Abstract: The invention uses the power of display selection methods to screen libraries of human immunoglobulin genes from nonhuman transgenic animals expressing human immunoglobulins. Such screening produces unlimited numbers of high affinity human antibodies to any target of interest.

Abstract: The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide of three amino acids, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by a trouase enzyme such as Thimet oligopeptidase. Also disclosed are methods of making and using the prodrug compounds.

Abstract: The present invention relates to monoclonal antibodies that bind to the extracellular domain of prostate-specific membrane antigen (PSMA), hybridoma cell lines producing the antibodies, and methods of using such antibodies for diagnosis and treatment of cancer. In. particular, thirty-five monoclonal antibodies reactive with PSMA expressed on the cell surface are exemplified. Additionally, the present invention relates to a novel protein variant (PSM?) of PSMA detected by a number of the antibodies of the invention. The hydrolase activity of PSMA and PSM? allows the use of an immunoenzymatic assay for their detection.

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 provides in vitro methods of detection using human antibodies. The methods are particularly useful for analyzing human samples containing HAMA or heterophilic antibodies. A human antibody can bind to an analyte in such samples without binding to HAMA or heterophilic antibodies present in the samples. The methods can be effected using a sandwich format among others.

Abstract: The invention provides peptides of about 9-12 amino acids having a sequence derived from the interferon binding site of the IFNAR1 chain of the Type 1-interferon (Type 1-IFN) receptor for use as a Type 1-IFN antagonist. In particular, the invention provides peptides having the 9 mer sequence FSSLKLNVY (SEQ ID no. 1) and analogues thereof for use as Type 1-IFN antagonists. Particularly preferred for this purpose is the peptide of SEQ ID no. 1 and analogues thereof including SEQ ID no. 1 having an additional asparagine residue (N) at the C-terminus and/or additional glutamic acid residue (E) at the N-terminus.

Abstract: The invention relates to a monoclonal antibody directed against the human interferon class I receptor (IFN-R) characterized by the following properties: it recognizes the extracellular domain of the human IFN-R, and it has a neutralizing capacity against the biological properties of the human type I-IFN. It further concerns their use for the diagnosis.

Abstract: The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide having an isoleucine residue, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by an enzyme associated with the target cell. Methods of making and using the compounds are also disclosed.

Abstract: The present invention provides isolated anti-interferon alpha monoclonal antibodies, particularly human monoclonal antibodies, that inhibit the biological activity of multiple interferon (IFN) alpha subtypes but do not substantially inhibit the biological activity of IFN alpha 21 or the biological activity of either IFN beta or IFN omega. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting the biological activity of IFN alpha using the antibodies of the invention, as well as methods of treating disease or disorders mediated by IFN alpha, such as autoimmune diseases, transplant rejection and graft versus host disease, by administering the antibodies of the invention.

Abstract: The invention uses the power of display selection methods to screen libraries of human immunoglobulin genes from nonhuman transgenic animals expressing human immunoglobulins. Such screening produces unlimited numbers of high affinity human antibodies to any target of interest.

Abstract: The present disclosure provides drug-cleavable substrate conjugates that are potent cytotoxins. The disclosure is also directed to compositions containing the drug-cleavable substrate conjugates, and to methods of treatment using them.

Abstract: The present invention provides analogues of duocarmycins that are potent cytotoxins. Also provided are peptidyl and disulfide linkers that are cleaved in vivo. The linkers are of use in forming prodrugs and conjugates of the cytotoxins of the invention as well as other diagnostic and therapeutic moieties. The invention provides prodrugs and conjugates of the duocarmycin analogues with the linker arms of the invention.

Abstract: The present invention is directed to methods for the identification of a prostate cancer cell that has metastatic potential or a cell that is or is derived from a secondary prostate tumor metastasis by screening for the expression of flt-4, the cellular receptor of vascular endothelial growth factor-C and -D (“VEGF-C”, “VEGF-D”). The present invention is also directed to methods for treating, inhibiting or preventing secondary prostate tumor metastases by inhibiting the expression or activity of flt-4, e.g., inhibiting flt-4: VEGF-C/D complex formation (binding), by administration of a therapeutic. Compositions useful in such methods are also provided.

Abstract: The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide having an isoleucine residue, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by an enzyme associated with the target cell. Methods of making and using the compounds are also disclosed.

Abstract: Methods for treating lymphomas characterized by expression of CD30 using anti-CD30 antibodies and proteasome inhibitors in combination are disclosed.

Abstract: The present invention provides analogues of duocarmycins that are potent cytotoxins. Also provided are peptidyl and disulfide linkers that are cleaved in vivo. The linkers are of use in forming prodrugs and conjugates of the cytotoxins of the invention as well as other diagnostic and therapeutic moieties. The invention provides prodrugs and conjugates of the duocarmycin analogues with the linker arms of the invention.

Abstract: The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.

Abstract: The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.

Abstract: The present invention provides isolated human monoclonal antibodies that bind to IFNAR-1 and that are capable of inhibiting the biological activity of Type I interferons. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting Type I interferon-mediated disorders using the antibodies of the invention, including methods for treating autoimmune disorders, transplant rejection or Graft Versus Host Disease using the antibodies of the invention.

Abstract: The present disclosure provides drug-ligand conjugates that are potent cytotoxins, wherein the drug is linked to the ligand through either a peptidyl, hydrazine, or disulfide linker. The disclosure is also directed to compositions containing the drug-ligand conjugates, and to methods of treatment using them.