Abstract: Described herein are methods, compositions, and systems useful for detecting transplant rejection and associated abnormal conditions in solid organ transplant recipients, such as kidney transplant recipients. Methods described herein may involve combined assessment of blood gene expression profiles from an assessment of particular, related mRNA transcript levels and donor-derived cell-free nucleic acids (dd-cfDNA).
Type:
Application
Filed:
January 26, 2024
Publication date:
June 13, 2024
Applicants:
Northwestern University, Transplant Genomics, Inc., The Scripps Research Institute
Inventors:
John Friedewald, Michael M. Abecassis, Rohita Sinha, Sook Hyeon Park, Lihui Zhao, Juston Weems, Sunil M. Kurian, Steve Kleiboeker
Abstract: This invention provides novel methods for treating or ameliorating symptoms of demyelinating diseases such as multiple sclerosis. The methods involve administering to subjects in need of treatment a pharmaceutical composition that contains a therapeutically effective amount of taurine and also a compound that induces oligodendrocyte precursor cell (OPC) differentiation (e.g., T3, benztropine, clemastine or miconazole). Some of the methods additionally involve administration to the subject a known agent for treating demyelinating diseases (e.g., SIP receptor agonists) or a known disease modifying drug. The invention also provides methods for increasing myelination and methods for promoting OPC differentiation into oligodendrocytes. These methods entail contacting a population of OPCs with a combination of taurine and a known OPC differentiation-inducing agent such as T3, clemastine, benztropine or miconazole.
Type:
Grant
Filed:
November 13, 2018
Date of Patent:
June 4, 2024
Assignee:
The Scripps Research Institute
Inventors:
Luke Lairson, Brittney Beyer, Mingliang Fang, Gary Siuzdak
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:
October 23, 2020
Date of Patent:
April 30, 2024
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: Coronavirus S ectodomain trimers stabilized in a prefusion conformation, nucleic acid molecules and vectors encoding these proteins, and methods of their use and production are disclosed. In several embodiments, the coronavirus S ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to coronavirus in a subject. In additional embodiments, the therapeutically effective amount of the coronavirus S ectodomain trimers and/or nucleic acid molecules can be administered to a subject in a method of treating or preventing coronavirus infection.
Type:
Grant
Filed:
March 8, 2021
Date of Patent:
April 23, 2024
Assignees:
The United States of America, as represented by the Secretary, Department of Health and Human Services, The Scripps Research Institute, Trustees of Dartmouth College
Inventors:
Barney Graham, Jason Mclellan, Andrew Ward, Robert Kirchdoerfer, Christopher Cottrell, Michael Gordon Joyce, Masaru Kanekiyo, Nianshuang Wang, Jesper Pallesen, Hadi Yassine, Hannah Turner, Kizzmekia Corbett
Abstract: Provided herein are compounds and compositions useful as modulators of ABHD12. Furthermore, the subject compounds and compositions are useful as immunotherapies in treating, for instance, cancer or infectious diseases.
Type:
Grant
Filed:
May 14, 2019
Date of Patent:
February 13, 2024
Assignee:
THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Daisuke Ogasawara, Taka-Aki Ichu, Jonathan Hulce, Benjamin F. Cravatt
Abstract: Compounds are provided that antagonize the kappa-opioid receptor (KOR) and products containing such compounds, as well as to methods of their use and synthesis. Such compounds have the structure of Formula (I), or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope or salt thereof: wherein X, Y, R1, R2, R4, R5, R6, R7, R8 and R11 are as defined herein.
Type:
Grant
Filed:
July 30, 2021
Date of Patent:
February 13, 2024
Assignees:
BLACKTHORN THERAPEUTICS, INC., THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Edward Roberts, Miguel A. Guerrero, Mariangela Urbano, Hugh Rosen, Robert M. Jones, Candace Mae Laxamana, Xianrui Zhao, Eric Douglas Turtle
Abstract: Disclosed herein are methods, compositions and kits for the synthesis of proteins which comprises unnatural amino acids that utilize a mutant tRNA.
Type:
Application
Filed:
October 4, 2023
Publication date:
February 8, 2024
Applicants:
Synthorx, Inc., The Scripps Research Institute
Inventors:
Jerod PTACIN, Carolina CAFFARO, Hans AERNI, Yorke ZHANG, Emil C. FISCHER, Aaron W. FELDMAN, Vivian T. DIEN, Floyd E. ROMESBERG
Abstract: There are disclosed imidazolinopyrimidinone compounds that have activity to induce TRAIL gene expression in macrophages. There is further disclosed a method for treating various cancers comprising administering effective amounts of an imidazolinopyrimidinone having the structure of Formula I herein.
