Abstract

Provided herein is an ionizable, cationic amino lipid or a pharmaceutically acceptable salt thereof. The ionizable, cationic amino lipid has: a protonatable amino head group; two lipophilic chains, wherein the protonatable amino head group has a central carbon atom to which each of the two lipophilic chains are directly bonded; at least one of the two lipophilic chains has a structure of Formula C: Provided herein is an ionizable, cationic amino lipid or a pharmaceutically acceptable salt thereof. The ionizable, cationic amino lipid has: a protonatable amino head group; two lipophilic chains, wherein the protonatable amino head group has a central carbon atom to which each of the two lipophilic chains are directly bonded; at least one of the two lipophilic chains has a structure of Formula C: wherein E is an ester in either orientation. The compounds may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acid.

IPC Classes  ?

• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
• A61K 9/51 - Nanocapsules
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 317/28 - Radicals substituted by nitrogen atoms

Abstract

Provided is lipid and methods of making such lipid, the lipid having the structure of: Provided is lipid and methods of making such lipid, the lipid having the structure of: each R is independently an alkyl of C12 to C16, each alkyl having 1 to 3 C═C double bonds, wherein at least one of the double bonds is of Z geometry; R′ is an optional alkyl; W is O, NH or NR″, wherein R″ is a C1 to C3 alkyl group, such as a methyl; X is either absent or present, and if present, X is O, NH, or the NR″; and Z is an alkylamino chain as defined by [—(CH2)m—NG1G2G3], wherein m is 1-5 and G1 and G2 are, independently, the C1 to C3 alkyl group, G3 is absent, a hydrogen or the C1 to C3 alkyl group.

IPC Classes  ?

• C07C 229/12 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
• A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant

Abstract

The present disclosure provides lipid nanoparticle for delivery of nucleic acid having an ionizable anionic lipid Further provided are ionizable anionic lipid having the structure of Formula A described herein.

IPC Classes  ?

• C07C 69/36 - Oxalic acid esters
• A61K 9/51 - Nanocapsules
• A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• C07C 69/38 - Malonic acid esters
• C07C 69/40 - Succinic acid esters
• C07C 69/42 - Glutaric acid esters
• C07C 69/708 - Ethers
• C07C 233/47 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• C07C 311/51 - Y being a hydrogen or a carbon atom
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/52 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07D 257/04 - Five-membered rings
• C07D 271/07 - 1,2,4-OxadiazolesHydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
• C07D 317/24 - Radicals substituted by singly bound oxygen or sulfur atoms esterified
• C07D 327/04 - Five-membered rings
• C07D 339/06 - Five-membered rings having the hetero atoms in positions 1 and 3, e.g. cyclic dithiocarbonates
• C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides

Abstract

Provided is lipid and methods of making such lipid having the structure of Formula A: Provided is lipid and methods of making such lipid having the structure of Formula A: each R is an alkyl having a carbon backbone of C12 to C16 having 1 to 3 C═C double bonds, at least one having Z-geometry; R′ is an optional alkyl of C2 to C24 having 0 to 3 C═C double bonds; each R, and the R′ alkyl group if present, is optionally substituted at one or more positions with a C1 to C3 alkyl; W and X are O or S; Y is absent and C1 and C2 are bonded, or Y is present and is a metheno, etheno or ethyno bridge optionally substituted with an alkylamino chain [—(CH2)m—NG1G2G3], wherein m is 1-5 and G1, G2 are, independently, C1 to C3 alkyl, G3 is absent, hydrogen or C1 to C3 alkyl, or wherein NG1G2G3 is a heterocycle; and Z and Z′ are H or alkylamino.

IPC Classes  ?

• C07D 317/28 - Radicals substituted by nitrogen atoms
• A61K 9/51 - Nanocapsules
• C07C 45/67 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by isomerisationPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by change of size of the carbon skeleton
• C07C 67/343 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisationPreparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms
• C07D 317/20 - Free hydroxyl or mercaptan
• C07D 317/24 - Radicals substituted by singly bound oxygen or sulfur atoms esterified

Abstract

Provided herein is a method for the preparation of ionizable, cationic amino lipids using a doubly alkylated nucleophilic intermediate to produce a ketone. The ketone, or a corresponding alcohol, is subjected to one or more synthesis steps to add an ionizable moiety thereto. The method can be advantageously employed for the synthesis of unsymmetrical analogues of the above lipids that would be considerably more difficult to make by alternative strategies. The method can also be used to prepare symmetrical ionizable, cationic amino lipids with fewer steps and/or with the use of fewer hazardous chemicals than known synthesis methods.

