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DANA-FARBER CANCER INSTITUTE, INC.

Boston, MA US

DANA-FARBER CANCER INSTITUTE, INC. Patent applications
Patent application numberTitlePublished
20160138112NON-INVASIVE BLOOD BASED MONITORING OF GENOMIC ALTERATIONS IN CANCER - The invention provides methods to monitor cell free nucleic acids. The method comprises obtaining a plasma sample from a subject known to have a cancer characterized by a pair of mutually exclusive mutations specific to the cancer; isolating cell free nucleic acids from the plasma sample obtained from the subject; measuring the amount a housekeeping gene and/or total DNA in the cell free nucleic acids isolated from the plasma sample to confirm that the amount of housekeeping gene and/or total DNA in the sample is within a selected range; measuring the amount of a first of the pair of mutually exclusive mutations specific to the cancer in the cell free nucleic acids isolated from the plasma sample; and indicating in a report that the subject has the first mutation when (a) the amount of the housekeeping gene and/or total DNA in the cell free nucleic acids isolated from the plasma sample is within the selected range and (b) the amount of the first mutation is increased as compared to a control amount, wherein the control amount is determined by measuring the apparent amount of the first mutation in control cell free nucleic acids isolated from plasma samples obtained from control subjects known to have the second of the pair of mutually exclusive mutations specific to the cancer using measuring conditions substantially the same as those used to measure the amount of the first mutation in the cell free nucleic acids isolated from the plasma sample from the subject.05-19-2016
20160137731HUMAN ANTI-PD-1, PD-L1, AND PD-L2 ANTIBODIES AND USES THEREFOR - The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-L1, and/or PD-L2 activity (e.g., persistent infectious diseases, autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein.05-19-2016
20160122323INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7) - The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.05-05-2016
20160082108WIREFRAME NANOSTRUCTURES - The present invention generally relates to nanotechnology and, in particular, to wireframe nanostructures which may be formed from nucleic acids. In various aspects, the invention relates to molecular structures having a plurality of vertices and pathways connecting the vertices, which may be formed from nucleic acids, including bundles or tubes of nucleic acids. Such molecular structures may form shapes such as icosahedrons, octahedrons, tetrahedrons, or other polyhedra, which may define an interior space. The interior space may be used, for example, to contain a molecule for further study, or to contain a molecule for drug delivery purposes. In some cases, the molecular structure may be stabilized using relatively short nucleic acid strands that interact with two or more nucleic acid portions within the structure, thereby substantially immobilizing the portions relative to each other. Other aspects of the invention relate to techniques for forming such molecular structures, techniques for using such molecular structures, techniques of promoting such molecular structures, kits involving such molecular structures, and the like.03-24-2016
20160068834STABLIZED EZH2 PEPTIDES - Provided herein are polypeptides containing stabilized therapeutic peptides related to enhancer of zeste homolog 2 (EZH2), histone lysine N-methyltransferase. Also provided are compositions containing these polypeptides and methods of using such peptides in the treatment of cancer that include administering to a subject one of the polypeptides.03-10-2016
20160046661RAS INHIBITORS AND USES THEREOF - Described herein are compounds of Formulae (I)-(II), and pharmaceutically acceptable salts, and pharmaceutical compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases such as cancers (e.g., lung cancer, large bowel cancer, pancreas cancer, biliary tract cancer, or endometrial cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases in a subject.02-18-2016
20160046636TYPE II RAF KINASE INHIBITORS - The present invention relates to novel compounds which are able to modulate b-raf kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.02-18-2016
20160033519BROMODOMAIN BINDING REAGENTS AND USES THEREOF - The present invention provides compounds of the Formula (I) and (II), and salts thereof, wherein L02-04-2016
20160032359Methods for Generating Nucleic Acid Molecule Fragments Having a Customized Size Distribution - The invention provides methods for generating nucleic acid molecule fragments having a customized distribution. In one aspect, a method of generating nucleic acid fragments having a customized fragment size distribution is provided comprising obtaining a master pool of nucleic acid molecules to be fragmented; fragmenting at least two independent aliquots of the master pool of nucleic acid molecules in separate reactions, wherein the fragmentation conditions are identical except for a single variable.02-04-2016
20160024589METHODS OF IDENTIFYING RESPONSES TO MAP KINASE INHIBITION THERAPY - The invention provides methods and devices for determining molecular signatures in a cancer that predict response to a MARPK pathway inhibitor and methods of use of such signatures.01-28-2016
20150354006MARKERS FOR ACUTE LYMPHOBLASTIC LEUKEMIA - The invention provides methods of detecting a NSD2 mutation in a cancer cell, methods cancer diagnosis and methods of screening for NSD2 inhibitors.12-10-2015
20150353935MELK Regulation for the Treatment of Breast Cancer - Methods for inhibiting growth or proliferation of breast cancer cells are provided. The methods include administering to a subject in need thereof in an amount that is effective to inhibit growth or proliferation of the breast cancer cells a MELK inhibitor, wherein the breast cancer cells are estrogen receptor (ER) negative. In some aspects, the methods include administering to a subject in need thereof in an amount that is effective to inhibit growth or proliferation of the breast cancer cells a MELK inhibitor, a FoxM1 inhibitor or a MELK inhibitor and a FoxM1 inhibitor, wherein the breast cancer cells are estrogen receptor (ER) negative. Methods of treatment for breast cancer and methods of identifying patients having cancer that are likely to benefit from treatment with a MELK inhibitor, a FoxM1 inhibitor or a MELK inhibitor and a FoxM1 inhibitor are also provided.12-10-2015
20150330984METABOLOMIC PROFILING DEFINES ONCOGENES DRIVING PROSTATE TUMORS - The invention provides methods and products to identify metabolic status of Akt1 and Myc in tumors, and to treat cancer. The method comprises performing an assay to measure a profile of metabolites in a prostate tumor sample obtained from a subject, wherein the metabolites are differentially produced in prostate tumors with high Akt1 expression versus prostate tumors with high Myc expression; and comparing, with at least one processor, the profile of metabolites with an appropriate reference profile of the metabolites to assign an Akt1 and Myc metabolic status to the sample based on results of the comparison.11-19-2015
20150322528BIOMARKERS ASSOCIATED WITH CDK INHIBITORS - The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Cyclin Dependent kinase inhibitors (CDKi), methods of determining the sensitivity of a cell to a CDKi, methods of treating a patient with a CDKi and methods of screening for candidate CDKi.11-12-2015
20150322460COMPOSITIONS AND METHODS FOR REGULATING THERMOGENESIS AND MUSCLE INFLAMMATION USING METRNL AND METRN - The invention provides compositions and methods for regulating thermogenesis and muscle inflammation through modulation of Metrnl and/or Metrn activity and/or expression. Also provided are methods for preventing or treating metabolic disorders and muscle inflammation disorders in a subject through modulation of Metrnl and/or Metrn activity and/or expression. Further provided are methods for identifying compounds that are capable of treating metabolic disorders and muscle inflammation disorders by modulating Metrnl and/or Metrn activity and/or expression.11-12-2015
20150313890KINASE INHIBITORS AND METHODS OF USE THEREOF - The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3α or GSK3β) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychiatric disorders, metabolic disorders, and cancer.11-05-2015
20150307444CLASS- AND ISOFORM-SPECIFIC HDAC INHIBITORS AND USES THEREOF - HDAC inhibitors of the general formula (I) and (II) and pharmaceutically acceptable salts thereof, as described herein, are useful as inhibitors of histone deacetylases or other deacetylases, and thus are useful for the treatment of various diseases and disorders associated with acetylase/deacetylase activity as described herein (e.g., cancer). In certain embodiments, the compounds of the invention selectively target either a class or isoform of the HDAC family. Another aspect of the invention provides an assay for determining the inhibitory effect of a test compound on an HDAC protein comprising: incubating the HDAC protein with a substrate of general formula (IIIc) in the presence of a test compound; and determining the activity of the HDAC protein.10-29-2015
20150299322Agents That Modulate Immune Cell Activation and Methods of Use Thereof - The present invention relates to compositions and methods for the immunomodulation mediated by the interaction of PD-L2 and RGMb.10-22-2015
20150274835HUMAN MONOCLONAL ANTI-PD-L1 ANTIBODIES AND METHODS OF USE - The present invention comprises human monoclonal antibodies that bind to PD-L1 (also known as programmed death ligand 1 or B7H1). Binding of the invented antibody to PD-L1 inhibits binding to its receptor, PD1 (programmed death 1), and ligand-mediated activities and can be used to treat cancer and chronic viral infections.10-01-2015
20150274738HYDROPHOBICALLY TAGGED SMALL MOLECULES AS INDUCERS OF PROTEIN DEGRADATION - Provided are bifunctional small molecules of Formula (I): or pharmaceutically acceptable salts thereof, wherein M represents a small organic molecule which binds, covalently or non-covalently, a kinase, such as Her3 protein kinase; L10-01-2015
20150246913BONE MARROW ON X CHROMOSOME KINASE (BMX) INHIBITORS AND USES THEREOF - The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I) or (II), or compositions thereof, for treating or preventing a wide range of diseases (e.g., proliferative diseases (e.g., cancers, benign neoplasms, angiogenesis, inflammatory diseases, autoimmune diseases) and metabolic diseases (e.g., diabetes (e.g., type 2 diabetes, gestational diabetes)) in a subject. Treatment of a subject with a disease using a compound of Formula (I) or (II), or compositions thereof, may downregulate the expression and/or inhibit the activity of a kinase (e.g., a tyrosine kinase, such as a Tec kinase, in particular, bone marrow on X chromosome kinase (BMX)), and therefore, suppress tyrosine kinase singling in the subject.09-03-2015
