WO2010129709A1 - Lipid compositions - Google Patents
Lipid compositions Download PDFInfo
- Publication number
- WO2010129709A1 WO2010129709A1 PCT/US2010/033777 US2010033777W WO2010129709A1 WO 2010129709 A1 WO2010129709 A1 WO 2010129709A1 US 2010033777 W US2010033777 W US 2010033777W WO 2010129709 A1 WO2010129709 A1 WO 2010129709A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lipid
- composition
- peg
- alkyl
- formula
- Prior art date
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- 150000002632 lipids Chemical class 0.000 title claims abstract description 413
- 239000000203 mixture Substances 0.000 title claims abstract description 330
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- 150000003432 sterols Chemical class 0.000 claims abstract description 47
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- 125000000217 alkyl group Chemical group 0.000 claims description 104
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- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims description 25
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- A61K48/0033—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being non-polymeric
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- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- B is NR or a cyclic moiety optionally substituted with 1-2 R;
- composition comprising a compound of formula (I) formula (I) wherein each X a and X b , for each occurrence, is independently Ci_ 6 alkylene; n is O, 1, 2, 3, 4, or 5;
- R for at least 3 occurrences, is .
- R is , and R alkyl optionally substituted with one or more substituent (e.g., a hydrophilic substituent).
- the composition includes a compound of formula (VII):
- the targeting lipid includes a PEG moiety (e.g., a PEG moiety having a molecular weight of at least about 500 Da, such as about 1000 Da, 1500 Da, 2000 Da or greater), for example, the targeting moiety is connected to the lipid via a PEG moiety.
- a PEG moiety e.g., a PEG moiety having a molecular weight of at least about 500 Da, such as about 1000 Da, 1500 Da, 2000 Da or greater
- a variant can comprise a protein or peptide having a substantially identical amino acid sequence to a native apolipoprotein provided herein in which one or more amino acid residues have been conservatively substituted with chemically similar amino acids.
- conservative substitutions include the substitution of at least one hydrophobic residue such as isoleucine, valine, leucine or methionine for another.
- the present invention contemplates, for example, the substitution of at least one hydrophilic residue such as, for example, between arginine and lysine, between glutamine and asparagine, and between glycine and serine (see U.S. Pat. Nos. 6,004,925, 6,037,323 and 6,046,166).
- the apolipoprotein is obtained from natural sources, it can be obtained from a plant or animal source. If the apolipoprotein is obtained from an animal source, the apolipoprotein can be from any species. In certain embodiments, the apolipoprotien can be obtained from an animal source. In certain embodiments, the apolipoprotein can be obtained from a human source. In preferred embodiments of the invention, the apolipoprotein is derived from the same species as the individual to which the apolipoprotein is administered.
- Alkyl means a straight chain or branched, noncyclic or cyclic, saturated aliphatic hydrocarbon containing from 1 to 24 carbon atoms.
- Representative saturated straight chain alkyls include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, and the like; while saturated branched alkyls include isopropyl, sec -butyl, isobutyl, tert- butyl, isopentyl, and the like.
- Alkenyl means an alkyl, as defined above, containing at least one double bond between adjacent carbon atoms. Alkenyls include both cis and trans isomers. Representative straight chain and branched alkenyls include ethylenyl, propylenyl, 1- butenyl, 2-butenyl, isobutylenyl, 1-pentenyl, 2-pentenyl, 3-methyl-l-butenyl, 2- methyl-2-butenyl, 2,3-dimethyl-2-butenyl, and the like.
- Scheme 10 depicts an alternate route to a protected ⁇ -hydroxy aldehyde 11, starting from (R)-glycidol.
- a ligand such as an antibody, for targeting the lipid particle is linked to the polar head group of lipids forming the lipid particle.
- Standard methods for coupling the target agents can be used.
- phosphatidylethanolamine which can be activated for attachment of target agents
- derivatized lipophilic compounds such as lipid-derivatized bleomycin
- Antibody-targeted liposomes can be constructed using, for instance, liposomes that incorporate protein A (see, Renneisen, et al., J. Bio. Chem., 265:16337-16342 (1990) and Leonetti, et al, Proc. Natl. Acad. Sci. (USA), 87:2448-2451 (1990).
- Other examples of antibody conjugation are disclosed in U.S. Patent No.
- Ribozymes may be designed as described in Int. Pat. Appl. Publ. No. WO 93/23569 and Int. Pat. Appl. Publ. No. WO 94/02595, each specifically incorporated herein by reference, and synthesized to be tested in vitro and in vivo, as described therein.
