Sign In to Follow Application
View All Documents & Correspondence

Improved Processes For Preparation Of Bilastine Using Novel Intermediates

Abstract: Provided herein are improved, commercially viable and industrially advantageous processes for the preparation of Bilastine or a pharmaceutically acceptable salt thereof using novel intermediates, in high yield and purity.

Get Free WhatsApp Updates!
Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
29 August 2016
Publication Number
10/2018
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
brinda@iprightsindia.com
Parent Application
Patent Number
Legal Status
Grant Date
2024-07-31
Renewal Date

Applicants

SYMED LABS LIMITED
8-2-293/174/3, B.N.REDDY COLONY, ROAD NO.14, BANJARA HILLS, HYDERABAD-500 034.

Inventors

1. MOHAN RAO DADDO
8-2-293/82/A/202, D.NO: 202, OPP. : JUBILEE INTERNATIONAL CLUB, ROAD NO: 14, JUBILEE HILLS, HYDERABAD - 500 033.
2. VENUGOPAL BINGI
RAMPOOR,JAMMIKUNTA ROAD,HUZURABAD,KARIMNAGAR-505468,TELANGANA,INDIA.

Specification

FIELD OF THE INVENTION The present invention relates to improved, commercially viable and industrially advantageous processes for the preparation of Bilastine or a pharmaceutically acceptable salt thereof using novel intermediates, in high yield and purity. BACKGROUND OF THE INVENTION U.S. Patent No. 5,877,187 (hereinafter referred to as the US' 187 patent) discloses a variety of benzimidazole derivatives, processes for their preparation, pharmaceutical compositions comprising the derivatives, and methods of use thereof. These compounds have high Hi antihistaminic and antiallergic activity and are devoid of effects on the central nervous and cardiovascular systems. Among them, Bilastine, chemically named 2-[4-[2-[4-[l-(2-ethoxyethyl)-benzimidazol-2-yl]piperidin-l-yl]ethyl]phenyl]-2-methyl propanoic acid, is a selective histamine Hj receptor antagonist used for treatment of allergic rhinoconjunctivitis and urticaria (hives). Bilastine is represented by the following structural formula I: Bilastine, a novel second-generation Hi-antihistamine, is approved for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children over 12 years of age. Bilastine has a favourable pharmacokinetic profile, being rapidly absorbed resulting in an onset of clinical effect within one hour of administration, and has a long duration of action, exceeding 24 hours, which allows for once-daily dosing. Bilastine was developed by FAES Farma and approved in the European Union for the symptomatic treatment of allereicLrJiinQconiLirictiviti^ under the trade names Bilaxten® (in Spain, Colombia, Australia, and several other countries), Ilaxten® (in United Kingdom), and Blexten™ (in Canada). Various processes for the preparation of Bilastine, its intermediates, and related compounds are described in U.S. Patent Nos. US 5,877,187 and US 8,367,704; PCT Publication Nos. WO 2014/188453, WO2014/026657; Chinese Patent Application Publication No. CN 102675101; and Journal Articles: Syn. Comm., 41(9), 1394-1402, 2011; and Drugs of future 35(2), 98-105,2010. The synthesis of Bilastine was first described in the US'187 patent. According to the US' 187 patent, Bilastine is prepared by a process as depicted in scheme 1: yl)-l-methylethyl)phenyl)ethylp-toluenesulphonate is reacted with 2-(4-piperidinyl)-lH-benzimidazole in the presence of sodium carbonate to produce 2-[l-(2-(4-(l-(4,4-dimethyl-A2-oxazoline-2-yl)4-methylethyl)phenyl)ethyl)piperidine-4-yl]-l H-benzimidazole; b) the resulting dimethyl-oxazoline intermediate is reacted with 2-chloroethyl ethylether in dimethylformamide in the presence of sodium hydride at a temperature of 80°C, followed by tedious work-up and isolation methods to produce the l-(2-ethoxyethyl)-2-l-(2-(4-(l-(4,4-dimethyl-A2-oxazoline-2-yl)-l-methylethyl)phenyl)ethyl)piperidine-4-yl-lH-benzimidazole; and c) the resulting 2-ethoxyethyl compound is reacted with. 3N Hydrochloric acid to produce 2-4-(2-(4-(l-(2-ethoxyethyl)benzimidazole-2-yl)piperidine-l-yl)ethyl)phenyl-2-methylpropanoic acid (Bilastine). The process for the preparation of Bilastine as described in the aforementioned prior art suffers from the following major disadvantages and shortcomings: (a) the introduction of the oxazoline group and its subsequent hydrolysis inevitably comprised in the process leads to the formation of several by-products, thereby resulting in a poor product yields and quality and making the whole process lengthy and cumbersome; b) the reaction between 2-[l -(2-(4-(l-(4,4-dimethyl-A2-oxazpline-2-yl)-l-methylethyl)phenyl) ethyl)piperidine-4-yl]-l H-benzimidazole and 2-chloroethyl ethylether is performed under very stringent reaction condition and involves the use of dangerous and explosive alkali metal hydrides such as sodium hydride; c) use of alkali metal hydrides is not advisable for commercial scale operations from safety point of view. A need remains for novel, commercially viable and environmentally friendly processes for the preparation