WO2004035523B1 - Cationic cardiolipin analogs and use thereof - Google Patents
Cationic cardiolipin analogs and use thereofInfo
- Publication number
- WO2004035523B1 WO2004035523B1 PCT/US2003/033099 US0333099W WO2004035523B1 WO 2004035523 B1 WO2004035523 B1 WO 2004035523B1 US 0333099 W US0333099 W US 0333099W WO 2004035523 B1 WO2004035523 B1 WO 2004035523B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- cationic cardiolipin
- composition
- analog
- cationic
- Prior art date
Links
- -1 Cationic cardiolipin analogs Chemical class 0.000 title claims abstract 64
- 238000000034 method Methods 0.000 claims abstract 55
- 239000000203 mixture Substances 0.000 claims abstract 52
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- 108091033319 polynucleotide Proteins 0.000 claims 29
- 102000040430 polynucleotide Human genes 0.000 claims 29
- 239000002157 polynucleotide Substances 0.000 claims 29
- 125000002091 cationic group Chemical group 0.000 claims 23
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 claims 23
- 239000000825 pharmaceutical preparation Substances 0.000 claims 21
- 239000013543 active substance Substances 0.000 claims 16
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims 8
- 201000010099 disease Diseases 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 238000001890 transfection Methods 0.000 claims 5
- 108091030071 RNAI Proteins 0.000 claims 4
- 239000003153 chemical reaction reagent Substances 0.000 claims 4
- 230000009368 gene silencing by RNA Effects 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 108020005544 Antisense RNA Proteins 0.000 claims 3
- 108090000994 Catalytic RNA Proteins 0.000 claims 3
- 102000053642 Catalytic RNA Human genes 0.000 claims 3
- 208000036142 Viral infection Diseases 0.000 claims 3
- 239000003184 complementary RNA Substances 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 3
- 239000005556 hormone Substances 0.000 claims 3
- 229940088597 hormone Drugs 0.000 claims 3
- 238000000338 in vitro Methods 0.000 claims 3
- 238000001727 in vivo Methods 0.000 claims 3
- 230000002452 interceptive effect Effects 0.000 claims 3
- 102000039446 nucleic acids Human genes 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 150000007523 nucleic acids Chemical class 0.000 claims 3
- 229920001184 polypeptide Polymers 0.000 claims 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims 3
- 108091092562 ribozyme Proteins 0.000 claims 3
- 230000009385 viral infection Effects 0.000 claims 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 2
- 230000000840 anti-viral effect Effects 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 229940041181 antineoplastic drug Drugs 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 230000002950 deficient Effects 0.000 claims 2
- 230000002163 immunogen Effects 0.000 claims 2
- 239000000463 material Substances 0.000 claims 2
- 239000002777 nucleoside Substances 0.000 claims 2
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 2
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims 2
- IPVFGAYTKQKGBM-BYPJNBLXSA-N 1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione Chemical compound F[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 IPVFGAYTKQKGBM-BYPJNBLXSA-N 0.000 claims 1
- GIMSJJHKKXRFGV-BYPJNBLXSA-N 4-amino-1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidin-2-one Chemical compound C1=C(I)C(N)=NC(=O)N1[C@H]1[C@@H](F)[C@H](O)[C@@H](CO)O1 GIMSJJHKKXRFGV-BYPJNBLXSA-N 0.000 claims 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 claims 1
- 208000009889 Herpes Simplex Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 claims 1
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 claims 1
- 229960004150 aciclovir Drugs 0.000 claims 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims 1
- 239000000074 antisense oligonucleotide Substances 0.000 claims 1
- 238000012230 antisense oligonucleotides Methods 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 229960002963 ganciclovir Drugs 0.000 claims 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims 1
- 238000001415 gene therapy Methods 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 230000000699 topical effect Effects 0.000 claims 1
- 239000002502 liposome Substances 0.000 abstract 2
- 208000031295 Animal disease Diseases 0.000 abstract 1
- 239000008186 active pharmaceutical agent Substances 0.000 abstract 1
- 238000003556 assay Methods 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 238000012637 gene transfection Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
- A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Virology (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention provides cationic cardiolipin compounds, and methods for synthesizing and using them in liposomal formulation, gene transfection, etc. In particular, the invention provides liposomes comprising cationic cardiolipin analog, pharmaceutical compositions comprising cationic cardiolipin analogs, and methods of using such liposomes and compositions, in delivering active pharmaceutical agents to treat human and animal diseases and/or in diagnostic assays.
