IP Library › Granted Patent US 12,390,523

Granted Patent B2

US 12,390,523 · App. 18/327,882 · Granted Aug 19, 2025

Coronavirus vaccine

Inventors: Susanne Rauch (Tübingen, DE); Hans Wolfgang Große (Tübingen, DE); Benjamin Petsch (Tübingen, DE)

Assignee: CureVac SE

A61K39/215 A61K9/0019 A61K47/26 A61P31/14 A61K2039/53 A61K2039/6018 A61K2039/6093

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 12,390,523
App. No.: 18/327,882
Granted: Aug 19, 2025
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention is directed to a nucleic acid suitable for use in treatment or prophylaxis of an infection with a coronavirus, preferably with a Coronavirus SARS-CoV-2, or a disorder related to such an infection, preferably COVID-19. The present invention is also directed to compositions, polypeptides, and vaccines. The compositions and vaccines preferably comprise at least one of said nucleic acid sequences, preferably nucleic acid sequences in association a lipid nanoparticle (LNP). The invention is also directed to first and second medical uses of the nucleic acid, the composition, the polypeptide, the combination, the vaccine, and the kit, and to methods of treating or preventing a coronavirus infection, preferably a Coronavirus infection.

Claims (137)

1. A purified RNA comprising:

(a) a 5′ cap structure;

(b) at least one coding sequence encoding a SARS-CoV-2 spike protein comprising an amino acid sequence at least 90% identical to SEQ ID NO: 10 that is a pre-fusion stabilized spike protein (S_stab) comprising K986P and V987P stabilizing substitutions and further comprising E484K and D614G amino acid substitutions relative to SEQ ID NO: 10; and

2. The purified RNA of claim 1 , wherein the 5′ cap is a m7G, cap0, cap1, cap2, a modified cap0, or a modified cap1 structure.

3. The purified RNA of claim 2 , wherein the 5′ cap is a cap1 structure.

4. The purified RNA of claim 1 , wherein the purified RNA comprises a terminal poly (A) sequence of 30 to 200 adenosine nucleotides.

5. The purified RNA of claim 1 , wherein the purified RNA further comprises a 5′ UTR.

6. The purified RNA of claim 1 , wherein the at least one coding sequence encoding the SARS-CoV-2 spike protein has a G/C content of at least about 50%.

7. The purified RNA of claim 1 , wherein the purified RNA is a replicon RNA.

8. The purified RNA of claim 7 , wherein the replicon RNA encodes replicase elements derived from an alphavirus.

9. The purified RNA of claim 8 , wherein the replicon RNA encodes replicase elements derived from VEE.

10. The purified RNA of claim 1 , wherein the SARS-CoV-2 spike protein comprises E484K, N501Y, and D614G amino acid substitutions relative to SEQ ID NO: 10.

11. The purified RNA of claim 10 , wherein the SARS-CoV-2 spike protein comprises at least one of the following amino acid substitutions relative to SEQ ID NO: 10:

D80A, D215G, K417N, N501Y, and/or A701V.

12. The purified RNA of claim 11 , wherein the SARS-CoV-2 spike protein comprises the following amino acid substitutions relative to SEQ ID NO: 10: K417N, E484K, N501Y, and D614G.

13. The purified RNA of claim 3 , wherein the purified RNA comprises a 1-methylpseudouridine nucleotide substitution at one or more uracil position(s).

14. The purified RNA of claim 1 , wherein the purified RNA has been purified by RP-HPLC and/or TFF.

15. The purified RNA of claim 14 , wherein the purified RNA has been purified by TFF.

16. The purified RNA of claim 1 , wherein the SARS-CoV-2 spike protein comprises an amino acid sequence at least 98% identical to SEQ ID NO: 10.

17. The purified RNA of claim 1 , wherein the at least one coding sequence comprises a nucleic acid sequence at least 80% identical to SEQ ID NO: 137.

18. The purified RNA of claim 17 , wherein the at least one coding sequence comprises a nucleic acid sequence at least 90% identical to SEQ ID NO: 137.

19. A pharmaceutical composition comprising the purified RNA of claim 1 and at least one pharmaceutically acceptable carrier.

20. The pharmaceutical composition of claim 19 , wherein the RNA is complexed or associated with lipid nanoparticles (LNPs).

21. A method of stimulating an immune response to a SARS-CoV-2 spike protein in a subject comprising administering to the subject an effective amount of the composition of claim 20 .

22. The method of claim 21 , wherein the purified RNA is a replicon RNA that encodes replicase elements derived from an alphavirus.

23. The method of claim 22 , wherein the SARS-CoV-2 spike protein comprises at least one of the following amino acid substitutions relative to SEQ ID NO: 10:

D80A, D215G, K417N, N501Y, and/or A701V.

24. The method of claim 21 , wherein the purified RNA comprises a terminal poly (A) sequence of 30 to 200 adenosine nucleotides and a 5′ cap that is a cap1 structure.

25. The method of claim 24 , wherein the at least one coding sequence comprises a nucleic acid sequence at least 80% identical to SEQ ID NO: 137.

26. The method of claim 25 , wherein the at least one coding sequence comprises a nucleic acid sequence at least 90% identical to SEQ ID NO: 137.

27. The method of claim 22 , wherein the replicon RNA encodes replicase elements derived from VEE.

28. The method of claim 22 , wherein the subject is a human subject.

29. The method of claim 28 , wherein the composition comprises about 1 μg to about 200 μg of the RNA.

30. The method of claim 29 , wherein the composition comprises about 5 μto about 100 μg of the RNA.

31. The method of claim 21 , wherein the method comprises administering the composition to the subject at least twice.

32. A container comprising a vaccine dose comprising a pharmaceutical composition of claim 20 , wherein about 1 μg to about 200 μg of the RNA is present in said vaccine dose.

33. The container of claim 32 , wherein about 5 μg to about 100 μg of the RNA is present in said vaccine dose.

34. The container of claim 32 , wherein the 5′ cap of the RNA is a m7G, cap0, cap1, cap2, a modified cap0, or a modified cap1 structure.

35. The container of claim 34 , wherein the 5′ cap is a cap 1 structure.

36. The container of claim 32 , wherein the purified RNA comprises a terminal poly (A) sequence of 30 to 200 adenosine nucleotides.

