Abstract: The invention relates to a single-chain antibody which is characterized in that (a) it contains a variable domain (scFv) binding specifically to human CD3, and (b) its constant domains are derived from a human IgM molecule and comprise the C&mgr;3 domain and the C&mgr;4 domain but not the C&mgr;1 domain and the C&mgr;2 domain. In a preferred embodiment, the antibody according to the invention contains a human IgG3 hinge region between the variable and constant domains. The invention also relates to DNA sequences coding for this antibody and to expression vectors containing these DNA sequences and finally to preparations containing the above compounds, preferably for the prevention of acute rejection reactions following organ transplantation.

Abstract: Chimeric, humanized and other RANK-L MAbs, derived from high affinity neutralizing MAbs, pharmaceutical compositions containing same, methods of treatment and diagnostics are provided.

Abstract: A method of treating an ocular disorder is disclosed, comprising administering to a patient in need of such treatment, an effective amount of a sub-immunoglobulin antigen-binding molecule that is immuno-interactive with a target antigen associated with the disorder. The invention is also directed to compositions comprising this sub-immunoglobulin antigen-binding molecule and to a method of diagnosing an ocular condition using such molecule.

Abstract: Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described.

Abstract: The present invention relates to single domain ligands derived from molecules in the immunoglobulin (Ig) superfamily, receptors comprising at least one such ligand, methods for cloning, amplifying and expressing DNA sequences encoding such ligands, preferably using the polymerase chain reaction, methods for the use of said DNA sequences in the productions of Ig-type molecules and said ligands or receptors, and the use of said ligand or receptors in therapy, diagnosis or catalysis.

Abstract: The invention discloses newly-discovered phosphorylation sites in human IRS-1 and IRS-2, serine 1101 (Ser1101) and serine 1149 (Ser1149) respectively, and provides antibodies, both polyclonal and monoclonal, that selectively bind to IRS-1 and/or IRS-2 when phosphorylated at these respective sites, but do not bind to IRS-1 and/or IRS-2 when not phosphorylated at these respective sites. The sites are relevant to insulin-resistance in type 2 diabetes. Also provided are methods for determining the phosphorylation of IRS-1/2 or activity of PKC theta in a biological sample, by using a detectable reagent, such as the disclosed antibodies, that binds to IRS-1/2 only when phosphorylated at Ser1101/Ser1149. Kits comprising the phosphor-IRS-1/2 (Ser1101/1149) antibodies of the invention are also provided.

Abstract: The present invention provides an antibody composition which specifically binds to CD20 and comprises an antibody molecule which has complex N-glycoside-linked sugar chains bound to the Fc region; a process for producing the antibody composition; and a medicament comprising the antibody composition.

Abstract: Diagnostic methods comprise measuring specifically the level of at least one iso-eosinophilic cationic protein (iso-ECP) in a sample from an individual to be diagnosed, and comparing the measured level of the iso-ECP with a predetermined level of the iso-ECP. The iso-ECP is cytotoxic and the cytotoxicity of the iso-ECP is not capable of neutralization by the monoclonal antibodies EG1 and EG2. Anti-iso-ECP antibody which may be used in the diagnostic methods specifically binds to a cytotoxic isoform of ECP having an epitope which is unique for the native form of the cytotoxic iso-ECP.

Abstract: The present invention contemplates methods of preventing or inhibiting breast cancer cell proliferation, compounds and compositions that interfere with or block sex steroid or growth factor binding to and induction of the Cyr61 gene and methods of screening ligands that regulate Cyr61 protein expression. The present invention further contemplates compounds that block Cyr61 activity. The invention further relates to methods of diagnosing and staging patients with cancers associated with an upregulation of Cyr61 expression. Assay methods and kits are also disclosed.

Abstract: The present invention relates to antibodies and antibody fragments thereof that bind to and activate an erythropoietin receptor. The present invention also relates to methods of modulating the endogenous activity of an erythropoietin receptor in a mammal using said antibodies as well as pharmaceutical compositions containing said antibodies.