20150239972METHODS FOR THE TREATMENT OF INFECTIONS AND TUMORS - PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist. Methods are also disclosed for determining the efficacy of a PD-1 antagonist in a subject administered the PD-1 antagonist. In some embodiments, these methods include measuring proliferation of memory B cells in a sample from a subject administered the PD-1 antagonist.08-27-2015
20150218204SELF-ASSEMBLY OF NUCLEIC ACID NANOSTRUCTURES - The invention involves the synthesis of nucleic acid structures of controlled size and shape and comprised of a plurality of oligonucleotides. The structures are formed, at least in part, by the self-assembly of single-stranded oligonucleotides. The location of each oligonucleotide in the resultant structure is known. Accordingly, the structures may be modified with specificity.08-06-2015
20150203549COMPOSITIONS AND METHODS FOR BROWN FAT INDUCTION AND ACTIVITY USING FNDC5 - The invention provides compositions and methods for brown fat induction and activity through modulation of Fndc5 activity and/or expression. Also provided are methods for preventing or treating metabolic disorders in a subject through modulation of Fndc5 activity and/or expression. Further provided are methods for identifying compounds that are capable of modulating Fndc5 activity and/or expression.07-23-2015
20150197785METHODS AND APPARATUS FOR ANALYZING AND QUANTIFYING DNA ALTERATIONS IN CANCER - Methods and apparatus for inferring purity and ploidy from a sample of cells (e.g., a sample comprising cancer and normal cells) are described. Copy number per cell of interest (e.g., cancer cell) is determined by optimizing purity and ploidy for the sample based, at least in part, on relative copy number profile information. One or more likelihood fit scores are determined for each of a plurality of candidate solutions generated by the methods described herein. A solution is selected based, at least in part on the likelihood fit score(s) and the copy number per cancer cell is determined in accordance with the selected solution.07-16-2015
20150197571Single Agent Anti-PD-L1 and PD-L2 Dual Binding Antibodies and Methods of Use - The present invention is based, in part, on the identification of novel antibodies that have binding affinity for both PD-L1 and PD-L2 and methods of using same. In one aspect, an isolated monoclonal antibody, or antigen-binding fragment thereof, which specifically binds both PD-L1 and PD-L2, is provided. In one embodiment, both PD-L1 and PD-L2 are human PD-L1 and human PD-L2.07-16-2015
20150197497SELECTIVE INHIBITORS OF HISTONE DEACETYLASE ISOFORM 6 AND METHODS THEREOF - The described invention provides histone deacetylase (HDAC) inhibitor compounds with substituted benzimidazole, benzimidazolone and benzotriazole heterocycles showing selective inhibition of histone deacetylase isoform HDAC6. The described invention further provides methods of making such compounds and methods of inhibiting HDAC, treating HDAC-associated diseases, including cell proliferative disorders, such as cancer, autoimmune or inflammatory diseases and neurodegenerative diseases.07-16-2015
20150191417ANTI-PROLIFERATIVE COMPOUNDS AND USES THEREOF - The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, hydrates, polymorphs, and compositions thereof. Also provided are methods and kits involving the inventive compounds for treating proliferative diseases (e.g., cancers (e.g., breast cancer, prostate cancer, lung cancer, and ovarian cancer), benign neoplasms, angiogenesis, inflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound of the invention may enhance the anti-tumor immune response by inhibiting or eliminating the immune suppression mediated by immune suppressor myeloid cells (MDSCs), inducing apoptosis, and/or inhibit or down-regulate proteins (e.g., epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), X-linked inhibitor of apoptosis protein (XIAP), and heat shock protein 90 (Hsp90)) in the subject.07-09-2015
20150183836Compositions and Methods for Conformationally Stabilizing Primate Immunodeficiency Virus Envelope Glycoprotein Trimers - The invention provides compositions and methods related to conformationally stabilizing primate immunodeficiency virus envelope glycoprotein trimers.07-02-2015
20150174138DIAGNOSTIC AND TREATMENT METHODS IN SUBJECTS HAVING OR AT RISK OF DEVELOPING RESISTANCE TO CANCER THERAPY - The invention relates to methods of treatment and diagnosis of subjects with cancer. In some aspects, the invention relates to methods of treatment and diagnosis of subjects with cancer, wherein the cancer is characterized by a Notch pathway activation mutation or by resistance to a Notch pathway inhibitor.06-25-2015
20150157629TYPE II RAF KINASE INHIBITORS - The present invention relates to novel compounds which are able to modulate b-raf kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.06-11-2015
20150152152MUC-1 CYTOPLASMIC DOMAIN PEPTIDES AS INHIBITORS OF CANCER - Peptides from the Mucin 1 (MUC1) cytoplasmic domain and methods of use therefor are described. These peptides can inhibit MUC1 oligomerization, thereby preventing tumor cell growth, inducing tumor cell apoptosis and necrosis of tumor tissue in vivo.06-04-2015
20150141470DIAGNOSTIC AND TREATMENT METHODS IN PATIENTS HAVING OR AT RISK OF DEVELOPING RESISTANCE TO CANCER THERAPY - A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a MAPK pathway inhibitor, such as a RAF inhibitor, MEK inhibitor, or ERK inhibitor, and a GEF or HDAC inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a MAPK inhibitor, such as a RAF inhibitor, MEK inhibitor, or ERK inhibitor, and an effective amount of a GEF or HDAC inhibitor. A method of identifying targets that confers resistance to a MAPK pathway inhibitor is also provided.05-21-2015
20150133478C-RAF MUTANTS THAT CONFER RESISTANCE TO RAF INHIBITORS - Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.05-14-2015
20150119551STABILIZED P53 PEPTIDES AND USES THEREOF - Cross-linked peptides related to human p53 and bind to HMD2 or a family member of HDM2 useful for promoting apoptosis, e.g., in the treatment of and identifying therapeutic agents that binding to HMD2 or a family member of HDM2.04-30-2015
20150111786METHODS OF TREATING A MEIOTIC KINESIN-ASSOCIATED DISEASE - The invention provides methods of treating a meiotic kinase-associated disease, preferably the meiotic kinase HSET, by administering an inhibitor of the meiotic kinase. Preferably, the disease is associated with the presence of supernumerary centrosomes, such as cancer. Methods of inhibiting the growth of a tumor cell by contacting the cell with an inhibitor of a meiotic kinase, preferably HSET, are also provided. Screening methods for identifying inhibitors of the meiotic Kinase HSET are also provided. Methods of selecting subjects for treatment with an inhibitor of a meiotic kinase, such as HSET, are also provides.04-23-2015
20150110717METHODS OF INCREASING THE NUMBER OF TARGET CELLS RECOVERED FROM A FLUID SAMPLE - Methods and materials for increasing the number of target cells recovered from a fluid sample containing cells are described. The methods include isolating the target cells on a filter and then implanting the filter containing the target cells in an immunodeficient non-human animal, where at least some of the target cells can proliferate.04-23-2015
20150094315FUSED 2-AMINOTHIAZOLE COMPOUNDS - The present application relates to therapeutic organic compounds, compositions comprising an effective amount of a therapeutic organic compound; and methods for treating and preventing disease comprising administering and effective amount of a therapeutic organic compound to a subject in need thereof.04-02-2015
20150094275SMALL MOLECULE MYRISTATE INHIBITORS OF BCR-ABL AND METHODS OF USE - The present invention provides novel heteroaryl compounds having a pyrimidine-containing core that is linked to a 4-trifluoromethoxyphenyl group via an amine linker. Such compounds are useful for the treatment of cancers.04-02-2015
20150087598TREATING MUC1-EXPRESSING CANCERS WITH HELICASE INHIBITORS - The invention provides method of treating cancers that express MUC1 by the administration of eIF4A helicase inhibitors. These inhibitors may advantageously be combined with peptides that inhibit MUC1 oligomerization, or with other standard anticancer therapies such as chemo-, radio- and surgical therapies.03-26-2015
20150045308Compositions and Methods of Treating Cancer - The present invention provides compositions and methods of treating various disorders associated with aberrant cell growth.02-12-2015
20150044230METHODS RELATED TO TIM 3, A TH1-SPECIFIC CELL SURFACE MOLECULE, FOR ACTIVATING ANTIGEN PRESENTING CELLS - The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.02-12-2015
20150044229METHODS RELATED TO TIM 3, A TH1-SPECIFIC CELL SURFACE MOLECULE, FOR ACTIVATING ANTIGEN PRESENTING CELLS - The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.02-12-2015
20150010576PHARMACEUTICALS AND METHODS FOR TREATING HYPOXIA AND SCREENING METHODS THEREFOR - Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. The ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is “turned on” only under such conditions.01-08-2015
20140378529COLLATERAL GENE INACTIVATION BIOMARKERS AND TARGETS FOR CANCER THERAPY - Methods for treating a subject determined to have a cancer comprising a heterozygous inactivation of a housekeeping gene (or a homozygous deletion of a functionally redundant housekeeping gene) by treating the subject with an inhibitor of the gene. For example, a subject having a cancer with an ENO gene deletion can be treated with a glycolysis inhibitor, such as an enolase inhibitor. In some aspects, a subject having a cancer with an ARS gene deletion can be treated with an ARS inhibitor.12-25-2014
20140371157METHODS OF DOWNREGULATING TRANSLOCATED ONCOGENE EXPRESSION USING BROMODOMAIN INHIBITORS - Disclosed herein are novel methods and compositions useful for inhibiting interaction between a bromodomain protein and an immunoglobulin (Ig) regulatory element. The methods and compositions are particularly useful for downregulating expression of an oncogene translocated with an Ig locus, as well as for treating a cancer (e.g., hematological malignancy) characterized by increased expression of an oncogene which is translocated with an Ig locus. Also disclosed herein are methods and assays for identifying agents that interfere with binding of bromodomain proteins to Ig regulatory elements, as well as methods and assays for identifying inhibitors of bromodomain12-18-2014
