IP Library › Granted Patent US 12,419,948
Granted Patent B2
US 12,419,948 · App. 17/463,429 · Granted Sep 23, 2025

Immunogenic compositions and use thereof

Inventors: Pardis Sabeti (Cambridge, MA); Shira Weingarten-Gabbay (Cambridge, MA); Susan Klaeger (Cambridge, MA); Jenn Abelin (Cambridge, MA); Mohsan Saeed (Boston, MA); Nir Hacohen (Boston, MA); Siranush Sarkizova (Cambridge, MA); Steven Carr (Cambridge, MA); Karl Clauser (Cambridge, MA)
Assignees: The Broad Institute, Inc.; President and Fellows of Harvard College; The General Hospital Corporation; Trustees of Boston University
A61K39/215A61K45/06A61P31/14G01N33/56983G01N33/6818A61K2039/53G01N2333/165G01N2800/26
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Quick Facts
Patent No.
US 12,419,948
App. No.
17/463,429
Granted
Sep 23, 2025
Kind
B2
Abstract

Immunogenic compositions comprising one or more polypeptides, wherein the one or more polypeptides: is capable of binding to Major Histocompatibility Complex (MHC) class I, and is derived from one or more proteins of SARS-COV-2. Also provided include methods of treating and preventing diseases using the immunogenic compositions.

Claims (44)

1. An immunogenic composition comprising:

one or more vectors each comprising one or more polynucleotides encoding one or more polypeptides, wherein the one or more polypeptides:

a. is capable of binding to Major Histocompatibility Complex (MHC) class I,

b. is derived from one or more proteins of SARS-COV-2 by expression of an internal out-of-frame open reading frame (ORF) of SARS-COV-2, wherein the internal out-of-frame ORF is S.iORF1 or S.iORF2, and

c. wherein at least one polypeptide of the one or more polypeptides derived from expression of S.iORF1 is MLLGSMLYM (SEQ ID NO: 4); or wherein at least one polypeptide of the one or more polypeptides is derived from expression of S.iORF1 or S.iORF2 is GPMVLRGLIT (SEQ ID NO: 6) or GLITLSYHL (SEQ ID NO: 5).

2. The immunogenic composition of claim 1 , wherein the MHC class I is Human Leukocyte Antigen class I (HLA-I).

3. The immunogenic composition of claim 2 , wherein the HLA-I is encoded by an HLA allele having a prediction rank score ranking cut-off of 0.1% or greater as determined with HLAthena.

4. The immunogenic composition of claim 2 , wherein the HLA-1 is encoded by HLA-A*02:01, HLA-A*25:01, HLA-A*30:01, HLA-B*18:01, HLA-B*44:03, HLA-C*12:03, HLA-B*16:01, HLA-A*02:01, HLA-B*07:02, HLA-C*07:02; HLA-A*01:01; HLA-A*02:06; HLA-A*26:01; HLA-A*02:07; HLA-A*29:02; HLA-A*02:03; HLA-A*30:02; HLA-A*32:01; HLA-A*68:02; HLA-A*02:05; HLA-A*02:02; HLA-A*36:01; HLA-A*02:11; HLA-A*02:04; HLA-B*35:01; HLA-B*51:01; HLA-B*40:01; HLA-B*40:02; HLA-B*07:02; HLA-B*07:04; HLA-B*08:01; HLA-B*13:01; HLA-B*46:01; HLA-B*52:01; HLA-B*44:02; HLA-B*40:06; HLA-B*13:02; HLA-B*56:01; HLA-B*54:01; HLA-B*15:02; HLA-B*35:07; HLA-B*27:05; HLA-B*15:03; HLA-B*42:01; HLA-B*55:02; HLA-B*45:01; HLA-B*50:01; HLA-B*35:03; HLA-B*49:01; HLA-B*58:02; HLA-B*15:17; HLA-C*57:02; HLA-C*04:01; HLA-C*03:04; HLA-C*01:02; HLA-C*07:01; HLA-C*06:02; HLA-C*03:03; HLA-C*08:01; HLA-C*15:02; HLA-C*12:02; HLA-C*02:02; HLA-C*05:01; HLA-C*03:02; HLA-C*16:01; HLA-C*08:02; HLA-C*04:03; HLA-C*17:01; or HLA-C*17:04.

5. The immunogenic composition of claim 2 , wherein the HLA-1 is encoded by HLA-A*02:01, HLA-A*25:01, HLA-A*30:01, HLA-B*18:01, HLA-B*44:03, HLA-C*12:03, HLA-B*16:01, HLA-A*02:01, HLA-B*07:02, or HLA-C*07:02.