Abstract: This invention provides methods of obtaining novel polynucleotides and encoded polypeptides by use of non-stochastic methods of directed evolution (DirectEvolution™). These methods include non-stochastic polynucleotide site-saturation mutagenesis (Gene Site Saturation Mutagenesis™) and non-stochastic polynucleotide reassembly (GeneReassembly™). Through use of the claimed methods, genetic vaccines, enzymes, and other desirable molecules can be evolved towards desirable properties. For example, vaccine vectors can be obtained that exhibit increased efficacy for use as genetic vaccines. Vectors obtained by using the methods can have, for example, enhanced antigen expression, increased uptake into a cell, increased stability in a cell, ability to tailor an immune response, and the like. This invention provides methods of obtaining novel enzymes that have optimized physical &/or biological properties.

Abstract: The present invention relates to antibodies, antibody fragments, conjugates of antibodies and antibody fragments with cytotoxic agents, and hybridomas producing the antibodies and antibody fragments, where the antibodies and antibody fragments recognize extracellular epitopes of plasma membrane proteins that are not released into the extracellular fluid, and to methods for the detection, monitoring and treatment of malignancies such as breast cancer and ovarian cancer using the antibodies, antibody fragments and conjugates.

Abstract: The invention provides monoclonal antibody mBLA3 that binds to integrin &agr;v&bgr;6 and other equivalent antibodies. The invention also provides the identification and characterization of cancer-associated antigen, integrin &agr;v&bgr;6, with various human cancers and methods of diagnosing and treating these human cancers.

Abstract: The present invention relates to novel members of the Tumor Necrosis Factor family of receptors. The invention provides isolated nucleic acid molecules encoding human TR11, TR11SV1, and TR11SV2 receptors. TR11, TR11SV1, and TR11SV2 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of TR11, TR11SV1, and TR11SV2 receptor activity. The present invention further relates to antibodies that specifically bind TR11, TR11SV1, and/or TR11SV2. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of TR11, TR11SV1, and TR11SV2 receptors. Further provided are therapeutic methods for treating disease states related to aberrant proliferation and differentiation of cells which express the TR11, TR11SV1, and TR11SV2 receptors.

Abstract: A novel subtype of the P2-purinergic receptor, referred to as the P2U2 receptor, is disclosed. This receptor is activated by four of its agonists in the following order of specificity: UTP>UDP>ADP>ATP. Nucleic acids encoding the receptor, antibodies that bind to the receptor and associated screening and therapeutic methods also are disclosed.

Abstract: The present invention features a novel combination therapy useful in the treatment of autoimmune disease that increases or maintains the number of functional cells of a predetermined type in a mammal by killing or inactivating autoimmune cells and re-educating the host immune system.

Abstract: Disclosed are protein ligands comprising an immunoglobulin heavy chain variable (VH) domain and an immunoglobulin light chain variable (VL) domain, wherein the proteins bind a complex comprising an MHC and a peptide, do not substantially bind the MHC in the absence of the bound peptide, and do not substantially bind the peptide in the absence of the MHC, and the peptide is a peptide fragment of gp100, MUC1, TAX, or hTERT. Also disclosed are methods of using and identifying such ligands.

Abstract: The present invention relates to immunotoxins that effectively kill malignant cells having a given marker. The immunotoxins are reagents that comprise internalizing antibodies conjugated to cytotoxic ribonucleases or fragments thereof. The internalizing antibodies are capable of binding with a chosen tumor cell, and thereby confer little non-specific toxicity to the immunotoxin in a host. The immunotoxins exhibit up to 2000-fold higher toxicity against malignant B cells than did the ribonuclease counterparts alone.

Abstract: Antibodies and other binding molecules having a specificity for a selectively expressed CD38 epitope. Using a binding molecule of the invention it is possible, among other things, to selectively mark a subset of CD38 expressing cells. An antibody or binding molecule of the invention is capable of binding to malignant B cells in a host thereby at least in part eliminating such malignant B cells from the body of the host. The invention among others provides pharmaceutical compositions, binding molecules, nucleic acids encoding binding molecules of the invention and gene delivery vehicles comprising said nucleic acid.