Claims
65
AMENDED CLAIMS
[received by the International Bureau on 19 May 2004 (19.05.2004); original claims 99-134 amended; new claims 135-202 added; remaining claims unchanged (9 pages)]
83. The preparation of claim 71, wherein said polynucleotide codes for an immunogenic peptide, a natural hormone, or a synthetic analogue of a natural hormone.
84. The preparation of claim 71, wherein said polynucleotide is deficient or absent in a disease state.
85. The preparation of claim 71, wherein said polynucleotide codes for a therapeutic polypeptide.
86. The preparation of claim 85, wherein said poypeptide is deficient or absent in a disease state.
87. The preparation of claim 85, wherein said polypeptide is a natural hormone or a synthetic analog thereof.
88. The preparation of claim 85, wherein said polypeptide is an immunogen.
89. The preparation of claim 60, wherein said active agent is a drug.
90. The preparation of claim 89, wherein said active agent is an anticancer drug.
91. The preparation of claim 69, wherein said active agent is a monoclonal antibody or a fragment thereof.
92. The preparation of claim 60, wherein said active agent is a bioaclive lipid.
93. The preparation of any of claims 59-92, which is a pharmaceutical preparation comprising one or more pharmaceutically acceptable carriers.
94. The pharmaceutical preparation of claim 93, which is formulated for topical administration.
95. The pharmaceutical preparation of claim 94, which is formulated for administration to the skin or to a mucosal surface.
96. The pharmaceutical preparation of claim 93, which is formulated for parenteral administration.
97. The pharmaceutical preparation of claim 93, which is formulated for oral administration.
98. The pharmaceutical preparation of any of claims 93-97, comprising a plurality of active agents.
99. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula I.
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100. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula II.
101. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula HI.
102. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula IV.
103. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula N.
104. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula VI.
105. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula VTI.
106. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula NHL
107. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula IX.
108. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula X.
109. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula XI.
110. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula XH.
111. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula XIII.
112. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula XIN.
113. The pharmaceutical preparation of any of claims 93-98, wherein the cationic cardiolipin analog has the structure of formula XV.
114. A method of treating a disease in a vertebrate, comprising the step of administering a composition comprising the preparation of any of claims 59-113 to a vertebrate in need of treatment in an amount and at a location sufficient to treat the disease within the vertebrate.
67
115. The method of claim 114, comprising the administration of said composition to the cells of said vertebrate in vitro, which cells are then returned to said vertebrate.
116. The method of claim 114, comprising the administration of said composition to the cells of said vertebrate in vivo.
117. The method of claim 116, comprising the topical application of said composition to the skin or to a mucosal surface.
118. The method of claim 116, comprising the injection of said body cavity or into the tissues of said vertebrate.
119. The method of claim 116, comprising the oral administration of said composition.
120. The method of any of claims 114-119, wherein the disease is cancer.
121. The method of claim 120, wherein the composition comprises an anticancer drug.
122. The method of claim 120 or 121, wherein the composition comprises a polynucleotide selected from the group consisting of ribozymes, interfering R A (RNAi) and antisense RNA or DNA sequences.
123. The method of claim 122, wherein the polynucleotide is a c-raf antisense oligonucleotide.
124. The method of any of claims 114-119, wherein the disease is a viral infection.
125. The method of claim 124, wherein the composition comprises an antiviral agent.
126. The method of claim 124 or 125, wherein the viral infection is herpes simplex.
127. The method of claim 126, wherein the composition comprises acyclovir, gancyclovir, l-(2-deoxy-2'-fluoro-l-β-D-arabinofuranosyl)-5-iodocytosine (FIAC) or l(2'-deoxy-2'-fluoro-l-β-D-arabinofuranosyl)5-iodouracil (FIAU).
128. The method of claim 124 or 125, wherein the viral infection is HIV.
129. The method of claim 128, wherein the composition comprises an antiviral nucleoside.
130. The method of claim 129, wherein the antiviral nucleoside is 3'-azido- 3'-deoxythymidine (AZT).
68
131. The method of any of claims 114-130, wherein said vertebrate is human.
132. A method of introducing an active agent into a cell, comprising (a) preparing a composition comprising a cationic cardiolipin of any of claims 1-45 and said active agent (b) contacting said cell with said composition whereby said active agent is taken up into said cell.
