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:
December 28, 2018
Date of Patent:
December 8, 2020
Assignee:
The Scripps Research Institute
Inventors:
Benjamin F. Cravatt, Micah J. Niphakis, Kenneth Lum, Bruno Correia, Armand Cognetta, Jonathan Hulce
Abstract: Provided is a process for oxidizing an alkene. The process comprises contacting an alkene, and either an oxidizing electrophile comprising a main group element in oxidized form or an oxidant and a reduced form of the oxidizing electrophile, in a liquid medium comprising an oxygen acid and optionally one or more additives selected from a non-oxidizable liquid, a salt additive, a Lewis acid, and water, to provide an oxygenate and a reduced form of the oxidizing electrophile. The process optionally further comprises separating the oxygenate and the reduced form of the oxidizing electrophile. The oxygenate can be further hydrolyzed to form an alcohol, diol, or polyol.
Type:
Grant
Filed:
May 25, 2018
Date of Patent:
December 8, 2020
Assignees:
The Scripps Research Institute, Hyconix, Inc.
Inventors:
Roy A. Periana, Brian G. Hashiguchi, Michael M. Konnick
Abstract: Disclosed herein are methods, cells, engineered microorganisms, and kits for increased production of a nucleic acid molecule that comprises an unnatural nucleotide.
Type:
Application
Filed:
December 16, 2016
Publication date:
December 3, 2020
Applicant:
The Scripps Research Institute
Inventors:
Floyd E. ROMESBERG, Brian LAMB, Yorke ZHANG
Abstract: Provided is a process for converting a hydrocarbon comprising at least one C—H bond to a nitrogen-functionalized product. The process comprises contacting a hydrocarbon and (i) an oxidizing electrophile comprising (a) a main group element or transition metal in oxidized form and (b) at least one nitrogen-containing ligand, or (ii) an oxidant and a reduced form of an oxidizing electrophile comprising (a) a main group element or transition metal and (b) at least one nitrogen-containing ligand, in a solvent to provide the nitrogen-functionalized product and an electrophile reduction product. Further provided is an oxidizing composition comprising the oxidizing electrophile with at least one nitrogen-containing ligand and a non-oxidizable liquid.
Type:
Application
Filed:
November 30, 2018
Publication date:
December 3, 2020
Applicants:
The Scripps Research Institute, Hyconix, Inc.
Inventors:
Roy A. PERIANA, Brian G. HASHIGUCHI, Sae Hume PARK, Niles Jensen GUNSALUS
Abstract: The present invention relates to compositions and methods for treating diseases, disorders or conditions associated with the expression of the Glycosyl-phosphatidylinositol (GPI)-linked GDNF family ?-receptor 4 (GFR?4).
Type:
Grant
Filed:
August 14, 2015
Date of Patent:
December 1, 2020
Assignees:
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, NOVARTIS AG, THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Donald L. Siegel, Michael C. Milone, Vijay Bhoj, Christoph Rader
Abstract: The invention provides heterocyclic compounds of formula A, B, and C as described herein that inhibit monocarboxylate transporters, such as MCT1 and MCT4. Compounds of the invention can be used for treatment of a condition in a patient, wherein the condition is characterized by the heightened activity or by the high prevalence of MCT1 and/or MCT4, such as cancer or type II diabetes.
Type:
Grant
Filed:
June 13, 2019
Date of Patent:
December 1, 2020
Assignee:
THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Thomas D. Bannister, William R. Roush, Jun Yong Choi, Reji Nair, Andy S. Tsai, Jitendra K. Mishra, John L. Cleveland
Abstract: Described are methods for providing personalized medicine for the treatment of B cell malignancies including lymphoma. The methods make use of Chimeric Antigen Receptor (CAR) technology.
Type:
Application
Filed:
August 3, 2020
Publication date:
November 19, 2020
Applicants:
OPKO Pharmaceuticals, LLC, The Scripps Research Institute, Shemyakin-Ovchinnikov institute of Bioorganic Chemistry, Russian Academy of Sciences, PJSC Pharmsynthez
Inventors:
Alexey Vyacheslavovich Stepanov, Dmitry Dmitrievich Genkin, Richard A. Lerner, Alexey Anatolievich Belogurov, Alexander Gabibovich Gabibov, Jia Xie
Abstract: The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.
Type:
Grant
Filed:
September 12, 2017
Date of Patent:
November 17, 2020
Assignees:
Theraclone Sciences, Inc., The Scripps Research Institute, International AIDS Vaccine Initiative
Inventors:
Po-Ying Chan-Hui, Katherine Doores, Michael Huber, Stephen Kaminsky, Steven Frey, Ole Olsen, Jennifer Mitcham, Matthew Moyle, Sanjay K. Phogat, Dennis R. Burton, Laura Majorie Walker, Pascal Raymond Georges Poignard, Wayne Koff, Melissa Danielle De Jean De St. Marcel Simek-Lemos
Abstract: Disclosed herein are chimeric polypeptides, including compositions thereof, expression vectors, and methods of use thereof, for the generation of transgenic cells, tissues, plants, and animals. The compositions, vectors, and methods of the present invention are also useful in gene therapy techniques.
Type:
Grant
Filed:
January 23, 2018
Date of Patent:
November 10, 2020
Assignee:
The Scripps Research Institute
Inventors:
Carlos F. Barbas, III, Andrew Mercer, Brian M. Lamb, Thomas Gaj
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 2, 2018
Date of Patent:
November 10, 2020
Assignees:
University of Kansas, THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Jeffrey Aube, Kevin Frankowski, Thomas Prisinzano, Laura Bohn
Abstract: The instant invention describes hydrazide-containing compounds having therapeutic activity, and methods of treating disorders such as cancer, tumors and cell proliferation related disorders, or affect cell differentiation, dedifferentiation or transdifferentiation.