Abstract: The invention provides a Vitaxin antibody and a LM609 grafted antibody exhibiting selective binding affinity to &agr;v&bgr;3. The Vitaxin antibody consists of at least one Vitaxin heavy chain polypeptide and at least one Vitaxin light chain polypeptide or functional fragments thereof. Also provided are the Vitaxin heavy and light chain polypeptides and functional fragments. The LM609 grafted antibody consists of at least one CDR grafted heavy chain polypeptide and at least one CDR grafted light chain polypeptide or functional fragment thereof. Nucleic acids encoding Vitaxin and LM609 grafted heavy and light chains as well as nucleic acids encoding the parental non-human antibody LM609 are additionally provided. Functional fragments of such encoding nucleic acids are similarly provided. The invention also provides a method of inhibiting a function of &agr;v&bgr;3.

Abstract: The present invention provides a monoclonal antibody which binds to a polypeptide as set forth in SEQ ID NO: 1 as described herein.

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

Abstract: The present invention relates to monoclonal antibodies immunospecific for &agr;d integrin, and antibodies that compete with said antibodies for &agr;d binding.

Abstract: The present invention relates to polyspecific binding molecules and particularly single-chain polyspecific binding molecules that include at least one single-chain T-cell receptor (sc-TCR) covalently linked through a peptide linker sequence to at least one single-chain antibody (sc-Ab). Further disclosed are methods and compositions for testing and using the molecules.

Abstract: The invention provides enhanced LM609 grafted antibodies exhibiting selective binding affinity to &agr;V&bgr;3, or a functional fragment thereof. The invention also provides nucleic acid molecules encoding the enhanced LM609 grafted antibodies. Additionally provided are methods of inhibiting a function of &agr;V&bgr;3 by contacting &agr;V&bgr;3 with an enhanced LM609 grafted antibody.

Abstract: The present invention relates to a novel human protein called Human G-protein Chemokine Receptor (CCR5) HDGNR10, and isolated polynucleotides encoding this protein. The invention is also directed to human antibodies that bind Human G-protein Chemokine Receptor (CCR5) HDGNR10 and to polynucleotides encoding those antibodies. Also provided are vectors, host cells, antibodies, and recombinant methods for producing Human G-protein Chemokine Receptor (CCR5) HDGNR10 and human anti-Human G-protein Chemokine Receptor (CCR5) HDGNR10 antibodies. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating diseases, disorders, and/or conditions related to this novel human protein and these novel human antibodies.

Abstract: The present invention relates to the detection of HLA-G. Antibodies to both soluble and membrane bound HLA-G are disclosed. Exemplary antibodies include 2C/C8, 3C/G4, and 4H84. 2C/C8 and 4H84 antibodies bind to the same region of HLA-G, which is a different region than that bound by 3C/G4. Methods of detection and diagnosis are disclosed as well as kits, including a miniaturized assay suitable for a clinical setting. Further, a method of selecting an embryos for in vitro fertilization is disclosed. A sandwich ELISA test is provided using two antibodies that bind to HLA-G at different regions. The HLA-G test according to the invention is over 1000 times more selective in binding to HLA-G than to antigens HLA-A2, HLA-B4, HLA-C, or mixed WBC preparations.

Abstract: This invention relates to novel humanized and other recombinant or engineered antibodies or monoclonal antibodies to the vitronectin &agr;v&bgr;3-receptor and to the genes encoding same. Such antibodies are useful for the therapeutic and/or prophylactic treatment of &agr;v&bgr;3-mediated disorders, such as restenosis, in human patients.

Abstract: The invention is directed to a methods for identifying compounds that inhibit or prevent infection of cells by enveloped viruses such as HIV-1 by preventing or disrupting conformational changes in the viral transmembrane protein that are required for virus fusion with those cells, and the compounds discovered by such methods. The invention also includes using these assays as diagnostic assays to detect antibodies in virus infected individuals that inhibit the viral entry processes.

Abstract: Disclosed is a composition for inhibiting the interactions of B7-1 and B7-2 with their natural ligands. Such compositions comprise an antibody specific for B7-2 and an antibody specific for B7-1, in a pharmaceutically acceptable carrier. The composition may be formulated for either separate or combined administration of the antibody components. The antibodies may be monoclonal antibodies, or humanized antibodies. Preferred antibodies are disclosed.

