Abstract: Aspects of the present invention relate to compositions and methods of reprogramming a somatic cell to give rise to an autologous embryonic stem cell. These methods involve providing a somatic cell of a donor subject, introducing the somatic cell into an embryo of a recipient subject to produce a chimeric embryo, allowing the chimeric embryo to develop further wherein the somatic cell will reprogram, and then selecting an autologous embryonic stem cell that has developed from the somatic cell. The methods and composition of producing pluripotent embryonic stem cells from a donor's own somatic cells invite the possibility of a number of therapeutic applications, including organ transplant and treatment of autoimmune diseases, cancer, and degenerative disorders such as diabetes, Alzheimer's, and Parkinson's.

Abstract: Methods of therapy for B-cell malignancies 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 when the antibody binds a CD40 antigen on a normal human B cell, exhibits antagonist activity when the antibody binds a CD40 antigen on a malignant human B cell, and can exhibit antagonist activity when the antibody binds a CD40 antigen on a normal human B cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of malignant human B cells.

Abstract: Modulators of phosphatidic acid phosphatase type 2C and other polypeptides, highly expressed in cancers as compared to normal tissues, are provided for treatment of proliferative disorders such as cancer. A method is provided for detecting polypeptides that are overexpressed in cancer, whereby antibodies or binding proteins that specifically recognize these molecules are contacted with a patient's bodily fluid. The method provides an early diagnosis of cancer, and can detect recurrence and metastasis following an initial diagnosis. The invention further provides methods of treating cancer with therapeutic agents directed toward these protein and peptide biomarkers.

Abstract: The invention provides novel polynucleotides, related polypeptides related nucleic acid and polypeptide compositions corresponding to novel human cDNA clones, and related modulators, such as antibodies and small molecule modulators. The invention also provides methods to make and use these polynucleotides, polypeptides, related compositions, and modulators. These methods include diagnostic, prophylactic and therapeutic applications. The compositions and methods of the invention are useful in treating proliferative disorders, e.g., cancers, and inflammatory, immune, bacterial, and viral disorders.

Abstract: Methods of therapy for B-cell malignancies 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 when the antibody binds a CD40 antigen on a normal human B cell, exhibits antagonist activity when the antibody binds a CD40 antigen on a malignant human B cell, and can exhibit antagonist activity when the antibody binds a CD40 antigen on a normal human B cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of malignant human B cells.

Abstract: A composition is provided that contains a polypeptide and a modulator or a cell comprising the polypeptide and a modulator, where the modulator specifically interferes with the activity of the polypeptide, and the polypeptide is either FGFR3 or FGFR4, inclusive of all polymorphic forms and variants thereof. The modulator can be an antibody or active fragments thereof, a small molecule drug, an RNAi molecule, an antisense molecule or a ribozyme. A method of treatment of tumors in a subject is also provided where an antagonist of FGFR3 or FGFR4 is administered to the subject.

Abstract: The invention provides novel human full-length cDNA clones, novel polynucleotides, related polypeptides, related nucleic acid and polypeptide compositions, and related modulators, such as antibodies and small molecule modulators. The invention also provides methods to make and use these cDNA clones, polynucleotides, polypeptides, related compositions, and modulators. These methods include diagnostic, prophylactic and therapeutic applications. The compositions and methods of the invention are useful in treating proliferative disorders, e.g., cancers, and inflammatory, immune, bacterial, and viral disorders.

Abstract: A stem cell library is created by genetically modifying stem cells with nucleic acids encoding polypeptides which can promote stem cell differentiation into specific cell types. Alternatively, the stem cell library is exposed to an externally added factor that promotes stem cell differentiation into a desired cell line, e.g., neuronal or muscle. The library is used to determine the effect of the encoded protein on the differentiation process. The library is also used to produce nucleic acids for insertion into embryonic stem cells to produce transfected embryonic stem cells. The nucleic acids are inserted into a locus that permits widespread expression of the encoded polypeptide in animals produced from blastocysts that incorporate the transfected cells. Non-human chimeric animals produced by combining blastocysts derived from animal models of human disease and embryonic stem cells transfected with molecules from the library provide an in vivo system for therapeutic design.

Abstract: A stem cell library is created by genetically modifying stem cells with nucleic acids encoding polypeptides which can promote stem cell differentiation into specific cell types. Alternatively, the stem cell library is exposed to an externally added factor that promotes stem cell differentiation into a desired cell line, e.g., neuronal or muscle. The library is used to determine the effect of the encoded protein on the differentiation process. The library is also used to produce nucleic acids for insertion into embryonic stem cells to produce transfected embryonic stem cells. The nucleic acids are inserted into a locus that permits widespread expression of the encoded polypeptide in animals produced from blastocysts that incorporate the transfected cells. Non-human chimeric animals produced by combining blastocysts derived from animal models of human disease and embryonic stem cells transfected with molecules from the library provide an in vivo system for therapeutic design.

