Abstract: Disclosed are anti-CD70 antibodies and derivatives thereof conjugated to cytotoxic, immunosuppressive, or other therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody- and antibody derivative-drug conjugates. Also disclosed are methods, for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the disclosed pharmaceutical compositions.

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: 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: The invention features compositions and methods for treating or alleviating a symptom of cancer. The compositions and methods of the invention direct supra-lethal doses of radiation, called Hot-Spots, to virtually all cancer cell types.

Abstract: Compositions including a trimeric OX-40 fusion protein are disclosed. Also disclosed are methods for enhancing the immune response of a mammal to an antigen by engaging the OX-40 receptor on the surface of T-cells involving administering to the mammal a composition comprising a trimeric OX-40 fusion protein and a pharmaceutically acceptable carrier.

Abstract: The present invention provides for chimeric Wnt antagonists comprising a Frz domain component derived from a Frizzled protein, a secreted Frizzled related protein or Ror protein and an Fc immunoglobulin component, and their use in the treatment and diagnostic detection of cellular Wnt signaling and Wnt-mediated disorders, including cancer.

Abstract: The present disclosure provides terminally activated monofunctional POZ derivatives having a range of functional active groups allowing conjugation of the monofunctional POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed terminally activated monofunctional POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives.

Abstract: The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and a therapeutic and/or diagnostic agent. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. The compositions may be part of a kit for administering the anti-CD74 immunoconjugate compositions in therapeutic and/or diagnostic methods.

Abstract: The present invention relates to conjugates of oligosaccharides of formula 1, wherein R is a linker to a carrier protein and optionally comprises up to three further saccharides, 5 and which are useful for vaccination, methods of synthesis of such conjugates, antibodies against this antigen, hybridoma producing monoclonal antibodies against this antigen, assays using these antibodies for the detection of B. anthracis spores and kits comprising these antibodies, and a vaccine for the prevention of B. anthracis infection comprising the conjugates of oligosaccharides of formula 1. Monoclonal antibodies 10 according to the invention selectively bind to B. anthracis, but not to related bacteria such as B. subtilis, B. cereus and other bacteria of this group such as B. thuringiensis.

Abstract: The present invention concerns methods and compositions for forming anti-cancer vaccine DNL complexes using dock-and-lock technology. In preferred embodiments, the anti-cancer vaccine DNL complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the DNL complex. The anti-cancer vaccine DNL complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138negCD20+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.

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 fusion proteins comprising a first molecule, and a second molecule which is a monovalent immunoglobulin or a fragment of a monovalent immunoglobulin with a long half-life when administered in vivo, methods of making such fusion proteins, pharmaceutical compositions comprising such fusion proteins, and uses thereof.

Abstract: The present invention is directed to a therapeutic agent comprising a GPIIIa(49-66) specific targeting agent and a thrombi-specific homing agent. Also disclosed is the use of the therapeutic agent in carrying out a method of treating thromboembolic disorders and a method of inducing platelet fragmentation.

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: Multivalent binding peptides, including bi-specific binding peptides, having immunoglobulin effector function are provided, along with encoding nucleic acids, vectors and host cells as well as methods for making such peptides and methods for using such peptides to treat or prevent a variety of diseases, disorders or conditions, as well as to ameliorate at least one symptom associated with such a disease, disorder or condition.

Abstract: A method of producing a binding surface for a target molecule having a functional binding site, which method comprises: (i) identifying within the target molecule an anchor site which is remote from the functional binding site; (ii) generating a pharmacophore model for the anchor site; (iii) using the pharmacophore model to identify an anchor site binding ligand; and (iv) providing the anchor site binding ligand on a surface of a substrate such that the ability of the anchor site binding ligand to bind to the anchor site is preserved.

Abstract: The present invention relates to the use of proteins comprising at least one follistatin domain to modulate the level or activity of growth and differentiation factor-8 (GDF-8). More particularly, the invention relates to the use of proteins comprising at least one follistatin domain, excluding follistatin itself, for treating disorders that are related to modulation of the level or activity of GDF-8. The invention is useful for treating muscular diseases and disorders, particularly those in which an increase in muscle tissue would be therapeutically beneficial. The invention is also useful for treating diseases and disorders related to metabolism, adipose tissue, and bone degeneration.

