MRNA vaccine for combination respiratory diseases
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- サノフィ ワクチンズ ユーエス インコーポレイテッド
- Filing Date
- 2024-05-10
- Publication Date
- 2026-06-09
Smart Images
Figure 2026518609000087 
Figure 2026518609000088 
Figure 2026518609000089
Abstract
Claims
1. A composition comprising at least two messenger RNAs (mRNAs), wherein the at least two mRNAs are (i) A first mRNA encoding the human respiratory syncytial virus (hRSV) F protein antigen, containing the amino acid sequence of Sequence ID No. 1; (ii) A second mRNA encoding the human metapneumovirus (hMPV) F protein antigen containing the amino acid sequence of Sequence ID No. 2; and (iii) A third mRNA encoding the human parainfluenza virus 3 (hPIV3) F protein antigen, containing the amino acid sequence of SEQ ID NO:
3. The open reading frame (ORF) includes an open reading frame (ORF) encoding a recombinant F protein antigenic polypeptide selected from the group consisting of the following: A composition comprising at least two messenger RNAs (mRNAs).
2. A first mRNA encoding the amino acid sequence of Sequence ID No. 1; and The second mRNA encoding the amino acid sequence of Sequence ID No.
2. The composition according to claim 1, comprising:
3. A first mRNA encoding the amino acid sequence of Sequence ID No. 1; and The third mRNA encoding the amino acid sequence of Sequence ID No.
3. The composition according to claim 1, comprising:
4. A second mRNA encoding the amino acid sequence of Sequence ID No. 2; and The third mRNA encoding the amino acid sequence of Sequence ID No.
3. The composition according to claim 1, comprising:
5. A first mRNA encoding the amino acid sequence of Sequence ID No. 1; A second mRNA encoding the amino acid sequence of Sequence ID No. 2; and The third mRNA encoding the amino acid sequence of Sequence ID No.
3. The composition according to claim 1, comprising at least three mRNAs, including the following.
6. A first mRNA encoding the amino acid sequence of Sequence ID No. 1; A second mRNA encoding the amino acid sequence of Sequence ID No. 2; and The third mRNA encoding the amino acid sequence of Sequence ID No.
3. The composition according to claim 1, comprising three mRNAs, including the following.
7. The composition according to any one of claims 1 to 3, 5, or 6, wherein the hRSV F protein comprises an amino acid sequence having at least 90% identity with SEQ ID NO:
1.
8. The composition according to any one of claims 1, 2, or 4 to 6, wherein the hMPV F protein comprises an amino acid sequence having at least 90% identity with SEQ ID NO:
2.
9. The composition according to any one of claims 1 or 3 to 6, wherein the hPIV3 F protein comprises an amino acid sequence having at least 90% identity with SEQ ID NO:
3.
10. The composition according to any one of claims 1 to 3, 5, or 6, wherein the first mRNA comprises a nucleic acid sequence having at least 80% identity with SEQ ID NO:
4.
11. The composition according to any one of claims 1, 2, or 4 to 6, wherein the second mRNA comprises a nucleic acid sequence having at least 80% identity with SEQ ID NO:
5.
12. The composition according to any one of claims 1 or 3 to 6, wherein the third mRNA comprises a nucleic acid sequence having at least 80% identity with SEQ ID NO:
6.
13. The composition according to any one of claims 1 to 12, wherein at least one of the recombinant F protein antigenic polypeptides is a pre-fusion protein.
14. The composition according to any one of claims 1 to 13, wherein at least one of the mRNAs comprises a codon-optimized ORF.
15. The composition according to any one of claims 1 to 14, wherein at least one mRNA comprises at least one 5' untranslated region (5'UTR), at least one 3' untranslated region (3'UTR), and at least one polyadenylated (poly(A)) sequence.
16. The composition according to any one of claims 1 to 15, wherein at least one of the mRNAs comprises a 5' UTR having at least 80% identity with the sequence number 7.
17. The composition according to any one of claims 1 to 16, wherein at least one of the mRNAs comprises a 3'UTR having at least 80% identity with the sequence number 8.
18. The composition according to any one of claims 1 to 17, wherein at least one of the mRNAs comprises at least one chemical modification.
