Patents Assigned to The Scripps Research Institute
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Patent number: 11779548Abstract: A high-throughput screening methods for identifying candidate anticancer medicinal agents is described herein. The candidate anticancer medicinal agents are arylfluorosulfate compounds derived from phenolic compounds. The method involves in situ generation of the arylfluorosulfate compounds in multi-well plates by reaction of phenolic compounds in DMSO with a saturated solution of SO2F2 dissolved in a solvent such as acetonitrile, in the presence of an organic base, followed by reaction of generated fluoride ion with trimethylsilanol to form volatile trimethylsilyl fluoride. Solvents, organic base, and silyl compounds are then removed, in vacuo, to afford the arylfluorosulfate compounds suitable for biological screening in cancer cell lines without further purification.Type: GrantFiled: May 11, 2020Date of Patent: October 10, 2023Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Jie Li, Zilei Liu, Suhua Li, Peng Wu, K. Barry Sharpless
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Patent number: 11771689Abstract: Disclosed herein are compositions and methods for modulating cereblon neosubstrates. A small molecule modulator of Formula (I*), or a pharmaceutically acceptable salt or solvate thereof can be used to modulate cereblon neosubstrates.Type: GrantFiled: November 17, 2020Date of Patent: October 3, 2023Assignees: VIVIDION THERAPEUTICS, INC., THE SCRIPPS RESEARCH INSTITUTEInventors: Benjamin F. Cravatt, Matthew Patricelli, Dean Stamos, Gabe Simon, Benjamin Horning, David Weinstein, Ekaterina Vinogradova
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Patent number: 11767347Abstract: The present invention provides HIV-1 vaccine immunogens. Some of the immunogens contain a soluble gp140-derived protein that harbors a modified N-terminus of the HR1 region in gp41. Some of the immunogens contain an HIV-1 Env-derived trimer protein that is presented on a nanoparticle platform. The invention also provides methods of using the HIV-1 vaccine immunogens for eliciting an immune response or treating HIV infections.Type: GrantFiled: December 16, 2021Date of Patent: September 26, 2023Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Leopold Kong, Ian A. Wilson, Natalia De Val, Andrew B. Ward, Dennis Burton, Linling He, Jiang Zhu
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Patent number: 11761007Abstract: Disclosed herein are methods, cells, engineered microorganisms, and kits for increased production of a nucleic acid molecule that comprises an unnatural nucleotide.Type: GrantFiled: December 16, 2016Date of Patent: September 19, 2023Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Floyd E. Romesberg, Brian Lamb, Yorke Zhang
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Patent number: 11759461Abstract: The present disclosure provides compounds, their pharmaceutical compositions, and methods of their use for treating mesenchymally-derived or mesenchymally transformed cancers, such as breast cancers and sarcomas, and for treating diseases or disorders that are characterized by the expression of vimentin.Type: GrantFiled: October 30, 2018Date of Patent: September 19, 2023Assignees: THE SCRIPPS RESEARCH INSTITUTE, THE UNIVERSTY OF TEXAS SYSTEM,BOARD OF REGENTSInventors: Luke L. Lairson, Michael J. Bollong, Peter G. Schultz, Sendurai A. Mani
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Patent number: 11752483Abstract: The present disclosure provides methods, compositions, and kits for methods that can improve techniques nucleic acid analysis, and can allow for more reliable and accurate targeted, multiplexed, high throughput sequencing. The methods, compositions, and kits can be used for sequencing target loci of nucleic acid. The methods, compositions, and kits disclosed herein can be used for assisted de novo targeted sequencing. The methods, compositions, and kits disclosed herein can also be used for library labeling for de novo sequencing and phasing.Type: GrantFiled: August 10, 2020Date of Patent: September 12, 2023Assignee: The Scripps Research InstituteInventors: Steven Robert Head, Phillip T. Ordoukhanian, Daniel R. Salomon
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Patent number: 11753619Abstract: Provided herein are engineered cells, comprising: a chemical or biological moiety covalently bound to a cell surface glycan, wherein the chemical or biological moiety is selected from the group consisting of small molecule, polynucleotide, polypeptide, and antibody. Also provided are compositions comprising these engineered cells and methods of making and using the same.Type: GrantFiled: February 1, 2018Date of Patent: September 12, 2023Assignee: The Scripps Research InstituteInventors: Peng Wu, Jie Li, Yiran Zhou, Mingkuan Chen
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Patent number: 11713349Abstract: This disclosure relates to antibodies and antigen binding fragments that specifically bind Ebola virus particles. In certain embodiments, the antibodies and fragments are capable of treating or preventing an Ebola viral infection. In certain embodiments, the antibodies and antigen binding fragments are also contemplated for diagnostic methods and compositions related thereto.Type: GrantFiled: March 9, 2021Date of Patent: August 1, 2023Assignees: Emory University, The Scripps Research InstituteInventors: Rafi Ahmed, Carl Davis, Erica Ollmann Saphire
