Compositions and Methods for Treating Alzheimer's Disease

Patent metadata

Field	Value
Publication number	US-2016280742-A1
Application number	US-201615056546-A
Country	US
Kind code	A1
Filing date	Feb 29, 2016
Priority date	Nov 10, 2011
Publication date	Sep 29, 2016
Grant date	—

Abstract

The present disclosure provides for a hyperimmune preparation comprising human polyclonal antibodies or fragments thereof specific to a cyclic peptide having an amino acid sequence comprising SNK. The cyclic peptide may comprise an amino acid sequence GSNK (SEQ ID NO: 1), SNKG (SEQ ID NO: 2), GSNKG (SEQ ID NO: 3), CSNKG (SEQ ID NO: 4), CGSNKGC (SEQ ID NO: 5), CGSNKGG (SEQ ID NO: 6), or CCGSNKGC (SEQ ID NO: 7). The antibodies in the hyperimmune preparation may have a titer ranging from about 200 to about 400 mean fluorescence intensity (MFI). In one embodiment, greater than about 80% of the antibodies in the hyperimmune preparation are IgG. The fragments of the antibodies are Fab, F(ab′)2, scFv, disulfide linked Fv, or mixtures thereof.

First claim

1 - 22 . (canceled)

23 . A conformational epitope-containing peptide comprising the amino acid sequence CGSNKGG (SEQ ID NO: 6), wherein said conformational epitope is in a cyclic constrained configuration.

24 . The peptide of claim 23 , wherein the peptide is a cyclic peptide.

25 . The peptide of claim 23 , wherein the peptide consists of SEQ ID NO: 6.

26 . A pharmaceutical composition comprising the peptide of claim 23 .

27 . The pharmaceutical composition of claim 26 , wherein the composition further comprises a pharmaceutically acceptable adjuvant.

28 . A pharmaceutical composition comprising the peptide of claim 25 .

29 . The pharmaceutical composition of claim 28 , wherein the composition further comprises a pharmaceutically acceptable adjuvant.

30 . A method for treatment or prophylaxis of Alzheimer's disease in a subject comprising the step of administering to the subject a pharmaceutically effective amount of the pharmaceutical composition of claim 26 .

31 . The method of claim 30 , wherein the pharmaceutical composition is administered intramuscularly, subcutaneously, intraperitoneally, orally, or with intraocular injection.

32 . A method of enriching plasma for high titers of antibodies that are capable of binding an oligomeric Aβ, the method comprising immunizing an animal with the pharmaceutical composition of claim 26 .

33 . The method of claim 32 , wherein the antibodies bind to oligomeric Aβ with greater affinity than to a non-oligomeric form of Aβ.

34 . The method of claim 32 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable adjuvant.

35 . The method of claim 32 , wherein the animal is a human.

36 . The method of claim 32 , wherein the method comprising the step of immunizing the animal is via intramuscular, subcutaneous, intraperitoneal or intraocular injection.

37 . A method of detecting a decreased level of antibodies against oligomeric forms of Aβ(1-42) in a subject comprising the steps of:
(a) quantifying in a biological sample obtained from the subject the level of antibodies specific to a cyclic peptide comprising the amino acid sequence CGSNKGG (SEQ ID NO: 6); and
(b) comparing the level of the antibodies in step (a) with a control sample.

38 . The method of claim 37 , wherein the biological sample is plasma, tissues, cells, cerebrospinal fluid (CSF), blood, or combinations thereof.

39 . A method for predicting a subject's risk of developing Alzheimer's Disease comprising the steps of:
(a) quantifying in a biological sample obtained from the subject the level of antibodies specific to a cyclic peptide comprising the amino acid sequence CGSNKGG (SEQ ID NO: 6); and (b) comparing the level of the antibodies in step (a) with a control sample, wherein a lower level of the antibodies specific to the cyclic peptide compared to the control sample is indicative of the subject developing Alzheimer's Disease.

40 . The method of claim 39 , wherein the biological sample is plasma, tissues, cells, cerebrospinal fluid (CSF), blood, or combinations thereof.

Assignees

• Univ British Columbia
• Cnj Holdings Inc

Inventors

• Cashman Neil R
• Mcclarty Grant

Classifications

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title

• G01N2800/2821

  Alzheimer · CPC title