of Bilastine and its intermediates with high yields and purity, to resolve the problems associated with the processes described in the prior art, and that will be suitable for large-scale preparation. SUMMARY OF THE INVENTION The object of the present invention is to provide novel, commercially viable and industrially advantageous processes for the preparation of Bilastine and its intermediates in high yields and purity. The present inventors have found that Bilastine or a pharmaceutically acceptable salt thereof can be prepared, in high purity and with high yield, by reacting 2-methyl-2-phenyl-propanoic acid with an acylating agent in the presence of a suitable Lewis acid to produce 2-[4-(2-chloroacetyl)phenyl]-2-methyl-propanoic acid, followed by reduction vvim a swta&e-reduGffl^a^e^^^ chloroethyl)phenyl]-2-methyl-propanoic acid, which is then condensed with l-(2-ethoxyethyl)-2-(piperidin-4-yl)-benzimidazole in the presence of a suitable base to produce Bilastine or a pharmaceutically acceptable salt thereof. In another aspect, provided herein is a novel intermediate compound, 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid, of formula IIIA: or a salt thereof. In another aspect, provided also herein is a process for the preparation of the novel intermediate compound, 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid, of formula IIIA. The novel process for the preparation of Bilastine disclosed in the present invention is represented by a schematic diagram as depicted in scheme-2: The process for the preparation of Bilastine described herein has the following advantages over the processes described in the prior art: .^i.V.,rtheprGcess4rfvoj-v^ ii) the overall process involves a reduced number of process steps, shorter reaction times and less expensive reagents, thereby making the process cost effective; iii) the process avoids the use of the explosive and difficult to handle reagents like Sodium hydride; iv) the process avoids the use of tedious and cumbersome procedures like prolonged reaction time periods, multiple process steps, column chromatographic purifications and additional purifications or isolations. DETAILED DESCRIPTION OF THE INVENTION According to one aspect, there is provided a novel and industrially advantageous process for the preparation of highly pure Bilastine of formula I: or a pharmaceutically acceptable salt thereof, which comprises: a) reacting 2-methyl-2-phenyl-propanoic acid of formula II: optionally in the presence of a Lewis acid, to produce 2-[4-(2-chloroacetyl)phenyl]-2-methyl-propanoic acid of formula III: b) reducing the compound of formula III obtained in step-(a) with a hydrosilane reagent in the presence of an acid to produce 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid compound of formula IIIA: or a salt thereof; and c) condensing the compound of formula IIIA obtained in step-(b) with 1 -(2-ethoxyethyl)-2-(piperidin-4-yl)benzimidazole of formula IV: , or an acid addition salt thereof; in the presence of a base, optionally in the presence of a phase transfer catalyst, in a suitable solvent to produce Bilastine of formula I or a salt thereof, and optionally purifying the Bilastine obtained using a suitable solvent to produce highly pure Bilastine or a pharmaceutically acceptable salt thereof. Unless otherwise specified, the solvent used for isolating, purifying and/or recrystallizing the compounds of formula I, III and IIIA obtained by the processes described in the present invention is selected from the group consisting of water, an alcohol, a ketone, an ether, an ester, a hydrocarbon, a halogenated hydrocarbon, and mixtures thereof. Specifically, the solvent is selected from the group consisting of water, methanol, ethanol, 1-propanol, isopropyl alcohol, acetone, tetrahydrofuran, 2-methyl-tetrahydrofuran, diisopropyl ether, methyl tert-butyl ether, ethyl acetate, butyl acetate, cyclohexane, toluene, xylene, dichloromethane, dichloroethane, chloroform, and mixtures thereof. Unless otherwise specified, the term 'base' as used herein includes, but is not limited to, organic bases and inorganic bases such as carbonates, bicarbonates, hydroxides, alkoxides,, acetates and amides of alkali or alkali earth metals. Specifically, the inorganic base is selected from the group consisting of sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate, sodium bicarbonate, nota^i",™. bicarbonate. lithium bicarbonate, cesium bicarbonate, sodium hydroxide, *t? i; ; i ij- nTrrri-j AI > ' i .■ rww .