CA2363486A1 - Compositions and methods for effecting the levels of high density lipoprotein (hdl) cholesterol and apolipoprotein ai, very low density lipoprotein (vldl) cholesterol and low density lipoprotein (ldl) cholesterol - Google Patents
Compositions and methods for effecting the levels of high density lipoprotein (hdl) cholesterol and apolipoprotein ai, very low density lipoprotein (vldl) cholesterol and low density lipoprotein (ldl) cholesterol Download PDFInfo
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- CA2363486A1 CA2363486A1 CA002363486A CA2363486A CA2363486A1 CA 2363486 A1 CA2363486 A1 CA 2363486A1 CA 002363486 A CA002363486 A CA 002363486A CA 2363486 A CA2363486 A CA 2363486A CA 2363486 A1 CA2363486 A1 CA 2363486A1
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- 238000000034 method Methods 0.000 title claims abstract 46
- 239000000203 mixture Substances 0.000 title claims abstract 46
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 title claims abstract 34
- 235000012000 cholesterol Nutrition 0.000 title claims abstract 17
- 102000005666 Apolipoprotein A-I Human genes 0.000 title claims abstract 14
- 108010059886 Apolipoprotein A-I Proteins 0.000 title claims abstract 14
- 108010010234 HDL Lipoproteins Proteins 0.000 title claims 13
- 102000015779 HDL Lipoproteins Human genes 0.000 title claims 13
- 108010007622 LDL Lipoproteins Proteins 0.000 title claims 3
- 102000007330 LDL Lipoproteins Human genes 0.000 title claims 3
- 108010062497 VLDL Lipoproteins Proteins 0.000 title claims 3
- 108010022197 lipoprotein cholesterol Proteins 0.000 title claims 3
- 102100031375 Endothelial lipase Human genes 0.000 claims abstract 49
- 101000941275 Homo sapiens Endothelial lipase Proteins 0.000 claims abstract 49
- 230000002255 enzymatic effect Effects 0.000 claims abstract 15
- 238000008214 LDL Cholesterol Methods 0.000 claims abstract 10
- 108010069201 VLDL Cholesterol Proteins 0.000 claims abstract 10
- 229920001184 polypeptide Polymers 0.000 claims 39
- 102000004196 processed proteins & peptides Human genes 0.000 claims 39
- 108090000765 processed proteins & peptides Proteins 0.000 claims 39
- 239000013598 vector Substances 0.000 claims 28
- 239000013604 expression vector Substances 0.000 claims 21
- 150000001875 compounds Chemical class 0.000 claims 10
- 238000006911 enzymatic reaction Methods 0.000 claims 10
- 108020004707 nucleic acids Proteins 0.000 claims 10
- 102000039446 nucleic acids Human genes 0.000 claims 10
- 150000007523 nucleic acids Chemical class 0.000 claims 10
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 9
- 230000000692 anti-sense effect Effects 0.000 claims 9
- 239000003623 enhancer Substances 0.000 claims 8
- 230000001177 retroviral effect Effects 0.000 claims 8
- 239000013603 viral vector Substances 0.000 claims 8
- 101150107380 LIPG gene Proteins 0.000 claims 6
- 108091061960 Naked DNA Proteins 0.000 claims 6
- 108090000994 Catalytic RNA Proteins 0.000 claims 5
- 102000053642 Catalytic RNA Human genes 0.000 claims 5
- 108091092562 ribozyme Proteins 0.000 claims 5
- 241000175212 Herpesvirales Species 0.000 claims 4
- 102000023732 binding proteins Human genes 0.000 claims 4
- 108091008324 binding proteins Proteins 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 4
- 239000003112 inhibitor Substances 0.000 claims 4
- 230000003834 intracellular effect Effects 0.000 claims 4
- 230000003472 neutralizing effect Effects 0.000 claims 4
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 239000002502 liposome Substances 0.000 claims 3
- 108020004414 DNA Proteins 0.000 claims 2
- 108091034117 Oligonucleotide Proteins 0.000 claims 2
- 230000002708 enhancing effect Effects 0.000 claims 2
- 108020004999 messenger RNA Proteins 0.000 claims 2
- 241001529453 unidentified herpesvirus Species 0.000 claims 2
- 102000053602 DNA Human genes 0.000 claims 1
- 108090001102 Hammerhead ribozyme Proteins 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 125000002091 cationic group Chemical group 0.000 claims 1
- 238000003018 immunoassay Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 108090001060 Lipase Proteins 0.000 abstract 2
- 102000004882 Lipase Human genes 0.000 abstract 2
- 230000000694 effects Effects 0.000 abstract 2
- 108090000790 Enzymes Proteins 0.000 abstract 1
- 102000004190 Enzymes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/18—Carboxylic ester hydrolases (3.1.1)
- C12N9/20—Triglyceride splitting, e.g. by means of lipase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Biophysics (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Compositions and methods for raising the level of HDL cholesterol and apolipoprotein AI in a patient and for lowering the levels of VLDL cholesterol and LDL cholesterol in a patient, including compositions and methods which effect the expression of a gene, LIPG, which encodes a lipase enzyme that is a member of the tryacylglycerol lipase family or which effect the enzymatic activity of the enzyme.
