# US 2021/0330692 A1 · Ccr7 aptamers and uses thereof

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- Number: US 2021/0330692 A1
- Document ID: US20210330692A1
- Status: Published application
- Kind: A1
- Application number: 17/319,391
- Filed: 2021-05-13
- Published: 2021-10-28
- Earliest claimed: 2018-01-07
- Assignees: City of Hope
- Applicants: City of Hope
- Inventors: John J. ROSSI; Jiehua ZHOU; Mayumi TAKAHASHI
- Web page: https://patentgrep.com/patent/US20210330692A1

## CPC

- A61K 31/7115: Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61P 35/00: Antineoplastic agents
- C12N 15/115: Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/16: Aptamers
- C12N 2310/317: with an inverted bond, e.g. a cap structure
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/322: 2'-R Modification
- C12N 2310/3519: Fusion with another nucleic acid
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N 2320/51: modulating the chemical stability, e.g. nuclease-resistance
- 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)
- 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)

## Abstract

Disclosed herein are CCR7 aptamers that specifically bind to and internalize into CCR7-expressing cells. The aptamers can be used as a therapeutic agent by itself or in combination with a small molecule by forming a conjugate with the small molecule. Targeted delivery of the small molecule can be achieved by such conjugates. Also disclosed are methods of treating a subject suffering from cancer by administering an effective amount of the aptamer or the aptamer-small molecule conjugate to the subject.

## Claims

### Claim 1

A cell-type specific aptamer-small molecule conjugate com prising:
an aptamer that specifically binds CCR7, and
a small molecule conjugated to the aptamer via non-covalent conjugation, wherein the CCR7 aptamer is C-1A (SEQ ID NO: 1), C-2A (SEQ ID NO: 2), DD9-9 (SEQ ID NO: 3), or C-6 (SEQ ID NO: 4).

### Claim 2 (depends on 1)

The aptamer-small molecule conjugate of claim 1, wherein the aptamer is an RNA molecule.

### Claim 3 (depends on 1)

The aptamer-small molecule conjugate of claim 1, wherein the aptamer is chemically modified in-SELEX or post-SELEX.

### Claim 4 (depends on 1)

The aptamer-small molecule conjugate of claim 1, wherein the aptamer is chemically modified by replacing the 2′ position with either a fluoro-(F), amino-(NH2), or O-methyl (OCH3) group, and by capping the 3′ end with inverted thymidine.

### Claim 5 (depends on 1)

The aptamer-small molecule conjugate of claim 1, wherein the small molecule is an saRNA, an siRNA, an shRNA, an miRNA, a different aptamer, a chemotherapeutic agent, or a toxin.

### Claim 6 (depends on 5)

The aptamer-small molecule conjugate of claim 5, wherein the saRNA targets CCAAT/enhancer-binding protein-α.

### Claim 7 (depends on 1)

The aptamer-small molecule conjugate of claim 1, wherein the conjugate is a bispecific aptamer-aptamer conjugate.

### Claim 8 (depends on 7)

The aptamer-small molecule conjugate of claim 7, wherein one aptamer binds CCR7 and the other aptamer binds PD-1 or PD-L1.

### Claim 9 (depends on 1)

The aptamer-small molecule conjugate of claim 1, wherein the aptamer is conjugated to the small molecule via one or more linkers.

### Claim 10 (depends on 9)

The aptamer-small molecule conjugate of claim 9, wherein the linker is a nucleotide linker or a polycarbon linker.

### Claim 11 (depends on 1)

The aptamer-small molecule conjugate of claim 1, wherein the aptamer is conjugated to the small molecule via a sticky bridge comprising a complementary sequence.

### Claim 12

A MATE comprising a CCR7 aptamer, a PD-1 aptamer, and a CD8 aptamer, wherein the CCR7 aptamer is C-1A (SEQ ID NO: 1), C-2A (SEQ ID NO: 2), DD9-9 (SEQ ID NO: 3), or C-6 (SEQ ID NO: 4).

### Claim 13

A method for treating a cancer patient comprising administering a therapeutically effective amount of a therapeutic composition, wherein the therapeutic composition comprises a CCR7 aptamer, a conjugate of a CCR7 aptamer and a small molecule, or a MATE comprising a CCR7 aptamer, a PD-1 aptamer, and a CD8 aptamer,
wherein the CCR7 aptamer is C-1A (SEQ ID NO: 1), C-2A (SEQ ID NO: 2), DD9-9 (SEQ ID NO: 3), or C-6 (SEQ ID NO: 4).

### Claim 14 (depends on 13)

The method of claim 13, wherein the aptamer is an RNA molecule.

### Claim 15 (depends on 13)

The method of claim 13, wherein the aptamer is chemically modified in-SELEX or post-SELEX.

### Claim 16 (depends on 13)

The method of claim 13, wherein the aptamer is chemically modified by replacing the 2′ position with either a fluoro-(F), amino-(NH2), or 0-methyl (OCH3) group, and by capping the 3′ end with inverted thymidine.

### Claim 17 (depends on 13)

The method of claim 13, wherein the small molecule includes an saRNA, an siRNA, an shRNA, an miRNA, a different aptamer, a chemotherapeutic agent, and a toxin.

### Claim 18 (depends on 13)

The method of claim 13, wherein the patient suffers from breast cancer, melanoma, non-small cell lung cancer, prostate cancer, chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), or T-cell leukemia.

### Claim 19 (depends on 1)

The aptamer-small molecule conjugate of claim 1, wherein the CCR7 aptamer is C-1A (SEQ ID NO: 1), or C-2A (SEQ ID NO: 2).

### Claim 20 (depends on 13)

The method of claim 13, wherein the CCR7 aptamer is C-1A (SEQ ID NO: 1), or C-2A (SEQ ID NO: 2).