Abstract: The present invention relates to antibodies that specifically bind to IL12R?1, the non-signal transducing chain of both the heterodimeric IL12 and IL23 receptors. The invention more specifically relates to specific antibodies that are IL12 and IL23 receptor antagonists capable of inhibiting IL12/IL18 induced IFN? production of blood cells and compositions and methods of use for said antibodies to treat pathological disorders that can be treated by inhibiting IFN? production, IL12 and/IL23 signaling, such as rheumatoid arthritis, psoriasis or inflammatory bowel diseases or other autoimmune and inflammatory disorders.

Abstract: Antibodies are disclosed which bind specifically to P-selectin and which block the binding of PSGL-1 to P-selectin. These anti-P-selectin antibodies may also cause dissociation of preformed P-selectin/PSGL-1 complexes. The disclosure identifies a heretofore unrecognized, near N-terminal, antibody binding domain (a conformational epitope) of P-selectin to which the function-blocking antibodies (which may be chimeric, human or humanized antibodies for example) bind. Antibodies are disclosed which bind to the conformational epitope of P-selectin and which have a dual function in blocking binding of PSGL-1 to P-selectin, and in causing dissociation of preformed P-selectin/PSGL-1 complexes. Such single and dual function anti-P-selectin antibodies and binding fragments thereof may be used in the treatment of a variety of inflammatory and thrombotic disorders and conditions. Screening methods for identifying such antibodies are also disclosed.

Abstract: Stable liquid pharmaceutical compositions comprising an antagonist anti-CD40 antibody as a therapeutically or prophylactically active component and methods useful in their preparation are provided. These compositions comprise the antagonist anti-CD40 antibody, a buffering agent to maintain the pH of the composition between about pH 5.0 and about pH 7.0, and an amount of arginine-HCl sufficient to render the liquid composition near isotonic. The stable liquid antagonist anti-CD40 antibody-containing pharmaceutical compositions of the invention find use in methods for treating proliferative diseases and diseases having an autoimmune and/or inflammatory component.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor and inhibits tumor growth. The present invention further provides a method of treating cancer, the method comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.

Abstract: An object of the present invention is to provide a monoclonal antibody which is useful for treating or diagnosing a disease relating to system ASC amino acid transporter 2 (hereinafter, referred to as “ASCT2”) or a method using the antibody. The present invention provides a monoclonal antibody which specifically recognizes a native three-dimensional structure of an extracellular region of ASCT2 and binds to the extracellular region, or an antibody fragment thereof; a hybridoma which produces the antibody; a DNA which encodes the antibody; a vector which contains the DNA; a transformant obtainable by introducing the vector; a process for producing an antibody or an antibody fragment thereof using the hybridoma or the transformant; and a therapeutic agent using the antibody or the antibody fragment thereof, and a diagnostic agent using the antibody or the antibody fragment thereof.

Abstract: The present inventors investigated the effects of anti-IL-6 receptor antibodies on improving the condition of infarcted areas in myocardial infarction, and on suppressing left ventricular remodeling after myocardial infarction. As a result, the administration of anti-IL-6 receptor antibodies significantly suppressed the increase of MPO activity in the infarcted area and suppressed myocardial MCP-1 expression in both the infarcted area and the non-infarcted area. Furthermore, echocardiography and histological examinations revealed that cardiac hypertrophy is also suppressed.

Abstract: The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.

Abstract: The present invention relates to antibodies or fragments thereof that specifically bind Fc?RIIB, particularly human Fc?RIIB, more particularly the extracellular domain of Fc?RIIB with greater affinity than said antibodies or fragments thereof bind Fc?RIIA, particularly human Fc?RIIA, and block the Fc binding site of Fc?RIIB. The present invention also encompasses the use of an anti-Fc?RIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The present invention also encompasses the use of an anti-Fc?RIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies.

Abstract: The present invention relates to Notch-binding agents and Notch antagonists and methods of using the agents and/or antagonists for treating diseases such as cancer. The present invention provides antibodies that specifically bind to a non-ligand binding region of the extracellular domain of one or more human Notch receptor, such as Notch2 and/or Notch3, and inhibit tumor growth. The present invention further provides methods of treating cancer, the methods comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor and inhibits tumor growth. The present invention further provides a method of treating cancer, the method comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.

Abstract: The present invention provides novel high affinity antibodies and fragments thereof that bind to the cancer antigen PSCA. The antibodies of the present invention may be used for cancer diagnosis, prognosis, treatment, visualization, and the like. The present invention also provides methods for the detection, visualization, and treatment of various cancers expressing PSCA.

