Abstract: The present invention relates to new humanized antagonistic anti-CD40 antibodies and therapeutic and diagnostic methods and compositions for using the same.

Abstract: The present invention relates to immunotherapies that are based on depletion of CD37-positive cells such as B-cells. The present invention provides methods for reduction of CD37-positive cells such as B-cells in an individual/patient using a combination of CD37 antibody/antibodies and ICE. The combination of CD37 antibodies and ICE is shown to have improved anti-tumor efficacy compared to single agent treatment. The application further provides materials and methods for treatment of diseases involving aberrant B-cell activity.

Abstract: The present invention relates to immunotherapies that are based on depletion of CD37-positive cells such as B-cells. The present invention provides methods for reduction of CD37-positive cells such as B-cells in an individual/patient using a combination of CD37 antibody/antibodies and bendamustine. The combination of CD37 antibodies, CD20 antibodies and bendamustine is shown to have a synergistic effect. The application further provides materials and methods for treatment of diseases involving aberrant B-cell activity.

Abstract: Methods are disclosed for treating or inhibiting an autoimmune disease in a subject. In some embodiments, the disclosed methods include administering to the subject a therapeutically effective amount of one or more Major Histocompatibility Complex (MHC) molecules including covalently linked first, second and third domains; wherein the first domain is an MHC class II ?1 domain and the second domain is an MHC class II ?1 domain, wherein the amino terminus of the ?1 domain is covalently linked to the carboxy terminus of the ?1 domain; or wherein the first domain is an MHC class I ?1 domain and the second domain is an MHC class I ?2 domain, wherein the amino terminus of the ?2 domain is covalently linked to the carboxy terminus of the ?1 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen associated with the autoimmune disorder.

Abstract: The present disclosure describes a pharmaceutical combination of an anti-CD38 antibody and lenalidomide and a pharmaceutical combination of an anti-CD38 antibody and bortezomib.

Abstract: The present invention relates to a binding compound which binds to human APRIL. More specifically the invention provides, compositions of anti-APRIL specific antibodies and methods to use such antibodies in modulating the biological activity APRIL, particularly in inflammatory diseases, inhibition of cell proliferation and cancer.

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

Abstract: The invention relates to the use of CD89 activating molecules, in particular Fc alpha comprising molecules, and more particularly, IgA, for inducing apoptosis in neutrophils. Anti-CD89 antibodies can alternatively be used. The CD89 activation is beneficial in the treatment of various disorders associated with increases in neutrophils, such as autoimmune disorders, inflammatory disorders, NETosis, or cystic fibrosis.

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

Abstract: The present invention relates to agents capable of binding sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) and their use in the treatment of cell proliferation and differentiation disorders. Furthermore, the present invention provides associated pharmaceutical formulations and methods.

Abstract: Described herein is a novel receptor-ligand interaction and agents that may modify and/or block the interaction. Methods, uses, reagents and kits for the modulation of ligand activities related to its interaction with the novel receptor are disclosed. Also disclosed are therapeutic uses of reagents in treating inflammation-related disorders.

Abstract: The present invention provides compositions and methods for the treatment of autoimmune diseases, in particular rheumatoid arthritis. Compounds which function as antagonists of Toll-like Receptor 2 are shown to suppress the immune response which result in the onset and progression of autoimmune disease. In particular monoclonal antibodies which have a binding specificity to Toll-like receptor 2 are disclosed for use in methods for the treatment and/or prophylaxis of autoimmune disease.

Abstract: The invention relates to the regulation of the immune system, and in particular to the finding that the CLEC9a molecule is a marker for dendritic cells which are capable of cross-presenting extracellular antigens via the MHC class I pathway. This makes them particularly suitable for generation of cytotoxic T lymphocyte responses. Materials and methods are provided both for the induction of immune responses against target antigens, and for the inhibition or suppression of undesirable immune responses in which these cells are involved.

Abstract: A medicament having a higher therapeutic effect than that provided by administration of a recombinant antibody against human CC chemokine receptor 4 or an antibody fragment thereof or an agent alone is provided.

Abstract: Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.

Abstract: A mutant of a potentially therapeutic anti-CD40 antibody is provided which mutant has reduced ADCC and CDC activities designed to be optimized as a pharmaceutical agent. A mutant of an agonistic anti-CD40 antibody, comprising mutation and/or substitution of at least one amino acid in the constant region to reduce the ADCC and/or CDC activities therein, and a mutant of an antagonistic anti-CD40 antibody, comprising at least one mutation or substitution in the constant region to reduce the ADCC and/or CDC activities therein, both mutants having at least a hinge region derived from a human IgG2.