Claims (65)
1. A composition for lowering the expression of the LIPG gene in a patient comprising an antisense nucleic acid.
2. The composition of Claim 1 comprising an expression vector which includes said antisense nucleic acid..
3. The composition of Claim 2 wherein said expression vector is selected from the group consisting of retroviral vectors, adenoviral vectors, adeno-associated viral vectors, herpesviral vectors, and naked DNA vectors.
4. The composition of Claim 1 wherein said composition is a synthetic antisense nucleic acid.
5. The composition of Claim 4 wherein said antisense nucleic acid is an oligonucleotide.
6. The composition of Claim 5 wherein said oligonucleotide contains chemically modified bases.
7. A composition for lowering the enzymatic activity of the LIPG polypeptide in a patient comprising a neutralizing antibody capable of binding to the LIPG
polypeptide and lowering its enzymatic activity.
polypeptide and lowering its enzymatic activity.
8. The composition of Claim 7 comprising an expression vector including a DNA sequence encoding said antibody.
9. The composition of Claim 8 wherein said expression vector is selected from the group consisting of retroviral vectors, adenoviral vectors, adeno-associated viral vectors, herpesviral vectors, and naked DNA vectors.
10. A composition for lowering the enzymatic activity of the LIPG polypeptide in a patient comprising an intracellular binding protein.
11. The composition of Claim 10 comprising an expression vector including a DNA sequence encoding said intracellular binding protein.
12. The composition of Claim 11 wherein said expression vector is selected from the group consisting of retroviral vectors, adenoviral vectors, adeno-associated viral vectors, herpesviral vectors, and naked DNA vectors.
13. A composition comprising an inhibitor capable of inhibiting the enzymatic activity of the LIPG polypeptide in a patient.
14. A composition comprising an inhibitor capable of lowering the expression of the LIPG gene in a patient.
15. A composition capable of lowering the expression of LIPG in a patient comprising a ribozyme.
16. The composition of Claim 15 comprising an expression vector including a DNA sequence encoding said ribozyme.
17. The composition of Claim 16 wherein said expression vector is selected from the group consisting of retroviral vectors, adenoviral vectors, adeno-associated viral vectors, herpesviral vectors, and naked DNA vectors.
18. The composition of Claim 14 wherein said ribozyme is a hammerhead ribozyme.
19. A composition for increasing the level of LIPG
polypeptide in a patient comprising an expression vector including a DNA sequence encoding the LIPG polypeptide.
polypeptide in a patient comprising an expression vector including a DNA sequence encoding the LIPG polypeptide.
20. A composition for increasing the level of LIPG
polypeptide in a patient comprising an LIPG polypeptide and a pharmaceutically acceptable carrier.
polypeptide in a patient comprising an LIPG polypeptide and a pharmaceutically acceptable carrier.
21. A composition for increasing the level of LIPG
polypeptide in a patient comprising an enhancer capable of increasing the expression of the LIPG gene.
polypeptide in a patient comprising an enhancer capable of increasing the expression of the LIPG gene.
22. A composition for increasing the enzymatic activity of LIPG polypeptide in a patient comprising an enhancer which binds to and enhances the enzymatic activity of the LIPG
polypeptide.
polypeptide.
23. A method for raising the level of high density lipoprotein (HDL) cholesterol and apolipoprotein AI in a patient comprising administering to said patient a composition which lowers the enzymatic activity of LIPG in said patient.
24. The method of Claim 23 wherein said composition lowers the level of LIPG polypeptide in a patient.
25. The method of Claim 23 wherein said composition comprises an antisense nucleic acid.
26. The method of Claim 25 wherein said antisense nucleic acid is a synthetic antisense nucleic acid.
27. The method of Claim 26 wherein said antisense nucleic acid is modified to increase the chemical stability of said nucleic acid.
28. The method of Claim 23 wherein said composition comprises a neutralizing antibody capable of binding to the LIPG polypeptide and lowering its enzymatic activity.
29. The method of Claim 23 wherein said composition comprises an inhibitor which inhibits the enzymatic activity of LIPG polypeptide.
30. The method of Claim 29 wherein said inhibitor comprises a compound which lowers the expression of the LIPG
gene.
gene.
31. The method of Claim 23 wherein said composition comprises a ribozyme which cleaves mRNA encoding LIPG.
32. The method of Claim 23 wherein said composition comprises a DNA molecule and a liposome.
33. The method of Claim 32 wherein said liposome is a cationic liposome.
34. The method of Claim 23 wherein said composition comprises DNA and a pharmaceutically acceptable carrier.
35. The method of Claim 23 wherein said composition comprises an expression vector.
36. The method of Claim 35 wherein said expression vector is selected from the group consisting of retroviral vectors, adenoviral vectors and adeno-associated viral vectors, herpesvirus vectors, and naked DNA vectors.
37. The method of Claim 35 wherein said expression vector includes a DNA sequence which encodes a ribozyme.
38. The method of Claim 36 wherein said expression vector is selected from the group consisting of retroviral vectors, adenoviral vectors and adeno-associated viral vectors, herpesvirus vectors, and naked DNA vectors.
39. The method of Claim 35 wherein said expression vector includes a DNA sequence which encodes an antisense nucleic acid.
40. The method of Claim 35 wherein said expression vector includes a DNA sequence which encodes a neutralizing antibody which binds LIPG.
41. The method of Claim 35 wherein said expression vector includes a DNA sequence which encodes an intracellular binding protein which is capable of binding and neutralizing LIPG.
42. The method of Claim 41, wherein said intracellular binding protein is an antibody.
43. The method of Claim 35 wherein said expression vector includes a DNA sequence which encodes an inhibitory molecule which inhibits the enzymatic activity of LIPG.
44. The method of Claim 23 further comprising administration of a composition capable of expressing apolipoprotein AI in said patient.
45. A method for lowering the level of very low density lipoprotein (VLDL) cholesterol in a patient comprising administering to said patient a composition capable of increasing the enzymatic activity of LIPG in said patient.
46. The method of Claim 45 wherein said composition is an LIPG polypeptide and a pharmaceutically acceptable carrier.
47. The method of Claim 46 wherein said composition is an expression vector capable of expressing an LIPG
polypeptide.
polypeptide.
48. The method of Claim 47 wherein said expression vector is selected from the group consisting of retroviral vectors, adenoviral vectors, and adeno-associated viral vectors.
49. The method of Claim 45 wherein said composition comprises an enhancer which enhances the enzymatic activity of LIPG polypeptide.
50. The method of Claim 45 wherein said composition comprises an enhancer which increases expression of the LIPG
gene.
gene.
51. A method for lowering the level of low density lipoprotein (LDL) cholesterol in a patient comprising administering to said patient a composition capable of increasing the enzymatic activity of LIPG in said patient.
52. The method of Claim 51 wherein said composition is an LIPG polypeptide and a pharmaceutically acceptable carrier.
53. The method of Claim 52 wherein said composition is an expression vector capable of expressing an LIPG
polypeptide.
polypeptide.
54. The method of Claim 53 wherein said expression vector is selected from the group consisting of retroviral vectors, adenoviral vectors, and adeno-associated viral vectors.
55. The method of Claim 53 wherein said composition comprises an enhancer which enhances the enzymatic activity of LIPG polypeptide.
56. The method of Claim 53 wherein said composition comprises an enhancer which increases the expression of the LIPG gene.
57. A method for lowering the level of LDL cholesterol in a patient comprising administering to the patient an enhancer which preferentially enhances the enzymatic reactions between LIPG polypeptide and LDL cholesterol relative to the enzymatic reactions between LIPG polypeptide and HDL cholesterol and apolipoprotein AI.
58. A method for lowering the level of VLDL cholesterol in a patient comprising administering to the patient an enhancer which preferentially enhances the enzymatic reactions between LIPG polypeptide and VLDL cholesterol relative to the enzymatic reactions between LIPG polypeptide and HDL cholesterol and apolipoprotein AI.
59. A method for diagnosing a predisposition to low HDL
cholesterol and apolipoprotein AI levels comprising obtaining a tissue sample from a patient and measuring the level of LIPG polypeptide in said sample.
cholesterol and apolipoprotein AI levels comprising obtaining a tissue sample from a patient and measuring the level of LIPG polypeptide in said sample.
60. The method of Claim 59 wherein said tissue is blood.
61. The method of Claim 60 wherein the level of LIPG
polypeptide in said sample is measured by an immunoassay.
polypeptide in said sample is measured by an immunoassay.
62. The method of Claim 59 wherein the levels of LIPG
polypeptide are measured by measuring the levels of LIPG
mRNA.
polypeptide are measured by measuring the levels of LIPG
mRNA.
63. A method for determining whether a test compound can inhibit the enzymatic reaction between the LIPG
polypeptide and HDL cholesterol and apolipoprotein AI
comprising: (A) comparing the level of HDL cholesterol and apolipoprotein AI in a first sample comprising: (1) HDL
cholesterol and apolipoprotein AI, (2) LIPG polypeptide, and (3) said test compound with the level of HDL cholesterol and apolipoprotein AI in another sample comprising: (4) HDL
cholesterol and apolipoprotein AI, and (5) LIPG polypeptide;
and (B) identifying whether or not said test compound is effective in inhibiting the enzymatic reaction between the LIPG polypeptide and HDL cholesterol and apolipoprotein AI by observing whether or not the first sample has a higher level of HDL cholesterol and apolipoprotein AI than that of said other sample.
polypeptide and HDL cholesterol and apolipoprotein AI
comprising: (A) comparing the level of HDL cholesterol and apolipoprotein AI in a first sample comprising: (1) HDL
cholesterol and apolipoprotein AI, (2) LIPG polypeptide, and (3) said test compound with the level of HDL cholesterol and apolipoprotein AI in another sample comprising: (4) HDL
cholesterol and apolipoprotein AI, and (5) LIPG polypeptide;
and (B) identifying whether or not said test compound is effective in inhibiting the enzymatic reaction between the LIPG polypeptide and HDL cholesterol and apolipoprotein AI by observing whether or not the first sample has a higher level of HDL cholesterol and apolipoprotein AI than that of said other sample.
64. A method for determining whether a test compound can enhance the enzymatic reaction between the LIPG
polypeptide and VLDL cholesterol comprising: (A) comparing the level of VLDL cholesterol in a first sample comprising:
(1) VLDL cholesterol, (2) LIPG polypeptide, and (3) said test compound with the level of VLDL cholesterol in another sample comprising: (4) VLDL cholesterol, and (5) LIPG polypeptide;
and (B) identifying whether or not said test compound is effective in enhancing the enzymatic reaction between the LIPG polypeptide and VLDL cholesterol by observing whether or not the first sample has a lower level of VLDL cholesterol than that of said other sample.
polypeptide and VLDL cholesterol comprising: (A) comparing the level of VLDL cholesterol in a first sample comprising:
(1) VLDL cholesterol, (2) LIPG polypeptide, and (3) said test compound with the level of VLDL cholesterol in another sample comprising: (4) VLDL cholesterol, and (5) LIPG polypeptide;
and (B) identifying whether or not said test compound is effective in enhancing the enzymatic reaction between the LIPG polypeptide and VLDL cholesterol by observing whether or not the first sample has a lower level of VLDL cholesterol than that of said other sample.
65. A method for determining whether a test compound can enhance the enzymatic reaction between the LIPG
polypeptide and LDL cholesterol comprising: (A) comparing the level of LDL cholesterol in a first sample comprising: (1) LDL cholesterol, (2) LIPG polypeptide, and (3) said test compound with the level of LDL cholesterol in another sample comprising: (4) LDL cholesterol, and (5) LIPG polypeptide;
and (B) identifying whether or not said test compound is effective in enhancing the enzymatic reaction between the LIPG polypeptide and LDL cholesterol by observing whether or not the first sample has a lower level of LDL cholesterol than that of said other sample.
polypeptide and LDL cholesterol comprising: (A) comparing the level of LDL cholesterol in a first sample comprising: (1) LDL cholesterol, (2) LIPG polypeptide, and (3) said test compound with the level of LDL cholesterol in another sample comprising: (4) LDL cholesterol, and (5) LIPG polypeptide;
and (B) identifying whether or not said test compound is effective in enhancing the enzymatic reaction between the LIPG polypeptide and LDL cholesterol by observing whether or not the first sample has a lower level of LDL cholesterol than that of said other sample.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/277,401 | 1999-03-26 | ||
| US09/277,401 US7008776B1 (en) | 1996-12-06 | 1999-03-26 | Compositions and methods for effecting the levels of high density lipoprotein (HDL) cholesterol and apolipoprotein AI very low density lipoprotein (VLDL) cholesterol and low density lipoprotein (LDL) cholesterol |
| PCT/US2000/007870 WO2000057837A2 (en) | 1999-03-26 | 2000-03-24 | Compositions and methods for effecting the levels of cholesterol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2363486A1 true CA2363486A1 (en) | 2000-10-05 |
| CA2363486C CA2363486C (en) | 2012-12-18 |
Family
ID=23060703
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2363486A Expired - Fee Related CA2363486C (en) | 1999-03-26 | 2000-03-24 | Compositions and methods for effecting the levels of high density lipoprotein (hdl) cholesterol and apolipoprotein ai, very low density lipoprotein (vldl) cholesterol and low density lipoprotein (ldl) cholesterol |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1171078A4 (en) |
| JP (1) | JP2002540127A (en) |
| KR (2) | KR20050044812A (en) |
| AU (1) | AU776684B2 (en) |
| BR (1) | BR0009333A (en) |
| CA (1) | CA2363486C (en) |
| HK (1) | HK1043309A1 (en) |
| IL (2) | IL145526A0 (en) |
| MX (1) | MXPA01009727A (en) |
| NO (2) | NO331779B1 (en) |
| NZ (2) | NZ531180A (en) |
| WO (1) | WO2000057837A2 (en) |
| ZA (1) | ZA200107598B (en) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7507808B2 (en) * | 2002-12-12 | 2009-03-24 | Isis Pharmaceuticals, Inc. | Modulation of endothelial lipase expression |
| CN101437933B (en) | 2005-12-28 | 2013-11-06 | 斯克里普斯研究所 | Natural antisense and non-coding RNA transcripts as drug targets |
| ES2600781T3 (en) | 2008-12-04 | 2017-02-10 | Curna, Inc. | Treatment for diseases related to vascular endothelial growth factor (vegf) by inhibiting natural antisense transcripts of vegf |
| US8921329B2 (en) | 2008-12-04 | 2014-12-30 | Curna, Inc. | Treatment of erythropoietin (EPO) related diseases by inhibition of natural antisense transcript to EPO |
| EP2370582B1 (en) | 2008-12-04 | 2017-05-10 | CuRNA, Inc. | Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene |
| CA2752237C (en) | 2009-02-12 | 2020-03-24 | Opko Curna, Llc | Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf |
| ES2656290T3 (en) | 2009-03-16 | 2018-02-26 | Curna, Inc. | Treatment of diseases related to nuclear factor (derived from erythroid 2) similar to 2 (NRF2) by inhibition of natural antisense transcript to NRF2 |
| WO2010107740A2 (en) | 2009-03-17 | 2010-09-23 | Curna, Inc. | Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1 |
| KR101835889B1 (en) | 2009-05-06 | 2018-03-08 | 큐알엔에이, 인크. | Treatment of lipid transport and metabolism gene related diseases by inhibition of natural antisense transcript to a lipid transport and metabolism gene |
| WO2010129746A2 (en) | 2009-05-06 | 2010-11-11 | Curna, Inc. | Treatment of tristetraproline (ttp) related diseases by inhibition of natural antisense transcript to ttp |
| KR101742334B1 (en) | 2009-05-08 | 2017-06-01 | 큐알엔에이, 인크. | Treatment of dystrophin family related diseases by inhibition of natural antisense transcript to dmd family |
| NO2432881T3 (en) | 2009-05-18 | 2018-04-14 | ||
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| EP2443237B1 (en) | 2009-06-16 | 2017-02-22 | CuRNA, Inc. | Treatment of collagen gene related diseases by inhibition of natural antisense transcript to a collagen gene |
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| WO2010151671A2 (en) | 2009-06-24 | 2010-12-29 | Curna, Inc. | Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2 |
| CN102482672B (en) | 2009-06-26 | 2016-11-09 | 库尔纳公司 | By suppressing the natural antisense transcript treatment Down syndrome gene-associated diseases of Down syndrome gene |
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| CN102762731B (en) | 2009-08-05 | 2018-06-22 | 库尔纳公司 | By inhibiting to treat insulin gene (INS) relevant disease for the natural antisense transcript of insulin gene (INS) |
| WO2011019815A2 (en) | 2009-08-11 | 2011-02-17 | Curna, Inc. | Treatment of adiponectin (adipoq) related diseases by inhibition of natural antisense transcript to an adiponectin (adipoq) |
| US8791087B2 (en) | 2009-08-21 | 2014-07-29 | Curna, Inc. | Treatment of ‘C terminus of HSP70-interacting protein’ (CHIP)related diseases by inhibition of natural antisense transcript to CHIP |
| US9023822B2 (en) | 2009-08-25 | 2015-05-05 | Curna, Inc. | Treatment of 'IQ motif containing GTPase activating protein' (IQGAP) related diseases by inhibition of natural antisense transcript to IQGAP |
| US20120295952A1 (en) | 2009-09-25 | 2012-11-22 | Curna, Inc. | Treatment of filaggrin (flg) related diseases by modulation of flg expression and activity |
| JP6025567B2 (en) | 2009-12-16 | 2016-11-16 | カッパーアールエヌエー，インコーポレイテッド | Treatment of MBTPS1-related diseases by inhibition of the natural antisense transcript against the membrane-bound transcription factor peptidase, site 1 (MBTPS1) |
| CN102781480B (en) | 2009-12-23 | 2018-07-27 | 库尔纳公司 | UCP2 relevant diseases are treated by inhibiting the natural antisense transcript of uncoupling protein-3 (UCP2) |
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| WO1994013791A1 (en) * | 1992-12-04 | 1994-06-23 | Innovir Laboratories, Inc. | Regulatable nucleic acid therapeutic and methods of use thereof |
| AP1313A (en) * | 1996-12-06 | 2004-10-04 | Aventis Pharma Inc | Polypeptides encoded by a human lipase-like gene, composition and method. |
| AU1941899A (en) * | 1997-12-19 | 1999-07-12 | Progenitor, Inc. | A lipase expressed in endothelial cells and methods for its use |
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| IL145526A (en) | 2010-11-30 |
| WO2000057837A3 (en) | 2001-01-25 |
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| NO331779B1 (en) | 2012-03-26 |
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| AU776684B2 (en) | 2004-09-16 |
| MXPA01009727A (en) | 2002-07-22 |
| KR20050044812A (en) | 2005-05-12 |
| CA2363486C (en) | 2012-12-18 |
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