IPC Classes  ?

• C07C 227/16 - Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
• C07C 213/00 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
• C07C 213/02 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
• C07C 319/02 - Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols

Abstract

Provided herein is a method for producing an ionizable lipid that comprises: (i) reacting fatty esters in a Claisen condensation reaction in the presence of a catalyst, the Claisen condensation employing a weak base and carried out at a temperature of between −10 and 60 degrees Celsius to produce a ketoester; (ii) reacting the ketoester produced in step (i) under conditions to produce a ketone from the ketoester in one or more steps via a hydrolysis and decarboxylation of the ketoester; and (iii) preparing the ionizable lipid from the ketone thereof using one or more synthesis steps resulting in an addition of an ionizable head group moiety to (a) the ketone; or (b) an alcohol produced from an optional reduction of the ketone to produce the alcohol, thereby producing the ionizable lipid. The ionizable lipid produced in step (iii) may be formulated in a drug delivery vehicle.

IPC Classes  ?

• C07D 317/28 - Radicals substituted by nitrogen atoms
• A61K 9/51 - Nanocapsules
• C07C 29/143 - Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen-containing functional group of C=O containing groups, e.g. —COOH of ketones
• C07C 45/65 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by splitting-off hydrogen atoms or functional groupsPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by hydrogenolysis of functional groups
• C07C 227/18 - Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
• C07C 319/20 - Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups

Abstract

The present disclosure provides a lipid nanoparticle for extrahepatic delivery of mRNA, the lipid nanoparticle comprising: (i) mRNA cargo; (ii) a phosphatidylcholine lipid content of from 30 mol % to 70 mol %; (iii) a ionizable, cationic lipid content of from 5 mol % to 50 mol %; (iv) a sterol selected from cholesterol or a derivative thereof; and (v) a hydrophilic polymer-lipid conjugate that is present at a lipid content of 0.5 mol % to 5 mol. Further provided is a lipid nanoparticle comprising encapsulated mRNA and 20 to 70 mol % of a phosphatidylcholine lipid, an ionizable lipid; and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticle exhibiting at least a 10% increase in gene expression of the mRNA in vivo as measured in one or more extrahepatic organs or tissues. Further provided are methods of administration of such lipid nanoparticles.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Abstract

The present disclosure provides a lipid nanoparticle comprising encapsulated DNA vector and 30 to 60 mol % of a neutral lipid selected from sphingomyelin and a phosphatidylcholine lipid, and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticle comprising a core comprising an electron dense region and an aqueous portion surrounded at least partially by a lipid layer comprising a bilayer and the lipid nanoparticle exhibiting at least a 10% increase in gene expression in a disease site or the liver, spleen or bone marrow at any time point after 24 or 48 hours post-injection as compared to a lipid nanoparticle encapsulating DNA vector with an Onpattro-type formulation of ionizable lipid/DSPC/cholesterol/PEG-lipid at 50/10/38.5/1.5, mol:mol, wherein the gene expression is measured in an animal model by detection of green fluorescent protein (GFP) or luciferase. Further provided are methods of medical treatment and uses of such lipid nanoparticles.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
• A61K 9/51 - Nanocapsules
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Abstract

at least one of the two lipophilic chains has a structure of Formula C: wherein E is an ester in either orientation. The compounds may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acid.

IPC Classes  ?

• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
• A61K 9/51 - Nanocapsules
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 317/28 - Radicals substituted by nitrogen atoms

Abstract

The present disclosure provides a lipid nanoparticle comprising: a nucleic acid cargo molecule; sterol or a derivative thereof present at elevated content; neutral lipid; an ionizable lipid; and a hydrophilic polymer-lipid conjugate present at a content between 0.5 and 3 mol %, wherein each mol % content is relative to total lipid present in the lipid nanoparticle.

