Abstract: The present invention relates to novel p75 heterodimer specific anti-human IL-12 antibodies that are characterized by a higher potency and greater efficacy in neutralizing human IL-12 bioactivity than known heterodimer specific IL-12 monoclonal antibodies. The heterodimer specific antibodies recognize one or more epitopes of the human IL-12 p75 heterodimer, but do not bind to the p40 subunit alone. The heterodimer specific IL-12 antibodies neutralize rhesus monkey IL-12 bioactivity with a potency similar to their potency for neutralizing human IL-12 bioactivity making them useful IL-12 antagonists for in vivo studies in the rhesus monkey.

Abstract: The present invention relates to methods for activating T lymphocytes using a synthetic matrix, and for specifically activating T lymphocytes reactive to a specific peptide.

Abstract: Nucleic acid molecules encoding a human B cell surface molecule are provided. Polypeptides and antibodies which bind to these polypeptides are also provided. In addition, methods of detecting mutated forms of the molecule are provided.

Abstract: The invention involves nonapeptides bound by HLA molecules such as HLA-A1. The resulting complexes are identified by cytolytic T cells. Such recognition may be used in diagnostics, or therapeutically.

Abstract: Specific netrin proteins, nucleic acids which encode netrin proteins and hybridization reagents, probes and primers capable of hybridizing with netrin genes and methods for screening chemical libraries for lead compounds for pharmacological agents useful in the diagnosis or treatment of disease associated undesirable cell growth are provided. An exemplary screen involves forming a mixture comprising a recombinant netrin protein, a natural intracellular netrin protein binding target, and a candidate pharmacological agent; incubating the mixture under conditions whereby, but for the presence of said candidate pharmacological agent, said netrin protein selectively binds said binding target; and detecting the presence or absence of specific binding of said netrin protein to said binding target.

Abstract: The invention relates a method of inhibiting chronic allograft rejection in a subject with an organ transplant. The method comprises administering an effective amount of one or more anti-angiogenic agents to a subject alone or in combination with one or more immunosuppressive agents. The invention provides new and improved methods of inhibiting allograft rejection.

Abstract: The instant invention discloses the unexpected result that two anti-4-1BB monoclonal antibodies can inhibit both primary and secondary humoral responses to at least T-cell dependent antigens in vivo. Such antibodies provide a novel approach to immunosuppression and cancer therapy in vivo.

Abstract: The present invention discloses that phosphorylation of cytoplasmic tyrosine residues in the &bgr;-subunit of integrins is needed for signal protein association. The invention provides methods of identifying signaling partners involved in integrin mediated signaling, methods of identifying agents which block integrin mediated signaling, methods of using agents which block integrin mediated signaling to modulate biological and pathological processes, and agents which block integrin mediated signaling.

Abstract: FK506 and geldanamycin promote nerve regeneration by a common mechanism that involves the binding of these compounds to polypeptide components of steroid receptor complexes other than the steroid hormone binding portion of the complex (FKBP52 and hsp90, respectively). These and other agents cause hsp90 dissociation from steroid receptor complexes or block association of hsp90 with steroid receptor complexes.

Abstract: The present invention relates to the identification, cloning and sequencing of nucleic acid molecules encoding an isoform of the enzyme glutamic acid decarboxylase and further relates to the use of these molecules and/or peptides and polypeptides encoded thereby in diagnostic tests for Insulin Dependent Diabetes Mellitus and other diseases in which glutamic acid decarboxylase is an autoantigen and in the treatment of patients suffering from these diseases.

Abstract: Methods for detecting human factor VIII or factor VIII-like polypeptides in and isolating it from solutions such as blood or conditioned media are disclosed, together with reagents suitable for the purpose comprising binding moieties that recognize human factor VIII and/or a factor VIII-like polypeptide and form a binding complex therewith. Preferred polypeptide binding moieties are particularly disclosed.

Abstract: The present invention provides the amino acid and nucleotide sequence of a protein that binds to &bgr;3 integrins, &agr;IIb and Src kinase and is involved in integrin mediated signaling. Based on this disclosure, the present invention provides methods for identifying agents that block integrin mediated signaling, methods of using agents that block integrin mediated signaling to modulate biological and pathological processes, and agents that block integrin mediated signaling.

