Back to results
US 2017/0304384 A1Published application
Substances and methods for the use in prevention and/or treatment in huntington's disease
AssigneeAffiris AG
InventorsOskar SMRZKA, Stefan BARTL
Life of this patent
Estimating the term…
Abstract
Disclosed are immunogenic peptides of the HTT protein and HTT specific antibodies for use in the prevention and/or treatment of Huntington's disease.
Claims21
1-20. (canceled)
21:
- A method of treating Huntington's disease or delaying the onset of its clinical symptoms, comprising vaccinating a subject in need thereof with an immunogenic peptide of an HTT protein.
22:
- An immunogenic peptide of an HTT protein, comprising a sequence selected from the group consisting of
- LPQPPPQAQPLLPQPQPC,
- (SEQ ID NO:
- 1)
- CPSDSSEIVLD,
- (SEQ ID NO:
- 2)
- GTDNQYLGLQIGC,
- (SEQ ID NO:
- 3)
- LPQPPPQAQPLLPC,
- (SEQ ID NO:
- 4)
- CGPAVAEEPLHRP,
- (SEQ ID NO:
- 5)
- SDSSEIVLDGTDC,
- (SEQ ID NO:
- 6)
- EIVLDGTDNQYLC,
- (SEQ ID NO:
- 7)
- IVLDGTDNQYLGC,
- (SEQ ID NO:
- 8)
- VLDGTDNQYLGLC,
- (SEQ ID NO:
- 9)
- LDGTDNQYLGLQC,
- (SEQ ID NO:
- 10)
- DGTDNQYLGLQIGC,
- (SEQ ID NO:
- 11)
- CTDNQYLGLQIGQ,
- (SEQ ID NO:
- 12)
- CGTDNQYLGLQIG,
- (SEQ ID NO:
- 13)
- CDNQYLGLQIGQP,
- (SEQ ID NO:
- 14)
- CNQYLGLQIGQPQ,
- (SEQ ID NO:
- 15)
- CPQLPQPPPQAQPLLP,
- (SEQ ID NO:
- 16)
- TDNQYLGLQIGQC,
- (SEQ ID NO:
- 17)
- DNQYLGLQIGQPC,
- (SEQ ID NO:
- 18)
- PPPQLPQPPPQAQPLLPQPQPaC,
- (SEQ ID NO:
- 19)
- PSDSSEIVLDGTC,
- (SEQ ID NO:
- 20)
- DSSEIVLDGTDNC,
- (SEQ ID NO:
- 21)
- SEIVLDGTDNQYC,
- (SEQ ID NO:
- 22)
- NQYLGLQIGQPQC,
- (SEQ ID NO:
- 23)
- QYLGLQIGQPQDC,
- (SEQ ID NO:
- 24)
- CaMATLEKLMKAFESLKSFQ,
- (SEQ ID NO:
- 25)
- CaKLMKAFESLKSFQ,
- (SEQ ID NO:
- 26)
- CEEQQRQQQQQQQ,
- (SEQ ID NO:
- 27)
- QQQQQQPPPPPPPPaKKKC,
- (SEQ ID NO:
- 28)
- CSEIVLD,
- (SEQ ID NO:
- 29)
- CSSEIVLD,
- (SEQ ID NO:
- 30)
- CDSSEIVLD,
- (SEQ ID NO:
- 31)
- CSDSSEIVLD,
- (SEQ ID NO:
- 32)
- CEIVLD,
- (SEQ ID NO:
- 33)
- CIVLD,
- (SEQ ID NO:
- 34)
- CSEIVL,
- (SEQ ID NO:
- 35)
- CSEIVLDGTDNQYL,
- (SEQ ID NO:
- 36)
- CSDSSEIVLDGTDN,
- (SEQ ID NO:
- 37)
- SEIVLDGTDNQYLC,
- (SEQ ID NO:
- 38)
- CAEIVLDGTDNQYL,
- (SEQ ID NO:
- 39)
- CSAIVLDGTDNQYL,
- (SEQ ID NO:
- 40)
- CSEAVLDGTDNQYL,
- (SEQ ID NO:
- 41)
- CSEIALDGTDNQYL,
- (SEQ ID NO:
- 42)
- CSEIVADGTDNQYL,
- (SEQ ID NO:
- 43)
- CSEIVLAGTDNQYL,
- (SEQ ID NO:
- 44)
- CSEIVLDATDNQYL,
- (SEQ ID NO:
- 45)
- CSEIVLDGADNQYL,
- (SEQ ID NO:
- 46)
- CSEIVLDGTANQYL,
- (SEQ ID NO:
- 47)
- CSEIVLDGTDAQYL,
- (SEQ ID NO:
- 48)
- CSEIVLDGTDNAYL,
- (SEQ ID NO:
- 49)
- CSEIVLDGTDNQAL,
- (SEQ ID NO:
- 50)
- CSEIVLDGTDNQYA,
- (SEQ ID NO:
- 51)
- DNQYLGLQIC,
- (SEQ ID NO:
- 88)
- TDNQYLGLQIC,
- (SEQ ID NO:
- 89)
- TDNQYLGLQIGC,
- (SEQ ID NO:
- 90)
- KTDNQYLGLQIGKC,
- (SEQ ID NO:
- 91)
- GTDNQYLGLQIGKKC,
- (SEQ ID NO:
- 92)
- KTDNQYLGLQIKKGC,
- (SEQ ID NO:
- 93)
- and
- KDNQYLGLQIKKGC;
- (SEQ ID NO:
- 94)
- wherein the N- or C-terminal cysteine residue (C) may be present or not, or may be provided alternatively at the C- or N-terminus.
