Lipid containing formulations

Abstract

Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described.

1 . A preparation comprising one or more compounds, each individually having a structure defined by formula (I) or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein 
         each X a  and X b , for each occurrence, is independently C 1-6  alkylene; 
         n is 0, 1, 2, 3, 4, or 5; each R is independently H, 
       
       
         
           
           
               
               
           
         
         wherein at least n+2 of the R moieties in at least about 80% of the molecules of the compound of formula (I) in the preparation are not H; 
         m is 1, 2, 3 or 4; Y is O, NR 2 , or S; 
         R 1  is alkyl alkenyl or alkynyl; each of which is optionally substituted with one or more substituents; and 
         R 2  is H, alkyl alkenyl or alkynyl; each of which is optionally substituted each of which is optionally substituted with one or more substituents; 
         provided that, if n=0, then at least n+3 of the R moieties are not H. 
       
     
     
         2 - 138 . (canceled) 
     
     
         139 . A compound of formula (X), 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 2  are each independently H, C 1 -C 6  alky], optionally substituted with 1-4 R 5 , C 2 -C 6  alkenyl, optionally substituted with 1-4 R 5 , or C(NR 6 )(NR 6 ) 2 ; 
         R 3  and R 4  are each independently alkyl, alkenyl, alkynly, each of which is optionally substituted with fluoro, chloro, bromo, or iodo; 
         L 1  and L 2  are each independently —NR 6 C(O)—, —C(O)NR 6 —, —OC(O)—, —C(O)O—, —S—S—, —N(R 6 )C(O)N(R 6 )—, —OC(O)N(R 6 )—, —N(R 6 )C(O)O—, —O—N═C—, OR, —OC(O)NH—N═C—, or —NHC(O)NH—N═C—, 
         L 1 -R 3  and L 2 -R 4  can be taken together to form an acetal, a ketal, or an orthoester, wherein 
         R 3  and R 4  are defined as above and can also be H or phenyl; 
         R 5  is fluoro, chloro, bromo, iodo, —OR 7 , —N(R 8 )(R 9 ), —CN, SR 10 , S(O)R 10 , S(O) 2 R 10    
         R 6  is H, C 1 -C 6  alkyl, 
         R 7  is H or C 1 -C 6  alkyl; 
         each R 8  and R 9  are independently H or C 1 -C 6  alkyl; 
         R 10  is H or C 1 -C 6  alkyl; 
         m is 1, 2, 3, 4, 5, or 6; 
         n is 0, 1, 2, 3, 4, 5, or 6; 
         and pharmaceutically acceptable salts thereof. 
       
     
     
         140 - 324 . (canceled) 
     
     
         325 . A compound of formula (XV) 
       
         
           
           
               
               
           
         
         wherein; 
         each L 1  and L 2  are independently a bond or C(O); 
         each R 1  and R 2  are independently alkyl alkenyl or alkynyl; each of which is optionally substituted with one or more substituents; 
         X is —C(O)NH—, —C(S)NH—, —C(O)C 1-3 alkylC(O)NH—; or —C(O)C 1-3 alkylC(O)O—; m is an integer from 0-11 and 
         n is an integer from 1-500. 
       
     
     
         326 . The compound of  claim 325 , wherein L 1  and L 2  are both a bond. 
     
     
         327 . The compound of  claim 325 , wherein L 1  and L 2  are both C(O). 
     
     
         328 . The compound of  claim 325 , wherein each R 1  and R 2  are independently alkyl. 
     
     
         329 . The compound of  claim 328 , wherein each R 1  and R 2  are independently C 6 -C 28  alkyl. 
     
     
         330 . The compound of  claim 325 , wherein both R 1  and R 2  are straight chain alkyl having the same length. 
     
     
         331 . The compound of  claim 330 , wherein both R 1  and R 2  are C 14  alkyl. 
     
     
         332 - 334 . (canceled) 
     
     
         335 . The compound of  claim 325 , wherein each R 1  and R 2  are independently alkenyl. 
     
     
         336 . (canceled) 
     
     
         337 . The compound of  claim 335 , wherein each R 1  and R 2  includes two double bond moieties. 
     
     
         338 . The compound of  claim 325 , wherein X is —C(O)NH—, providing a compound of formula (XV′) below: 
       
         
           
           
               
               
           
         
       
     
     
         339 - 341 . (canceled) 
     
     
         342 . The compound of  claim 325 , wherein the compound is a compound of formula (XV), 
       
         
           
           
               
               
           
         
         wherein both L 1  and L 2  are a bond. 
       
     
     
         343 . The compound of  claim 342 , wherein each R 1  and R 2  are independently alkyl. 
     
     
         344 . The compound of  claim 343 , wherein, both R 1  and R 2  are straight chain alkyl having the same length. 
     
     
         345 - 346 . (canceled) 
     
     
         347 . The compound of  claim 342 , wherein, the compound is a compound of formula (XV), wherein L 1  and L 2  are both bonds, R 1  and R 2  are both alkyl, and n is an integer from about 40-400. 
     
     
         348 . The compound of  claim 325 , wherein, the compound has a formula (XVI) below: 
       
         
           
           
               
               
           
         
         formula (XVI), wherein the repeating PEG moiety has an average molecular weight of 2000 with n value between 42 and 47. 
       
     
     
         349 . (canceled) 
     
     
         350 . A lipid nanoparticle comprising a compound of  claim 325 . 
     
     
         351 . The lipid nanoparticle of  claim 350 , which further comprises a therapeutic agent. 
     
     
         352 . A method for treating a patient having a disease or disorder comprising administering a therapeutically effective amount of the lipid nanoparticle of  claim 351  to the patient.