Abstract: The present disclosure provides combinations of immunotherapeutics and methods for treating medical conditions that are characterized by the lack of an effective immune response, for example as would result following a down-regulation of MHC class I, such as in cancer. The immunotherapeutic compositions of the invention, which can be used to treat the medical conditions, include one or more immunostimulatory antibodies or molecules having specificity for CTLA-4, PD-1, PD-L1, PD-L2, CD40, OX40, CD137, GITR, ILT2, or ILT3, or ligands for these molecules (e.g., an isolated fully-human monoclonal antibody) in association with one or more alloantigens, such as, vector(s) capable of expressing protein(s) or peptide(s) that stimulate T-cell immunity against tissues or cells, formulated in a pharmaceutically acceptable carrier. The proteins or peptides may comprise class I major histocompatibility complex (MHC) antigens, ?2-microglobulins, or cytokines. The MHC antigen may be foreign to the subject.

Abstract: An isolated antibody capable of binding Siglec-15 which inhibits osteoclast formation and/or osteoclastic bone resorption, or a functional fragment thereof. The heavy chain of the antibody comprises a CDRH1 comprising a sequence having at least 80% sequence identity to SEQ ID NO: 106, a CDRH2 comprising a sequence having at least 80% sequence identity to SEQ ID NO: 107, and a CDRH3 comprising a sequence having at least 80% sequence identity to one of SEQ ID NOS: 35, 45, 55, 65 or 80. The light chain of the antibody comprises a CDRL1 comprising a sequence having at least 80% sequence identity to SEQ ID NO: 73 or 83, a CDRL2 comprising a sequence having at least 80% sequence identity to SEQ ID NO: 108, and a CDRL3 comprising a sequence having at least 80% sequence identity to one of SEQ ID NOS: 40, 50, 60, 70, 90, 100 or 109.

Abstract: Human antibodies, preferably recombinant human antibodies, both humanized and chimeric, which specifically bind to human OX40 are disclosed. Preferred antibodies have high affinity for OX40 receptor and activate the receptor in vitro and in vivo. The antibody can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, are useful for modulating receptor activity, e.g., in a human subject suffering from a disorder in which OX40 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies are provided, and methods of synthesizing the recombinant human antibodies, are also provided.

Abstract: Methods are provided to manipulate phagocytosis of cancer cells, including e.g. leukemias, solid tumors including carcinomas, etc.

Abstract: The present invention concerns treatment of autoimmune diseases with antagonists which bind to B cell surface markers, such as CD19 or CD20.

Abstract: The present disclosure provides combinations of immunotherapeutics and methods for treating medical conditions that are characterized by the lack of an effective immune response, for example as would result following a down-regulation of MHC class I, such as in cancer. The immunotherapeutic compositions of the invention, which can be used to treat the medical conditions, include one or more immunostimulatory antibodies or molecules having specificity for CTLA-4, PD-1, PD-L1, PD-L2, CD40, OX40, CD137, GITR, ILT2, or ILT3, or ligands for these molecules (e.g., an isolated fully-human monoclonal antibody) in association with one or more alloantigens, such as, vector(s) capable of expressing protein(s) or peptide(s) that stimulate T-cell immunity against tissues or cells, formulated in a pharmaceutically acceptable carrier. The proteins or peptides may comprise class I major histocompatibility complex (MHC) antigens, ?2-microglobulins, or cytokines. The MHC antigen may be foreign to the subject.

Abstract: The use of anti-CD20 antibodies as in vivo purging agents for patients receiving bone marrow or peripheral blood stem cell transplant during treatment of B-cell-related diseases, e.g., B-cell lymphomas or leukemias, is disclosed. Such purging may enhance engraftment and/or prevent disease relapse in such patients.

Abstract: Anti-NTB-A antibodies and antigen-binding fragments thereof, as well as pharmaceutical compositions comprising such antibodies and antigen-binding fragments are described. Also described are methods of using such antibodies and antigen-binding regions to bind NTB-A and treat diseases, such as hematologic malignancies, which are characterized by expression of NIB-A.

Abstract: The present invention relates to the use of a tri-substituted glycerol compound for the manufacture of a medicament for the treatment of hematological malignancies. The invention also refers to a kit-of-parts comprising such a medicament. Finally, the invention also relates to a corresponding method for the treatment of such conditions as well as to an in vitro method for determining the susceptibility of such malignant cells to a medicament as defined in the invention.