Abstract: The present invention relates to humanized antibodies that specifically bind an EC1 domain of a mammalian Cadherin-11 protein and compositions (e.g., pharmaceutical compositions) comprising such antibodies. The invention also relates to methods for treating Cadherin-11-mediated disorders in a mammalian subject by administering a therapeutically effective amount of a humanized antibody of the invention. Cadherin-11-mediated disorders suitable for treatment by the methods of the invention include inflammatory disorders (e.g., inflammatory joint disorders, such as rheumatoid arthritis), fibrosis and cancer.

Abstract: The invention provides novel humanized antibody fragments that specifically bind prostate cell-surface antigen (PSCA), a protein which is overexpressed in variety of cancers, including prostate, bladder, and pancreatic cancer. Methods are provided for the use of the compositions of the invention for the treatment of cancer, diagnosis of cancer, to provide a prognosis of cancer progression, and for cancer imaging.

Abstract: The present invention relates to particular polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes.

Abstract: The present invention relates to Fc variants having increased affinity for Fc?RIIc, methods for their generation, Fc polypeptides comprising optimized Fc variants, and methods for using optimized Fc variants.

Abstract: The present invention relates to fibronectin based scaffold domain protein that bind interleukin 23 (IL-23), specifically the p19 subunit of IL-23. The invention also relates to the use of the innovative proteins in therapeutic applications to treat autoimmune diseases. The invention further relates to cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative proteins.

Abstract: An anti-E1 ion channel antibody or binding fragment thereof, pharmaceutical compositions comprising said antibodies, use of the antibodies and compositions comprising the same, in treatment, for example in the treatment/modulation of pain and processes for generating and preparing said antibodies.

Abstract: Methods for treating a human patient for a cancer or pre-malignant condition that is associated with CD40-expressing cells are provided, where the human patient is heterozygous or homozygous for Fc?RIIIa-158F (genotype V/F or F/F). Also provided are methods of inhibiting antibody production by B cells in a human patient who is heterozygous or homozygous for Fc?RIIIa-158F (genotype V/F or F/F). The methods comprise administering to the human patient a therapeutically or prophylactically effective amount of an anti-CD40 antibody. Methods and kits for identifying a human patient with a cancer or pre-malignant condition that is treatable with an anti-CD40 antibody and which is refractory to treatment with rituximab (Rituxan®), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having a cancer or pre-malignant condition that is refractory to treatment with rituximab (Rituxan®), are also provided.

Abstract: Isolated monoclonal antibodies which bind to human CD32b 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: A method for the treatment of a condition which is characterized by CD 123-expressing cells in a patient comprises administering to the patient (i) an antibody or antibody fragment which binds selectively to IL-3R?(CD 123), and (ii) an immunostimulating complex which comprises saponin, a sterol and a phospholipid.

Abstract: Isolated antibodies that specifically binds to an extracellular conserved ligand binding region of a human Notch receptor and inhibits growth of a tumor are described. Also described are methods of treating cancer, the method comprising administering an anti-Notch antibody in an amount effective to inhibit tumor growth.

Abstract: The present invention relates generally to binding agents useful in the selective depletion of T cells in vivo. More specifically, the invention relates to ICOS-binding agents which once bound to ICOS expressed on the surface of cells, in particular ICOS-bearing activated T cells, result in the in vivo depletion of cells to which they are bound. Methods of treating T cell related diseases using said ICOS-binding agents, and pharmaceutical compositions comprising said ICOS-binding agents, a method of identifying an ICOS-binding agent, and monoclonal anti-ICOS antibodies capable of eliminating cells in vivo which express ICOS on their surface are also provided.

Abstract: A highly stable mutant of human IgG4 antibody is provided. Such antibody is an antibody in which the CH3 domain of human IgG4 is substituted with the CH3 domain of human IgG1 and which exhibits inhibited aggregate formation, an antibody in which the CH3 and CH2 domains of human IgG4 are substituted with the CH3 and CH2 domains of human IgG1, respectively, or an antibody in which arginine at position 409 indicated in the EU index proposed by Kabat et al. of human IgG4 is substituted with lysine and which exhibits inhibited aggregate formation.

Abstract: Provided are monoclonal antibodies and antigen-binding fragments thereof that bind to CD47 of multiple mammalian species, block the binding of SIRPalpha and TSP1 to CD47, promote phagocytosis of susceptible cancer cells, and reverse TSP1 inhibition of nitric oxide signaling, as well as monoclonal antibodies and antigen binding fragments thereof that compete with the former for binding to CD47 and that exhibit similar biological activities. Also provided are combinations of any of the foregoing. Such antibody compounds are variously effective in 1) treating tissue ischemia and ischemia-reperfusion injury (IRI) in the setting of organ preservation and transplantation, pulmonary hypertension, sickle cell disease, myocardial infarction, stroke, and other instances of surgery and/or trauma in which IRI is a component of pathogenesis; 2) in treating autoimmune and inflammatory diseases; and 3) as anti-cancer agents for treating susceptible cancer cells, promoting their phagocytic uptake and clearance.