19. The composition according to any one of claims 1 to 18, wherein at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of the uracil nucleotides in at least one mRNA are chemically modified.
20. The composition according to any one of claims 1 to 18, wherein at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of the uracil nucleotide in at least one ORF is chemically modified.
21. The composition according to any one of claims 18 to 20, wherein the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudridine, 2-thiouridine, 4'-thiouridine, 5-methylcytosine, 2-thio-l-methyl-1-deazapseudridine, 2-thio-l-methylpseudridine, 2-thio-5-azauridine, 2-thio-dihydropseudridine, 2-thio-dihydrouridine, 2-thiopseudridine, 4-methoxy-2-thiopseudridine, 4-methoxypseudridine, 4-thio-l-methylpseudridine, 4-thiopseudridine, 5-azauridine, dihydropseudridine, 5-methyluridine, 5-methyluridine, 5-methoxyuridine, and 2'-O-methyluridine.
22. The composition according to claim 21, wherein the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudridine, 5-methylcytosine, 5-methoxyuridine, and combinations thereof.
23. The composition according to claim 22, wherein the chemical modification is N1-methylpsuduridine.
24. The composition according to any one of claims 1 to 23, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:1:1 (w / w).
25. The composition according to any one of claims 1 to 23, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:2:1 (w / w).
26. The composition according to any one of claims 1 to 23, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:3:1 (w / w).
27. The composition according to any one of claims 1 to 23, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:5:1 (w / w).
28. The composition according to any one of claims 1 to 23, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of about 1:1:1 to about 1:10:
1.
29. The composition according to any one of claims 1 to 23, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of about 1:1:0.1 to about 1:1:1 (w / w).
30. The composition according to any one of claims 24 to 29, wherein the ratio is expressed in micrograms (μg).
31. The composition according to claim 24, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 1 microgram of the second mRNA to approximately 1 microgram of the third mRNA.
32. The composition according to claim 25, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 2 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
33. The composition according to claim 26, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 3 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
34. The composition according to claim 27, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 5 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
35. The composition according to claim 24, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 0.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
36. The composition according to claim 26, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 1.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
37. The composition according to claim 29, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 0.5 micrograms of the second mRNA to approximately 0.1 micrograms of the third mRNA.
38. The composition according to claim 25, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 1 microgram of the second mRNA to approximately 0.5 micrograms of the third mRNA.
39. The composition according to claim 27, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 2.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
40. The composition according to any one of claims 1 to 39, wherein the first mRNA, the second mRNA, and the third mRNA are not covalently bonded to each other.
41. The composition according to any one of claims 1 to 39, wherein one or more of the first mRNA, the second mRNA, and the third mRNA are covalently bonded to each other.
42. The composition according to any one of claims 1 to 41, wherein the first mRNA, the second mRNA, and the third mRNA are each formulated into separate nanoparticles (LNPs).
43. The composition according to any one of claims 1 to 41, wherein the first mRNA, the second mRNA, and the third mRNA are formulated into the same LNP.
44. The composition according to claim 42 or 43, wherein the LNP comprises at least one cationic lipid.
45. The composition according to claim 44, wherein the cationic lipid is biodegradable.
46. The composition according to claim 44, wherein the cationic lipid is not biodegradable.
47. The composition according to claim 44, wherein the cationic lipid is cleavable.
48. The composition according to claim 44, wherein the cationic lipid is not cleavable.
49. The composition according to claim 44, wherein the cationic lipid is selected from the group consisting of OF-02, cKK-E10, GL-HEPES-E3-E10-DS-3-E18-1, GL-HEPES-E3-E12-DS-4-E10, GL-HEPES-E3-E12-DS-3-E14, and IM-001.
50. The composition according to claim 49, wherein the cationic lipid is cKK-E10.
51. The composition according to claim 49, wherein the cationic lipid is GL-HEPES-E3-E12-DS-4-E10.
52. The composition according to claim 49, wherein the cationic lipid is IM-001.
53. The composition according to any one of claims 42 to 52, wherein the LNP further comprises polyethylene glycol (PEG) conjugate (PEG-modified) lipids, cholesterol-based lipids, and helper lipids.
