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Crystalline Forms Of (3 A,5ß,6 A,7 A) 6 Ethyl 3,7 Dihydroxycholan 24 Oic Acid (Obeticholic Acid) And Processes Thereof

Abstract: ABSTRACT The present invention relates to the crystalline forms of (3a,5p\6a,7a)-6-ethyl-3,7-dihydroxycholan-24-oic acid, commonly known as Obeticholic acid (1) and process for the preparation of the same.

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
09 April 2018
Publication Number
50/2019
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
afzal@hasanandsingh.com
Parent Application
Patent Number
Legal Status
Grant Date
2023-12-14
Renewal Date

Applicants

Biophore India Pharmaceuticals Pvt. Ltd
PLOT#92; 1-98/2/92, KAVURI HILLS-PHASE II, JUBILEE HILLS, HYDERABAD, TELANGANA, INDIA - 500 033.

Inventors

1. Manik Reddy Pullagurla
PLOT#92; 1-98/2/92, KAVURI HILLS-PHASE II, JUBILEE HILLS, HYDERABAD, TELANGANA, INDIA - 500 033
2. Jagadeesh Babu Rangisetty
PLOT#92; 1-98/2/92, KAVURI HILLS-PHASE II, JUBILEE HILLS, HYDERABAD, TELANGANA, INDIA - 500 033

Specification

We claim:
1. A crystalline form B1 of Obeticholic acid (1),
wherein the by X-ray powder diffraction (XRPD) pattern of crystalline form Bl is having 2 theta values at 3.06, 5.61, 6.23, 7.64, 7.95, 8.21, 9.39, 11.09, 12.46, 13.47, 13.90, 15.4, 15.7,16.48, 18.52, 18.87, 20.03, 20.40, 21.06,22.05, 22.53, 23.02, 23.28, 23.90, 24.58, 25.30, 25.64, 26.04, 27.54, 38.74 and 39.63 ± (0.2) degrees.
2. A process for preparing crystalline form Bl of Obeticholic acid (1) as claimed
in claim 1 comprising:
i. adding a suitable solvent to Obeticholic acid (1);
ii. heating the reaction mixture to 40 °C - 70 °C; iii. cooling the reaction mixture to a suitable temperature; iv. isolating the crystalline forms of Obeticholic acid (1); and
v. optionally, drying crystalline Obeticholic acid (1) using a suitable technique at a suitable temperature.
3. The process of claim 2, wherein the solvents is selected from a group
comprising of acetone, acetonitrile, nitromethane, 1,4-dioxane, diethyl ether,
dichloromethane, ethyl acetate, N, N-dimethylformamide, methyl tertiary butyl
ether, hexane, butyl acetate cyclohexane, toluene, tetrahydrofuran or mixtures
thereof.

4. Crystalline form Bl of Obeticholic acid (1) as claimed in claim 1, characterized
by:
a) differential scanning calorimetry (DSC) having endothermic peak at 295.68 °C as shown in figure 2, and
b) thermal gravimetric analysis (TGA) thermogram as shown in figure 3.

5. Crystalline form B2 of Obeticholic acid (1) characterized by X-ray powder diffraction (XRPD) pattern having 2 theta values at 4.30, 5.94, 6.50, 8.14, 8.39, 9.25, 9.51, 10.09, 11.12, 12.64, 14.31, 15.81, 16.05, 16.80, 17.28, 18.08, 18.86, 20.32, 20.53, 21.98 and 22.22 + 0.2 degrees.
6. A process for preparing crystalline forms B2 of Obeticholic acid (1) as claimed in claim 4 comprising:

1) adding a suitable solvent to Obeticholic acid (1) and stirring;
2) adding another suitable solvent to the step 1) reaction mass;
3) cooling the reaction mixture to a suitable temperature;
4) isolating the crystalline form B2 of Obeticholic acid (1); and
5) optionally, drying the isolated crystalline form of Obeticholic acid (1) using a suitable technique at a suitable temperature.

7. The process of claim 5, wherein the solvents is selected from a group comprising of acetone, acctonitrile, nitromethane, 1,4-dioxane, diethyl ether, dichloromethane, ethyl acetate, N, N-dimethylformamide, methyl tertiary butyl ether, hexane, butyl acetate cyclohexane, toluene, tetrahydrofuran or mixtures thereof.
8. A process for preparing crystalline forms B3 of Obeticholic acid (1) comprising:
a. adding a suitable solvent to Obeticholic acid (1) and stirring;
b. heating the reaction mixture to a suitable temperature;
c. adding another suitable solvent to the step b) reaction mixture;
d. filtering the reaction mixture and cooling the filtrate to a suitable
temperature;