Abstract: Disclosed are antibody fusion proteins with a modified FcRn binding site and nucleic acid molecules encoding them. The antibody fusion protein include two polypeptide chains, wherein the first polypeptide chain includes a biologically active molecule linked to at least a portion of an immunoglobulin constant region. The second polypeptide chain includes at least a portion of an immunoglobulin constant region. One of the polypeptide chains includes a mutation in the FcRn binding site that reduces binding to FcRn. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins for treating diseases and conditions alleviated by the administration of the fusion proteins.

Abstract: The present invention relates to the use of inhibitors of leukotriene B4 receptor BLT2 for treating asthma. More particularly, the present invention relates to a pharmaceutical composition for treating asthma comprising BLT2 inhibitors and a method for treating asthma using BLT2 inhibitors.

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: Detection of human antibodies directed against the tumor-specific protein Epidermal Growth Factor Receptor variant Class III (EGFRvIII) provide information on tumor burden and vaccine response. The methods of the invention permit the specific identification of antibodies that are able to bind to EGFRvIII. The methods are useful in determining the presence of an EGFRvIII-expressing tumor and in detecting immune responses following immunization with EGFRvIII-derived peptide as part of a cancer immunotherapy regimen.

Abstract: Described herein are anti-NKG2A antibodies suitable for human therapy, including humanized versions of murine anti-NKG2A antibody Z270, as well as related methods and materials for producing and using such antibodies. Exemplary complementarity-determining regions (CDRs) sequences and sites for optional amino acid back-substitutions in framework region (FR) and/or CDRs of such antibodies are also described.

Abstract: Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed.

Abstract: The present invention provides binding molecules that specifically bind to ILT3, e.g., human ILT3 (hILT3), on antigen presenting cells, such as for example, monocytes, macrophages and dendritic cells (DC), e.g., monocyte-derived dendritic cells (MDDC). Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof. Methods of using the binding molecules of the invention to detect human ILT3 or to modulate human ILT3 activity, either in vitro or in vivo, are also encompassed by the invention.

Abstract: The present invention relates to an antibody binding to the domain 2 of human intercellular adhesion molecules-1 (ICAM-1) where the antibody is able to modulate the differentiation status of dendritic cells and induce antigen-specific T cell tolerance, thereby be effective in the prevention and/or treatment of T cell-mediated immune disorders such as transplantation rejection, graft-versus-host disease, and autoimmune disease. In addition, the present invention provides a pharmaceutical composition comprising the antibody, and method of using them for the treatment of disease.

Abstract: The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

Abstract: Provided are felinized antibodies and methods for treating or reducing the likelihood of developing a retroviral infection in a feline, decreasing retroviral virion entry into a feline cell, decreasing retroviral virion budding from a feline cell, or decreasing syncytium transmission in a feline. These methods require the administration of at least one felinized antibody or fragment thereof that specifically binds to CD11a and/or CD18, or ICAM-1, and/or decreases or prevents the binding of LFA-1 (CD11a/CD18 heterodimer) to ICAM-1. Also provided are veterinary compositions and methods of identifying candidate agents useful for treating or reducing retroviral infection in a feline, decreasing retroviral virion entry into a feline cell, decreasing retroviral virion budding from a feline cell, or decreasing syncytium transmission in a feline.

Abstract: Provided herein are compositions comprising anti-HLA-Ib antibodies (monoclonal, mixed monoclonal, recombinant, chimeric, humanized or human antibodies) as IVIg mimetics and methods for using the same for the prevention, treatment, therapy and/or amelioration of inflammation induced diseases and allograft rejection. In certain embodiments, the anti-HLA-Ib antibodies strongly mimic IVIg in immunoreactivity to HLA class Ia (HLA-A, HLA-B and HLA-Cw) and Ib antigens (HLA-E, HLA-F and HLA-G). In certain embodiments, the anti-HLA-Ib antibodies strongly mimic IVIg in immunomodulatory or immunosuppressive activities. Methods are also provided herein to induce production of polyclonal anti-HLA-Ib antibodies in cancer patients for restoring anti-tumor activities of CD8+ T cells and NK cells, by active specific immunotherapy.

Abstract: The present invention provides antibodies which bind to an epitope in the extracellular domain of human CC chemokine receptor 4 (CCR4) and which are capable of inhibiting the binding of macrophage-derived chemokine (MDC) and/or thymus and activation regulated chemokine (TARC) to CCR4. Also provided are inter alia immunoconjugates and compositions comprising such antibodies and methods and uses involving such antibodies, particularly in the medical and diagnostic fields.