54. The aforementioned LNP is Cationic lipids in a molar ratio of 35% to 55%; Polyethylene glycol (PEG) conjugated lipids in a molar ratio of 0.25% to 2.75%; Cholesterol-based lipids in a molar ratio of 20% to 45%; and Helper lipids in a molar ratio of 5% to 35% Includes, The composition according to any one of claims 42 to 53, wherein all of the aforementioned molar ratios are relative to the total lipid content of the LNP.
55. The aforementioned LNP is Cationic lipids at a molar ratio of 40%; PEG-treated lipids at a molar ratio of 1.5%; Cholesterol-based lipids in a molar ratio of 28.5%; and Helper lipids at a 30% molar ratio The composition according to claim 54, comprising:
56. The composition according to any one of claims 53 to 55, wherein the PEGylated lipid is dimyristoyl-PEG2000 (DMG-PEG2000) or 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159).
57. The composition according to any one of claims 53 to 56, wherein the cholesterol-based lipid is cholesterol.
58. The composition according to any one of claims 53 to 57, wherein the helper lipid is 1,2-dioleoyl-SN-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).
59. The aforementioned LNP is GL-HEPES-E3-E12-DS-4-E10 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE A composition according to any one of claims 42 to 58, comprising:
60. The aforementioned LNP is cKK-E10 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE A composition according to any one of claims 42 to 58, comprising:
61. The aforementioned LNP is IM-001 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE A composition according to any one of claims 42 to 58, comprising:
62. The composition according to any one of claims 42 to 61, wherein the LNP has an average diameter of 30 nm to 200 nm.
63. The composition according to claim 62, wherein the LNP has an average diameter of 80 nm to 150 nm.
64. At least one of the mRNAs contains the following structural elements: (i) A 5' cap having the following structure: 【Chemistry 1】 ； (ii) The 5' untranslated region (5'UTR) having the nucleic acid sequence of sequence number 7, (iii) Protein coding region having the nucleic acid sequence of sequence number 4, 5, or 6; (iv) The 3' untranslated region (3'UTR) having the nucleic acid sequence of SEQ ID NO: 8; and (v) Poly(A) Tail A composition according to any one of claims 1 to 63, comprising:
65. A composition comprising at least two messenger RNAs (mRNAs), each of which comprises an open reading frame (ORF) encoding a recombinant F protein antigenic polypeptide, and at least one of the mRNAs comprising the following structural elements: (i) A 5' cap having the following structure: 【Chemistry 2】 ； (ii) The 5' untranslated region (5'UTR) having the nucleic acid sequence of sequence number 7, (iii) Protein coding region having the nucleic acid sequence of sequence number 4, 5, or 6; (iv) The 3' untranslated region (3'UTR) having the nucleic acid sequence of SEQ ID NO: 8; and (v) Poly(A) Tail Includes, The aforementioned mRNA is GL-HEPES-E3-E12-DS-4-E10 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE Formulated in lipid nanoparticles (LNPs) containing A composition comprising at least two messenger RNAs (mRNAs).
66. A composition comprising at least two messenger RNAs (mRNAs), each of which comprises an open reading frame (ORF) encoding a recombinant F protein antigenic polypeptide, and at least one of the mRNAs comprising the following structural elements: (i) A 5' cap having the following structure: 【Transformation 3】 ； (ii) The 5' untranslated region (5'UTR) having the nucleic acid sequence of sequence number 7, (iii) Protein coding region having the nucleic acid sequence of sequence number 4, 5, or 6; (iv) The 3' untranslated region (3'UTR) having the nucleic acid sequence of SEQ ID NO: 8; and (v) Poly(A) Tail Includes, The aforementioned mRNA is cKK-E10 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE Formulated in lipid nanoparticles (LNPs) containing A composition comprising at least two messenger RNAs (mRNAs).
67. A composition comprising at least two messenger RNAs (mRNAs), each of which comprises an open reading frame (ORF) encoding a recombinant F protein antigenic polypeptide, and at least one of the mRNAs comprising the following structural elements: (i) A 5' cap having the following structure: 【Chemistry 4】 ； (ii) The 5' untranslated region (5'UTR) having the nucleic acid sequence of sequence number 7, (iii) Protein coding region having the nucleic acid sequence of sequence number 4, 5, or 6; (iv) The 3' untranslated region (3'UTR) having the nucleic acid sequence of SEQ ID NO: 8; and (v) Poly(A) Tail Includes, The aforementioned mRNA is IM-001 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE Formulated in lipid nanoparticles (LNPs) containing A composition comprising at least two messenger RNAs (mRNAs).