- nucleotide overhang refers to the unpaired nucleotide or nucleotides that protrude from the duplex structure of a dsRNA when a 3 '-end of one strand of the dsRNA extends beyond the 5'-end of the other strand, or vice versa.
- Bount or “blunt end” means that there are no unpaired nucleotides at that end of the dsRNA, i.e., no nucleotide overhang.
- a “blunt ended" dsRNA is a dsRNA that is double-stranded over its entire length, i.e., no nucleotide overhang at either end of the molecule.
- treat refers to relief from or alleviation of a disease or disorder.
- the terms “treat,” “treatment,” and the like mean to relieve or alleviate at least one symptom associated with such condition, or to slow or reverse the progression of such condition.
- Sonicating a liposome suspension either by bath or probe sonication produces a progressive size reduction down to small unilamellar vesicles (SUVs) less than about 0.05 microns in size.
- Homogenization is another method which relies on shearing energy to fragment large liposomes into smaller ones.
- multilamellar vesicles are recirculated through a standard emulsion homogenizer until selected liposome sizes, typically between about 0.1 and 0.5 microns, are observed.
- the particle size distribution can be monitored by conventional laser-beam particle size determination.
- extrusion is used to obtain a uniform vesicle size.
- the nucleic acid may be, e.g., an antisense oligonucleotide, siRNA, or microRNA that comprises a polynucleotide sequence that specifically hybridizes to a polnucleotide that encodes the target polypeptide, thereby disrupting expression of the target polynucleotide or polypeptide.
- the nucleic acid may be a plasmid that expresses such an antisense oligonucletoide, siRNA, or microRNA.
- antigens suitable for use in the invention include, but are not limited to, polypeptide antigens and DNA antigens.
- Specific examples of antigens are Hepatitis A, Hepatitis B, small pox, polio, anthrax, influenza, typhus, tetanus, measles, rotavirus, diphtheria, pertussis, tuberculosis, and rubella antigens.
- the antigen is a Hepatitis B recombinant antigen.
- the dosage unit can also be compounded for delivery over several days, e.g., using a conventional sustained release formulation which provides sustained release of the dsRNA over a several day period.
- Sustained release formulations are well known in the art and are particularly useful for vaginal delivery of agents, such as could be used with the agents of the invention.
- the dosage unit contains a corresponding multiple of the daily dose.
- the target genes may be components of a same biological pathway (e.g., immune response such as an antiviral response, apoptosis, cholesterol metabolism), or may be components of distinct biological pathways.
- the target genes can include a gene that is not from the subject (e.g., a viral gene).
- the lipid composition comprises at least one cationic lipid described herein.
- the lipid composition can further comprise a PEG- or PEG-modified lipid.
- the lipid composition further comprises a sterol (e.g., cholesterol).
- the lipid composition further comprises a neutral lipid.
Abstract
Description
Claims
Priority Applications (26)
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EP10772790.1A EP2416760A4 (en) | 2009-05-05 | 2010-05-05 | Lipid compositions |
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JP2012509956A JP5769701B2 (en) | 2009-05-05 | 2010-05-05 | Lipid composition |
KR1020217007578A KR20210031549A (en) | 2009-05-05 | 2010-05-05 | Lipid compositions |
CA2760776A CA2760776C (en) | 2009-05-05 | 2010-05-05 | Lipid compositions for the delivery of therapeutic agents |
KR1020187023298A KR20180094137A (en) | 2009-05-05 | 2010-05-05 | Lipid compositions |
CN201080020203.7A CN102421417B (en) | 2009-05-05 | 2010-05-05 | Lipid composition |
SG2011081130A SG176553A1 (en) | 2009-05-05 | 2010-05-05 | Lipid compositions |
IL216142A IL216142A (en) | 2009-05-05 | 2011-11-03 | Lipid compositions |
US14/508,805 US9694077B2 (en) | 2009-05-05 | 2014-10-07 | Lipid compositions |
AU2017200272A AU2017200272A1 (en) | 2009-05-05 | 2017-01-16 | Lipid compositions |
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US15/594,244 US10456473B2 (en) | 2009-05-05 | 2017-05-12 | Lipid compositions |
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AU2022202352A AU2022202352A1 (en) | 2009-05-05 | 2022-04-08 | Lipid compositions |
US18/110,654 US20240066129A1 (en) | 2009-05-05 | 2023-02-16 | Lipid compositions |
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