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Patent number: 11708348Abstract: Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions: wherein R1, R2, R3a, R3b, R4, R5, and A are defined in the present disclosure. The compounds are potent inhibitors of the main protease (Mpro) of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), and they are useful in treating or preventing COVID-19 in a subject.Type: GrantFiled: June 10, 2022Date of Patent: July 25, 2023Assignee: The Scripps Research InstituteInventors: Arnab K. Chatterjee, Jian Jeffrey Chen, Elshan Nakath, Alireza Rahimi, Anil Kumar Gupta, Gennadii Grabovyi, Katy Wilson, Sourav Ghorai, Armen Nazarian, James Pedroarena, Wrickban Mazumdar, Frank Weiss, Lirui Song, Malina A. Bakowski, Laura Riva, Karen Wolff, Case W. McNamara, Thomas F. Rogers, Jacqueline Malvin, Shuangwei Li, Sean Joseph, Ashley Woods, Yuyin Liu, Neechi Okwor
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Patent number: 11701364Abstract: The invention provides compounds having STimulator of INterferon Genes (STING) agonistic bioactivity that can be used in the treatment of tumors in patients afflicted therewith. The compounds are of formula (I): as defined herein. Compounds for practice of a method of the invention can be delivered via oral delivery for systemic exposure, as well as delivered intratumorally. Antitumor therapy using a compound of formula (I) can further comprise administration of an effective dose of an immune-checkpoint targeting drug.Type: GrantFiled: February 21, 2019Date of Patent: July 18, 2023Assignee: The Scripps Research InstituteInventors: Luke L. Lairson, Emily Chin, Arnab K. Chatterjee, Manoj Kumar, Ana Maria Gamo Albero, Hank Michael James Petrassi, Peter G. Schultz, Chenguang Yu, Junko Tamiya, William Vernier, Anil Gupta, Ramkumar Modukuri
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Patent number: 11691984Abstract: Disclosed herein are methods and compounds for inducing DDB1- and CUL4-associated factor 16 (DCAF16)-mediated protein degradation in mammalian cells. In some embodiments, also disclosed herein are methods of modulating the substrate selectivity of a DCAF16-CUL4-RBX1-DDB1 complex (CRL4) for modulating protein degradation.Type: GrantFiled: October 11, 2019Date of Patent: July 4, 2023Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Benjamin Cravatt, Vincent Crowley, Xiaoyu Zhang
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Patent number: 11673959Abstract: Disclosed herein are immunoglobulin fusion proteins comprising a first antibody region, a first therapeutic agent, and a first connecting peptide; wherein the first therapeutic agent is attached to the first antibody region by the connecting peptide; and wherein the connecting peptide does not comprise a region having beta strand secondary structure. The connecting peptide may comprise an extender peptide. The extender peptide may have an alpha helical secondary structure. The connecting peptide may comprise a linker peptide. The linker peptide may not comprise any secondary structure. Also disclosed herein are compositions comprising the immunoglobulin fusion proteins and methods for using the immunoglobulin fusion proteins for the treatment or prevention of a disease or condition in a subject.Type: GrantFiled: March 30, 2020Date of Patent: June 13, 2023Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Feng Wang, Yong Zhang, Yan Liu, Peter G. Schultz
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Patent number: 11660331Abstract: An improved heroin conjugate vaccine is detailed; to accomplish this task the systematic exploration of twenty vaccine formulations with varying combinations of carrier proteins and adjuvants were undertaken. In regard to adjuvants, a Toll-like receptor 9 (TLR9) agonist and a TLR3 agonist in the presence of alum were explored. The vaccine formulations containing TLR3 or TLR9 agonist alone-elicited strong anti-heroin antibody titers and blockade of heroin-induced antinociception when formulated with alum; however, a combination of TLR3 and 9 adjuvants did not result in improved efficacy. Investigation of stability of the two lead formulations revealed that the TLR9 but not the TLR3 formulation was stable when stored over 30 days. Furthermore, mice immunized with the TLR9+alum heroin vaccine gained significant protection from lethal heroin doses, suggesting that this vaccine formulation is suitable for mitigating the lethal effects of heroin, even following long-term storage at room temperature.Type: GrantFiled: November 8, 2018Date of Patent: May 30, 2023Assignee: The Scripps Research InstituteInventor: Kim D. Janda