Abstract: A multivalent antigen-binding protein comprises a first Fv fragment bound to at least one further Fv fragment by a connecting structure which links the Fv fragments to each other but which maintains them spaced apart such that the proteins are capable of binding to adjacent antigenic determinants. Typically the connecting structure comprises a spacing polypeptide sequence, which may be about 3 to 16 amino acids in length, connected to a linkage unit which may be a synthetic chemical linker, e.g., a maleimide linker, or is a polypeptide sequence leading from the spacing sequence. In a particularly preferred embodiment, the multivalent antigen binding protein comprises a VH domain having attached to its C-terminal end a V-C joining sequence and an antibody hinge sequence. Preferably one or more of the Fv fragments is a single chain Fv (scFv). The proteins are preferably prepared by recombinant DNA techniques and are useful for in vivo therapeutic and especially diagnostic applications.

Abstract: Recombinant antibody constructs comprise the variable regions of the heavy and light chains of anti-GD2 antibodies. These antibody constructs may be coupled to a label such as a radiolabel or to a protein such as streptavidin or pro-drug converting enzymes for use in imaging or therapeutic applications. The antibody constructs may also be transduced into T cells to produce populations of T cells which target GD2-producing tumor cells.

Abstract: DNA encoding Antibodies to tumor necrosis factor receptors (TNF-Rs) are disclosed. The antibodies are preferably those which inhibit the cytotoxic effect of TNF but not its binding to the TNF-Rs. Most preferably, the antibodies bind to an extracellular domain of the C-terminal cysteine loop of the p75 TNF receptor, which loop consists of the amino acid sequence Cys-185 to Thr-201 of SEQ ID NO:3.

Abstract: The present invention relates to the identification of MHC-I and MHC-II hTRT restricted epitopes and the use of these identified epitopes to elicit an immune response against the epitope. More particularly, the identified epitopes are administered to a subject to treat hyperproliferative diseases.

Abstract: Various human monoclonal antibodies that bind to human LOX-1 and inhibit the binding of in-vivo LOX-1 ligands to LOX-1, and the LOX-1-mediated incorporation of the ligands into cells, were obtained by immunizing human antibody-producing transgenic mice (created by genetic engineering) with soluble human oxidized LDL receptor (LOX-1). Furthermore, the human monoclonal antibodies were found to be effective in preventing and treating a variety of diseases.

Abstract: Provided herein is disclosure about the development and characterization of an antibody (mhoe-4) which binds to antigen cytokeratin 8, which is present on a variety of human cancers such as ovarian, breast, lung, prostate, colon, kidney, thyroid, bone, upper digestive tract, and pancreatic cancers. Methods of diagnosing and treating various cancers by using antibodies such as mhoe-4 directed against this antigen are also disclosed.

Abstract: A monoclonal antibody which binds to baboon and human CD2, and in particular LO-CD2b antibody. The antibody may be employed to prevent and inhibit an immune response in human patients, such as when the immune response is mediated by the activation and proliferation of T-cells or natural killer cells.

Abstract: A specific locus (hot spot) for recombinant gene expression has been identified in the genome of Chinese hamster ovary cells. A DNA vector containing the hot spot causes high levels of recombinant gene expression following transfection and stable integration. The selection and cloning of the specific locus and the expression of recombinant genes is disclosed, as are the DNA vectors and the host cells.

Abstract: An isolated antibody that specifically binds a peptide coded by a nucleotide sequence coding for a variable region of &agr; chain of an human T lymphocyte receptor, said nucleotide sequence having a nucleotide sequence chosen from any of: V&agr; segments having any one of the sequences SEQ ID Nos. 1 to 11 or J&agr; segments having one of the sequence SEQ ID Nos. 13 or 15 to 19 and hybridomas producing said antibodies.

Abstract: The invention relates to inhibitors that bind to C5 and C5a, but which do not prevent the activation of C5 and do not prevent formation of or inhibit the activity of C5b. One example of such an inhibitor molecule is the monoclonal antibody designated MAb137-26, which binds to a shared epitope of human C5 and C5a. These inhibitors may be used to inhibit the activity of C5a in treating diseases and conditions mediated by excessive or uncontrolled production of C5a. The inhibitor molecules are also useful for diagnostic detection of the presence/absence or amount of C5 or C5a.