68. A composition comprising at least two messenger RNAs (mRNAs), each of which comprises an open reading frame (ORF) encoding a recombinant F protein antigenic polypeptide, and at least one of the mRNAs comprising the following structural elements: (i) A 5' cap having the following structure: 【Transformation 5】 ； (ii) The 5' untranslated region (5'UTR) having the nucleic acid sequence of sequence number 7, (iii) Protein coding region having the nucleic acid sequence of sequence number 4, 5, or 6; (iv) The 3' untranslated region (3'UTR) having the nucleic acid sequence of SEQ ID NO: 8; and (v) Poly(A) Tail Includes, The mRNA is formulated in lipid nanoparticles (LNPs) containing GL-HEPES-E3-E12-DS-4-E10, IM-001, OF-02, or cKK-E10 in a molar ratio of 35% to 55%. A composition comprising at least two messenger RNAs (mRNAs).
69. A method for inducing an immune response to hRSV or protecting a subject from hRSV infection, comprising administering to a subject the composition described in any one of claims 1 to 68.
70. A method for inducing an immune response to hMPV or protecting a subject from hMPV infection, comprising administering to the subject a composition according to any one of claims 1 to 68.
71. A method for inducing an immune response to hPIV3 or protecting a subject from hPIV3 infection, comprising administering to the subject a composition according to any one of claims 1 to 68.
72. The method according to claim 69, wherein, compared to a subject administered a single antigen composition comprising mRNA ORF encoding the hRSV F protein antigen of SEQ ID NO: 1, the serum concentration of neutralizing antibodies against hRSV after administration of the composition is approximately the same as or higher than that of a subject administered the composition.
73. The method according to claim 70, wherein, compared to a subject administered a single antigen composition comprising mRNA ORF encoding the hMPV F protein antigen of SEQ ID NO: 2, the serum concentration of neutralizing antibodies against hMPV after administration of the composition is approximately the same as or higher than that of a subject administered the composition.
74. The method according to claim 71, wherein, compared to a subject administered with a single antigen composition comprising mRNA ORF encoding the hPIV3 F protein antigen of SEQ ID NO: 3, the serum concentration of neutralizing antibodies against hPIV3 after administration of the composition is approximately the same as or higher than that of a subject administered with the composition.
75. The method according to claim 69, wherein the subject has an equivalent serum concentration of neutralizing antibodies against hRSV after administration of the composition, compared to a subject administered with the protein hRSV vaccine.
76. The method according to claim 70, wherein the subject has an equivalent serum concentration of neutralizing antibodies against hMPV after administration of the composition, compared to a subject administered with the protein hMPV vaccine.
77. The method according to claim 71, wherein the subject has an equivalent serum concentration of neutralizing antibody against hPIV3 after administration of the composition, compared to a subject administered with the protein hPIV3 vaccine.
78. The method according to claim 69, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hRSV immunity.
79. The method according to claim 70, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hMPV immunity.
80. The method according to claim 71, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hPIV3 immunity.
81. A composition for use in inducing an immune response to hRSV or protecting a subject from hRSV infection, comprising administering the composition according to any one of claims 1 to 68 to the subject.
82. A composition for use in inducing an immune response to hMPV or protecting a subject from hMPV infection, comprising administering the composition according to any one of claims 1 to 68 to the subject.
83. A composition for use in inducing an immune response to hPIV3 or protecting a subject from hPIV3 infection, comprising administering the composition according to any one of claims 1 to 68 to the subject.
84. Use of the composition according to any one of claims 1 to 68 in the manufacture of a pharmaceutical product for inducing an immune response to hRSV or for protecting a subject from hRSV infection.
85. Use of the composition according to any one of claims 1 to 68 in the manufacture of a pharmaceutical product for inducing an immune response to hMPV or for protecting a subject from hMPV infection.
86. Use of the composition according to any one of claims 1 to 68 in the manufacture of a pharmaceutical product for inducing an immune response to hPIV3 or for protecting a subject from hPIV3 infection.
