US2014346397A1PendingUtilityA1

Compounds and methods for purification of serine proteases

Assignee: PORTOLA PHARM INCPriority: Dec 27, 2012Filed: Dec 27, 2013Published: Nov 27, 2014
Est. expiryDec 27, 2032(~6.4 yrs left)· nominal 20-yr term from priority
C12N 9/6424C07D 213/75C07D 213/72B01J 2220/80B01J 20/286B01J 20/267C12Y 304/21006C12N 9/6432
57
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Claims

Abstract

Disclosed herein are compounds, compositions, methods and kits for purifying a serine protease and serine proteases purified with the compounds, compositions and methods.

Claims

exact text as granted — not AI-modified
1 - 18 . (canceled) 
     
     
         19 . A compound selected from: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         20 . (canceled) 
     
     
         21 . An affinity solid support of Formula II: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, 
       wherein:
 R 21  is —CF 3 , —SO 2 CH 3 , —X-L-Y—Z, 
 
       
         
           
           
               
               
           
         
         R 22  is —OCH 3 , chloro, or X-L-Y—Z; 
         R 23  is hydrogen or chloro; 
         X is a covalent bond, O, S, SO 2 , C(O)NH, NHC(O) or NH; 
         L-Y—Z is -L 1 -Y—Z, 
       
       
         
           
           
               
               
           
         
         L 1 -Y—Z is 
       
       
         
           
           
               
               
           
         
         L 2 -Y—Z is 
       
       
         
           
           
               
               
           
         
         L 3 -Y—Z is 
       
       
         
           
           
               
               
           
         
         Y—Z is 
       
       
         
           
           
               
               
           
         
         Z is Capto™ resin; 
         q is 1, 2, 3, 4, 5, 6 or 7; 
         r is 1, 2, 3, 4, 5, 6 or 7; 
         s is 1, 2, 3, 4, 5, 6 or 7; 
         t is 1, 2, 3, 4, 5, 6 or 7; 
         v is 1, 2, 3, 4, 5, 6 or 7; 
         u is 1, 2, 3, 4, 5, 6 or 7; 
         w is 1, 2 or 3; 
         n, m, and p are either 0 or 1, with the provisos that 
         (1) when R 21  is 
       
       
         
           
           
               
               
           
         
       
       —CF 3  or —SO 2 CH 3 , and R 22  is —OCH 3  or chloro, then one of n, m, and p must be 1, and the others of n, m, and p must be zero; and
 (2) when R 21  is other than 
 
       
         
           
           
               
               
           
         
       
       —CF 3  or —SO 2 CH 3 , or R 22  is X-L-Y—Z, then all of n, m, and p must be zero. 
     
     
         22 . The affinity solid support of  claim 21  of Formula II-A: 
       
         
           
           
               
               
           
         
       
       wherein the variables are as defined in  claim 21 . 
     
     
         23 . The affinity solid support of  claim 21  of Formula II-B: 
       
         
           
           
               
               
           
         
       
       wherein the variables are as defined in  claim 21 . 
     
     
         24 . The affinity solid support of  claim 21  of Formula II-C: 
       
         
           
           
               
               
           
         
       
       wherein the variables are as defined in  claim 21 . 
     
     
         25 . The affinity solid support of  claim 21  of Formula II-D: 
       
         
           
           
               
               
           
         
       
       wherein the variables are as defined in  claim 21 . 
     
     
         26 . The affinity solid support of  claim 21 , wherein R 21  is 
       
         
           
           
               
               
           
         
       
     
     
         27 . The affinity solid support of  claim 21 , wherein R 22  is —OCH 3 . 
     
     
         28 . The affinity solid support of  claim 21 , wherein R 22  is X-L-Y—Z. 
     
     
         29 . The affinity solid support of  claim 21 , wherein R 23  is hydrogen. 
     
     
         30 . The affinity solid support of  claim 21 , wherein R 23  is chloro. 
     
     
         31 . The affinity solid support of  claim 21 , wherein X is O. 
     
     
         32 . The affinity solid support of  claim 21 , wherein X is a covalent bond. 
     
     
         33 . The affinity solid support of  claim 21 , wherein X is S or SO 2 . 
     
     
         34 . The affinity solid support of  claim 21 , wherein X is NH. 
     
     
         35 . The affinity solid support of any  claim 21 , wherein L-Y—Z is -L 1 -Y—Z or 
       
         
           
           
               
               
           
         
       
     
     
         36 . The affinity solid support of  claim 21 , wherein L-Y—Z is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         37 . The affinity solid support of  claim 21 , wherein L 1 -Y—Z is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         38 . The affinity solid support of  claim 21 , wherein each of q, r, s, and t is at least 3. 
     
     
         39 . The affinity solid support of  claim 21 , wherein —X-L-Y—Z is selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         40 . The affinity solid support of  claim 21  which is 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         41 . (canceled) 
     
     
         42 . An affinity solid support of formula: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein v is 1, 2, 3, 4, 5, 6 or 7 and Z is Capto™ resin. 
     
     
         43 - 52 . (canceled) 
     
     
         53 . A kit for purifying a serine protease comprising
 (1) an affinity solid support of any  claim 21 , and   (2) an elution buffer comprising a competitive agent.   
     
     
         54 . (canceled) 
     
     
         55 . A kit for purifying a serine protease comprising a compound of Formula I-D: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, 
       and a resin of the Formula 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is —CF 3 , —SO 2 CH 3 , —X-L-R, 
 
       
         
           
           
               
               
           
         
         R 2  is —OCH 3 , chloro, or X-L-R; 
         R 3  is hydrogen or chloro; 
         X is a covalent bond, O, S, SO 2 , C(O)NH, NHC(O) or NH; 
         L-R is —(CH 2 ) w —CO 2 H; 
         R is CO 2 H; 
         n, m, and p are either 0 or 1, with the provisos that 
         (1) when R 1  is 
       
       
         
           
           
               
               
           
         
       
       —CF 3  or —SO 2 CH 3 , and R 2  is —OCH 3  or chloro, then one of n, m, and p must be 1, and the others of n, m, and p must be zero; and
 (2) when R 1  is other than 
 
       
         
           
           
               
               
           
         
       
       —CF 3  or —SO 2 CH 3 , or R 2  is X-L-R, then all of n, m, and p must be zero;
 u is 1, 2, 3, 4, 5, 6 or 7, w is 1, 2 or 3 and Z is Capto™ resin. 
 
     
     
         56 . The kit of  claim 54 , further comprising an elution buffer comprising a competitive agent. 
     
     
         57 . The kit of  claim 54 , further comprising a washing buffer. 
     
     
         58 - 59 . (canceled)

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