IP Library › Granted Patent US 12,268,735
Granted Patent B2
US 12,268,735 · App. 18/179,668 · Granted Apr 8, 2025

Patent

Inventors: David Weiner (Merion, PA); Ami Patel (Philadelphia, PA); Sarah Elliott (Pullman, WA)
Assignees: The Wistar Institute of Anatomy and Biology; The Trustees of the University of Pennsylvania
A61K39/12A61P31/14A61P37/04C07K14/005A61K2039/53C12N2760/14222C12N2760/14234
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 12,268,735
App. No.
18/179,668
Granted
Apr 8, 2025
Kind
B2
Abstract

Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus Marburgvirus filovirus glycoprotein immunogens. Immunomodulatory methods and methods of inducing an immune response against Marburgvirus are disclosed. Method of preventing infection by Marburgvirus and methods of treating individuals infected with Marburgvirus are disclosed. Consensus Marburgvirus filovirus glycoprotein immunogens are disclosed.

Claims (56)

1. An immunogenic composition comprising a nucleic acid molecule, wherein the nucleic acid molecule encodes a peptide comprising an amino acid sequence selected from the group consisting of

a) an amino acid sequence having at least about 90% identity over an entire length of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

b) an immunogenic fragment comprising at least about 90% identity over at least 60% of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

c) the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4 and SEQ ID NO:6, and

d) an immunogenic fragment comprising at least 70% of the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4 and SEQ ID NO:6.

2. The immunogenic composition of claim 1 , wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of

a) a nucleotide sequence having at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5,

b) an immunogenic fragment of a nucleotide sequence having at least about 60% of the nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5, and

c) a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO: 3 and SEQ ID NO:5.

3. The immunogenic composition of claim 1 , wherein a nucleotide sequence encoding the peptide is operably linked to at least one regulatory sequence selected from the group consisting of a start codon, an IgE leader sequence and a stop codon.

4. The immunogenic composition of claim 3 , wherein the nucleic acid molecule encodes a peptide comprising an amino acid sequence selected from the group consisting of

a) an amino acid sequence having at least about 90% identity over an entire length of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

b) an immunogenic fragment comprising at least about 90% identity over at least 60% of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

c) the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4 and SEQ ID NO:6, and

d) an immunogenic fragment comprising at least 70% of the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4 and SEQ ID NO:6,

operably linked to an amino acid sequence as set forth in SEQ ID NO:8.

5. The immunogenic composition of claim 4 , wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of

a) a nucleotide sequence having at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5,

b) an immunogenic fragment of a nucleotide sequence having at least about 60% of the nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5, and

c) a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO: 3 and SEQ ID NO:5

operably linked to an nucleotide sequence encoding SEQ ID NO:8.

6. The immunogenic composition of claim 1 , wherein the nucleic acid molecule comprises an expression vector.

7. The immunogenic composition of claim 1 , further comprising a pharmaceutically acceptable excipient or an adjuvant.

8. A nucleic acid molecule encoding a peptide comprising an amino acid sequence selected from the group consisting of

a) an amino acid sequence having at least about 90% identity over an entire length of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

b) an immunogenic fragment comprising at least about 90% identity over at least 60% of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

c) the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4 and SEQ ID NO:6, and

d) an immunogenic fragment comprising at least 70% of the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4 and SEQ ID NO:6.

9. The nucleic acid molecule of claim 8 , wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of

a) a nucleotide sequence having at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5,

b) an immunogenic fragment of a nucleotide sequence having at least about 60% of the nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5, and

c) a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO: 3 and SEQ ID NO:5.

10. The nucleic acid molecule of claim 8 , wherein the encoded peptide is operably linked to at least one regulatory sequence selected from the group consisting of a start codon, an IgE leader sequence and a stop codon.

11. The nucleic acid molecule of claim 10 , wherein the nucleic acid molecule encodes a peptide comprising an amino acid sequence selected from the group consisting of

a) an amino acid sequence having at least about 90% identity over an entire length of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

b) an immunogenic fragment comprising at least about 90% identity over at least 60% of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

c) the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4 and SEQ ID NO:6, and

d) an immunogenic fragment comprising at least 70% of the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4 and SEQ ID NO:6,

operably linked to an amino acid sequence as set forth in SEQ ID NO:8.

12. The nucleic acid molecule of claim 11 , wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of

a) a nucleotide sequence having at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5,

b) an immunogenic fragment of a nucleotide sequence having at least about 60% of the nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5, and

c) a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO: 3 and SEQ ID NO:5

operably linked to an nucleotide sequence encoding SEQ ID NO:8.

13. The nucleic acid molecule of claim 8 , wherein the nucleic acid molecule comprises an expression vector.

14. A peptide comprising an amino acid sequence selected from the group consisting of

a) an amino acid sequence having at least about 90% identity over an entire length of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

b) an immunogenic fragment comprising at least about 90% identity over at least 60% of the amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4,

c) the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4 and SEQ ID NO:6, and

d) an immunogenic fragment comprising at least 70% of the amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4 and SEQ ID NO:6.

15. A method of inducing an immune response against a Marburgvirus antigen in a subject in need thereof, the method comprising administering an immunogenic composition of claim 1 to the subject.

16. The method of claim 15 , wherein administering includes at least one of electroporation and injection.

17. A method of treating or preventing a Marburgvirus associated pathology in subject in need thereof, the method comprising administering an immunogenic composition of claim 1 to the subject.