Abstract: The present invention relates to single domain ligands derived from molecules in the immunoglobulin (Ig) superfamily, receptors comprising at least one such ligand, methods for cloning, amplifying and expressing DNA sequences encoding such ligands, preferably using the polymerase chain reaction, methods for the use of said DNA sequences in the production of Ig-type molecules and said ligands or receptors, and the use of said ligands or receptors in therapy, diagnosis or catalysis.

Abstract: A parallel high throughput method and kit for the discovery of small molecule interactors of target proteins, in particular, target proteins expressed from entire genomes or subsets thereof. The target module is prepared by binding selectively a target protein, modified to allow its detection, to a surrogate ligand that is linked to an individually detectable bead. Sets of target modules are mixed together in each chamber of a multi-chamber container. A test compound or collection of test compounds is added to each chamber, and the interaction of a compound with each target module is observed. A compound that is specific for a particular target protein will displace that protein from its target module. The identity of the target module so disrupted is determined by identifying the particular bead to which the displaced target protein was attached.

Abstract: Hepatocyte growth factor (HGF) receptor antagonists are provided. The HGF receptor antagonists include HGF receptor antibodies and fragments thereof. The HGF receptor antagonists can be employed to block binding of HGF to HGF receptors or substantially inhibit HGF receptor activation. The HGF receptor antagonists may be included in pharmaceutical compositions, articles of manufacture, or kits. Methods of treating cancer using the HGF receptor antagonist are also provided.

Abstract: Provided herein is disclosure about the development and characterization of an antibody (mPA7) which binds to antigen CD46 which is present on a variety of human cancers from ovary, breast, lung, prostate, colon, kidney, and pancreas. Methods of diagnosing and treating various cancers by using antibodies such as mPA7 directed against this antigen are also disclosed.

Abstract: A G protein-coupled receptor (GPCR) which is activated by oncogenes. The receptor is found predominantly in hematopoietic cells and tissues and functions as a tumor suppressor gene and induces cell cycle arrest. This receptor may play an important role in regulating the proliferation and differentiation of hematopoietic cells. Regulation of receptor activity has several therapeutic applications.

Abstract: Provided are purified and isolated VEGF-C polypeptides capable of binding to at least one of KDR receptor tyrosine kinase (VEGFR-2) and Flt4 receptor tyrosine kinase (VEGFR-3); analogs of such peptides that have VEGF-C-like or VEGF-like biological activities or that are VEGF or VEGF-C inhibitors; polynucleotides encoding the polypeptides; vectors and host cells that embody the polynucleotides; pharmaceutical compositions and diagnostic reagents comprising the polypeptides; and methods of making and using the polypeptides.

Abstract: Provided herein are isolated antibodies that specifically bind a RANK polypeptide.

Abstract: Compositions and methods for detection of estrogen receptor-&bgr; in human tissues are provided. The compositions are monoclonal antibodies specific for estrogen receptor-&bgr; binding. The method provided is a prognostic method and/or a predictive assay for cancer, including breast cancer. The assay provided uses a estrogen receptor-&bgr; antibody that has both high affinity and specificity and can be used in archival tissue sections.

Abstract: Human monoclonal antibodies which bind specifically to Fc alpha receptor (CD89), including monoclonal antibodies which react specifically to Fc receptor for IgA of human effector cells are disclosed. The binding agents, e.g., antibodies are useful for targeting human effector cells (e.g. macrophages) against a target cell (e.g. a cancer cell, an infectious agent, etc.). For this purpose, bifunctional antibodies or heteroantibodies can be constructed containing the binding region derived from an anti-Fc-alpha receptor antibody and the binding region of a target-specific antibody. Targeted effector cells can specifically lyse target cells.

Abstract: The invention concerns bifunctional fusion molecules for the treatment of IgE-mediated allergic conditions and Fc&egr;RI-mediated autoimmune conditions. The invention provides a new therapeutic approach for the treatment of both acute and late-phase allergic responses due to ingestion, inhalation, cutaneous and parenteral exposure to allergens, responses including asthma, allergic rhinitis, atopic dermatitis, severe food allergies, chronic urticaria and angioedema, as well as anaphylactic reactions due to exposures such as bee stings or penicillin allergy. In addition, the invention provides for a novel, safer and more efficacious form of allergy vaccination.