JO3767B1 - تراكيب اوليغو نوكليوتيد و طرق تصنيعها - Google Patents
تراكيب اوليغو نوكليوتيد و طرق تصنيعهاInfo
- Publication number
- JO3767B1 JO3767B1 JOP/2015/0089A JOP20150089A JO3767B1 JO 3767 B1 JO3767 B1 JO 3767B1 JO P20150089 A JOP20150089 A JO P20150089A JO 3767 B1 JO3767 B1 JO 3767B1
- Authority
- JO
- Jordan
- Prior art keywords
- free
- linkage
- amino group
- solid phase
- dinucleotide
- Prior art date
Links
- 108091034117 Oligonucleotide Proteins 0.000 title abstract 5
- 238000000034 method Methods 0.000 title abstract 3
- 239000000203 mixture Substances 0.000 title abstract 3
- 125000003277 amino group Chemical group 0.000 abstract 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 2
- 230000008878 coupling Effects 0.000 abstract 2
- 238000010168 coupling process Methods 0.000 abstract 2
- 238000005859 coupling reaction Methods 0.000 abstract 2
- 239000000539 dimer Substances 0.000 abstract 2
- 239000002777 nucleoside Substances 0.000 abstract 2
- 239000012011 nucleophilic catalyst Substances 0.000 abstract 1
- 150000003833 nucleoside derivatives Chemical class 0.000 abstract 1
- 125000003835 nucleoside group Chemical group 0.000 abstract 1
- 230000001590 oxidative effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 abstract 1
- 150000008300 phosphoramidites Chemical class 0.000 abstract 1
- 239000007790 solid phase Substances 0.000 abstract 1
- 238000010532 solid phase synthesis reaction Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- 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
- C12N15/09—Recombinant DNA-technology
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- 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
- C12N15/09—Recombinant DNA-technology
- 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
- C12N15/1137—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 against enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
- C12P19/34—Polynucleotides, e.g. nucleic acids, oligoribonucleotides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/07—Nucleotidyltransferases (2.7.7)
- C12Y207/07049—RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/314—Phosphoramidates
- C12N2310/3145—Phosphoramidates with the nitrogen in 3' or 5'-position
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
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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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
يتعلق الاختراع بتوفير طريقة ذات طور صلب لعمل أوليجو نوكليوتيدات من خلال دورات الإقران المتعاقب بما في ذلك خطوة إقران واحدة على الأقل لوحدة فرعية من داي نوكليوتيد دايمر بمجموعة طرفية 3’ حرة لسلسلة متنامية. تتضمن أوليجو نوكليوتيد وحدتين فرعيتين على الأقل من النوكليوزيد مرتبطة بواسطة رابط فوفسوراميدات N3′ ←P5′. يمكن أن تتضمن الطريقة الخطوات (أ) نزع حماية مجموعة أمينية 3' تمت حمايتها للنوكليوزيد الطرفي المرتبط بمادة حاملة في الطور الصلب، تُشكل خطوة نزع مجموعة الحماية المذكورة مجموعة أمينية 3' حرة؛ (ب) تلامس المجموعة الأمينية 3' الحرة مع أمينو -داي نوكليوتيد- 5 - فوسفوراميديت دايمر تمت حمايته عند الطرف 3? في وجود محفز نوكليوتيد لتشكيل رابط نوكليوزيد N3′ ←P5′فوسفوراميديت؛ و (ج) أكسدة الرابط (أي، المعالجة بالسلفر). يمكن أن تتضمن التركيبات المنتجة بواسطة الطرق المذكورة كمية قليلة من واحدة او أكثر (N-x) من منتجات أوليجو نوكليوتيد. يتم أيضاً توفير تركيبات صيدلية تتضمن تركيبات أوليجو نوكليوتيد التي يتعلق بها الاختراع.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461987396P | 2014-05-01 | 2014-05-01 | |
| US201562151909P | 2015-04-23 | 2015-04-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JO3767B1 true JO3767B1 (ar) | 2021-01-31 |
Family
ID=54359301
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JOP/2020/0257A JOP20200257A1 (ar) | 2014-05-01 | 2014-05-01 | تركيبات أوليجو نوكليوتيد وطرق لتحضيرها |
| JOP/2015/0089A JO3767B1 (ar) | 2014-05-01 | 2015-04-29 | تراكيب اوليغو نوكليوتيد و طرق تصنيعها |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JOP/2020/0257A JOP20200257A1 (ar) | 2014-05-01 | 2014-05-01 | تركيبات أوليجو نوكليوتيد وطرق لتحضيرها |
Country Status (33)
| Country | Link |
|---|---|
| US (6) | US9796747B2 (ar) |
| EP (2) | EP4286519A3 (ar) |
| JP (7) | JP7040892B2 (ar) |
| KR (4) | KR102316282B1 (ar) |
| CN (3) | CN106459134B (ar) |
| AP (1) | AP2016009489A0 (ar) |
| AU (3) | AU2015253158B2 (ar) |
| BR (1) | BR112016025196B1 (ar) |
| CL (4) | CL2016002749A1 (ar) |
| DK (1) | DK3137479T5 (ar) |
| EA (1) | EA034882B9 (ar) |
| ES (1) | ES2963740T3 (ar) |
| FI (1) | FI3137479T3 (ar) |
| HR (1) | HRP20231505T1 (ar) |
| HU (1) | HUE064289T2 (ar) |
| IL (2) | IL248044B (ar) |
| JO (2) | JOP20200257A1 (ar) |
| LT (1) | LT3137479T (ar) |
| MA (1) | MA63525B1 (ar) |
| MX (2) | MX382233B (ar) |
| MY (2) | MY178617A (ar) |
| PE (1) | PE20170147A1 (ar) |
| PH (1) | PH12016502080A1 (ar) |
| PL (1) | PL3137479T3 (ar) |
| PT (1) | PT3137479T (ar) |
| RS (1) | RS64860B1 (ar) |
| SG (2) | SG10201911086XA (ar) |
| SI (1) | SI3137479T1 (ar) |
| SM (1) | SMT202300405T1 (ar) |
| TW (2) | TWI709406B (ar) |
| UA (1) | UA126108C2 (ar) |
| WO (1) | WO2015168310A1 (ar) |
| ZA (2) | ZA201606624B (ar) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100558739C (zh) * | 2004-07-02 | 2009-11-11 | 杰龙公司 | 合成被保护的3’-氨基核苷单体 |
| JOP20200257A1 (ar) * | 2014-05-01 | 2017-06-16 | Geron Corp | تركيبات أوليجو نوكليوتيد وطرق لتحضيرها |
| CN113564168B (zh) * | 2015-04-23 | 2024-10-25 | 美国杰龙生物医药公司 | 使用多价阳离子盐组合物制备多核苷酸的方法 |
| BR112020000410A2 (pt) * | 2017-07-10 | 2020-07-14 | Geron Corporation | processo aprimorado para preparar imetelstat |
| KR102861357B1 (ko) * | 2019-10-28 | 2025-09-18 | 제론 코포레이션 | 비정질 고체 석신일화 3-(지방산 아미도)-2-하이드록시-1-(보호된 하이드록시)-프로판 염 및 이를 제조하는 방법 |
| AU2020375734B2 (en) | 2019-10-28 | 2026-04-09 | Geron Corporation | Crystalline solids of 3-palmitoyl-amido-1,2-propanediol and 3-palmitoyl-amido-2-hydroxy-1-dimethoxytriphenylmethylether-propane and methods of making and using the same |
| US20240391945A1 (en) * | 2020-01-08 | 2024-11-28 | Nitto Denko Corporation | Nucleic acid synthesis method using segment-type amidite |
| WO2023069865A1 (en) | 2021-10-15 | 2023-04-27 | Codexis, Inc. | Engineered terminal deoxynucleotidyl transferase variants |
| KR20250008345A (ko) | 2023-07-07 | 2025-01-14 | 주식회사 엘지에너지솔루션 | 체결기구 및 체결기구를 포함하는 전지팩 |
Family Cites Families (80)
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| US4046720A (en) | 1974-01-17 | 1977-09-06 | California Institute Of Technology | Crosslinked, porous, polyacrylate beads |
| US4394448A (en) | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| US4678814A (en) | 1981-03-30 | 1987-07-07 | California Institute Of Technology | Polyacrolein microspheres |
| US4413070A (en) | 1981-03-30 | 1983-11-01 | California Institute Of Technology | Polyacrolein microspheres |
| US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US6448392B1 (en) | 1985-03-06 | 2002-09-10 | Chimerix, Inc. | Lipid derivatives of antiviral nucleosides: liposomal incorporation and method of use |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US4757141A (en) | 1985-08-26 | 1988-07-12 | Applied Biosystems, Incorporated | Amino-derivatized phosphite and phosphate linking agents, phosphoramidite precursors, and useful conjugates thereof |
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| DK0462145T3 (da) | 1989-03-07 | 1994-08-08 | Genentech Inc | Covalente konjugater mellem lipid og oligonucleotid |
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| US5420330A (en) | 1990-09-07 | 1995-05-30 | Pharmacia P-L Biochemicals Inc. | Lipo-phosphoramidites |
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