6. The immunogenic composition of claim 1 , wherein one or more of the one or more polypeptides is capable of stimulating a T-cell response.

7. The immunogenic composition of claim 1 , wherein at least one polypeptide of the one or more polypeptides derived from expression of S.iORF1 or S.iORF2 comprises one or more oxidized methionines.

8. The immunogenic composition of claim 7 , wherein the at least one polypeptide is SEQ ID NO: 193 or 204.

9. The immunogenic composition of claim 1 , wherein the one or more polypeptides are expressed and/or is bound by MHC-I 0-12, 0-11, 0-10, 0-9, 0-8, 0-7, 0-6, 0-5, 0-4, 0-3, 0-2, or 0-1 hours post infection.

10. The immunogenic composition of claim 1 , wherein the immunogenic composition is a synthetic mRNA vaccine.

11. The immunogenic composition of claim 1 , further comprising one or more SARS-COV-2 antigenic polypeptides capable of stimulating production of an antibody targeting SARS-COV-2, or one or more polynucleotides encoding the one or more SARS-COV-2 antigenic polypeptides.

12. The composition of claim 11 , wherein the one or more SARS-CoV-2 antigenic polypeptides are from a nucleocapsid phosphoprotein of SARS-COV-2, a spike glycoprotein of SARS-COV-2, or a combination thereof.

13. A therapeutic composition comprising:

the immunogenic composition of claim 1 ;

one or more SARS-COV-2 antigenic polypeptides capable of stimulating production of an antibody targeting SARS-COV-2, or one or more polynucleotides encoding the one or more SARS-COV-2 antigenic polypeptides; and

an anti-viral therapeutic.

14. The composition of claim 13 , wherein the immunogenetic composition is formulated as a synthetic mRNA vaccine and wherein one or more polynucleotides encoding the one or more antigenic polypeptides are mRNA.

15. A method of treating or inhibiting a SARS-CoV-2 infection in a subject in need thereof comprising: administering, to the subject in need thereof, the immunogenic composition of claim 1 and one or more antigenic components capable of stimulating production of an antibody targeting SARS-COV-2; and an anti-viral therapeutic.

16. An immunogenic composition comprising:

a delivery vehicle comprising:

one or more polypeptides, one or more polynucleotides each encoding one or more of the one or more polypeptides, or any combination thereof, wherein the one or more polypeptides:

a. is capable of binding to Major Histocompatibility Complex (MHC) class I, and

b. is derived from one or more proteins of SARS-COV-2 by expression of an internal out-of-frame open reading frame (ORF) of SARS-COV-2, wherein the internal out-of-frame ORF is S.iORF1 or S.iORF2, and

wherein at least one polypeptide of the one or more polypeptides derived from expression of S.iORF1 is MLLGSMLYM (SEQ ID NO: 4); or wherein at least one polypeptide of the one or more polypeptides is derived from expression of S.iORF1 or S.iORF2 is GPMVLRGLIT (SEQ ID NO: 6) or GLITLSYHL (SEQ ID NO: 5).

17. The immunogenic composition of claim 16 , wherein the MHC class I is Human Leukocyte Antigen class I (HLA-I).

18. The immunogenic composition of claim 17 , wherein the HLA-1 is encoded by HLA-A*02:01, HLA-A*25:01, HLA-A*30:01, HLA-B*18:01, HLA-B*44:03, HLA-C*12:03, HLA-B*16:01, HLA-A*02:01, HLA-B*07:02, HLA-C*07:02; HLA-A*01:01; HLA-A*02:06; HLA-A*26:01; HLA-A*02:07; HLA-A*29:02; HLA-A*02:03; HLA-A*30:02; HLA-A*32:01; HLA-A*68:02; HLA-A*02:05; HLA-A*02:02; HLA-A*36:01; HLA-A*02:11; HLA-A*02:04; HLA-B*35:01; HLA-B*51:01; HLA-B*40:01; HLA-B*40:02; HLA-B*07:02; HLA-B*07:04; HLA-B*08:01; HLA-B*13:01; HLA-B*46:01; HLA-B*52:01; HLA-B*44:02; HLA-B*40:06; HLA-B*13:02; HLA-B*56:01; HLA-B*54:01; HLA-B*15:02; HLA-B*35:07; HLA-B*27:05; HLA-B*15:03; HLA-B*42:01; HLA-B*55:02; HLA-B*45:01; HLA-B*50:01; HLA-B*35:03; HLA-B*49:01; HLA-B*58:02; HLA-B*15:17; HLA-C*57:02; HLA-C*04:01; HLA-C*03:04; HLA-C*01:02; HLA-C*07:01; HLA-C*06:02; HLA-C*03:03; HLA-C*08:01; HLA-C*15:02; HLA-C*12:02; HLA-C*02:02; HLA-C*05:01; HLA-C*03:02; HLA-C*16:01; HLA-C*08:02; HLA-C*04:03; HLA-C*17:01; or HLA-C*17:04.