Abstract: Methods of treating, inhibiting, or ameliorating gout, including chronic acute (refractory) gout, pseudogout, or drug-induced gout, in a human subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the incidence of a gout flare is reduced or inhibited.

Abstract: The present invention provides methods for treating disorders arising from hypogonadism, rheumatoid cachexia, cachexia due to burns, cachexia due to administration of chemical agents, cachexia due to diabetes, diabetic nephropathy, Prader Willi syndrome, excessive TNF-?, and other muscle-related, metabolic and inflammatory disorders by administering myostatin antagonists to subjects suffering from such disorders.

Abstract: The invention relates to a chimeric monomer-dimer hybrid protein that comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first polypeptide chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

Abstract: The present invention relates to a composition for treating obesity-related diseases comprising an insulinotropic peptide conjugate, more particularly, to a composition for treating obesity-related diseases comprising a conjugate prepared by covalently linking the insulinotropic peptide with a carrier substance via a non-peptidyl linker, and a method for treating obesity-related diseases by using the same. In particular, the composition for treating obesity-related diseases according to the present invention remarkably improves the efficacy of suppressing food intake and its duration to reduce body weight and body fat, thereby being useful for the treatment of obesity-related diseases.

Abstract: The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Preferred embodiments concern hexameric stably tethered structures comprising one or more IgG antibody fragments and which may be monospecific or bispecific. The disclosed methods and compositions provide a facile and general way to obtain stably tethered structures of virtually any functionality and/or binding specificity. The stably tethered structures may be administered to subjects for diagnostic and/or therapeutic use, for example for treatment of cancer or autoimmune disease. The stably tethered structures may bind to and/or be conjugated to a variety of known effectors, such as drugs, enzymes, radionuclides, therapeutic agents and/or diagnostic agents.

Abstract: Disclosed are human VEGF-2 antibodies, antibody fragments, or variants thereof. Also provided are processes for producing such antibodies. The present invention relates to methods and compositions for preventing, treating or ameliorating a disease or disorder comprising administering to an animal, preferably a human, an effective amount of one or more VEGF-2 antibodies or fragments or variants thereof.

Abstract: The invention refers to the use of L19IL2 for treatment of pancreatic cancer. In another embodiment, the invention relates to a combination (i) of a fusion protein, comprising an Interleukin 2 part and an antibody part, specifically recognizing the extra domain B of fibronectin (ED-B-fibronectin), and (ii) gemcitabine.

Abstract: The present invention provides methods of using unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities, and the uses thereof. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: The invention provides isolated human DEC-205, its extracellular domain and functionally equivalent fragments thereof. Also provided are polynucleotides encoding same and vectors which include such polynucleotides. Further provided are methods of recombinantly producing human DEC-205, an extracellular domain thereof or a functionally equivalent fragment, and ligands that bind to human DEC-205 or a fragment thereof. Also provided are constructs for use in prophylaxis or therapy comprising such a ligand, human DEC-205 or an extracellular domain thereof coupled to a toxin or to an antigen capable of inducing a protective immune response in a patient.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and a therapeutic and/or diagnostic agent. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates compositions in therapeutic and/or diagnostic methods.

Abstract: The present invention relates to melanocortin receptor binding conjugates and methods of making and using the foregoing.

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: The invention provides compositions and method for delivering a therapeutic or diagnostic agent to a disease site in a mammal, the method comprising administering to the mammal a therapeutically or diagnostically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises the therapeutic or diagnostic agent coupled to a Procaspase 8 polypeptide and a pharmaceutically acceptable carrier.

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: Polyallylamine conjugates and applications thereof for biological signal amplification are provided by utilizing the essential amino group of polyallylamine to covalently bind with capture agents and signal molecules having the functional groups selected from a group consisting of —NHS, —CO, —S?O2 and —C?O—C?O. The resulting conjugates having more than one signaling entities can be further implemented for biological expression with enhancing effect on biological signal intensity, such that the sensitivity of detection for the variation between biological interactions is largely increased.

Abstract: Antibody A or a fusion protein thereof specifically binding to a leptin receptor (leptin-R) or a leptin-binding protein (leptin-BP), as well as compositions and methods for the use of these antibodies or fusion proteins for quantitative analysis, for therapeutic purposes and for the preparation of therapeutic drugs. Also disclosed is a method for quantitative determination of leptin in a sample of solubilized or suspended leptin-binding proteins by using specific antibodies or fusion proteins according to the invention, as well as diagnostic agents and (diagnostic) kits containing this antibody or fusion protein.