18. The method of claim 17 , wherein administering includes at least one of electroporation and injection.

19. The method of claim 17 , wherein the Marburgvirus associated pathology is at least one of Marburgvirus infection and hemorrhagic fever.

20. An immunogenic composition comprising a peptide of claim 14 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 23, 2023
From: WEINER, DAVID; PATEL, AMI; ELLIOTT, SARAH
To: THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY
Reel/Frame 064676/0984 →
Continuity (3)
Continuation 16465691
Provisional Application 62429473 · Dec 2, 2016
Related Publication 20230293664A1 · Sep 21, 2023
References Cited (34)
US 7731975B2 · Grogan · 2010 [cited by examiner]
US 9597388B2 · Weiner · 2017 [cited by applicant]
US 10034930B2 · Weiner · 2018 [cited by applicant]
US 10765733B2 · Weiner · 2020 [cited by applicant]
US 11596678B2 · Weiner · 2023 [cited by examiner]
US 20030108560A1 · Grogan · 2003 [cited by applicant]
US 20070041941A1 · Weiner · 2007 [cited by applicant]
US 20110104105A1 · Weiner · 2011 [cited by applicant]
US 20150335726A1 · Weiner · 2015 [cited by examiner]
US 20170165350A1 · Weiner · 2017 [cited by applicant]
WO 2016097065A1 · 2016 [cited by applicant]
Towner et al. (Journal of Virology, 2006, p. 6497-6516) in Towner et al. (Journal of Virology, 2006, p. 6497-6516) Towner et al. (Journal of Virology, 2006, p. 6497-6516) in parent U.S. Appl. No. 16/465,691. [cited by examiner]
“UniProtKB-P35253—Envelope glycoprotein precursor—Lake Victoria marburgvirus (strain Musoke-80) (MARV)—GP gene & protein”, Jan. 25, 2016, XP055244338, Retrieved from the Internet: URL: http://www.uniprot.org/uniprot/P35… [cited by applicant]
Bagarazzi ML et al., “Immunotherapy Against HPV16/18 Generates Potent TH1 and Cytotoxic Cellular Immune Responses”, Sci. Transl. Med., 2011, 4:155ral38, 33 pages. [cited by applicant]
Blaney JE et al., “Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses”, Nat. Med., 2005, 11:786-790. [cited by applicant]
Bradfute SB et al., “Filovirus vaccines”, Hum. Vaccin., 2011, 7:701-711. [cited by applicant]
Falzarano D et al., “Progress in filovirus vaccine development: evaluating the potential for clinical use”, Expert Rev. Vaccines, 2011, 10:63-77. [cited by applicant]
Feldmann H et al., “Ebola virus: from discovery to vaccine”, Nat. Rev. Immunol., 2003, 3:677-685. [cited by applicant]
Geisbert et al., “Single-Injection Vaccine Protects Nonhuman Primates against Infection with Marburg Virus and Three Species of Ebola Virus,” Journal of Virology, 2009, 83:7296-7304. [cited by applicant]
Geisbert TW et al., “Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates”, J. Virol., 2010, 84:10386-10394. [cited by applicant]
Geisbert, T et al., ‘Recombinant Vesicular Stomatitis Virus-Based Vaccines Against Ebola and Marburg Virus Infections.’, JID., (2011), vol. 204, No. SUPPL, pp. S1075-S1081, XP002688258. [cited by applicant]
Grant-Klein RJ et al., “A multiagent filovirus DNA vaccine delivered by intramuscular electroporation protects mice from ebola and Marburg virus challenge”, Hum. Vaccin. Immunother., 2012, 8:1703-1706. [cited by applicant]
He et al., “Emerging Vaccine Informatics”, J Biomed Biotechnol 2010:1-26. [cited by applicant]
Hirao LA et al., “Multivalent smallpox DNA vaccine delivered by intradermal electroporation drives protective immunity in nonhuman primates against lethal monkeypox challenge”, J. Infect. Dis., 2011, 203:95-102. [cited by applicant]
Kalina WV et al., “Discovery of common marburgvirus protective epitopes in a BALB/c mouse model”, Virol. J., 2009, 6:132. [cited by applicant]
Kobinger GP et al., “Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs”, J. Infect. Dis., 2011, 204:200-208. [cited by applicant]
Mire et al., “Durability of a Vesicular Stomatitis Virus-Based Marburg Virus Vaccine in Nonhuman Primates,” PLoS One, 2014, 9:e94355, 7 pages. [cited by applicant]
Outbreak news, “Ebola Reston in pigs and humans, Philippines”, Wkly Epidemiol Rec., 2009, 84:49-50. [cited by applicant]
Riemenschneider et al., “Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus,” 2003, Vaccine 21: 4071-4080. [cited by applicant]
Sardesai et al., “Electroporation Delivery of DNA Vaccines: Prospects for Success”, Curr. Opin. Immunol., 2011, 23:421-429. [cited by applicant]
Swenson et al., “Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections,” 2005, Vaccine 23: 3033-3042. [cited by applicant]
Towner et al. (Journal of Virology, 2006, p. 6497-6516). [cited by applicant]
Towner JS et al., “Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola”, J . Virol., 2006, 80:6497-6516. [cited by applicant]
Warfield KL et al., “Protective role of cytotoxic T lymphocytes in filovirus hemorrhagic fever”, J. Biomed. Biotechnol., 2011:984241, 14 pages. [cited by applicant]