CA2439831A1 - Polymorphic and other crystalline forms of cis-ftc - Google Patents
Polymorphic and other crystalline forms of cis-ftc Download PDFInfo
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- CA2439831A1 CA2439831A1 CA002439831A CA2439831A CA2439831A1 CA 2439831 A1 CA2439831 A1 CA 2439831A1 CA 002439831 A CA002439831 A CA 002439831A CA 2439831 A CA2439831 A CA 2439831A CA 2439831 A1 CA2439831 A1 CA 2439831A1
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- Prior art keywords
- ftc
- cis
- sesquihydrate
- compound
- treatment
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- 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
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Abstract
Solid phases of (-)-cis-FTC, which are designated herein as amorphous (-)-FTC
and Forms II and III (-)-cis-FTC) are provided that can be distinguished from Form I (-)-cis-FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture. A hydrated crystalline form of (.plusmn.)-cis-FTC
(i.e. racemic cis-FTC), and a dehydrated form of the hydrate, are also provided, and can similarly be distinguished from other forms of FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture.
These FTC forms can be used in the manufacture of other forms of FTC, or in pharmaceutical compositions. Particularly preferred uses of these forms are in the treatment of HIV or hepatitis B.
and Forms II and III (-)-cis-FTC) are provided that can be distinguished from Form I (-)-cis-FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture. A hydrated crystalline form of (.plusmn.)-cis-FTC
(i.e. racemic cis-FTC), and a dehydrated form of the hydrate, are also provided, and can similarly be distinguished from other forms of FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture.
These FTC forms can be used in the manufacture of other forms of FTC, or in pharmaceutical compositions. Particularly preferred uses of these forms are in the treatment of HIV or hepatitis B.
Claims (58)
1) A polymorphic compound of (-)-cis-FTC, wherein the compound displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern:
a) 14.7° ~ 0.1°, 16.7° ~ 0.1°, 19.6° ~
0.1°, 21.1° ~ 0.1°, 21.8° ~ 0.1°, 24.6°
~ 0.1°, and 25.6° ~ 0.1° (Form II (-)-cis-FTC); or b) 14.5° ~ 0.1°, 16.7° ~ 0.1°, 19.6° ~
0.1°, 20.4° ~ 0.1°, 21.4° ~ 0.1°, 21.7°
~ 0.1°, 25.2° ~ 0.1°, and 26.2° ~ 0.1°
(Form III (-)-cis-FTC).
a) 14.7° ~ 0.1°, 16.7° ~ 0.1°, 19.6° ~
0.1°, 21.1° ~ 0.1°, 21.8° ~ 0.1°, 24.6°
~ 0.1°, and 25.6° ~ 0.1° (Form II (-)-cis-FTC); or b) 14.5° ~ 0.1°, 16.7° ~ 0.1°, 19.6° ~
0.1°, 20.4° ~ 0.1°, 21.4° ~ 0.1°, 21.7°
~ 0.1°, 25.2° ~ 0.1°, and 26.2° ~ 0.1°
(Form III (-)-cis-FTC).
2) The compound of claim 1 which is Form II (-)-cis-FTC.
3) The compound of claim 1 which is Form III (-)-cis-FTC.
4) The compound of claim 1 which is substantially pure Form II (-)-cis-FTC.
5) The compound of claim 4 which is at least 97% pure.
6) The compound of claim 1 which is substantially pure Form III (-)-cis-FTC.
7) The compound of claim 6 which is at least 97% pure.
