Abstract: In one aspect, the invention relates to novel substituted 2-alkyl-1-oxo-N-phenyl-3-heteroaryl -1,2,3,4-tetrahydroisoquinoline-4-carboxamides; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating and/or preventing malaria. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Type:
Grant
Filed:
August 24, 2012
Date of Patent:
August 16, 2016
Assignees:
ST. JUDE CHILDREN'S RESEARCH HOSPITAL, MMV MEDICINES FOR MALARIA VENTURE, RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Inventors:
Rodney Kiplin Guy, Fangyi Zhu, Wendyam Armand Guiguemde, David Floyd, Spencer Knapp, Philip Stein, Steve Castro
Abstract: The invention provides methods for overcoming glucocorticoid resistance of cancers by inhibition of CASP1. Also disclosed are diagnostic methods for determining glucocorticoid resistance potential by measuring expression level or promoter methylation status of CASP1 gene and/or NLRP3 gene.
Type:
Application
Filed:
September 16, 2014
Publication date:
August 11, 2016
Applicant:
St. Jude Children's Research Hospital, Inc.
Inventors:
Steven W. Paugh, William E. Evans, Erik Bonten
Abstract: Methods are provided for the prognosis, diagnosis and treatment of various pathological states, including cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. The methods provided herein are based on the discovery that various proteins with a high level of sialylation are shown herein to be associated with disease states, such as, cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. Such methods provide a lysosomal exocytosis activity profile comprising one or more values representing lysosomal exocytosis activity. Also provided herein, is the discovery that low lysosomal sialidase activity is associated with various pathological states. Thus, the methods also provide a lysosomal sialidase activity profile, comprising one or more values representing lysosomal sialidase activity. A lysosomal sialidase activity profile is one example of a lysosomal exocytosis activity profile.
Abstract: An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes are alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.
Type:
Grant
Filed:
July 8, 2010
Date of Patent:
July 19, 2016
Assignees:
UCL BUSINESS PLC, THROMBOSIS RESEARCH INSTITUTE, ST. JUDE CHILDREN'S RESEARCH HOSPITAL
Inventors:
Amit Nathwani, Natalie Ward, Adrian Thrasher, Edward Tuddenham, John McVey, John Gray, Andrew Davidoff
Abstract: Apparatus, methods, and other embodiments associated with the spectral analysis of T2 spectral data are described. One example magnetic resonance imaging (MRI) method includes accessing a data set comprising T2 spectral data associated with a magnetic resonance imaging (MRI) signal received from an object. The T2 spectral data is decomposed with multi-exponential functions to determine T2 spectra. The T2 spectral amplitude is regularized with a regularized constant. The regularized constant is sufficiently large to smooth the T2 spectra so adjacent pixels of the T2 spectral data have similar characteristics. The T2 spectral data is weighted so that the regularization is uniformly weighted for the spectral amplitudes. The T2 spectra is partitioned into intervals corresponding to myelin water fraction (MWF), tissue water fraction (TWF), Long T2 water fraction (LWF), and cerebrospinal fluid fraction (CSF). Parametric maps are generated based, at least in part, on the T2 spectral data.
Abstract: The invention provides methods and compositions for inducing necroptosis in target cells, including for example cancer cells. This invention provides compositions and methods for the controlled expression and formation of full length RDPK3 homodimers, truncated RTPK3 oligomers and/or full length RIPK3/RIPK1 heterodimers in target cells both in vitro and in vivo therapeutic and research applications.
Abstract: In one aspect, the invention relates to novel, broad-spectrum anti-viral, pyrimidinone compounds, methods of use, compositions and kits useful in treating and/or preventing influenza. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Abstract: Combinations of anti-cancer antibodies and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.
Type:
Application
Filed:
December 18, 2015
Publication date:
April 21, 2016
Applicants:
The Johns Hopkins University, St. Jude's Children's Research Hospital Inc.
Inventors:
Drew M. Pardoll, Ching-Tai Huang, Jonathan Powell, Charles Drake, Dario A. Vignali, Creg J. Workman
Abstract: A method of verifying therapeutic proton beam delivery accuracy by ultrasound tomographic imaging to map three dimensional (3D) proton dose through the detection of ionizing radiation induced thermo-acoustic signal from the proton beam.
Type:
Application
Filed:
April 30, 2014
Publication date:
March 17, 2016
Applicant:
St. Jude Children's Research Hospital, Inc.
Abstract: The compounds of the invention are antagonists of MDM2 and MDMX, with excellent specificity for MDM2 and MDMX over other proteins, and with selective binding affinity to MDMX over MDM2. The compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Type:
Grant
Filed:
September 30, 2011
Date of Patent:
February 23, 2016
Assignee:
St. Jude Children's Research Hospital
Inventors:
R. Kiplin Guy, Yiqun Zhang, Brandon Young, Michael Dyer, Kristin Finch, Donald Bashford, Nagakumar Bharatham, Richard Kriwacki, Grace Roy-Appa, Lie Min, Jaeki Min, Antonio Ferreira
Abstract: The present invention is an attenuated mutant strain of Streptococcus pneumonia that has a mutation in the FtsY gene. Vaccines, kits and methods for protecting a subject against Streptococcus pneumonia disease or colonization using the attenuated mutant strain are also provided.
