Abstract: The present invention provides an immunotherapeutic agent and immunotherapy allowing the extension of the survival time of patients with pancreatic cancer. The immunotherapy of the present invention is characterized by comprising the steps of culturing peripheral blood lymphocytes of a patient with pancreatic cancer by stimulating the lymphocytes with an anti-CD3 antibody and an anti-CD52 antibody, thereby to obtain an immunotherapeutic agent, and administering at least four infusions of the resultant immunotherapeutic agent to the same patient, wherein each of the infusions of the immunotherapeutic agent comprises at least 15×109 cells of activated lymphocytes, the percentage of CD3? CD56+ NK cells in the activated lymphocytes is at least 30%, and the administration of the immunotherapeutic agent is begun for the patient who is in at least one state of two or more particular immunocompromised states.

Abstract: The present invention concerns human antibodies recognizing the human C5a receptor. By binding to C5aR the antibodies inhibit C5a signalling, whereby the pro-inflammatory signal is inhibited. Based on the role of C5a and its receptor in stimulation of inflammation the invention further relates to therapeutic use of said human anti-C5aR antibodies and in particular in relation to treatment of immunological disorders.

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

Abstract: 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 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: Disclosed are processes for producing a variant polypeptide (e.g. antibodies) having modified binding characteristics for human Fc gamma receptor IIA (CD32A) leading to increased inhibition of proinflammatory mediators while retaining binding to a target antigen via its Fv portion, which processes comprise altering the polypeptides by substitution of at least two amino acid residues at EU position 325, 326 or 328 of a human IgG CH2 region for a sequence selected from SAAF, SKAF, NAAF and NKAF. Also disclosed are molecules, particularly polypeptides, more particularly immunoglobulins (e.g. antibodies) that include a variant CDR3 region, wherein the variant CDR3 region includes at least one amino acid modified relative to a wild-type CDR3 region. The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof.

Abstract: The invention is based on the discovery that interleukin-1 alpha (IL-1alpha) is expressed on the proinflammatory CD14+CD16+ monocyte subset. Importantly, since IL-1alpha appears to be almost exclusively expressed on this monocyte subset and not other leukocytes, it represents an ideal marker for targeting the CD14+CD16+ monocyte subset. The effectiveness of an agent that depletes such pathogenic cells or modulates IL-1alpha function on such cells type can be monitored by assessing CD14+CD16+ monocyte levels or functionality.

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: Antibodies that target CD19, wherein the antibodies comprise at least one modification relative to a parent antibody, wherein the modification alters affinity to an FcyR or alters effector function as compared to the parent antibody, and methods of using the antibodies.

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: 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 disclosure relates to methods of predicting and diagnosing preeclampsia and eclampsia in pregnant subjects. These methods include detecting a decrease of soluble c-kit in a sample obtained from the pregnant subject. A significantly reduced concentration of soluble c-kit in the sample as compared to a gestational age-adjusted control indicates that the pregnant subject will develop or has preeclampsia or eclampsia.

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: Provided herein, in one aspect, are antibodies that immunospecifically bind to PSGL-1, polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to PSGL-1, as well as methods of treating a disorder or disease caused by or associated with increased proliferation and/or numbers of activated T cells using the antibodies described herein.

Abstract: The present disclosure relates generally to methods and materials for modulating the recruitment of macrophages or monocytes to sites at which they may contribute to disease initiation or progression. Embodiments of the disclosure comprise providing a modulator of the activity of ICAM-3 or proximal to the site.

Abstract: The present invention provides novel antibodies and functional fragments thereof specific for CD38, and methods of using the same for the treatment of diseases associated with CD38 expression, including hematological malignancies such as multiple myeloma.

Abstract: The present invention includes compositions and methods for targeting the LOX-1 receptor on immune cells and uses for the anti-LOX-1 antibodies.

Abstract: The invention relates to binding compounds that specifically bind to human TSLPR, as well as uses thereof, e.g., in the treatment of inflammatory disorders.