37. The container of claim 32 , wherein the RNA further comprising a 5′ UTR.

38. The container of claim 32 , wherein the at least one coding sequence encoding the SARS-CoV-2 spike protein has a G/C content of at least about 50%.

39. The container of claim 38 , wherein 100% of the uracil positions in the RNA are replaced with 1-methylpseudouridine.

40. The container of claim 38 , wherein the purified RNA is a replicon RNA.

41. The container of claim 40 , wherein the replicon RNA encodes replicase elements derived from an alphavirus.

42. The container of claim 41 , wherein the replicon RNA encodes replicase elements derived from VEE.

43. The purified RNA of claim 1 , wherein the purified RNA is a mRNA.

44. The purified RNA of claim 1 , wherein the SARS-CoV-2 spike protein comprises an amino acid sequence at least 92% identical to SEQ ID NO: 10.

45. The purified RNA of claim 44 , wherein the SARS-CoV-2 spike protein comprises an amino acid sequence at least 94% identical to SEQ ID NO: 10.

46. The purified RNA of claim 17 , wherein the SARS-CoV-2 spike protein comprises an amino acid sequence at least 94% identical to SEQ ID NO: 10.

47. The pharmaceutical composition of claim 20 , wherein the SARS-CoV-2 spike protein comprises an amino acid sequence at least 94% identical to SEQ ID NO: 10.

48. The pharmaceutical composition of claim 20 , wherein the SARS-CoV-2 spike protein comprises the E484K, N501Y, and D614G amino acid substitutions relative to SEQ ID NO: 10.

49. The pharmaceutical composition of claim 48 , wherein the SARS-CoV-2 spike protein comprises K417N, E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO: 10.

50. The method of claim 30 , wherein the SARS-CoV-2 spike protein comprises an amino acid sequence at least 94% identical to SEQ ID NO: 10.

51. The method of claim 30 , wherein the SARS-CoV-2 spike protein comprises K417N, E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO: 10.

52. The container of claim 38 , wherein the SARS-CoV-2 spike protein comprises an amino acid sequence at least 94% identical to SEQ ID NO: 10.

53. The container of claim 38 , wherein the SARS-CoV-2 spike protein comprises K417N, E484K, N501Y, and D614G amino acid substitutions relative to SEQ ID NO: 10.

54. The method of claim 21 , wherein the SARS-CoV-2 spike protein comprises K417N, E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO: 10.

55. The method of claim 54 , wherein the SARS-CoV-2 spike protein further comprises H69del and H70del amino acid deletions relative to SEQ ID NO: 10.

56. The method of claim 54 , wherein the SARS-CoV-2 spike protein further comprises a R403K amino acid substitution relative to SEQ ID NO: 10.

57. The pharmaceutical composition of claim 48 , wherein the SARS-CoV-2 spike protein further comprises H69del and H70del amino acid deletions relative to SEQ ID NO: 10.

58. The pharmaceutical composition of claim 48 , wherein the SARS-CoV-2 spike protein further comprises a R403K amino acid substitution relative to SEQ ID NO:10.

59. A container comprising a vaccine dose comprising a purified RNA and at least one pharmaceutically acceptable carrier, said RNA comprising:

(a) a 5′ cap structure;

(b) at least one coding sequence encoding a SARS-CoV-2 spike protein comprising an amino acid sequence at least 90% identical to SEQ ID NO: 10 that is a pre-fusion stabilized spike protein (S_stab) comprising K986P and V987P stabilizing substitutions and further comprising a D 614 G amino acid substitution relative to SEQ ID NO: 10, wherein said at least one coding sequence comprises an RNA sequence at least 90% identical to the RNA sequence of SEQ ID NO: 147; and

wherein the vaccine dose comprises lipid nanoparticles, and

1 wherein about 1 μg to about 200 μg of the RNA is present in said vaccine dose.

60. The container of claim 59 , wherein about 5 μg to about 100 μg of the RNA is present in said vaccine dose.

61. The container of claim 59 , wherein the 5′ cap of the RNA is a m7G, cap0, cap1, cap2, a modified cap0, or a modified cap1 structure.

62. The container of claim 61 , wherein the 5′ cap is a cap1 structure.

63. The container of claim 61 , wherein the 5′ cap is a modified cap1 structure.

64. The container of claim 61 , wherein the purified RNA comprises a terminal poly (A) sequence of 30 to 200 adenosine nucleotides.

65. The container of claim 61 , wherein the purified RNA further comprises a 5′ UTR.

66. The container of claim 61 , wherein the at least one coding sequence encoding the SARS-CoV-2 spike protein has a G/C content of at least about 50%.

67. The container of claim 66 , wherein 100% of the uracil positions in the RNA are replaced with 1-methylpseudouridine.

68. The container of claim 66 , wherein the purified RNA is a replicon RNA.

69. The container of claim 68 , wherein the replicon RNA encodes replicase elements derived from an alphavirus.

70. The container of claim 69 , wherein the replicon RNA encodes replicase elements derived from VEE.

71. The container of claim 67 , wherein the purified RNA is a mRNA.

72. The container of claim 66 , wherein the SARS-CoV-2 spike protein comprises the D614G amino acid substitution and a E484K amino acid substitution relative to SEQ ID NO: 10.

73. The container of claim 66 , wherein the vaccine dose comprises lipid nanoparticles.

74. The container of claim 73 , wherein the SARS-CoV-2 spike protein comprises E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO: 10.

75. The container of claim 74 , wherein the SARS-CoV-2 spike protein comprises K417N, E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO: 10.

76. The container of claim 74 , wherein the SARS-CoV-2 spike protein comprises an amino acid sequence at least 94% identical to SEQ ID NO: 10.

77. A purified RNA comprising:

(a) a 5′ cap structure;

(b) at least one coding sequence encoding a SARS-CoV-2 spike protein comprising an amino acid sequence at least 90% identical to SEQ ID NO: 10 that is a pre-fusion stabilized spike protein (S_stab) comprising K986P and V987P stabilizing substitutions and further comprising a D614G amino acid substitutions relative to SEQ ID NO: 10, wherein said at least one coding sequence comprises an RNA sequence at least 90% identical to the RNA sequence of SEQ ID NO: 147; and

wherein the 5′ cap structure is a cap1 structure or a modified cap 1 structure.

78. The purified RNA of claim 77 , wherein the purified RNA comprises a terminal poly (A) sequence of 30 to 200 adenosine nucleotides.

