US2008021201A1PendingUtilityA1

Protease inhibitor conjugates and antibodies useful in immunoassay

Individually held — no corporate assignee on recordPriority: Jul 13, 2001Filed: Feb 1, 2007Published: Jan 24, 2008
Est. expiryJul 13, 2021(expired)· nominal 20-yr term from priority
C07K 16/38A61P 31/18A61P 43/00C07K 16/44
63
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Claims

Abstract

Activated haptens useful for generating immunogen to HIV protease inhibitors, immunogens useful for producing antibodies to HIV protease inhibitors, and antibodies and labeled conjugates useful in immunoassays for the HIV protease inhibitor saquinavir. The novel haptens feature an activated functionality at the central, non-terminal hydroxyl group. Also described are monoclonal antibodies specific for saquinavir having less than 10% cross-reactivity with lopinavir, nelfinavir, amprenavir, ritonavir, and indinavir, and a murine hybridoma producing said antibodies.

Claims

exact text as granted — not AI-modified
1 . A compound having the structure  
         I—X—(C═Y) m -L-A  wherein    I is amprenavir lacking only a hydroxyl or an amino group,    X is O or NR wherein R is H or lower alkyl,    Y is O, S, or NH,    m is 0 or 1,    L is a linker comprising from 0 to 40 carbon atoms arranged in a straight chain or a branched chain, saturated or unsaturated, and containing up to two ring structures and 0-20 heteroatoms, with the proviso that not more than two heteroatoms may be linked in sequence, and    A is an activated functionality chosen from the group consisting of active esters, isocyanates, isothiocyanates, thiols, imidoesters, anhydrides, maleimides, thiolactones, diazonium groups and aldehydes.    
     
     
         2 . The compound of  claim 1  wherein X is O, Y is O and m is 1.  
     
     
         3 . The compound of  claim 1  wherein X is NH, Y is O and m is 1.  
     
     
         4 . The compound of  claim 1  wherein X is O, Y is O, m is 1 and the first atom in L adjacent to C═Y is N.  
     
     
         5 . The compound of  claim 1  wherein X is NH, Y is O, m is 1 and the first atom in L adjacent to C═Y is N.  
     
     
         6 . The compound of  claim 1  wherein X is NH, Y is S, m is 1 and the first atom in L adjacent to C═Y is N.  
     
     
         7 . The compound of  claim 1  wherein X is NH, Y is NH, and m is 1.  
     
     
         8 . The compound of  claim 1  wherein X is O and m is 0.  
     
     
         9 . The compound O c -(succinimido-oxycarbonyl-butyryl-aminocaproyl)-amprenavir.  
     
     
         10 . The compound O c -[4′-(succinimido-oxycarbonyl)-benzoyl-aminocaproyl]-amprenavir.  
     
     
         11 . A compound having the structure  
         [I—X—(C═Y) m L-Z] n —P  wherein    I is amprenavir lacking only a hydroxyl or an amino group,    X is O or NR wherein R is H or lower alkyl,    Y is O, S, or NH,    m is 0 or 1,    L is a linker comprising 0 to 40 carbon atoms arranged in a straight chain or a branched chain, saturated or unsaturated, and further comprising up to two ring structures and 0-20 heteroatoms, with the proviso that not more than two heteroatoms are linked in sequence,    Z is a moiety selected from the group consisting of —CONH—, —NHCO—, —NHCONH—, —NHCSNH—, —OCONH—, —NHOCO—, —S—, —NH(C═NH)—, —N═N—, —NH—, and                          P is selected from the group consisting of polypeptides, polysaccharides and synthetic polymers, and    n is a number from 1 to 50 per 50 kilodaltons molecular weight of P.    
     
     
         12 . The compound of  claim 11  wherein P is an aminated dextran.  
     
     
         13 . The compound of  claim 11  wherein P is bovine serum albumin.  
     
     
         14 . The compound of  claim 11  wherein P is keyhole limpet hemocyanin.  
     
     
         15 . The compound of  claim 11  wherein P is  Limulus polyphemus  hemocyanin.  
     
     
         16 . The compound of  claim 11  wherein P is bovine thyroglobulin.  
     
     
         17 . The compound O c -(succinimido-oxycarbonyl-butyryl-aminocaproyl)-amprenavir conjugate with keyhole limpet hemocyanin.  
     
     
         18 . The compound O c -[4′-(succinimido-oxycarbonyl)-benzoyl-aminocaproyl]-amprenavir conjugate with bovine serum albumin.  
     
     
         19 . A compound having the structure  
         [I—X—(C═Y) m -L-Z] n -Q  wherein    I is amprenavir lacking only a hydroxyl or an amino group,    X is O or NR wherein R is H or lower alkyl,    Y is O, S, or NH,    m is 0 or 1,    L is a linker comprising 0 to 40 carbon atoms arranged in a straight chain or a branched chain, saturated or unsaturated, and further comprising up to two ring structures and 0-20 heteroatoms, with the proviso that not more than two heteroatoms are linked in sequence,    Z is a moiety chosen from the group consisting of —CONH—, —NHCO—, —NHCONH—, —NHCSNH—, —OCONH—, —NHOCO—, —S—, —NH(C═NH)—, —N═N—, —NH—, and                          Q is selected from the group consisting of non-isotopic labels, and    n is a number from 1 to 50 per 50 kilodaltons molecular weight of Q.    
     
     
         20 . The compound of  claim 19  wherein Q is biotin.  
     
     
         21 . The compound O c -[4′-(1-biotinyl-amino-3,6-dioxa-octylamino)-terephthaloyl-aminocaproyl]-amprenavir.  
     
     
         22 . An antibody generated in response to a compound having the structure  
         [I—X—(C═Y) m -L-Z] n —P  wherein    I is amprenavir lacking only a hydroxyl or an amino group,    X is O or NR wherein R is H or lower alkyl,    Y is O, S, or NH,    m is 0 or 1,    L is a linker comprising 0 to 40 carbon atoms arranged in a straight chain or a branched chain, saturated or unsaturated, and further comprising up to two ring structures and 0-20 heteroatoms, with the proviso that not more than two heteroatoms are linked in sequence,    Z is a moiety selected from the group consisting of —CONH—, —NHCO—, —NHCONH—, —NHCSNH—, —OCONH—, —NHOCO—, —S—, —NH(C═NH)—, —N═N—, —NH—, and                          P is selected from the group consisting of potypeptides, a polysaccharides, and synthetic polymers, and    n is a number from 1 to 50 per 50 kilodaltons molecular weight of P.    
     
     
         23 . A monoclonal antibody specific for amprenavir having less than 10% cross-reactivity with saquinavir, nelfinavir, indinavir, ritonavir and lopinavir.  
     
     
         24 . Murine hybridoma <AMPREN> M 1.1.52 having DSMZ No. ACC 2612.

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