Abstract: The present invention provides novel heteroaryl compounds of formula (I) 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.
Type:
Application
Filed:
October 25, 2018
Publication date:
March 21, 2019
Applicants:
Dana-Farber Cancer Institute, Inc., The Scripps Research Institute
Inventors:
Nathanael S. Gray, Jianming Zhang, Barun Okram, Xianming Deng, Jae Won Chang, Amy Wojciechowski
Abstract: A computer-based genomic annotation system, including a database configured to store genomic data, non-transitory memory configured to store instructions, and at least one processor coupled with the memory, the processor configured to implement the instructions in order to implement an annotation pipeline and at least one module filtering or analysis of the genomic data.
Abstract: In one aspect, the present disclosure provides new analogs of uncialamycin. The present disclosure also provides novel synthetic pathways to obtaining uncialamycin and analogs thereof. Additionally, the present disclosure also describes methods of use of uncialamycin and analogs thereof. In another aspect, the present disclosure provides antibody-drug conjugates which may be used to treat cancer or another disease or disorder.
Type:
Grant
Filed:
August 15, 2017
Date of Patent:
March 19, 2019
Assignees:
WILLIAM MARSH RICE UNIVERSITY, THE SCRIPPS RESEARCH INSTITUTE, BRISTOL-MYERS SQUIBB COMPANY
Inventors:
Kyriacos C. Nicolaou, Min Lu, Debashis Mandal, Sanjeev Gangwar, Naidu S. Chowdari, Yam B. Poudel
Abstract: Potent modulators of RNA function can be assembled in cellulo by using the cell as a reaction vessel and a disease-causing RNA as a catalyst. When designing small molecule effectors of function, a balance between permeability and potency must be struck. Low molecular weight compounds are more permeable while higher molecular weight compounds are more potent. The advantages of both types of compounds could be synergized if low molecular weight molecules could be transformed into potent, multivalent ligands via a reaction catalyzed by binding to a target in cells expressing a genetic defect. We demonstrate that this approach is indeed viable in cellulo. Small molecule modules with precisely positioned alkyne and azide moieties bind adjacent internal loops in r(CCUG)exp, the causative agent of myotonic dystrophy type 2 (DM2), and are transformed into oligomeric, potent inhibitors of DM2 RNA dysfunction via a 1,3 Huisgen dipolar cycloaddition reaction, a variant of click chemistry.
Abstract: The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.
Type:
Grant
Filed:
December 22, 2015
Date of Patent:
March 5, 2019
Assignees:
University of Washington, Center for Commercialization, The Scripps Research Institute, International AIDS Vaccine Initiative
Inventors:
Po-Ssu Huang, Joseph Graham Jardine, Sergey V. Menis, William Ray Schief, Neil P. King
Abstract: The invention relates to processes for preparing (S,S)-secoisolariciresinol diglucoside and (R,R)-secoisolariciresinol diglucoside and compositions comprising the same.
Type:
Application
Filed:
July 23, 2018
Publication date:
February 28, 2019
Applicants:
The Trustees of the University of Pennsylvania, The Scripps Research Institute
Inventors:
Melpo CHRISTOFIDOU-SOLOMIDOU, Kyriacos C. Nicolaou, Roman A. Valiulin, Nicholas Simmons, Philipp M. Heretsch
Abstract: The present invention provides for methods, compositions, and kits for producing an induced pluripotent stem cell from a non-pluripotent mammalian cell using a 3?-phosphoinositide-dependent kinase-1 (PDK1) activator or a compound that promotes glycolytic metabolism as well as other small molecules.
Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Brain derived neurotrophic factor (BDNF), in particular, by targeting natural antisense polynucleotides of Brain derived neurotrophic factor (BDNF). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of BDNF.
Type:
Grant
Filed:
January 4, 2017
Date of Patent:
February 26, 2019
Assignees:
The Scripps Research Institute, Curna, Inc.
Abstract: The present specification discloses APY cyclic peptides having EphA4 antagonistic activity, pharmaceutical compositions containing such EphA4 antagonists, and methods and uses of treating an EphA4-based disease, disorder or pathology in an individual using such APY cyclic peptides or pharmaceutical compositions.
Type:
Application
Filed:
July 15, 2015
Publication date:
February 7, 2019
Applicants:
Sanford Burnham Prebys Medical Discovery Institute, The Scripps Research Institute
Inventors:
Elena B. Pasquale, Philip Dawson, Erika Olson, Stefan J. Riedl
Abstract: This application describes a compound represented by Formula (I): Y?Z?X1—S(O)(X2)F)m]n??(I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.