IPC Classes  ?

• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
• A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

Provided herein is an ionizable, cationic amino lipid or a pharmaceutically acceptable salt thereof. The ionizable, cationic amino lipid has: a protonatable amino head group; two lipophilic chains, wherein the protonatable amino head group has a central carbon atom to which each of the two lipophilic chains are directly bonded; at least one of the two lipophilic chains has a structure of Formula C: Formula C wherein E is an ester in either orientation. The compounds may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acid.

IPC Classes  ?

• C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• A61K 9/51 - Nanocapsules
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/30 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
• C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
• C07D 317/28 - Radicals substituted by nitrogen atoms
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

The present disclosure provides a lipid nanoparticle to treat, prevent or diagnose a central nervous system disease, disorder, trauma or injury, the lipid nanoparticle comprising: a non-cationic helper lipid; a sterol; a hydrophilic polymer-lipid conjugate; an ionizable, amino lipid having a pKa between 5.0 and 7.0; and an mRNA having a nucleic acid sequence encoding for a secretory polypeptide for treating, preventing or diagnosing the central nervous system disease, disorder, trauma or injury, the secretory polypeptide being capable of secretion from a cell of the central nervous system into a interstitial and/or cerebrospinal fluid of a subject. Further provided arc methods for administration of the lipid nanoparticles to treat, prevent or diagnose the central nervous system disease, disorder, trauma or injury and uses of such lipid nanoparticles.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

Provided herein is a lipid nanoparticle encapsulating nucleic acid and having at least 30 mol% neutral lipid, a sterol or derivative thereof and a targeting moiety anchored in a lipid layer thereof via a lipophilic moiety. Further provided are methods of using the lipid nanoparticles for targeted delivery in vivo. Such lipid nanoparticle may exhibit significantly improved delivery and targeting to extrahepatic tissues and/or organs.

IPC Classes  ?

• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
• A61K 9/51 - Nanocapsules
• A61K 47/06 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Abstract

Provided herein is a lipid nanoparticle comprising an encapsulated oligonucleotide molecule, wherein the oligonucleotide molecule is single-stranded or double-stranded and has a length of between 5 and 500 nucleotides; and 20 to 70 mol% of a neutral lipid content relative to total lipid present in the lipid nanoparticle, an ionizable lipid; a sterol; and optionally a hydrophilic polymer-lipid conjugate.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Abstract

The present disclosure relates to a sulfur-containing ionizable lipid or a pharmaceutically acceptable salt thereof that incorporates a dithioacetal or dithioketal moiety in one or more of its lipophilic chains. Further provided is a delivery vehicle, such as a lipid nanoparticle, comprising the ionizable lipid for the delivery of cargo, such as nucleic acid.

IPC Classes  ?

• C07C 323/52 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• A61K 9/51 - Nanocapsules
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07D 317/28 - Radicals substituted by nitrogen atoms
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

Provided are novel sulfur-containing lipids and nanoparticles containing such lipids and a cargo molecule, such as a nucleic acid, methods to formulate said lipids with nucleic acids to produce lipid nanoparticles and chemical routes for making said lipids. The lipids may have the structure of Formula A as defined herein. Formula A

IPC Classes  ?

• C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• A61K 9/51 - Nanocapsules
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/17 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
• C07D 317/28 - Radicals substituted by nitrogen atoms
• C07D 319/06 - 1,3-DioxanesHydrogenated 1,3-dioxanes not condensed with other rings
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

Provided are lipids and nanoparticles containing such lipids and a cargo molecule, such as nucleic acid, methods to formulate said lipids with nucleic acids to produce lipid nanoparticles and chemical routes for making the lipids. The lipids may have the structure of Formula A as defined herein.

IPC Classes  ?