79. The purified RNA of claim 77 , wherein the purified RNA further comprises a 5′ UTR.

80. The purified RNA of claim 79 , wherein the at least one coding sequence encoding the SARS-CoV-2 spike protein has a G/C content of at least about 50 %.

81. The purified RNA of claim 80 , wherein the purified RNA is a replicon RNA.

82. The purified RNA of claim 81 , wherein the replicon RNA encodes replicase elements derived from an alphavirus.

83. The purified RNA of claim 82 , wherein the replicon RNA encodes replicase elements derived from VEE.

84. The purified RNA of claim 80 , wherein the purified RNA is a mRNA.

85. The purified RNA of claim 80 , wherein the SARS-CoV-2 spike protein comprises the D614G amino acid substitution and a E484K amino acid substitution relative to SEQ ID NO: 10.

86. The purified RNA of claim 85 , wherein the SARS-CoV-2 spike protein comprises E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO: 10.

87. The purified RNA of claim 86 , wherein the SARS-CoV-2 spike protein comprises K417N, E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO:10.

88. The purified RNA of claim 80 , wherein the purified RNA comprises a 1-methylpseudouridine nucleotide substitution at one or more uracil position(s).

89. The purified RNA of claim 80 , wherein the purified RNA has been purified by RP-HPLC and/or TFF.

90. The purified RNA of claim 89 , wherein the purified RNA has been purified by TFF.

91. The purified RNA of claim 80 , wherein the at least one coding sequence comprises a nucleic acid sequence at least 80% identical to SEQ ID NO: 137.

92. A pharmaceutical composition comprising the purified RNA of claim 88 and at least one pharmaceutically acceptable carrier.

93. The pharmaceutical composition of claim 92 , wherein the RNA is complexed or associated with lipid nanoparticles (LNPs).

94. A method of stimulating an immune response to a SARS-CoV-2 spike protein in a subject comprising administering to the subject an effective amount of the composition of claim 93 .

95. A method of stimulating an immune response to a SARS-CoV-2 spike protein in a human subject comprising administering to the subject an effective amount of a pharmaceutical comprising a purified RNA, said RNA comprising:

(a) a 5′ cap structure;

(b) at least one coding sequence encoding a SARS-CoV-2 spike protein comprising an amino acid sequence at least 90% identical to SEQ ID NO: 10 that is a pre-fusion stabilized spike protein (S_stab) comprising K986P and V987P stabilizing substitutions and further comprising a D 614 G amino acid substitution relative to SEQ ID NO: 10, wherein said at least one coding sequence comprises an RNA sequence at least 90% identical to the RNA sequence of SEQ ID NO: 147; and

wherein the RNA is complexed or associated with lipid nanoparticles (LNPs).

96. The method of claim 95 , wherein the 5′ cap structure is a cap1 structure or a modified cap1 structure.

97. The method of claim 96 , wherein the purified RNA comprises a terminal poly(A) sequence of 30 to 200 adenosine nucleotides.

98. The method of claim 97 , wherein the purified RNA further comprises a 5′ UTR.

99. The method of claim 98 , wherein the at least one coding sequence encoding the SARS-CoV-2 spike protein has a G/C content of at least about 50%.

100. The method of claim 95 , wherein the purified RNA is a replicon RNA.

101. The method of claim 100 , wherein the replicon RNA encodes replicase elements derived from an alphavirus.

102. The method of claim 101 , wherein the replicon RNA encodes replicase elements derived from VEE.

103. The method of claim 99 , wherein the purified RNA is a mRNA.

104. The method of claim 99 , wherein the SARS-CoV-2 spike protein comprises the D614G amino acid substitution and a E484K amino acid substitution relative to SEQ ID NO: 10.

105. The method of claim 104 , wherein the SARS-CoV-2 spike protein comprises E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO: 10.

106. The method of claim 105 , wherein the SARS-CoV-2 spike protein comprises K417N, E484K, N501Y and D614G amino acid substitutions relative to SEQ ID NO: 10.

107. The method of claim 99 , wherein the purified RNA comprises a 1 -methylpseudouridine nucleotide substitution at one or more uracil position(s).

108. The method of claim 99 , wherein the purified RNA has been purified by TFF.

109. The method of claim 99 , wherein the at least one coding sequence comprises a nucleic acid sequence at least 80% identical to SEQ ID NO: 137.

110. The method of claim 99 , wherein about 1 μg to about 200 μg of the RNA is administered to the subject.

111. The method of claim 110 , wherein about 5 μg to about 100 μg of the RNA is administered to the subject.

112. The method of claim 111 , wherein the purified RNA is a mRNA.

113. The method of claim 110 , wherein stimulating an immune response in the subject comprises stimulating a SARS-CoV-2 neutralizing antibody response in the subject.

114. The method of claim 113 , wherein stimulating an immune response in the subject comprises stimulating a SARS-CoV-2 spike protein-specific T cell response in the subject.

115. The method of claim 114 , wherein stimulating an immune response in the subject comprises stimulating a SARS-CoV-2 spike protein-specific CD8 + T cell response in the subject.

116. The method of claim 99 , wherein the SARS-CoV-2 spike protein comprises H69del and H 70 del amino acid deletions relative to SEQ ID NO: 10.

117. The method of claim 99 , wherein the SARS-CoV-2 spike protein comprises a R403K amino acid substitution relative to SEQ ID NO: 10.

118. The purified RNA of claim 1 , wherein said at least one coding sequence comprises an RNA sequence at least 90% identical to the RNA sequence of SEQ ID NO: 147.