20140370042Stabilized Antiviral Fusion Helices - Internally cross-linked peptides useful for interfering with Respiratory Syncytial Virus (RSV) infection is based on RSV-F protein. These peptides are capable of reducing infection in cellular and animal models.12-18-2014
20140364439MARKERS ASSOCIATED WITH CHRONIC LYMPHOCYTIC LEUKEMIA PROGNOSIS AND PROGRESSION - The present invention provides methods and devices related to markers (or biomarkers) associated with chronic lymphocytic leukemia (CLL). Examples of these markers include drivers of CLL progression. The invention contemplates, inter alia, detecting the clonal, including subclonal, profile of CLL in a subject and the presence (or absence) of subclonal driver mutations, and utilizing this information in predicting disease progression, need, timing and/or nature of treatment regimen, and likelihood and frequency of relapse.12-11-2014
20140357687Pyrazol-3-ones That Activate Pro-apoptotic BAX - This application features pyrazol-3-one compounds that activate pro-apoptotic BAX. Also featured are methods of using such compounds, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., insufficient apoptosis of diseased or damaged cells or essentially the absence of apoptosis of diseased or damaged cells).12-04-2014
20140349965COMPOSITIONS AND METHODS FOR TREATING NEOPLASTIC DISEASES - Disclosed herein are compositions and methods for treating neoplastic diseases. Included are compositions and methods that are effective against multiple myeloma cells resistant to conventional and bortezomib treatment. Furthermore, combination treatment with two different proteosome inhibitors is shown to be synergistic for treating multiple myeloma.11-27-2014
20140348819Methods of Treating Cancer - The present invention provides methods of treating cancer.11-27-2014
20140328858LIN28-MEDIATED CONTROL OF LET-7 BIOGENESIS - The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3′ terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.11-06-2014
20140322332ANTAGONISTS OF MUC1 - The present invention is directed to improved compositions for cellular delivery of peptides. Using segments of only 3-5 positively-charged residues, one can effectively transfer peptides, including therapeutic peptides, into cells. Also provided are modified peptides such as those include stapled and cyclized peptide technology, as well as peptoids/peptidomimetics.10-30-2014
20140314765SIGNATURES AND DETERMINANTS ASSOCIATED WITH PROSTATE CANCER PROGRESSION AND METHODS OF USE THEREOF - The present invention provides a set of DETERMINANTS (e.g., genes and gene products) that can accurately inform about the risk of cancer progression and recurrence, as well as methods of their use.10-23-2014
20140309221METHOD OF INHIBITING HAMARTOMA TUMOR CELLS - Dimorpholinopyrimidines are useful for inhibiting growth or proliferation of hamartoma tumor cells. Because the Dimorpholinopyrimidines inhibit the growth and proliferation of hamartoma tumor cells they are also useful in treating PTEN hamartoma tumor syndromes. The therapeutic and prophylactic treatments provided by this invention are practiced by administering to a patient in need thereof an amount of a compound of dimorpholinopyrimidine derivative that is effective to inhibit growth or proliferation of the hamartoma tumor cells.10-16-2014
20140303146Method of Treating Mixed Lineage Leukemia Gene-Rearranged Acute Lymphoblastic Leukemias - The present invention relates to a method of treating a warm-blooded animal, especially a human, having Mixed Lineage Leukemia (MLL rearranged ALL) comprising administering to said animal a therapeutically effective amount of a staurosporine derivative, especially PKC412 or a pharmaceutically acceptable salt thereof, alone or in combination with further therapeutic measures, for example, those defined herein; to the use of a staurosporine derivative for the preparation of a medicament for the treatment of MLL rearranged ALL; and to a commercial package comprising a staurosporine derivative together with instructions for its use in the treatment of MLL rearranged ALL.10-09-2014
20140302042METHODS OF PREDICTING PROGNOSIS IN CANCER - A set of biomarkers (e.g., genes and gene products) that can accurately inform about the risk of cancer progression and recurrence, as well as methods of their use are disclosed.10-09-2014
20140296160STABILIZED ALPHA HELICAL PEPTIDES AND USES THEREOF - Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.10-02-2014
20140249142DISCOVERY OF A SOMATIC MUTATION IN MYD88 GENE IN LYMPHOPLASMACYTIC LYMPHOMA - Diagnostic assays for facilitating the diagnosis of lymphoplasmacytic lymphoma (LPL) are provided. The method comprises assessing a biological sample of the subject for the presence of a mutation at position 38182641 in chromosome 3p22.2, wherein presence of the mutation is indicative that the subject has LPL. Also, provided are targeted therapies, methods for monitoring the progression or recurrence of LPL, and a sensitive and inexpensive real-time allele specific polymerase chain reaction assay for reliable and quantitative assessments of the mutation.09-04-2014
20140242094METHODS RELATED TO TIM 3, A TH1-SPECIFIC CELL SURFACE MOLECULE, FOR ACTIVATING ANTIGEN PRESENTING CELLS - The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.08-28-2014
20140235686ZNF365/ZFP365 Biomarker Predictive of Anti-Cancer Response - The present invention is based on the identification of novel biomarkers predictive of response to anti-cancer therapies.08-21-2014
20140187604THERAPEUTIC AND DIAGNOSTIC TARGET GENE IN ACUTE MYELOID LEUKEMIA - Methods are provided for treating a cancer in a subject comprising administering to the subject an agent which inhibits expression of an HLX gene in the subject, or an agent which inhibits activity of an expression product of the HLX gene, and also for diagnosing a subject as likely to develop a cancer comprising determining whether a stem cell obtained from the subject expresses a HLX gene at a level in excess of predetermined control level. Kits therefor are also provided.07-03-2014
20140187494INHIBITION OF INFLAMMATION USING ANTAGONISTS OF MUC1 - The invention provides for peptides from the MUC1 cytoplasmic domain and methods of use therefor. These peptides can inhibit MUC1 oligomerization, inhibit the interaction of MUC1 with NF-κB or a STAT, and block inflammatory response mediated by NF-κB or STAT signaling.07-03-2014
20140178370METHODS AND COMPOSITIONS FOR THE TREATMENT OF PERSISTENT INFECTIONS AND CANCER BY INHIBITING THE PROGRAMMED CELL DEATH 1 (PD-1) PATHWAY - The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.06-26-2014
20140155399BRAF Mutations Conferring Resistance to BRAF Inhibitors - The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of BRAF. In particular embodiments, the invention concerns mutations in a BRAF sequence that confer resistance to a BRAF inhibitor. Identification of such mutations in a BRAF sequence allows the identification and design of second-generation BRAF inhibitors. Methods and kits for detecting the presence of a mutant BRAF sequence in a sample are also provided.06-05-2014
20140142024BPI AND ITS CONGENERS AS RADIATION MITIGATORS AND RADIATION PROTECTORS - Described herein is a method of mitigating, in a subject (individual), tissue injury resulting from exposure to radiation (accidental/unintentional or intentional, such as therapeutic), chemoradiotherapy, disease, toxin, or drug or biologic mediated therapy.05-22-2014
20140127690Mutation Signatures for Predicting the Survivability of Myelodysplastic Syndrome Subjects - Somatic non-silent mutations on selected biomarkers are reliable indicators for the overall survival of Myelodysplastic Syndrome subjects.05-08-2014
20140113857TARGETING DEREGULATED WNT SIGNALING IN CANCER USING STABILIZED ALPHA-HELICES OF BCL-9 - The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to β-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/β-catenin interaction, and thereby interfering with deregulated Wnt/β-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.04-24-2014
20140107166HISTONE DEACETYLASE INHIBITORS AND METHODS OF USE THEREOF - The present invention provides novel compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of a compound of the invention to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.04-17-2014
20140106362Full COLD-PCR Enrichment with Reference Blocking Sequence - The present invention is directed to methods, compositions and software for enriching low abundance alleles in a sample. It is directed in particular to the use of an excess amount of reference blocking sequence in an amplification reaction mixture in order to improve the enrichment efficiency, and reduce cycle time, of full COLD-PCR.04-17-2014
20140093449Method for Preparing Largazole Analogs and Uses Thereof - Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.04-03-2014
20140072968Novel Genes Encoding Proteins Having Prognostic, Diagnostic, Preventive, Therapeutic, and Other Uses - The invention provides isolated TANGO 509 nucleic acid molecules and polypeptide molecules. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.03-13-2014
20140051087METHODS AND COMPOSITIONS TO ENABLE MULTIPLEX COLD-PCR - The present invention is directed to methods, compositions and reaction mixtures for multiplexing COLD-PCR/ice-COLD-PCR to enrich simultaneously several low abundance alleles (mutant target sequences) from a sample. The invention also involves COLD-PCR/ice-COLD-PCR amplification performed on DNA fragments that have different melting temperatures, and therefore different critical denaturation temperatures, in a graded temperature approach such that mutation enrichment is achieved on all diverse DNA fragments simultaneously (temperature-independent COLD-PCR or TI-COLD-PCR). The invention also involves methods for enabling identification of variant-sequence alleles in the presence of a large excess of non-variant alleles in nucleic acids without the complication of polymerase-introduced errors or other primer-introduced artifacts.02-20-2014
20140050707MIR-150 FOR THE TREATMENT OF BLOOD DISORDERS - The invention provides methods of treating certain blood related disorders, in particular, thrombocytopenia and anemia comprising increasing miR-150 expression or inhibiting miR-150 in progenitor cells respectively.02-20-2014
20140037630METHODS FOR TREATING MICA-RELATED DISORDERS - Disclosed herein are materials and methods for treating cancer. In particular, the compositions and methods for treating cancers associated with MICA overexpression are provided.02-06-2014
