Compositions of Phosphorylated Tau Peptides and Uses Thereof

Abstract

Liposomes containing tau peptides, preferably phosphorylated tau peptides, and conjugates containing tau peptides, preferably phosphorylated tau peptides, conjugated to an immunogenic carrier are described. Pharmaceutical compositions and uses of the liposomes and/or conjugates for treating or preventing a neurodegenerative disease or disorder, such as Alzheimer's Disease, are also described.

We claim: 
     
         1 . A conjugate comprising a tau phosphopeptide and an immunogenic carrier conjugated thereto via a linker, the conjugate having the structure of: 
       
         
           
           
               
               
           
         
         wherein 
         x is an integer of 0 to 10; and 
         n is an integer of 3 to 15. 
       
     
     
         2 . The conjugate of  claim 1 , wherein the immunogenic carrier is selected from the group consisting of keyhole limpet hemocyanin (KLH), tetanus toxoid, CRM197 and an outer membrane protein mixture from  N. meningitidis  (OMP), or a derivative thereof. 
     
     
         3 . The conjugate of  claim 1 , wherein the tau peptide has an amino acid sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:12. 
     
     
         4 . The conjugate of  claim 1 , wherein x is 2 to 6. 
     
     
         5 . The conjugate of  claim 1 , wherein n is 3 to 12. 
     
     
         6 . The conjugate of  claim 4 , wherein x is 3. 
     
     
         7 . The conjugate of  claim 4 , wherein n is 3 to 12. 
     
     
         8 . The conjugate of  claim 6 , wherein n is 3 to 12. 
     
     
         9 . The conjugate of  claim 7 , wherein the tau peptide consists of the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO:3. 
     
     
         10 . The conjugate of  claim 9 , wherein the conjugate has the structure of formula (I) and the immunogenic carrier is CRM197. 
     
     
         11 . The conjugate of  claim 9 , wherein the conjugate has the structure of formula (II) and the immunogenic carrier is KLH. 
     
     
         12 . A pharmaceutical composition comprising the conjugate of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         13 . The pharmaceutical composition of  claim 12 , further comprising an adjuvant. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the adjuvant comprises at least one of an aluminum salt and a CpG. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the adjuvant comprises the aluminum salt and the CpG. 
     
     
         16 . A pharmaceutical composition comprising the conjugate of  claim 10  and a pharmaceutically acceptable carrier. 
     
     
         17 . A pharmaceutical composition comprising the conjugate of  claim 11  and a pharmaceutically acceptable carrier. 
     
     
         18 . A conjugate having the structure of: 
       
         
           
           
               
               
           
         
         wherein n is an integer of 3 to 7. 
       
     
     
         19 . A pharmaceutical composition comprising the conjugate of  claim 18  and a pharmaceutically acceptable carrier. 
     
     
         20 . The pharmaceutical composition of  claim 19 , further comprising an adjuvant. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the adjuvant comprises at least one of an aluminum salt and a CpG. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the adjuvant comprises the aluminum salt and the CpG. 
     
     
         23 . A conjugate having the structure of: 
       
         
           
           
               
               
           
         
         wherein
 the Tau peptide consisting of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:3; 
 x is an integer of 0 to 10; and 
 
         n is an integer of 2 to 15. 
       
     
     
         24 . A pharmaceutical composition comprising the conjugate of  claim 23  and a pharmaceutically acceptable carrier. 
     
     
         25 . The pharmaceutical composition of  claim 24 , further comprising an adjuvant. 
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein the adjuvant comprises at least one of an aluminum salt and a CpG. 
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein the adjuvant comprises the aluminum salt and the CpG. 
     
     
         28 . A method for inducing an immune response in a subject suffering from a neurodegenerative disorder, comprising administering to the subject the pharmaceutical composition of  claim 12 . 
     
     
         29 . A method for treating or preventing a neurodegenerative disease or disorder in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 12 , wherein the neurodegenerative disease or disorder is caused by or associated with the formation of neurofibrillary lesions.