Therapeutic rna for lung cancer

Patent metadata

Field	Value
Publication number	US-2024415946-A1
Application number	US-202218699937-A
Country	US
Kind code	A1
Filing date	Oct 10, 2022
Priority date	Oct 11, 2021
Publication date	Dec 19, 2024
Grant date	—

Abstract

This disclosure relates to the field of RNA to treat lung cancer, in particular non-small-cell lung carcinoma (NSCLC). Lung cancer is the third most frequent malignancy in women and the second most frequent malignancy in men. NSCLC accounts for about 85% of all lung cancers. Disclosed herein are compositions, uses, and methods for treatment of lung cancers. Administration of therapeutic RNAs to a patient having lung cancer disclosed herein can reduce tumor size, prolong time to progressive disease, and/or protect against metastasis and/or recurrence of the tumor and ultimately extend survival time.

First claim

1 . A composition or medical preparation comprising at least one RNA, wherein the at least one RNA encodes the following amino acid sequences:
(i) an amino acid sequence comprising claudin 6 (CLDN6), an immunogenic variant thereof, or an immunogenic fragment of the CLDN6 or the immunogenic variant thereof; (ii) an amino acid sequence comprising Kita-kyushu lung cancer antigen 1 (KK-LC-1), an immunogenic variant thereof, or an immunogenic fragment of the KK-LC-1 or the immunogenic variant thereof; (iii) an amino acid sequence comprising Melanoma antigen A3 (MAGE-A3), an immunogenic variant thereof, or an immunogenic fragment of the MAGE-A3 or the immunogenic variant thereof; (iv) an amino acid sequence comprising Melanoma antigen 4 (MAGE-A4), an immunogenic variant thereof, or an immunogenic fragment of the MAGE-A4 or the immunogenic variant thereof; (v) an amino acid sequence comprising Preferentially Expressed Antigen In Melanoma (PRAME), an immunogenic variant thereof, or an immunogenic fragment of the PRAME or the immunogenic variant thereof; and (vi) an amino acid sequence comprising Melanoma antigen C1 (MAGE-C1), an immunogenic variant thereof, or an immunogenic fragment of the MAGE-C1 or the immunogenic variant thereof.

2 . The composition or medical preparation of claim 1 , which comprises:
(i) RNA encoding an amino acid sequence comprising claudin 6 (CLDN6), an immunogenic variant thereof, or an immunogenic fragment of the CLDN6 or the immunogenic variant thereof; (ii) RNA encoding an amino acid sequence comprising Kita-kyushu lung cancer antigen 1 (KK-LC-1), an immunogenic variant thereof, or an immunogenic fragment of the KK-LC-1 or the immunogenic variant thereof; (iii) RNA encoding an amino acid sequence comprising Melanoma antigen A3 (MAGE-A3), an immunogenic variant thereof, or an immunogenic fragment of the MAGE-A3 or the immunogenic variant thereof; (iv) RNA encoding an amino acid sequence comprising Melanoma antigen 4 (MAGE-A4), an immunogenic variant thereof, or an immunogenic fragment of the MAGE-A4 or the immunogenic variant thereof; (v) RNA encoding an amino acid sequence comprising Preferentially Expressed Antigen In Melanoma (PRAME), an immunogenic variant thereof, or an immunogenic fragment of the PRAME or the immunogenic variant thereof; and (vi) RNA encoding an amino acid sequence comprising Melanoma antigen C1 (MAGE-C1), an immunogenic variant thereof, or an immunogenic fragment of the MAGE-C1 or the immunogenic variant thereof.

3 . The composition or medical preparation of claim 1 or 2 , wherein each of the amino acid sequences under (i), (ii), (iii), (iv), (v), or (vi) is encoded by a separate RNA.

4 . The composition or medical preparation of any one of claims 1 to 3 , wherein
(i) the RNA encoding the amino acid sequence under (i) comprises the nucleotide sequence of SEQ ID NO: 3 or 4, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 3 or 4; and/or (ii) the amino acid sequence under (i) comprises the amino acid sequence of SEQ ID NO: 1 or 2, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 1 or 2.

