US2006024667A1PendingUtilityA1

Compositions and methods for Alzheimer's disease

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Assignee: MANUCHARYAN KARENPriority: Jul 29, 2004Filed: Jul 29, 2004Published: Feb 2, 2006
Est. expiryJul 29, 2024(expired)· nominal 20-yr term from priority
Inventors:Karen ManucharyanGohar Gevorgyan
A61K 2039/505A61P 25/28G01N 33/6896C07K 16/18G01N 2333/4709C07K 2317/565C07K 2317/21C07K 2317/622C07K 2317/10
54
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Claims

Abstract

The present invention concerns methods and compositions of use for treatment of Alzheimer's Disease (AD). In certain embodiments, the methods concern preparation of phage-display single chain antibody libraries and screening against amyloid-beta (Aβ) protein or peptide. Anti-Aβ antibodies are selected and sequenced. In certain embodiments, synthetic Aβ binding peptides are designed and prepared, using portions of the anti-Aβ antibody sequences. The antibodies and peptides are of use for treatment of AD or for treatment of individuals at risk of developing AD. Compositions comprising anti-Aβ antibodies or Aβ binding peptides are also disclosed.

Claims

exact text as granted — not AI-modified
1 . A method comprising: 
 a) obtaining a library of phage-displayed human antibodies;    b) exposing the library to human amyloid-beta;    c) selecting one or more phage that encode one or more antibodies that bind to human amyloid-beta; and    d) determining one or more amino acid sequences that bind to human amyloid-beta.    
     
     
         2 . The method of  claim 1 , wherein the one or more amino acid sequences are determined from one or more immunoglobin (Tg) heavy chain (V H ) complementarity-determining regions (HCDR3).  
     
     
         3 . A method comprising 
 a) determining one or more amino acid sequences that bind to human amyloid-beta wherein the one or more amino acid sequences are determined from one or more immunoglobin (Ig) heavy chain (V H ) complementarity-determining regions (HCDR3) of one or more antibodies that bind to human amyloid-beta; and    b) administering one or more peptides comprising the one or more amino acid sequences to a subject, wherein said administering ameliorates the symptoms of Alzheimer's disease (AD) or decreases the risk of developing AD in the subject.    
     
     
         4 . A method comprising: 
 a) obtaining one or more peptides comprising one or more human antibody sequences that bind to human amyloid-beta; and    b) administering the one or more peptides to a subject;    wherein said administering ameliorates the symptoms of AD or decreases the risk of developing AD in the subject.    
     
     
         5 . The method of  claim 4 , wherein the one or more amino acid sequences are human single chain variable fragment (scFv) sequences that arc selected by phage display screening against human amyloid-beta.  
     
     
         6 . The method of  claim 4 , wherein the one or more amino acid sequences are selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO;7, SEQ ID NO:12 and SEQ ID NO:13.  
     
     
         7 . The method of  claim 4 , wherein the one or more amino acid sequences are human immunoglobulin heavy chain complementarity determining regions (HCDR3) that are selected by phage display screening against human amyloid-beta.  
     
     
         8 . The method of  claim 3 , wherein the one or more amino acid sequences are selected from the group consisting of SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11.  
     
     
         9 . The method of  claim 7 , further comprising incorporating a cysteine residue at each end of the one or more amino acid sequences.  
     
     
         10 . The method of  claim 4 , wherein the one or more peptides comprise one or more residues selected from the group consisting of amino acid analogues, derivatized amino acids and D-amino acids.  
     
     
         11 . The method of  claim 4 , wherein the one or more peptides are expressed as part of a surface protein in M13 phage.  
     
     
         12 . The method of  claim 4 , wherein each peptide consists of 19 or less amino acid residues.  
     
     
         13 . A composition comprising a peptide that binds to human amyloid-beta.  
     
     
         14 . The composition of  claim 13 , wherein administration of the composition to a subject with AD ameliorates the symptoms of AD.  
     
     
         15 . The composition of  claim 13 , wherein administration of the composition to a subject at risk or developing AD decreases the risk of developing AD.  
     
     
         16 . The composition of  claim 13 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO;6, SEQ ID NO:7, SEQ ID NO:5, SEQ ID NO;9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13.  
     
     
         17 . The composition of  claim 15 , wherein the peptide comprises at least six contiguous amino acids from an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO. 10, SEQ ID NO:11, SEQ ID NO: 12 and SEQ ID NO: 13.  
     
     
         18 . The composition of  claim 17 , wherein the peptide consists of 19 or less amino acid residues.  
     
     
         19 . A kit comprising: 
 a) a peptide that binds to human amyloid-beta; and    b) a container to contain the peptide.    
     
     
         20 . The kit of  claim 19 , further comprising Aβ42.  
     
     
         21 . The kit of  claim 20 , further comprising a control peptide that does not bind to human amyloid-beta.  
     
     
         22 . The kit of  claim 19 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO.7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO: 12 and SEQ ID NO. 13.  
     
     
         23 . A method comprising: 
 a) obtaining a library of phage-displayed mouse antibodies;    b) exposing the library to human amyloid-beta;    c) selecting one or more phage that encode one or more antibodies that bind to human amyloid-beta;    d) determining one or more HCDR3 sequences that bind to human amyloid-beta; and    c) preparing one or more peptides that bind to human amyloid-beta from the one or more HCDR3 sequences.    
     
     
         24 . The method of  claim 1 , further comprising administering the one or more peptides to a subject, wherein wherein said administering ameliorates the symptoms of AD or decreases the risk of developing AD in the subject.

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