Abstract: The present invention describes a method of treating diabetes or metabolic syndrome with a compound that inhibits (a) IL-1, (b) the synthesis of IL-1, or (c) the release of IL-1.

Abstract: The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Abstract: The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Abstract: The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone.

Abstract: The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Abstract: Provided are monospecific and bispecific antibodies that are useful as anti-neoplastic agents and that bind specifically to human IGF-1R and human ErbB3. Exemplary antibodies inhibit signal transduction through either or both of IGF-1R and ErbB3. Exemplary polyvalent proteins comprise at least one anti-IGF-1R binding site and at least one anti-ErbB3 binding site. In certain embodiments the binding sites may be linked through an immunoglobulin constant region. AntiErbB3 and anti-IGF-1R antibodies (e.g., monoclonal antibodies) are also provided.

Abstract: The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Abstract: The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Abstract: Engineered multivalent and multispecific binding proteins that bind IL-13 and/or IL-17 are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: The disclosure relates to a protein composed of a first polypeptide or polypeptide domain having a first specific binding activity for Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) expressed on a T-cell cell surface and a second specific binding activity for Glucose Transporter 2 (GLUT2) or an extracellular ectodomain thereof expressed on a pancreatic ?-cell surface, wherein binding of the first polypeptide or polypeptide domain to CTLA-4 induces a CTLA-4 specific agonist response in the T-cell, and binding of the second polypeptide or polypeptide domain to GLUT2 or an ectodomain thereof does not inhibit GLUT2 glucose transporter function, wherein said agonist response in the T-cell induces a response that reduces immunoreactivity against pancreatic ?-cells.

Abstract: The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, with greater affinity than said antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.

Abstract: The invention relates to improved variants of the anti-serum albumin immunoglobulin single variable domain DOM7h-14-10, as well as ligands and drug conjugates comprising such variants, compositions, nucleic acids, vectors and hosts.

Abstract: Provided herein in certain embodiments are polypeptide complexes capable of binding to an antigen. Pharmaceutical compositions, method of using the polypeptide complexes are also provided.

Abstract: The present invention relates to new uses of CDCP1 in the diagnosis, screening, treatment and prophylaxis of ovarian cancer. The invention also provides compositions comprising CDCP1, including vaccines, antibodies that are immunospecific for CDCP1 and agents which interact with or modulate the expression or activity of CDCP1 or which modulate the expression of the nucleic acid which codes for CDCP1.

Abstract: The invention relates to antibody polypeptides that monovalently bind CD40L. Antibody polypeptides that are monovalent for binding of CD40L can inhibit CD40L activity while avoiding potential undesirable effects that can occur with antibodies capable of divalent or multivalent binding of CD40L. In one aspect, a monovalent anti-CD40L antibody polypeptide consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD40L, preferably without substantially agonizing CD40 and/or CD40L activity. In another aspect, the monovalent anti-CD40L antibody polypeptide is a human antibody polypeptide. The invention further encompasses methods of antagonizing CD40/CD40L interactions in an individual and methods of treating diseases or disorders involving CD40/CD40L interactions, the methods involving administering a monovalent anti-CD40L antibody polypeptide to the individual.

Abstract: Described herein is a method of identifying a monoclonal antibody (or antigen-binding fragment thereof) that specifically binds a plurality of lyssaviruses for use in post-exposure rabies prophylaxis or in the treatment of clinical rabies. The method includes using a naïve antibody phage display library to screen for phage clones that bind whole recombinant rabies virus or cells expressing glycoprotein from multiple lyssaviruses (such as RABV, MOKV and WCBV) and/or specifically bind recombinant glycoprotein from different lyssaviruses.

Abstract: The present invention provides a cytotoxically active CD3 specific binding construct comprising a first domain specifically binding to human CD3 and an Ig-derived second binding domain. Furthermore, a nucleic acid sequence encoding a CD3 specific binding construct of the invention is provided. Further aspects of the invention are vectors and host cells comprising said nucleic acid sequence, a process for the production of the construct of the invention and composition comprising said construct. The invention also provides the use of said constructs for the preparation of pharmaceutical compositions for the treatment of particular diseases, a method for the treatment of particular diseases and a kit comprising the binding construct of the invention.

Abstract: This invention provides compositions of matter, articles of manufacture and methods for delivering and/or affixing a stem cell to a target tissue. This invention also provides related nucleic acids, vectors, cells, methods of production, and kits.

Abstract: A composite polypeptide, said composite polypeptide comprising a desired polypeptide and an expression enhancing domain (“EED”), said EED comprising first and second cysteine amino acid residues Cys1 and Cys2, respectively, Cys1 being located closer to the N-terminus of the composite polypeptide molecule than Cys2, wherein Cys1 and Cys2 are separated by a polypeptide linker, said linker—being free of cysteine and proline;—defining a length sufficient to allow Cys1 and Cys2 to engage in an intramolecular disulfide bond with one another; and—having a flexible polypeptide conformation essentially free of secondary polypeptide structure in aqueous solution, wherein at least one of Cys1 and Cys2 is derivatized with a derivatization moiety.