133. A method for introducing an active agent into a cell, comprising (a) preparing a composition comprising a cationic cardiolipin of any of claims 1-45 and (b) contacting said cell with said composition in the presence of said active agent, whereby said agent is taken up into said cell.
134. A method of introducing an active agent into a cell, comprising (a) preparing a composition comprising a cationic cardiolipin and said active agent (b) contacting said cell with said composition whereby said active agent is taken up into said cell.
135. A method for introducing an active agent into a cell, comprising (a) preparing a composition comprising a cationic cardiolipin and (b) contacting said cell with said composition in the presence of said active agent, whereby said agent is taken up into said cell.
136. A method according to any of claims 132-135, wherein said contacting step occurs in vitro.
137. A method according to any of claims 132-135, wherein said contacting step occurs in vivo.
138. The method of any of claims 132-137, wherein said active agent is a polynucleotide.
139. The method of claim 138, wherein the polynucleotide is a ribozyme, an interfering RNA (RJSfAi) or an antisense RNA or D A sequence.
140. A method of transfecting a cell with a polynucleotide, comprising (a) preparing a composition comprising a cationic cardiolipin of any of claims 1-45 and said polynucleotide (b) contacting said cell with said composition whereby said polynucleotide is taken up into said cell.
141. A method of transfecting a cell with a polynucleotide, comprising (a) preparing a composition comprising a cationic cardiolipin of any of claims 1-45, and (b) contacting said cell with said composition in the presence of said polynucleotide, whereby said polynucleotide is taken up into said cell.
142. A method of transfecting a cell with a polynucleotide, comprising (a) preparing a composition comprising a cationic cardiolipin and said polynucleotide (b)
69
contacting said cell with said composition whereby said polynucleotide is taken up into said cell.
143. A method of transfecting a cell with a polynucleotide, comprising (a) preparing a composition comprising a cationic cardiolipin, and (b) contacting said cell with said composition in the presence of said polynucleotide, whereby said polynucleotide is taken up into said cell.
144. The method of any of claims 140- 143, wherein the cells are in vitro.
145. The method of any of claims 140-143, wherein the cells are in vivo.
146. The method of any of claims 140-145, wherein the polynucleotide is a ribozyme, an interfering RNA (RNAi) or an antisense RNA or DNA sequence.
147. The method of claim 146, wherein the polynucleotide is an expression construct encoding a gene, which is expressed in said cell upon transfection.
148. A method of gene therapy comprising administering a pharmaceutical composition comprising one or more nucleic acids to a patient in need of treatment, wherein the composition comprises cationic cardiolipin.
149. The method of claim 148, wherein the cationic cardiolipin is the cationic cardiolipin of any of claims 1-45.
150. The method of any of claims 114-149, wherein the composition further comprises one or more pharmaceutically acceptable carriers.
151. The method of any of claims 114-150, wherein the composition is a liposomal composition.
152. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula I.
153. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula II.
154. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula HI.
155. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula IV.
156. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula V.
157. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula VI.
70
158. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula VII.
159. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula Viπ.
160. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula IX.
161. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula X.
162. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula XI.
163. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula XII
164. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula XIII.
165. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula XIV.
166. The method of any of claims 114-151, wherein the cationic cardiolipin analog has the structure of formula XV.
167. A kit for transfecting cells, said kit comprising a cationic cardiolipin of any of claims 1-45, and one or more elements selected from the group consisting of a polynucleotide, instructions for formulating the polynucleotide and the cationic cardiolipin into a preparation, instructions for transfecting cells using the cationic cardiolipin, reagents for facilitating transfection, containers for storing the cationic cardiolipin, containers for storing the polynucleotide, containers for storing the reagents, containers for storing a preparation including the cationic cardiolipin and polynucleotide, or containers for preparing the preparation, and materials to facilitate transfection.
168. A kit for transfecting cells, said kit comprising a cationic cardiolipin, and one or more elements selected from the group consisting of a polynucleotide, instructions for formulating the polynucleotide and the cationic cardiolipin into a preparation, instructions for transfecting cells using the cationic cardiolipin, reagents for facilitating transfection, containers for storing the cationic cardiolipin, containers for storing the polynucleotide, containers for storing the reagents, containers for storing a preparation including the cationic cardiolipin and polynucleotide, or containers for preparing the preparation, and materials to facilitate transfection.
169. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula I.
170. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula II.
171. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula III.
172. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula IV.
173. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula V.
174. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula VI.
175. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula VII.
176. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula NIII
177. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula IX.
178. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula X.
179. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula XI.
180. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula XIL
181. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula XIII.
182. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula XIN.
183. The kit of claims 167- 68, wherein the cationic cardiolipin analog has the structure of formula XV.
184. A composition comprising cationic cardiolipin and a nucleic acid.
72
185. A composition comprising cationic cardiolipin of any of claims 1-45 and a nucleic acid.
186. The composition of claim 184 or 185, further comprising one or more pharmaceutically acceptable carriers.
187. The composition of any of claims 184-186, which is a liposomal composition.
188. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula I.
189. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula II
190. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula IE.
191. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula IV.
192. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula V.
193. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula VI.
194. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula VII.
195. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula VH3.
196. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula IX.
197. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula X.
198. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula XI.
199. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula XII
73
200. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula XHI
201. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula XIN.
202. The composition of any of claims 184-187, wherein the cationic cardiolipin analog has the structure of formula XV.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003277445A AU2003277445A1 (en) | 2002-10-16 | 2003-10-16 | Cationic cardiolipin analogs and use thereof |
| EA200500661A EA200500661A1 (en) | 2002-10-16 | 2003-10-16 | CATION ANALOGUE OF CARDIOLIPINE (OPTIONS), ITS APPLICATION (OPTIONS), COMPOSITION AND SET FOR TRANSFECTION OF CELLS (OPTIONS) |
| CA002501990A CA2501990A1 (en) | 2002-10-16 | 2003-10-16 | Cationic cardiolipin analogs and use thereof |
| JP2005501473A JP2006503112A (en) | 2002-10-16 | 2003-10-16 | Cationic cardiolipin analogues and uses thereof |
| EP03809159A EP1558562A1 (en) | 2002-10-16 | 2003-10-16 | Cationic cardiolipin analogs and use thereof |
| US11/106,406 US20050277611A1 (en) | 2002-10-16 | 2005-04-14 | Cationic cardiolipin analoges and its use thereof |
Applications Claiming Priority (14)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41927702P | 2002-10-16 | 2002-10-16 | |
| US60/419,277 | 2002-10-16 | ||
| US42928502P | 2002-11-26 | 2002-11-26 | |
| US60/429,285 | 2002-11-26 | ||
| US43865903P | 2003-01-07 | 2003-01-07 | |
| US60/438,659 | 2003-01-07 | ||
| US46733103P | 2003-05-02 | 2003-05-02 | |
| US60/467,331 | 2003-05-02 | ||
| USPCT/US03/13917 | 2003-05-04 | ||
| PCT/US2003/013917 WO2004062569A2 (en) | 2003-01-07 | 2003-05-04 | Cardiolipin compositions their methods of preparation and use |
| USPCT/US03/16412 | 2003-05-23 | ||
| PCT/US2003/016412 WO2003099830A2 (en) | 2002-05-24 | 2003-05-23 | Cardiolipin compositions, methods of preparation and use |
| USPCT/US03/27806 | 2003-09-05 | ||
| PCT/US2003/027806 WO2004039817A1 (en) | 2002-10-16 | 2003-09-05 | Cardiolipin molecules and method of synthesis |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US11/106,406 Continuation US20050277611A1 (en) | 2002-10-16 | 2005-04-14 | Cationic cardiolipin analoges and its use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2004035523A1 WO2004035523A1 (en) | 2004-04-29 |
| WO2004035523B1 true WO2004035523B1 (en) | 2004-08-26 |
Family
ID=32234368