87. A composition comprising three messenger RNAs (mRNAs), (i) The first mRNA encodes the human respiratory syncytial virus (hRSV) F protein antigen, which contains the amino acid sequence of Sequence ID No.
1. (ii) The second mRNA encodes the human metapneumovirus (hMPV) F protein antigen, which contains the amino acid sequence of Sequence ID No.
2. (iii) The third mRNA encodes the human parainfluenza virus 3 (hPIV3) F protein antigen, which contains the amino acid sequence of SEQ ID NO:
3. Here, the first mRNA, the second mRNA, and the third mRNA are, OF-02, cKK-E10, GL-HEPES-E3-E10-DS-3-E18-1, GL-HEPES-E3-E12-DS-4-E10, GL-HEPES-E3-E12-DS-3-E14, or IM-001, all in a 40% molar ratio; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE The same lipid nanoparticles (LNPs) containing are formulated, A composition containing three messenger RNAs (mRNAs).
88. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:1:1 (w / w).
89. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:2:1 (w / w).
90. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:3:1 (w / w).
91. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:5:1 (w / w).
92. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of about 1:1:1 to about 1:10:
1.
93. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of about 1:1:0.1 to about 1:1:1 (w / w).
94. The composition according to any one of claims 88 to 93, wherein the ratio is expressed in micrograms (μg).
95. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 1 microgram of the second mRNA to approximately 1 microgram of the third mRNA.
96. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 2 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
97. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 3 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
98. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 5 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
99. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 0.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
100. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 1.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
101. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 0.5 micrograms of the second mRNA to approximately 0.1 micrograms of the third mRNA.
102. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 1 microgram of the second mRNA to approximately 0.5 micrograms of the third mRNA.
103. The composition according to claim 87, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 2.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
104. A method for inducing an immune response to hRSV or protecting a subject from hRSV infection, comprising administering to a subject the composition according to any one of claims 87 to 103.
105. A method for inducing an immune response to hMPV or protecting a subject from hMPV infection, comprising administering to the subject the composition according to any one of claims 87 to 103.
106. A method for inducing an immune response to hPIV3 or protecting a subject from hPIV3 infection, comprising administering to the subject the composition according to any one of claims 87 to 103.
107. The method according to claim 104, wherein, compared to a subject administered a single antigen composition comprising mRNA ORF encoding the hRSV F protein antigen of SEQ ID NO: 1, the serum concentration of neutralizing antibodies against hRSV after administration of the composition is approximately the same as or higher.
108. The method according to claim 105, wherein, compared to a subject administered a single antigen composition comprising mRNA ORF encoding the hMPV F protein antigen of SEQ ID NO: 2, the serum concentration of neutralizing antibodies against hMPV after administration of the composition is approximately the same as or higher than that of a subject administered the composition.
109. The method according to claim 106, wherein, compared to a subject administered with a single antigen composition comprising mRNA ORF encoding the hPIV3 F protein antigen of SEQ ID NO: 3, the serum concentration of neutralizing antibodies against hPIV3 after administration of the composition is approximately the same as or higher than that of a subject administered with the composition.
110. The method according to claim 104, wherein the subject has an equivalent serum concentration of neutralizing antibodies against hRSV after administration of the composition, compared to a subject administered with the protein hRSV vaccine.
111. The method according to claim 105, wherein the subject has an equivalent serum concentration of neutralizing antibody against hMPV after administration of the composition, compared to a subject administered with the protein hMPV vaccine.
112. The method according to claim 106, wherein the subject has an equivalent serum concentration of neutralizing antibody against hPIV3 after administration of the composition, compared to a subject administered with the protein hPIV3 vaccine.
113. The method according to claim 104, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hRSV immunity.
114. The method according to claim 105, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hMPV immunity.
115. The method according to claim 106, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hPIV3 immunity.
116. A composition for use in inducing an immune response to hRSV or protecting a subject from hRSV infection, comprising administering the composition according to any one of claims 87 to 103 to the subject.
117. A composition for use in inducing an immune response to hMPV or protecting a subject from hMPV infection, comprising administering the composition according to any one of claims 87 to 103 to the subject.