■ n i ■>. t ,■ ■ i > potassium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium tertbutoxide, potassium tert.butoxide, sodium amide, potassium amide, lithium amide, ammonia, sodium acetate, potassium acetate, magnesium acetate, calcium acetate, and mixtures thereof. Specifically, the organic base is selected from the group consisting of dimethylamine, diethylamine, diisopropyl amine, diisopropylethylamine, di n-butylamine, diisobutylamine, triethylamine, tributylamine, tert-butyl amine, - pyridine, 4-dimethylaminopyridine (DMAP), and mixtures thereof. Unless otherwise specified, the term 'phase transfer catalysts' as used herein include, but are not limited to, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium iodide, benzyltrimethyl ammonium chloride, benzyltriethyl ammonium chloride, methyltributyl ammonium chloride, crown ethers and the like. Unless otherwise specified, the term 'salt' as used herein may include acid addition salts and base addition salts. Acid addition salts may be derived from organic and inorganic acids. Exemplary acid addition salts include, but are not limited to, hydrochloride, hydrobromide, sulphate, nitrate, phosphate, acetate, propionate, oxalate, succinate, maleate, fumarate, benzenesulfonate, toluenesulfonate, citrate, tartrate, and the like. A most specific acid addition salt is hydrochloride salt. Base addition salts may be derived from an organic or an inorganic base. For example, the base addition salts are derived from alkali or alkaline earth metals such as sodium, calcium, potassium and magnesium, ammonium salt and the like. The highly pure Bilastine or a pharmaceutically acceptable salt thereof obtained by the process disclosed herein has a purity of greater than about 99.5%, specifically greater than about 99.8%, more specifically greater than about 99.9% as measured by HPLC. For example, the purity of the highly pure Bilastine or a pharmaceutically acceptable salt thereof obtained by the processes disclosed herein is about 99.5% to about 99.99% as measured by HPLC. As used herein, the term "reflux temperature" means the temperature at which the solvent or solvent system refluxes or boils at atmospheric pressure. As used herein, the term "room temperature" refers to a temperature of about 20°C to about 35°C. For example, "room temperature" can refer to a temperature of about 25°C to about 30°C. , , , Exemplary^pMds^acids^usejJJp^Jep^a) include^ but are not limited to, aluminum chloride, aluminum bromide, boron trifluoride, boron tribromide, boron trichloride, tin tetrachloride, tin tetrabromide, stannous chloride, ferric chloride, zinc chloride, titanium tetrachloride, and hydrates or solvates thereof. A most specific Lewis acid used in step-(a) is aluminum chloride. The reaction in step-(a) is carried out in a suitable solvent. Exemplary solvents used in step-(a) include, but are not limited to, a halogenated hydrocarbon, a ketone, an ether, an ester, a hydrocarbon, and mixtures thereof. Specifically, the solvent used in step-(a) is selected from the group consisting of dichloromethane, dichloroethane, chloroform, acetone, methyl ethyl ketone, tetrahydrofuran, 2-methyl-tetrahydrofuran, diisopropyl ether, methyl tert-butyl ether, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, cyclohexane, toluene, xylene, arid mixtures thereof. A most specific solvent is dichloromethane. Specifically, the reaction in step-(a) is carried out at a temperature of about -10°C to about 50°C, and more specifically at a temperature of about -5°C to about 35°C. The reaction time may vary between about 30 minutes to about 5 hours, and specifically about 1 hour to about 3 hours. The reaction mass containing the compound of formula III or a salt thereof obtained in step-(a) may be subjected to usual work up methods such as a washing, a quenching, an extraction, a pH adjustment, an evaporation, a layer separation, decolorization, a carbon treatment, or a combination thereof. The reaction mass may be used directly in the next step to produce the compound of formula III A, or the compound of formula III or a salt thereof may be isolated and/or recrystallized and then used in the next step. Unless otherwise specified, the carbon treatment is carried out by methods known in the art, for example, by stirring the reaction mass/solution with finely powdered carbon at a temperature of about 40°C to the reflux temperature for at least 5 minutes, specifically at the reflux temperature; and filtering the resulting mixture through charcoal bed to obtain a filtrate containing compound by removing charcoal. Specifically, finely powdered carbon is a special carbon or an active carbon. In one embodiment, the compound of formula III or a salt thereof may be isolated and/or re-crystallized from a suitable solvent by conventional methods such as cooling, seeding, partial removal of the solvent from the solution, by adding an anti-solvent to the solution, evaporation, vacuum distillation, or a combination thereof. The solvent used for work up, isolation and/or recrystallization of the compound of formula III obtained by the process described herein is selected from the group as described hereinabove. In one embodiment, the hydrosilane reducing" agent used in step-(b) is selected from the group consisting of triethylsilane, trimethylsilane, dimethyl phenyl silane, phenyl silane, triphenylsilane, trichlorosilane, and the like; and a most specific reducing agent is triethylsilane. In another embodiment, the acid used in step-(b) is selected from the group consisting of boron trifluoride diethyl etherate, titanium tetrachloride, aluminum chloride, aluminum bromide, boron tribromide, tin tetrachloride, tin tetrabromide, stannous chloride, ferric chloride, zinc chloride, trifluoroacetic acid and methanesulfonic acid. A most specific acid used is titanium tetrachloride. Exemplary solvents used in step-(b) include, but are not limited to, a hydrocarbon solvent, a chlorinated hydrocarbon solvent, and mixtures thereof. Specifically, the solvent used in step-(b) is selected from the group consisting of toluene, xylene, dichloromethane, dichloroethane, chloroform, and mixtures thereof; and a most specific solvent is dichloromethane. In another embodiment, the reaction in step-(b) is carried out at a temperature of about -10°C to 50°C; and specifically at a temperature of about 10°C to about 40°C. The reaction time may vary between about 2 hours to 8 hours, and more specifically about 4 hours to 6 hours. The reaction mass containing the compound of formula IIIA or a salt thereof obtained in step-(b) may be subjected to usual work up methods such as a washing, a quenching, an extraction, a pH adjustment, an evaporation, a layer separation, decolorization, a carbon treatment, or a combination thereof. The reaction mass may be used directly in the next step to produce the compound of formula I, or the compound of formula IIIA or a salt thereof may be isolated and/or recrystallized and then used in the next step. In one embodiment, the compound of formula IIIA or a salt thereof may be isolated and/or re-crystallized from a suitable solvent by conventional methods as described hereinabove. The solvent used for work up, isolation and/or recrystallization of the compound of I—formula IIIA^obtaine^b^the^ro described hereinabove. In one embodiment, the base used in step-(c) is an organic base or an inorganic base selected from the group as described hereinabove. Specifically, the base used in step-(c) is an inorganic base. A most specific base used in step-(c) is sodium carbonate or potassium carbonate. In another embodiment, the reaction in step-(c) is carried out in the presence of a phase transfer catalyst. The phase transfer catalyst can be selected from the group as described hereinabove. Exemplary solvents used in step-(c) include, but are not limited, water, acetone, methyl ethyl ketone, methyl isobutyl ketone, acetonitrile, propionitrile and mixtures thereof. A most specific solvent used in step-(c) is water. In one embodiment, the reaction in step-(c) is carried out at a temperature of about 10°C to the reflux temperature of the solvent used, specifically at a temperature of about 30°C to the reflux temperature of the solvent used, and more specifically at the reflux temperature of the solvent used. The reaction time may vary from about 15 hours to about 25 hours. The reaction mass containing the Bilastine of formula I or a salt thereof obtained in step-(c) may be subjected to usual work up methods such as a washing, a quenching, an extraction, a pH adjustment, an evaporation, a layer separation, decolorization, a carbon treatment, or a combination thereof. In one embodiment, the Bilastine of formula I or a salt thereof may be isolated, purified and/or re-crystallized from a suitable solvent by conventional methods as described hereinabove. The solvent used for work up, isolation, recrystallization and/or purification of the Bilastine of formula I or a salt thereof obtained by the process described herein is selected from the group as described hereinabove. The crude Bilastine obtained in step-(c) is, optionally subjected to carbon treatment or silica gel treatment. The carbon treatment or silica gel treatment is carried out by methods known in the art, for example, as per the methods described hereinabove. 1 In one embodiment, the solvent used for purification of Bilastine obtained in step-(c) is selected from the group consisting of water, acetone, methanol, ethanol, isopropyl alcohol, ethyl acetate, butyl acetate, and mixtures thereof. The term "anti-solvent" refers to a solvent which when added to an existing -sc^on-Qf^subst^^ , t __ Exemplary anti-solvents include, but are not limited to, water, an alcohol, a ketone, a chlorinated hydrocarbon, a hydrocarbon, an ester, a nitrile, an ether, a polar aprotic solvent, and mixtures thereof. Removal of solvent is accomplished, for example, by substantially complete evaporation of the solvent, concentrating the solution or distillation of solvent, under inert atmosphere to obtain highly pure Bilastine or a salt thereof. According to another aspect, there is provided a novel compound, 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid, of formula IIIA: or a salt thereof. According to another aspect, there is provided a process for the preparation of 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid of formula IIIA: or a salt thereof, comprising: a) reacting the 2-methyl-2-phenyl-propanoic acid of formula II: or a salt thereof, with chloroacetyl chloride of formula VI: optionally in the presence of a Lewis acid, to produce 2-[4-(2-chloroacetyl)phenyl]-2-methyl-propanoic acid compound of formula III: . or a salt thereof; and b) reducing the compound of formula III obtained in step-(a) with a hydrosilane reagent in the presence of an acid to produce 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid of formula IIIA or a salt thereof. The preparation of the 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid compound of formula IIIA or a salt.thereof as described in the above process steps-(a) and (b) can be carried out by using the suitable solvents, reagents, methods, parameters and conditions as described hereinabove. According to another aspect, there is provided a process for the preparation of highly pure Bilastine of formula I:- or a pharmaceutically acceptable salt thereof, which comprises:. a) reducing the 2-[4-(2-chloroacetyl)phenyl]-2-methyl-propanoic acid compound of formula III: or a salt thereof, with a hydrosilane reagent in the presence of an acid to produce the 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid compound of formula IIIA: b) condensing the compound of formula IIIA obtained in step-(a) with l-(2-ethoxyethyl)-2-(piperidin-4-yl)benzimidazole of formula IV: or an acid addition salt thereof, in the presence of a base, optionally in the presence of a phase transfer catalyst, in a suitable solvent to produce Bilastine of formula I or a salt thereof, and optionally purifying the Bilastine obtained with a suitable solvent to produce highly pure Bilastine or a pharmaceutically acceptable salt thereof. The preparation of the Bilastine of formula I or a pharmaceutically acceptable salt thereof as described in the above process steps-(a) and (b) can be carried out by using the suitable solvents, reagents, methods, parameters and conditions as described hereinabove. According to another aspect, there is provided a process for the preparation of highly pure Bilastine of formula I: or a pharmaceutically acceptable salt thereof, comprising condensing the 2-[4-(2-chloroethyl)phenyl]-2-methyl-propanoic acid compound of formula IIIA: or a salt thereof, with l-(2-ethoxyethyl)-2-(piperidin-4-yl)benzimidazole of formula IV: or an acid addition salt thereof, in the presence of a base, optionally in the presence of a phase transfer catalyst, in a suitable solvent to produce Bilastine of formula I or a salt thereof, and optionally purifying the Bilastine obtained with a_suitable,SDlv.ent_tO-P^Hiirp highly pure Bilastine or a pharmaceutically acceptable salt thereof, The preparation of the Bilastine of formula I or a pharmaceutically acceptable salt thereof can be carried out by using the suitable solvents, reagents, methods, parameters and conditions as described hereinabove. The highly pure Bilastine or a salt thereof obtained by the above processes may be further dried in, for example, a Vacuum Tray Dryer, a Rotocon Vacuum Dryer, a Vacuum Paddle Dryer or a pilot plant Rota vapor, to further lower residual solvents. Drying can be ' carried out under reduced pressure until the residual solvent content reduces to the desired amount such as an amount that is within the limits given by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use ("ICH") guidelines. In one embodiment, the drying is carried out at atmospheric pressure or reduced pressures, such as below about 200 mm Hg, or below about 50 mm Hg, at temperatures such as about 35°C to about 90°C, and specifically at about 75°C to about 85°C. The drying can be carried out for any desired time period that achieves the desired result, such as times about 1 to 20 hours. Drying may also be carried out for shorter or longer periods of time depending on the product specifications. Temperatures and pressures will be chosen based on the volatility of the solvent being used and the foregoing should be considered as only a general guidance. Drying can be suitably carried out in a tray dryer, vacuum oven, air .. oven, or using a fluidized bed drier, spin flash dryer, flash dryer, and the like. The following examples are given only to illustrate the present invention. However, they should not be considered as limitation on the scope or spirit of the invention. EXAMPLES Example 1 Preparation of 2-[4-(2-Chloroacetyl)phenyl]-2-methyI-propanoic acid Aluminum chloride (122 g) was slowly added to a mixture of 2-methyl-2-phenyl-propanoic acid (25 g) and dichloromethane (250 ml) at room temperature. The resulting . mixture was cooled to -5 to -10CC, followed by drop wise addition of chloroacetyl chloride (34.5. g) at the same temperature. The temperature of the reaction mass was raised to 25-30°C and then stirred for 2 hours at the same temperature. After completion of the reaction, the reaction mass was poured into water (1300 ml), ice (160 g) and hydrochloric J_a