Type:
Grant
Filed:
March 30, 2015
Date of Patent:
October 20, 2020
Assignees:
University of Florida Research Foundation, Inc., The Scripps Research Institute
Inventors:
Daiqing Liao, William R. Roush, Ryan L. Stowe
Abstract: Disclosed herein are switchable chimeric receptors, switchable chimeric receptor effector cells and chimeric receptor effector cell switches. The switchable chimeric receptor-ECs are generally T cells. The chimeric receptors have non-antibody extracellular domains that recognize a chimeric receptor binding partner on the chimeric receptor-EC switch or target cell. The chimeric receptor-ECs and switches may be used for the treatment of a disease or condition in a subject in need thereof.
Type:
Grant
Filed:
March 28, 2016
Date of Patent:
October 13, 2020
Assignee:
THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Travis Young, Chanhyuk Kim, Peter G. Schultz
Abstract: In alternative embodiments, the invention provides nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). The hydroxyimino-acetamido alkylamines of the invention are designed to fit within AChE active center gorge dimensions, bind with reasonable affinity, and react with the conjugated phosphate atom in the gorge. The hydroxyimino-acetamido alkylamines of the invention are also designed to possess ionization states that govern affinity and reactivity for the two linked hAChE re-activation steps.
Type:
Grant
Filed:
July 11, 2019
Date of Patent:
October 13, 2020
Assignees:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Palmer Taylor, Zoran Radic, K. Barry Sharpless, Valery Fokin, Rakesh Sit
Abstract: The present invention provides compounds, pharmaceutical compositions and methods for treating and/or preventing a metabolic condition, such as diabetes.
Type:
Application
Filed:
March 21, 2018
Publication date:
October 8, 2020
Applicants:
Dana-Farber Cancer Institute, Inc., The Scripps Research Institute
Inventors:
Pere PUIGSERVER, Kfir SHARABI, Theodore KAMENECKA, Patrick GRIFFIN, Stuart L. SCHREIBER, Roger SCHILLING, Partha P. NAG, Joshua A. BITTKER
Abstract: In this study, we capitalized on the antimicrobial property and low oral bioavailability of known salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. The anthelmintics displayed excellent potency against C. difficile strains 630 and 4118 (with MIC values as low as 0.06-0.13 ?g/mL for rafoxanide) via a membrane depolarization mechanism, interestingly, closantel, rafoxanide and compound 8 were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. Further evaluation of the salicylanilides showed their preferential activity against Gram-positive over Gram-negative bacteria. Moreover, the salicylanilides were non-hemolytic and were non-toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable bactericidal and pharmacokinetic properties and are amenable to repositioning as anti-C. difficile agents.
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:
Grant
Filed:
October 25, 2018
Date of Patent:
September 29, 2020
Assignees:
DANA-FARBER CANCER INSTITUTE, INC., THE SCRIPPS RESEARCH INSTITUTE
Abstract: Cells produce electrophilic products with the potential to modify and affect the function of proteins. Chemoproteomic methods have provided a means to qualitatively inventory proteins targeted by endogenous electrophiles; however, ascertaining the potency and specificity of these reactions to identify the most sensitive sites in the proteome to electrophilic modification requires more quantitative methods. Here, we describe a competitive activity-based profiling method for quantifying the reactivity of electrophilic compounds against 1000+ cysteines in parallel in the human proteome. Using this approach, we identify a select set of proteins that constitute hot spots for modification by various lipid-derived electrophiles, including the oxidative stress product 4-hydroxnonenal (HNE).
Type:
Grant
Filed:
August 13, 2014
Date of Patent:
September 22, 2020
Assignee:
The Scripps Research Institute
Inventors:
Benjamin Cravatt, Chu Wang, Keriann Backus
Abstract: Disclosed herein are in vivo engineered cereblon protein and methods of making the same. The in vivo engineered cereblon protein can include a site-specific non-naturally occurring modification at cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO:2 or 3, the modification comprising a moiety resulting from an in vivo Michael addition reaction between an exogenous Michael acceptor and the cysteine 287 as set forth in SEQ ID NO:1, or cysteine 286 as set forth in SEQ ID NO:2 or 3.
Type:
Grant
Filed:
August 8, 2019
Date of Patent:
September 22, 2020
Assignees:
VIVIDION THERAPEUTICS, INC., THE SCRIPPS RESEARCH INSTITUTE
Inventors:
David Weinstein, Benjamin F. Cravatt, Matthew Patricelli, Dean Stamos, Gabe Simon, Benjamin Horning, Ekaterina Vinogradova, Brian Nordin, Kristen Baltgalvis, Todd Kinsella
Abstract: The present invention provides novel scaffolded HIV-1 vaccine immunogens. Some of the scaffolded immunogens contain a soluble gp140 trimer linked to the N-terminus of the nanoparticle subunit and a T-helper epitope that is fused via a short peptide spacer to the C-terminus of the nanoparticle subunit. Some other immunogens of the invention contain a soluble gp140 trimer protein that is linked to a stable nanoparticle via a short peptide spacer that is a T-helper epitope. Some of the scaffolded immunogens contain a gp140 trimer immunogen presented on a nanoparticle platform formed with I3-01 protein, E2p, or variants of protein 1VLW. Also provided in the invention are nucleic acids that encode the various vaccine immunogens described herein, and expression vectors and host cells harboring the nucleic acids. The invention further provides methods of using the scaffolded HIV-1 vaccine immunogens for preventing or treating HIV infections.