US2021236399A1PendingUtilityA1

Reagents and methods for mineralization of tooth enamel

Assignee: UNIV WASHINGTONPriority: Jan 13, 2016Filed: Feb 17, 2021Published: Aug 5, 2021
Est. expiryJan 13, 2036(~9.5 yrs left)· nominal 20-yr term from priority
A61K 8/64A61K 8/19A61K 8/24A61K 2800/86A61K 8/21A61Q 11/00
52
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Claims

Abstract

Reagents and methods for whitening and remineralizing teeth using biomineralizing peptides are described.

Claims

exact text as granted — not AI-modified
1 . A method for mineralizing teeth, comprising administering to one or more teeth of a subject in need thereof an effective amount to mineralize teeth of a polypeptide comprising or consisting of the amino acid sequence selected from the group consisting of: 
       
         
           
                 
               
                   (shADP5; SEQ ID NO: 16) 
                 
                   (SYENSHSQAINVDRT) 1-10 ; 
                 
                     
                 
                   (sADP5; SEQ ID NO: 24) 
                 
                   (SYEKSHSQAINTDRT) 1-10   
                 
                     
                 
                   (ADP3; SEQ ID NO: 7) 
                 
                   (WP( A / S )TDKTKREEVD) 1-10 ; 
                 
                     
                 
                   (ADP5; SEQ ID NO: 13) 
                 
                   (PGYIN( L / F )SYE( K / N )SHSQAIN( T / V )DRTA) 1-10 ; 
                 
                     
                 
                   (ADP6; SEQ ID NO: 17) 
                 
                   (LPPLFSMPLSPILPELPLEAWPAT) 1-10 ; 
                 
                     
                 
                   (ADP7; SEQ ID NO: 18) 
                 
                   (HPP( S / T )HTLQPHHH( L / I )PVVPAQQPV( A / I )PQQPMMPVPG(H/Q) 
                 
                     
                 
                   HSMTP( T / I )QH) 1-10 ; 
                 
                   and 
                 
                     
                 
                   12-42 contiguous amino acids of 
                 
                   (ADP7; SEQ ID NO: 18) 
                 
                   (HPP( S / T )HTLQPHHH( L / I )PVVPAQ 
                 
                     
                 
                   QPV( A / I )PQQPMMPVPG( H / Q )HSMTP( T / I )QH) 1-10 ; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or a functional equivalent thereof, or any combination thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the polypeptide comprises or consists of the amino acid sequence (SYENSHSQAINVDRT) 1-10  (shADP5; SEQ ID NO:16), or a functional equivalent thereof. 
     
     
         3 . The method of  claim 1 , wherein the polypeptide comprises or consists of the amino acid sequence (SYEKSHSQAINTDRT) 1-10  (sADP5; SEQ ID NO:24), or a functional equivalent thereof. 
     
     
         4 . The method of  claim 1 , wherein the polypeptide comprises or consists of an amino acid sequence selected from the group consisting of: 
       
         
           
                 
               
                   (ADP1; SEQ ID NO: 1) 
                 
                   (HTLQPHHH( L / I )PVV) 1-10 ; 
                 
                     
                 
                   (ADP2; SEQ ID NO: 4) 
                 
                   (VPG( H / Q )HSMTP( T / I )QH) 1-10 ; 
                 
                     
                 
                   (ADP4; SEQ ID NO: 10) 
                 
                   (HPP( S / T )HTLQPHHH( L / I )PVV) 1-10 ; 
                 
                     
                 
                   (ADP8; SEQ ID NO: 21) 
                 
                   (PAQQPV( A / I )PQQPMMP) 1-10 ; 
                 
                     
                 
                   (ADP7; SEQ ID NO: 18) 
                 
                   (HPP( S / T )HTLQPHHH( L / I )PVVPAQQPV( A / I )PQQPMMPVPG( H / Q ) 
                 
                     
                 
                   HSMTP( T / I )QH) 1-10 ; 
                 
                     
                 
                   (ADP1M; SEQ ID NO: 2) 
                 
                   HTLQPHHH L PVV) 1-10 ; 
                 
                     
                 
                   (ADP1H; SEQ ID NO: 3) 
                 
                   (HTLQPHHH IP VV) 1-10 ; 
                 
                     
                 
                   (ADP2M; SEQ ID NO: 5) 
                 
                   (VPG H HSMTP T QH) 1-10 ; 
                 
                     
                 
                   (ADP2H; SEQ ID NO: 6) 
                 
                   (VPG Q HSMTP I QH) 1-10 ; 
                 
                     
                 
                   (ADP4M; SEQ ID NO: 11) 
                 
