557results about "Apoptosis related proteins" patented technology

The present invention relates to an integration defective retroviral vector particle for gene therapy comprising a viral genome, wherein said vector particle is capable of infecting a mammalian target cell.

Peptides and peptidomimetics capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins) are disclosed. The peptides and mimetics are based on the N-terminal tetrapeptide of IAP-binding proteins, such as Smac / DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptides and peptidomimetics for therapeutic purposes and for rational drug design.

The present invention provides novel peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production.

The present invention provides biologically active peptidomimetic macrocycles with improved properties relative to their corresponding polypeptides. The invention additionally provides methods of preparing and using such macrocycles, for example in therapeutic applications.

The present invention provides novel peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production.

The invention provides methods for determining a prognosis for survival for a cancer patient. One method involves (a) measuring a level of a TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) comparing the level of TUCAN in the sample to a reference level of TUCAN, wherein a low level of TUCAN in the sample correlates with increased survival of the patient. Another method involves (a) measuring a level of TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) classifying the patient as belonging to either a first or second group of patients, wherein the first group of patients having low levels of TUCAN is classified as having an increased likelihood of survival compared to the second group of patients having high levels of TUCAN.

Disclosed herein are novel polypeptides and the nucleic acid sequences that encode them. Also disclosed are antibodies that immunospecifically bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the novel polypeptide, polynucleotide, or antibody specific to the polypeptide. Vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using same are also included. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of apoptosis associated disorders involving these novel human nucleic acids and proteins.

The present invention provides polypeptides and specific binding agents that modify the activity of an initiator caspase involved in apoptosis, caspase-9. The polypeptides include the third baculoviral IAP repeat (BIR3) of an IAP and form a heterodimer complex with caspase-9. Nucleic acid molecules including expression vectors encoding the polypeptides and variants thereof as well as variants of caspase-9 are provided. Such polypeptide and nucleic acid molecules may be used for modifying apoptosis.

The present invention relates to a composition comprising at least one mRNA encoding a combination of antigens capable of eliciting an (adaptive) immune response in a mammal, wherein the antigens are selected from the group consisting of 5T4 (Trophoblast glycoprotein, TPBG), Survivin (Baculoviral TAP repeat-containing protein 5; BIRC5), NY-ESO-1 (New York esophageal squamous cell carcinoma 1, CTAG1B), MAGE-C1 (Melanoma antigen family C1), MAGE-C2 (Melanoma antigen family C2), and MUC1 (Mucin 1). The invention furthermore relates to a vaccine comprising at least one mRNA encoding such a combination of antigens, and to the use of said composition (for the preparation of a vaccine) and / or of the vaccine for eliciting an (adaptive) immune response for the treatment of lung cancer, preferably of non-small cell lung cancer (NSCLC), and diseases or disorders related thereto. Finally, the invention relates to kits, particularly to kits of parts, containing the composition and / or the vaccine.

The present invention relates to compositions and methods for the treatment and diagnosis of conditions, disorders, or diseases involving cell death. The invention encompasses protective nucleic acids which, when introduced into a cell predisposed to undergo cell death or in the process of undergoing cell death, prevent, delay, or rescue the cell from death relative to a corresponding cell into which no exogenous nucleic acids have been introduced. The invention encompasses nucleic acids of the protective sequence, host cell expression systems of the protective sequence, and hosts that have been transformed by these expression systems, including transgenic animals. The invention also encompasses novel protective sequence products, including proteins, polypeptides and peptides containing amino acid sequences of the proteins, fusion proteins of proteins, polypeptides and peptides, and antibodies directed against such gene products. The invention further relates to target sequences, including upstream and downstream regulatory sequences or complete gene sequences, antibodies, antisense molecules or sequences, ribozyme molecules, and other inhibitors or modulators directed against such protective sequences, protective sequence products, genes, gene products, and / or their regulatory elements involved in cell death. The present invention also relates to methods and compositions for the diagnosis and treatment of conditions, disorders, or diseases, involving cell death, including, but not limited to, treatment of the types of conditions, disorders, or diseases, which can be prevented, delayed or rescued from cell death and include, but are not limited to, those associated with the central nervous system, including neurological and psychiatric conditions, disorders, or diseases, and those of the peripheral nervous system. Further, the invention relates to methods of using the protective sequence, protective sequence products, and / or their regulatory elements for the identification of compounds that modulate the expression of the protective sequence and / or the activity of the protective sequence product. Such compounds can be useful as therapeutic agents in the treatment of various conditions, disorders, or diseases involving cell death.

Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transfection under serum-free conditions. In preferred embodiments, the cells of use are SpESF or SpESF-X cells.

The present invention relates to a RUNX3 gene showing anti-tumor activity which is essentially involved in TGF-β dependent-programmed cell death (apoptosis) and use thereof. In addition, the present invention finds that the RUNX3 gene expression is suppressed in the various gastric cancer and lung cancer cell lines. The suppression of the RUNX3 gene expression is due to hyper-methylation of CpG island located around RUNX3 exon (1). The RUNX3 gene and its gene product of the present invention can be used effectively for the development of anti-cancer agents. CpG island around RUNX3 exon (1) could also be used not only for the development of anti-cancer agents which regulate the abnormal DNA methylation and there by induce RUNX3 expression but also for the development of methods for cancer diagnosis by measuring the abnormal DNA methylation.