20140031383METHODS FOR TREATMENT OF MELANOMA - The present invention is directed to methods for treatment of melanoma using an inhibitor of dihydroorotate dehydrogenase (DHODH) and to combination therapies that involve administering to a subject an inhibitor of oncogenic BRAF (e.g. BRAF(V600E)), as well as an inhibitor of dihydroorotate dehydrogenase (DHODH). Assays for identifying compounds useful for the treatment of melanoma are also provided. The methods herein are directed to screening for compounds or agents that inhibit neural crest progenitor formation in a zebra fish model of melanoma.01-30-2014
20140018302Cancer Therapies and Diagnostics - Compositions and methods for increasing p53-dependent transcriptional activity in a cell.01-16-2014
20140011982Antibodies Against Influenza Virus and Methods of Use Thereof - The invention provides human scFv antibodies and monoclonal antibodies that neutralize influenza virus. Also provided are methods of treating and/or preventing a influenza related disease or disorder such bird flu The invention also provides methods of vaccinating a patient against influenza. Also provided are methods of diagnosing influenza-related diseases or disorders and methods of detecting the presence of a influenza in a sample.01-09-2014
20140011862Compositions and Methods for Treating Leukemia - The invention provides compositions, methods, and kits for the treatment of acute myeloid leukemia in a subject.01-09-2014
20140011748Methods Of Predicting Response To JNK Inhibitor Therapy - This present invention provides methods of treating of accessing/monitoring the responsiveness of a cancer cell to JNK inhibitor therapy.01-09-2014
20140004112Therapeutic Peptides01-02-2014
20130336923Carbonic Anhydrase IX (G250) Antibodies and Methods of Use Thereof - The invention provides scFv antibodies and monoclonal antibodies that bind to and decrease an activity of Carbonic Anhydrase IX (G250). Also provided are methods of treating and/or preventing cancer, such as renal clear cell cancer. Also provided are methods of identifying a carbonic anhydrase IX (G250) protein. The invention additionally provides methods of modifying immune effector cells, and the immune effector cells modified thereby.12-19-2013
20130331455DEACETYLASE INHIBITORS AND USES THEREOF - The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.12-12-2013
20130323744Signatures and Determinants Associated with Cancer and Methods of Use Thereof - The present invention provides methods of detecting cancer using biomarkers.12-05-2013
20130316935METHOD TO DETERMINE RESPONSIVENESS OF CANCER TO EPIDERMAL GROWTH FACTOR RECEPTOR TARGETING TREATMENTS - Disclosed herein are methods and reagents for determining the responsiveness of cancer to an epidermal growth factor receptor (EGFR) targeting treatment. The detection of these mutations will allow for the administration of gefitinib, erlotinib and other tyrosine kinase inhibitors to those patients most likely to respond to the drug.11-28-2013
20130281312METHODS FOR PREDICTING ANTI-CANCER RESPONSE - The present invention is based, in part, on the identification of novel methods for defining predictive biomarkers of response to anti-cancer drugs.10-24-2013
20130267594PROLYL HYDROXYLASE INHIBITORS AS RADIATION MITIGATORS AND RADIATION PROTECTORS - A method to inhibit tissue injury in a subject resulting from exposure to radiation is provided. The method involves administering to the subject a prolyl hydroxylase (PH) inhibitor in an amount effective to inhibit tissue injury caused by radiation exposure of the subject. The invention also involves a screen for PH inhibitors that inhibit tissue damage resulting from exposure to radiation. Compounds that inhibit the enzymatic activity of PHs are tested for their ability to protect against radiation damage.10-10-2013
20130261023SMALL MOLECULE PRINTING - The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support using isocyanate or isothiocyanate chemistry, wherein the density of the array of compounds is at least 1000 spots per cm10-03-2013
20130253005SMALL MOLECULE INHIBITORS OF USP1 DEUBIQUITINATING ENZYME ACTIVITY - Provided are small molecule inhibitors of ubiquitin specific protease 1 (USP1) activity and methods for their use in treating and characterizing cancers. The small molecule USP1 inhibitors of the invention are particularly useful in the treatment of cancers that are resistant to DNA cross-linking agents.09-26-2013
20130243749Humanized Monoclonal Antibodies and Methods of Use - Disclosed is a humanized monoclonal antibody that binds to the human immunoglobulin heavy chain variable region germline gene VHI-69. The antibody is derived from Mab G6 and recognizes the same epitope. Moreover, the antibody is used in combination with vaccines to augment an immune response to the antigen.09-19-2013
20130225432SOLUTION-BASED METHODS FOR RNA EXPRESSION PROFILING - The present invention is directed to novel high-throughput, low-cost, and flexible solution-based methods for RNA expression profiling, including expression of microRNAs and mRNAs.08-29-2013
20130202707Controlled Delivery of TLR Agonists in Structural Polymeric Devices - The present invention comprises compositions, methods, and devices for creating an stimulating an antigen-specific dendritic cell immune response. Devices and methods provide prophylactic and therapeutic immunity to subjects against cancer and infectious agents.08-08-2013
20130184287INDAZOLE COMPOUNDS AND THEIR USES - The present application relates to therapeutic organic compounds, compositions comprising an effective amount of a therapeutic organic compound; and methods for treating and preventing disease comprising administering and effective amount of a therapeutic organic compound to a subject in need thereof.07-18-2013
20130177577NLRC5 AS A TARGET TO INTERVENE MHC CLASS 1-MEDIATED IMMUNE RESPONSES - A method to modulate MHC class I gene expression by modulating NLRC5 expression and/or NLRC5 activity in a subject is provided. The method comprises administering to the subject a compound HLA-A HLA-B that modulates NLRC5 expression and/or NLRC5 activity in an amount effective to modulates MHC class I gene expression. Also described is a screen for compounds that modulate NLRC5 expression. Candidate compounds are tested for their ability to modulate NLRC5 expression.07-11-2013
20130165331CHROMOSOME COPY NUMBER GAIN AS A BIOMARKER OF UROTHELIAL CARCINOMA LETHALITY - Diagnostic assays for medically classifying cancer patients are provided. The method comprises assessing a tissue sample of the patient for the presence of a copy number gain of chromosome regions 1q23.3 and/or 1q21.2. Copy number gain of chromosome regions 1q23.3 and/or 1q21.2 is indicative of a less favorable prognosis as compared to the prognosis if there was no copy number gain in the same regions.06-27-2013
20130157942STABILIZED INSULINOTROPIC PEPTIDES AND METHODS OF USE - The present invention provides stably cross-linked insulionotropic polypeptides having superior and un-expected benefits in the treatment of conditions involving abnormal glucose homeostasis, e.g., type 2 diabetes and conditions relating to type 2 diabetes. Such benefits include, but are not limited to, extended polypeptide half-life, enhanced alpha-helicity, improved thermal stability and protease resistance, increased functional activity and pharmacologic properties, improved bioavailability when administered by any route, and improved bioavailability and gastrointestinal absorption when delivered orally, as compared to the corresponding unmodified polypeptides. The invention also provides compositions for administering the polypeptides of the invention, as well as methods for pre-paring and evaluating the polypeptides of the invention.06-20-2013
20130157294Methods and Compositions for the Diagnosis of Cancer Susceptibilities and Defective DNA Repair Mechanisms and Treatment Thereof - Methods and compositions for the diagnosis of cancer susceptibilities, defective DNA repair mechanisms and treatments thereof are provided. Among sequences provided here, the FANCD2 gene has been identified, and probes and primers are provided for screening patients in genetic-based tests and for diagnosing Fanconi Anemia and cancer. The FANCD2 gene can be targeted in vivo for preparing experimental mouse models for use in screening new therapeutic agents for treating conditions involving defective DNA repair. The FANCD2 polypeptide has been sequenced and has been shown to exist in two isoforms identified as FANCD2-S and the monoubiquinated FANCD-L form. Antibodies including polyclonal and monoclonal antibodies have been prepared that distinguish the two isoforms and have been used in diagnostic tests to determine whether a subject has an intact Fanconi Anemia/BRCA pathway.06-20-2013
20130150259BIOMARKERS FOR THE EARLY DETECTION OF BREAST CANCER - The present invention provides reagents and methods for breast cancer detection.06-13-2013
20130143911MEK1 Mutation Conferring Resistance to RAF and MEK Inhibitors - Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.06-06-2013
20130115221HIFa prolyl hydroxylation assay - Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. The ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is “turned on” only under such conditions.05-09-2013
20130095481METHODS FOR PREDICTING LIKELIHOOD OF RESPONDING TO TREATMENT - The disclosure provides materials and methods related to using biomarkers for prediction of duration of response to prostate cancer treatment and for treating prostate cancer.04-18-2013
20130074199Compositions and Methods for Brown Fat Induction and Activity Using FNDC5 - The invention provides compositions and methods for brown fat induction and activity through modulation of Fndc5 activity and/or expression. Also provided are methods for preventing or treating metabolic disorders in a subject through modulation of Fndc5 activity and/or expression. Further provided are methods for identifying compounds that are capable of modulating Fndc5 activity and/or expression.03-21-2013
20130072485SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF - The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.03-21-2013
20130072392Compositions, Kits, and Methods for Identification, Assessment, Prevention, and Therapy of Cancer - The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.03-21-2013
20130064843Identification of conserved peptide blocks in homologous polypeptides - Methods for identifying at least one conserved peptide block in three or more homologous polypeptides are provided and compositions comprising conserved peptides are provided. More particularly, methods for selecting conserved peptides in variable viral polypeptides for use in immunogenic compositions are provided.03-14-2013
20130059851Methods of Diagnosing and Treating Cancer in Patients Having or Developing Resistance to a First Cancer Therapy - A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2/COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.03-07-2013