Type:
Grant
Filed:
September 19, 2012
Date of Patent:
February 23, 2016
Assignee:
St. Jude Children's Research Hospital
Inventors:
Jason W. Rosch, Elaine I. Tuomanen, Jonathan A. McCullers
Abstract: The present invention embraces methods for the diagnosis and treatment of learning or mental disorders such as schizophrenia using miR-25, miR-98, or miR-185.
Type:
Grant
Filed:
February 1, 2013
Date of Patent:
February 9, 2016
Assignee:
St. Jude Children's Research Hospital
Inventors:
Stanislav S. Zakharenko, Laurie R. Earls
Abstract: In one aspect, the invention relates to pharmaceutical compositions comprising agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof; and agents that inhibit the expression of p27Kip1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof, which are useful for inducing the formation of cochlear hair cells; and methods of treating hearing impairments or disorders using the compositions. In one aspect, the invention relates to pharmaceutical compositions comprising ?-catenin; and agents that activate the expression of Atoh1, or pharmaceutically acceptable salts, solvates, or polymorphs thereof. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Abstract: Compositions and methods for preventing and treating pneumococcal infections are provided. Compositions include novel polypeptides comprising an amino acid sequence corresponding to the R21 or R22 domain of CbpA or a consensus sequence of one of these domains, and variants and fragments thereof, wherein the polypeptide is stabilized in a desired conformation, particularly a loop conformation. The polypeptides of the invention may be engineered to comprise a first and a second cysteine residue, thereby resulting in the formation of a disulfide bond that stabilizes the polypeptide in the desired conformation. Alternatively, a polypeptide of the invention may be modified to create a synthetic linkage between a first and second amino acid residue present within the polypeptide, wherein the synthetic linkage stabilizes the polypeptide in the desired conformation. The polypeptides of the invention may further comprise an amino acid sequence for a T cell epitope.
Type:
Grant
Filed:
March 20, 2014
Date of Patent:
February 2, 2016
Assignee:
St. Jude Children's Research Hospital
Inventors:
Karim C. El Kasmi, Brad Jordan, Richard Kriwacki, Beth Mann, Carlos J. Orihuela, Elaine Tuomanen
Abstract: Compositions and methods are provided for the prevention and treatment of bacterial infections, including pneumo-coccal infections. Compositions provided herein comprise a variety of immunogenic fusion proteins, wherein at least one poly-peptide component of a given fusion protein comprises a CbpA polypeptide and/or a cytolysoid polypeptide, or an active variant or fragment thereof. Methods are provided for the prevention and treatment of bacterial infections, including pneumococcal infections by employing the various immunogenic fusion proteins having at least one polypeptide component comprising a CbpA polypeptide and/or a cytolysoid polypeptide, or an active variant or fragment thereof.
Abstract: Provided herein are methods for a novel combination therapy for treating a glutamine-addicted cancer in a subject in need thereof, which comprises the administration of a glutaminase antagonist and a pro-apoptotic compound. Specific glutaminase antagonists and pro-apoptotic compounds are provided. In some embodiments, the glutaminase antagonist is 6-diazo-5-oxo-1-norleucine (DON) and the pro-apoptotic compound is a Bcl-2 family member antagonist. In some embodiments, the pro-apoptotic compound is obatoclax mesylate, navitoclax, or fenretinide. In some embodiments, the glutamine-addicted cancer is a cancer in which Myc is deregulated. In some embodiments, the cancer is a pediatric cancer.
Abstract: The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for the use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases.
Type:
Application
Filed:
January 28, 2014
Publication date:
January 7, 2016
Applicants:
ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC., NATIONAL UNIVERSITY OF SINGAPORE
Abstract: This invention relates is a label-free, enzyme-free, aptamer-free method for simultaneously measuring adenosine, and its intracellular metabolites, e.g., AMP, ADP and ATP, using high pressure liquid chromatography coupled to electrochemical detector (HPLC-ECD).
Abstract: Methods for regulating T cell function in a subject, particularly regulatory T cell activity are provided. Methods of the invention include administering to a subject a therapeutically effective amount of an Interleukin 35-specific binding agent, such as an antibody or small molecule inhibitor. The invention further provides methods for enhancing the immunogenicity of a vaccine or overcoming a suppressed immune response to a vaccine in a subject, including administering to the subject a therapeutically effective amount of an IL35-specific binding agent and administering to the subject a vaccine. In one embodiment the vaccine is a cancer vaccine.
Type:
Grant
Filed:
February 24, 2014
Date of Patent:
December 22, 2015
Assignee:
St. Jude Children's Research Hospital
Inventors:
Dario Vignali, Creg Workman, Lauren Collison, Kate Vignali
Abstract: Compositions and methods are provided for the prevention and treatment of bacterial infections, including pneumococal infections. Compositions provided herein comprise a variety of immunogenic fusion proteins, wherein at least one polypeptide component of a given fusion protein comprises a CbpA polypeptide and/or a cytolysoid polypeptide, or an active variant or fragment thereof. Methods are provided for the prevention and treatment of bacterial infections, including pneumococcal infections by employing the various immunogenic fusion proteins having at least one polypeptide component comprising a CbpA polypeptide and/or a cytolysoid polypeptide, or an active variant or fragment thereof.