Mutant BNIP3 plays a functionally important role in the development of solid tumors and in resistance to chemotherapy and radiation treatments. The invention relates to methods of detecting cancer, methods of monitoring the progression of cancer, methods of identifying patients with cancer that is resistant to chemotherapy or radiation treatments, and diagnostic kits for performing the methods of the invention.

The present invention relates to kinase inhibiting compositions and uses thereof. The invention further provides isolated kinase inhibiting peptides and uses thereof for inhibiting hyperplasia, for inhibiting the growth of neoplasms, and for inducing programmed cell death in a cell population.

The present invention is based, at least in part, on the identification of a novel active site on BCL-2 family polypeptide such as BAX, which when bound by a compound, modifies the activity of the BCL-2 family polypeptide.

The present invention relates to compositions and methods for the treatment and diagnosis of conditions, disorders, or diseases involving cell death. The invention encompasses protective nucleic acids which, when introduced into a cell predisposed to undergo cell death or in the process of undergoing cell death, prevent, delay, or rescue the cell from death relative to a corresponding cell into which no exogenous nucleic acids have been introduced. The invention encompasses nucleic acids of the protective sequence, host cell expression systems of the protective sequence, and hosts that have been transformed by these expression systems, including transgenic animals. The invention also encompasses novel protective sequence products, including proteins, polypeptides and peptides containing amino acid sequences of the proteins, fusion proteins of proteins, polypeptides and peptides, and antibodies directed against such gene products. The invention further relates to target sequences, including upstream and downstream regulatory sequences or complete gene sequences, antibodies, antisense molecules or sequences, ribozyme molecules, and other inhibitors or modulators directed against such protective sequences, protective sequence products, genes, gene products, and / or their regulatory elements involved in cell death. The present invention also relates to methods and compositions for the diagnosis and treatment of conditions, disorders, or diseases, involving cell death, including, but not limited to, treatment of the types of conditions, disorders, or diseases, which can be prevented, delayed or rescued from cell death and include, but are not limited to, those associated with the central nervous system, including neurological and psychiatric conditions, disorders, or diseases, and those of the peripheral nervous system. Further, the invention relates to methods of using the protective sequence, protective sequence products, and / or their regulatory elements for the identification of compounds that modulate the expression of the protective sequence and / or the activity of the protective sequence product. Such compounds can be useful as therapeutic agents in the treatment of various conditions, disorders, or diseases involving cell death.

The present invention relates to a novel member of the TNF-Ligand superfamily. More specifically, isolated nucleic acid molecules are provided encoding a human Apoptosis Inducing Molecule II (AIM II). AIM II 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 AIM II activity. Also provided are therapeutic methods for treating lymphadenopathy, aberrant bone development, autoimmune and other immune system diseases, graft versus host disease, rheumatoid arthritis, osteoarthritis and to inhibit neoplasia, such as tumor cell growth.

The invention relates to methods for treating and diagnosing hematologic malignancies, Chronic lymphocytic leukemia and Small Lymphocytic Lymphoma in particular, using PD-1 ligands (PD-L1, PD-L2 or anti-PD-1 antibodies).

Conformationally constrained peptides that mimic BH3-only proteins, compositions containing them and their use in the regulation of cell death are disclosed. The conformationally constrained peptides are capable of binding to and neutralising pro-survival Bcl-2 proteins. Processes for preparing the conformationally constrained peptides and their use in the treatment and / or prophylaxis of diseases or conditions associated with deregulation of cell death are also disclosed.

Provided by the invention are novel methods, vectors and cells for the recombinant production of desired gene products. In particular, the invention relates to increased production of desired gene products by inducibly arresting cell proliferation. The invention also provides novel multicistronic expression vectors that are useful not only for recombinant gene expression, but also for other applications such as gene therapy, tissue engineering and metabolic engineering.

The invention provides novel inhibitors of IAP that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: X1 and X2 are independently O or S; L is a bond or —C(X3)—, —C(X3)NR12, —C(X3)O— wherein X3 is O or S and R12 is H or R1; R1 is alkyl, a carbocycle, carbocycle-substituted alkyl, a heterocycle or heterocycle-substituted alkyl, wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, haloalkyl, alkoxy, alkylsulfonyl, amino, nitro, aryl and heteroaryl; R2 is alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, a heterocycle or heterocyclylalkyl; R3 is H or alkyl; R4 and R4′ are independently H, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, or heteroaralkyl wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, alkoxy, amino and nitro; R5, and R5 are each independently H or alkyl; R6 is H or alkyl; and salts and solvates thereof.

Peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production, are provided.

The invention relates to an attenuated Salmonella sp. that is capable of targeting a solid tumor when administered in vivo comprising a short hairpin (sh) RNA construct, and methods of inhibiting the growth or reducing the volume of a solid tumor cancer comprising administering an effective amount of an attenuated Salmonella sp. to a patient having a solid tumor cancer, wherein said attenuated Salmonella sp. is a tumor targeting attenuated Salmonella sp. expressing a short hairpin (sh) RNA which attenuated Salmonella sp. is capable of inhibiting the growth or reducing the volume of the solid tumor cancer when administered in vivo.