119. The method of claim 24 , wherein said at least one coding sequence comprises an RNA sequence at least 90% identical to the RNA sequence of SEQ ID NO: 147.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2024

From: RAUCH, SUSANNE; GROSSE, HANS WOLFGANG; PETSCH, BENJAMIN

To: CUREVAC AG

Reel/Frame 067521/0887 →

CHANGE OF NAME Recorded May 24, 2024

From: CUREVAC AG

To: CUREVAC SE

Reel/Frame 067529/0610 →

Priority Claims (6)

WO PCT/EP2020/052775 · Feb 4, 2020 · international

WO PCT/EP2020/059687 · Apr 3, 2020 · international

WO PCT/EP2020/065091 · May 29, 2020 · international

WO PCT/EP2020/079831 · Oct 23, 2020 · international

WO PCT/EP2020/079973 · Oct 23, 2020 · international

WO PCT/EP2020/080713 · Nov 2, 2020 · international

Continuity (9)

Continuation 18179352 · Mar 6, 2023

Continuation 17818699 · Aug 9, 2022

Continuation 17526912 · Nov 15, 2021

Continuation 17276788

Provisional Application 63129395 · Dec 22, 2020

Provisional Application 63119390 · Nov 30, 2020

Provisional Application 63113159 · Nov 12, 2020

Provisional Application 63112106 · Nov 10, 2020

Related Publication 20230302122A1 · Sep 28, 2023

References Cited (400)

US 8691966B2 · Kariko et al. · 2014 [cited by applicant]

US 9364435B2 · Yaworski et al. · 2016 [cited by applicant]

US 9428535B2 · de Fougerolles et al. · 2016 [cited by applicant]

US 9476055B2 · Sahin et al. · 2016 [cited by applicant]

US 9504651B2 · Maclachlan et al. · 2016 [cited by applicant]

US 9518272B2 · Yaworski et al. · 2016 [cited by applicant]

US 9657295B2 · Schrum et al. · 2017 [cited by applicant]

US 9758795B2 · Cullis et al. · 2017 [cited by applicant]

US 9850269B2 · DeRosa et al. · 2017 [cited by applicant]

US 9868692B2 · Benenato · 2018 [cited by applicant]

US 9943612B2 · Scharenberg et al. · 2018 [cited by applicant]

US 10017543B2 · Kwong et al. · 2018 [cited by applicant]

US 10022435B2 · Ciaramella et al. · 2018 [cited by applicant]

US 10064959B2 · Schrum et al. · 2018 [cited by applicant]

US 10266485B2 · Benenato · 2019 [cited by applicant]

US 10442756B2 · Benenato et al. · 2019 [cited by applicant]

US 10577403B2 · De Fougerolles et al. · 2020 [cited by applicant]

US 10702600B1 · Ciaramella et al. · 2020 [cited by applicant]

US 10703789B2 · De Fougerolles et al. · 2020 [cited by applicant]

US 10772975B2 · Bancel et al. · 2020 [cited by applicant]

US 10898574B2 · de Fougerolles et al. · 2021 [cited by applicant]

US 10933127B2 · Ciaramella et al. · 2021 [cited by applicant]

US 10953089B1 · Smith et al. · 2021 [cited by applicant]

US 11060107B2 · Weissman et al. · 2021 [cited by applicant]

US 11078242B1 · Roy et al. · 2021 [cited by applicant]

US 11202793B2 · Hoge et al. · 2021 [cited by applicant]

US 11241493B2 · Rauch et al. · 2022 [cited by applicant]

US 11471525B2 · Rauch · 2022 [cited by examiner]

US 11566051B2 · Zhang et al. · 2023 [cited by applicant]

US 11576966B2 · Rauch · 2023 [cited by examiner]

US 11596686B2 · Rauch · 2023 [cited by examiner]

US 11872280B2 · Roth · 2024 [cited by examiner]

US 11918643B2 · Roth · 2024 [cited by examiner]

US 20050032730A1 · von der Mülbe et al. · 2005 [cited by applicant]

US 20050059624A1 · Hoerr et al. · 2005 [cited by applicant]

US 20050250723A1 · Hoerr et al. · 2005 [cited by applicant]

US 20060188490A1 · Hoerr et al. · 2006 [cited by applicant]

US 20080025944A1 · Hoerr et al. · 2008 [cited by applicant]

US 20080267873A1 · Hoerr et al. · 2008 [cited by applicant]

US 20090324584A1 · Hoerr et al. · 2009 [cited by applicant]

US 20100048883A1 · Ketterer et al. · 2010 [cited by applicant]

US 20100189729A1 · Hoerr et al. · 2010 [cited by applicant]

US 20100203076A1 · Fotin-Mleczek et al. · 2010 [cited by applicant]

US 20100291156A1 · Barner et al. · 2010 [cited by applicant]

US 20100305196A1 · Probst et al. · 2010 [cited by applicant]

US 20110053829A1 · Baumhof et al. · 2011 [cited by applicant]

US 20110250225A1 · Fotin-Mleczek et al. · 2011 [cited by applicant]

US 20120021043A1 · Kramps et al. · 2012 [cited by applicant]

US 20120258046A1 · Mutzke · 2012 [cited by applicant]

US 20130129754A1 · Thess et al. · 2013 [cited by applicant]

US 20130142818A1 · Baumhof et al. · 2013 [cited by applicant]

US 20130259879A1 · Baumhof et al. · 2013 [cited by applicant]

US 20130280283A1 · Lorenz et al. · 2013 [cited by applicant]

US 20130295043A1 · Kallen et al. · 2013 [cited by applicant]

US 20130336998A1 · Kallen et al. · 2013 [cited by applicant]

US 20150037326A1 · Butler-Ransohoff et al. · 2015 [cited by applicant]

US 20150050302A1 · Thess · 2015 [cited by applicant]

US 20150057340A1 · Thess et al. · 2015 [cited by applicant]

US 20150093413A1 · Thess et al. · 2015 [cited by applicant]

US 20150118183A1 · Baumhof · 2015 [cited by applicant]

US 20150118264A1 · Baumhof et al. · 2015 [cited by applicant]

US 20150165006A1 · Thess et al. · 2015 [cited by applicant]

US 20150184195A1 · Thess · 2015 [cited by applicant]

US 20150218554A1 · Thess · 2015 [cited by applicant]

US 20150306249A1 · Baumhof et al. · 2015 [cited by applicant]

US 20150320847A1 · Thess et al. · 2015 [cited by applicant]

US 20160024139A1 · Berlanda Scorza et al. · 2016 [cited by applicant]

US 20160130345A1 · Fotin-Mleczek et al. · 2016 [cited by applicant]

US 20160166668A1 · Kallen et al. · 2016 [cited by applicant]

US 20160166678A1 · Kallen et al. · 2016 [cited by applicant]

US 20160166710A1 · Baumhof · 2016 [cited by applicant]

US 20160166711A1 · Schnee et al. · 2016 [cited by applicant]

US 20160168207A1 · Kramps et al. · 2016 [cited by applicant]

US 20160168227A1 · Kallen et al. · 2016 [cited by applicant]

US 20160235864A1 · Schlake · 2016 [cited by applicant]

US 20160304883A1 · Grund · 2016 [cited by applicant]