• C07C 233/47 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• A61K 9/51 - Nanocapsules
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• C07C 235/12 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/60 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
• C07D 207/16 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• C07D 317/24 - Radicals substituted by singly bound oxygen or sulfur atoms esterified
• C07D 317/28 - Radicals substituted by nitrogen atoms

Abstract

The present disclosure provides a lipid nanoparticle for extrahepatic delivery of mRNA, the lipid nanoparticle comprising: (i) mRNA cargo; (ii) a phosphatidylcholine lipid content of from mol % to 70 mol %; (iii) a ionizable, cationic lipid content of from 5 mol % to 50 mol %; (iv) a sterol selected from cholesterol or a derivative thereof; and (v) a hydrophilic polymer-lipid conjugate that is present at a lipid content of 0.5 mol % to 5 mol. Further provided is a lipid nanoparticle preparation comprising lipid nanoparticles having encapsulated mRNA and 20 to mol % of a phosphatidylcholine lipid, an ionizable lipid; and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticles exhibiting at least a 10% increase in gene expression of the mRNA in vivo as measured in one or more extrahepatic organs or tissues. The lipid nanoparticles have an electron dense region and a nitrogen-to-phosphate charge ratio of between 4 and 15.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Abstract

Provided herein are novel sulfur-containing lipids having a structure of Formula A or a salt thereof. The compounds may be formulated in a lipid nanoparticle for use in the delivery of charged cargo such as nucleic acids for use in the targeting of a non-liver organ, tissue or cell. Further provided are methods for making the compounds. (Formula A)

IPC Classes  ?

• C07D 317/28 - Radicals substituted by nitrogen atoms
• A61K 9/51 - Nanocapsules
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/25 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07D 317/24 - Radicals substituted by singly bound oxygen or sulfur atoms esterified
• C07D 317/30 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Abstract

The present disclosure provides a lipid nanoparticle for extrahepatic delivery of mRNA, the lipid nanoparticle comprising: (i) mRNA cargo; (ii) a phosphatidylcholine lipid content of from 30 mol% to 70 mol%; (iii) a ionizable, cationic lipid content of from 5 mol% to 50 mol%; (iv) a sterol selected from cholesterol or a derivative thereof; and (v) a hydrophilic polymer-lipid conjugate that is present at a lipid content of 0.5 mol% to 5 mol. Further provided is a lipid nanoparticle comprising encapsulated mRNA and 20 to 70 mol% of a phosphatidylcholine lipid, an ionizable lipid; and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticle exhibiting at least a 10% increase in gene expression of the mRNA in vivo as measured in one or more extrahepatic organs or tissues. Further provided are methods of administration of such lipid nanoparticles.

IPC Classes  ?

• A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• A61K 9/51 - Nanocapsules
• A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
• A61K 47/10 - AlcoholsPhenolsSalts thereof, e.g. glycerolPolyethylene glycols [PEG]PoloxamersPEG/POE alkyl ethers
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• A61P 35/00 - Antineoplastic agents
• A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present disclosure provides a lipid nanoparticle comprising: a nucleic acid cargo molecule; sterol or a derivative thereof present at elevated content; neutral lipid; an ionizable lipid; and a hydrophilic polymer-lipid conjugate present at a content between 0.5 and 3 mol %, wherein each mol % content is relative to total lipid present in the lipid nanoparticle.

IPC Classes  ?

• A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
• A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• A61K 31/661 - Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The present disclosure provides a lipid nanoparticle comprising: a nucleic acid cargo molecule; sterol or a derivative thereof present at elevated content; neutral lipid; an ionizable lipid; and a hydrophilic polymer–lipid conjugate present at a content between 0.5 and 3 mol%, wherein each mol% content is relative to total lipid present in the lipid nanoparticle.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

Provided herein is a method for a method for producing an ionizable amino lipid, or a pharmaceutically acceptable salt thereof, the method comprising a nucleophilic displacement of a leaving group L in a compound of Formula (II), wherein G12nn, wherein n is 2 to 10, and wherein R1and R212020 alkyl having 0 to 3 double bonds, with an amino alcohol, resulting in an N-double alkylation of the amino alcohol by the compound of Formula (II) to form the ionizable amino lipid. Further provided are intermediates of Formula (II) and methods for preparing the intermediates by an esterification step.

IPC Classes  ?

