutical composition including at least one recombinant heteromultimeric neutralizing binding protein including two or multiple binding regions, such that the binding regions are not identical, and each binding region specifically binds a non-overlapping portion of the disease agent, thereby treating the subject for exposure to the disease agent. In a related embodiment, the heteromultimeric neutralizing binding protein includes two or multiple binding regions that neutralize a plurality of disease agents. In certain embodiments, the disease agent includes a bacterium, a bacterial protein, a virus, a viral protein, a cancer cell, and a protein or molecule produced therefrom. In certain embodiments, the disease agent is a plurality of different disease agents.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a carrier such as a polymer, nanoparticle, complex or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing cell death of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate.

Abstract: Disclosed herein are antibody-nanoparticle conjugates that include two or more nanoparticles (such as gold, palladium, platinum, silver, copper, nickel, cobalt, iridium, or an alloy of two or more thereof) directly linked to an antibody or fragment thereof through a metal-thiol bond. Methods of making the antibody-nanoparticle conjugates disclosed herein include reacting an arylphosphine-nanoparticle composite with a reduced antibody to produce an antibody-nanoparticle conjugate. Also disclosed herein are methods for detecting a target molecule in a sample that include using an antibody-nanoparticle conjugate (such as the antibody-nanoparticle conjugates described herein) and kits for detecting target molecules utilizing the methods disclosed herein.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: The present invention relates to method detecting analytes by surface enhanced Raman spectroscopy (SERS), comprising contacting the analytes with at least one analyte binding molecule attached to a metal substrate surface that enhances Raman scattering via a Raman-active molecular linker; and detecting a surface enhanced Raman signal from said compound. In a further aspect, this invention relates to a conjugate and a biosensor suitable for the invented SERS-based analyte detection method.

Abstract: According to the present invention, a novel polyazamacrocyclic compound which is used as a bifunctional chelating agent (BFC) can be synthesized selectively and in high yield. The novel polyazamacrocyclic compound synthesized by this method chelates with metals and thus can be conjugated with bioactive molecules such as peptides, and can be used in the diagnosis and treatment of medical conditions.

Abstract: Provided is luminescent gold nanomaterial functionalized by N-(4-aminobutyl)-N-ethylisoluminol, methods of preparation and application thereof. The functionalized gold nanoparticle nanomaterial are formed by N-(4-aminobutyl)-N-ethylisoluminol bonding to the surface of the gold nanomaterial. The functionalized gold nanomaterial are prepared by directly reducing chloroauric acid with N-(4-aminobutyl)-N-ethylisoluminol, wherein N-(4-aminobutyl)-N-ethylisoluminol acts as reducer and stabilizer simultaneously. The preparation method is simple, fast and no need of special conditions. The preparation methods can be performed in a wide temperature range, for example, 15-35° C. The size and pattern of the functionalized gold nanomaterial can be specified by choosing the ratio of chloroauric acid to N-(4-aminobutyl)-N-ethylisoluminol. The obtained functionalized nano gold particles exhibit excellent chemiluminescence properties.

Abstract: A magnetic nanoparticle is provided in the disclosure. The magnetic nanoparticle includes a magnetic nanoparticle; a biocompatible polymer of the following formula (II) covalently coupled to the magnetic nanoparticle, wherein R1 is alkyl, aryl, carboxyl, or amino; n is an integer from 5 to 1000; and m is an integer from 1 to 10.

Abstract: The present invention is directed to ligand/receptor and antigen/antibody specificity exchangers comprising a saccharide or glycoconjugate. Methods of making these specificity exchangers and methods of using said specificity exchangers to treat or prevent human disease are described herein.

Abstract: Bioconjugates for use in imaging are disclosed include a linker sequence fused to a polypeptide capable of binding a target in a biological system. The linker sequence is designed so that it is capable of being radiolabelled, e.g. with a complex comprising a radionuclide, via a free cysteine residue and the polyhistidine sequence in the label that are both capable of simultaneously binding to a complex comprising the radionuclide. These interactions can improve significantly the rate and efficiency of radiolabelling compared to either protein with the His-tag or the free cysteine alone. Optionally, the free cysteine residue provides a site which can be covalently bonded to a moiety such as a second label, in a site-specific manner.

Abstract: Provided are a cross-bridged tetraaza macrocyclic compound of a novel structure that can be used, for example, as a contrast agent for diagnostic imaging or a radiopharmaceutical and a method for preparing the same. The disclosed tetraaza macrocyclic compound is able to form a stable metal complex at a lower temperature and allows easy conjugation with a bioactive substance or a chemically active substance, when compared to the existing cross-bridged tetraaza macrocyclic compounds.

Abstract: A method of immobilising a target molecule on a substrate, which comprises exposing the target molecule to the substrate in the presence of a metal complex, wherein the target molecule is an unmodified target molecule, and wherein the metal complex is selected to provide a stable binding interaction between the target molecule and the substrate.