Transthyretin antibodies and uses thereof

Abstract

The present invention provides compositions comprising anti-transthyretin antibodies. The compositions are particularly useful for diagnosis, prognosis and/or treatment of amyloid diseases or symptoms thereof.

What is claimed is: 
     
         1 . A method of administering an anti-aggregate agent to a subject in need thereof, comprising:
 a) administering said anti-aggregate agent to said subject at multiple time points;   b) measuring a level of non-native TTR in said subject upon at least a first and second time point of said administration;   c) adjusting dosage of said anti-aggregate agent and/or selecting a different anti-aggregate agent for administration based on said detected level of non-native TTR.   
     
     
         2 . The method of  claim 1 , wherein said non-native TTR is measured by an assay utilizing an antibody that exhibits selective binding to non-native TTR under physiologically relevant conditions as compared to tetrameric TTR for said antibody binding. 
     
     
         3 . The method of  claim 1 , wherein said anti-aggregate agent or therapy comprises a TTR kinetic stabilizer, wherein said TTR kinetic stabilizer stabilizes the TTR tetrameric form against dissociation. 
     
     
         4 . The method of  claim 1 , wherein said anti-aggregate agent or therapy comprises an anti-TTR that reduces total TTR protein level. 
     
     
         5 . The method of  claim 1 , wherein said first time point occurs before administering a first dosage of said anti-aggregate agent. 
     
     
         6 . The method of  claim 1 , wherein said second time point occurs after administering a first dosage of said anti-aggregate agent. 
     
     
         7 . The method of  claim 1 , comprising increasing dosage of said anti-aggregate agent if said detected level is increased by 20% or more at said second time point as compared to said first time point. 
     
     
         8 . A method of assessing the efficacy of an anti-aggregate therapy applied to a subject, comprising: measuring a change in the level of non-native TTR in said subject during said therapy, wherein said measuring is performed using an antibody that exhibits selective binding to non-native TTR under physiologically relevant conditions as compared to tetrameric TTR for said antibody binding, and wherein a decrease in the level of non-native TTR during said therapy indicates that said therapy is efficacious. 
     
     
         9 . The method of  claim 8 , further comprising alerting said subject or caregiver thereof that said therapy is efficacious (1) if said change is a decrease in the level of non-native TTR, or (2) that said therapy is not efficacious if said change is not a decrease in the level of non-native TTR. 
     
     
         10 . The method of  claim 8 , further comprising alerting said subject or caregiver thereof that said therapy is efficacious if said change is a decrease in the level of non-native TTR. 
     
     
         11 . The method of  claim 8 , further comprising alerting said subject or caregiver thereof that said therapy is not efficacious if said change is not a decrease in the level of non-native TTR. 
     
     
         12 . The method of  claim 8 , wherein said detection or measuring a level of non-native TTR comprises detecting or measuring in a biological sample obtained from said subject. 
     
     
         13 . The method of  claim 12 , wherein said biological sample is a liquid sample. 
     
     
         14 . The method of  claim 8 , wherein said subject is a human. 
     
     
         15 . The method of  claim 8 , wherein said anti-aggregate agent or therapy comprises a TTR kinetic stabilizer, wherein said TTR kinetic stabilizer stabilizes the TTR tetrameric form against dissociation. 
     
     
         16 . The method of  claim 15 , wherein said kinetic stabilizer is a benzoxazole. 
     
     
         17 . The method of  claim 16 , wherein said benzoxazole is tafamidis. 
     
     
         18 . The method of  claim 16 , wherein said kinetic stabilizer is diflunisal. 
     
     
         19 . The method of  claim 8 , wherein said anti-aggregate agent or therapy comprises an anti-TTR that reduces total TTR protein level.