8) A pharmaceutical composition comprising a polymorphic compound of (-)-cis-FTC, wherein the compound displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern:
a) 14.7° ~ 0.1°, 16.7° ~ 0.1°, 19.6° ~
0.1°, 21.1° ~ 0.1°, 21.8° ~ 0.1°, 24.6°
~ 0.1°, and 25.6° ~ 0.1° (Form II (-)-cis-FTC); or b) 14.5° ~ 0.1°, 16.7° ~ 0.1°, 19.6° ~
0.1°, 20.4° ~ 0.1 °, 21.4° ~ 0.1 °, 21.7°
~ 0.1°, 25.2° ~ 0.1°, and 26.2° ~ 0.1°
(Form III (-)-cis-FTC).
and a pharmaceutically acceptable carrier.
a) 14.7° ~ 0.1°, 16.7° ~ 0.1°, 19.6° ~
0.1°, 21.1° ~ 0.1°, 21.8° ~ 0.1°, 24.6°
~ 0.1°, and 25.6° ~ 0.1° (Form II (-)-cis-FTC); or b) 14.5° ~ 0.1°, 16.7° ~ 0.1°, 19.6° ~
0.1°, 20.4° ~ 0.1 °, 21.4° ~ 0.1 °, 21.7°
~ 0.1°, 25.2° ~ 0.1°, and 26.2° ~ 0.1°
(Form III (-)-cis-FTC).
and a pharmaceutically acceptable carrier.
9) A polymorphic form of (-)-cis-FTC prepared by a method comprising:
a) melting Form I (-)-cis-FTC, and b) recrystallizing the melted (-)-cis-FTC, wherein the Form I (-)-cis-FTC displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern: 14.1 ° ~
0.1°, 19.9° ~ 0.1°, 20.2° ~ 0.1°, 20.6° ~ 0.1°, 21.0° ~ 0.1°, 22.4° ~
0.1°, 28.5° ~
0.1°, 29.5° ~ 0.1°, and 32.6° ~ 0.1°.
a) melting Form I (-)-cis-FTC, and b) recrystallizing the melted (-)-cis-FTC, wherein the Form I (-)-cis-FTC displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern: 14.1 ° ~
0.1°, 19.9° ~ 0.1°, 20.2° ~ 0.1°, 20.6° ~ 0.1°, 21.0° ~ 0.1°, 22.4° ~
0.1°, 28.5° ~
0.1°, 29.5° ~ 0.1°, and 32.6° ~ 0.1°.
10) The polymorphic form of (-)-cis-FTC of claim 9 wherein the method further comprises cooling the recrystallized FTC to below about 96 °C.
11) A polymorphic form of (-)-cis-FTC prepared by a method comprising cooling a Form II polymorph of (-)-cis-FTC to below about 96 °C, wherein the Form II
polymorph displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern: 14.7° ~
0.1°, 16.7° ~
0.1°, 19.6° ~ 0.1°, 21.1° ~ 0.1°, 21.8° ~ 0.1°, 24.6° ~ 0.1°, and 25.6° ~
0.1°.
polymorph displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern: 14.7° ~
0.1°, 16.7° ~
0.1°, 19.6° ~ 0.1°, 21.1° ~ 0.1°, 21.8° ~ 0.1°, 24.6° ~ 0.1°, and 25.6° ~
0.1°.
12) A polymorphic form of (-)-cis-FTC prepared by a method comprising heating a Form III polymorph of (-)-cis-FTC to above about 112 °C, wherein the Form III polymorph displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern: 14.5° ~
0.1°, 16.7° ~
0.1°, 19.6° ~ 0.1°, 20.4° ~ 0.1°, 21.4° ~ 0.1°, 21.7° ~ 0.1°, 25.2° ~
0.1°, and 26.2° ~ 0.1°.
0.1°, 16.7° ~
0.1°, 19.6° ~ 0.1°, 20.4° ~ 0.1°, 21.4° ~ 0.1°, 21.7° ~ 0.1°, 25.2° ~
0.1°, and 26.2° ~ 0.1°.