US 20160304938A1 · Wochner · 2016 [cited by applicant]

US 20160326575A1 · von der Mülbe · 2016 [cited by applicant]

US 20160331844A1 · Fotin-Mleczek et al. · 2016 [cited by applicant]

US 20170014496A1 · Fotin-Mleczek et al. · 2017 [cited by applicant]

US 20170029847A1 · Thess · 2017 [cited by applicant]

US 20170114378A1 · Wochner et al. · 2017 [cited by examiner]

US 20170182150A1 · Kallen · 2017 [cited by examiner]

US 20170252430A1 · Fotin-Mleczek · 2017 [cited by applicant]

US 20170326225A1 · Rauch · 2017 [cited by applicant]

US 20180044687A1 · Thess et al. · 2018 [cited by applicant]

US 20180125952A1 · Fotin-Mleczek · 2018 [cited by applicant]

US 20180126003A1 · Hoerr · 2018 [cited by applicant]

US 20180142275A1 · Roos et al. · 2018 [cited by applicant]

US 20180147146A1 · Eber et al. · 2018 [cited by applicant]

US 20180148727A1 · Grund · 2018 [cited by applicant]

US 20180201967A1 · Eber et al. · 2018 [cited by applicant]

US 20180208957A1 · Roos et al. · 2018 [cited by applicant]

US 20180214537A1 · Mutzke et al. · 2018 [cited by applicant]

US 20180237786A1 · Schlake · 2018 [cited by applicant]

US 20180237817A1 · Roos et al. · 2018 [cited by applicant]

US 20180243219A1 · Ketterer et al. · 2018 [cited by applicant]

US 20180296663A1 · Hipp et al. · 2018 [cited by applicant]

US 20180298372A1 · Funkner et al. · 2018 [cited by applicant]

US 20180303925A1 · Weissman et al. · 2018 [cited by applicant]

US 20180312545A1 · Baumhof et al. · 2018 [cited by applicant]

US 20180371392A1 · Mayer · 2018 [cited by applicant]

US 20190010485A1 · Yazdan Panah et al. · 2019 [cited by applicant]

US 20190017100A1 · Wochner · 2019 [cited by applicant]

US 20190024096A1 · Schmid et al. · 2019 [cited by applicant]

US 20190040378A1 · Fotin-Mleczek et al. · 2019 [cited by applicant]

US 20190049414A1 · Wochner et al. · 2019 [cited by applicant]

US 20190083602A1 · Roos et al. · 2019 [cited by applicant]

US 20190100784A1 · Eber et al. · 2019 [cited by applicant]

US 20190125857A1 · Rauch et al. · 2019 [cited by applicant]

US 20190133950A1 · Eber et al. · 2019 [cited by applicant]

US 20190160164A1 · Rauch · 2019 [cited by applicant]

US 20190177714A1 · Kunze et al. · 2019 [cited by applicant]

US 20190185859A1 · Fotin-Mleczek et al. · 2019 [cited by applicant]

US 20190194760A1 · Koch et al. · 2019 [cited by applicant]

US 20190225971A1 · Williams · 2019 [cited by applicant]

US 20190241633A1 · Fotin-Mleczek · 2019 [cited by applicant]

US 20190249219A1 · Reichert et al. · 2019 [cited by applicant]

US 20190336608A1 · Baumhof · 2019 [cited by applicant]

US 20190336611A1 · Baumhof · 2019 [cited by applicant]

US 20190343933A1 · Horscroft et al. · 2019 [cited by applicant]

US 20190343942A1 · Fotin-Mleczek · 2019 [cited by applicant]

US 20190351044A1 · Jasny · 2019 [cited by applicant]

US 20190351047A1 · Jasny · 2019 [cited by applicant]

US 20190351048A1 · Rauch · 2019 [cited by applicant]

US 20190381180A1 · Baumhof · 2019 [cited by applicant]

US 20200023076A1 · Fotin-Mleczek · 2020 [cited by applicant]

US 20200030432A1 · Ciaramella et al. · 2020 [cited by applicant]

US 20200061185A1 · Graham et al. · 2020 [cited by applicant]

US 20200085852A1 · Fotin-Mleczek · 2020 [cited by applicant]

US 20200085944A1 · Heidenreich et al. · 2020 [cited by applicant]

US 20200149026A1 · Horscroft et al. · 2020 [cited by applicant]

US 20200163878A1 · Baumhof et al. · 2020 [cited by applicant]

US 20200179526A1 · Baumhof · 2020 [cited by applicant]

US 20200197510A1 · Ciaramella et al. · 2020 [cited by applicant]

US 20200282046A1 · Ciaramella et al. · 2020 [cited by applicant]

US 20200318097A1 · Funkner et al. · 2020 [cited by applicant]

US 20200392572A1 · Yazdan Panah et al. · 2020 [cited by applicant]

US 20210023199A1 · Kallen et al. · 2021 [cited by applicant]

US 20210030864A1 · Petsch et al. · 2021 [cited by applicant]

US 20210030866A1 · Kallen et al. · 2021 [cited by applicant]

US 20210060175A1 · Fotin-Mleczek et al. · 2021 [cited by applicant]

US 20210069315A1 · Baumhof et al. · 2021 [cited by applicant]

US 20210162037A1 · Jasny et al. · 2021 [cited by applicant]

US 20210170017A1 · Lutz et al. · 2021 [cited by applicant]

US 20210180106A1 · Wochner et al. · 2021 [cited by applicant]

US 20210205434A1 · Petsch et al. · 2021 [cited by applicant]

US 20210222178A1 · Linke et al. · 2021 [cited by applicant]

US 20210228707A1 · Metkar et al. · 2021 [cited by applicant]

US 20210228708A1 · Smith et al. · 2021 [cited by applicant]

US 20210228709A1 · Smith et al. · 2021 [cited by applicant]

US 20210246170A1 · Langedijk et al. · 2021 [cited by applicant]

US 20210253645A1 · Gershoni et al. · 2021 [cited by applicant]

US 20210260178A1 · Jasny et al. · 2021 [cited by applicant]

US 20210261897A1 · Yazdan Panah et al. · 2021 [cited by applicant]

US 20210361761A1 · Lutz et al. · 2021 [cited by applicant]

US 20210379181A1 · Rauch et al. · 2021 [cited by applicant]

US 20210403925A1 · Chevessier-Tünnesen et al. · 2021 [cited by applicant]

