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Olmalinc as a diagnostic and therapeutic target for NAFLD, NASH, metabolic syndrome, and hepatic fibrosis

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  • Publication Date:
    March 15, 2022
  • معلومة اضافية
    • Patent Number:
      11274,303
    • Appl. No:
      16/753962
    • Application Filed:
      October 05, 2018
    • نبذة مختصرة :
      An oligonucleotide that inhibits expression of an OLMALINC nucleic acid molecule, such as a small inhibitory RNA (siRNA) molecule, can be used for inhibiting the expression of OLMALINC in a subject. Methods of assaying for OLMALINC in a tissue sample can be used for detecting a disorder associated with obesity and/or type 2 diabetes in a tissue sample obtained from a subject. A method of ameliorating symptoms associated with obesity and/or type 2 diabetes comprises administering to a subject in need thereof an effective amount of an oligonucleotide of the invention or an antibody or equivalent thereof that specifically binds to and inactivates an OLMALINC nucleic acid molecule. Representative examples of a disorder associated with obesity and/or type 2 diabetes include, but are not limited to, a disorder of appetite, glycemia, body weight, liver steatosis, NASH, NAFLD, or a lipid disorder.
    • Inventors:
      THE REGENTS OF THE UNIVERSITY OF CALIFORNIA (Oakland, CA, US); UNITED STATES GOVERNMENT REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (Washington, DC, US); UNIVERSITY OF EASTERN FINLAND (Kuopio, FI)
    • Assignees:
      THE REGENTS OF THE UNIVERSITY OF CALIFORNIA (Oakland, CA, US), UNITED STATES GOVERNMENT REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS (Washington, DC, US), UNIVERSITY OF EASTERN FINLAND (Kuopio, FI)
    • Claim:
      1. An oligonucleotide that inhibits expression of an OLMALINC nucleic acid molecule, wherein the oligonucleotide is selected from SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.
    • Claim:
      2. The oligonucleotide of claim 1 , wherein the OLMALINC nucleic acid molecule is SEQ ID NO: 1.
    • Claim:
      3. The oligonucleotide of claim 1 , which is CTCCGTGAGGAGATCCACCTA (SEQ ID NO: 4).
    • Claim:
      4. A method of inhibiting the expression of OLMALINC in a subject, the method comprising administering to the subject an effective amount of an oligonucleotide of claim 1 or equivalent thereof that specifically binds to and inactivates an OLMALINC nucleic acid molecule.
    • Claim:
      5. A method of ameliorating symptoms associated with obesity and/or type 2 diabetes, the method comprising administering to a subject in need thereof an effective amount of an oligonucleotide of claim 1 or equivalent thereof that specifically binds to and inactivates an OLMALINC nucleic acid molecule, wherein the equivalent thereof is selected from TACACCTATCCCAAACCTATA (SEQ ID NO: 10); GAGATTCTTTGTGGGCTCTTA (SEQ ID NO: 11); CCCACGCTAACTGATACCATA (SEQ ID NO: 12); AAGGAACAUCUUGCCAAUUUCAAAT (SEQ ID NO: 13); and UGCCCCACGCUAACUGAUACCAUAT (SEQ ID NO: 14).
    • Claim:
      6. A pharmaceutical composition comprising an oligonucleotide of claim 1 , formulated for delivery to a patient in need of ameliorating appetite, glycemia, body weight, obesity, liver steatosis, NASH, NAFLD, lipid disorder, and/or other symptoms associated with obesity disorders and type 2 diabetes.
    • Claim:
      7. The pharmaceutical composition of claim 6 , further comprising a pharmaceutically acceptable carrier.
    • Claim:
      8. The method of claim 5 , wherein the disorder associated with obesity and/or type 2 diabetes is a disorder of appetite, glycemia, body weight, liver steatosis, NASH, NAFLD, or a lipid disorder.
    • Claim:
      9. The method of claim 5 , wherein the method comprises administering an oligonucleotide selected from SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4, to the subject.
    • Claim:
      10. The method of claim 9 , wherein the oligonucleotide is SEQ ID NO: 4.
    • Patent References Cited:
      2012/0276192 November 2012 Reich et al.
      2013/0317202 November 2013 Kawamura et al.
      2016/0339022 November 2016 Tamang et al.
      WO2016071513 May 2016


    • Other References:
      Benhammou, Jihane N., et al. “The role of a novel long intergenic non-coding RNA, Olmalinc, in the regulation of lipid metabolism”, Poster presented Oct. 6, 2017 at UCLA Specialty Training and Advanced Research (STAR) Program. cited by applicant
      Mills, James D., et al. “High Expression of Long Intervening Non-Coding RNA OLMALINC in the Human Cortical White Matter is Associated With Regulation of Oligodendrocyte Maturation”, Mol Brain. Jan. 10, 2015;8:2. doi: 10.1186/s13041-014-0091-9. cited by applicant
      International Search Report for PCT/US18/54735 (WO2019071214 Published Apr. 11, 2019), dated Jan. 22, 2019. cited by applicant
    • Primary Examiner:
      Mcgarry, Sean
    • Attorney, Agent or Firm:
      Canady, Karen S.
      canady + lortz LLP
    • الرقم المعرف:
      edspgr.11274303