                   (HPP S HTLQPHHH L PVV) 1-10 ; 
                 
                     
                 
                   (ADP4H; SEQ ID NO: 12) 
                 
                   (HPP T HTLQPHHH I PVV) 1-10 ; 
                 
                     
                 
                   (ADP7M; SEQ ID NO: 19) 
                 
                   (HPP S HTLQPHHH L PVVPAQQPV A PQQPMMPVPG H HSMTP T QH) 1-10 ; 
                 
                     
                 
                   (ADP7H; SEQ ID NO: 20) 
                 
                   (HPP T HTLQPHHH I PVVPAQQPV I PQQPMMPVPG Q HSMTP I QH) 1-10 ; 
                 
                     
                 
                   (ADP8M; SEQ ID NO: 22) 
                 
                   (PAQQPV A PQQPMMP) 1-10 ; 
                 
                   and 
                 
                     
                 
                   (ADP8H; SEQ ID NO: 23) 
                 
                   (PAQQPV I PQQPM1VIP) 1-10 ; 
                 
                     
                 
                   (ADP3M; SEQ ID NO: 8) 
                 
                   (WPATDKTKREEVD) 1-10 ; 
                 
                   and 
                 
                     
                 
                   (ADP3H; SEQ ID NO: 9) 
                 
                   (WP S TDKTKREEVD) 1-10 , 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or a functional equivalent thereof, or a combination thereof. 
       
     
     
         5 . The method of  claim 1 , wherein the polypeptide comprises a fusion polypeptide comprising two or more of the amino acid sequences selected from the group consisting of: 
       
         
           
                 
               
                   (shADP5; SEQ ID NO: 16) 
                 
                   (SYENSHSQAINVDRT) 1-10 ; 
                 
                     
                 
                   (sADP5; SEQ ID NO: 24) 
                 
                   (SYEKSHSQAINTDRT) 1-10   
                 
                     
                 
                   (ADP1; SEQ ID NO: 1) 
                 
                   (HTLQPHHH( L / I )PVV) 1-10 ; 
                 
                     
                 
                   (ADP2; SEQ ID NO: 4) 
                 
                   (VPG( H / Q )HSMTP( T / I )QH) 1-10 ; 
                 
                     
                 
                   (ADP3; SEQ ID NO: 7) 
                 
                   (WP( A / S )TDKTKREEVD) 1-10 ; 
                 
                     
                 
                   (ADP4; SEQ ID NO: 10) 
                 
                   (HPP( S / T )HTLQPHHH( L / I )PVV) 1-10 ; 
                 
                     
                 
                   (ADP5; SEQ ID NO: 13) 
                 
                   (PGYIN( L / F )SYE( K / N )SHSQAIN( T / V )DRTA) 1-10 ; 
                 
                     
                 
                   (ADP6; SEQ ID NO: 17) 
                 
                   (LPPLFSMPLSPILPELPLEAWPAT) 1-10 ; 
                 
                     
                 
                   (ADP8; SEQ ID NO: 21) 
                 
                   (PAQQPV( A / I )PQQPMMP) 1-10 ; 
                 
                     
                 
                   (ADP7; SEQ ID NO: 18) 
                 
                   (HPP( S / T )HTLQPHHH( L / I )PVVPAQQPV( A / I )PQQPMMPVPG( H / Q ) 
                 
                     
                 
                   HSMTP( T / I )QH) 1-10 ; 
                 
                     
                 
                   (ADP1M; SEQ ID NO: 2) 
                 
                   HTLQPHHH L PVV) 1-10 ; 
                 
                     
                 
                   (ADP1H; SEQ ID NO: 3) 
                 
                   (HTLQPHHH I PVV) 1-10 ; 
                 
                     
                 
                   (ADP2M; SEQ ID NO: 5) 
                 
                   (VPG H HSMTP T QH) 1-10 ; 
                 
                     
                 
                   (ADP2H; SEQ ID NO: 6) 
                 
                   (VPG Q HSMTP I QH) 1-10 ; 
                 
                     
                 
                   (ADP4M; SEQ ID NO: 11) 
                 
                   (HPP S HTLQPHHH L PVV) 1-10 ; 
                 
                     
                 
                   (ADP4H; SEQ ID NO: 12) 
                 
                   (HPP T HTLQPHHH I PVV) 1-10 ; 
                 
                     
                 
                   (ADP7M; SEQ ID NO: 19) 
                 
                   (HPP S HTLQPHHE L PVVPAQQPV A PQQPMMPVPG H HSMTP T QH) 1-10 ; 
                 
                     
                 
                   (ADP7H; SEQ ID NO: 20) 
                 
                   (HPP T HTLQPHHH I PVVPAQQPV I PQQPMMPVPG Q HSMTP I QH) 1-10 ; 
                 
                     
                 
                   (ADP8M; SEQ ID NO: 22) 
                 
                   (PAQQPV A PQQPMMP) 1-10 ; 
                 
                   and 
                 
                     
                 
                   (ADP8H; SEQ ID NO: 23) 
                 
                   (PAQQPV I PQQPMMP) 1-10 ; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or a functional equivalent thereof. 
       
