# US 10,370,664 B2 · Use of IKK epsilon inhibitors to activate NFAT and T cell response

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- Number: US 10,370,664 B2
- Document ID: US10370664B2
- Status: Granted
- Kind: B2
- Application number: 15/034,529
- Filed: 2014-11-07
- Published: 2016-10-06
- Granted: 2019-08-06
- Earliest claimed: 2013-11-07
- Assignees: University of Southern California
- Applicants: University of Southern California
- Inventors: Pinghui Feng; Junjie Zhang; Hao Feng
- Web page: https://patentgrep.com/patent/US10370664B2

## CPC

- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- C07K 16/40: against enzymes
- 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)}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/531: Stem-loop; Hairpin
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

Disclosed herein are compositions and methods of activating nuclear factor of activated T cells (NFAT) and T cell response by inhibiting IKKε.

## Claims

### Claim 1

A method for suppressing, repressing, or ameliorating cancer in a subject, the method comprising administering to the subject an IKKε inhibitor, wherein the IKKε inhibitor comprises a polynucleotide sequence selected from SEQ ID NO:1 or SEQ ID NO: 2.

### Claim 2 (depends on 1)

The method of claim 1, wherein the IKKε inhibitor increases NFAT activation relative to a control.

### Claim 3 (depends on 1)

The method of claim 1, wherein the IKKε inhibitor increases T cell response relative to a control.

### Claim 4 (depends on 3)

The method of claim 3, wherein CD8 T cell response is increased relative to a control.

### Claim 5 (depends on 3)

The method of claim 3, wherein the IKKε inhibitor increases anti-cancer T-cell mediated immunity.

### Claim 6 (depends on 3)

The method of claim 3, wherein the T cell response is increased by at least about 2-fold to at least about 10-fold.

### Claim 7 (depends on 1)

The method of claim 1, wherein a therapeutically effective amount of the IKKε inhibitor is administered.

### Claim 8

A method of increasing NFAT activation in a subject, the method comprising administering to the subject an IKKε inhibitor comprising a polynucleotide sequence selected from SEQ ID NO:1 or SEQ ID NO: 2.

### Claim 9

A method of increasing NFAT activation in a subject, the method comprising administering to the subject an IKKε inhibitor comprising an inhibitory RNA that targets IKKε, wherein CD8 T cell response is increased relative to a control.

### Claim 10 (depends on 9)

The method of claim 9, wherein the inhibitory RNA comprises a shRNA.

### Claim 11

A method of increasing T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor comprising an inhibitory RNA that targets IKKε, wherein CD8 T cell response is increased relative to a control.

### Claim 12

A method of increasing NFAT activation and T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor comprising an inhibitory RNA that targets IKKε, wherein CD8 T cell response is increased relative to a control.

### Claim 13

A method of increasing T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor comprising a polynucleotide sequence selected from SEQ ID NO:1 or SEQ ID NO: 2.

### Claim 14

A method of increasing NFAT activation and T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor comprising a polynucleotide sequence selected from SEQ ID NO:1 or SEQ ID NO: 2.