aPL immunoreactive peptides, conjugates thereof and methods of treatment for aPL antibody-mediated pathologies

Abstract

aPL analogs that (a) bind specifically to B cells to which an aPL epitope binds and are disclosed. Optimized analogs lack T cell epitope(s) are useful as conjugates for treating aPL antibody-mediated diseases. Conjugates comprising aPL analogs and nonimmunogenic valency platform molecules are provides as are novel nonimmunogenic valency platform molecules and linkers. Methods of preparing and identifying said analogs, methods of treatment using said analogs, methods and compositions for preparing conjugates of said analogs and diagnostic immunoassays for aPL antibodies are disclosed.

1 . An aPL analog that binds specifically to B cells to which an aPL epitope binds.  
     
     
         2 . The analog of  claim 1  wherein the analog lacks a T cell epitope.  
     
     
         3 . The analog of  claim 1  wherein the analog is a peptide.  
     
     
         4 . The analog of  claim 3  wherein the peptide comprises the sequence CLILAPDRC, CLILTPDRC, CLLLAPDRC, CTILTLDRC, CLVLALDRC, CTILTPDRC, CILLAHDRC, CGNAADARC, CTNWADPRC, CGNIADPRC, CTNLTDSRC, CGNPTDVRC, GILLNEFA, GILTIDNL, GILNALDYV, LSDPGYVRNIFH or LTDPRYTRDISNFTD.  
     
     
         5 . The analog of  claim 3  wherein the peptide comprises the sequence AGPCLGVLGKLCPG, GPCLGVLGKLCPG, PCLGVLGKLCPG, CLGVLGKLCPG, AGPCLGVLGKLCG, CLGVLGKLC, GPCILLARDRCG or AGPILLARDRCPG.  
     
     
         6 . The analog of  claim 3  wherein the peptide contains at least one proline and further wherein α-methyl proline is substituted for at least one said proline.  
     
     
         7 . The analog of  claim 3  wherein a D-amino acid is substituted for at least one L-amino acid.  
     
     
         8 . The analog of  claim 3  wherein the peptide is cyclized by a disulfide bond.  
     
     
         9 . The analog of  claim 8  wherein a thioether bond is substituted for the disulfide bond.  
     
     
         10 . The analog of  claim 3  wherein the peptide contains at least one leucine and further wherein isoleucine is substituted for at least one said leucine.  
     
     
         11 - 74 . (canceled)