Rna for cancer therapy

{
  "publication_number": "US2022396796A1",
  "country": "US",
  "kind": "A1",
  "title": "Rna for cancer therapy",
  "abstract": "The present invention relates to RNA, particularly an immunostimulatory RNA (isRNA), a coding RNA or a combination thereof, for use in the treatment or prophylaxis of a disease, in particular a tumor and/or cancer disease. The present invention also provides pharmaceutical compositions, and a kit comprising the RNA(s). Further, the invention also comprises medical uses of the RNA(s) and compositions comprising the RNA(s).",
  "claims": [
    "1. A method for the treatment or prophylaxis of a tumor or cancer disease selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of mycosis fungoides subtype, and vulvar squamous cell cancer (VSCC), wherein the tumor or the cancer disease is preferably at an advanced stage and/or refractory to standard therapy comprising administering to a subject in need thereof an immunostimulatory RNA (isRNA). 2. The method according to claim 1, wherein the isRNA is administered intratumorally, intradermally, intramuscularly or subcutaneously. 3. (canceled) 4. The method according to claim 1, wherein the isRNA is a non-coding RNA. 5. The method according to claim 1, wherein the isRNA comprises a nucleic acid sequence according to formula (I) (G l X m G n), wherein: G is guanosine (guanine), uridine (uracil) or an analogue of guanosine (guanine) or uridine (uracil); X is guanosine (guanine), (uridine) uracil, adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of the above-mentioned nucleotides (nucleosides); l is an integer from 1 to 40, wherein when l=1 G is guanosine (guanine) or an analogue thereof, when l>1 at least 50% of the nucleotides (nucleosides) are guanosine (guanine) or an analogue thereof; m is an integer and is at least 3; wherein when m=3 X is uridine (uracil) or an analogue thereof, when m>3 at least 3 successive uridines (uracils) or analogues of uridine (uracil) occur; n is an integer from 1 to 40, wherein when n=1 G is guanosine (guanine) or an analogue thereof, when n>1 at least 50% of the nucleotides (nucleosides) are guanosine (guanine) or an analogue thereof; or a nucleic acid sequence according to formula (III) (N u G l X m G n N v) a wherein: G is guanosine (guanine), uridine (uracil) or an analogue of guanosine (guanine) or uridine (uracil), preferably guanosine (guanine) or an analogue thereof; X is guanosine (guanine), uridine (uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine), or an analogue of these nucleotides (nucleosides), preferably uridine (uracil) or an analogue thereof; N is a nucleic acid sequence having a length of about 4 to 50, preferably of about 4 to 40, more preferably of about 4 to 30 or 4 to 20 nucleic acids, each N independently being selected from guanosine (guanine), uridine (uracil), adenosine (adenine), thymidine (thymine), cytidine (cytosine) or an analogue of these nucleotides (nucleosides); a is an integer from 1 to 20, preferably from 1 to 15, most preferably from 1 to 10; l is an integer from 1 to 40, wherein when l=1, G is guanosine (guanine) or an analogue thereof, when l>1, at least 50% of these nucleotides (nucleosides) are guanosine (guanine) or an analogue thereof; m is an integer and is at least 3; wherein when m=3, X is uridine (uracil) or an analogue thereof, and when m>3, at least 3 successive uridines (uracils) or analogues of uridine (uracil) occur; n is an integer from 1 to 40, wherein when n=1, G is guanosine (guanine) or an analogue thereof, when n>1, at least 50% of these nucleotides (nucleosides) are guanosine (guanine) or an analogue thereof; u,v may be independently from each other an integer from 0 to 50, preferably wherein when u=0, v≥1, or when v=0, u≥1; wherein the nucleic acid molecule of formula (III) has a length of at least 50 nucleotides, preferably of at least 100 nucleotides, more preferably of at least 150 nucleotides, even more preferably of at least 200 nucleotides and most preferably of at least 250 nucleotides. 