IP Library Granted Patent US 12,024,707
Granted Patent B2
US 12,024,707 · App. 17/158,845 · Granted Jul 2, 2024

Methods and compositions for modulating lncRNAs and methods of treatment based on lncRNA expression

Inventors: Christopher Maher (St. Louis, MO); Jessica Silva-Fisher (St. Louis, MO); Ryan Fields (St. Louis, MO)
Assignee: Washington University
C12N15/113A61K45/06C12N15/102C12Q1/6886C12N2310/11C12N2320/30C12Q2600/106C12Q2600/178
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Quick Facts
Patent No.
US 12,024,707
App. No.
17/158,845
Granted
Jul 2, 2024
Kind
B2
Abstract

Among the various aspects of the present disclosure is the provision of a methods and compositions for modulating lncRNAs and methods of treatment based on lncRNA expression.

Claims (45)

1. A method of treating a subject having cancer expressing RAMS11, the method comprising:

providing a biological sample from the subject, the biological sample comprising long noncoding RNA associated with metastasis (RAMS);

measuring a level of RAMS11 (SEQ ID NO: 1) in the biological sample;

administering to the subject, when the measured level of RAMS11 is overexpressed compared to a control sample, a treatment comprising at least one antisense oligonucleotide (ASO) selected from CAACTTCCAGCAAGAT (SEQ ID NO: 41) and AGAACTGCTAAAAGTG (SEQ ID NO: 42); and

wherein the cancer expressing RAMS11 is selected from the group consisting of colorectal cancer (CRC), lung cancer, head or neck cancer, and kidney cancer.

2. The method of claim 1 , wherein the subject is not treated with a topoisomerase inhibitor.

3. The method of claim 1 , wherein the subject is further administered a therapeutically effective amount of: a kinase inhibitor, an alkylating agent, an antineoplastic antibiotic, or an anthracycline antibiotic.

4. The method of claim 1 , wherein the ASO reduces expression of one or more RAMS11 exons selected from the group consisting of:

 (SEQ ID NO: 2)

AGAATGCCAAAGAGCAGCAGGATGGATCCAGCATCCTCTCCTGATAAAAG

AGGGCTAGAAGACGGGAGGCTCCGGGAAGTCTACTGG;

(SEQ ID NO: 3)

AGTCATGAAGACACTGAAAAGTGATGAATCCACATAACCATGACACTGGA

AATGAAGTTTGAGTGGCAGTCAGAATCTGGGAGGAAGCATTGCTAAGTGA

AAATCTTATGGAGCTTGACTAAAAATCCCTGTCAGGAACCGTCAAAAGCT

GTGTCCCTGACATGAAAAATCTTGCTGGAAGTTGAGAGAGGTTTATGCCT

ACTCCGTGATCCGGGAACACAAGACCTTTACCAACCAAAAAAGTGGATAG

CTGTTCTTCTGCTGTGAAGGTTAATAAAG;

(SEQ ID NO: 4)

AACGCCAGAAGTGCCAAGCAATTAACAACCCCAGAAGCAACCCTTAACCA

ATGATTAAATAAAGTGGATGATTACATACCCAAGCTCCTTCAACTCCCAG

GGACATAATTCTGAG;

 (SEQ ID NO: 5)

GGATGGAAAACAAACTGAAACTGGCTCAAGTGAATGCTCACTGGAAGGCT

TACTGGAAAACTTACTGGAAGGATGTGAGGACATGTTCGGGAATCTATTT

GCAGAAAACATATTCAG; 

and

 (SEQ ID NO: 6)

CCCTGTCCACCACAGCCAGCTGGCTGAAGAGCTCAAAAGGCAAGAAATCA

GCAAGAGAGAGAGATGAAGCATGAGAAATGAGCAAAAAACACCCAGCACA

TCATAATCTTGGACAGTTTAGCAGTACATGAAAATAGATGGTCCTCGCCC

CAAGGGACTGCAGTAACCCTGAATAAACAGGATGTCTCTCACTTTTAGCA

GTTCTTTCTGTGCTAGTATTGGGGAAATATATTTTTGGCTGCATGCAAAA

TGGTAAAAGACATCTATTAAGAAAATGAAAACAATGCTTCTGTTTTAGAC

GAAGCTTTTGAAGGTTTAAGGATCACCTATTTATTGACAAAATTGTTTCC

GTGGCTTAAAA.

5. The method of claim 1 , wherein the biological sample comprises tumor cells, circulating tumor cells (CTCs), or formalin-fixed paraffin-embedded (FFPE) tissue, or frozen tissue.

6. The method of claim 1 , wherein the biological sample comprises tumor long noncoding RNAs (lncRNAs).

7. The method of claim 1 , wherein the biological sample is tumor tissue.

8. The method of claim 1 , wherein the biological sample is a biopsy sample.

9. The method of claim 1 , wherein the cancer is selected from the group consisting of: colorectal adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, head and neck squamous cell carcinoma (HNSC), and kidney renal papillary cell carcinoma (KIRP).

10. The method of claim 1 , wherein overexpressed RAMS11, indicates a bad outcome.

11. The method of claim 1 , wherein overexpressed RAMS11 indicates aggressive CRC.

12. The method of claim 1 , wherein overexpressed RAMS11 indicates a poor prognosis.

13. The method of claim 1 , wherein RAMS11 is detected by qPCR.

Assignments (2)
CONFIRMATORY LICENSE Recorded Nov 2, 2023
From: WASHINGTON UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065431/0122 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 2, 2021
From: MAHER, CHRISTOPHER; SILVA-FISHER, JESSICA; FIELDS, RYAN
To: WASHINGTON UNIVERSITY
Reel/Frame 055107/0988 →
Continuity (2)
Provisional Application 62965984 · Jan 26, 2020
Related Publication 20210277395A1 · Sep 9, 2021