IP Library › Granted Patent US 12,239,697
Granted Patent B2
US 12,239,697 · App. 17/857,303 · Granted Mar 4, 2025

Virus-like particle conjugates

Inventors: Subhash V. Kapre (Redmond, WA); Anup K. Datta (Renton, WA)
Assignee: Inventprise, Inc.
A61K39/0258A61K39/12A61K39/39A61K47/65C07K14/025C12N7/00C12N2710/20023
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Quick Facts
Patent No.
US 12,239,697
App. No.
17/857,303
Granted
Mar 4, 2025
Kind
B2
Abstract

This invention is directed to immunogenic composition, conjugates, virus-like particles (VLP) compositions, vaccines and methods directed to the treatment and/or prevent of infection by Human Papillomavirus.

Claims (40)

1. A method for manufacture of an immunogenic composition comprising:

coupling a first set of L1 or L2 proteins of Human papilloma virus (HPV) to a first set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming a first set of coupled L1 or L2 proteins;

coupling a second set of L1 or L2 proteins of HPV to a second set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming a second set of coupled L1 or L2 proteins; and

coupling each of the first and second sets of coupled L1 or L2 proteins to a carrier protein forming the immunogenic composition.

2. The method of claim 1 , wherein the L1 or L2 proteins are selected from the group consisting of HPV serotype 6, HPV serotype 11, HPV serotype 16, HPV serotype 18, HPV serotype 31, HPV serotype 33, HPV serotype 45, HPV serotype 52, HPV serotype 58, and combinations thereof.

3. The method of claim 1 , wherein the spacer arms comprise NH 2 -PEG-NH 2 /NHS, NHS/NH 2 -PEG-COOH, Mal-PEG-NH 2 , Mal-PEG-NHS, CHO-PEG-CHO, SH-PEG-NH 2 , ADH, HZ-PEG-HZ, SMPH, SMCC, 4-Arm-PEG-NH 2 , or combinations thereof.

4. The method of claim 1 , wherein the carrier protein comprises tetanus toxoid, diphtheria toxoid, CRM197, tetanus toxoid fragments (TTHc), N. meningitidis protein PorB, RSV virus proteins, B. Pertussis proteins, Pertussis toxoid (PT), adenylate cyclase toxin (ACT), 69 KDa protein, Human Papilloma viral protein antigens, Human Papilloma virus VLP forms, Hepatitis B virus core antigen, Hepatitis B virus VLP forms, derivatives of HBsAg, and/or combinations thereof.

5. The method of claim 1 , wherein the immunogenic composition comprises an L1 protein and an L2 protein each coupled to the same carrier protein.

6. The method of claim 1 , wherein the immunogenic composition comprises two L1 proteins coupled to the same carrier protein.

7. The method of claim 1 , wherein the immunogenic composition comprises two L2 proteins coupled to the same carrier protein.

8. The method of claim 1 , further comprising formulating the immunogenic composition at about 20-40 μg per dose.

9. The method of claim 1 , further comprising formulating the immunogenic composition at about 8-10 μg per dose.

10. A method for manufacture of an immunogenic composition comprising:

coupling a first set of L1 or L2 proteins of Human papilloma virus (HPV) to a first set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming a first set of coupled L1 or L2 proteins;

coupling carrier proteins to a second set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming coupled carrier proteins; and

coupling the first set of coupled L1 or L2 proteins and a second set of L1 or L2 proteins to the coupled carrier proteins forming the immunogenic composition.

11. The method of claim 10 , wherein the L1 or L2 proteins are selected from the group consisting of HPV serotype 6, HPV serotype 11, HPV serotype 16, HPV serotype 18, HPV serotype 31, HPV serotype 33, HPV serotype 45, HPV serotype 52, HPV serotype 58, and combinations thereof.

12. The method of claim 10 , wherein the spacer arms comprise NH 2 -PEG-NH 2 /NHS, NHS/NH 2 -PEG-COOH, Mal-PEG-NH 2 , Mal-PEG-NHS, CHO-PEG-CHO, SH-PEG-NH 2 , ADH, HZ-PEG-HZ, SMPH, SMCC, 4-Arm-PEG-NH 2 , or combinations thereof.

