# US 10,767,167 B2 · Polynucleotides encoding MHC class I-restricted hTERT epitopes, analogues thereof or polyepitopes

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- Number: US 10,767,167 B2
- Document ID: US10767167B2
- Status: Granted
- Kind: B2
- Application number: 15/481,452
- Filed: 2017-04-06
- Published: 2017-10-19
- Granted: 2020-09-08
- Earliest claimed: 2005-07-29
- Assignees: Institut Pasteur; Inserm (Institut National De La Sante Et De La Recherche Medicale)
- Applicants: Institut Pasteur; Inserm (Institut National De La Sante Et De La Recherche Medicale)
- Inventors: Pierre Langlade-Demoyen; Fransisco Garcia Pons; Olivier Adotevi; Sylvain Cardinaud; Christine Neuveut
- Web page: https://patentgrep.com/patent/US10767167B2

## CPC

- C12N 9/1276: {RNA-directed DNA polymerase (2.7.7.49), i.e. reverse transcriptase or telomerase}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/4246: {Telomerase or [telomerase reverse transcriptase [TERT]}
- C12N 9/1241: {Nucleotidyltransferases (2.7.7)}
- 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 2039/572: {cytotoxic response}
- A61K 2039/605: {MHC molecules or ligands thereof}
- A61K 2239/56: Kidney
- A61K 2239/57: Skin; melanoma
- 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

This invention relates to the field of anticancer therapy, and to the identification of immunogenic peptides derived from the human telomerase reverse transcriptase (hTERT). The present invention relates to polynucleotides encoding hTERT epitopes restricted to MHC class I molecule, analogues thereof and polyepitopes containing such epitopes and/or analogues. Are also included in the present invention, vector and cell comprising such polynucleotides. The present invention also concerns composition comprising hTERT polypeptides, corresponding polynucleotides, vectors and cells, for use in the treatment and/or prevention of cancer.

## Claims

### Claim 1

A method of inducing an HLA-A2 and/or HLA-B7-restricted immune response against at least one hTERT epitope, comprising:
A) administering to an animal a vector comprising a polynucleotide sequence that encodes a modified hTERT protein comprising the amino acid sequence of SEQ ID NO: 39;
B) expressing the modified hTERT protein; and
C) inducing:
1) an HLA-A2-restricted immune response against at least one hTERT epitope selected from:
a) p540, and
b) pY572; and/or
2) inducing an HLA-B7-restricted immune response against at least one hTERT epitope selected from:
a)
(SEQ ID NO: 6)
MPRAPRCRA (p1),
b)
(SEQ ID NO: 7)
APRCRAVRSL (p4),
c)
(SEQ ID NO: 8)
APSFRQVSCL (p68),
d)
(SEQ ID NO: 9)
RPAEEATSL (p277),
e)
(SEQ ID NO: 10)
RPSFLLSSL (p342),
and
f)
(SEQ ID NO: 11)
RPSLTGARRL (p351).

### Claim 2 (depends on 1)

The method of claim 1, wherein the vector is a viral vector.

### Claim 3 (depends on 1)

The method of claim 1, further comprising providing antigen presenting cells (APCs), transforming the APCs in vitro with the vector comprising the polynucleotide sequence that encodes a modified hTERT protein, and administering the APCs to the animal.

### Claim 4 (depends on 3)

The method of claim 3, wherein the APCs are dendritic cells.

### Claim 5 (depends on 1)

The method of claim 1, wherein the animal is a human.

### Claim 6 (depends on 1)

The method of claim 1, the method comprising inducing an HLA-A2-restricted immune response against the hTERT epitopes a) p540 and b) pY572.

### Claim 7 (depends on 6)

The method of claim 6, wherein the vector is a viral vector.

### Claim 8 (depends on 6)

The method of claim 6, wherein the vector is a lentiviral vector, and wherein the method further comprises providing antigen presenting cells (APCs), transforming the APCs in vitro with the lentiviral vector comprising the polynucleotide sequence that encodes a modified hTERT protein, and administering the APCs to the animal.

### Claim 9 (depends on 8)

The method of claim 8, wherein the APCs are dendritic cells.

### Claim 10 (depends on 6)

The method of claim 6, wherein the animal is a human.

### Claim 11 (depends on 1)

The method of claim 1, the method comprising inducing an HLA-B7-restricted immune response against at least two hTERT epitopes selected from:
a.
(SEQ ID NO: 6)
MPRAPRCRA (p1),
b.
(SEQ ID NO: 7)
APRCRAVRSL, (p4)
c.
(SEQ ID NO: 8)
APSFRQVSCL (p68),
d.
(SEQ ID NO: 9)
RPAEEATSL (p277),
e.
(SEQ ID NO: 10)
RPSFLLSSL (p342),
and
f.
(SEQ ID NO: 11)
RPSLTGARRL (p351).

### Claim 12 (depends on 11)

The method of claim 11, wherein the vector is a viral vector.

### Claim 13 (depends on 11)

The method of claim 11, further comprising providing antigen presenting cells (APCs), transforming the APCs in vitro with the vector comprising the polynucleotide sequence that encodes a modified hTERT protein, and administering the APCs to the animal.

### Claim 14 (depends on 13)

The method of claim 13, wherein the APCs are dendritic cells.

### Claim 15 (depends on 11)

The method of claim 11, wherein the animal is a human.

### Claim 16 (depends on 1)

The method of claim 1, the method comprising inducing an HLA-B7-restricted immune response against each of hTERT epitopes:
a.
(SEQ ID NO: 6)
MPRAPRCRA (p1),
b.
(SEQ ID NO: 7)
APRCRAVRSL, (p4)
c.
(SEQ ID NO: 8)
APSFRQVSCL (p68),
d.
(SEQ ID NO: 9)
RPAEEATSL (p277),
e.
(SEQ ID NO: 10)
RPSFLLSSL (p342),
and
f.
(SEQ ID NO: 11)
RPSLTGARRL (p351).

### Claim 17 (depends on 16)

The method of claim 16, wherein the vector is a viral vector.

### Claim 18 (depends on 16)

The method of claim 16, further comprising providing antigen presenting cells (APCs), transforming the APCs in vitro with the vector comprising the polynucleotide sequence that encodes a modified hTERT protein, and administering the APCs to the animal.

### Claim 19 (depends on 18)

The method of claim 18, wherein the APCs are dendritic cells.

### Claim 20 (depends on 16)

The method of claim 16, wherein the animal is a human.