| abstract |
NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS Abstract: The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure (I) wherein R, and R2 are each independently for each occurrence optionally substituted Cio-C 30 alkyl, optionally substituted C1 0 -C 30 alkenyl, optionally substituted C 10-C30 alkynyl, optionally substituted C1 0-C 30 acyl, or -linker-ligand; R3 is H, optionally substituted C1 -Cio alkyl, optionally substituted C2 -C1 0 alkenyl, optionally substituted C2-Cio alkynyl, alkylheterocycle, alkylphosphate,alkylphosphorothioate,alkylphosphorodithioate,alkylphosphonates,alkylamines, hydroxyalkyls, w-aminoalkyls, (o-(substituted)aminoalkyls, o-phosphoalkyls, to o thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is 0, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(0) 2N(Q), S(0) 2 , N(Q)S(0) 2 , SS, O=N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, o-aminoalkyl, o-(substituted)aminoalkyl, o-phosphoalkyl or o-thiophosphoalkyl. Figure t. R P= 0 n=i1AO X= NH(CO), {CO)NH, NH(CO)O O(CO)NH, 0, NH(CO)NH, S-S = COH,.-(C- 2)1 0 -, Y= (CA 1)R- Ga(NAc, Mannose, Lactose, Glucose, Fucose Y= (CH2)- (GalNAc), (Mannose)2 ,(Lactose)2 , (Glucose) (Fucose)2 Y= (CH2)n- (GalNAc), (Mannose),(Laose) 3.(Glucose), (Fucose), Y= (CH 2CrO)-GaNAc, Mannose, Lactose, Glucose, Fucose Y= (CHrCHrO)a- (GaINAc)2 , (Mannose)h,(Lactose, (Glucosa)2 , (Fucose)a Y= (C(4-lCH 2 O)a- (GaNAc) 3, (Mannose),( Lactose), (GkRcose), (Fucose) 3 n ~n= 1-10 X= N(CO),(CO)NF.fl)O O(CO)NH 0, NH(CO)NH, -S Y= (CI)n- GalNA, Mannose, Laclose, Glucose, Fucose Y= (CH12)n-IGalNAc), (Mannose),.(Lactose), (Glucose 2, (Fucosez Y= (CH)n- (GNAc)3, (Manrosa),(Lacose)3 , (Grucoseh, (Fucose)3 Y= (C142-CH 2-)a- GANAc, Mannose, Lartoss, Glucose, Fucoen Y= (CH-Crl2-0)a- (GalNAc) (Mannose)z,(Lactose, (Glucose) 2 (Fucase) Y= (C-H2 -rO)a- (GaINAc), (Mannose),(Lactose)3.(Glucose), (Fucose)3 a - 1-100 |