US2022118087A1PendingUtilityA1

Methods for treating gi syndrome and graft versus host disease

Assignee: SLOAN KETTERING INST CANCER RESPriority: May 25, 2012Filed: Jul 17, 2020Published: Apr 21, 2022
Est. expiryMay 25, 2032(~5.8 yrs left)· nominal 20-yr term from priority
A61K 45/06C07K 2317/24A61K 31/496A61K 39/39533A61K 31/4709C07K 2317/76A61P 1/00A61K 31/55A61P 39/00C07K 16/44A61K 39/39541A61P 43/00C07K 16/18
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Claims

Abstract

It has been discovered that administering therapeutically effective amounts of an antibiotic that kills Gram-negative bacteria, together with an anti-ceramide antibody or anti-ceramide mimetic, treats and prevents an array of diseases mediated by cytolytic T lymphocyte (CTL)-induced killing and/or by damage to endothelial microvasculature, including Radiation GI syndrome, GvHD disease, inflammatory diseases and autoimmune diseases.

Claims

exact text as granted — not AI-modified
1 .- 9 . (canceled) 
     
     
         10 . An anti-ceramide antibody or antigen-binding fragment thereof, comprising a variable heavy chain (VH) and a variable light chain (VL),
 wherein the VH comprises a VH-CDR1 sequence of NYWMH, a VH-CDR2 sequence of AIYPGDSDTSYNQKFKG, and a VH-CDR3 sequence of LYYGYD, and   wherein the VL comprises a VL-CDR1 sequence of KSSQSLIDSDGKTFLNW, a VL-CDR2 sequence of LVSKLDS, and a VL-CDR3 sequence of WQGTHFPYT; wherein the VH comprises   
       
         
           
                 
               
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMHWVRQAPGQGLEWMGA 
                 
                     
                 
                   IYPGDSDTSYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARLY 
                 
                     
                 
                   YGYDWGQGTTVTVSS. 
                 
             
                
                
                
                
                
               
            
           
         
       
     
     
         11 . The anti-ceramide antibody or antigen-binding fragment thereof according to  claim 10 , wherein the VL comprises 
       
         
           
                 
               
                   DVVMTQSPLSLPVTLGQPASISCKSSQSLIDSDGKTFLNWFQQRPGQSPR 
                 
                     
                 
                   RLIYLVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTHFP 
                 
                     
                 
                   YTFGQGTKLEIK. 
                 
             
                
                
                
                
                
               
            
           
         
       
     
     
         12 . The anti-ceramide antibody or antigen-binding fragment thereof according to  claim 10 , wherein the antibody is an IgG antibody. 
     
     
         13 . The anti-ceramide antibody or antigen-binding fragment thereof according to  claim 12 , wherein the antibody is an IgG1 antibody. 
     
     
         14 . The anti-ceramide antibody or antigen-binding fragment thereof according to  claim 10 , wherein the antibody is an IgM antibody. 
     
     
         15 . The anti-ceramide antibody or antigen-binding fragment thereof according to  claim 10 , wherein the antigen-binding fragment is a scFv. 
     
     
         16 . The anti-ceramide antibody or antigen-binding fragment thereof according to  claim 10 , comprising a heavy chain comprising 
       
         
           
                 
               
                   QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMHWVRQAPGQGLEWMGA 
                 
                     
                 
                   IYPGDSDTSYNQKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARLY 
                 
                     
                 
                   YGYDWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE 
                 
                     
                 
                   PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV 
                 
                     
                 
                   NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM 
                 
                     
                 
                   ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV 
                 
                     
                 
                   VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP 
                 
                     
                 
                   PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG 
                 
                     
                 
                   SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         17 . The anti-ceramide antibody or antigen-binding fragment thereof according to  claim 10 , comprising a light chain comprising 
       
         
           
                 
               
                   DVVMTQSPLSLPVTLGQPASISCKSSQSLIDSDGKTFLNWFQQRPGQSPR 
                 
                     
                 
                   RLIYLVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTHFP 
                 
                     
                 
                   YTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK 
                 
                     
                 
                   VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE 
                 
                     
                 
                   VTHQGLSSPVTKSFNRGEC. 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         18 . The anti-ceramide antibody or antigen-binding fragment thereof according to  claim 10 , comprising a heavy chain according to SEQ ID NO: 6. 
     
     
         19 . The anti-ceramide antibody according to  claim 10 , comprising a light chain according to SEQ ID NO: 8. 
     
     
         20 . An anti-ceramide antibody or antigen-binding fragment thereof, comprising a variable heavy chain (VH) and a variable light chain (VL),
 wherein the VH comprises a VH-CDR1 sequence of NYWMH, a VH-CDR2 sequence of AIYPGDSDTSYNQKFKG, and a VH-CDR3 sequence of LYYGYD, and   wherein the VL comprises a VL-CDR1 sequence of KSSQSLIDSDGKTFLNW, a VL-CDR2 sequence of LVSKLDS, and a VL-CDR3 sequence of WQGTHFPYT; wherein the VL comprises   
       
         
           
                 
               
                   DVVMTQSPLSLPVTLGQPASISCKSSQSLIDSDGKTFLNMTQQRPGQSPR 
                 
                     
                 
                   RLIYLVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTHFP 
                 
                     
                 
                   YTFGQGTKLEIK.

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