5 . The composition or medical preparation of any one of claims 1 to 4 , wherein
(i) the RNA encoding the amino acid sequence under (ii) comprises the nucleotide sequence of SEQ ID NO: 7 or 8, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 7 or 8; and/or (ii) the amino acid sequence under (ii) comprises the amino acid sequence of SEQ ID NO: 5 or 6, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 5 or 6.

6 . The composition or medical preparation of any one of claims 1 to 5 , wherein
(i) the RNA encoding the amino acid sequence under (iii) comprises the nucleotide sequence of SEQ ID NO: 11 or 12, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 11 or 12; and/or (ii) the amino acid sequence under (iii) comprises the amino acid sequence of SEQ ID NO: 9 or 10, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 9 or 10.

7 . The composition or medical preparation of any one of claims 1 to 6 , wherein
(i) the RNA encoding the amino acid sequence under (iv) comprises the nucleotide sequence of SEQ ID NO: 15 or 16, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 15 or 16; and/or (ii) the amino acid sequence under (iv) comprises the amino acid sequence of SEQ ID NO: 13 or 14, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 13 or 14.

8 . The composition or medical preparation of any one of claims 1 to 7 , wherein
(i) the RNA encoding the amino acid sequence under (v) comprises the nucleotide sequence of SEQ ID NO: 19 or 20, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 19 or 20; and/or (ii) the amino acid sequence under (v) comprises the amino acid sequence of SEQ ID NO: 17 or 18, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 17 or 18.

9 . The composition or medical preparation of any one of claims 1 to 8 , wherein
(i) the RNA encoding the amino acid sequence under (vi) comprises the nucleotide sequence of SEQ ID NO: 23 or 24, or a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 23 or 24; and/or (ii) the amino acid sequence under (vi) comprises the amino acid sequence of SEQ ID NO: 21 or 22, or an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 21 or 22.

10 . The composition or medical preparation of any one of claims 1 to 9 , which comprises:
(i) RNA comprising the nucleotide sequence of SEQ ID NO: 4; (ii) RNA comprising the nucleotide sequence of SEQ ID NO: 8; (iii) RNA comprising the nucleotide sequence of SEQ ID NO: 12; (iv) RNA comprising the nucleotide sequence of SEQ ID NO: 16; (v) RNA comprising the nucleotide sequence of SEQ ID NO: 20; and (vi) RNA comprising the nucleotide sequence of SEQ ID NO: 24.

11 . The composition or medical preparation of any one of claims 1 to 10 , wherein at least one amino acid sequence under (i), (ii), (iii), (iv), (v), or (vi) comprises an amino acid sequence which breaks immunological tolerance and/or at least one RNA is co-administered with RNA encoding an amino acid sequence which breaks immunological tolerance.

12 . The composition or medical preparation of any one of claims 1 to 11 , wherein each amino acid sequence under (i), (ii), (iii), (iv), (v), or (vi) comprises an amino acid sequence which breaks immunological tolerance and/or each RNA is co-administered with RNA encoding an amino acid sequence which breaks immunological tolerance.

13 . The composition or medical preparation of claim 11 or 12 , wherein the amino acid sequence which breaks immunological tolerance comprises helper epitopes, preferably tetanus toxoid-derived helper epitopes.

14 . The composition or medical preparation of any one of claims 11 to 13 , wherein
(i) the R

Assignees

• BioNTech SE
• Tron Translationale Onkologie An Der Univ Der Johannes Gutenbe

Inventors

• Sahin Ugur
• Weber David
• Walter Carina
• Barea Roldán Diana
• Kuner Ruprecht
• Hein Melanie
• Suchan Martin
• Kissler Vetena
• Kranz Lena Mareen

Classifications

• A61K2039/572

  cytotoxic response · CPC title

• A61K2039/55555

  Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers · CPC title

• A61K2039/55544

  Bacterial toxins · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title