Ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, the compounds, compositions and methods are to provide nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.

Ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, the compounds, compositions and methods are to provide nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.

This invention includes ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.

This invention includes ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.

This disclosure relates to flavour modification and to compounds of formula (I) or edible salts thereof, ##STR00001## wherein R.sup.1 is selected from C.sub.6-C.sub.20 alkyl, and C.sub.9-C.sub.25 alkenyl, and i) R.sup.3 and R.sup.4 are hydrogen and R.sup.2 the residue of a proteinogenic amino acid; ii) R.sup.2 and R.sup.3 are methyl and R.sup.4 is hydrogen; or R.sup.4 is hydrogen and R.sup.2 and R.sup.3 form together with the carbon atom to which they are attached cyclopropyl; iii) R.sup.2 is hydrogen, and R.sup.3 and R.sup.4 together are —CH.sub.2—CH.sub.2—CH.sub.2— useful in modifying flavours.

This disclosure relates to flavour modification and to compounds of formula (I) or edible salts thereof, ##STR00001## wherein R.sup.1 is selected from C.sub.6-C.sub.20 alkyl, and C.sub.9-C.sub.25 alkenyl, and i) R.sup.3 and R.sup.4 are hydrogen and R.sup.2 the residue of a proteinogenic amino acid; ii) R.sup.2 and R.sup.3 are methyl and R.sup.4 is hydrogen; or R.sup.4 is hydrogen and R.sup.2 and R.sup.3 form together with the carbon atom to which they are attached cyclopropyl; iii) R.sup.2 is hydrogen, and R.sup.3 and R.sup.4 together are —CH.sub.2—CH.sub.2—CH.sub.2— useful in modifying flavours.

The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.

The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.

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.sub.1 and R.sub.2 are each independently for each occurrence optionally substituted C.sub.10-C.sub.30 alkyl, optionally substituted C.sub.10-C.sub.30 alkenyl, optionally substituted C.sub.10-C.sub.30 alkynyl, optionally substituted C.sub.10-C.sub.30 acyl, or -linker-ligand; R.sub.3 is H, optionally substituted C.sub.1-C.sub.10 alkyl, optionally substituted C.sub.2-C.sub.10 alkenyl, optionally substituted C.sub.2-C.sub.10 alkynyl, alkylheterocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)2N(Q), S(O)2, N(Q)S(O)2, SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ω-aminoalkyl, ω-(substituted)aminoalkyl, ω-phosphoalkyl or ω-thiophosphoalkyl.

##STR00001##

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.sub.1 and R.sub.2 are each independently for each occurrence optionally substituted C.sub.10-C.sub.30 alkyl, optionally substituted C.sub.10-C.sub.30 alkenyl, optionally substituted C.sub.10-C.sub.30 alkynyl, optionally substituted C.sub.10-C.sub.30 acyl, or -linker-ligand; R.sub.3 is H, optionally substituted C.sub.1-C.sub.10 alkyl, optionally substituted C.sub.2-C.sub.10 alkenyl, optionally substituted C.sub.2-C.sub.10 alkynyl, alkylheterocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)2N(Q), S(O)2, N(Q)S(O)2, SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ω-aminoalkyl, ω-(substituted)aminoalkyl, ω-phosphoalkyl or ω-thiophosphoalkyl.

##STR00001##