SYNTHETIC IMMUNOGENIC BUT NON-DEPOSIT-FORMING POLYPEPTIDES AND PEPTIDES HOMOLOGOUS TO AMYLOID BETA, PRION PROTEIN, AMYLIN, ALPHA-SYNUCLEIN, OR POLYGLUTAMINE REPEATS FOR INDUCTION OF AN IMMUNE RESPONSE THERETO

• US 20090163420A1
• Filed: 12/19/2008
• Published: 06/25/2009
• Est. Priority Date: 11/21/2001
• Status: Abandoned Application

• Current Assignee: New York University
• Original Assignee: New York University
• Inventors: Wisniewski, Thomas, Frangione, Blas, Sigurdsson, Einar M.
• Application Number:
  US12/339,587
• Publication Number:
  US 20090163420A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695

Abstract

The present invention relates to immunogenic but non-depositing-forming polypeptides or peptides homologous to amyloid β, prion, amylin or α-synuclein which can be used alone or conjugated to an immunostimulatory molecule in an immunizing composition for inducing an immune response to amyloid β peptides and amyloid deposits, to prion protein and prion deposits, to amylin and amylin deposits, to α-synuclein and deposits containing α-synuclein, or to polyglutamine repeats and deposits of proteins containing polyglutamine repeats. Described are also antibodies directed against such peptides, their generation, and their use in methods of passive immunization to such peptides and deposits.

Claims

1. An isolated peptide represented by the formula

(A)_n-(N-Xaa₁GlyAlaXaa₂Xaa₃-C)_n—

(B)_p

wherein;

m is 0, 4, 5, 6, 7, 8, 9, or 10;

p is 0, 4, 5, 6, 7, 8, 9, or 10;

A is Lys or Asp;

B is Lys or Asp;

n is 1 or 2;

N is residues 1-22 of SEQ ID NO;

46;

C is residues 28-37 of SEQ ID NO;

46;

Xaa₁, Xaa₂, and Xaa₃ are Phe, Ile, and Leu, respectively, in which zero, one, two or three of residues Xaa₁, Xaa₂, and Xaa₃ is substituted with Pro, Asp, Glu, Lys, Gly, or Ser; and

when zero residues is substituted, then either or both m and p is not zero.

2. The peptide of claim 1, wherein all residues are D-amino residues.

3. The peptide of claim 1, wherein p is 0.

4. The peptide of claim 3, wherein the amino acid sequence of said peptide is selected from the group consisting of SEQ ID NO:

48 and SEQ ID NO;

49.

5. The peptide of claim 1, wherein m is 0.

6. The peptide of claim 5, wherein the amino acid sequence of said peptide is selected from the group consisting of SEQ ID NO:

50 and SEQ ID NO;

51.

7. The peptide of claim 1, wherein m is not zero and p is not zero.

8. The peptide of claim 7, wherein the amino acid sequence of said peptide is selected from the group consisting of SEQ ID NO:

52 and SEQ ID NO;

53.

9. A conjugate of the peptide of claim 1 cross-linked to a polymer molecule.

10. The conjugate of claim 9, wherein said polymer molecule is a peptide comprising a promiscuous T helper cell epitope.

11. An immunizing composition, comprising an immunizing effective amount of the peptide of claim 1 or a conjugate thereof, and a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, or auxiliary agent.