Patents Assigned to The Salk Institute for Biological Studies
  • Publication number: 20180355374
    Abstract: Recombinant adenovirus genomes that include a heterologous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. The recombinant adenovirus genomes and recombinant adenoviruses produced by the disclosed genomes can be used, for example, in high-throughput assays to measure virus replication kinetics. Methods for measuring replication kinetics of a recombinant adenovirus are also described.
    Type: Application
    Filed: August 22, 2018
    Publication date: December 13, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Clodagh O'Shea, William Partlo, Colin Powers
  • Publication number: 20180355379
    Abstract: Recombinant adenovirus genomes that include an exogenous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. Optimal placement of the exogenous genes for minimal impact on viral kinetics is further disclosed. Therapeutic applications of the recombinant adenoviruses are also described.
    Type: Application
    Filed: August 23, 2018
    Publication date: December 13, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Clodagh O'Shea, William Partlo, Colin Powers
  • Publication number: 20180325914
    Abstract: The present disclosure provides compositions that include a nanoparticle and a compound that reduces the biological activity of one or more bromodomain and extra-terminal family member (BET) proteins (e.g., a bromodomain inhibitor), and methods of using such compounds to increase retention or storage of vitamin A, vitamin D, and/or lipids by a cell, such as an epithelial or stellate cell.
    Type: Application
    Filed: May 18, 2018
    Publication date: November 15, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Ronald M. Evans, Michael Downes, Mara Sherman, Ning Ding
  • Publication number: 20180319857
    Abstract: The present disclosure provides FGF2 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Thus, the disclosed mutant FGF2 proteins can be used to treat one or more metabolic diseases. In some examples, mutant FGF2 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels, for example to treat a metabolic disorder are also provided.
    Type: Application
    Filed: July 13, 2018
    Publication date: November 8, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Ronald M. Evans, Michael Downes, Annette Atkins, Ruth T. Yu
  • Publication number: 20180305403
    Abstract: Provided herein are deuterated compounds and compositions useful in increasing PPAR? activity. The compounds have a formula where L5 comprises at least one deuterium. Exemplary species include The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
    Type: Application
    Filed: June 28, 2018
    Publication date: October 25, 2018
    Applicant: The Salk Institute for Biological Studies
    Inventors: Ronald M. Evans, Michael Downes
  • Publication number: 20180267059
    Abstract: The invention features compositions and methods treating or preventing for age-related insulin resistance, type 2 diabetes and related disorders. The method involves depleting fTreg cells with an anti-ST2 antibody to decrease age-related fTreg accumulation and restore insulin sensitivity, thereby treating age-related insulin resistance, type 2 diabetes and related disorders.
    Type: Application
    Filed: January 12, 2016
    Publication date: September 20, 2018
    Applicant: SALK INSTITUTE FOR BIOLOGICAL STUDIES
    Inventors: SAGAR P. BAPAT, YE ZHENG, RONALD EVANS, MICHAEL DOWNES, ANNETTE R. ATKINS, RUTH T. YU
  • Patent number: 10077268
    Abstract: Novel FXR agonists are disclosed, embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.
    Type: Grant
    Filed: September 12, 2016
    Date of Patent: September 18, 2018
    Assignee: Salk Institute for Biological Studies
    Inventors: Ronald M. Evans, Michael Downes, Thomas J. Baiga, John F.W. Keana, Christopher Liddle
  • Publication number: 20180228869
    Abstract: Methods of using FGF1 analogs, such as FGF1 mutant proteins having an N-terminal deletion, point mutation(s), or combinations thereof, to reduce blood glucose levels in subjects with steroid-induced diabetes, hypercortisolemia, or diabetes due to treatment with an antipsychotic agent, are provided. Such mutant FGF1 proteins can be part of a chimeric protein that includes a ?-Klotho-binding protein, an FGFR1-binding protein, a ?-Klotho-binding protein and a FGFR1-binding protein, a C-terminal region from FGF19 or FGF21.
    Type: Application
    Filed: April 13, 2018
    Publication date: August 16, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Ronald M. Evans, Michael Downes, Annette Atkins, Ruth T. Yu
  • Publication number: 20180221423
    Abstract: Synthetic adenoviruses having chimeric fiber proteins and liver detargeting mutations are described. The synthetic adenovirus vectors are capable of specifically infecting cells at wound sites or in regions of damaged tissue. The synthetic adenovirus vectors also are capable of expressing transgenes, such as wound healing factors, at sites of wounded or damaged tissue. Accordingly, the described vectors can be used to detect wounded or damaged tissue, and/or to promote wound healing and regeneration of damaged tissue, such as by expression of heterologous wound healing or tissue regeneration factors.
    Type: Application
    Filed: April 4, 2018
    Publication date: August 9, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Clodagh O'Shea, Colin Powers, Lei Zhang
  • Patent number: 10035819
    Abstract: Provided herein are deuterated compounds and compositions useful in increasing PPAR? activity. The compounds have a formula where L5 comprises at least one deuterium. Exemplary species include The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
    Type: Grant
    Filed: April 7, 2017
    Date of Patent: July 31, 2018
    Assignee: The Salk Institute for Biological Studies
    Inventors: Ronald M. Evans, Michael Downes
  • Publication number: 20180207114
    Abstract: Brown adipose tissue (BAT) plays a role in keeping an organism warm in response to a cold environment. In response to cold, transcription factors, including peroxisome proliferator receptor alpha (PGC1?), mediate the adaptive changes in the expression of oxidative and thermogenic genes in BAT. However, even without cold, BAT exhibits high expression of these genes relative to white adipose tissue (WAT). It is shown herein that estrogen related receptor gamma (ERR?) is a critical factor that controls the expression of key metabolic genes in BAT under basal conditions. ERR? is highly expressed in BAT versus WAT, yet is not transcriptionally induced by cold, suggesting it plays an important role in innate basal BAT function rather than in the adaptive response to cold. Based on these observations, methods of increasing thermogenesis in a subject by administering a therapeutically effective amount of one or more agents that increase ERR? activity are provided.
