Pharmaceutical targeting of a mammalian cyclic di-nucleotide signaling pathway

Abstract

Cyclic-GMP-AMP (cGAMP), including 2′,3′-cGAMP, are used in pharmaceutical formulations (including vaccine adjuvants), drug screens, therapies and diagnostics.

1 - 15 . (canceled) 
     
     
         16 . A composition comprising cyclic-GMP-AMP. 
     
     
         17 . The composition of  claim 16 , wherein cyclic-GMP-AMP is 2′,3′-cGAMP. 
     
     
         18 . The composition of  claim 16 , wherein cyclic-GMP-AMP has a molecular mass of 675.107 and a product ion peak of m/z 675.107 at a charge state of positive 1 or a product ion peak of m/z 338.057 at a charge state of positive 2, wherein the mass spectrometer is an orbitrap. 
     
     
         19 . The composition of  claim 16 , wherein cyclic-GMP-AMP MS/MS fragment ion peaks of m/z 338 at a charge state of positive 2 are comprising one or more peaks at about m/z 136, about 152, about 232, about 330, about 428, about 506, about 524 and about 540, wherein the mass spectrometer is a linear trap quadrupole and the fragmentation method is collision-induced dissociation. 
     
     
         20 . The composition of  claim 19 , wherein the peak at about 506 is more than half the intensity of the peak at about 152 or the peak at about 524. 
     
     
         21 . The composition of  claim 19 , wherein the peak at about 428 is less than half the intensity of the peak at about 152 or the peak at about 524. 
     
     
         22 . The composition of  claim 16 , wherein cyclic-GMP-AMP having a MS/MS fragmentation pattern comprising one or more peaks at about m/z 136.06, about 152.06, about 312.05, about 330.06, about 392.02, about 476.04, about 506.05, about 524.06, or about 675.11, wherein the mass spectrometer is an orbitrap and the fragmentation method is higher-energy collision dissociation. 
     
     
         23 . The composition of  claim 22 , wherein the peak at about 312.05 is approximately the same intensity as the peak at about 476.04. 
     
     
         24 . The composition of  claim 22 , wherein the peak at about 524.06 is at a lower intensity than the peak at about 312.05 or the peak at about 476.04. 
     
     
         25 . The composition of  claim 22 , wherein the peak at about 152.06 is not at a higher intensity than the peak at about 312.05 or the peak at about 476.04. 
     
     
         26 . The composition of  claim 16  essentially free of other cyclic di-nucleotides. 
     
     
         27 . An adjuvant comprising a composition according to  claim 16 . 
     
     
         28 . A vaccine comprising a predetermined immunogen and a composition according to  claim 16 . 
     
     
         29 . The vaccine of  claim 28  wherein the immunogen is selective for a target pathogen. 
     
     
         30 . The vaccine of  claim 28  wherein the immunogen is selective for a target tumor antigen. 
     
     
         31 . A method of inducing or promoting an immune response comprising administering to a mammal in need thereof an effective amount of a composition of  claim 16 . 
     
     
         32 . The method of  claim 31  wherein the composition activates an immune response through direct binding to STING. 
     
     
         33 . The method of  claim 31  wherein the immune response is against tumors. 
     
     
         34 . The method of  claim 31  wherein the immune response is against an infectious pathogen. 
     
     
         35 . The method of  claim 31  wherein the administering is mucosal (sublingual or intranasal), intramuscular or subcutaneous or intravenous.