IP Library › Granted Patent US 12,503,695
Granted Patent B2
US 12,503,695 · App. 17/792,507 · Granted Dec 23, 2025

RAB13 and NET1 antisense oligonucleotides to treat metastatic cancer

Inventor: Stavroula Mili (Bethesda, MD)
Assignee: The United States of America, as represented by the Secretary, Department of Health and Human Services
C12N15/113A61K45/06A61P35/04C12N2310/11
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,503,695
App. No.
17/792,507
Granted
Dec 23, 2025
Kind
B2
Abstract

Provided herein are antisense oligonucleotides (ASOs) specific for Rab13 and Net1, for example specific for a GA-rich region of the 3′-UTR. In some examples, the ASOs are modified. Methods of using these ASOs to reduce the migration of metastatic cancer cells are provided, for example as a use to treat metastatic cancer.

Claims (25)

1 . An isolated antisense oligonucleotide (ASO) no more than 28 nucleotides in length, comprising the sequence of any one of SEQ ID NO: 8, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 30, SEQ ID NO: 31 and SEQ ID NO: 32, wherein:

the ASO comprises one or more chemical modifications;

a detectable label is covalently attached to the ASO; and/or

a nanoparticle is covalently attached to the ASO.

2 . The isolated ASO of elaine-Her claim 1 , wherein the sequence of the ASO consists of the sequence of any one of SEQ ID NO: 8, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 30, SEQ ID NO: 31 and SEQ ID NO: 32.

3 . The isolated ASO of claim 1 , wherein the ASO comprises one or more chemical modifications.

4 . The isolated ASO of claim 3 , wherein the one or more chemical modifications comprises at least one phosphorothioate, at least one 2′-fluoro, at least one 2′-O-methyl, at least one 2′-O-methoxy-ethyl, at least one morpholino, at least one 2′,4′-constrained ethyl nucleic acid, and/or at least one locked nucleic acid (LNA).

5 . The isolated ASO of claim 1 , wherein a detectable label is covalently attached to the ASO.

6 . The isolated ASO of claim 1 , wherein a nanoparticle is covalently attached to the ASO.

7 . The isolated ASO of claim 6 , wherein the nanoparticle comprises a polymeric nanoparticle, nanosphere, nanocapsule, liposome, dendrimer, polymeric micelle, or niosome.

8 . An in vitro cell comprising the isolated ASO of claim 2 .

9 . The in vitro cell of claim 7 , wherein the cell is a bacterial cell or mammalian cell.

10 . A composition comprising one or more isolated ASOs of claim 1 , and a pharmaceutically acceptable carrier.

11 . A method of treating a metastatic tumor, comprising:

administering a therapeutically effective amount of one or more of the isolated ASOs of, claim 1 to a subject with the metastatic tumor, thereby treating the metastatic tumor.

12 . The method of claim 11 , wherein the method reduces a number of metastases of the metastatic tumor, reduces the size of a metastasis, reduces the volume of a metastasis, or combinations thereof.

13 . The method of claim 11 , wherein the administering is intratumoral.

14 . A method of reducing migration of a cell, comprising:

contacting a cell with a therapeutically effective amount of one or more of the isolated ASOs of claim 1 , thereby reducing migration of the cell.

15 . The method of claim 14 , wherein the method reduces a migration speed of the cell, protrusion velocity of the cell, retraction velocity of the cell, or combinations thereof.

16 . The method of claim 14 , wherein the cell is a metastatic tumor cell.

17 . The method of claim 11 , wherein the metastatic tumor is a tumor of the breast, lung, colon, pancreas, ovary, uterus, cervix, skin, prostate, bone, central nervous system, kidney, or head and neck.

18 . The method of claim 14 , wherein the cell is in a subject, and contacting comprises administration to the subject.

19 . The method of claim 11 , further comprising administering a therapeutically effective amount of an additional anti-cancer agent to the subject.

20 . The method of claim 19 , wherein the anti-cancer agent comprises a chemotherapeutic, radiation therapy, and/or a biologic.

Assignments (2)
CHANGE OF NAME Recorded Jul 19, 2023
From: SORTERA ALLOYS, INC.
To: SORTERA TECHNOLOGIES, INC.
Reel/Frame 064414/0101 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 4, 2022
From: MILI, STAVROULA
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 060722/0428 →
Continuity (2)
Provisional Application 62966204 · Jan 27, 2020
Related Publication 20230057461A1 · Feb 23, 2023
References Cited (28)
US 20050118625A1 · Mounts · 2005 [cited by applicant]
EP 2311530 · 2011 [cited by applicant]
WO WO2010040571 · 2010 [cited by applicant]
WO WO2014028884A2 · 2014 [cited by examiner]
GenBank: BC000799.1. [cited by examiner]
Buck et al. Design Strategies and Performance of Custom DNA Sequencing Primers. (1999) BioTechniques, 27:3, 528-536. (Year: 1999). [cited by examiner]
Mayr. What Are 3' UTRs Doing? Cold Spring Harb Perspect Biol 2019; 11:a034728. (Year: 2019). [cited by examiner]
NCBI Reference Sequence: NM_001047160.3. [cited by examiner]
NCBI Reference Sequence: NM_002870.5. [cited by examiner]
Carr et al., “Regulation of Focal Adhesion Kinase Activation, Breast Cancer Cell Motility, and Amoeboid Invasion by the RhoA Guanine Nucleotide Exchange Factor Net1,” [cited by applicant]
Chrisafis and Mili, “Polarized Distribution of Rab13 and Net1 mRNAs During Collective Invasion,” poster presentation, FASEB conference, Sep. 2018. [cited by applicant]
Chrisafis et al., “Collective Cancer Cell Invasion requires RNA Accumulation at the Invasive Front,” [cited by applicant]
Diao et al., “Rab13 Silencing Causes Inhibition of Growth and Induction of Apoptosis in Human Glioma Cells,” [cited by applicant]
Havens and Hastings, “Splice-switching antisense oligonucleotides as therapeutic drugs,” [cited by applicant]
International Search Report and Written Opinion of PCT/US2021/015053, mailed May 20, 2021 (15 pages). [cited by applicant]
Ioannou et al., “DENND2B Activates Rab13 at the Leading Edge of Migrating Cells and Promotes Metastatic Behavior,” [cited by applicant]
Ioannou et al., “Regulation of Cancer Cell Behavior by the Small GTPase Rab13,” [cited by applicant]
Jakobsen et al., Direct RNA Sequencing Mediated Identification of mRNA Localized in Protrusions of Human MDA-MB-231 Metastatic Breast Cancer Cells, [cited by applicant]
Juliano, “The delivery of therapeutic oligonucleotides,” [cited by applicant]
Mili et al., “Genome-Wide Screen Identifies Localized RNAs Anchored at Cell Protrusions Through Microtubules and APC,” [cited by applicant]
Mili, “Regulation of cell migration and GTPase function through mechanical control of RNA localization,” Presentation at Signaling by Adhesion Receptors Gordon Research Conference, Jun. 25, 2018. [cited by applicant]
Moissoglu et al., “Translational Regulation of Protrusion-Localized RNAs Involves Silencing and Clustering after Transport,” [cited by applicant]
Moissoglu et al., “Translational regulation of protrusion-localized RNAs involves silencing and clustering after transport,” poster presentation, EMBO Conference, Jun. 2019. [cited by applicant]
Moissoglu et al., “RNA Localization and Co-Translational Interactions Control RAB13 GTPase Function and Cell Migration,” [cited by applicant]
Murray et al., “NET I-mediated RhoA Activation Facilitates Lysophosphatidic Acid-Induced Cell Migration and Invasion in Gastric Cancer,” [cited by applicant]
Sahgal et al., “GGA2 and RAB13 Promote Activity-Dependent β1-integrin Recycling,” [cited by applicant]
Wang et al., “Extracellular Matrix Stiffness and Cell Contractility Control RNA Localization to Promote Cell Migration,” [cited by applicant]
Zuo et al., “Contributions of the RhoA Guanine Nucleotide Exchange Factor Net1 to Polyoma Middle T Antigen-Mediated Mammary Gland Tumorigenesis and Metastasis,” [cited by applicant]