19. The immunogenic composition of claim 17 , wherein the HLA-1 is encoded by HLA-A*02:01, HLA-A*25:01, HLA-A*30:01, HLA-B*18:01, HLA-B*44:03, HLA-C*12:03, HLA-B*16:01, HLA-A*02:01, HLA-B*07:02, or HLA-C*07:02.

20. The immunogenic composition of claim 16 , wherein one or more of the one or more polypeptides is capable of stimulating a T-cell response.

21. The immunogenic composition of claim 16 , wherein at least one polypeptide of the one or more polypeptides derived from expression of S.iORF1 or S.iORF2 comprises one or more oxidized methionines.

22. The immunogenic composition of claim 21 , wherein the at least one polypeptide is SEQ ID NO: 193 or 204.

23. The immunogenic composition of claim 16 , further comprising one or more SARS-CoV-2 antigenic polypeptides capable of stimulating production of an antibody targeting SARS-CoV-2, or one or more polynucleotides encoding the one or more SARS-COV-2 antigenic polypeptides.

24. The immunogenic composition of claim 23 , wherein the one or more SARS-COV-2 antigenic polypeptides are from a nucleocapsid phosphoprotein of SARS-COV-2, a spike glycoprotein of SARS-COV-2, or a combination thereof.

25. The immunogenic composition of claim 16 , wherein the one or more polypeptides are expressed and/or is bound by MHC-I 0-12, 0-11, 0-10, 0-9, 0-8, 0-7, 0-6, 0-5, 0-4, 0-3, 0-2, or 0-1 hours post infection.

26. The immunogenic composition of claim 16 , wherein the immunogenic composition is a synthetic mRNA vaccine.

27. The immunogenic composition of claim 26 , wherein the immunogenetic composition is formulated as a synthetic mRNA vaccine and wherein one or more polynucleotides encoding the one or more antigenic polypeptides are mRNA.

28. A therapeutic composition comprising:

the immunogenic composition of claim 16 ;

one or more SARS-COV-2 antigenic polypeptides capable of stimulating production of an antibody targeting SARS-COV-2, or one or more polynucleotides encoding the one or more SARS-CoV-2 antigenic polypeptides; and

an anti-viral therapeutic.

29. A method of treating or inhibiting a SARS-CoV-2 infection in a subject in need thereof comprising: administering, to the subject in need thereof, the immunogenic composition of claim 16 and one or more antigenic components capable of stimulating production of an antibody targeting SARS-COV-2; and an anti-viral therapeutic.

Assignments (11)
LICENSE Recorded Apr 3, 2025
From: BROAD INSTITUTE, INC.
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 070724/0875 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 14, 2022
From: CLAUSER, KARL
To: THE BROAD INSTITUTE, INC.
Reel/Frame 061761/0788 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 14, 2022
From: HACOHEN, NIR
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 061762/0261 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 13, 2022
From: SARKIZOVA, SIRANUSH
To: THE BROAD INSTITUTE, INC.
Reel/Frame 059585/0931 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 17, 2021
From: SAEED, MOHSAN
To: TRUSTEES OF BOSTON UNIVERSITY
Reel/Frame 058137/0703 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2021
From: ABELIN, JENN
To: THE BROAD INSTITUTE, INC.
Reel/Frame 057700/0955 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2021
From: CARR, STEVEN
To: THE BROAD INSTITUTE, INC.
Reel/Frame 057701/0052 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2021
From: KLAEGER, SUSAN
To: THE BROAD INSTITUTE, INC.
Reel/Frame 057701/0100 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2021
From: WEINGARTEN-GABBAY, SHIRA
To: THE BROAD INSTITUTE, INC.
Reel/Frame 057701/0148 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2021
From: PARDIS SABETI, FOR HERSELF AND AS AGENT OF HOWARD HUGHES MEDICAL INSTITUTE
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 057701/0199 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2021
From: SABETI, PARDIS
To: HOWARD HUGHES MEDICAL INSTITUTE
Reel/Frame 057700/0849 →
Continuity (3)
Provisional Application 63186742 · May 10, 2021
Provisional Application 63072898 · Aug 31, 2020
Related Publication 20220088180A1 · Mar 24, 2022
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