• C07D 207/16 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• C07C 69/24 - Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with monohydroxylic compounds
• C07C 213/06 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
• C07C 219/06 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
• C07C 309/66 - Methanesulfonates

Abstract

The present disclosure provides a method for producing one or more intermediates for the synthesis of one or more ionizable lipids, the method comprising: (i) producing a beta-ketoacid by reacting a cyclic ester, a terminal hydroxy ester or a derivative thereof, a dicarboxylic acid half ester, or an acid chloride derivative of the dicarboxylic acid half ester, in a condensation reaction, thereby producing the beta-ketoacid or a beta-ketoester that is hydrolyzed to produce the beta-ketoacid and (ii) decarboxylating the beta-ketoacid, thereby producing the one or more intermediates, wherein the one or more intermediates have a structure that may be defined by Formula A. Further provided is a method for producing an ionizable lipid from the intermediate comprising adding an ionizable head group moiety to (a) a ketone group of one or more intermediates having the structure that may be defined by Formula A; or (b) a corresponding alcohol of the intermediate.

IPC Classes  ?

• C07C 45/57 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds from heterocyclic compounds with oxygen as the only hetero atom
• C07C 49/17 - Saturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Goods & Services

Lipid-based delivery vehicle preparations in the form of lipid formulations that facilitate the delivery of nucleic acid for the diagnosis, treatment or prevention of diseases and disorders, namely, cancer, infectious diseases, genetic disorders, inflammation and immunological disorders associated with aging

Abstract

The disclosure provides a compact and high-rate bioreactor for wastewater treatment comprising a feeding port for introducing a feed of waste material, a reaction zone in liquid communication with the feed port when the bioreactor is in operation and having an aerator to provide an airlift configuration in the reaction zone; a settling zone comprising a separator for separating a liquid effluent from solid particles; a liquid effluent outlet port for withdrawing the liquid effluent; and a solids outlet port for removing solids. Further provided is a spiral separator for use in a bioreactor and a system comprising the bioreactor and a membrane separator to provide hygienic water.

IPC Classes  ?

• C02F 3/22 - Activated sludge processes using circulation pipes
• C02F 3/30 - Aerobic and anaerobic processes
• C02F 1/44 - Treatment of water, waste water, or sewage by dialysis, osmosis or reverse osmosis

Goods & Services

(1) Lipids for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid, namely RNA and DNA, for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; proteins and peptides for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; chemical ingredients, namely small molecule drugs for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging. (2) Lipid-based pharmaceuticals, namely lipid-based delivery vehicles for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging. (1) Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals. (2) Providing pharmaceutical, lipid, nucleic acid and drug review services; providing pharmaceutical information to others; providing formulation development services; provision of pharmaceutical formulation information; provision of lipid formulation information and services; provision of nucleic acid pharmaceutical information and services, namely RNA and DNA; provision of small molecule, protein, and peptide pharmaceutical information; providing pharmacological information and services for lipids, nucleic acids, small molecule drugs, proteins, and peptides; providing diagnostic information and services in relation to lipid formulations.

Abstract

The present disclosure provides a lipid nanoparticle comprising encapsulated DNA vector and 30 to 60 mol% of a neutral lipid selected from sphingomyelin and a phosphatidylcholine lipid, and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticle comprising a core comprising an electron dense region and an aqueous portion surrounded at least partially by a lipid layer comprising a bilayer and the lipid nanoparticle exhibiting at least a 10% increase in gene expression in a disease site or the liver, spleen or bone marrow at any time point after 24 or 48 hours post-injection as compared to a lipid nanoparticle encapsulating DNA vector with an Onpattro-type formulation of ionizable lipid/DSPC/cholesterol/PEG-lipid at 50/10/38.5/1.5, mol:mol, wherein the gene expression is measured in an animal model by detection of green fluorescent protein (GFP) or luciferase. Further provided are methods of medical treatment and uses of such lipid nanoparticles.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 31/12 - Antivirals
• A61P 35/00 - Antineoplastic agents
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
• C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Abstract

The present disclosure provides a lipid nanoparticle comprising encapsulated DNA vector and 30 to 60 mol% of a neutral lipid selected from sphingomyelin and a phosphatidylcholine lipid, and at least one of a sterol and a hydrophilic polymer-lipid conjugate, the lipid nanoparticle comprising a core comprising an electron dense region and an aqueous portion surrounded at least partially by a lipid layer comprising a bilayer and the lipid nanoparticle exhibiting at least a 10% increase in gene expression in a disease site or the liver, spleen or bone marrow at any time point after 24 or 48 hours post-injection as compared to a lipid nanoparticle encapsulating DNA vector with an Onpattro-type formulation of ionizable lipid/DSPC/cholesterol/PEG-lipid at 50/10/38.5/1.5, mol:mol, wherein the gene expression is measured in an animal model by detection of green fluorescent protein (GFP) or luciferase. Further provided are methods of medical treatment and uses of such lipid nanoparticles.