Abstract: The present invention describes humanized antibodies that target CD40, wherein the antibodies comprise at least one modification relative to a parent antibody, wherein the modification alters affinity to an Fc?R or alters effector function as compared to the parent antibody. Also disclosed are methods of using the antibodies of the invention.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind HLA-B*27 (also called HLA-B27). In certain embodiments, the antibodies of the invention bind soluble and/or cell surface-expressed forms of HLA-B*27. The antibodies of the present invention, in certain embodiments, inhibit HLA-B*27-mediated activation of T cells. Certain exemplary antibodies of the present invention exhibit enhanced binding to HLA-B*27 as compared to other HLA-B allelic variants (e.g., HLA-B*07). The present invention also provides anti-HLA-B*27 antibodies with pH-dependent binding characteristics (e.g., higher affinity binding at neutral pH than at acidic pH). The antibodies of the invention are useful for the treatment of diseases and disorders associated with HLA-B*27 expression, including ankylosing spondylitis and other spondyloarthropathies.

Abstract: Provided herein are methods of treatment of Amyotrophic Lateral Sclerosis comprising administration of adrenocorticotropic hormone (ACTH), or fragment, analog, complex or aggregate thereof, or any combination thereof, to an individual in need thereof.

Abstract: The present invention concerns treatment of autoimmune diseases with antagonists which bind to B cell surface markers, such as CD19 or CD20.

Abstract: Provided is methods for producing mixtures of antibodies from a single host cell clone, wherein, a nucleic acid sequence encoding a light chain and nucleic acid sequences encoding different heavy chains are expressed in a recombinant host cell. The recombinantly produced antibodies in the mixtures according to the invention suitably comprise identical light chains paired to different heavy chains capable of pairing to the light chain, thereby forming functional antigen-binding domains. Mixtures of the recombinantly produced antibodies are also provided by the invention. Such mixtures can be used in a variety of fields.

Abstract: Human antibodies immunospecific for human CD27 are capable of blocking CD27 binding to its ligand CD70 and neutralizing bioactivity of CD27 including, but not limited to, CD27 intracellular signaling, T-cell proliferation and activation, B-cell proliferation and differentiation, plasmablast formation and alleviation of antibody responses, stimulation of tumor cells by CD70, and the production of soluble mediators from T and B-cells. The antibodies are useful in diagnosing or treating CD27 activity associated diseases and conditions.

Abstract: The present invention describes CD37 antibodies, especially A2 and B2, for the treatment of patients with CLL, especially of patients belonging to a “high risk” or “ultra-high risk” group of patients. Those patients are either patients who are refractory to fludarabine treatment or patients who carry a genetic marker which is indicative for poor prognosis or increased risk of treatment failure, e.g. patients with TP53 dysfunction or deletion of chromosome 17p13, or patients after failure to previous anti-CD20 treatment. The ability of A2 and B2 to deplete CLL cells is high both in patient samples derived from patients with normal risk and with increased risk (“high risk” patients) and clearly superior to that of rituximab and alemtuzumab.

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: Methods and compositions for treating or preventing acute graft-versus-host disease (aGVHD) in a subject using miR-155 specific inhibitors are described.

Abstract: Isolated human monoclonal antibodies which bind to and inhibit human CD20, and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced by a transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Abstract: The disclosure relates to a monovalent polypeptide domain which specifically binds CD28, as well as to an antagonist of CD28, where the antagonist comprises a monovalent polypeptide domain which specifically binds CD28. This disclosure encompasses monovalent polypeptide domains comprising an antibody single variable domain that monovalently binds CD28. An antibody single variable domain that is monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a monovalent anti-CD28 antibody single variable domain consists of or comprises an antibody single variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the monovalent anti-CD28 antibody single variable domain is a human antibody single variable domain.

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: The drug for the prophylaxis of HIV infection and for the prophylaxis and treatment of diseases caused by or associated with HIV, including AIDS, comprises an activated, potentiated form of antibodies to a protein or peptide of the immune system which interacts with the HIV or has a content and/or functional activity which changes in connection with an HIV infection.

Abstract: The present invention relates to CX3CR1-binding polypeptides, in particular polypeptides comprising specific immunoglobulin domains. The invention also relates to nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions comprising such polypeptides; and to uses of such polypeptides or such compositions, in particular for prophylactic, therapeutic and diagnostic purposes.