Abstract: The invention relates to antibodies against the human La protein and to their use in immunotargeting, in particular the immunotargeting of tumour cells. The object of the invention is to provide improved antibodies which bind universal target structures on the surface of tumour cells, and to provide novel anti-La antibodies, in particular with a high affinity for La, a universal target structure on tumour cells, which make it possible to use the antibodies as recombinant fragments for immunotargeting. The invention comprises recombinant antibodies comprising: i. a binding unit of an antibody which specifically binds to an epitope of a human nuclear antigen, preferably human La protein, and ii. a binding unit of an antibody which specifically binds to an effector cell or of a ligand which specifically binds to an effector cell. The invention furthermore comprises novel antibodies which specifically bind the human La protein.

Abstract: The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

Abstract: The invention is based upon the discovery that the EGFR pathway can stimulate a previously unknown tumorigenic function of CA IX, via phosphorylation of the sole tyrosine residue present in CA IX's intracellular domain. EGFR-phosphorylated CA IX then interacts with the p85 subunit of PI3K to activate Akt, which in turn is associated with anti-apototic function and increased cell survival. The latter finding indicates that there is a positive feedback loop for CA9 expression mediated by the PI3K pathway in preneoplastic/neoplastic diseases. Disclosed herein are novel therapeutic methods for treating preneoplastic/neoplastic diseases associated with abnormal MN/CA IX expression, using EGFR pathway inhibitors. Preferably, the EGFR pathway inhibitors are tyrosine kinase inhibitors or EGFR-specific antibodies.

Abstract: The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-17A and IL-17F. IL-17A and IL-17F are cytokines that are involved in inflammatory processes and human disease. The present invention includes antibodies that bind both IL-17A and IL-17F, as well as methods of using the same in inflammation.

Abstract: The present invention relates to novel methods and compositions for increasing AMPK activity and glucose uptake comprising administering a macrophage migration inhibitory factor (MIF) pathway agonist in a subject in need thereof. The invention also relates to methods for selecting a subject for treatment with an agonist of MIF, identifying a subject at risk for developing a condition in which increased AMPK activity is desirable, and for predicting whether a subject is susceptible to a condition in which increased AMPK activity is desirable.

Abstract: Isolated monoclonal antibodies which bind to human CD38 and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies.

Abstract: The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds Fc?RIIIA and/or Fc?RIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by Fc?R is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Abstract: Proteins that bind IL-1? and IL-1? are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1? and IL-1? in cells, tissues, samples, and compositions.

Abstract: The present invention concerns somatic ErbB3 mutations in cancer including methods of identifying, diagnosing, and prognosing ErbB3 cancers, as well as methods of treating cancer, including certain subpopulations of patients.

Abstract: Engineered multivalent and multispecific binding proteins that bind two different (e.g., nonoverlapping) epitopes of the same receptor or two different receptors expressed on the same cell are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.

Abstract: This invention provides fully human monoclonal antibodies that recognize IL-17F, the IL-17F homodimer, IL-17A, the IL-17A homodimer, and/or the heterodimeric IL-17A/IL-17F protein complex. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Abstract: The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, auto-immune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes and in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.

Abstract: Compositions and methods are provided for treating diseases associated with CD100, including certain autoimmune diseases, inflammatory diseases, and cancers. In particular, anti-CD100 monoclonal antibodies have been developed to neutralize CD100.

Abstract: The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-17A, IL-17F, and IL-23. Antagonists include antibodies and antibody fragments that bind IL-23 and that bind IL-17A or IL-17F, such as antibodies that are cross-reactive for IL-17A and Il-17F. Antagonists that include an antibody or antibody fragment that binds IL-23 and an antibody or antibody fragment that binds IL-17A or IL-17F on one molecule are also disclosed. Antibodies and antibody fragments that bind IL-23 and IL-17F but that do not bind IL-17A are also disclosed. IL-17 and IL-23 are cytokines that are involved in inflammatory processes and human disease.

Abstract: Compositions and methods are provided for alleviating endometriosis, kidney disease, inflammatory disease and/or transplant rejection in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits AXL, MER or Tyro3 protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL, MER or Tyro3 and its ligand GAS6.

Abstract: The present disclosure relates to anti-CD200 antibodies and to use of the antibodies in methods for treating autoimmune disorders and cancer. Also featured are biomarkers for use in selecting or prescribing a treatment modality for a patient with an autoimmune disorder and/or cancer. In addition, the disclosure features methods of treatment using an anti-CD200 antibody in combination with one or more additional therapeutic agents such as an anti-CD20 therapeutic agent.

Abstract: This invention relates to bispecific fusion proteins effective in viral neutralization. More specifically, such proteins have two different binding domains, an inducing-binding domain and an induced-binding domain, functionally linked by a peptide linker. Such proteins, nucleic acid molecules encoding them, and their production and use in preventing or treating viral infections are provided. One prototypical bispecific fusion protein is sCD4-SCFv(17b), in which a soluble CD4 fragment (containing domains D1 and D2) is fused to a single chain Fv portion of antibody 17b via a linker.