118. A composition for use in inducing an immune response to hPIV3 or protecting a subject from hPIV3 infection, comprising administering the composition according to any one of claims 87 to 103 to the subject.
119. Use of the composition according to any one of claims 87 to 103 in the manufacture of a pharmaceutical product for inducing an immune response to hRSV or for protecting a subject from hRSV infection.
120. Use of the composition according to any one of claims 87 to 103 in the manufacture of a pharmaceutical product for inducing an immune response to hMPV or for protecting a subject from hMPV infection.
121. Use of the composition according to any one of claims 87 to 103 in the manufacture of a pharmaceutical product for inducing an immune response to hMPV or for protecting a subject from hPIV3 infection.
122. A composition comprising three messenger RNAs (mRNAs), (i) The first mRNA encodes the human respiratory syncytial virus (hRSV) F protein antigen, which contains the amino acid sequence of Sequence ID No.
1. (ii) The second mRNA encodes the human metapneumovirus (hMPV) F protein antigen, which contains the amino acid sequence of Sequence ID No.
2. (iii) The third mRNA encodes the human parainfluenza virus 3 (hPIV3) F protein antigen, which contains the amino acid sequence of SEQ ID NO:
3. A composition containing three messenger RNAs (mRNAs).
123. The composition according to claim 122, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:1:1 (w / w).
124. The composition according to claim 122, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:2:1 (w / w).
125. The composition according to claim 122, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:3:1 (w / w).
126. The composition according to claim 122, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of approximately 1:5:1 (w / w).
127. The composition according to claim 122, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of about 1:1:1 to about 1:10:
1.
128. The composition according to claim 122, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio of about 1:1:0.1 to about 1:1:1 (w / w).
129. The composition according to any one of claims 123 to 128, wherein the ratio is expressed in micrograms (μg).
130. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 1 microgram of the second mRNA to approximately 1 microgram of the third mRNA.
131. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 2 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
132. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 3 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
133. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 1 microgram of the first mRNA to approximately 5 micrograms of the second mRNA to approximately 1 microgram of the third mRNA.
134. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 0.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
135. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 1.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
136. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 0.5 micrograms of the second mRNA to approximately 0.1 micrograms of the third mRNA.
137. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 1 microgram of the second mRNA to approximately 0.5 micrograms of the third mRNA.
138. The composition according to claim 129, wherein the first mRNA, the second mRNA, and the third mRNA are present in a ratio (w / w) of approximately 0.5 micrograms of the first mRNA to approximately 2.5 micrograms of the second mRNA to approximately 0.5 micrograms of the third mRNA.
139. A method for inducing an immune response to hRSV or protecting a subject from hRSV infection, comprising administering to a subject the composition according to any one of claims 122 to 138.
140. A method for inducing an immune response to hMPV or protecting a subject from hMPV infection, comprising administering to the subject the composition according to any one of claims 122 to 138.
141. A method for inducing an immune response to hPIV3 or protecting a subject from hPIV3 infection, comprising administering to the subject the composition according to any one of claims 122 to 138.
142. The method according to claim 139, wherein, compared to a subject administered a single antigen composition comprising mRNA ORF encoding the hRSV F protein antigen of SEQ ID NO: 1, the serum concentration of neutralizing antibodies against hRSV after administration of the composition is approximately the same as or higher than that of a subject administered the composition.
143. The method according to claim 140, wherein, compared to a subject administered with a single antigen composition comprising mRNA ORF encoding the hMPV F protein antigen of SEQ ID NO: 2, the serum concentration of neutralizing antibodies against hMPV after administration of the composition is approximately the same as or higher than that of a subject administered with the composition.
144. The method according to claim 141, wherein, compared to a subject administered with a single antigen composition comprising mRNA ORF encoding the hPIV3 F protein antigen of SEQ ID NO: 3, the serum concentration of neutralizing antibodies against hPIV3 after administration of the composition is approximately the same as or higher than that of a subject administered with the composition.
145. The method according to claim 139, wherein the subject has an equivalent serum concentration of neutralizing antibody against hRSV after administration of the composition, compared to a subject administered with the protein hRSV vaccine.
146. The method according to claim 140, wherein the subject has an equivalent serum concentration of neutralizing antibody against hMPV after administration of the composition, compared to a subject administered with the protein hMPV vaccine.
