# US 11,306,312 B2 · Compositions and methods for MYC messenger RNA inhibitors

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- Number: US 11,306,312 B2
- Document ID: US11306312B2
- Status: Granted
- Kind: B2
- Application number: 16/643,820
- Filed: 2018-08-31
- Published: 2020-07-02
- Granted: 2022-04-19
- Earliest claimed: 2017-09-01
- Assignees: Thomas Jefferson University; Bound Therapeutics, LLC
- Applicants: Thomas Jefferson University; Bound Therapeutics, LLC
- Inventors: Eric Wickstrom; Yuan-Yuan Jin
- Web page: https://patentgrep.com/patent/US11306312B2

## CPC

- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- C07K 14/47: from mammals
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C12N 2310/11: Antisense
- C12N 2310/3231: having an additional ring, e.g. LNA, ENA
- C12N 2310/341: Gapmers, i.e. of the type ===---===
- C12N 2310/3513: Protein; Peptide
- C12N 2320/30: Special therapeutic applications
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention provides compositions and methods of making and using MYC mRNA antisense inhibitors. In a particular embodiment, the invention features compositions and methods useful for the treatment of a condition (e.g., cancer).

## Claims

### Claim 1

A 2′-O, 4′-C-aminomethylene bridged nucleic acid (BNA)-deoxyribonucleic acid (DNA)-2′O, 4′-C-aminomethylene bridged nucleic acid (BNA) chimeric antisense oligonucleotide for reduction of MYC activity, wherein the BNA-DNA-BNA chimeric antisense oligonucleotide comprises SEQ ID NO: 2.

### Claim 2 (depends on 1)

The BNA-DNA-BNA chimeric antisense oligonucleotide of claim 1, wherein the DNA comprises a modified backbone linkage selected from at least one of a boranophosphate, methylphosphonate, phosphorothioate, and phosphoramidates backbone linkage.

### Claim 3 (depends on 2)

The BNA-DNA-BNA chimeric anti sense oligonucleotide of claim 2, further comprising a conjugated peptide which undergoes endocytosis via the insulin-like growth factor 1 (IGF1) receptor.

### Claim 4 (depends on 3)

The BNA-DNA-BNA chimeric anti sense oligonucleotide of claim 3, wherein the peptide comprises SEQ ID NO: 3.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising the BNA-DNA-BNA chimeric antisense oligonucleotide of claim 1 and a pharmaceutically acceptable carrier.

### Claim 6

A kit comprising a 2′-O, 4′-C-aminomethylene bridged nucleic acid (BNA)-deoxyribonucleic acid (DNA)-2′O, 4′-C-aminomethylene bridged nucleic acid (BNA) chimeric antisense oligonucleotide which reduces MYC activity, wherein the BNA-DNA-BNA chimeric anti sense oligonucleotide comprises SEQ ID NO: 2, and instructional material for use thereof.

### Claim 7 (depends on 6)

The kit of claim 6, wherein said deoxynucleic acid (DNA) comprises a backbone modification selected from at least one of a boranophosphate, methylphosphonate, phosphorothioate, and phosphoramidates backbone linkage.

### Claim 8

A method for reducing MYC mRNA translation in a cell, the method comprising contacting the cell with a 2′-O, 4′-C-aminomethylene bridged nucleic acid (BNA)-deoxyribonucleic acid (DNA)-2′O, 4′-C-aminomethylene bridged nucleic acid (BNA) chimeric antisense oligonucleotide comprising SEQ ID NO: 2.

### Claim 9 (depends on 8)

The method of claim 8, wherein reduction of MYC mRNA translation causes a reduction in PD-L1 protein expression.

### Claim 10 (depends on 8)

The method of claim 8, wherein the BNA-DNA-BNA chimeric antisense oligonucleotide further comprises a conjugated peoptide which undergoes endocytosis via the insulin-like growth factor 1 (IGF1) receptor.

### Claim 11 (depends on 10)

The method of claim 10, wherein the peptide comprises SEQ ID NO: 3.

### Claim 12 (depends on 8)

The method of claim 8, wherein reduction of MYC mRNA translation causes a reduction in PD-L2, CD47, and Jak2 protein expression.

### Claim 13

A method of treating a condition in a subject, the method comprising administering to the subject a therapeutically effective amount of a 2′-O, 4′-C-aminomethylene bridged nucleic acid (BNA)-deoxyribonucleic acid (DNA)-2′O, 4′-C-aminomethylene bridged nucleic acid (BNA) chimeric antisense oligonucleotide for reducing MYC mRNA translation, wherein the BNA-DNA-BNA chimeric antisense oligonucleotide comprises SEQ ID NO: 2.

### Claim 14 (depends on 13)

The method of claim 13, wherein reduction in MYC mRNA translation causes a reduction in PD-L1 protein expression.

### Claim 15 (depends on 13)

The method of claim 13, wherein the BNA-DNA-BNA chimeric antisense oligonucleotide further comprises a conjugated peptide which undergoes endocytosis via the insulin-like growth factor 1 (IGF1) receptor.

### Claim 16 (depends on 15)

The method of claim 15, wherein the peptide comprises SEQ ID NO: 3.

### Claim 17 (depends on 13)

The method of claim 13, wherein the condition is cancer.

### Claim 18 (depends on 17)

The method of claim 17, wherein the cancer is selected from the group consisting of breast cancer and lung cancer.

### Claim 19 (depends on 13)

The method of claim 13, wherein the condition is selected from the group consisting of inflammation, arthritis, neurodegeneration, cardiovascular disease, and autoimmune disorders.

### Claim 20 (depends on 13)

The method of claim 13, wherein reduction of MYC mRNA translation causes a reduction in PD-L2, CD47, and Jak2 protein expression.

### Claim 21 (depends on 13)

The method of claim 13, wherein said deoxynucleic acid (DNA) comprises a backbone modification selected from at least one of a boranophosphate, methylphosphonate, phosphorothioate, and phosphoramidates backbone linkage.