US 20220040281A1 · Schwendt et al. · 2022 [cited by applicant]

US 20220073962A1 · Schwenger et al. · 2022 [cited by applicant]

US 20220133908A1 · Rejman et al. · 2022 [cited by applicant]

US 20220144877A1 · Heinz et al. · 2022 [cited by applicant]

US 20220202930A1 · Roth et al. · 2022 [cited by applicant]

US 20220331422A1 · Roth et al. · 2022 [cited by applicant]

US 20220347289A1 · Chen et al. · 2022 [cited by applicant]

US 20240156946A1 · Roth et al. · 2024 [cited by applicant]

US 20240207389A1 · Penaloza-MacMaster · 2024 [cited by applicant]

CN 111228475 · 2020 [cited by applicant]

CN 111606980 · 2020 [cited by applicant]

CN 111606981 · 2020 [cited by applicant]

CN 111647053 · 2020 [cited by applicant]

CN 111732638 · 2020 [cited by applicant]

CN 111778264 · 2020 [cited by applicant]

CN 111821433 · 2020 [cited by applicant]

CN 111333704B · 2021 [cited by applicant]

CN 112226445 · 2021 [cited by applicant]

CN 112266411 · 2021 [cited by applicant]

CN 111518175B · 2021 [cited by applicant]

CN 112300251 · 2021 [cited by applicant]

CN 112390863 · 2021 [cited by applicant]

EP 2791160B1 · 2014 [cited by applicant]

EP 3035959 · 2016 [cited by applicant]

EP 3336082 · 2020 [cited by applicant]

WO WO2006068663 · 2006 [cited by applicant]

WO WO2006078294 · 2006 [cited by applicant]

WO WO2007024708 · 2007 [cited by applicant]

WO WO2007024941 · 2007 [cited by applicant]

WO WO2008016473 · 2008 [cited by applicant]

WO WO2008157688 · 2008 [cited by applicant]

WO WO2008077592 · 2008 [cited by applicant]

WO WO2009030481 · 2009 [cited by applicant]

WO WO2009149253 · 2009 [cited by applicant]

WO WO2011005799 · 2011 [cited by applicant]

WO WO2011015347 · 2011 [cited by applicant]

WO WO2011068810 · 2011 [cited by applicant]

WO WO2011071931 · 2011 [cited by applicant]

WO WO2011076807 · 2011 [cited by applicant]

WO WO2012006369 · 2012 [cited by applicant]

WO WO2012006372 · 2012 [cited by applicant]

WO WO2012006377 · 2012 [cited by applicant]

WO WO2012006378 · 2012 [cited by applicant]

WO WO2012030901 · 2012 [cited by applicant]

WO WO2012031043 · 2012 [cited by applicant]

WO WO2012031046 · 2012 [cited by applicant]

WO WO2012116810 · 2012 [cited by applicant]

WO WO2012116811 · 2012 [cited by applicant]

WO WO2013006825 · 2013 [cited by applicant]

WO WO2013033563 · 2013 [cited by applicant]

WO WO2013059475 · 2013 [cited by applicant]

WO WO2013151736 · 2013 [cited by applicant]

WO WO2014152966 · 2014 [cited by applicant]

WO WO2014152027 · 2014 [cited by applicant]

WO WO2015164674 · 2015 [cited by applicant]

WO WO2015164773 · 2015 [cited by applicant]

WO WO2015199952 · 2015 [cited by applicant]

WO WO2016022914 · 2016 [cited by applicant]

WO WO2016165831 · 2016 [cited by applicant]

WO WO2016176330 · 2016 [cited by applicant]

WO WO2016193206 · 2016 [cited by applicant]

WO WO2017004143 · 2017 [cited by applicant]

WO WO2017053297 · 2017 [cited by applicant]

WO WO2017053297A1 · 2017 [cited by examiner]

WO WO2017066781 · 2017 [cited by applicant]

WO WO2017066782 · 2017 [cited by applicant]

WO WO2017066789 · 2017 [cited by applicant]

WO WO2017066791 · 2017 [cited by applicant]

WO WO2017066793 · 2017 [cited by applicant]

WO WO2017066797 · 2017 [cited by applicant]

WO WO2017070620 · 2017 [cited by applicant]

WO WO2017070626 · 2017 [cited by applicant]

WO WO2017075531 · 2017 [cited by applicant]

WO WO2017137095 · 2017 [cited by applicant]

WO WO2017140905 · 2017 [cited by applicant]

WO WO2018075827 · 2018 [cited by applicant]

WO WO2018078053 · 2018 [cited by applicant]

WO WO2018081318 · 2018 [cited by applicant]

WO WO2018170347 · 2018 [cited by applicant]

WO WO2018081480 · 2018 [cited by applicant]

WO WO2018172556 · 2018 [cited by applicant]

WO WO2018211038 · 2018 [cited by applicant]

WO WO2019077001 · 2019 [cited by applicant]

WO WO2019092153 · 2019 [cited by applicant]

WO WO2019193183 · 2019 [cited by applicant]

WO WO2019222424 · 2019 [cited by applicant]

WO WO2019226925 · 2019 [cited by applicant]

WO WO2019232095 · 2019 [cited by applicant]

WO WO2019232097 · 2019 [cited by applicant]

WO WO2019232208 · 2019 [cited by applicant]

WO WO2020002525 · 2020 [cited by applicant]

WO WO2020002598 · 2020 [cited by applicant]

WO WO2020123300 · 2020 [cited by applicant]

WO WO2020127959 · 2020 [cited by applicant]

WO WO2020128031 · 2020 [cited by applicant]

WO WO2020254535 · 2020 [cited by applicant]

WO WO2021028439 · 2021 [cited by applicant]

WO WO2021030701 · 2021 [cited by applicant]

WO WO2021123332 · 2021 [cited by applicant]

WO WO2021147025 · 2021 [cited by applicant]

WO WO2021151099 · 2021 [cited by applicant]

WO WO2021154763 · 2021 [cited by applicant]

WO WO2021154828 · 2021 [cited by applicant]

WO WO2021155323 · 2021 [cited by applicant]

WO WO2021155760 · 2021 [cited by applicant]

WO WO2021156267 · 2021 [cited by applicant]

WO WO2021159040 · 2021 [cited by applicant]

WO WO2021159985 · 2021 [cited by applicant]

WO WO2021160036 · 2021 [cited by applicant]