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: This invention provides a method of reducing viral load in an HIV-1-infected human subject which comprises administering to the subject an effective HIV-1 viral load reducing dose of a CCR5 receptor antagonist, such as a humanized antibody designated PRO 140 or an anti-CCR5 receptor monoclonal antibody, wherein the viral load reducing dose achieves an average maximum decrease of viral load in the subject of at least 1.83 log10 to 2.5 log10 at about ten days following administration of the CCR5 receptor antagonist and wherein the viral load reducing dose further achieves a mean viral load reduction of 1.7 log10 at about nine days following administration of the CCR5 receptor antagonist.

Abstract: TREM-like transcript 2 (TLT2), is expressed on neutrophils, macrophages, and B lymphocytes. Expression of TLT2 is up-regulated on neutrophils and macrophages in response to inflammatory stimuli in vivo and synergizes with agonists that bind to G-protein coupled receptors (GPCR) to potentiate the neutrophil antibacterial and chemotactic response. Administration of anti-TLT2 mAb enhances the acute inflammatory response in vivo that is associated with increased neutrophil recruitment to sites of inflammation. TLT2 ligation in vivo also potentiates chemokine and growth factor production indicating that TLT2 can exert both neutrophil intrinsic and extrinsic effects. The administration of anti-TLT2 mAb alone promotes neutrophil recruitment to the lung and peritoneum, as well as the rapid production of G-CSF, CXCL1 (KC) and CXCL2 (MIP-2).

Abstract: The present invention relates to novel uses of the MLN 51 gene or protein. The MLN 51 gene and protein is closely related to the development of rheumatoid arthritis and serve as biomarker and therapeutic target for rheumatoid arthritis, particularly chronic synovitis.

Abstract: The present invention relates to human papillomavirus E7 antigen compounds and compositions for treating human papillomavirus infection and associated conditions. The invention provides, in part, polypeptide and nucleic acid molecules including sequences substantially identical to the sequences of two or more human papillomavirus (HPV) E7 antigens, where the E7 antigens are selected from at least two different HPV strains, and methods of using the same.

Abstract: The present invention relates to methods of treating cancer, such as melanoma, by administering a CTLA4 antagonist to a subject with a serum C-Reactive Protein (CRP) concentration that is less than or equal to some amount. The invention further relates to methods of treating cancer by determining the level of serum CRP concentration in a subject, and then administering a CTLA4 antagonist if the CRP concentration is less than or equal to a certain amount. The invention further relates to, among other things, the use of serum CRP concentration as a predictive factor for a subject's response to a cancer treatment.

Abstract: The invention is directed to novel methods for modulating inflammatory and/or immune responses. Such methods utilize compositions comprising extraembryonic cells (herein referred to as EE cells) including but not limited to extraembryonic HLA-G positive cells (herein referred to as EHP cells) and amnion-derived multipotent progenitor cells (herein referred to as AMP cells); compositions comprising expanded EE cell populations, and/or cell lysates and/or conditioned media derived therefrom, alone or in combination with each other and/or in combination with various extracellular matrices and/or devices and/or other suitable active agents.

Abstract: The present invention is directed to isolated populations of human natural immunoglobulin-producing B1 lymphocytes, wherein the B1 lymphocytes display surface biomarkers CD20, CD43 and CD27 and are either CD11b+ or GD11b?. The present invention is also directed to a method of isolating human natural immunoglobulin-producing B1 lymphocytes from a blood sample comprising isolating B lymphocytes from the sample that express surface biomarkers CD20, CD43 and CD27, and, optionally, CD11b. In addition, the present invention is directed to a methods for diagnosing a B1 cell disorder in a patient, determining the prognosis of a patient having a B1 cell disorder, and treating a patient having a B1 cell disorder.

Abstract: Methods, uses, compositions and kits for modulating HIV replication based on PD-1 modulation are disclosed. Methods, uses, compositions and kits useful for the elimination of latent HIV reservoirs based on PD-1 inhibition are also disclosed. Methods and kits useful for identifying agents useful for modulating HIV replication are also disclosed.

Abstract: In the present invention there is provided an oral pharmaceutical composition, comprising bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient, which is a pharmaceutically acceptable non-ionic hydrophilic surfactant.

Abstract: The present invention is directed to a combination therapy involving a type I anti-CD20 antibody and a type II anti-CD20 antibody for the treatment of a patient suffering from cancer, particularly a CD20-expressing cancer. An aspect of the invention is a composition comprising a type I anti-CD20 antibody and a type II anti-CD20 antibody. Another aspect of the invention is a kit comprising a type I anti-CD20 antibody and a type II anti-CD20 antibody. Yet another aspect of the invention is a method for the treatment of a patient suffering from cancer comprising co-administering, to a patient in need of such treatment, a type I anti-CD20 antibody and a type II anti-CD20 antibody.