IP Library Granted Patent US 10,933,123
Granted Patent B2
US 10,933,123 · App. 15/984,800 · Granted Mar 2, 2021

Peptide vaccines usable for hypercholesterolemia related diseases

Inventors: Sylvia Brunner (Vienna, AT); Gergana Galabova (Vienna, AT); Gabriele Winsauer (Vienna, AT); Erika Bilcikova (Bratislava, SK); Claudia Juno (Vienna, AT); Pola Linzmayer-Hirt (Wiener Neudorf, AT); Birgit Schuh (Vienna, AT); Guenther Staffler (Vienna, AT)
Assignee: AFFIRIS AG
A61K39/0005A61K39/385A61K39/39A61K47/643A61K47/646A61K47/6415C12N9/6424C12N9/6454C12Y304/21061A61K2039/55505A61K2039/6081
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Quick Facts
Patent No.
US 10,933,123
App. No.
15/984,800
Granted
Mar 2, 2021
Kind
B2
Abstract

The present invention relates to a vaccine capable to induce the formation of antibodies directed to PCSK9 in vivo.

Claims (10)

1. A vaccine, comprising at least one peptide consisting of 9 to 13 amino acid residues having the amino acid sequence selected from the group consisting of TIPWNLERIT (SEQ ID NO: 5), VIPWNLERIT (SEQ ID NO: 6), AIPWNLERIT (SEQ ID NO: 7), SVPWNLERIT (SEQ ID NO: 8), SQPWNLERIT (SEQ ID NO: 9), SAPWNLERIT (SEQ ID NO: 10), SGPWNLERITPPR (SEQ ID NO: 11), SITWNLERIT (SEQ ID NO: 12), SIAWNLERIT (SEQ ID NO: 13), SIVWNLERITPPR (SEQ ID NO: 14), SIVWNLERIT (amino acids 1-10 of SEQ ID NO: 14), SIPWSLERIT (SEQ ID NO: 21), SIPWALERIT (SEQ ID NO: 22), SIPWQLERITPPR (SEQ ID NO: 23), SIPWDLERITPPR (SEQ ID NO: 24), SIPWNAERIT (SEQ ID NO: 25), SIPWNGERIT (SEQ ID NO: 26), SIPWNYERIT (SEQ ID NO: 27), SIPWNDERIT (SEQ ID NO: 28), SIPWNFERITPPR (SEQ ID NO: 29), SIPWNVERITPPR (SEQ ID NO: 30), SIPWNLDRITPPR (SEQ ID NO: 32), SIPWNFERIT (amino acids 1-10 of SEQ ID NO: 29), SIPWNVERIT (amino acids 1-10 of SEQ ID NO: 30), SIPWNLDRIT (amino acids 1-10 of SEQ ID NO: 32), SIPWNLERLT (SEQ ID NO: 36), SIPWNLERTT (SEQ ID NO: 37), SIPWNLERAT (SEQ ID NO: 38), SIPWNLERIL (SEQ ID NO: 39), SIPWNLERIQ (SEQ ID NO: 40), SIPWNLERIA (SEQ ID NO: 41), SIVWNLERITPPR (SEQ ID NO: 42), SIPWNLERIS (amino acids 1-10 of SEQ ID NO: 42), SIPWNLERITAPR (SEQ ID NO: 43), SIPWNLERITSPR (SEQ ID NO: 44), SIPWNLERITPAR (SEQ ID NO: 45), SIPWNLERITPVR (SEQ ID NO: 46), SIPWNLERITPTR (SEQ ID NO: 47), SIPWNLERITPNR (SEQ ID NO: 48), SIPWNLERITPPA (SEQ ID NO: 49), SIPWNLERITPPK (SEQ ID NO: 50), SIPWNLERITPPS (SEQ ID NO: 51), SIPWNLERITPPL (SEQ ID NO: 52), VIPWNLERLT (SEQ ID NO: 53), VIPWNLERTT (SEQ ID NO: 54), VIPWNLERIL (SEQ ID NO: 55), VIPWNLERILPPR (SEQ ID NO: 101), VIPWNLERIQ (SEQ ID NO: 56), SVPWNLERLT (SEQ ID NO: 57), SVPWNLERTT (SEQ ID NO: 58), SVPWNLERIL (SEQ ID NO: 59), SVPWNLERIQ (SEQ ID NO: 60), SVPWNLERIQPPR (SEQ ID NO: 106), SIPWSLERTTPPR (SEQ ID NO: 107), SQPWNLERLT (SEQ ID NO: 61), SQPWNLERIL (SEQ ID NO: 62), SQPWNLERIQ (SEQ ID NO: 63), SIPWSLERLT (SEQ ID NO: 64), SIPWSLERTT (SEQ ID NO: 65), SIPWSLERIL (SEQ ID NO: 66), SIPWSLERIQ (SEQ ID NO: 67), VQPWSLERTL (SEQ ID NO: 68), SQPWSLERTL (SEQ ID NO: 69), VQPWNLERLQ (SEQ ID NO: 71), VQPWSLERLL (SEQ ID NO: 72) and SVPWSLERLT (SEQ ID NO: 73).

2. The vaccine according to claim 1 , wherein the at least one peptide is selected from the group consisting of SIPWSLERITPPR (SEQ ID NO: 87), SIPWSLERTT (SEQ ID NO: 65), SIPWSLERTTPPR (SEQ ID NO: 107), VIPWNLERIL (SEQ ID NO: 55), VIPWNLERILPPR (SEQ ID NO: 101), SVPWNLERIQ (SEQ ID NO: 60) and SVPWNLERIQPPR (SEQ ID NO: 106).

3. The vaccine according to claim 1 , wherein the at least one peptide further comprises at its N- and/or C-terminus at least one cysteine residue bound directly or via a spacer sequence thereto.