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Publication number: 20230146239Abstract: A series of vancomycin C-terminus guanidine modifications are disclosed that improve antimicrobial activity, enhance the durability of antimicrobial action against selection or induction of resistance, and provide two synergistic mechanisms of action independent of D-Ala-D-Ala binding that cause inhibition of cell wall biosynthesis, while inducing bacterial cell permeability. A contemplated compound contains two combined peripheral modifications, a (4-chlorobiphenyl)methyl (CBP) and C-terminus guanidine modification, that provide new treatments against not only vancomycin-sensitive, but especially vancomycin-resistant bacteria. The data demonstrate that the synergistic behavior of the peripheral modifications requires the presence of both the CBP and guanidine modifications in a single molecule versus their combined use as an equimolar mixture of singly modified compounds.Type: ApplicationFiled: April 13, 2021Publication date: May 11, 2023Applicant: THE SCRIPPS RESEARCH INSTITUTEInventors: Dale L. BOGER, Zhi-Chen WU
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Patent number: 11634451Abstract: Provided herein are analogs of unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs that form unnatural base pairs during DNA polymerase-mediated replication of DNA or RNA polymerase-mediated transcription of RNA. In this manner, the unnatural nucleobases can be introduced in a site-specific way into oligonucleotides (single or double stranded DNA or RNA), where they can provide for site-specific cleavage, or can provide a reactive linker than can undergo functionalization with a cargo-bearing reagent by means of reaction with a primary amino group or by means of click chemistry with an alkyne group of the unnatural nucleobase linker.Type: GrantFiled: July 22, 2019Date of Patent: April 25, 2023Assignee: THE SCRIPPS RESEARCH INSTITUTEInventors: Floyd E. Romesberg, Denis A. Malyshev, Lingjun Li, Thomas Lavergne, Zhengtao Li
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Patent number: 11613554Abstract: The present invention relates to novel phosphorous (V) (P(V)) reagents, methods for preparing thereof, and methods for preparing organophosphorous (V) compounds by using the novel reagents.Type: GrantFiled: April 12, 2019Date of Patent: March 28, 2023Assignees: Bristol-Myers Squibb Company, The Scripps Research InstituteInventors: Michael Anthony Schmidt, Bin Zheng, Kyle Knouse, Justine deGruyter, Martin D. Eastgate, Phil Baran, William R. Ewing, Richard E. Olson, Ivar M. McDonald
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Patent number: 11613535Abstract: There is disclosed a compound, a pharmaceutical composition and a method of cancer treatment with an improved Myc inhibitor compound. More specifically, there is disclosed an improved compound having with improved solubility, improved binding characteristics and better efficacy and therapeutic activity inhibiting c-MYC wherein the improved compound comprises a tri-substituted pyridine having a thiazoyl moiety at position R1 versus an earlier disclosed genus of tri-substituted pyridine structures.Type: GrantFiled: July 8, 2019Date of Patent: March 28, 2023Assignee: The Scripps Research InstituteInventor: Kim D. Janda
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Publication number: 20230085158Abstract: The invention provides seminal computational approaches utilizing data from non-rare cells to detect rare cells, such as circulating tumor cells (CTCs). The invention is applicable at two distinct stages of CTC detection; the first being to make decisions about data collection parameters and the second being to make decisions during data reduction and analysis. Additionally, the invention utilizes both one and multi-dimensional parameterized data in a decision making process.Type: ApplicationFiled: May 17, 2022Publication date: March 16, 2023Applicants: The Scripps Research Institute, Epic Sciences, Inc.Inventors: Peter Kuhn, Anand Kolatkar, Joshua Kunken, Dena Marrinucci, Xing Yang, John R. Stuelpnagel
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Patent number: 11584789Abstract: 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 are 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: GrantFiled: October 28, 2020Date of Patent: February 21, 2023Assignees: INTERNATIONAL AIDS VACCINE INITIATIVE, INC., THE SCRIPPS RESEARCH INSTITUTE, THERACLONE SCIENCES, INC.Inventors: Po-Ying Chan-Hui, Steven Frey, Ole Olsen, Jennifer Mitcham, Matthew Moyle, Sanjay K. Phogat, Dennis R. Burton, Laura Marjorie Walker, Pascal Raymond Georges Poignard, Wayne Koff, Melissa Danielle De Jean De St. Marcel Simek-Lemos, Stephen Kaminsky
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Publication number: 20230049529Abstract: The disclosure is directed to dual variable domain immunoglobulin double-stranded RNA conjugates that are advantageous for inhibition of target gene expression, as well as compositions suitable for therapeutic use. The dual variable domain immunoglobulin comprises a first variable domain that binds to a binding target, and a second variable domain that comprises a reactive residue, where the linker is covalently conjugated to the reactive residue. The dsRNA is linked to the linker and is capable of inhibiting the expression of the target gene by RNA interference. The disclosure also provides pharmaceutical compositions comprising these conjugate and methods of inhibiting the expression of a target gene by administering these conjugates, e.g., for the treatment of various disease conditions.Type: ApplicationFiled: June 18, 2020Publication date: February 16, 2023Applicants: Alnylam Pharmaceuticals, Inc., THE SCRIPPS RESEARCH INSTITUTEInventors: Alexander V. KEL'IN, Alex R. NANNA, Christopher RADER, Christopher THEILE, Justin PIERSON, Kevin FITZGERALD, Zhi Xiang VOO