Abstract: In one aspect, the present invention relates to an antigen-binding molecule specific for albumin and CD3 which may comprise two polypeptide chains, each polypeptide chain having at least four variable domains in an orientation preventing Fv formation and the two polypeptide chains are dimerized with one another thereby forming a multivalent antigen-binding molecule. On each of the two polypeptide chains the four variable domains may be arranged in the order VLA-VHB-VLB-VHA from the N-terminal to the C-terminal of the polypeptide. Compositions of the antigen-binding molecule and the methods of using the antigen-binding molecule or the compositions thereof for treatment of various diseases are also provided herein.

Abstract: Disclosed herein is a method of treating dry eye with a KLK-13 antibody.

Abstract: Methods for improving the biological and pharmaceutical properties of bispecific binding agents are described herein where the bispecific binding agents are able to target cells by a high affinity binding domain to a first cell surface marker that does not induce a significant biological effect and a low affinity binding domain that binds specifically to a second cell surface marker, causing a significant and desired biological effect. Compositions of such bispecific binding agents, uses for them, and kits containing them are also provided.

Abstract: Provided herein are methods for making targeted therapeutics. In several embodiments, the therapeutics are directed against soluble agents such as toxins, venoms, and/or other factors that alter physiological biopathways as well as methods of using such therapeutics to treat patients or patient populations to reduce, eliminate, or inactivate, detrimental soluble agents that such patients or patient populations have been exposed to. In several embodiments, the therapeutics are directed to patient-specific disease markers. In several embodiments, the methods comprise screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent.

Abstract: Monoclonal antibodies, synthetic and biotechnological derivatives thereof (ScFv or others) are able to recognise the NGF high affinity receptor, TrkA, and act as NGF-antagonist molecules. Pharmacological compositions for therapy, gene therapy, diagnostics of neurological pathologies are also described. Transgenic animal models to study such pathologies are also described.

Abstract: Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases, using multispecific antagonists that target at least two different markers are disclosed. The different targets include proinflammatory effectors of the innate immune system and targets specifically associated with an inflammatory or immune-dysregulatory disorder, wherein the targets included in the latter group are not a proinflammatory effector of the immune system. Thus, the multispecific antagonist contains at least one binding specificity related to the diseased cell or condition being treated and at least one specificity to a component of the immune system. The multispecific antagonists are used in the treatment of various diseases that are generated or exacerbated by, or otherwise involve, proinflammatory effectors of the innate immune system.

Abstract: The invention provides an isolated, dual-specific antibody, or an antigen-binding portion thereof, which is specific for human IL-1? and human IL-1?. The dual specific antibodies of the invention also neutralize both human IL-1? and human IL-1?. The invention also provides domain antibodies (dAbs) specific for human IL-1? and human IL-1?.

Abstract: Multivalent and multispecific binding proteins, methods of making, and their uses in the diagnosis, prevention, and/or treatment diseases are provided.

Abstract: Compounds and compositions useful for the treatment of liver diseases and methods of treating liver diseases are disclosed. The compounds of the invention specifically interact with heteromers of cannabinoid receptors as compared to monomers or homodimers. The invention also relates to methods of screening for compounds useful for the treatment of liver diseases and to methods of screening for diacylglycerol lipase inhibitors.

Abstract: Antibodies having dual specificity for two different but structurally related antigens are provided. The antibodies can be, for example, entirely human antibodies, recombinant antibodies, or monoclonal antibodies. Preferred antibodies have dual specificity for IL-1? and IL-1? and neutralize IL-1? and IL-1? activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting two different but structurally related antigens (e.g., IL-1? and IL-1?) and for inhibiting the activity of the antigens, e.g., in a human subject suffering from a disorder in which IL-1? and/or IL-1? activity is detrimental.

Abstract: Disclosed herein are compositions and methods of use comprising combinations of anti-CD74 antibodies with a therapeutic agent. The therapeutic agent may be attached to the anti-CD74 antibody or may be separately administered, either before, simultaneously with or after the anti-CD74 antibody. In preferred embodiments, the therapeutic agent is an antibody or fragment thereof that binds to an antigen different from CD74, such as CD19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80, IL-6, CXCR4 and HLA-DR. However, the therapeutic agent may an immunomodulator, a cytokine, a toxin or other therapeutic agent known in the art. More preferably, the anti-CD74 antibody is part of a DNL complex, such as a hexavalent DNL complex. Most preferably, combination therapy with the anti-CD74 antibody or fragment and the therapeutic agent is more effective than the antibody alone, the therapeutic agent alone, or the combination of anti-CD74 antibody and therapeutic agent that are not conjugated to each other.

Abstract: Provided are bispecific antibodies that are useful as anti-neoplastic agents and that bind specifically to human IGF-1R and human ErbB3. Exemplary antibodies inhibit signal transduction through either or both of IGF-1R and ErbB3.

Abstract: Disclosed herein are methods and compositions comprising anti-CD74 and/or anti-HLA-DR antibodies for treatment of GVHD and other immune dysfunction diseases. In preferred embodiments, the anti-CD74 and/or anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8+ memory T cells. The compositions and methods provide a novel conditioning regimen for preventing aGVHD and/or treating chronic GVHD, without altering preexisting anti-viral immunity.