20130040998FLUORINATED HDAC INHIBITORS AND USES THEREOF - Fluorinated deacetylase inhibitors of the general formulae (I), (II), and (III): and pharmaceutically acceptable salts thereof, as described herein, are useful as inhibitors of histone deacetylases or other deacetylases, and thus are useful for the treatment of various diseases and disorders associated with acetylase activity as described herein (e.g., cancer, neurodegenerative diseases, inflammatory diseases).02-14-2013
20130040949TYPE II RAF KINASE INHIBITORS - The present invention relates to novel compounds which are able to modulate b-raf kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.02-14-2013
20130040853Context Specific Genetic Screen Platform to Aid in Gene Discovery and Target Validation - The present invention relates to a context-specific forward genetic screen designed to systematically assign relative weight of biological evidence to a library of high-probability driver genetic elements in a genetically defined cancer-sensitized model system whose constellation of engineered mutations reflects a particular clinically relevant genetic subclass of a given tumor type. The screen may be formed in vivo or ex vivo. The screen allows for the formulation of clinical path hypotheses for targeting driver genetic elements and, in parallel, the rapid functional validation of the role of the driver genetic element(s) in the cancer. In this manner, the context-specific genetic screen can systematically assign the biological relevance of a library of genetic elements to a clinically-definable genetic and disease context, as well as inform combinations of drugs in the clinic such one uses one drug that targets the newly discovered genetic element or its protein and another drug that targets those genetic elements or its associated proteins which have been engineered into the primary cell model.02-14-2013
20130039895MIR-150 FOR THE TREATMENT OF BLOOD DISORDERS - The invention provides methods of treating certain blood related disorders, in particular, thrombocytopenia and anemia comprising increasing miR-150 expression or inhibiting miR-150 in progenitor cells respectively.02-14-2013
20130019326Compositions, Kits, and Methods for Identification, Assessment, Prevention, and Therapy of Metabolic Disorders - The invention provides methods and compositions for selectively promoting anti-metabolic disorder activity over classical PPAR gamma activation through modulation of PPAR gamma phosphorylation (e.g., Ser-273 phosphorylation of murine peroxisome proliferator activated receptor gamma (PPAR gamma) 2 or a corresponding serine residue in a murine PPAR gamma 2 homolog, including a human). Also provided are methods for preventing, treating, or predictiving responsiveness of therapies for metabolic disorders in a subject through selective inhibition of such PPAR gamma phosphorylation. Further provided are methods for identifying compounds that are capable of modulating such PPAR gamma phosphorylation.01-17-2013
20130018103BIFUNCTIONAL HISTONE DEACETYLASE INHIBITORS - In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.01-17-2013
20130011409Compositions, Kits, and Methods for the Diagnosis, Prognosis, Monitoring, Treatment and Modulation of Post-Transplant Lymphoproliferative Disorders and Hypoxia Associated Angiogenesis Disorders Using Galectin-1 - The present invention is based, in part, on the discovery that galectin-1 (Gal1) plays a role in viral-associated PTLD, e.g., EBV-associated PTLD and hypoxia associated angiogenesis disorders. Accordingly, the invention relates to compositions, kits, and methods for diagnosing, prognosing, monitoring, treating and modulating viral-associated PTLD, e.g., EBV-associated PTLD and hypoxia associated angiogenesis disorders.01-10-2013
20120328641CONFORMATIONALLY STABILIZED HIV ENVELOPE IMMUNOGENS - Stabilized forms of gp120 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gp120, and gp120 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.12-27-2012
20120315286COMPOSITIONS AND METHODS RELATED TO TIM 3, A TH1-SPECIFIC CELL SURFACE MOLECULE - The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.12-13-2012
20120315283METHODS OF PROMOTING TISSUE GROWTH AND TISSUE REGENERATION - Described herein are methods of using soluble epoxide hydrolase inhibitors to modulate the levels of epoxyeicosatrienoic acids (EETs) in order to increase angiogenesis and promote wound healing and tissue regeneration.12-13-2012
20120295807CHROMOSOME COPY NUMBER GAIN AS A BIOMARKER OF UROTHELIAL CARCINOMA LETHALITY - Diagnostic assays for medically classifying cancer patients are provided. The method comprises assessing a tissue sample of the patient for the presence of a copy number gain of chromosome regions 1q23.3 and/or 1q21.2. Copy number gain of chromosome regions 1q23.3 and/or 1q21.2 is indicative of a less favorable prognosis as compared to the prognosis if there was no copy number gain in the same regions.11-22-2012
20120282258CRLF2 IN PRECURSOR B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA - The invention relates to cytokine receptor-like factor 2 (CRLF2), and particularly certain mutant forms of CRLF2, as prognostic and therapeutic targets in precursor B-cell acute lymphoblastic leukemia (B-ALL). Mutant CRLF2 with a Phe232-Cys (F232C) mutation is overexpressed and constitutively activates STAT5 in a subset of B-ALL patients with particularly poor prognosis. Methods and compositions useful for identifying, inhibiting expression, and inhibiting activity of the mutant CRLF2 are provided. Also provided are methods and compositions useful for treating B-ALL.11-08-2012
20120264794Method for Preparing Largazole Analogs and Uses Thereof - Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.10-18-2012
20120264627Oligonucleotide Array For Tissue Typing - Oligonucleotide-based microarrays for tissue typing (e.g., HLA tissue typing) are provided. More particularly, the microarrays are high resolution arrays useful for diagnostic evaluations and determining donor/recipient transplant compatibility.10-18-2012
20120258886PROTECTED AMINE LABELS AND USE IN DETECTING ANALYTES - The invention is directed towards novel amino acid based compounds, which may be isotopically enriched, and methods of use of such compounds for characterising one or more molecules of a sample by mass spectrometry, the method comprising: (a) reacting the one or more molecules with the compound; and (b) characterising the one or more molecules by mass spectrometry.10-11-2012
20120251537COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFECTIONS AND TUMORS - PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.10-04-2012
20120238460RANTES LEVELS AS A DIAGNOSTIC AND THERAPEUTIC FOR ACUTE GRAFT VERSUS HOST DISEASE - Disclosed herein are methods for determining the likelihood of a subject to develop Acute graft versus host disease (aGVHD) upon receiving myeloablative allogeneic hematopoietic stem cell transplantation (HSCT). One such method comprises assaying for baseline plasma concentration of RANTES in a sample obtained from the subject, and comparing the baseline plasma concentration of RANTES to a predetermined level. The method may further comprise assaying for day 7 plasma concentration of RANTES in sample obtained from the subject, and comparing the day 7 plasma concentration of RANTES to a predetermined level. Another such method comprises assaying for day 7 plasma concentration of RANTES in a sample obtained from the subject, and comparing the day 7 plasma concentration of RANTES to a predetermined level. Another such method comprises assaying for donor plasma concentration of RANTES in a sample obtained from a donor of the hemtopoietic stem cells, and comparing the donor plasma concentration of RANTES to a predetermined level, wherein a donor plasma concentration of RANTES less than the predetermined level indicates a likelihood of the subject to develop aGVHD upon receiving myeloablative allogeneic HSCT from that donor. Other methods include assaying for day 0, or for day 7, plasma concentration of MCP-1 in a sample obtained from the subject, and comparing the day 0 or day 7, plasma concentration of MCP-1 to a predetermined level.09-20-2012
20120214757Methods and Compositions for Treating Cancer Using Proteasome Inhibitors - The present invention relates to therapeutic compositions for treating cancer or preventing the growth of cancer cells, e.g., tumor growth, in a subject. The present invention also relates to methods for treating cancer, e.g., inhibiting tumor growth, in a subject who has become resistant to treatment, by administering to a subject an effective amount of a proteasome inhibitor and an effective amount of a therapeutic agent, e.g., a chemotherapeutic agent. The present invention further relates to methods for purging bone marrow, i.e., removing cancer cells from bone marrow, by exposing the bone marrow cells to a proteasome inhibitor and a therapeutic agent, e.g., a chemotherapeutic agent.08-23-2012
20120167240Compositions and Methods for Modulating PGC-1Alpha to Treat Neurological Diseases and Disorders - The present invention provides methods for modulating mitochondrial function, modulating lesion formation in the brain, modulating neurite growth, modulating neuronal degeneration, and treating and preventing neurological diseases or disorders comprising modulating the expression of activity of PGC-1α. The present invention also provides an animal, e.g., transgenic mouse, in which the PGC-1α gene is misexpressed. Methods for identifying compounds which are capable of treating or preventing a neurological disease or disorder are also described.06-28-2012
20120148594MIMOTOPES OF HIV AND USES THEREOF - The invention provides methods, compositions and kits for treating and or preventing diseases having immunological components associated with their etiology and/or progression (e.g., an HIV infection). A mimotope that mimics an epitope of an antigen may be administered to an individual to induce or enhance an immune response for the treatment of a disease. For example, HIV envelope-like polypeptides (wild-type HIV polypeptides and mimotopes) may be administered to an individual so as to induce a protective immune response to HIV. Alternatively, antibodies directed to a mimotope may be administered to an individual to treat or prevent a disease. Antibodies directed to HIV envelope-like polypeptides may be administered to an individual to treat or prevent an HIV infection and/or one or more symptoms associated with the infection (e.g., AIDS). In another embodiment, the invention provides compositions and methods for isolating an epitope specific B cell.06-14-2012
20120141527STRUCTURED VIRAL PEPTIDE COMPOSITIONS AND METHODS OF USE - The invention provides structurally constrained viral peptides for use as therapeutic and vaccination agents, and for the production of antibodies for use in a number of applications including as therapeutic agents. The invention further provides methods and kits for use of the structurally constrained peptides and antibodies of the instant invention. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.06-07-2012