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2003/027806 WO2004039817A1 (en) | 2002-05-24 | 2003-09-05 | Cardiolipin molecules and method of synthesis |
| PCT/US2003/033099 WO2004035523A1 (en) | 2002-10-16 | 2003-10-16 | Cationic cardiolipin analogs and use thereof |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2003/027806 WO2004039817A1 (en) | 2002-05-24 | 2003-09-05 | Cardiolipin molecules and method of synthesis |
Country Status (7)
| Country | Link |
|---|---|
| EP (2) | EP1556392A1 (en) |
| JP (2) | JP2006510733A (en) |
| AU (2) | AU2003268478A1 (en) |
| CA (2) | CA2502285A1 (en) |
| EA (2) | EA200500659A1 (en) |
| HK (1) | HK1080087A1 (en) |
| WO (2) | WO2004039817A1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8815599B2 (en) | 2004-06-01 | 2014-08-26 | Pronai Therapeutics, Inc. | Methods and compositions for the inhibition of gene expression |
| WO2006004935A2 (en) * | 2004-06-29 | 2006-01-12 | Neopharm, Inc. | Pegylated cardiolipin analogs, methods of synthesis, and uses thereof |
| JP2008519058A (en) * | 2004-11-08 | 2008-06-05 | ネオファーム、インコーポレイティッド | Synthesis of cardiolipin analogues and their use |
| EP1874793A4 (en) | 2005-04-15 | 2008-12-24 | Univ Texas | Delivery of sirna by neutral lipid compositions |
| WO2007014150A2 (en) * | 2005-07-22 | 2007-02-01 | Neopharm, Inc. | Method of administering liposomes containing oligonucleotides |
| WO2007065017A2 (en) * | 2005-12-01 | 2007-06-07 | Pronai Therapeutics, Inc. | Oligonucleotide cationic liposomal delivery system |
| CA2631677C (en) | 2005-12-01 | 2014-08-12 | Pronai Therapeutics, Inc. | Amphoteric liposome formulation |
| JP2009527576A (en) * | 2006-02-24 | 2009-07-30 | ネオフアーム・インコーポレイテツド | Methods and steps for cardiolipin preparation |
| LT2344198T (en) * | 2008-09-27 | 2021-02-25 | Jina Pharmaceuticals Inc. | Lipid based pharmaceutical preparations for topical application |
| RU2639497C2 (en) * | 2012-04-11 | 2017-12-21 | Лайпоксен Текнолоджиз Лимитед | Liposomes containing oligopeptide fragments of myelin basic protein, pharmaceutical composition and method for multiple sclerosis treatment |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2113606A (en) * | 1934-05-24 | 1938-04-12 | Alba Pharmaceutical Company In | Quaternary ammonium compounds |
| US6461637B1 (en) * | 2000-09-01 | 2002-10-08 | Neopharm, Inc. | Method of administering liposomal encapsulated taxane |
| EP2298728A1 (en) * | 1998-11-12 | 2011-03-23 | Life Technologies Corporation | Transfection reagents |
| DE60016205T2 (en) * | 1999-05-28 | 2005-12-01 | Vical, Inc., San Diego | CYTOFECTIN DIMERS AND METHOD FOR THEIR USE |
-
2003
- 2003-09-05 JP JP2005501873A patent/JP2006510733A/en active Pending
- 2003-09-05 WO PCT/US2003/027806 patent/WO2004039817A1/en not_active Application Discontinuation
- 2003-09-05 CA CA002502285A patent/CA2502285A1/en not_active Abandoned
- 2003-09-05 EA EA200500659A patent/EA200500659A1/en unknown
- 2003-09-05 AU AU2003268478A patent/AU2003268478A1/en not_active Abandoned
- 2003-09-05 EP EP03749443A patent/EP1556392A1/en not_active Withdrawn
- 2003-10-16 EA EA200500661A patent/EA200500661A1/en unknown
- 2003-10-16 EP EP03809159A patent/EP1558562A1/en not_active Withdrawn
- 2003-10-16 WO PCT/US2003/033099 patent/WO2004035523A1/en not_active Application Discontinuation
- 2003-10-16 AU AU2003277445A patent/AU2003277445A1/en not_active Abandoned
- 2003-10-16 CA CA002501990A patent/CA2501990A1/en not_active Abandoned
- 2003-10-16 JP JP2005501473A patent/JP2006503112A/en active Pending
-
2005
- 2005-12-30 HK HK05112200.6A patent/HK1080087A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1556392A1 (en) | 2005-07-27 |
| EA200500661A1 (en) | 2005-10-27 |
| EP1558562A1 (en) | 2005-08-03 |
| CA2501990A1 (en) | 2004-04-29 |
| JP2006510733A (en) | 2006-03-30 |
| JP2006503112A (en) | 2006-01-26 |
| WO2004039817A1 (en) | 2004-05-13 |
| WO2004035523A1 (en) | 2004-04-29 |
| WO2004039817A9 (en) | 2004-07-22 |
| CA2502285A1 (en) | 2004-05-13 |
| AU2003268478A1 (en) | 2004-05-25 |
| EA200500659A1 (en) | 2005-10-27 |
| HK1080087A1 (en) | 2006-04-21 |
| AU2003277445A1 (en) | 2004-05-04 |
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