Abstract: Antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The antibody polypeptides are useful in the treatment of diseases involving CD40L activation, such as graft-related diseases and autoimmune diseases. The antibody polypeptides may be domain antibodies (dAbs) comprising a single VH or VK domain. The half-life of the antibody polypeptides may be increased by modifying the antibody polypeptides to be dual specific reagents that can also bind human serum albumin (HSA) or another antigen.

Abstract: The present invention is directed to a cross-reactive antibody, which specifically inhibits or blocks the mammalian Toll-like receptor 2 (TLR2)-mediated immune cell activation. The invention is further directed to an isolated nucleic acid or vector coding for the variable regions of the heavy and/or light chain of said antibody. It is further providing a pharmaceutical composition comprising said antibody, nucleic acid or vector and is directed to the use of said composition in the prevention and/or treatment of inflammatory processes or any other process induced by bacterial infection, trauma, or chronic inflammation, or for the prevention and/or treatment of bacteriaemia or sepsis.

Abstract: Provided are a pharmaceutical composition for suppressing a resistance to a targeted anticancer drug, which at least one selected from the group consisting of an integrin ?3 neutralizing antibody, integrin ?3 siRNA, Src inhibitor, and Src siRNA as an active ingredient, and an anticancer supplement. The pharmaceutical composition may increase an anticancer therapeutic effect when administered in combination with a conventional targeted anticancer drug. In addition, the pharmaceutical composition is expected to be used in development of an integrin ?3-targeted targeted anticancer drug.

Abstract: The present disclosure relates to AM-14 pharmaceutical formulations and therapeutic dosing regimens for the treatment of disease.

Abstract: In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucleotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.

Abstract: The present invention relates to antigen binding molecules (ABMs). In particular embodiments, the present invention relates to recombinant monoclonal antibodies, including chimeric, primatized or humanized antibodies specific for human CD20. In addition, the present invention relates to nucleic acid molecules encoding such ABMs, and vectors and host cells comprising such nucleic acid molecules. The invention further relates to methods for producing the ABMs of the invention, and to methods of using these ABMs in treatment of disease. In addition, the present invention relates to ABMs with modified glycosylation having improved therapeutic properties, including antibodies with increased Fc receptor binding and increased effector function.

Abstract: Provided herein are glycovariant Fc fusion proteins having increased serum half lives. Also provided are methods for increasing the serum half life of an Fc fusion protein by introducing one or more non-endogenous glycosylation sites.

Abstract: The prediction of protein function as well as the reconstruction of evolutionary genesis employing sequence comparison at large is still the most powerful tool in sequence analysis. Due to the exponential growth of the number of known protein sequences and the subsequent quadratic growth of the similarity matrix, the computation of the Similarity Matrix of Proteins (SIMAP) becomes a computational intensive task. The SIMAP database provides a comprehensive and up-to-date pre-calculation of the protein sequence similarity matrix, sequence-based features and sequence clusters. As of September 2009, SIMAP covers 48 million proteins and more than 23 million non-redundant sequences. Novel features of SIMAP include the expansion of the sequence space by including databases such as ENSEMBL as well as the integration of metagenomes based on their consistent processing and annotation.

Abstract: The present invention relates to LRP6 constructs that bind to LRP6 receptor. The LRP6 constructs comprise at least one LRP6 binding moiety and a half-life extender molecule such that the LRP6 construct inhibit the Wnt signaling pathway without potentiation of the Wnt signal. The LRP6 constructs also have an increased half-life to provide more time for the therapeutic benefit.

Abstract: Binding members, especially antibody molecules, for interleukin (IL)-4 receptor alpha (IL-4R?), and their therapeutic use e.g. in treating or preventing disorders associated with IL-4R?, IL-4 and/or IL-13, examples of which are asthma and COPD.

Abstract: Monoclonal neutralizing antibodies that specifically bind to HIV-1 gp120 and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV infection is disclosed.

Abstract: The invention provides a two-step chromatography process for small and large-scale purification of proteins, specifically monoclonal antibodies, using only four buffer solutions made from a mother solution.

Abstract: There are disclosed alpha4beta7 heterodimer-specific antigen binding proteins, nucleic acids encoding them, and methods of making and using them.

Abstract: This invention pertains to methods and compositions for the diagnosis and treatment of cardiovascular conditions. More specifically, the invention relates to isolated molecules that can be used to diagnose and/or treat cardiovascular conditions including cardiac hypertrophy, myocardial infarction, stroke, arteriosclerosis, and heart failure.