.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 8,101,663

« Back to Dashboard

Claims for Patent: 8,101,663

Title:Polymorphs of suberoylanilide hydroxamic acid
Abstract: The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.
Inventor(s): Miller; Thomas A. (Brookline, MA), Richon; Victoria M. (Wellesley, MA)
Assignee: Merck HDAC Research, LLC (Boston, MA)
Application Number:12/653,073
Patent Claims: 1. A method of treating cancer in a patient, comprising the step of orally administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising an active ingredient consisting of suberoylanilide hydroxamic acid (SAHA) Form I characterized by an X-ray diffraction pattern including characteristic peaks at about 9.0, 9.4, 17.5, 19.4, 20.0, 24.0, 24.4, 24.8, 25.0, 28.0, and 43.3 degrees 2.theta., wherein the X-ray diffraction is measured with a Copper X-ray source; and further characterized by a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 164.4.+-.2.0, as measured by a Perkins Elmer DSC 6 Instrument, and a pharmaceutically acceptable carrier.

2. A method of treating cancer in a patient, comprising the step of orally administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising an active ingredient consisting of suberoylanilide hydroxamic acid (SAHA) Form I characterized by an X-ray diffraction pattern including characteristic peaks at about 9.4, 17.5, 19.4, 20.0, 24.0, and 28.0 degrees 2.theta., wherein the X-ray diffraction is measured with a Copper X-ray source; and further characterized by a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 164.4.+-.2.0, as measured by a Perkins Elmer DSC 6 Instrument, and a pharmaceutically acceptable carrier.

3. A method of treating cancer in a patient, comprising the step of orally administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising an active ingredient consisting of suberoylanilide hydroxamic acid (SAHA) Form I characterized by an X-ray diffraction pattern including characteristic peaks at about 9.4, 17.5, 19.4, 20.0, 24.0, and 28.0 degrees 2.theta., and lacking peaks at about 13.4-14.0 and 22.7-23.0 degrees 2.theta., wherein the X-ray diffraction is measured with a Copper X-ray source, and a pharmaceutically acceptable carrier.

4. The method according to claim 3, wherein the SAHA Form I is further characterized by a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 164.4.+-.2.0, as measured by a Perkins Elmer DSC 6 Instrument.

5. A method of treating cancer in a patient, comprising the step of orally administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising an active ingredient consisting of a crystalline form of SAHA designated as Form I and a pharmaceutically acceptable carrier, wherein the SAHA Form I is characterized by an X-ray diffraction pattern including characteristic peaks at about 9.4, 17.5, 19.4, 20.0, 24.0, and 28.0 degrees 2.theta., wherein the X-ray diffraction is measured with a Copper X-ray source, obtainable by a method comprising the step of recrystallizing a crude preparation of SAHA from an organic solvent, or a mixture of an organic solvent and water, wherein the organic solvent is at least one of methanol, ethanol or isopropanol.

6. The method according to claim 5, wherein the method comprises the step of recrystallizing a crude preparation of SAHA from a mixture of 15-85% methanol, ethanol or isopropanol and about 1-15% water.

7. The method according to claim 5, wherein the method comprises the step of recrystallizing a crude preparation of SAHA from methanol, ethanol or isopropanol.

8. The method of claim 5, wherein the crude preparation of SAHA is obtainable by a method comprising the steps of: a. reacting suberic acid with aniline to form suberanilic acid having the structure: ##STR00057## or a salt thereof b. reacting suberanilic acid with methanol to form methyl suberanilate having the structure: ##STR00058## c. reacting the methyl suberanilate with hydroxylamine hydrochloride to form a crude suberoylanilide hydroxamic acid in a reaction mixture.

9. The method of claim 6, wherein the crude preparation of SAHA is obtainable by a method comprising the steps of: a. reacting suberic acid with aniline to form suberanilic acid having the structure: ##STR00059## or a salt thereof b. reacting suberanilic acid with methanol to form methyl suberanilate having the structure: ##STR00060## c. reacting the methyl suberanilate with hydroxylamine hydrochloride to form a crude suberoylanilide hydroxamic acid in a reaction mixture.

10. The method of claim 7, wherein the crude preparation of SAHA is obtainable by a method comprising the steps of: a. reacting suberic acid with aniline to form suberanilic acid having the structure: ##STR00061## or a salt thereof b. reacting suberanilic acid with methanol to form methyl suberanilate having the structure: ##STR00062## c. reacting the methyl suberanilate with hydroxylamine hydrochloride to form a crude suberoylanilide hydroxamic acid in a reaction mixture.

11. The method according to claim 8, wherein step (c) further comprises the steps of: (1) adding sodium methoxide to the reaction mixture to obtain a clear solution; and (2) adding glacial acetic acid to the clear solution to form a precipitate comprising crude suberoylanilide hydroxamic acid.

12. The method according to claim 9, wherein step (c) further comprises the steps of: (1) adding sodium methoxide to the reaction mixture to obtain a clear solution; and (2) adding glacial acetic acid to the clear solution to form a precipitate comprising crude suberoylanilide hydroxamic acid.

13. The method according to claim 10, wherein step (c) further comprises the steps of: (1) adding sodium methoxide to the reaction mixture to obtain a clear solution; and (2) adding glacial acetic acid to the clear solution to form a precipitate comprising crude suberoylanilide hydroxamic acid.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc