# US 11,999,953 B2 · Compositions and methods for treating transposon associated diseases

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,999,953 B2
- Document ID: US11999953B2
- Status: Granted
- Kind: B2
- Application number: 16/645,083
- Filed: 2018-09-12
- Published: 2020-08-20
- Granted: 2024-06-04
- Earliest claimed: 2017-09-13
- Assignees: Children's Medical Center Corporation
- Applicants: The Children's Medical Center Corporation
- Inventors: Timothy Yu; Eunjung Alice Lee
- Web page: https://patentgrep.com/patent/US11999953B2

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 31/712: Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
- A61K 31/7125: Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
- C12Q 1/68: involving nucleic acids
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/31: of the backbone
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/33: of the base
- C12N 2320/33: Alteration of splicing
- C12N 2320/34: Allele or polymorphism specific uses
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The present invention features antisense oligonucleotides (AONs) for the treatment of diseases and disorders associated with the deleterious effects of transposable element insertion (e.g., long interspersed nuclear element-i (LINE-1), Arthrobacter luteus element (Alu), short interspersed nuclear element variable number tandem repeat Arthrobacter luteus element (SINE-VNTR-Alu) or (SVA), or endogenous retrovirus (ERV). In one aspect, the invention provides one or more antisense oligonucleotides complementary to a transposable element present in an intronic sequence within a gene. In another aspect, the invention provides a method for treating a subject having a genetic disorder associated with the insertion of a transposable element, the method involving administering to the subject one or more antisense oligonucleotides of any aspect delineated herein.

## Claims

### Claim 1

One or more antisense oligonucleotides complementary to an intronic sequence within a genome, wherein the one or more antisense oligonucleotides comprises a modified backbone, wherein the modified backbone comprises a 2′ methoxy ethyl modification or a 2′ O-methyl modification, wherein the one or more antisense oligonucleotides binds a splice acceptor site activated by a transposable element or a predicted splice enhancer sequence flanking the splice acceptor site, wherein the one or more antisense oligonucleotides induces exon skipping of an exon, and wherein the one or more antisense oligonucleotides have at least 85% sequence identity to the entire length of the nucleotide sequence AGCUUUUCAGGCUUACAUUUACUCAUCU (SEO ID NO. 2578) or the nucleotide sequence AAUGUUAGUGCUUGUUGAGGGC (SEO ID NO. 2579).

### Claim 2 (depends on 1)

The antisense oligonucleotide of claim 1, further comprising at least one modified nucleobase.

### Claim 3 (depends on 1)

A set of antisense oligonucleotides comprising 2 or more of the antisense oligonucleotides of claim 1.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising of the antisense oligonucleotide of claim 1 in a pharmaceutically acceptable excipient.

### Claim 5 (depends on 1)

The one or more antisense oligonucleotides of claim 1, wherein the antisense oligonucleotides further comprise a 5-methyl cytosine and/or a 5-methyl uracil.