13) A method of preparing a polymorphic form of (-)-cis-FTC comprising:
a) melting Form I (-)-cis-FTC, and b) recrystallizing the melted (-)-cis-FTC, wherein the Form I (-)-cis-FTC displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern:
a) melting Form I (-)-cis-FTC, and b) recrystallizing the melted (-)-cis-FTC, wherein the Form I (-)-cis-FTC displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern:
14.1° ~
0.1°, 19.9° ~ 0.1°, 20.2° ~ 0.1°, 20.6° ~ 0.1°, 21.0° ~ 0.1°, 22.4° ~
0.1°, 28.5° ~
0.1°, 29.5° ~ 0.1°, and 32.6° ~ 0.1°.
14) The method of claim 13 wherein the method further comprises cooling the recrystallized FTC to below about 96 °C.
0.1°, 19.9° ~ 0.1°, 20.2° ~ 0.1°, 20.6° ~ 0.1°, 21.0° ~ 0.1°, 22.4° ~
0.1°, 28.5° ~
0.1°, 29.5° ~ 0.1°, and 32.6° ~ 0.1°.
14) The method of claim 13 wherein the method further comprises cooling the recrystallized FTC to below about 96 °C.
15) A method of preparing a polymorphic form of (-)-cis-FTC comprising cooling a Form II polymorph of (-)-cis-FTC to below about 96 °C, wherein the Form II
polymorph displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern: 14.7° ~
0.1°, 16.7° ~
0.1°, 19.6° ~ 0.1°, 21.1° ~ 0.1°, 21.8° ~ 0.1°, 24.6° ~ 0.1°, and 25.6° ~
0.1°.
polymorph displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern: 14.7° ~
0.1°, 16.7° ~
0.1°, 19.6° ~ 0.1°, 21.1° ~ 0.1°, 21.8° ~ 0.1°, 24.6° ~ 0.1°, and 25.6° ~
0.1°.
16) A method of preparing a polymorphic form of (-)-cis-FTC comprising heating a Form III polymorph of (-)-cis-FTC to above about 112 °C, wherein the Form III polymorph displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern: 14.5° ~
0.1°, 16.7° ~
0.1°, 19.6° ~ 0.1°, 20.4° ~ 0.1°, 21.4° ~ 0.1°, 21.7° ~ 0.1°, 25.2° ~
0.1°, and 26.2° ~ 0.1°.
0.1°, 16.7° ~
0.1°, 19.6° ~ 0.1°, 20.4° ~ 0.1°, 21.4° ~ 0.1°, 21.7° ~ 0.1°, 25.2° ~
0.1°, and 26.2° ~ 0.1°.
17) A crystalline form of (~)-cis-FTC prepared by a method comprising:
a) dissolving a first crystalline form of (~)-cis-FTC in water, and b) recrystallizing the dissolved (~)-cis-FTC.
a) dissolving a first crystalline form of (~)-cis-FTC in water, and b) recrystallizing the dissolved (~)-cis-FTC.
18) The crystalline form of (~)-cis-FTC of claim 17 wherein the method further comprises dehydrating the recrystallized (~)-cis-FTC.
19) The crystalline form of (~)-cis-FTC of claim 17 wherein the first crystalline form of (~)-cis-FTC is present in a composition of cis-FTC that comprises up to 98% of the (-) or (+) enantiomer.
20) (~)-cis-FTC sesquihydrate.
21) (~)-cis-FTC sesquihydrate in substantially pure form.
22) (~)-cis-FTC sesquihydrate in a purity of at least 97%.
23) A pharmaceutical composition comprising (~)-cis-FTC sesquihydrate and a pharmaceutically acceptable carrier.
24) Dehydrated (~)-cis-FTC sesquihydrate.
25) Dehydrated (~)-cis-FTC sesquihydrate in substantially pure form.
26) Dehydrated (~)-cis-FTC sesquihydrate in a purity of at least 97%.
27) A pharmaceutical composition comprising dehydrated (~)-cis-FTC
sesquihydrate and a pharmaceutically acceptable carrier.
sesquihydrate and a pharmaceutically acceptable carrier.