e. isolating the crystalline form B3 of Obeticholic acid (1); and
f. optionally, drying the isolated crystalline form B3 of Obeticholic acid
(1) using a suitable technique at a suitable temperature.
9. A process for preparing crystalline forms B4 of Obeticholic acid (1)
comprising:
A. adding a suitable first solvent to Obeticholic acid (1) and stirring;
B. heating the reaction mixture to a suitable temperature;
C. adding a second solvent to the step B) reaction mixture;
D. filtering the reaction mixture and optionally, cooling the filtrate to a
suitable temperature;
E. isolating crystalline form B4 of Obeticholic acid (1); and
F. optionally, drying the isolated crystalline form B4 of Obeticholic acid
(1) using a suitable technique at a suitable temperature.
10. The process of claim 8 and 9, wherein the solvents is selected from a group
comprising of acetone, acctonitrile, nitromethane, 1,4-dioxane, diethyl ether,
dichloromethane, ethyl acetate, N, N-dimethylformamide, methyl tertiary butyl
ether, hexane, butyl acetate cyclohexanc, toluene, tetrahydrofuran or mixtures
thereof.

Documents

Application Documents

# Name Date
1 Form 5_As Filed_09-04-2018.pdf 2018-04-09
2 Form 3_As Filed_09-04-2018.pdf 2018-04-09
3 Form 2 Title Page_Provisional_09-04-2018.pdf 2018-04-09
4 Form 1_As Filed_09-04-2018.pdf 2018-04-09
5 Drawings_As Filed_09-04-2018.pdf 2018-04-09
6 Description Provisional_As Filed_09-04-2018.pdf 2018-04-09
7 Correspondence by Applicant_As Filed_09-04-2018.pdf 2018-04-09
8 Abstract_As Filed_09-04-2018.pdf 2018-04-09
9 201841013461-FORM 3 [03-04-2019(online)].pdf 2019-04-03
10 201841013461-ENDORSEMENT BY INVENTORS [03-04-2019(online)].pdf 2019-04-03
11 201841013461-COMPLETE SPECIFICATION [03-04-2019(online)].pdf 2019-04-03
12 Correspondence by Applicant_Form2,Form3,Form5,_08-04-2019.pdf 2019-04-08
13 201841013461-Request Letter-Correspondence [27-04-2019(online)].pdf 2019-04-27
14 201841013461-Form 1 (Submitted on date of filing) [27-04-2019(online)].pdf 2019-04-27
15 201841013461-FORM 3 [30-04-2019(online)].pdf 2019-04-30
16 Correspondence by Agent _Form-3 _06-05-2019.pdf 2019-05-06
17 201841013461-FORM 3 [20-01-2020(online)].pdf 2020-01-20
18 201841013461-Form3_(As Filed)_24-01-2020.pdf 2020-01-24
19 201841013461-Correspondence_24-01-2020.pdf 2020-01-24
20 201841013461-POA [09-04-2022(online)].pdf 2022-04-09
21 201841013461-FORM-26 [09-04-2022(online)].pdf 2022-04-09
22 201841013461-FORM 18 [09-04-2022(online)].pdf 2022-04-09
23 201841013461-FORM 13 [09-04-2022(online)].pdf 2022-04-09
24 201841013461-AMENDED DOCUMENTS [09-04-2022(online)].pdf 2022-04-09
25 201841013461-FER.pdf 2022-04-19
26 201841013461-Information under section 8(2) [13-09-2022(online)].pdf 2022-09-13
27 201841013461-FORM 3 [13-09-2022(online)].pdf 2022-09-13
28 201841013461-FER_SER_REPLY [13-09-2022(online)].pdf 2022-09-13
29 201841013461-DRAWING [13-09-2022(online)].pdf 2022-09-13
30 201841013461-CORRESPONDENCE [13-09-2022(online)].pdf 2022-09-13
31 201841013461-CLAIMS [13-09-2022(online)].pdf 2022-09-13
32 201841013461-ABSTRACT [13-09-2022(online)].pdf 2022-09-13
33 201841013461-US(14)-HearingNotice-(HearingDate-29-11-2023).pdf 2023-10-30
34 201841013461-FORM-26 [27-11-2023(online)].pdf 2023-11-27
35 201841013461-Correspondence to notify the Controller [27-11-2023(online)].pdf 2023-11-27
36 201841013461-Written submissions and relevant documents [09-12-2023(online)].pdf 2023-12-09
37 201841013461-PatentCertificate14-12-2023.pdf 2023-12-14
38 201841013461-IntimationOfGrant14-12-2023.pdf 2023-12-14

Search Strategy

1 SearchE_18-04-2022.pdf

ERegister / Renewals

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