147. The method according to claim 141, wherein the subject has an equivalent serum concentration of neutralizing antibody against hPIV3 after administration of the composition, compared to a subject administered with the protein hPIV3 vaccine.
148. The method according to claim 139, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hRSV immunity.
149. The method according to claim 140, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hMPV immunity.
150. The method according to claim 141, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hPIV3 immunity.
151. A composition for use in inducing an immune response to hRSV or protecting a subject from hRSV infection, comprising administering the composition according to any one of claims 122 to 138 to the subject.
152. A composition for use in inducing an immune response to hMPV or protecting a subject from hMPV infection, comprising administering the composition according to any one of claims 122 to 138 to the subject.
153. A composition for use in inducing an immune response to hPIV3 or protecting a subject from hPIV3 infection, comprising administering the composition according to any one of claims 122 to 138 to the subject.
154. Use of the composition according to any one of claims 122 to 138 in the manufacture of a pharmaceutical product for inducing an immune response to hRSV or for protecting a subject from hRSV infection.
155. Use of the composition according to any one of claims 122 to 138 in the manufacture of a pharmaceutical product for inducing an immune response to hMPV or for protecting a subject from hMPV infection.
156. Use of the composition according to any one of claims 122 to 138 in the manufacture of a pharmaceutical product for inducing an immune response to hMPV or for protecting a subject from hPIV3 infection.
157. A composition comprising a first messenger RNA (mRNA) and a second mRNA, (i) The first mRNA encodes a human respiratory syncytial virus (hRSV) F protein antigen containing the amino acid sequence of SEQ ID NO: 1, (ii) The second mRNA encodes a human metapneumovirus (hMPV) F protein antigen containing the amino acid sequence of SEQ ID NO: 2 A composition comprising a first messenger RNA (mRNA) and a second mRNA.
158. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 1:1 (w / w).
159. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 1:2 (w / w).
160. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 1:3 (w / w).
161. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 1:5 (w / w).
162. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of about 1:1 to about 1:10 (w / w).
163. The composition according to any one of claims 157 to 162, wherein the ratio is expressed in micrograms (μg).
164. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 0.5 micrograms of the first mRNA to approximately 0.5 micrograms of the second mRNA (w / w).
165. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 0.5 micrograms of the first mRNA to approximately 1.5 micrograms of the second mRNA (w / w).
166. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 0.5 micrograms of the first mRNA to approximately 1 microgram of the second mRNA (w / w).
167. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 0.5 micrograms of the first mRNA to approximately 2.5 micrograms of the second mRNA (w / w).
168. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 1 microgram of the first mRNA to approximately 1 microgram of the second mRNA (w / w).
169. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 1 microgram of the first mRNA to approximately 2 micrograms of the second mRNA (w / w).
170. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 1 microgram of the first mRNA to approximately 3 micrograms of the second mRNA (w / w).
171. The composition according to claim 157, wherein the first mRNA and the second mRNA are present in a ratio of approximately 1 microgram of the first mRNA to approximately 5 micrograms of the second mRNA (w / w).
172. The composition according to any one of claims 157 to 171, wherein the first mRNA and the second mRNA are each formulated into separate lipid nanoparticles (LNPs).
173. The composition according to any one of claims 157 to 171, wherein the first mRNA and the second mRNA are formulated into the same LNP.
174. The composition according to claim 172 or 173, wherein the LNP comprises at least one cationic lipid.
175. The composition according to claim 174, wherein the cationic lipid is biodegradable.
176. The composition according to claim 174, wherein the cationic lipid is not biodegradable.
177. The composition according to claim 174, wherein the cationic lipid is cleavable.
178. The composition according to claim 174, wherein the cationic lipid is not cleavable.
179. The composition according to claim 174, wherein the cationic lipid is selected from the group consisting of OF-02, cKK-E10, GL-HEPES-E3-E10-DS-3-E18-1, GL-HEPES-E3-E12-DS-4-E10, GL-HEPES-E3-E12-DS-3-E14, and IM-001.