6. The method according to claim 1, wherein the isRNA comprises at least one nucleic acid sequence according to any one of SEQ ID NOs: 433 to 437, 1014 to 1016. 7. The method according to claim 1, wherein the isRNA is complexed with a cationic or polycationic compound, preferably with a cationic or polycationic polymer, a cationic or polycationic peptide or protein, a cationic or polycationic polysaccharide and/or a cationic or polycationic lipid. 8. The method according to claim 7, wherein the cationic or polycationic compound is a polymeric carrier. 9. The method according to claim 8, wherein the polymeric carrier is formed by a disulfide-crosslinked cationic component, preferably a disulfide-crosslinked cationic peptide, wherein the disulfide-crosslinked cationic peptide preferably comprises a peptide according to formula V (Arg) l;(Lys) m;(H is) n;(O rn) o;(X aa) x, (formula (V), wherein l+m+n+o+x=8-15, and l, m, n or o independently of each other may be any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, provided that the overall content of Arg, Lys, His and Orn represents at least 50% of all amino acids of the oligopeptide; and Xaa may be any amino acid selected from native (=naturally occurring) or non-native amino acids except of Arg, Lys, His or Orn; and x may be any number selected from 0, 1, 2, 3 or 4, provided, that the overall content of Xaa does not exceed 50% of all amino acids of the oligopeptide; a peptide according to formula Va {(Arg) l;(Lys) m;(H is) n;(O rn) o;(X aa ′) x (Cys) y } formula (Va), wherein (Arg) l;(Lys) m;(His) n;(Orn) o; and x are as defined for formula V, Xaa′ is any amino acid selected from native (=naturally occurring) or non-native amino acids except of Arg, Lys, His, Orn or Cys and y is any number selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-90, provided that the overall content of Arg (Arginine), Lys (Lysine), His (Histidine) and Orn (Ornithine) represents at least 10% of all amino acids of the oligopeptide; a peptide according to formula Vb Cys1{(Arg) l;(Lys) m;(H is) n;(O rn) o;(X aa) x }Cys2 formula (Vb) wherein empirical formula {(Arg) l;(Lys) m;(His) n;(Orn) o;(Xaa) x } is as defined for formula (V) and forms a core of an amino acid sequence according to (semiempirical) formula (V) and wherein Cys1 and Cys2 are cysteines proximal to, or terminal to (Arg) l;(Lys) m;(His) n;(Orn) o;(Xaa) x; and/or 10. The method according to claim 8, wherein the polymeric carrier comprises at least one of the disulfide-crosslinked cationic peptides Cys-Arg 12 or Cys-Arg 12 -Cys. 11. (canceled) 12. The method according to claim 1, wherein the isRNA is complexed with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes. 13. The method according to claim 1, wherein the treatment comprises administration of at least one additional pharmaceutically active ingredient. 14. The method according to claim 13, wherein the at least one additional pharmaceutically active ingredient is a compound that is used in the treatment of a tumor or cancer disease preferably selected from the group consisting of cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), cutaneous T-cell lymphoma, preferably cutaneous T-cell lymphoma of mycosis fungoides subtype, and vulvar squamous cell cancer (VSCC), wherein the tumor or the cancer disease is preferably at an advanced stage and/or refractory to standard therapy. 15. The method according to claim 13, wherein the at least one additional pharmaceutically active ingredient is a checkpoint modulator. 16. The method according to claim 15, wherein the checkpoint modulator is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a LAG3 inhibitor, a TIM3 inhibitor, a TIGIT-inhibitor an OX40 stimulator, a 4-1BB stimulator, a CD40L stimulator, a CD28 stimulator and a GITR stimulator. 