Abstract: The invention provides a novel process for conjugating a polymer, especially PEG, to a protein or peptide, which comprises reacting a polymeric conjugation reagent with a protein or peptide containing a polyhistidine tag under conditions such that conjugation occurs via said polyhistidine tag. The resulting conjugates are novel.

Abstract: The present invention provides single chain antibody-directed polymeric prodrugs containing multifunctional linkers. Methods of making the polymeric delivery systems and methods of treating mammals using the same are also disclosed.

Abstract: A method for in situ formation of a medical device on biological tissue includes attaching a plurality of reactive members of a primary specific binding pair to a surface of the biological tissue, and providing a plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, wherein upon contact of the reactive members on the surface of the biological tissue with the complimentary reactive members on the fibers, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the fibers to the tissue. The fibers can incorporate functionalities which may cause them to bind to one another.

Abstract: The present invention concerns methods and compositions for forming anti-cancer vaccine complexes. In preferred embodiments, the anti-cancer vaccine complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the vaccine complex. The anti-cancer vaccine complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138negCD20+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.

Abstract: A method for selectively orienting molecules on a surface of a solid support. The method includes the steps of: (a) attaching a linker molecule to the surface of the solid support, the linker molecule including a head group that is capable of binding to the solid support, and a tail group that is capable of chelating to a metal ion; (b) subsequently treating the solid support with a solution containing the metal ion; (c) attaching a metal ion chelating tag to the molecules to form tagged molecules; and (d) capturing the tagged molecules on the solid support by contacting it with the tagged molecules to form a monolayer of molecules on the surface of the solid support in which a majority of the molecules are held in the same orientation with respect to the surface. The invention also provides a sensor chip formed using the methods of the invention.

Abstract: Gold nanoparticles conjugated to polyethylene glycol and active binding molecules such as antibodies, proteins, lectins and DNA are suspended in a water vehicle at concentration from 107 to 1015 and then placed in a sealed container such as a centrifuge tube, and then the centrifuge tube is sealed in a film package that is non-air permeable.

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: The present invention provides means and method for detecting an activation epitope on FcyRII (CD32) on Fc? (CD32) expressing cells. The presence of epitope on Fc?RII (CD32) correlates with priming of the cell containing Fc?RII (CD32) expressing said epitope. The invention further provides binding molecules specific for said activation epitope on Fc?RII (CD32), and uses thereof in the detection of activated cells. Further uses are the treatment of individuals suffering from inflammation or at risk of suffering thereof. Also provided, among others, are uses for detecting and/or following an inflammation in an individual.

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: Antibodies which bind to activated members of the erbB, TNF, and IgSF family of receptors and pharmaceutical compositions comprising the same are disclosed. Peptides and mimetics of erbB, TNF, and IgSF receptors and pharmaceutical compositions comprising the same are also described. Methods of using such antibodies, peptides, and mimetics in tumor therapeutic, prophylactic, imaging and diagnostic applications are disclosed.

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 VEGF binding peptides. In addition, the invention provides VEGF peptides conjugated to antibodies alone and in conjunction with other anti-angiogenic molecules. Various uses of the peptides and compounds are provided, including methods to treat disorders associated with abnormal angiogenesis.

Abstract: The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragma assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.

Abstract: Active agent-loaded nanoparticles that are based on a hydrophilic protein or a combination of hydrophilic proteins, and methods for producing the nanoparticles and the use thereof. Functional proteins or peptide fragments are bound to the nanoparticles via polyethylene glycol-?-maleimide-?-NHS esters.

Abstract: The present invention relates to novel antibodies, particularly antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to the type III deletion mutant, EGFRvIII. The invention also relates to human monoclonal antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to EGFRvIII. Diagnostic and therapeutic formulations of such antibodies, and immunoconjugates thereof, are also provided.

Abstract: A chemical conjugate for treating a nerve cell related disorder is provided. This conjugate includes an active or inactive Clostridial toxin having specificity for a target nerve cell. The toxin is conjugated to a drug or other bioactive molecule without affecting the toxin's ability to enter the target nerve cell.