     
     
         6 . The method of  claim 1 , wherein the polypeptide is present in a single copy. 
     
     
         7 . The method of  claim 1 , further comprising administering to the subject at least one calcium ion source and at least one phosphate ion source. 
     
     
         8 . The method of  claim 7  wherein the calcium ion source is selected from the group consisting of calcium acetate, calcium carbonate, calcium citrate, calcium chloride, calcium gluconate, calcium glycerophosphate, calcium lactate, and calcium phosphate. 
     
     
         9 . The method of  claim 7 , wherein the phosphate ion source is selected from the group consisting of aluminum phosphates, calcium phosphates, potassium phosphates, and sodium phosphates. 
     
     
         10 . The method of  claim 7 , wherein the method comprising administering a formulation of the polypeptide, at least one calcium ion source and at least one phosphate ion source, wherein the formulation has
 (a) a Ca 2+  concentration ranging between about 1 mM and about 2 M, between about 1 mM and about 1M, between about 1 mM and about 0.5M, between about 1 mM and about 100 mM, between about 1 mM and about 50 mM, between about 1 mM and about 10 mM, between about 2 mM and about 8 mM, between about 3 mM and about 7 mM, between about 4 mM and about 6 mM, or between about 4.5 mM and about 5.5 mM; and   (b) a PO 4   3−  concentration ranging between about 0.5 mM and about 2 M, between about 0.5 mM and about 1M, between about 0.5 mM and about 0.5M, between about 0.5 mM and about 100 mM, between about 0.5 mM and about 50 mM, between about 0.5 mM and about 10 mM, between about 0.5 mM and about 7 mM, or between about 1 mM and about 6 mM, between about 1.5 mM and about 5 mM, between about 2 mM and about 4 mM, or between about 2.5 mM and about 3.5 mM.   
     
     
         11 . The method of  claim 1 , wherein the polypeptide is detectably labeled. 
     
     
         12 . The method of  claim 1 , wherein the method further comprises administering fluoride to the subject. 
     
     
         13 . The method of  claim 1 , wherein the formulation further comprises fluoride. 
     
     
         14 . The method of  claim 13 , wherein the fluoride is present in the formulation at between about between about 50 parts per million (ppm) and about 20,000 ppm, between about 50 ppm and about 10,000 ppm, between about 50 ppm and about 5000 ppm, between about 50 ppm and about 1000 ppm, between about 50 ppm and about 500 ppm, or about 75 ppm and about 400 ppm, between about 100 ppm and about 300 ppm, between about 150 ppm and about 250 ppm, or about 200 ppm. 
     
     
         15 . The method of  claim 10 , wherein the formulation is selected from the group consisting of toothpaste, toothpowders, mouthwash, gel, dental floss, liquid dentifrices, dental tablets, topical gels, troches, chewing gums, dental pastes, gingival massage creams, gargle tablets, lozenges, tooth trays, tooth varnishes, and food products. 
     
     
         16 . The method of  claim 10 , wherein the formulation comprises a lozenge, a gel, or mouthwash. 
     
     
         17 . The method of  claim 1  wherein the polypeptide is administered in a formulation at a concentration of between about 0.01 mM and about 0.5M, between about 0.01 mM and about 0.1M, between about 0.01 mM and about 50 mM, between about 0.01 mM to about 20 mM, or between about 0.1 mM to about 15 mM, or between about 0.5 mM to about 12.5 mM, or between about 0.8 mM and about 10 mM. 
     
     
         18 . The method of  claim 1 , wherein the subject is one suffering from demineralization of enamel of one or more tooth. 
     
     
         19 - 21 . (canceled) 
     
     
         22 . A polypeptide consisting of the amino acid sequence of
 (SYENSHSQAINVDRT) 1-10  (shADP5; SEQ ID NO:16); or   (SYEKSHSQAINTDRT) 1-10  (sADP5; SEQ ID NO:24).   
     
     
         23 . (canceled) 
     
     
         24 . An oral care product, comprising
 (a) the polypeptide of  claim 22 ,   (b) at least one calcium ion source, and   (c) at least one phosphate ion source.   
     
     
         25 - 34 . (canceled)

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