28) A crystalline form of (~)-cis-FTC that displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern:
11.5°
~ 0.1°, 13.4° ~ 0.1°, 19.1° ~ 0.1°, 20.3° ~ 0.1°, 20.8° ~ 0.1°, 21.5° ~
0.1°, 21.9° ~
0.1°, and 30.9° ~ 0.1°.
11.5°
~ 0.1°, 13.4° ~ 0.1°, 19.1° ~ 0.1°, 20.3° ~ 0.1°, 20.8° ~ 0.1°, 21.5° ~
0.1°, 21.9° ~
0.1°, and 30.9° ~ 0.1°.
29) A crystalline form of (t)-cis-FTC that displays the following angular positions (two theta) of characteristic peaks in a powder X-ray diffraction pattern:
12.3°
~ 0.1°, 14.0° ~ 0.1°, 20.7° ~ 0.1°, 22.6° ~ 0.1°, 23.3° ~ 0.1°, and 25.5° ~
0.1°.
12.3°
~ 0.1°, 14.0° ~ 0.1°, 20.7° ~ 0.1°, 22.6° ~ 0.1°, 23.3° ~ 0.1°, and 25.5° ~
0.1°.
30) A method of preparing a crystalline form of (~)-cis-FTC comprising:
a) dissolving a first crystalline form of (~)-cis-FTC in water, and b) recrystallizing the dissolved (t)-cis-FTC.
a) dissolving a first crystalline form of (~)-cis-FTC in water, and b) recrystallizing the dissolved (t)-cis-FTC.
31) The method of claim 30 further comprising dehydrating the recrystallized (~)-cis-FTC.
32) The method of claim 30 wherein the first crystalline form of (~)-cis-FTC
is present in a composition of cis-FTC that comprises up to 98% of the (-) or (+) enantiomer.
is present in a composition of cis-FTC that comprises up to 98% of the (-) or (+) enantiomer.
33) Amorphous (-)-cis-FTC.
34) Amorphous (-)-cis-FTC in substantially pure form.
35) Amorphous (-)-cis-FTC in a purity of at least 97%.
36) A pharmaceutical composition comprising amorphous (-)-cis-FTC and a pharmaceutically acceptable carrier.
37) A method of preparing amorphous (-)-cis-FTC comprising:
a) melting a (-)-cis-FTC, and b) quench cooling the melt to avoid recrystallization.
a) melting a (-)-cis-FTC, and b) quench cooling the melt to avoid recrystallization.
38) The method of claim 37 further comprising cooling the amorphous (-)-cis-FTC
to below about 96 °C.
to below about 96 °C.
39) A method of treating a HIV comprising administering to a patient afflicted with HIV a treatment effective amount of the compound of claim 1.
40) A method of treating a HBV comprising administering to a patient afflicted with HBV a treatment effective amount of the compound of claim 1.
41) A method of treating HIV comprising administering to a patient afflicted with HIV a treatment effective amount of (t)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC.
42) A method of treating HIV comprising administering to a patient afflicted with HIV a treatment effective amount of (~)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC.
43) Use of the compound of claim 1 in the manufacture of a medicament for the treatment of HIV.
44) Use of the compound of claim 1 in the manufacture of a medicament for the treatment of HBV.
45) Use of (~)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC, in the manufacture of a medicament for the treatment of HIV.
46) Use of (t)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC, in the manufacture of a medicament for the treatment of HBV.
47) A pharmaceutical composition comprising the compound of claim 1 for the treatment of HIV.
48) A pharmaceutical composition comprising the compound of claim 1 for the treatment of a HBV.
49) A pharmaceutical composition comprising (~)-cis-FTC sesquihydrate;
dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC for the treatment of HIV.
dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC for the treatment of HIV.
50) A pharmaceutical composition comprising (~)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC for the treatment of HBV.
51) A pharmaceutical composition comprising the compound of claim 1 when used in the treatment of a HIV.
52) A pharmaceutical composition comprising the compound of claim 1 when used in the treatment of HBV.