WO WO2021160346 · 2021 [cited by applicant]

WO WO2021160850 · 2021 [cited by applicant]

WO WO2021160881 · 2021 [cited by applicant]

WO WO2021161043 · 2021 [cited by applicant]

WO WO2021163222 · 2021 [cited by applicant]

WO WO2021163365 · 2021 [cited by applicant]

WO WO2021163371 · 2021 [cited by applicant]

WO WO2021163398 · 2021 [cited by applicant]

WO WO2021163427 · 2021 [cited by applicant]

WO WO2021163438 · 2021 [cited by applicant]

WO WO2021163456 · 2021 [cited by applicant]

WO WO2021163536 · 2021 [cited by applicant]

WO WO2021163584 · 2021 [cited by applicant]

WO WO2021163622 · 2021 [cited by applicant]

WO WO2021202734 · 2021 [cited by applicant]

WO WO2021209970 · 2021 [cited by applicant]

WO WO2021213924 · 2021 [cited by applicant]

WO WO2021213945 · 2021 [cited by applicant]

WO WO2021214204 · 2021 [cited by applicant]

WO WO2021222304 · 2021 [cited by applicant]

WO WO2021228842 · 2021 [cited by applicant]

WO WO2021236854 · 2021 [cited by applicant]

WO WO2021239880 · 2021 [cited by applicant]

WO WO2021243122 · 2021 [cited by applicant]

WO WO2021245611 · 2021 [cited by applicant]

WO WO2022067010 · 2022 [cited by applicant]

WO WO2022110099 · 2022 [cited by applicant]

WO WO2022155524 · 2022 [cited by applicant]

WO WO2022155530 · 2022 [cited by applicant]

WO WO2022180219 · 2022 [cited by applicant]

WO WO2023051701 · 2023 [cited by applicant]

WO WO2023064907 · 2023 [cited by applicant]

WO WO2023086961 · 2023 [cited by applicant]

Hou et al., Nature, 2021, 6:1078-1094. (Year: 2021). [cited by examiner]

Kemp et al., BioRXiv, posted Dec. 15, 2020:2020.12.14.422555, 23 pages. (Year: 2020). [cited by examiner]

“Comirnaty, Common name: COVID-19 mRNA vaccine (nucleoside-modified),” Assessment Report, European Medicines Agency, Dec. 21, 2020. [cited by applicant]

“COVID-19 vaccine moderna, Common name: COVID-19 mRNA Vaccine (nucleoside-modified),” Assessment Report, European Medicines Agency, Jan. 6, 2021. [cited by applicant]

“CureVac Final Data from Phase 2b/3 Trial of First-Generation COVID-19 Vaccine Canidate, CVnCoV, Demonstrates Protection in Age Group of 18 to 60”, press release, Jun. 30, 2021. [cited by applicant]

“CureVac Provides Update on Phase 2b/3 Trial of First-Generation COVID-19 Vaccine Canidated CVnCoV”, press release, Jun. 16, 2021. [cited by applicant]

“CureVac: Final Analysis of Pivotal Phase 2b/3 Herald Study”, presentation, Jul. 1, 2021. [cited by applicant]

“CureVac: Second Interim Analysis of Pivotal Phase 2b/3 Herald Study”, presentation, Jun. 17, 2021. [cited by applicant]

“Final Analysis of Phase 2b/3 Clinical Trial of First-Generation COVID-19 Vaccine Canidate, CVnCoV”, transcript of conference call, Jul. 1, 2021. [cited by applicant]

“Pfizer and BioNTech Achieve First Authorization in the World for a Vaccine to CVnCoV”, press release, Dec. 2, 2020. [cited by applicant]

“Results of Second Interim Analysis of CureVac's Pivotal Phase 2b/3 Herald Study”, transcript of conference call, Jun. 17, 2021. [cited by applicant]

Anderson et al., “Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation,” [cited by applicant]

Anderson et al., “Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults,” [cited by applicant]

Andries et al., “N(1)-Methylpseudouridine-Incorporated mRNA Outperforms Pseudouridine-Incorporated mRNA by Providing Enhanced Protein Expression and Reduced Immunogenicity in Mammalian Cell Lines and Mice,” [cited by applicant]

Baden et al., “Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine,” [cited by applicant]

Benton et al., “The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2,” [cited by applicant]

BioNTech Annual Report, “For a medicine of tomorrow” pp. 1, 24, and 70-94, 2021. [cited by applicant]

Cai et al., “Distinct conformational states of SARS-CoV-2 spike protein,” [cited by applicant]

Chan et al., “A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster,” Lancet 395:514-523, 2020. [cited by applicant]

Corbett et al., “Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates,” [cited by applicant]

Corbett et al., “SARS-CoV-2 mRNA vaccine development enabled by prototype pathogen preparedness,” bioRxiv preprint, Jun. 11, 2020. [cited by applicant]

Daniloski et al., “The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types,” [cited by applicant]

Dao et al., “SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence,” [cited by applicant]

Database EMBL Accession No. MN908947, 2020. [cited by applicant]

Deering et al., “Nucleic acid vaccines: prospects for non-viral delivery of mRNA vaccines,” [cited by applicant]

Gebre et al., “Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine,” Nature, 601:410-414, 2022. [cited by applicant]

Gebre et al., “Optimization of non-coding regions improves protective efficacy of an mRNA SARS-CoV-2 vaccine in nonhuman primates,” bioRxiv Preprint, Aug. 16, 2021. [cited by applicant]

GenBank Accession No. MN908947.1, “Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome,” Jan. 12, 2020. [cited by applicant]

GenBank Accession No. MN908947.2, “Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome,” Jan. 14, 2020. [cited by applicant]

Gerhardt et al., “A thermostable, flexible RNA vaccine delivery platform for pandemic response,” bioRxiv preprint, Feb. 2, 2021. [cited by applicant]

Gobeil et al., “D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction,” [cited by applicant]

Gorbalenya et al., “The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2,” Nat. Microbiology, 5:536-544, 2020. [cited by applicant]

Grifoni et al., “Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals,” [cited by applicant]

Hassett et al., “Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines,” Molecular Therapy: Nucleic Acids 15:1-11, 2019. [cited by applicant]

Hoffmann et al., “CVnCoV protects human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2,” bioRxiv preprint, Mar. 22, 2021. [cited by applicant]

