# US 10,870,687 B2 · Anti-human papillomavirus 16 E7 T cell receptors

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- Number: US 10,870,687 B2
- Document ID: US10870687B2
- Status: Granted
- Kind: B2
- Application number: 16/205,631
- Filed: 2018-11-30
- Published: 2019-03-21
- Granted: 2020-12-22
- Earliest claimed: 2014-05-29
- Assignees: The United States of America as represented by the Secretary, Department of Health and Human Service
- Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Inventors: Christian S. Hinrichs; Steven A. Rosenberg
- Web page: https://patentgrep.com/patent/US10870687B2

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 11/04: for throat disorders
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/02: for disorders of the vagina
- A61P 31/20: for DNA viruses
- A61P 35/00: Antineoplastic agents
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- G01N 33/56983: {Viruses}
- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- 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)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/32: fusions with soluble part of a cell surface receptor, "decoy receptors"
- G01N 2333/025: Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
- 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)
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Disclosed is a synthetic T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of human papillomavirus (HPV) 16 E7, E711-19. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of a condition in a mammal and methods of treating or preventing a condition in a mammal, wherein the condition is cancer, HPV 16 infection, or HPV-positive premalignancy.

## Claims

### Claim 1

A T cell receptor (TCR) comprising a human variable region and a murine constant region, or a functional variant of the TCR, wherein the TCR and the functional variant comprise the amino acid sequences of SEQ ID NOs: 3-8 and have antigenic specificity for human papillomavirus (HPV) 16 E7.

### Claim 2 (depends on 1)

The TCR or functional variant of claim 1, wherein the TCR has antigenic specificity for HPV 16 E711-19 SEQ ID NO: 2.

### Claim 3 (depends on 1)

The TCR or functional variant of claim 1, comprising the amino acid sequences of (a) SEQ ID NO: 9 and (b) SEQ ID NO: 10, wherein X at position 2 is Ala or Gly.

### Claim 4 (depends on 1)

The TCR or functional variant of claim 1, comprising the amino acid sequences of
(a) SEQ ID NO: 16, wherein
(i) X at position 48 is Thr or Cys;
(ii) X at position 112 is Ser, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
(iii) X at position 114 is Met, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp; and
(iv) X at position 115 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp; and
(b) SEQ ID NO: 18, wherein X at position 56 is Ser or Cys.

### Claim 5 (depends on 1)

The TCR or functional variant of claim 1, comprising the amino acid sequences of
(a) any one of SEQ ID NOs: 17, 21, 24, and 25; and
(b) any one of SEQ ID NOs: 19 and 23.

### Claim 6 (depends on 1)

The TCR or functional variant of claim 1, comprising the amino acid sequences of
(a) (i) SEQ ID NO: 22, (ii) SEQ ID NO: 26, (iii) SEQ ID NO: 9 and 24, (iv) SEQ ID NO: 9 and 16, or (v) SEQ ID NOs: 9 and 17; and
(b) (i) SEQ ID NOs: 10 and 18 or (ii) any one of SEQ ID NOs: 20 and 27.

### Claim 7 (depends on 1)

The TCR or functional variant of claim 1, comprising the amino acid sequence of SEQ ID NO: 29 or 30.

### Claim 8

An isolated or purified polypeptide comprising the amino acid sequences of (a) SEQ ID NOs: 3-5, (b) SEQ ID NOs: 6-8, or (c) SEQ ID NOs: 3-8.

### Claim 9 (depends on 8)

The polypeptide of claim 8, comprising the amino acid sequence of (a) SEQ ID NO: 9, (b) SEQ ID NO: 10, or (c) SEQ ID NOs: 9 and 10,
wherein X at position 2 of SEQ ID NO: 10 is Ala or Gly, and when X at position 2 of SEQ ID NO: 10 is Gly, the polypeptide is isolated or purified.

### Claim 10 (depends on 8)

The polypeptide of claim 8, comprising:
(a) (i) SEQ ID NOs: 9 and 24; (ii) SEQ ID NOs: 9 and 17; (iii) SEQ ID NO: 9 and 16; (iv) SEQ ID NO: 10 and 18; or (v) any one of SEQ ID NOs: 20, 22, 26, 27, 29 and 30;
(b) SEQ ID NOs: 20 and 22;
(c) SEQ ID NOs: 26 and 27;
(d) SEQ ID NOs: 9, 24, and 27;
(e) SEQ ID NOs: 9, 17, and 20; or
(f) SEQ ID NOs: 9, 10, 16, and 18.

### Claim 11

An isolated or purified protein comprising a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 3-5 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs: 6-8.

### Claim 12 (depends on 11)

The isolated or purified protein of claim 11, wherein:
the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 9 and
the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 10, wherein X at position 2 of SEQ ID NO: 10 is Ala or Gly.

### Claim 13 (depends on 11)

The isolated or purified protein of claim 11, wherein:
the first polypeptide chain comprises the amino acid sequence of (i) SEQ ID NO: 22, (ii) SEQ ID NO: 26, (iii) SEQ ID NO: 9 and 16, (iv) SEQ ID NO: 9 and 17, or (v) SEQ ID NO: 9 and 24 and
the second polypeptide chain comprises the amino acid sequence of (i) SEQ ID NO: 10 and 18, or (ii) any one of SEQ ID NOs: 20 and 27.

### Claim 14

A protein comprising SEQ ID NO: 29 or 30, wherein the protein is a fusion protein or a recombinant antibody.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising the TCR or functional variant according to claim 1 and a pharmaceutically acceptable carrier.

### Claim 16 (depends on 1)

A method of detecting the presence of a condition in a mammal, comprising:
(a) contacting a sample comprising one or more cells from the mammal with the TCR or functional variant according to claim 1, thereby forming a complex, and
(b) detecting the complex, wherein detection of the complex is indicative of the presence of the condition in the mammal, wherein the condition is cancer, HPV 16 infection, or HPV-positive premalignancy.

### Claim 17 (depends on 1)

A method of treating or preventing cancer in a mammal, the method comprising administering to the mammal the TCR or functional variant according to claim 1 in an amount effective to treat or prevent cancer in the mammal, wherein the condition is cancer, HPV 16 infection, or HPV-positive premalignancy.

### Claim 18 (depends on 17)

The method of claim 17, wherein the condition is cancer of the uterine cervix, oropharynx, anus, anal canal, anorectum, vagina, vulva, or penis.

### Claim 19 (depends on 17)

The method of claim 17, wherein the condition is an HPV 16-positive cancer.

### Claim 20 (depends on 2)

A pharmaceutical composition comprising the TCR according to claim 2 and a pharmaceutically acceptable carrier.

### Claim 21 (depends on 8)

A pharmaceutical composition comprising the isolated or purified polypeptide according to claim 8 and a pharmaceutically acceptable carrier.

### Claim 22 (depends on 11)

A pharmaceutical composition comprising the isolated or purified protein according to claim 11 and a pharmaceutically acceptable carrier.

### Claim 23 (depends on 3)

A pharmaceutical composition comprising the TCR according to claim 3 and a pharmaceutically acceptable carrier.

### Claim 24 (depends on 9)

A pharmaceutical composition comprising the polypeptide according to claim 9 and a pharmaceutically acceptable carrier.