IPC Classes  ?

• A61K 9/51 - Nanocapsules
• C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 31/12 - Antivirals
• A61P 35/00 - Antineoplastic agents
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Abstract

Provided is lipid and methods of making such lipid having the structure of Formula A: each R is an alkyl having a carbon backbone of C12 to C16 having 1 to 3 C=C double bonds, at least one having Z-geometry; R' is an optional alkyl of C2 to C24 having 0 to 3 C=C double bonds; each R, and the R' alkyl group if present, is optionally substituted at one or more positions with a C1 to C3 alkyl; W and X are O or S; Y is absent and C1 and C2 are bonded, or Y is present and is a metheno, etheno or ethyno bridge optionally substituted with an alkylamino chain [-(CH2)m-NG1G2G3], wherein m is 1-5 and G1, G2 are, independently, C1 to C3 alkyl, G3 is absent, hydrogen or C1 to C3 alkyl, or wherein NG1G2G3 is a heterocycle; and Z and Z' are H or alkylamino.

IPC Classes  ?

• C07D 317/22 - Radicals substituted by singly bound oxygen or sulfur atoms etherified

Abstract

Provided herein is a method for producing an ionizable lipid that comprises: (i) reacting fatty esters in a Claisen condensation reaction in the presence of a catalyst, the Claisen condensation employing a weak base and carried out at a temperature of between -10 and 60 degrees Celsius to produce a ketoester; (ii) reacting the ketoester produced in step (i) under conditions to produce a ketone from the ketoester in one or more steps via a hydrolysis and decarboxylation of the ketoester; and (iii) preparing the ionizable lipid from the ketone thereof using one or more synthesis steps resulting in an addition of an ionizable head group moiety to (a) the ketone; or (b) an alcohol produced from an optional reduction of the ketone to produce the alcohol, thereby producing the ionizable lipid. The ionizable lipid produced in step (iii) may be formulated in a drug delivery vehicle.

IPC Classes  ?

• C07C 323/23 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
• A61K 9/51 - Nanocapsules
• A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• C07C 45/65 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by splitting-off hydrogen atoms or functional groupsPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by hydrogenolysis of functional groups
• C07C 49/203 - Unsaturated compounds containing keto groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
• C07C 69/42 - Glutaric acid esters
• C07C 229/12 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/22 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• C07C 323/52 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07D 323/52 -
• C07D 317/24 - Radicals substituted by singly bound oxygen or sulfur atoms esterified
• C07D 317/28 - Radicals substituted by nitrogen atoms
• C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
• C11C 3/00 - Fats, oils or fatty acids obtained by chemical modification of fats, oils or fatty acids, e.g. by ozonolysis
• C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Abstract

1216 2241 33 alkyl; W and X are O or S; Y is absent and C1and C22mm-NG1G2G3], wherein m is 1-5 and G1, G213 3 alkyl, G313 3 alkyl, or wherein NG1G2G3 is a heterocycle; and Z and Z' are H or alkylamino.

IPC Classes  ?

• C07D 317/22 - Radicals substituted by singly bound oxygen or sulfur atoms etherified
• A61K 9/14 - Particulate form, e.g. powders
• A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones

Abstract

1216 132mm-NG1G2G3], wherein m is 1-5, G1and G21-31-3 alkyl, and G31-31-3 alkyl, or absent). Such lipids are useful in the preparation of delivery vehicles for siRNA and other pharmaceutical substances. In select embodiments, such delivery vehicles take the form of lipid nanoparticles.

IPC Classes  ?