17. The method according to claim 16, wherein the checkpoint modulator is a PD 1 inhibitor or a PD-L1 inhibitor. 18 - 19. (canceled) 20. The method according to claim 1, wherein the treatment comprises administration of at least one coding RNA, preferably at least one mRNA. 21. The method according to claim 20, wherein the at least one coding RNA comprises at least one coding sequence encoding at least one peptide or protein comprising at least one peptide or protein selected from the group consisting of IL-12, CD40L, a decoy PD-1 receptor, and an antagonistic antibody directed against CTLA4. 22 - 48. (canceled) 49. The method according to claim 20, wherein the at least one coding RNA comprises at least one coding sequence encoding a peptide or protein comprising a tumor antigen. 50 - 66. (canceled) 67. The method according to claim 1, wherein the treatment comprises chemotherapy, radiation therapy and/or surgery. 68 - 73. (canceled)"
  ],
  "description_excerpt": "The present invention relates to RNA, particularly an immunostimulatory RNA (isRNA), a coding RNA or a combination thereof, for use in the treatment or prophylaxis of a disease, in particular a tumor and/or cancer disease. The present invention also provides pharmaceutical compositions, and a kit comprising the RNA(s). Further, the invention also comprises medical uses of the RNA(s) and compositions comprising the RNA(s).\n\nCancer diseases, also known as malignant tumors, are a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. In 2012, about 14.1 million new cases of cancer occurred globally (not including skin cancer other than melanoma).\n\nThe standard treatments of cancer include chemotherapy, radiation and surgery, or immunotherapy wherein these treatments are applied individually or in combination. Cancer immunotherapy which is focused on stimulating the immune system through vaccination, adoptive cellular immunotherapy, immune checkpoint blockade or other immunostimulants or immunomodulators to elicit an anti-tumor response.\n\nSome approaches use gene therapy and genetic vaccination for treatment of cancer or other tumor diseases. Gene therapy and genetic vaccination are molecular medicine methods, which are based on the introduction of a nucleic acid into cells or into tissues of a patient. Subsequently the information encoded by the nucleic acid introduced is processed in the organism, i.e. resulting in expression of a therapeutic peptide or protein or in expression of an antigen, which is coded by the nucleic acid.",
  "cpc": [
    "C12N 15/117",
    "A61K 2039/505",
    "A61K 2039/53",
    "A61K 2039/54",
    "A61K 2039/55538",
    "A61K 2039/572",
    "A61K 2039/585",
    "A61K 31/7088",
    "A61K 31/7105",
    "A61K 38/177",
    "A61K 38/208",
    "A61K 39/0011",
    "A61K 39/001104",
    "A61K 39/001106",
    "A61K 39/001119",
    "A61K 39/001122",
    "A61K 39/001152",
    "A61K 39/001166",
    "A61K 39/001168",
    "A61K 39/001182",
    "A61K 39/001184",
    "A61K 39/001186",
    "A61K 39/39",
    "A61K 39/3955",
    "A61K 39/39558",
    "A61K 45/06",
    "A61K 47/543",
    "A61K 47/61",
    "A61K 47/645",
    "A61K 47/6911",
    "A61K 47/6929",
    "A61K 48/005",
    "A61K 9/0019",
    "A61P 35/00",
    "C07K 19/00",
    "C07K 5/0606",
    "C07K 5/081",
    "C12N 2310/17",
    "C12N 2310/334",
    "C12N 2310/336",
    "C12N 2310/351",
    "C12N 2310/3513",
    "C12N 2310/3515",
    "C12N 2310/531",
    "C12N 2320/32"
  ],
  "ipc": [
    "A61K 38/20",
    "A61K 39/00",
    "A61P 35/00",
    "C12N 15/117"
  ],
  "assignees": [
    "Curevac AG"
  ],
  "inventors": [
    "Mariola Fotin-Mleczek",
    "Aleksandra KOWALCZYK",
    "Regina HEIDENREICH",
    "Ulrike Gnad-Vogt",
    "Ute Klinkhardt",
    "Katja Fiedler"
  ],
  "filing_date": "2022-01-10",
  "publication_date": "2022-12-15",
  "priority_date": "2016-08-19",
  "application_number": "US-202217571893-A",
  "family_id": "59772586",
  "cited_by_count": 1,
  "citations": [
    "US20030232074A1"
  ]
}