4. The vaccine according to claim 1 , wherein the pharmaceutically acceptable carrier is a protein carrier.

5. The vaccine according to claim 4 , wherein the protein carrier is selected from the group consisting of keyhole limpet haemocyanin (KLH), tetanus toxoid (TT), protein D or diphtheria toxin (DT).

6. The vaccine according to claim 1 , wherein the compound is formulated with an adjuvant.

7. The vaccine according to claim 1 , wherein the at least one peptide is selected from the group consisting of SIPWSLERIT (SEQ ID NO: 21), SIPWSLERTTPPR (SEQ ID NO: 87), SIPWSLERTT (SEQ ID NO: 65), SIPWSLERTTPPR (SEQ ID NO: 107), VIPWNLERIL (SEQ ID NO: 55), VIPWNLERILPPR (SEQ ID NO: 101), SVPWNLERIQ (SEQ ID NO: 60) and SVPWNLERIQPPR (SEQ ID NO: 106).

8. A peptide, consisting of an amino acid sequence selected from the group consisting of TIPWNLERIT (SEQ ID NO: 5), VIPWNLERIT (SEQ ID NO: 6), AIPWNLERIT (SEQ ID NO: 7), SVPWNLERIT (SEQ ID NO: 8), SQPWNLERIT (SEQ ID NO: 9), SAPWNLERTT (SEQ ID NO: 10), SGP\VNLERITPPR (SEQ ID NO: 11), SITWNLERIT (SEQ ID NO: 12), SIAWNLERIT (SEQ ID NO: 13), SIVWNLERITPPR (SEQ ID NO: 14), SIVWNLERIT (amino acids 1-10 of SEQ ID NO: 14), SIPWSLERIT (SEQ ID NO: 21), SIPWALERTT (SEQ ID NO: 22), SIPWQLER[TPPR (SEQ ID NO: 23), SIPWDLERITPPR (SEQ ID NO: 24), SIPWNAERIT (SEQ ID NO: 25), SIPWNGERIT (SEQ ID NO: 26), SIPWNYERIT (SEQ ID NO: 27), SIPWNDERIT (SEQ ID NO: 28), SIPWNFERITPPR (SEQ ID NO: 29), SIPWNVERITPPR (SEQ ID NO: 30), SIPWNLDRITPPR (SEQ ID NO: 32), SIPWNFERIT (amino acids 1-10 of SEQ ID NO: 29), SIPWNVERIT (amino acids 1-10 of SEQ ID NO: 30), SIPWNLDRIT (amino acids 1-10 of SEQ ID NO: 32), SIPWNLERLT (SEQ ID NO: 36), SIPWNLERTT (SEQ ID NO: 37), SIPWNLERAT (SEQ ID NO: 38), SIPWNLERIL (SEQ ID NO: 39), SIPWNLERIQ (SEQ ID NO: 40), SIPWNLERIA (SEQ ID NO: 41), SIPWNLERISPPR (SEQ ID NO: 42), SIPWNLERIS (amino acids 1-10 of SEQ ID NO: 42), SIPWNLERITAPR (SEQ ID NO: 43), SIPWNLERITSPR (SEQ ID NO: 44), SIPWNLERITPAR (SEQ ID NO: 45), SIPWNLERITPVR (SEQ ID NO: 46), SIPWNLERITPTR (SEQ ID NO: 47), SIPWNLERITPNR (SEQ ID NO: 48), SIPWNLERITPPA (SEQ ID NO: 49), SIPWNLERITPPK (SEQ ID NO: 50), SIPWNLERITPPS (SEQ ID NO: 51), SIPWNLERITPPL (SEQ ID NO: 52), VIPWNLERLT (SEQ ID NO: 53), VIPWNLERTT (SEQ ID NO: 54), VIPWNLERIL (SEQ ID NO: 55), VIPWNLERILPPR (SEQ ID NO: 101), VIPWNLERIQ (SEQ ID NO: 56), SVP\VNLERLT (SEQ ID NO: 57), SVPWNLERTT (SEQ ID NO: 58), SVPWNLERIL (SEQ ID NO: 59), SVP\VNLERIQ (SEQ ID NO: 60), SVPWNLERIQPPR (SEQ ID NO: 106), SIPWSLERTTPPR (SEQ ID NO: 107), SQPWNLERLT (SEQ ID NO: 61), SQPWNLERIL (SEQ ID NO: 62), SQPWNLERIQ (SEQ ID NO: 63), SIPWSLERLT (SEQ ID NO: 64), SIPWSLERTT (SEQ ID NO: 65), SIPWSLERIL (SEQ ID NO: 66), SIPWSLERIQ (SEQ ID NO: 67), VQPWSLERTL (SEQ ID NO: 68), SQPWSLERTL (SEQ ID NO: 69), VQPWNLERLQ (SEQ ID NO: 71), VQPWSLERLL (SEQ ID NO: 72) and SVPWSLERLT (SEQ ID NO: 73).

9. A method of reducing High LDL cholesterol (LDLc) in a subject in need thereof, the method comprising administering an effective amount of the vaccine according to claim 1 to the subject.

10. The method according claim 9 , wherein the subject is in need of treatment and/or prevention of disorders caused by hyperlipidemia, hypercholesterolemia and/or atherosclerosis.

Assignments (1)
CONFIRMATORY ASSIGNMENT Recorded May 11, 2022
From: AFFIRIS AG
To: AFFIRIS CVD GMBH
Reel/Frame 059929/0690 →
Priority Claims (1)
EP 12182241 · Aug 29, 2012 · regional
Continuity (3)
Continuation 15367711 · Dec 2, 2016
Continuation 14418139
Related Publication 20180289781A1 · Oct 11, 2018