Abstract: The invention pertains to the generation and utility of antibodies that can bind effectively to C?mX domain on membrane-bound IgE (mIgE) expressed on the surface of human B lymphocytes. The C?mX domain of 52 amino acid residues, located between the CH4 domain and the C-terminal membrane-anchor peptide on human membrane-bound epsilon chain, had been suggested as an antigenic site for immunological targeting of B cells expressing mIgE. Previous reported monoclonal antibodies, including a20, which bind to RADWPGPP (SEQ ID NO:1) peptide at the C-terminal of C?mX, have now been found to bind poorly to mIgE on human B cells. We have discovered that only monoclonal antibodies specific for certain segments, such as GLAGGSAQSQRAPDRVL (SEQ ID NO:2) and HSGQQQGLPRAAGGSVPHPR (SEQ ID NO:3), of C?mX can bind effectively to mIgE on human B cells and hence have the utility for targeting those B cells for the treatment of diseases mediated by IgE.

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: The present invention provides variant target binding agents and methods relating to the use of such binding agents for the prophylaxis or treatment of cancers and immunological disorders. The variant target binding agent is conjugated to a therapeutic agent that exerts a cytotoxic, cytostatic, or immunomodulatory effect on target cells.

Abstract: The present invention is directed to an antibody or derivative thereof of human origin for inhibiting platelet aggregation, characterized in that it is effective by substantially exclusive binding to the activated state of platelet integrin receptor GPIIb/IIIa.

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: The present invention relates to the identification of proteins located on the cell surface of dendritic cells or precursors thereof, particularly antigen presenting dendritic cells. In particular, the present invention relates to compounds such as antibodies that bind these proteins. These compounds can be used to detect and/or enrich a subset of dendritic cells or precursors thereof. These compounds can also be used to target antigens to dendritic cells or precursors thereof to modulate a humoral and/or T cell mediated immune response to an antigen, or used to target cytotoxic agents to dendritic cells or precursors thereof involved in diseased states.

Abstract: The present invention provides methods of determining platelet aggregation, methods of determining susceptibility to clotting upon administration of a CD40L-binding moiety, and kits related thereto.

Abstract: The invention concerns a method for obtaining and selecting monoclonal antibodies by an ADDC-type test, said antibodies capable of activating type III Fcy receptors and having a particular glycan structure. The inventive anti-D antibodies can be used for preventing Rhesus isoimmunization in Rh negative persons, in particular for haemolytic disease in a new-born baby of for uses such as idiopathic thrombocytopenic purpura (ITP).

Abstract: Targeted binding agents, such antibodies directed to the antigen ?V?6 and uses of such agents are described. In particular, fully human monoclonal antibodies directed to the antigen ?V?6 are disclosed. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3 are disclosed. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also disclosed.

Abstract: An Fc variant of a parent Fc polypeptide, wherein said Fc variant exhibits altered binding to one or more Fc?Rs, wherein said Fc variant comprises at least one amino acid insertion in the Fc region of said parent Fc polypeptide.

Abstract: The present invention relates to antibodies and antigen-binding portions thereof that specifically bind to CD40, preferably human CD40, and that function as CD40 agonists. The invention also relates to human anti-CD40 antibodies and antigen-binding portions thereof. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins derived from human anti-CD40 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-CD40 antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-CD40 antibodies.

Abstract: Fully human monoclonal Abs includes (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1? and (ii) a constant region that is effective at both activating the complement system though C1q binding and binding to several different Fc receptors.

Abstract: Fully human monoclonal Abs includes (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1? and (ii) a constant region that is effective at both activating the complement system though C1q binding and binding to several different Fc receptors.

Abstract: The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: Compositions and methods for inducing cell membrane wounding, cell permeabilization and cell killing are provided. The composition comprises a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell. Preferably, the cell surface antigen is associated with the cytoskeleton of the cell. A preferred polyvalent agent is an IgM, and enhanced cell wounding and killing can be provided by the addition of a crosslinking agent. At sublethal concentrations in vivo, the cell wounding antibodies permeabilize cells and dramatically enhance response to chemotherapeutic agents, even in patients refractory to the chemotherapeutic agents.

Abstract: Isolated monoclonal antibodies which bind to human DEC-205 and related antibody-based compositions and molecules are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, as well as therapeutic and diagnostic methods for using the antibodies.

Abstract: Immunoglobulin chains or antibodies having light or heavy chain complementarity determining regions of antibodies that bind to P-Selectin Glycoprotein Ligand-1. Also disclosed are methods of inducing death of an activated T-cell and of modulating a T cell-mediated immune response in a subject.

