IP Library › Granted Patent US 12,661,392
Granted Patent B2
US 12,661,392 · App. 18/020,034 · Granted Jun 23, 2026

Multiepitope vaccine for the treatment of ALZHEIMER'S disease

Inventors: Robin Barbour (Walnut Creek, CA); Gene Kinney (Boca Raton, FL); Wagner Zago (San Carlos, CA)
Assignee: OTHAIR PROTHENA LIMITED
A61K39/0007A61P25/28A61P37/04C07K14/4711A61K2039/545A61K2039/55555A61K2039/55566A61K2039/55572A61K2039/55577A61K2039/6037A61K2039/645C07K2319/40
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Quick Facts
Patent No.
US 12,661,392
App. No.
18/020,034
Granted
Jun 23, 2026
Kind
B2
Abstract

The disclosure provides peptide compositions and immunotherapy compositions comprising an amyloid-beta (Aβ, Abeta) peptide, a tau peptide, and an alpha-synuclein peptide. The disclosure also provides methods of treating or effecting prophylaxis of Alzheimer's disease or other diseases with beta-amyloid deposition in a subject, including methods of clearing deposits, inhibiting or reducing aggregation of Aβ and tau and an alpha-synuclein, blocking the uptake by neurons, clearing amyloid, and inhibiting propagation of tau seeds and an alpha-synuclein synucleinopathies in a subject having or at risk of developing Alzheimer's disease or other diseases containing tau and amyloid-beta and an alpha-synuclein accumulations. The methods include administering to such patients the compositions comprising an amyloid-beta (Aβ) peptide and a tau peptide and an alpha-synuclein peptide.

Claims (53)

1 . A polypeptide comprising an amino acid sequence of:

DAEFRHDRRPDNEAYERRQIVYKPVKKC (SEQ ID NO:130);

DAEFRHDRRQIVYKPVRRPDNEAYEKKC (SEQ ID NO:131);

DAEFRHDRRPDNEAYERRNIKHVPGKKC (SEQ ID NO:132);

DAEFRHDRRNIKHVPGRRPDNEAYEKKC (SEQ ID NO: 133);

DAEFRHDRRQIVYKPVRRPDNEAYERRNIKHVPGGC (SEQ ID NO:134);

DAEFRHDRRDPDNEAYRRNIKHVPGRRQIVYKPVGGC (SEQ ID NO:135);

EFRHDSGRRQIVYKPVRRPDNEAYERRNIKHVPGGC (SEQ ID NO: 136);

EFRHDSGRRDPDNEAYRRNIKHVPGRRQIVYKPVGGC (SEQ ID NO:137);

DAEFRHDRRDPDNEAYERRENLKHQPGGGC (SEQ ID NO:1058);

DAEFRHDRRENLKHQPGRRDPDNEAYEGGC (SEQ ID NO:1059);

DAEFRHDRRPDNEAYERRENLKHOPGGGC (SEQ ID NO:1060);

DAEFRHDRRENLKHQPGRRPDNEAYEGGC (SEQ ID NO:1061);

DAEFRHDRRSKIGSKDNIKHRRDPDNEAYEGGC (SEQ ID NO:1062); or

DAEFRHDRRDPDNEAYERRSKIGSKDNIKHGGC (SEQ ID NO:1063).

2 . The polypeptide of claim 1 , wherein the polypeptide further comprises a blocked amine at the N-terminus.

3 . The polypeptide of claim 1 , wherein the polypeptide is EFRHDSGRRQIVYKPVRRPDNEAYERRNIKHVPGGC (SEQ ID NO:136), and further comprises a blocked amine at the N-terminus.

4 . The polypeptide of claim 1 , wherein the polypeptide is EFRHDSGRRDPDNEAYRRNIKHVPGRRQIVYKPVGGC (SEQ ID NO:137), and further comprising a blocked amine at the N-terminus.

5 . An immunotherapy composition, comprising the polypeptide of claim 1 , wherein the polypeptide is linked to a carrier.

6 . The immunotherapy composition of claim 5 , wherein the carrier comprises serum albumins, immunoglobulin molecules, thyroglobulin, ovalbumin, tetanus toxoid (TT), diphtheria toxoid (DT), a genetically modified cross-reacting material (CRM) of diphtheria toxin, CRM197, meningococcal outer membrane protein complex (OMPC) and H. influenzae protein D (HiD), rEPA ( Pseudomonas aeruginosa exotoxin A), KLH (keyhole limpet hemocyanin), and flagellin.

7 . The immunotherapy composition of claim 6 , wherein the carrier is CRM197.

8 . The immunotherapy composition of claim 6 , wherein the carrier is diphtheria toxoid.

9 . A pharmaceutical composition comprising the immunotherapy composition of claim 5 and an adjuvant.