20120128684Conserved Hemagglutinin Epitope, Antibodies to the Epitope and Methods of Use - Disclosed are antibodies that bind to the stem region of influenza hemagglutinin in the neutral pH conformation, hemagglutinin epitopes in the stem region, and methods of making and using both.05-24-2012
20120122991METHOD FOR TREATING CANCER BY INCREASING AMP-ACTIVATED KINASE ACTIVITY - The invention relates to modulation of LKB1 or AMP kinase protein activity for treating disorders including diabetes and cancer. The invention also relates to screening for agents that modulate the activity of LKB1 or AMP kinase protein, which are useful in the treatment of diabetes and cancer, as well as preparing compounds for treatment of diabetes and cancer.05-17-2012
20120122834SMALL MOLECULE CD4 MIMETICS AND USES THEREOF - The invention provides for compounds of formula I: wherein Z is absent or (CR05-17-2012
20120094999EGFR INHIBITORS AND METHODS OF TREATING DISORDERS - The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Her-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.04-19-2012
20120094293PGC-1 , A NOVEL PGC-1 HOMOLOGUE AND USES THEREFOR - The invention provides isolated nucleic acid molecules, designated PGC-1β nucleic acid molecules, which encode novel PGC-1 related coactivator molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1β nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1β gene has been introduced or disrupted. The invention still further provides isolated PGC-1β proteins, fusion proteins, antigenic peptides and anti-PGC-1β antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.04-19-2012
20120088766FUSED HETEROCYCLIC COMPOUNDS AND THEIR USES - The present application relates to therapeutic organic compounds, compositions comprising an effective amount of a therapeutic organic compound; and methods for treating and preventing disease comprising administering and effective amount of a therapeutic organic compound to a subject in need thereof.04-12-2012
20120082643Compositions and Methods for Modulating a Cytotoxic T Lymphocyte Immune Response - The present invention provides compositions and methods for the treatment and prevention of immune disorders.04-05-2012
20120022500Compositions and Methods for Induced Brown Fat Differentiation - The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of both Prdm1β and C/EBPβ activity and/or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of both Prdm1β and C/EBPβ expression and/or activity. Further provided are methods for identifying compounds that are capable of modulating both Prdm1β and C/EBPβ expression and/or activity.01-26-2012
20120015973MEK MUTATIONS CONFERRING RESISTANCE TO MEK INHIBITORS - The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of MEK. In particular embodiments, the invention concerns mutations in a MEK sequence that confer resistance to a MEK inhibitor. Identification of such mutations in a MEK sequence allows the identification and design of second-generation MEK inhibitors. Methods and kits for detecting the presence of a mutant MEK sequence in a sample are also provided.01-19-2012
20110318352COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS - The invention provides compositions, kits and methods utilizing polypeptides having a viral alpha-helix heptad repeat domain in a stabilized a-helical structure (herein also referred to as SAH). The compositions are useful for treating and/or preventing viral infections. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled alpha helical peptides display excellent proteolytic, acid, and thermal stability, restore the native alpha-helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.12-29-2011
20110312908SMALL MOLECULE MYRISTATE INHIBITORS OF BCR-ABL AND METHODS OF USE - The present invention provides novel heteroaryl compounds that are linked to an aryl group via an amine linker. Such compounds are useful for the treatment of cancers.12-22-2011
20110312514Method For Determination And Quantification Of Radiation Or Genotoxin Exposure - The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.12-22-2011
20110311536PREVENTION OF TYPE 1 DIABETES BY TREG VACCINATION WITH AN INSULIN MIMETOPE - The invention involves methods and products for inducing Treg cells for immune suppression in connection with autoimmune disease and transplant rejection.12-22-2011
20110311535NKG2D-FC FOR IMMUNOTHERAPY - Methods for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising an NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands.12-22-2011
20110293637COMPOSITIONS AND METHODS OF IDENTIFYING TUMOR SPECIFIC NEOANTIGENS - The present invention related to immunotherapeutic peptides and their use in immunotherapy, in particular the immunotherapy of cancer. Specifically, the invention provides a method of identifying tumor specific neoantigens that alone or in combination with other tumor-associated peptides serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor responses.12-01-2011
20110288091SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF - The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.11-24-2011
20110275697REGULATION OF CYCLIN D - The present invention provides methods for modulating the level or activity of cyclin D by inhibiting EGLN2 expression or activity. The methods are particularly useful for treating or preventing a disorder associated with elevated cyclin D levels or activity, such as cancer.11-10-2011
20110271358HUMAN ANTI-PD-1, PD-L1, AND PD-L2 ANTIBODIES AND USES THEREFOR - The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-L1, and/or PD-L2 activity (e.g., persistent infectious diseases, autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein.11-03-2011
20110265197Signatures and PCDeterminants Associated with Prostate Cancer and Methods of Use Thereof - The present invention provides methods of detecting cancer using biomarkers.10-27-2011
20110263693CELASTROL, GEDUNIN, AND DERIVATIVES THEREOF AS HSP90 INHIBITORS - Based on the discovery that celastrol and gedunin are Hsp90 inhibitors, the present invention provides novel inhibitors of Hsp90. and pharmaceutically acceptable salts, derivatives, and compositions thereof. The invention provides two classes of compounds. One class includes celastrol and its derivatives. The other class includes gedunin and its derivatives. The present invention further provides methods for treating disorders wherein Hsρ90 inhibition is desired (e.g., proliferative diseases, cancer, inflammatory diseases, fungal infections, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. Celastrol, gedunin, and derivatives thereof are particularly useful in the treatment of prostate cancer, breast cancer, ovarian cancer, lung cancer, and leukemia.10-27-2011
20110260105NUCLEIC ACID NANOTUBE LIQUID CRYSTALS AND USE FOR NMR STRUCTURE DETERMINATION OF MEMBRANE PROTEINS - Compositions and methods for preparing nucleic acid nanotubes using DNA origami techniques are described, which provide for nanotubes of predictable and uniform length. The nucleic acid nanotubes thus formed are suitable as liquid crystal preparations enabling liquid-crystal NMR spectroscopy of proteins solubilized in detergent.10-27-2011
20110257036Methods and Compositions for the Diagnosis of Cancer Susceptibilities and Defective DNA Repair Mechanisms and Treatment Thereof - Methods and compositions for the diagnosis of cancer susceptibilities, defective DNA repair mechanisms and treatments thereof are provided. Among sequences provided here, the FANCD2 gene has been identified, and probes and primers are provided for screening patients in genetic-based tests and for diagnosing Fanconi Anemia and cancer. The FANCD2 gene can be targeted in vivo for preparing experimental mouse models for use in screening new therapeutic agents for treating conditions involving defective DNA repair. The FANCD2 polypeptide has been sequenced and has been shown to exist in two isoforms identified as FANCD2-S and the monoubiquinated FANCD-L form. Antibodies including polyclonal and monoclonal antibodies have been prepared that distinguish the two isoforms and have been used in diagnostic tests to determine whether a subject has an intact Fanconi Anemia/BRCA pathway.10-20-2011
20110243910 MAMMALIAN RNA DEPENDENT RNA POLYMERASE - The invention provides compositions comprising a TERT-RMRP or TERT-RNA complex and methods of treating subjects with genetic diseases in which gene silencing is either increased by administering the compositions of the invention or decreased by administering an inhibitor of the RNA-dependent RNA polymerase (RdRP) activity of these compositions. Moreover, the invention provides methods of screening for agonists and antagonists of RdRP activity and TERT-RMRP complex formation. Finally, the invention provides a method of identifying a RNA molecule that forms a complex with a TERT polypeptide and has RdRP activity.10-06-2011
20110218155CHEMICAL MODULATORS OF PRO-APOPTOTIC BAX AND BCL-2 POLYPEPTIDES - The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 family polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an α1 helix, α2 helix, a loop between α1-α2, α.6 helix, and select residues of α4, α.5, and α.8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta-loop, or combination thereof.09-08-2011
20110217714Full Cold-PCR Enrichment with Reference Blocking Sequence - The present invention is directed to methods, compositions and software for enriching low abundance alleles in a sample. It is directed in particular to the use of an excess amount of reference blocking sequence in an amplification reaction mixture in order to improve the enrichment efficiency, and reduce cycle time, of full COLD-PCR.09-08-2011
20110207656MUC1, CASPASE-8, and DED-CONTAINING PROTEINS - The disclosure features a variety of compositions and methods for modulating an interaction between MUC1 and caspase-8 and/or an interaction between MUC1 and a DED-containing protein (e.g., an anti-apoptotic DED-containing protein or a pro-apoptotic DED-containing protein). Such methods and compositions are useful for the treatment or prevention of, e.g., a variety of pathological disorders characterized by elevated or decreased levels of apoptosis. Moreover, the compositions and methods are also useful to identify, design, and generate compounds that modulate the interactions. The compounds and/or pharmaceutical compositions containing the compounds can be used in the treatment of disease.08-25-2011
20110206689Molecular Determinants Associated With Prostate Cancer And Methods Of Use Thereof - The present invention provides methods of treating cancer by inhibiting pserine threonine kinase activity and detecting cancer using biomarkers.08-25-2011