Abstract: The invention provides for DNA encoding Fas ligand muteins and chimeras and the proteins encoded thereby. The invention further includes the use of DNA and vectors to produce transformed cells expressing the mutant or chimeric Fas ligand. When the Fas ligand of the invention is a non cleavable form, the cells expressing the Fas ligand are useful in vitro for identifying Fas expressing cells and in vitro or in vivo for reducing populations of Fas expressing cells. Thus, in other embodiments, the present invention is also directed to a method for treating a patient, for example a mammal, for autoimmune disease or transplant rejection by administering a Fas ligand therapeutic agent. The therapeutic agent is a polypeptide, a polynucleotide encoding the polypeptide or a small molecule. The polypeptides include full-length Fas ligand polypeptide, or a biologically active variant, derivative, portion, fusion or peptide thereof.

Abstract: Methods of therapy for B-cell malignancies 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 when the antibody binds a CD40 antigen on a normal human B cell, exhibits antagonist activity when the antibody binds a CD40 antigen on a malignant human B cell, and can exhibit antagonist activity when the antibody binds a CD40 antigen on a normal human B cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of malignant human B cells.

Abstract: CD40 antagonists are used to prepare compositions, including pharmaceutical compositions, for treating autoimmune and neoplastic diseases in a mammal. The CD40 antagonist compositions are useful for reversing or substantially diminishing such autoimmune diseases as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and psoriasis.

Abstract: The invention provides for DNA encoding Fas ligand muteins and chimeras and the proteins encoded thereby. The invention further includes the use of DNA and vectors to produce transformed cells expressing the mutant or chimeric Fas ligand. When the Fas ligand of the invention is a non cleavable form, the cells expressing the Fas ligand are useful in vitro for identifying Fas expressing cells and in vitro or in vivo for reducing populations of Fas expressing cells. Thus, in other embodiments, the present invention is also directed to a method for treating a patient, for example a mammal, for autoimmune disease or transplant rejection by administering a Fas ligand therapeutic agent. The therapeutic agent is a polypeptide, a polynucleotide encoding the polypeptide or a small molecule. The polypeptides include full-length Fas ligand polypeptide, or a biologically active variant, derivative, portion, fusion or peptide thereof.

Abstract: A novel kinase has been identified which phosphorylates I.kappa.B. Reagents which inhibit this kinase can be used as therapeutic tools to inhibit inflammation. The kinase can also be used as a target for drug screening to identify anti-inflammatory compounds.

Abstract: A novel kinase has been identified which phosphorylates I.kappa.B. Reagents which inhibit this kinase can be used as therapeutic tools to inhibit inflammation. The kinase can also be used as a target for drug screening to identify anti-inflammatory compounds.

Abstract: The present invention identifies a novel, Fas-associated factor 1 termed FAF1 which potentiates Fas-induced cell killing. The invention provides FAF1 nucleic acid and polypeptide compositions as well as methods of using these compositions in the therapeutic treatment of diseases resulting from dysregulation in apoptosis. Also provided are cells carrying and expressing the nucleic acid compositions and methods of using these cells to screen for agonists and antagonists of Fas-mediated apoptosis. Methods of isolating FAF1-interacting proteins are disclosed. Also provided are antibodies that bind FAF1, a hybridoma and a kit comprising the antibodies.

Abstract: The present invention identifies a novel, Fas-associated factor 1 termed FAF1 which potentiates Fas-induced cell killing. The invention provides FAF1 nucleic acid and polypeptide compositions as well as methods of using these compositions in the therapeutic treatment of diseases resulting from dysregulation in apoptosis. Also provided are cells carrying and expressing the nucleic acid compositions and methods of using these cells to screen for agonists and antagonists of Fas-mediated apoptosis. Methods of isolating FAF1-interacting proteins are disclosed.

Abstract: Recombinant polynucleotides are provided that confer at least partial immunity on an individual to an infectious intracellular pathogenic agent. The recombinant polynucleotides encode a costimulatory factor and/or a target antigen polypeptide. The immune response that confers the immunity results from the expression of both polypeptides in an antigen presenting cell in the individual. The immunity is to the pathogenic agent that naturally encodes the target antigen polypeptide.