180. The composition according to claim 179, wherein the cationic lipid is cKK-E10.
181. The composition according to claim 179, wherein the cationic lipid is GL-HEPES-E3-E12-DS-4-E10.
182. The composition according to claim 179, wherein the cationic lipid is IM-001.
183. The composition according to any one of claims 174 to 182, wherein the LNP further comprises polyethylene glycol (PEG) conjugate (PEG-modified) lipids, cholesterol-based lipids, and helper lipids.
184. The aforementioned LNP is Cationic lipids in a molar ratio of 35% to 55%; Polyethylene glycol (PEG) conjugated lipids in a molar ratio of 0.25% to 2.75%; Cholesterol-based lipids in a molar ratio of 20% to 45%; and Helper lipids in a molar ratio of 5% to 35% Includes, The composition according to any one of claims 174 to 183, wherein all of the aforementioned molar ratios are relative to the total lipid content of the LNP.
185. The aforementioned LNP is Cationic lipids at a molar ratio of 40%; PEG-treated lipids at a molar ratio of 1.5%; Cholesterol-based lipids in a molar ratio of 28.5%; and Helper lipids at a 30% molar ratio A composition according to any one of claims 174 to 184, comprising:
186. The composition according to any one of claims 183 to 185, wherein the PEGylated lipid is dimyristoyl-PEG2000 (DMG-PEG2000) or 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159).
187. The composition according to any one of claims 183 to 186, wherein the cholesterol-based lipid is cholesterol.
188. The composition according to any one of claims 183 to 187, wherein the helper lipid is 1,2-dioleoyl-SN-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).
189. The aforementioned LNP is GL-HEPES-E3-E12-DS-4-E10 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE A composition according to any one of claims 174 to 188, comprising:
190. The aforementioned LNP is cKK-E10 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE A composition according to any one of claims 174 to 188, comprising:
191. The aforementioned LNP is IM-001 with a molar ratio of 40%; 1.5% molar ratio of DMG-PEG2000; Cholesterol at a molar ratio of 28.5%; and 30% molar ratio DOPE A composition according to any one of claims 174 to 188, comprising:
192. The composition according to any one of claims 174 to 191, wherein the LNP has an average diameter of 30 nm to 200 nm.
193. The composition according to any one of claims 174 to 191, wherein the LNP has an average diameter of 80 nm to 150 nm.
194. A method for inducing an immune response to hRSV or protecting a subject from hRSV infection, comprising administering to a subject the composition described in any one of claims 157 to 193.
195. A method for inducing an immune response to hMPV or protecting a subject from hMPV infection, comprising administering to the subject a composition according to any one of claims 157 to 193.
196. The method according to claim 194, wherein, compared to a subject administered a single antigen composition comprising mRNA ORF encoding the hRSV F protein antigen of SEQ ID NO: 1, the serum concentration of neutralizing antibodies against hRSV after administration of the composition is approximately the same as or higher.
197. The method according to claim 195, wherein, compared to a subject administered with a single antigen composition comprising mRNA ORF encoding the hMPV F protein antigen of SEQ ID NO: 2, the serum concentration of neutralizing antibodies against hMPV after administration of the composition is approximately the same as or higher than that of a subject administered with the composition.
198. The method according to claim 194, wherein the subject has an equivalent serum concentration of neutralizing antibodies against hRSV after administration of the composition, compared to a subject administered with the protein hRSV vaccine.
199. The method according to claim 195, wherein the subject has an equivalent serum concentration of neutralizing antibody against hMPV after administration of the composition, compared to a subject administered with the protein hMPV vaccine.
200. The method according to claim 194, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hRSV immunity.
201. The method according to claim 195, wherein the composition increases the serum concentration of a neutralizing antibody in a subject having pre-existing hMPV immunity.
202. A composition for use in inducing an immune response to hRSV or protecting a subject from hRSV infection, comprising administering the composition according to any one of claims 157 to 193 to the subject.
203. A composition for use in inducing an immune response to hMPV or protecting a subject from hMPV infection, comprising administering the composition according to any one of claims 157 to 193 to the subject.
204. Use of the composition according to any one of claims 157 to 193 in the manufacture of a pharmaceutical product for inducing an immune response to hRSV or for protecting a subject from hRSV infection.
205. Use of the composition according to any one of claims 157 to 193 in the manufacture of a pharmaceutical product for inducing an immune response to hMPV or for protecting a subject from hMPV infection.