13. The method of claim 10 , wherein the carrier protein comprises tetanus toxoid, diphtheria toxoid, CRM197, tetanus toxoid fragments (TTHc), N. meningitidis protein PorB, RSV virus proteins, B. Pertussis proteins, Pertussis toxoid (PT), adenylate cyclase toxin (ACT), 69 KDa protein, Human Papilloma viral protein antigens, Human Papilloma virus VLP forms, Hepatitis B virus core antigen, Hepatitis B virus VLP forms, derivatives of HBsAg, and/or combinations thereof.

14. The method of claim 10 , wherein the immunogenic composition comprises an L1 protein and an L2 protein each coupled to the same carrier protein.

15. The method of claim 10 , wherein the immunogenic composition comprises two L1 proteins coupled to the same carrier protein.

16. The method of claim 10 , wherein the immunogenic composition comprises two L2 proteins coupled to the same carrier protein.

17. The method of claim 10 , further comprising formulating the immunogenic composition at about 20-40 μg per dose.

18. The method of claim 10 , further comprising formulating the immunogenic composition at about 8-10 μg per dose.

19. A method for manufacture of an immunogenic composition comprising:

coupling carrier proteins to a first and a second set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming carrier proteins containing multiple spacers arms; and

coupling L1 or L2 proteins of Human papilloma virus (HPV) to the multiple spacer arms of the carrier proteins forming the immunogenic composition.

20. The method of claim 19 , wherein the L1 or L2 proteins are selected from the group consisting of HPV serotype 6, HPV serotype 11, HPV serotype 16, HPV serotype 18, HPV serotype 31, HPV serotype 33, HPV serotype 45, HPV serotype 52, HPV serotype 58, and combinations thereof.

21. The method of claim 19 , wherein the spacer arms comprises NH 2 -PEG-NH 2 /NHS, NHS/NH 2 -PEG-COOH, Mal-PEG-NH 2 , Mal-PEG-NHS, CHO-PEG-CHO, SH-PEG-NH 2 , ADH, HZ-PEG-HZ, SMPH, SMCC, 4-Arm-PEG-NH 2 , or combinations thereof.

22. The method of claim 19 , wherein the carrier proteins comprise tetanus toxoid, diphtheria toxoid, CRM197, tetanus toxoid fragments (TTHc), N. meningitidis protein PorB, RSV virus proteins, B. Pertussis proteins, Pertussis toxoid (PT), adenylate cyclase toxin (ACT), 69 KDa protein, Human Papilloma viral protein antigens, Human Papilloma virus VLP forms, Hepatitis B virus core antigen, Hepatitis B virus VLP forms, derivatives of HBsAg, and/or combinations thereof.

23. The method of claim 19 , wherein the immunogenic composition comprises an L1 protein and an L2 protein each coupled to the same carrier protein.

24. The method of claim 19 , wherein the immunogenic composition comprises two L1 proteins coupled to the same carrier protein.

25. The method of claim 19 , wherein the immunogenic composition comprises two L2 proteins coupled to the same carrier protein.

26. The method of claim 19 , further comprising formulating the immunogenic composition at about 20-40 μg per dose.

27. The method of claim 19 , further comprising formulating the immunogenic composition at about 8-10 μg per dose.

28. A method for manufacture of an immunogenic composition comprising:

providing L1 or L2 proteins of Human papilloma virus (HPV) and carrier proteins; and

coupling the L1 or L2 proteins and carrier proteins to heterobifunctional, homobifunctional, or multifunctional spacer arms forming the immunogenic composition which comprises the L1 or L2 protein coupled to a spacer arm which is coupled to a carrier protein which is coupled to another spacer arm which is coupled to another L1 or L2 protein.

29. The method of claim 28 , wherein the L1 or L2 protein comprises HPV serotypes 6, 11, 16, 18, 31, 33, 45, 52, or 58, and at least one spacer arm comprises a hetero-bifunctional spacer arm, which contains polyethylene glycol and a hydrazide or modified hydrazide.

30. The method of claim 28 , wherein the carrier proteins comprises tetanus toxoid or diphtheria toxoid.

Assignments (1)
CHANGE OF NAME Recorded Nov 29, 2022
From: INVENTPRISE LLC
To: INVENTPRISE, INC.
Reel/Frame 062014/0478 →
Continuity (4)
Continuation 16435502 · Jun 9, 2019
Provisional Application 62683787 · Jun 12, 2018
Provisional Application 62683543 · Jun 11, 2018
Related Publication 20230093700A1 · Mar 23, 2023
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