Abstract: Provided herein, in one aspect, are antibodies that immunospecifically bind to PSGL-1, polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to PSGL-1, as well as methods of treating a disorder or disease caused by or associated with increased proliferation and/or numbers of activated T cells using the antibodies described herein.

Abstract: This application relates to agents capable of specifically recognizing GPIb?, a key receptor required for platelet adhesion and aggregation. More specifically, this application relates to monoclonal antibodies and derivatives thereof capable of specifically recognizing both the murine and the human GPIb?. These monoclonal antibodies and derivatives are particularly useful in the treatment or prevention of thrombosis as well as research tools.

Abstract: A therapeutic composition for treatment of cancer in a mammal is disclosed. The composition comprises an effective amount of a yeast beta-glucan composition which is suitable for oral administration and for absorption through the gastrointestinal tract of the mammal. The above therapeutic composition may further comprise antitumor antibodies or cancer vaccine composition, wherein the antitumor activities of the antitumor antibodies or the cancer vaccine composition are enhanced by the yeast glucan.

Abstract: Based on the discovery of the nucleotide and amino acid differences which distinguish the Gova and Govb allelic forms of the membrane glycoprotein CD109, and which comprise the biallelic Gov platelet alloantigen system, compositions and methods are provided for determining the Gov genotype and phenotype of individuals. Also provided, on the basis of this discovery, are compositions and methods for treating disorders associated with Gov alloantigen incompatibility, such as the bleeding disorders post-transfusion purpura, post-transfusion platelet refractoriness, and neonatal alloimmune thrombocytopenia. The two allelic forms of CD109 differ by a single amino acid. The Gova allelic form has Tyr at amino acid position 703 in the CD109 sequence. The Govb allelic form has Ser at the same position. This amino acid difference is due to a single change, from A for the Gova allele to C for the Govb allele, in the CD109 gene.

Abstract: The present invention is directed to the creation of human equivalent CDRs and antibodies containing them by a method of producing an antibody which specifically binds to an antigen.

Abstract: The invention relates to the use of substances which are specific to CEACAM8 for the manufacture of a medicament for the prophylactic or therapeutic treatment of human autoimmune diseases and/or gout. Another object of the invention concerns the use of CEACAM8-specific substances for apoptosis induction in-vitro. The invention also relates to a method for screening substances which induce apoptosis and a method for inducing apoptosis in human granulocytes.

Abstract: Provided are humanized anti-CD40 antibodies and antigen-binding fragments and methods for treating disease characterized by expression of CD40 antigen.

Abstract: Compounds that bind to P-Selectin Glycoprotein 1 (PSGL-1) on the surface of T cells or natural killer (NK) cells can be used to induce T cell or NK cell depletion and/or to induce T cell or NK cell apoptosis. The compounds and methods of the invention can be used to control unwanted T cell- or NK cell-mediated immune responses in conditions such as autoimmune diseases, transplant rejection, and allergic diseases.

Abstract: Immunoglobulin chains or antibodies having light or heavy chain complementarity determining regions of antibodies that bind to P-Selectin Glycoprotein Ligand-1. Also disclosed are methods of inducing death of an activated T-cell and of modulating a T cell-mediated immune response in a subject.

Abstract: The present invention provides for the in vitro establishing of a prognosis for a subject in severe sepsis with at least two organ failures or in septic shock with at least two organ failures. Embodiments of the invention comprise the steps of measuring the level of the S100A8/A9 complex from a biological sample from a subject, and comparing the measured level to a predetermined threshold in which the measured level of the S100A8/A9 complex above the predetermined threshold is indicative of a bad prognosis and a measured level of the S100A8/A9 complex below the predetermined threshold is indicative of a good prognosis.

Abstract: Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.

Abstract: The invention is based on the discovery that interleukin-1 alpha (IL-1alpha) is expressed on the proinflammatory CD14+CD16+ monocyte subset. Importantly, since IL-1alpha appears to be almost exclusively expressed on this monocyte subset and not other leukocytes, it represents an ideal marker for targeting the CD14+CD16+ monocyte subset. The effectiveness of an agent that depletes such pathogenic cells or modulates IL-1alpha function on such cells type can be monitored by assessing CD14+CD16+ monocyte levels or functionality.

Abstract: This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).

Abstract: This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).