53) A pharmaceutical composition comprising (~)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC when used in the treatment of HIV.
54) A pharmaceutical composition comprising (~)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC when used in the treatment of HBV.
55) Use of a pharmaceutical composition comprising the compound of claim 1 in the treatment of HIV.
56) Use of a pharmaceutical composition comprising the compound of claim 1 in the treatment of HBV.
57) Use of a pharmaceutical composition comprising (~)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC in the treatment of HIV.
58) Use of a pharmaceutical composition comprising (~)-cis-FTC sesquihydrate, dehydrated (~)-cis-FTC sesquihydrate, or amorphous (-)-cis-FTC in the treatment of HBV.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2690137A CA2690137C (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27256001P | 2001-03-01 | 2001-03-01 | |
| US60/272,560 | 2001-03-01 | ||
| US30960501P | 2001-08-02 | 2001-08-02 | |
| US60/309,605 | 2001-08-02 | ||
| PCT/US2002/006184 WO2002070518A1 (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2690137A Division CA2690137C (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2439831A1 true CA2439831A1 (en) | 2002-09-12 |
| CA2439831C CA2439831C (en) | 2010-01-12 |
Family
ID=26955597
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2867970A Abandoned CA2867970A1 (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
| CA2690137A Expired - Fee Related CA2690137C (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
| CA2788498A Expired - Fee Related CA2788498C (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
| CA002439831A Expired - Fee Related CA2439831C (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2867970A Abandoned CA2867970A1 (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
| CA2690137A Expired - Fee Related CA2690137C (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
| CA2788498A Expired - Fee Related CA2788498C (en) | 2001-03-01 | 2002-03-01 | Polymorphic and other crystalline forms of cis-ftc |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US6723728B2 (en) |
| EP (3) | EP1574512B1 (en) |
| JP (4) | JP5105689B2 (en) |
| KR (4) | KR100927024B1 (en) |
| CN (4) | CN102911166B (en) |
| AT (2) | ATE312097T1 (en) |
| AU (1) | AU2002335489B2 (en) |
| CA (4) | CA2867970A1 (en) |
| CY (2) | CY1107983T1 (en) |
| DE (2) | DE60207850T2 (en) |
| DK (2) | DK1389207T3 (en) |
| ES (3) | ES2537007T3 (en) |
| PT (2) | PT1574512E (en) |
| WO (1) | WO2002070518A1 (en) |
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| TWI244393B (en) * | 2002-08-06 | 2005-12-01 | Idenix Pharmaceuticals Inc | Crystalline and amorphous forms of beta-L-2'-deoxythymidine |
| EP1923063A3 (en) | 2003-01-14 | 2009-04-08 | Gilead Sciences, Inc. | Compositions and methods for combination antiviral therapy |
| US6943249B2 (en) | 2003-03-17 | 2005-09-13 | Ash Stevens, Inc. | Methods for isolating crystalline Form I of 5-azacytidine |
| US6887855B2 (en) | 2003-03-17 | 2005-05-03 | Pharmion Corporation | Forms of 5-azacytidine |
| US20060014949A1 (en) * | 2004-07-13 | 2006-01-19 | Supergen Inc. | Compositions and formulations of decitabine polymorphs and methods of use thereof |
| TWI375560B (en) | 2005-06-13 | 2012-11-01 | Gilead Sciences Inc | Composition comprising dry granulated emtricitabine and tenofovir df and method for making the same |
| TWI471145B (en) | 2005-06-13 | 2015-02-01 | Bristol Myers Squibb & Gilead Sciences Llc | Unitary pharmaceutical dosage form |
| WO2009005338A2 (en) * | 2007-07-05 | 2009-01-08 | Ultimorphix Technologies B.V. | Solid forms ult-i, ult-2 and ult-3 of emtricitabine |
| WO2010055526A1 (en) | 2008-11-12 | 2010-05-20 | Lupin Limited | A novel polymorph of emtricitabine and a process for preparing of the same |
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