Type:
Grant
Filed:
July 12, 2021
Date of Patent:
February 6, 2024
Assignee:
The Scripps Research Institute
Inventors:
Kim D. Janda, Nicholas T. Jacob, Jonathan W. Lockner
Abstract: Disclosed herein are compositions, methods, cells, engineered microorganisms, and kits for increasing the production of proteins or polypeptides comprising one or more unnatural amino acids. Further provided are compositions, cells, engineered microorganisms, and kits for increasing the retention of unnatural nucleic acids encoding the unnatural amino acids in an engineered cell, or semi-synthetic organism.
Type:
Grant
Filed:
June 12, 2020
Date of Patent:
January 23, 2024
Assignee:
The Scripps Research Institute
Inventors:
Floyd E. Romesberg, Vivian T. Dien, Aaron W. Feldman, Rebekah J. Karadeema, Lingjun Li, Michael P. Ledbetter, Anne Xiaozhou Zhou
Abstract: The present invention provides novel engineered Ebolavirus GP proteins and polypeptides, scaffolded vaccine compositions that display the engineered proteins, and polynucleotides encoding the engineered proteins and scaffolded vaccine compositions. The invention also provides methods of using such engineered Ebolavirus GP proteins and vaccine compositions in various therapeutic applications, e.g., for preventing or treating Ebolavirus infections.
Type:
Grant
Filed:
April 7, 2022
Date of Patent:
January 16, 2024
Assignee:
The Scripps Research Institute
Inventors:
Linling He, Jiang Zhu, Anshul Chaudhary, Ian Wilson
Abstract: Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.
Type:
Grant
Filed:
May 11, 2021
Date of Patent:
January 9, 2024
Assignee:
THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Weijun Shen, Pengyu Yang, Huafei Zou, Peter G. Schultz
Abstract: Provided herein is a method of forming a beta-lactone from a carboxylic acid having a beta-carbon with a hydrogen atom disposed thereon. The method comprises contacting a carboxylic acid of formula (1) as described herein with an effective amount of a palladium(II) catalyst, an effective amount of an N-protected aminoacid ligand, and t-butylhydroperoxide in a solvent comprising hexafluoroisopropanol (HFIP), at about 60° C. to provide a beta-lactone of formula (2) as described herein.
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:
July 15, 2021
Date of Patent:
December 19, 2023
Assignees:
THERACLONE SCIENCES, INC., THE SCRIPPS RESEARCH INSTITUTE, INTERNATIONAL AIDS VACCINE INITIATIVE, INC.
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: The present invention provides redesigned soluble coronavirus S protein derived immunogens that are stabilized via specific modifications in the wildtype soluble S sequences. Also provided in the invention are nanoparticle vaccines that contain the redesigned soluble S immunogens displayed on self-assembling nanoparticles. Polynucleotide sequences encoding the redesigned immunogens and the nanoparticle vaccines are also provided in the invention. The invention further provides methods of using the vaccine compositions in various therapeutic applications, e.g., for preventing or treating coronaviral infections.
Abstract: Disclosed herein are methods, compositions and kits for the synthesis of proteins which comprises unnatural amino acids that utilize a mutant tRNA.
Type:
Grant
Filed:
March 9, 2021
Date of Patent:
December 5, 2023
Assignees:
THE SCRIPPS RESEARCH INSTITUTE, SYNTHORX, INC.
Inventors:
Jerod Ptacin, Carolina Caffaro, Hans Aerni, Yorke Zhang, Emil C. Fischer, Aaron W. Feldman, Vivian T. Dien, Floyd E. Romesberg
Abstract: Disclosed herein are proteins, methods, cells, engineered microorganisms, and kits for generating a modified nucleoside triphosphate transporter from Phaeodactylum tricornutum. Also disclosed herein proteins, methods, cells, engineered microorganisms, and kits for production of a nucleic acid molecule that comprises an unnatural nucleotide utilizing a modified nucleoside triphosphate transporter from Phaeodactylum tricornutum.
Abstract: By a genome-wide gene analysis of expression profiles of over 50,000 known or putative gene sequences in peripheral blood, the present inventors have identified a consensus set of gene expression-based molecular biomarkers associated with chronic allograft nephropathy and/or interstitial fibrosis and tubular atrophy CAN/IFTA and subtypes thereof. These genes sets are useful for diagnosis, prognosis, monitoring and/or subtyping of CAN/IFTA.
Type:
Grant
Filed:
February 27, 2020
Date of Patent:
November 21, 2023
Assignee:
THE SCRIPPS RESEARCH INSTITUTE
Inventors:
Daniel R. Salomon, Sunil M. Kurian, Steven R. Head
Abstract: 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:
Application
Filed:
July 11, 2023
Publication date:
November 2, 2023
Applicants:
The Scripps Research Institute, Board of Regents, The University of Texas System
Inventors:
Luke L. LAIRSON, Michael J. BOLLONG, Peter G. SCHULTZ, Sendurai A. Mani