• C07C 229/12 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
• A61K 9/14 - Particulate form, e.g. powders
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids

Abstract

MC-3 type lipids and methods of preparing such lipids are provided. The lipids take the form of Formula (A) (wherein each R is independently an alkylene of C12 to C16 having 1 to 3 C=C double bonds, wherein at least one of the double bonds is of Z geometry; R' is an optional alkyl; W is O, NH, or NR", wherein R" is a C1 to C3 alkyl group; X is O, NH, NR", or is absent; and Z is [-(CH2)m-NG1G2G3], wherein m is 1-5, G1 and G2 independently are C1-3 alkyl, and G3 is hydrogen, C1-3 alkyl, or absent). Such lipids are useful in the preparation of delivery vehicles for siRNA and other pharmaceutical substances. In select embodiments, such delivery vehicles take the form of lipid nanoparticles.

IPC Classes  ?

• C07C 229/12 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids

Abstract

Provided herein is a method for producing an ionizable lipid that comprises: (i) reacting fatty esters in a Claisen condensation reaction in the presence of a catalyst, the Claisen condensation employing a weak base and carried out at a temperature of between -10 and 60 degrees Celsius to produce a ketoester; (ii) reacting the ketoester produced in step (i) under conditions to produce a ketone from the ketoester in one or more steps via a hydrolysis and decarboxylation of the ketoester; and (iii) preparing the ionizable lipid from the ketone thereof using one or more synthesis steps resulting in an addition of an ionizable head group moiety to (a) the ketone; or (b) an alcohol produced from an optional reduction of the ketone to produce the alcohol, thereby producing the ionizable lipid. The ionizable lipid produced in step (iii) may be formulated in a drug delivery vehicle.

IPC Classes  ?

• C07C 323/23 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
• A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• C07C 45/65 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by splitting-off hydrogen atoms or functional groupsPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by hydrogenolysis of functional groups
• C07C 49/203 - Unsaturated compounds containing keto groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
• C07C 69/42 - Glutaric acid esters
• C07C 229/12 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
• C07C 323/12 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07C 323/22 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
• C07C 323/52 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
• C07D 317/24 - Radicals substituted by singly bound oxygen or sulfur atoms esterified
• C07D 317/28 - Radicals substituted by nitrogen atoms
• C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle

Goods & Services

Lipids for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid, namely rna and dna, for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; proteins and peptides for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; chemical ingredients, namely small molecule drugs for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging. Lipid-based pharmaceuticals, namely lipid-based delivery vehicles for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely dna- and rna-based pharmaceuticals for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging. Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals; providing formulation development services. Providing pharmaceutical, lipid, nucleic acid and drug review services; providing pharmaceutical information to others; provision of pharmaceutical formulation information; provision of lipid formulation information and services; provision of nucleic acid pharmaceutical information and services, namely rna and dna; provision of small molecule, protein, and peptide pharmaceutical information; providing pharmacological information and services for lipids, nucleic acids, small molecule drugs, proteins, and peptides; providing diagnostic information and services in relation to lipid formulations.

Goods & Services

Lipid-based pharmaceuticals, namely, lipid-based drug delivery vehicle preparations in the form of lipid formulations that facilitate the delivery of pharmaceuticals for the diagnosis, treatment or prevention of diseases and disorders, namely, cancer, infectious diseases, genetic disorders, inflammation and immunological disorders, and for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely, DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases and disorders, namely, cancers, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of cancer, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of cancer, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals; pharmaceutical formulation development services

Goods & Services

Lipid-based pharmaceuticals, namely, lipid-based drug delivery vehicle preparations in the form of lipid formulations that facilitate the delivery of pharmaceuticals for the diagnosis, treatment or prevention of diseases and disorders, namely, cancer, infectious diseases, genetic disorders, inflammation and immunological disorders, and for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely, DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases and disorders, namely, cancers, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of cancer, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of cancer, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals; pharmaceutical formulation development services

Goods & Services

Lipid-based pharmaceuticals, namely, lipid-based drug delivery vehicle preparations in the form of lipid formulations that facilitate the delivery of pharmaceuticals for the diagnosis, treatment or prevention of diseases and disorders, namely, cancer, infectious diseases, genetic disorders, inflammation and immunological disorders, and for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely, DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases and disorders, namely, cancers, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of cancer, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of cancer, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals; pharmaceutical formulation development services