Type:
Application
Filed:
October 12, 2018
Publication date:
January 31, 2019
Applicant:
THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Jiajia Dong, K. Barry Sharpless, Jeffery W. Kelly, Aleksandra Baranczak, Wentao Chen
Abstract: This invention provides methods of generating induced sensory neurons (iSNs) from non-neuronal cells such as fibroblasts. The invention also provides methods of using iSNs in various therapeutic or non-therapeutic applications, e.g., methods to identify agents or cellular modulations that enhance iSN formation from non-neuronal cells.
Type:
Grant
Filed:
December 19, 2014
Date of Patent:
January 29, 2019
Assignee:
The Scripps Research Institute
Inventors:
Joel W. Blanchard, Kevin T. Eade, Kristin Baldwin
Abstract: Described herein are methods and compositions for treating nicotine addiction, promoting smoking cessation, reducing the risk of relapse of nicotine consumption, and/or treating nicotine poisoning in a subject in need thereof, using a nicotine-degrading enzyme or an expression vector capable of expressing a nicotine-degrading enzyme in vivo.
Type:
Application
Filed:
August 2, 2016
Publication date:
January 17, 2019
Applicants:
The Scripps Research Institute, Antidote Therapeutics, Inc., Antidote Therapeutics, Inc.
Inventors:
Kim D. JANDA, Matt KALNIK, Thomas THISTED
Abstract: The present application relates to novel HIV-1 envelope glycoproteins which may be utilized as an HIV-1 vaccine immunogens, antigens for crystallization and for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions which are formulated into the vaccines of the present invention.
Type:
Grant
Filed:
March 21, 2016
Date of Patent:
January 8, 2019
Assignees:
International AIDS Vaccine Initiative, The Scripps Research Institute
Inventors:
Viktoriya Dubrovskaya, Francisco Javier Guenaga, Richard Wyatt
Abstract: Provided herein are fluoropyrimidine-modified RNA aptamers capable of binding CCR5. The compositions and methods provided herein are, inter alia, useful for the delivery of antiviral drugs (e.g., siRNAs) and preventing HIV entry into a target cell.
Type:
Grant
Filed:
March 24, 2017
Date of Patent:
January 1, 2019
Assignees:
City of Hope, The Scripps Research Institute
Inventors:
John Rossi, Jiehua Zhou, Marc Weinberg, Kevin Morris
Abstract: Disclosed herein are methods, compositions, probes, assays and kits for identifying a lipid binding protein as a drug binding target. Also disclosed herein are methods, compositions, and probes for mapping a ligand binding site on a lipid binding protein, identification of lipid binding proteins, generating drug-lipid binding protein profiles, high throughput drug screening, and identification of drugs as potential lipid binding protein ligands.
Type:
Grant
Filed:
March 25, 2016
Date of Patent:
January 1, 2019
Assignee:
The Scripps Research Institute
Inventors:
Benjamin F. Cravatt, Micah J. Niphakis, Kenneth Lum, Bruno Correia, Armand Cognetta, Jonathan Hulce
Abstract: The present invention provides compounds and compositions for the amelioration of arthritis and joint injuries by inducing mesenchymal stem cells into chondrocytes.
Abstract: Methods and computer systems are described herein for identifying small molecules that bind to selected RNA structural features (e.g., to RNA secondary structures). Also described are compounds and compositions that modulate RNA function and/or activity.
Abstract: The present technology is directed to compounds, compositions, and methods related to non-morphinan-like kappa opioid receptor (KOR) antagonists. The technology is suited to treat addiction, diuresis, depression, post traumatic stress disorder, an eating disorder, panic disorder, social anxiety disorder, general anxiety disorder, obsessive compulsive disorders, excessive or unreasonable specific phobias, and/or other conditions related to anxiety or aversion-reward responses.
Type:
Grant
Filed:
November 25, 2015
Date of Patent:
November 6, 2018
Assignees:
UNIVERSITY OF KANSAS, THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Jeffrey Aube, Kevin Frankowski, Thomas Prisinzano, Laura Bohn
Abstract: This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.
Type:
Grant
Filed:
June 5, 2015
Date of Patent:
November 6, 2018
Assignee:
The Scripps Research Institute
Inventors:
Jiajia Dong, K. Barry Sharpless, Jeffery W. Kelly, Wentao Chen