# US 10,370,665 B2 · Compositions and methods for treating cancer, inhibiting cell proliferation, and inducing cell death

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- Number: US 10,370,665 B2
- Document ID: US10370665B2
- Status: Granted
- Kind: B2
- Application number: 15/122,663
- Filed: 2015-03-04
- Published: 2017-03-09
- Granted: 2019-08-06
- Earliest claimed: 2014-03-04
- Assignees: University of Louisville Research Foundation, Inc.
- Applicants: University of Louisville Research Foundation, Inc.
- Inventors: Donald M. Miller; Shelia D. Thomas; Alexandra Sokolova; Francine Rezzoug
- Web page: https://patentgrep.com/patent/US10370665B2

## CPC

- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12N 2310/13: Decoys
- C12N 2310/151: more than 3 strands, e.g. tetrads, H-DNA
- C12N 2310/18: acting by a non-sequence specific mechanism
- C12N 2320/31: Combination therapy
- 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)

## Abstract

Quadruplex-forming guanine-rich nucleic acid sequences are useful in compositions and methods for inhibiting cellular growth and proliferation and inducing cell death. Compositions for treating a patient are provided, including (i) a safe and effective amount of a sequence having at least 80% nucleic acid identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and combinations thereof, and (ii) a carrier, wherein the isolated oligonucleotide forms at least one quadruplex.

## Claims

### Claim 1

A composition comprising: (i) at least two different isolated oligonucleotides and each oligonucleotide has at least 80% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, (ii) a carrier, and (iii) a growth inhibiting agent.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the composition comprises at least three different isolated oligonucleotides and each oligonucleotide has at least 80% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

### Claim 3 (depends on 1)

The composition of claim 1, wherein at least one isolated oligonucleotide has at least 90% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

### Claim 4 (depends on 1)

The composition of claim 1, wherein at least one isolated oligonucleotide has at least 95% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

### Claim 5 (depends on 1)

The composition of claim 1, wherein at least one isolated oligonucleotide has at least 98% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

### Claim 6 (depends on 1)

The composition of claim 1, wherein at least one isolated oligonucleotide has at least 99% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

### Claim 7 (depends on 1)

The composition of claim 1, wherein at least one isolated oligonucleotide has a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12.

### Claim 8 (depends on 1)

The composition of claim 1, wherein at least one isolated oligonucleotide has at least 80% nucleic acid sequence identity with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 7, and SEQ ID NO: 8.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the growth inhibiting agent is a chemotherapeutic agent.

### Claim 10 (depends on 1)

A method of inhibiting cell growth, comprising contacting a cell with the composition of claim 1.

### Claim 11 (depends on 1)

A method of inhibiting telomerase activity of a cell, comprising contacting the cell with the composition of claim 1.

### Claim 12 (depends on 10)

The method of claim 10, wherein the composition comprises an isolated oligonucleotide with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 8.

### Claim 13 (depends on 11)

The method of claim 11, wherein the composition comprises an isolated oligonucleotide with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 8.

### Claim 14 (depends on 10)

The method of claim 10, wherein the composition comprises an isolated oligonucleotide with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 7, and SEQ ID NO: 8.

### Claim 15 (depends on 10)

The method of claim 10, wherein the composition comprises an isolated oligonucleotide with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 7, and SEQ ID NO: 8.

### Claim 16 (depends on 1)

The composition of claim 1, wherein the composition comprises an isolated oligonucleotide with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 7, and SEQ ID NO: 8.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the composition comprises (a) two or more isolated oligonucleotides selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 7, and SEQ ID NO: 8 and (b) a chemotherapeutic agent.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the composition comprises an isolated oligonucleotide with a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 8.

### Claim 19 (depends on 1)

The composition of claim 1, wherein the composition comprises (a) two or more isolated oligonucleotides selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 8 and (b) a chemotherapeutic agent.

### Claim 20 (depends on 2)

The composition of claim 2, wherein the composition comprises (a) two or more isolated oligonucleotides selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 8 and (b) a chemotherapeutic agent.

### Claim 21 (depends on 1)

The composition of claim 1, wherein at least one oligonucleotide is no more than 68 nucleotides long.