Goods & Services

Lipid-based pharmaceuticals, namely, lipid-based drug delivery vehicle preparations in the form of lipid formulations that facilitate the delivery of pharmaceuticals for the diagnosis, treatment or prevention of diseases and disorders, namely, cancer, infectious diseases, genetic disorders, inflammation and immunological disorders, and for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely, DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases and disorders, namely, cancers, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of cancer, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of cancer, infectious diseases, genetic disorders, inflammation and immunological disorders and for reducing symptoms associated with aging Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals; pharmaceutical formulation development services

Goods & Services

(1) Lipids for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid, namely RNA and DNA, for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; proteins and peptides for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; chemical ingredients, namely small molecule drugs for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging. (2) Lipid-based pharmaceuticals, namely lipid-based delivery vehicles for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging. (1) Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals. (2) Providing pharmaceutical, lipid, nucleic acid and drug review services; providing pharmaceutical information to others; providing formulation development services; provision of pharmaceutical formulation information; provision of lipid formulation information and services; provision of nucleic acid pharmaceutical information and services, namely RNA and DNA; provision of small molecule, protein, and peptide pharmaceutical information; providing pharmacological information and services for lipids, nucleic acids, small molecule drugs, proteins, and peptides; providing diagnostic information and services in relation to lipid formulations.

Goods & Services

(1) Lipids for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid, namely RNA and DNA, for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; proteins and peptides for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; chemical ingredients, namely small molecule drugs for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging. (2) Lipid-based pharmaceuticals, namely lipid-based delivery vehicles for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging. (1) Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals. (2) Providing pharmaceutical, lipid, nucleic acid and drug review services; providing pharmaceutical information to others; providing formulation development services; provision of pharmaceutical formulation information; provision of lipid formulation information and services; provision of nucleic acid pharmaceutical information and services, namely RNA and DNA; provision of small molecule, protein, and peptide pharmaceutical information; providing pharmacological information and services for lipids, nucleic acids, small molecule drugs, proteins, and peptides; providing diagnostic information and services in relation to lipid formulations.

Goods & Services

(1) Lipids for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid, namely RNA and DNA, for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; proteins and peptides for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; chemical ingredients, namely small molecule drugs for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging. (2) Lipid-based pharmaceuticals, namely lipid-based delivery vehicles for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging. (1) Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals. (2) Providing pharmaceutical, lipid, nucleic acid and drug review services; providing pharmaceutical information to others; providing formulation development services; provision of pharmaceutical formulation information; provision of lipid formulation information and services; provision of nucleic acid pharmaceutical information and services, namely RNA and DNA; provision of small molecule, protein, and peptide pharmaceutical information; providing pharmacological information and services for lipids, nucleic acids, small molecule drugs, proteins, and peptides; providing diagnostic information and services in relation to lipid formulations.

Goods & Services

(1) Lipids for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid, namely RNA and DNA, for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; proteins and peptides for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging; chemical ingredients, namely small molecule drugs for use in the manufacture of pharmaceuticals for the treatment or prevention of diseases or for reducing symptoms associated with aging. (2) Lipid-based pharmaceuticals, namely lipid-based delivery vehicles for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; nucleic acid-based pharmaceuticals, namely DNA- and RNA-based pharmaceuticals for the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; small molecule pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging; protein- and peptide-based pharmaceuticals for use in the diagnosis, treatment or prevention of diseases or for reducing symptoms associated with aging. (1) Pharmaceutical research and development services; pharmaceutical drug development services; providing medical and scientific research information in the field of pharmaceuticals. (2) Providing pharmaceutical, lipid, nucleic acid and drug review services; providing pharmaceutical information to others; providing formulation development services; provision of pharmaceutical formulation information; provision of lipid formulation information and services; provision of nucleic acid pharmaceutical information and services, namely RNA and DNA; provision of small molecule, protein, and peptide pharmaceutical information; providing pharmacological information and services for lipids, nucleic acids, small molecule drugs, proteins, and peptides; providing diagnostic information and services in relation to lipid formulations.