Abstract: A variant of a polypeptide comprising a human IgG Fc region is described, which variant comprises an amino acid substitution at amino acid position 329, or at two or all of amino acid positions 329, 331 and 322 of the human IgG Fc region. Such variants display altered effector function. For example, C1q binding and/or complement dependent cytotoxicity (CDC) activity may be reduced or abolished in the variant polypeptide. The application also describes an immune complex and an assay for determining binding of an analyte, such as an Fc region-containing polypeptide, to a receptor.

Abstract: A chimeric LL2 monoclonal antibody is described in which the complementarity determining regions (CDRs) of the light and heavy chains of the murine LL2 anti-B-lymphoma, anti-leukemia cell monoclonal antibody has been recombinantly joined to the human kappa and IgG1 constant region domains, respectively, which retains the immunospecificity and B-cell lymphoma and leukemia cell internalization capacity of the parental murine LL2 monoclonal antibody, and which has the potential of exhibiting reduced human anti-mouse antibody production activity.

Abstract: Thiol-containing peptides can be radiolabeled with fluorine-18 (18F) by reacting a peptide comprising a free thiol group with an 18F-bound labelling reagent which also has a group that is reactive with thiols. The resulting 18F-labeled peptides may be targeted to a tissue of interest using bispecific antibodies or bispecific antibody fragments having one arm specific for the 18F-labeled peptide or a low molecular weight hapten conjugated to the 18F-labeled peptide, and another arm specific to the targeted tissue. The targeted tissue is subsequently visualized by clinical positron emission tomography.

Abstract: The present invention provides a method of identifying a tumor homing molecule that homes to angiogenic vasculature by contacting a substantially purified NGR receptor with one or more molecules and determining specific binding of a molecule to the NGR receptor, where the presence of specific binding identifies the molecule as a tumor homing molecule that homes to angiogenic vasculature. The invention also provides a method of directing a moiety to angiogenic vasculature in a subject by administering to the subject a conjugate including a moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor, whereby the moiety is directed to angiogenic vasculature. In addition, the invention provides a method of imaging the angiogenic vasculature of a tumor in a subject by administering to the subject a conjugate having a detectable moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor and detecting the conjugate.

Abstract: A novel nucleolus protein has been identified and cloned using human autoimmune serum. Its cDNA and amino acid sequences have been determined and are disclosed. This antigenic protein, termed ASE-1, has an approximate molecular mass of 55 kDa. Immunoblot analysis indicates that both the native protein and the in vitro translation products of the cDNA migrate on SDS-PAGE at an apparent molecular mass of 90 kDa. Indirect immunofluorescence analysis using antibodies generated to cloned regions of ASE-1 indicates that this protein occurs at the fibrillar centers of the nucleolus in the putative sites of rDNA transcription. During cell division ASE-1 localizes to the nucleolus organizer regions of the chromosomes, where it is closely associated with RNA polymerase 1. As an autoantigenic nucleolar protein, ASE-1 has been found to be a reliable serum marker for systemic lupus erthyematosus (SLE). This finding makes ASE-1 useful in the clinical detection and characterization of the disease.

Abstract: A variety of heparanase specific molecular probes which can be used for research and medical applications including diagnosis and therapy. Specific applications include the use of a heparanase specific molecular probe for detection of the presence, absence or level of heparanase expression; the use of a heparanase specific molecular probe for therapy of a condition associated with expression of heparanase; the use of a heparanase specific molecular probe for quantification of heparanase in a body fluid; the use of a heparanase specific molecular probe for targeted drug delivery; and the use of a heparanase specific molecular probe as a therapeutic agent.

Abstract: The present invention relates to a method for adjusting the affinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of substituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.

Abstract: The present invention relates to: parasitic helminth asparaginase proteins; parasitic helminth asparaginase nucleic acid molecules, including those that encode such asparaginase proteins; antibodies raised against such asparaginase proteins; and compounds that inhibit parasitic helminth asparaginase activity. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. Also included in the present invention are therapeutic compositions comprising such proteins, nucleic acid molecules, antibodies and/or inhibitory compounds as well as the use of such therapeutic compositions to protect animals from diseases caused by parasitic helminths.