Targeting immunotherapy for amyloidosis

Patent metadata

Field	Value
Publication number	US-2016243230-A1
Application number	US-201615052772-A
Country	US
Kind code	A1
Filing date	Feb 24, 2016
Priority date	Aug 26, 2014
Publication date	Aug 25, 2016
Grant date	—

Abstract

Disclosed are methods and compositions for targeting antibodies to amyloid deposits. For example, amyloid-reactive peptides that bind amyloid deposits are administered to a subject. Antibodies to the amyloid-reactive peptides are then administered to the subject. Upon administration of the antibodies, the amyloid-reactive peptides bind the antibodies and thus pre-target the antibodies to the amyloid deposits. In other examples, an amyloid-reactive fusion peptide contains an epitope of a known antibody. When the fusion peptide is administered to a subject, the fusion peptide binds amyloids in the subject. Administration to the subject of the known antibody that binds the epitope of the fusion peptide then targets the antibody to the amyloid deposit to which the fusion peptide is bound.

First claim

1 . A method of targeting an amyloid deposit for clearance, comprising:
contacting an amyloid deposit with an amyloid-reactive peptide that binds the amyloid deposit, wherein the amyloid-reactive peptide comprises an HEDT amino acid sequence epitope (SEQ ID NO: 52); contacting the amyloid-reactive peptide with an antibody or functional fragment thereof that binds the HEDT epitope (SEQ ID NO: 52) of the amyloid-reactive peptide, wherein contacting the amyloid-reactive peptide with the antibody that binds the amyloid-reactive peptide targets the amyloid deposit for clearance.

2 . The method of claim 1 , wherein targeting the amyloid deposit for clearance results in clearance of the amyloid deposit.

3 . The method of claim 1 , wherein the antibody or functional fragment thereof is an amyloid-reactive antibody or functional fragment thereof.

4 . The method of claim 3 , wherein binding of the antibody or functional fragment thereof to the amyloid deposit results in increased clearance of the amyloid deposit.

5 . The method of claim 1 , wherein the antibody is a 7D8, 2A4, or 8G9 antibody or functional fragment thereof.

6 . The method of claim 1 , wherein the amyloid-reactive peptide binds to one or more amyloid deposit types comprising AA, AL, AH, ATTR, Aβ2M, ALect2, Wild type, TTR, AApoAI, AApoAII, AGel, ALys, ALect2, Afib, ACys, ACal, AMedin, AIAPP, APro, AIns, APrP, or Aβ.

7 . The method of claim 1 , wherein the amyloid-reactive peptide comprising the HEDT epitope (SEQ ID NO: 52) is at least 95% identical to the amino acid sequence set forth as SEQ ID NO:26.

8 . The method of claim 1 , wherein the amyloid-reactive peptide comprising the HEDT epitope (SEQ ID NO: 52) is at least 95% identical to the amino acid sequence set forth as SEQ ID NO:31.

9 . A method for treating amyloidosis in a subject, comprising:
selecting a subject with amyloidosis; administering to the subject an amyloid-reactive peptide that binds to an amyloid deposit, the amyloid-reactive peptide comprising an HEDT amino acid sequence epitope (SEQ ID NO: 52); administering to the subject an antibody or functional fragment thereof that binds to the HEDT epitope (SEQ ID NO: 52) of the amyloid-reactive peptide, wherein administration of the antibody or functional fragment thereof to the subject results in clearance of the amyloid deposit in the subject.

10 . The method of claim 9 , further comprising testing the subject to determine whether the subject has amyloidosis before administering the amyloid-reactive peptide or the antibody or functional fragment thereof.

11 . The method of claim 9 , wherein the antibody is an amyloid-reactive antibody.

12 . The method of claim 11 , wherein binding of the antibody or functional fragment thereof to the amyloid deposit results in increased clearance of the amyloid deposit.

13 . The method of claim 11 , wherein the antibody is a 7D8, 2A4, or 8G9 antibody or functional fragment thereof.

14 . The method of claim 9 , wherein the amyloid-reactive peptide binds to one or more amyloid deposit types comprising AA, AL, AH, ATTR, Aβ2M, ALect2, Wild type, TTR, AApoAI, AApoAII, AGel, ALys, ALect2, Afib, ACys, ACal, AMedin, AIAPP, APro, AIns, APrP, or Aβ.

15 . The method of claim 9 , wherein the amyloid-reactive peptide comprising the HEDT sequence (SEQ ID NO: 52) is at least 95% identical the amino acid sequence set forth as SEQ ID NO:26.

16 . A method of targeting an antibody to an amyloid deposit in a subject, comprising:
administering to a subject an effective amount of an amyloid-reactive fusion peptide, wherein the amyloid-reactive fusion peptide comprises an amyloid-reactive peptide that binds to an amyloid deposit and an HEDT epitope (SEQ ID NO: 52) that binds an antibody; and, administering to the subject an effective amount the antibody or functional fragment thereof that binds the HEDT epitope (SEQ ID NO: 52), thereby targeting the antibody or functional fragment thereof to the amyloid deposit.

17 . The method of claim 16 , wherein targeting the antibody or functional fragment thereof to the amyloid deposit results in clearance of the amyloid deposit.

18 . The method of claim 16 , wherein the amyloid reactive-peptide of the amyloid-reactive fusion peptide is at least 95% identical to the amino acid sequence set forth as any one of SEQ ID NO:1 to SEQ ID NO:17.

19 . The method of claim 16 , wherein the amyloid-reactive peptide of the amyloid-reactive fusion peptide binds to one or more amyloid deposit types comprising AA, AL, AH, ATTR, Aβ2M, ALect2, Wild type, TTR, AApoAI, AApoAII, AGel, ALys, ALect2, Afib, ACys, ACal, AMedin, AIAPP, APro, AIns, APrP, or Aβ.

20 . The method of claim 16 , wherein the amyloid-reactive fusion peptide is at least 95% identical the amino acid sequence set forth as SEQ ID NO:26.

Assignees

• Univ Tennessee Res Found

Inventors

• Wall Jonathan S
• Kennel Stephen J
• Foster James S

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61K47/6891

  Pre-targeting systems involving an antibody for targeting specific cells · CPC title

• A61K38/1716

  Amyloid plaque core protein · CPC title