Hseih et al., “Structure-based design of prefusion-stabilized SARS-CoV-2 spikes,” Science, 369:1501-1505, 2020. [cited by applicant]

Huang et al., “Clinical features of patients infection 2019 novel coronavirus in Wuhan, China,” [cited by applicant]

Jackson et al., “An mRNA vaccine against SARS-CoV-2—preliminary report,” [cited by applicant]

Jiang et al., “SARS vaccine development,” [cited by applicant]

Kakodkar et al., “A comprehensive literature review on the clinical presentation, and management of the pandemic coronavirus disease 2019 (COVID-19),” [cited by applicant]

Kariko et al., “Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA,” [cited by applicant]

Kariko et al., “Incorporation of Pseudouridine into mRNA yields Superior Nonimmunogenic Vector with Increased Translational Capacity and Biological Stability,” [cited by applicant]

Ke et al., “Structures and distributions of SARS-CoV-2 spike proteins on intact virions,” [cited by applicant]

Kirchdoerfer et al., “Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis,” [cited by applicant]

Kober et al., “Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus,” [cited by applicant]

Kusters et al., “Manufacturing vaccines for an emerging viral infection—specific issues associated with the development of a prototype SARS vaccine,” Vaccine for Biodefense and Emerging and Neglected Diseases, 147-156, … [cited by applicant]

Le et al., “The COVID-19 vaccine development landscape,” [cited by applicant]

Lee et al., “Human neutralzising antibodies elicited by SARS-CoV-2 non-D614G variants offer cross-protection against the SARS-CoV-2 D614G variant,” Clinical & Translational Immunology, 10:e1241, pp. 1-10, 2021. [cited by applicant]

Letko et al., “Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses,” [cited by applicant]

Lu et al., “Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding,” Lancet 395:565-574, 2020. [cited by applicant]

MacLachlan, “Liposomal formulations for nucleic acid delivery,” [cited by applicant]

Maruggi et al., “mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases,” [cited by applicant]

Muik et al., “Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera,” bioRxiv preprint, Jan. 19, 2021. [cited by applicant]

NCBI Accession No. NC_045512.1, “Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome,” Jan. 13, 2020. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/067,614, dated Oct. 18, 2021. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/067,614, dated Apr. 1, 2021. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/067,614, dated Dec. 10, 2020. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/067,709, dated Oct. 18, 2021. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/067,709, dated Jul. 14, 2021. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/067,709, dated Mar. 10, 2021. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/067,709, dated Nov. 27, 2020. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/090,885, dated Jun. 1, 2021. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/090,885, dated Feb. 18, 2021. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/231,261, dated Dec. 22, 2021. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/526,912, dated Jun. 20, 2022. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/546,414, dated Apr. 20, 2022. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/546,414, dated May 9, 2022. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/546,414, dated Aug. 18, 2022. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/546,414, dated Aug. 31, 2022. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/818,699, dated Dec. 13, 2022. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/818,699, dated Oct. 31, 2022. [cited by applicant]

Office Communication issued in U.S. Appl. No. 17/818,699, dated Jan. 20, 2023. [cited by applicant]

Ou et al., “Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV,” [cited by applicant]

Pallesen et al “Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen,” PNAS, 14(35):E7348-E7357, 2017. [cited by applicant]

Pardi et al., “Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses,” J. Exp. Med., 215:1571-1588, 2018. [cited by applicant]

Pascolo, “Vaccination with Messenger RNA (mRNA),” [cited by applicant]

PCT International Search Report and Written Opinion issued in International Application No. PCT/EP2021/052455 dated Jun. 25, 2021. [cited by applicant]

PCT Invitation to Pay Additional Fees, Partial Search Report, and Provisional Opinion issued in International Application No. PCT/EP2021/052455, dated Apr. 29, 2021. [cited by applicant]

Perlman et al., “Immunopathogenesis of coronavirus infections: Implications for SARS,” Nature Reviews Immunology, 5:917-927, 2005. [cited by applicant]

Pinto et al., “Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody,” [cited by applicant]

Plante et al., “Spike mutation D614G alters SARS-CoV-2 fitness,” [cited by applicant]

Polack et al., “Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine,” [cited by applicant]

Programme from the 1 [cited by applicant]

Rauch et al., “mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents,” bioRxiv preprint, Feb. 9, 2021. [cited by applicant]

Rauch et al., “mRNA vaccine CVnCoV protects non-human primates from SARS-CoV-2 challenge infection,” bioRxiv preprint, Dec. 23, 2020. [cited by applicant]

Rauch et al., “New vaccine technologies to combat outbreak situations,” [cited by applicant]

Registry Nos. 2749948-25-0, 2692611-88-2, 2758016-89-4, 2755828-88-5, 2741858-84-2, 2730004-45-0, 2696398-77-1, and 2695574-78-6, STN Database, Accessed Feb. 9, 2022. [cited by applicant]

Riley et al., “Enhancing the Prefusion Conformational Stability of SARS-CoV-2 Spike Protein Through Structure-Guided Design,” [cited by applicant]

Sahin et al., “Concurrent human antibody and T [cited by applicant]

Sahin et al., “mRNA-based therapeutics—developing a new class of drugs,” [cited by applicant]

Schrörs et al., “Large-scale analysis of SARS-CoV-2 spike-glycoprotein mutants demonstrates the need for continuous screening of virus isolates,” bioRxiv preprint, Mar. 15, 2021. [cited by applicant]

Tian et al., “Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody,” [cited by applicant]

Toyoshima et al., “SARS-CoV-2 genomic variations associated with mortality rate of COVID-19,” Journal of Human Genetics, 65:1075-1082, 2020. [cited by applicant]

U.S. Appl. No. 62/967,006, entitled “Coronavirus RNA vaccines,” filed Jan. 28, 2020. [cited by applicant]

Vogel et al., “A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates,” bioRxiv preprint, Sep. 8, 2020. [cited by applicant]

Vogel et al., “BNT162b vaccines are immunogenic and protect non-human primates against SARS-CoV-2,” bioRxiv preprint, Dec. 11, 2020. [cited by applicant]

Wan et al., “Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus,” [cited by applicant]

Wang et al., “An evidence based perspective on mRNA-SARS-CoV-2 vaccine development,” [cited by applicant]

Wang et al., “Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2,” [cited by applicant]

Widge et al., “Durability of responses after SARS-CoV-2 mRNA-1273 vaccination,” [cited by applicant]