20110190374METHODS OF TREATING A MEIOTIC KINESIN ASSOCIATED DISEASE - The invention provides methods of treating a meiotic kinase-associated disease, preferably the meiotic kinase HSET, by administering an inhibitor of the meiotic kinase. Preferably, the disease is associated with the presence of supernumerary centrosomes, such as cancer. Methods of inhibiting the growth of a tumor cell by contacting the cell with an inhibitor of a meiotic kinase, preferably HSET, are also provided. Screening methods for identifying inhibitors of the meiotic kinase HSET are also provided. Methods of selecting subjects for treatment with an inhibitor of a meiotic kinase, such as HSET, are also provided.08-04-2011
20110182881SIGNATURE AND DETERMINANTS ASSOCIATED WITH METASTASIS AND METHODS OF USE THEREOF - The present invention provides methods of detecting cancer using biomarkers.07-28-2011
20110172303DEACETYLASE INHIBITORS AND USES THEREOF - The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.07-14-2011
20110172288Compositions and Methods for the Identification, Assessment, Prevention and Therapy of Thymic Lymphoma or Hamartomatous Tumours - The subject matter relates to newly discovered nucleic acid molecules and proteins associated with thymic lymphoma and hamartomatous tumors. Compositions and methods for detecting, characterizing, preventing, and treating human thymic lymphoma and hamartomatous tumors are provided.07-14-2011
20110171210HUMANIZED MONOCLONAL ANTIBODIES AND METHODS OF USE - The present invention comprises a humanized monoclonal antibody that binds to the chemokine receptor CCR4. This antibody is derived from Mab 1567 and recognizes the same epitope. Binding of the invented antibody to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. Moreover, the antibody is used in combination with vaccines to suppress the activity of regulatory T cells.07-14-2011
20110159021XBP1, CD138, AND CS1 PEPTIDES - The disclosure features, inter alia, immunogenic XBP1-, CD138-, and CS1-derived peptides (and pharmaceutical compositions thereof). The peptides can be used in a variety of methods such as methods for inducing an immune response, methods for producing an antibody, and methods for treating a cancer (e.g., a plasma cell disorder such as multiple myeloma or Waldenstrom's macroglobulinemia). The peptides can also be included in MHC molecule multimer compositions and used in, e.g., methods for detecting a T cell in a population of cells.06-30-2011
20110154522BH3 Peptides And Method Of Use Thereof - The invention provides peptides and the nucleic acid sequences that encode them. The invention further provides therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of apoptosis associated disorders.06-23-2011
20110150845METHODS AND COMPOSITIONS FOR MODULATING IMMUNOLOGICAL TOLERANCE - The invention provides compositions and methods for modulating immune responses using mesenchymal stem cells. The invention further provides methods for inducing tolerance to self antigens using mesenchymal stem cells.06-23-2011
20110144107COMPOUNDS AND COMPOSITIONS USEFUL FOR THE TREATMENT OF MALARIA - The invention provides a class of compounds of formula I, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.06-16-2011
20110142854COMPOSITIONS AND METHODS FOR INHIBITION OF RETROVIRUSES - Described herein are methods and compositions for the inhibition of retroviral integration and replication. The methods and compositions inhibit the activity of one or more components of the SET complex or base excision repair enzymes and induce autointegration of retroviral double-stranded nucleic acid.06-16-2011
20110135691IMMUNOMODULATION BY IAP INHIBITORS - The present invention is directed to immune adjuvants containing IAP inhibitors, including Smac mimetics. The invention further provides pharmaceutical compositions and vaccines containing an IAP inhibitor and an antigen. Methods of enhancing an immune response by administration of an IAP inhibitor, methods of treating or preventing cancer, methods of treating or preventing infections, methods of treating autoimmune disorders, and methods of potentiating cytokine or antibody production are also provided.06-09-2011
20110091375USE OF THE COMBINATION COMPRISING TEMOZOLOMIDE AND TNF-ALPHA FOR TREATING GLIOBLASTOMA - Disclosed are methods of synergistically inhibiting growth of a glioma cell comprising contacting the cell with temozolomide and TNFα, or with temozolomide, TNFα, and radiation. Also disclosed are methods of synergistically inhibiting growth of a glioma in a human cancer patient comprising administering temozolomide and TNFα, or with temozolomide, TNFα, and radiation. Pharmaceutical combinations and therapeutic combinations suitable for use in the methods of the invention are also disclosed.04-21-2011
20110059051Molecular Control of Brown Fat Differentiation and Engergy Expenditure - The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of Prdm 16 activity or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of Prdm 16 expression or activity. Further provided are methods for identifying compounds that are capable of modulating Prdm 16 expression or activity.03-10-2011
20110054001CHK1 SUPPRESSES A CASPASE-2 APOPTOTIC RESPONSE TO DNA DAMAGE THAT BYPASSES P53, BCL-2 AND CASPASE-3 - The invention describes methods that are useful for treating cancer by administering a Chk1 inhibitor which can induce apoptosis in p53-defective cells when combined with a chemotherapy and/or radiotherapy. Methods for screening candidates for a Chk1 inhibitor-based cancer treatment regimen are also described.03-03-2011
20110033522REAGENTS FOR INDUCING AN IMMUNE RESPONSE - The present disclosure relates to reagents (antigenic and/or immunogenic reagents) and kits that are useful in a variety of in vitro, in vivo, and ex vivo methods including, e.g., methods for inducing an immune response, or for generating an antibody, in a subject. The reagents described herein can be used in the treatment or prevention of HIV-1 infections. In addition, the disclosure provides methods and compositions useful for designing (or identifying) an agent that binds to an membrane proximal external region (MPER) of an HIV-1 gp160 polypeptide or an agent that inhibits the fusion of an HIV-1 particle to a cell.02-10-2011
20110015080Solution-based methods for RNA expression profiling - The present invention is directed to novel high-throughput, low-cost, and flexible solution-based methods for RNA expression profiling, including expression of microRNAs and mRNAs.01-20-2011
20100330599INHIBITORS OF USP1 DEUBIQUITINATING ENZYME COMPLEX - The invention provides compositions and methods used to inhibit USP1 deubiquitinase activity and to identify new inhibitors of USP1 deubiquitinase. The inhibitors can be used to treat or prevent cancer, bone marrow failure, and damage to cells or DNA resulting from genotoxic agents such as antineoplasic agents, including chemotherapeutic agents and radiation. The inhibitors include siRNA directed at inhibiting the expression of USP1 or UAF1, a protein which forms a heterodimeric complex with USP1. The inhibitors can be used to enhance cell survival if administered either before or after radiation exposure. Methods are also provided to enhance chemotherapy or radiotherapy of cancer and to enhance DNA repair. Transgenic knockout animals and knockdown cells are provided, whose USP1 expression is impaired.12-30-2010
20100298158Compositions, Kits, and Methods for Identification, Assessment, Prevention, and Therapy of Cancer - The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.11-25-2010
20100273158HIN-1, A Tumor Suppressor Gene - The invention encompasses isolated DNAs encoding HIN-1 polypeptides, vectors containing such DNAs, cells containing the vectors, and isolated HIN-1 polypeptides. The invention also features methods of making and using HIN-1 polypeptides.10-28-2010
20100196891IBC-1 (Invasive Breast Cancer-1), a Putative Oncogene Amplified in Breast Cancer - This invention encompasses antibodies specific for IBC-1 (Invasive Breast Cancer-1), methods for diagnosis and prognosis of metastatic breast cancer and degenerative neural conditions, methods of identifying and manufacturing therapeutic compounds, and methods of treating patients with invasive and metastatic breast cancer or degenerative neural conditions.08-05-2010
20100183658Novel Compounds for Enhancing MHC Class II Therapies - The invention provides classes of novel compounds that accelerate peptide loading to DR in the absence of DM and related pharmaceutical compositions. The invention also provides conjugates of these compounds with peptides, antigens or other MHC-based therapeutics, including peptides that self-catalyze their loading onto MHC Class II molecules. Methods are provided for modulating an immune response in a subject. Also disclosed are methods of using the novel compounds, e.g., in combination with MHC-based therapeutics, for the treatment of autoimmune diseases and for the manufacture of medicaments. Methods of improving loading of viral peptides and tumor peptides for enhancing the CD4 T cell response following vaccination against viruses or tumors, and related vaccines, are also provided.07-22-2010
20100129438Methods and Compositions for the Treatment and Prevention of HIV Infection Using TRIM5ALPHA - The invention provides novel TRIM polypeptides, proteins, and nucleic acid molecules. In addition to isolated, full-length TRIM proteins, the invention further provides isolated TRIM fusion proteins, antigenic peptides and anti-TRIM antibodies. The invention also provides TRIM nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which an TRIM gene has been introduced or disrupted. The present invention also provides methods and compositions for the diagnosis and treatment of viral infection and/or replication, e.g., HIV infection. The invention further provides methods for identifying a compound capable of treating or preventing viral infection and/or replication, e.g., HIV infection and AIDS. In addition, the invention provides a method for treating a subject having a viral infection and/or replication, e.g., HIV infection using the modulators of the invention.05-27-2010
20100098683MUC1 and Galectin-3 - The invention provides methods of identifying and making compounds that inhibit the interaction between MUC1 and galectin-3. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction and of inhibiting the expression of galectin-3 by a cell.04-22-2010
20100087358NOTCH mutations leading to increased receptor signaling - The present invention is based upon the identification of regions within the NOTCH-1 receptor that, when mutated, lead to increase receptor signaling. The mutations are associated with uncontrolled cellular growth and this growth may be arrested using agents that interfere with NOTCH-1 activity, such as inhibitors of gamma-secretase. Assays for the NOTCH-1 mutations may be used diagnostically or as part of a treatment regimen for cancer patients.04-08-2010
20100056467COMBINATION OF IAP INHIBITORS AND FLT3 INHIBITORS - The present invention relates to methods of treating hematological malignancies, including acute myeloid leukemia (AML), comprising the combination of a compound that inhibits the binding of the Smac protein to IAPs (“IAP inhibitor”) and one or more pharmaceutically active agents; pharmaceutical compositions comprising said combination; and a commercial package comprising said combination. The present invention also relates to the use of IAP inhibitors in combination with one or more pharmaceutically active agents for the preparation of a medicament to treat hematological malignancies, including AML.03-04-2010
20100041996Ultrasound Probe - An ultrasound probe for cavity scanning of a body, comprising: an elongated rod-like member (02-18-2010
20100034800COMPOSITIONS FOR DETECTING CELL DEATH AND METHODS OF USE THEREOF - The invention provides compounds and methods of their use in the detection of apoptosis and necrosis both in vitro and in vivo. Also provided are compounds and methods of their use in selective delivery of agents to cells undergoing apoptosis or necrosis. The compounds and methods are based on conjugates formed with a dehydrogenase such as lactate dehydrogenase, alcohol dehydrogenase, aldehyde dehydrogenase, and malate dehydrogenase. The compounds and methods are useful in the diagnosis and treatment of conditions characterized by apoptosis, including cancer, cardiac disease, neurologic disease including stroke, and autoimmunity. The compounds and methods offer distinct advantages over corresponding compounds and methods based on Annexin V. Also provided are methods for screening for compounds that modulate, i.e., inhibit or promote, apoptosis.02-11-2010
20100029731Method for preparing largazole analogs and uses thereof - Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.02-04-2010
20090297536Compositions, kits, and methods for identification, assessment, prevention and therapy of cancer - The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.12-03-2009
20090297525Compositions, kits and methods for identification, assessment, prevention and therapy of cancer - The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.12-03-2009
20090280478GENE METHYLATION AND EXPRESSION - The invention provides a method of analyzing the methylation status of all or part of an entire genome. Moreover, the invention features methods of and reagents for characterizing biological cells containing DNA that is susceptible to methylation. Such methods include methods of diagnosing cancer, e.g., breast cancer.11-12-2009
20090202493MIR-150 FOR THE TREATMENT OF BLOOD DISORDERS - The invention provides methods of treating certain blood related disorders, in particular, thrombocytopenia and anemia comprising increasing miR-150 expression or inhibiting miR-150 in progenitor cells respectively.08-13-2009
20090191182Compositions, Kits, and Methods for the Modulation of Immune Responses Using Galectin-1 - The present invention is based, in part, on the discovery that galectin-1 (Gal1) plays a role in immune disorders, including Hodgkin lymphoma. Accordingly, the invention relates to compositions, kits, and methods for detecting, characterizing, modulating, preventing, and treating immune disorders, e.g., Hodgkin lymphoma.07-30-2009
20090176223Compositions, Kits, and Methods for the Diagnosis, Prognosis, and Monitoring of Immune Disorders Using Galectin-1 - The present invention is based, in part, on the discovery that galectin-1 (Gal1) plays a role in immune disorders, including Hodgkin lymphoma, anaplastic large cell lymphoma, or MLL07-09-2009
20090170079Regulation of RUNX1 for Treatment of Pain - Methods are provides for identifying candidate agents for use in inhibiting expression of certain receptors and ion channels in nociceptors. Also provided are methods for identifying candidates agents for use in inhibiting neurophathic and other types of pain.07-02-2009
20090136521Method for Selectively Depleting Hypoxic Cells - An improved method for selectively depleting hypoxic cells within the bone marrow is disclosed. The method can be used to enhance engraftment of hematopoietic stem cells (HSCs) in the bone marrow of a host subject. Also disclosed is a method for treating a cancer within the bone marrow of a host subject.05-28-2009
20090110687COMPOSITIONS AND METHODS RELATED TO TIM 3, A TH1-SPECIFIC CELL SURFACE MOLECULE - The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.04-30-2009
20090104618Psoriasin Expression By Breast Epithelial Cells - The invention features methods of diagnosing high grade ductal carcinoma in situ (DCIS) These methods involve measuring: (1) the level of HID-5 in a body fluid (e.g., blood or urine) of a subject suspected of having, or at risk of having, high grade DCIS; or (2) the level of HID-5 gene expression in breast tissue from a subject suspected of having, or at risk of having, high grade DCIS. The invention also embodies a method of inhibiting expression of HID-5 protein in DCIS cells and methods of treating a subject suspected of having, or at risk of having, high grade DCIS.04-23-2009
20090098569Novel PGC-1 Isoforms and Uses Therefor - The invention provides isolated nucleic acid molecules, designated PGC-1b and PGC-1c nucleic acid molecules, which encode novel isoforms of PGC-1 family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic methods utilizing compositions of the invention are also provided.04-16-2009
20090047675Compositions and methods for indentifying transforming and tumor suppressor genes - Provided herein are nucleic acids, proteins, vectors, cells, kits, devices and methods useful for identifying regulatable proteins that are able to complement components of cellular signaling pathways. Also provided are compositions and methods using these complementing genes directly as markers for cancer diagnosis or prognosis and as targets for anti-neoplastic therapeutics. Further provided are methods for using changes caused by expression of the complementing genes to indirectly identify associated genes to be used as markers for cancer diagnosis or prognosis and as targets for anti-neoplastic therapeutics.02-19-2009
20090008543MASS SPECTROSCOPY SYSTEM AND METHOD INCLUDING AN EXCITATION GATE - An ion extraction method and system includes: i) confining ions within an ion trap extending along a longitudinal axis; ii) exciting a subset of the ions to cause them to oscillate along at least one transverse coordinate; iii) after the transverse excitation, applying a first field and a second field in the region of the transverse excitation to move the excited ions towards one end of the ion trap and extract at least some of the excited ions at the end of the ion trap.01-08-2009
20080307537Compositions and Methods for the Identification, Assessment, Prevention, and Therapy of Neurological Diseases, Disorders and Conditions - A material comprising a plurality of closed cells is provided, the space within each cell being substantially evacuated. This may be achieved by sealing a dimpled film to a sealing film in a vacuum so that each dimple is closed while under vacuum to form an evacuated closed cell.12-11-2008
20080286264Modulation of Muc1 Activity - The invention provides methods of identifying and making compounds that inhibit the interaction between MUC1 and either p53 or TBP. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction and of inhibiting the expression of MUC1 by a cell.11-20-2008
20080274490PD-1, a receptor for B7-4, and uses therefor - Disclosed is a method for modulating an immune response by modulating signaling via PD-1. The immune response may be downregulated by increasing signaling via PD-1, or may be upregulated by decreasing signaling via PD-1. Agents which are useful for stimulating signaling via PD-1 to downregulate an immune response include an activating antibody that recognizes PD-1, a form of B7-4 that binds to an inhibitory receptor, and a small molecule that binds to PD-1. Agents which are useful for inhibiting signaling via PD-1 to upregulate an immune response include a blocking antibody that recognizes PD-1, a non-activating form of B7-4, an antibody that recognizes B7-4, and a soluble form of PD-1. Also disclosed is a method for modulating the interaction of B7-4 with an inhibitory receptor on an immune cell. The method comprises contacting an antigen presenting cell which expresses B7-4 with an agent such as a form of B7-4, a form of PD-1, or an agent that modulates the interaction of B7-4 and PD-1. Also disclosed is a method for inhibiting activation of an immune cell via a non-apoptotic mechanism by increasing the activity or expression of PD-1 in the immune cell. The disclosed methods for modulating an immune response are useful, for instance as therapeutic treatment of a subject with conditions that would benefit from immune response modulation. For instance, a condition such as a tumor, a neurological disease, or an immunosuppressive disease, would be treated by upregulating an immune response, and conditions such as a transplant, an allergy, or an autoimmune disorder would benefit from downregulation of an immune response. Assays for identifying compounds which modulate the activity of, or signaling via, B7-4, or PD-1, especially which modulate the binding of B7-4 or PD-1 to a target molecule are also disclosed. Further disclosed are a vaccine and also other compositions which contain agents that modulate signaling via PD-1.11-06-2008
20080262093Methods and Compositions for Treating Obesity - The present invention relates to therapeutic compositions for treating or preventing obesity and obesity-related disorders in a subject. The present invention also relates to the use of PGC-1 expression levels to determine the safe dosage range for known or putative respiration uncoupling agents for use as anti-obesity therapeutics. The present invention further relates to methods for identifying new compounds that have respiration uncoupling activity.10-23-2008
20080261224PGC-1Beta, A Novel PGC-1 Homologue and Uses Therefor - The invention provides isolated nucleic acid molecules, designated PGC-1β nucleic acid molecules, which encode novel PGC-1 related coactivator molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1β nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1β gene has been introduced or disrupted. The invention still further provides isolated PGC-1β proteins, fusion proteins, antigenic peptides and anti-PGC-1β antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.10-23-2008

Patent applications by DANA-FARBER CANCER INSTITUTE, INC.

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