    Type: Application
    Filed: March 21, 2018
    Publication date: July 26, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Ronald M. Evans, Michael Downes, Annette Atkins, Ruth T. Yu, Maryam Ahmadian
  • Publication number: 20180200379
    Abstract: Provided herein are methods of treating pancreatic ductal adenocarcinoma in a mammalian subject. In some examples, such methods include administering a therapeutically effective amount of a VDR agonist (such as calcipotriol and/or paricalcitol) and administering a therapeutically effective amount of one or more chemotherapeutic agents, wherein the one or more chemotherapeutic agents comprise gemcitabine, 5-fluorouracil, cisplatin, protein-bound paclitaxel, and a PD-1 monoclonal antibody and/or PDL-1 monoclonal antibody.
    Type: Application
    Filed: February 19, 2018
    Publication date: July 19, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Mara Sherman, Michael Downes, Ronald M. Evans
  • Publication number: 20180200334
    Abstract: The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidemia, obesity, and fatty liver.
    Type: Application
    Filed: February 26, 2018
    Publication date: July 19, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Johan W. Jonker, Michael Downes, Ronald M. Evans, Jae Myoung Suh
  • Publication number: 20180193418
    Abstract: The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a ?-Klotho-binding protein, an FGFR1c-binding protein, a ?-Klotho-binding protein and a FGFR1c-binding protein, a C-terminal region from FGF19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.
    Type: Application
    Filed: March 2, 2018
    Publication date: July 12, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Jae Myoung Suh, Michael Downes, Ronald M. Evans, Annette Atkins, Ruth T. Yu
  • Publication number: 20180170857
    Abstract: Provided herein are compounds and compositions useful in increasing PPAR? activity. The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
    Type: Application
    Filed: February 15, 2018
    Publication date: June 21, 2018
    Applicants: Salk Institute for Biological Studies, Mitobridge, Inc.
    Inventors: Ronald M. Evans, Michael Downes, Thomas J. Baiga, Joseph P. Noel, Emi Kanakubo Embler, Weiwei Fan, John F.W. Keana, Mark G. Bock, Authur F. Kluge, Mike A. Patane
  • Publication number: 20180171305
    Abstract: The finding that phosphatidylserine (PtdSer) exposure on the outer leaflet of virally transduced cells triggers their engulfment by resident immune cells is described. It is demonstrated that inhibition of phospholipid scramblase 1 (PLSCR1) activity prevents PtdSer externalization and enables prolonged protection of vector-transduced cells from phagocytosis. Methods of inhibiting a virus vector-induced inflammatory response in tissue, methods of prolonging virus vector encoded transgene expression, and methods of modulating an inflammatory response in tissue of a subject, by administering an inhibitor of PLSCR1 are described.
    Type: Application
    Filed: December 20, 2017
    Publication date: June 21, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Axel Nimmerjahn, Charles L. Clark
  • Publication number: 20180147245
    Abstract: Compositions and methods for retargeting adenovirus to a cell using chemical dimers are described. In particular, a recombinant adenovirus comprising a nucleic acid comprising a capsid-dimerizing agent binder conjugate and a ligand-dimerizing agent binder conjugate is provided.
    Type: Application
    Filed: January 23, 2018
    Publication date: May 31, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Clodagh O'Shea, Shigeki Miyake-Stoner, Colin Powers
  • Patent number: 9957294
    Abstract: A peptide is disclosed of the general structure: Z—W—Y, wherein Z and Y are independently a one to eight amino acid sequence wherein the amino acids are selected from glycine and alanine and W is a non-hydrolyzable pHis analogue. Such peptides can be used to produce sequence-independent anti-phosphohistidine antibodies. Also provided are antibodies that specifically bind to a peptide comprising a phosphohistidine (or a non-hydrolyzable pHis analogue) but fail to specifically bind to an identical peptide containing histidine instead of phosphohistidine.
    Type: Grant
    Filed: September 12, 2014
    Date of Patent: May 1, 2018
    Assignees: Salk Institute for Biological Studies, Sanofi
    Inventors: Magda Stankova, Fahad Al-Obeidi, Jacques Mauger, Robert A. Binnie, Tony Hunter, Jill Meisenhelder, Stephen Rush Fuhs
  • Publication number: 20180112228
    Abstract: This disclosure provides methods of downregulating or eliminating gene expression of one or more Dynamic Influencer of Gene expression (DIG) and/or one or more DIG-like (DIL) sequences in plants and plant cells, as well as constructs and compositions useful in such methods. Such recombinant plants can have decreased abscisic acid (ABA) sensitivity, decreased salt sensitivity, or both.
    Type: Application
    Filed: October 26, 2017
    Publication date: April 26, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Joseph R. Ecker, Liang Song
  • Publication number: 20180100204
    Abstract: Compositions and methods for detecting a cancer in a subject using a recombinant reporter adenovirus are described. In particular, recombinant adenovirus is used to diagnose a cancer in a patient and further used for screening compounds effective in treating the cancer in said patient.
    Type: Application
    Filed: December 8, 2017
    Publication date: April 12, 2018
    Applicant: Salk Institute for Biological Studies
    Inventors: Clodagh O'Shea, Colin Powers