10 . The pharmaceutical composition of claim 9 , wherein the adjuvant is selected from the group consisting of aluminum hydroxide, aluminum phosphate, aluminum sulfate, 3 De-O-acylated monophosphoryl lipid A (MPL), QS-21, TQL1055, QS-18, QS-17, QS-7, Complete Freund's Adjuvant (CFA), Incomplete Freund's Adjuvant (IFA), oil in water emulsions (such as squalene or peanut oil), CpG, polyglutamic acid, polylysine, AddaVax™, MF59®, and combinations thereof.

11 . The pharmaceutical composition of claim 10 , wherein the adjuvant is QS-21 or TQL1055.

12 . The pharmaceutical composition of claim 10 , wherein the adjuvant is MPL.

13 . The pharmaceutical composition of claim 10 , wherein the adjuvant is a combination of MPL and QS-21 or a combination of MPL and TQL1055.

14 . A method of treating or effecting prophylaxis of Alzheimer's disease in a subject, comprising administrating to the subject the immunotherapy composition of claim 5 .

15 . The method of claim 14 , further comprising repeating the administering at least a second time, at least a third time, at least a fourth time, at least a fifth time, or at least a sixth time.

16 . The method of claim 15 , further comprising repeating the administering at an interval of about 21 to about 28 days.

17 . A method of inhibiting or reducing aggregation of at least one of Aβ, tau, and alpha-synuclein in a subject having or at risk of developing Alzheimer's disease, comprising, administering to the subject the immunotherapy composition of claim 5 .

18 . A method of inducing an immune response in an animal, comprising administering to the animal the immunotherapy composition of claim 5 in a regimen effective to generate an immune response comprising antibodies that specifically bind to Aβ, tau, and/or alpha-synuclein.

19 . The method of claim 18 , wherein the immune response comprises antibodies that specifically bind to Aβ, antibodies that specifically bind to tau, and antibodies that specifically bind to alpha-synuclein.

20 . The method of claim 18 , wherein the inducing the immune response comprises antibodies that specifically bind to the N-terminal region of AB, the microtubule region of tau, and/or the C-terminal region of alpha-synuclein.

21 . An immunization kit comprising the immunotherapy composition of claim 5 .

22 . The kit of claim 21 , further comprising an adjuvant.

23 . The kit of claim 22 , wherein the immunotherapy composition is in a first container and the adjuvant is in a second container.

24 . A pharmaceutical formulation comprising (a) the polypeptide of claim 1 and (b) an adjuvant.

25 . The pharmaceutical formulation of claim 24 , wherein the adjuvant is selected from the group consisting of aluminum hydroxide, aluminum phosphate, aluminum sulfate, 3 De-O-acylated monophosphoryl lipid A (MPL), QS-21, TQL1055, QS-18, QS-17, QS-7, Complete Freund's Adjuvant (CFA), Incomplete Freund's Adjuvant (IFA), oil in water emulsions (such as squalene or peanut oil), CpG, polyglutamic acid, polylysine, AddaVax™, MF59®, and combinations thereof.

26 . The pharmaceutical formulation of claim 25 , wherein the adjuvant is QS-21 or TQL1055.

27 . The pharmaceutical formulation of claim 25 , wherein the adjuvant is MPL.

28 . The pharmaceutical formulation of claim 25 , wherein the adjuvant is a combination of MPL and QS-21 or a combination of MPL and TQL1055.

29 . The pharmaceutical formulation of claim 24 , wherein the adjuvant comprises a liposomal formulation.

30 . The pharmaceutical formulation of claim 24 , wherein the composition comprises at least one pharmaceutically acceptable diluent.

31 . The pharmaceutical formulation of claim 24 , comprising a multiple antigen presenting system (MAP).

32 . The pharmaceutical formulation of claim 31 , wherein the MAP comprises one or more of a Lys-based dendritic scaffold, helper T-cell epitopes, immune stimulating lipophilic moieties, cell penetrating peptides, radical induced polymerization, self-assembling nanoparticles as antigen-presenting platforms and gold nanoparticles.

33 . A nucleic acid comprising a nucleic acid sequence encoding a polypeptide of claim 1 .

34 . A nucleic acid immunotherapy composition comprising the nucleic acid of claim 33 and at least one adjuvant.

35 . A method of treating or effecting prophylaxis of Alzheimer's disease in a subject, comprising administrating to the subject the nucleic acid immunotherapy composition of claim 34 .

36 . A method of inhibiting or reducing aggregation of at least one of Aβ, tau, and alpha-synuclein in a subject having or at risk of developing Alzheimer's disease, comprising administering to the subject the nucleic acid immunotherapy composition of claim 34 .

37 . A kit comprising the nucleic acid immunotherapy composition of claim 34 .

38 . The kit of claim 37 , further comprising an adjuvant.

39 . The kit of claim 38 , wherein the nucleic acid is in a first container and the adjuvant is in a second container.

Continuity (2)
Provisional Application 63062919 · Aug 7, 2020
Related Publication 20250186567A1 · Jun 12, 2025
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