174 more elements
23:
- A peptide-based vaccine comprising the immunogenic peptide of claim 22 and an adjuvant.
24:
- The peptide-based vaccine of claim 23, wherein the immunogenic peptide is coupled to a pharmaceutically acceptable carrier.
25:
- The peptide-based vaccine of claim 23, wherein the vaccine is formulated for intravenous, subcutaneous, intradermal or intramuscular administration.
26:
- The peptide-based vaccine of claim 23, wherein the adjuvant comprises aluminum hydroxide.
27:
- The peptide-based vaccine of claim 23, wherein the immunogenic peptide is present in an amount from 0.1 ng to 10 mg.
28:
- The peptide-based vaccine of claim 23, wherein the immunogenic peptide is at least one peptide having a sequence selected from the group consisting of SEQ ID NOS:
- 1, 2, 3, 4, 5, 88, 89, 90, 91, 92, 93 and 94, wherein the N- or C-terminal cysteine residue (C) may be present or not, or may be provided alternatively at the C- or N-terminus.
29:
- The peptide-based vaccine of claim 23, comprising a peptide from the C6 region of HTT and a peptide from the PRR region of HTT.
30:
- A pharmaceutical preparation comprising the immunogenic peptide of claim 2, wherein the preparation is suitable for eliciting an immune response in a subject.
31:
- The pharmaceutical preparation of claim 30, wherein the subject has Huntington's disease.
32:
- A monoclonal antibody having a binding domain capable of binding to a peptide of the HTT protein having the sequence of SEQ ID NO:
- 1.
33:
- The monoclonal antibody of claim 32, comprising a heavy chain variable region CDR1 comprising a sequence GYSFTDFY (SEQ ID NO:
- 54), a heavy chain variable region CDR2 comprising a sequence IDPKNGDT (SEQ ID NO:
- 55), a heavy chain variable region CDR3 comprising a sequence ATYYGYTMDY (SEQ ID NO:
- 56), a light chain variable region CDR1 comprising a sequence SSVTSSY (SEQ ID NO:
- 57), a light chain variable region CDR2 comprising a sequence STS (SEQ ID NO:
- 58), and a light chain variable region comprising a sequence HQYRRPPRT (SEQ ID NO:
- 59).
4 more elements
34:
- A monoclonal antibody having a binding domain capable of binding to a peptide of the HTT protein having the sequence of SEQ ID NO:
- 3.
35:
- The monoclonal antibody of claim 34, comprising a heavy chain variable region CDR1 comprising a sequence GYTFTEYT (SEQ ID NO:
- 66), a heavy chain variable region CDR2 comprising a sequence INPNNGGT (SEQ ID NO:
- 67), a heavy chain variable region CDR3 comprising a sequence ASLDGRDY (SEQ ID NO:
- 68), a light chain variable region CDR1 comprising a sequence QSLLNSRTRKNY (SEQ ID NO:
- 69), a light chain variable region CDR2 comprising a sequence WAS (SEQ ID NO:
- 70), and a light chain variable region comprising a sequence KQSYNLLT (SEQ ID NO:
- 71).
4 more elements
36:
- A monoclonal antibody having a binding domain capable of binding to a peptide of the HTT protein having the sequence of SEQ ID NO:
- 2.
37:
- The monoclonal antibody of claim 36, comprising a heavy chain variable region CDR1 comprising a sequence GFTFNTYA (SEQ ID NO:
- 72), a heavy chain variable region CDR2 comprising a sequence IRSKSNNYAT (SEQ ID NO:
- 73), a heavy chain variable region CDR3 comprising a sequence VRHGEYGNPWFAY (SEQ ID NO:
- 74), a light chain variable region CDR1 comprising a sequence QSLVHSNGNTY (SEQ ID NO:
- 75), a light chain variable region CDR2 comprising a sequence KVS (SEQ ID NO:
- 76), and a light chain variable region comprising a sequence SQSTHVPYT (SEQ ID NO:
- 77).
4 more elements
38:
- The monoclonal antibody of claim 32, wherein the monoclonal antibody is a human, humanized, bispecific or chimeric monoclonal antibody.
39:
- A pharmaceutical composition comprising the monoclonal antibody of claim 32.
40:
- An antibody or antigen-binding molecule targeting the caspase region 586 region of HTT, generated by immunization with a peptide-based vaccines comprising the immunogenic peptide of claim 22.