Documents

Orders

Section Controller Decision Date
Section 15 AHILAN B 2024-07-31
Section 15 AHILAN B 2024-07-31
Section 15 AHILAN B 2024-07-31

Application Documents

# Name Date
1 Form3_As Filed_29-08-2016.pdf 2016-08-29
2 Form2 Title Page_Provisional_29-08-2016.pdf 2016-08-29
3 Form1_As Filed_29-08-2016.pdf 2016-08-29
4 Description Provisional_As Filed_29-08-2016.pdf 2016-08-29
5 Correspondence by Agent_Provisional_29-08-2016.pdf 2016-08-29
6 Form5_Complete After Provisional_28-08-2017.pdf 2017-08-28
7 Form3_Complete After Provisional_28-08-2017.pdf 2017-08-28
8 Form2 Title Page_Complete After Provisional_28-08-2017.pdf 2017-08-28
9 Form1_Complete After Provisional_28-08-2017.pdf 2017-08-28
10 Description Complete_Complete After Provisional_28-08-2017.pdf 2017-08-28
11 Correspondence By Applicant_Form1,2,3,5_28-08-2017.pdf 2017-08-28
12 Claims_Complete After Provisional_28-08-2017.pdf 2017-08-28
13 Abstract_Complete After Provisional_28-08-2017.pdf 2017-08-28
14 Correspondence by Applicant_Request For Certified Copy_31-08-2017.pdf 2017-08-31
15 Correspondence by Applicant_Form30_18-09-2017.pdf 2017-09-18
16 Form 3 _ISR,Writien Opinion_15-01-2018.pdf 2018-01-15
17 Form 3 _After Filing_15-01-2018.pdf 2018-01-15
18 Correspondence by applicant_Form 3_15-01-2018.pdf 2018-01-15
19 Others_PCT_ 21-01-2019.pdf 2019-01-21
20 Form3_After Filing_21-01-2019.pdf 2019-01-21
21 Correspondence by Applicant_Form3_21-01-2019.pdf 2019-01-21
22 201641029306-FORM 18 [18-08-2020(online)].pdf 2020-08-18
23 201641029306-FORM 13 [18-08-2020(online)].pdf 2020-08-18
24 201641029306-FORM-26 [19-09-2020(online)].pdf 2020-09-19
25 201641029306_Correspondence_23-09-2020.pdf 2020-09-23
26 201641029306-Proof of Right [27-09-2020(online)].pdf 2020-09-27
27 201641029306-Correspondence_Form1_30-09-2020.pdf 2020-09-30
28 201641029306-PRE GRANT OPPOSITION FORM [18-12-2020(online)].pdf 2020-12-18
29 201641029306-PRE GRANT OPPOSITION DOCUMENT [18-12-2020(online)].pdf 2020-12-18
30 201641029306-OTHERS [18-12-2020(online)].pdf 2020-12-18
31 201641029306-FORM-26 [22-12-2020(online)].pdf 2020-12-22
32 201641029306-FORM 4(ii) [29-05-2021(online)].pdf 2021-05-29
33 201641029306-Retyped Pages under Rule 14(1) [09-09-2021(online)].pdf 2021-09-09
34 201641029306-Retyped Pages under Rule 14(1) [09-09-2021(online)]-1.pdf 2021-09-09
35 201641029306-FORM 3 [09-09-2021(online)].pdf 2021-09-09
36 201641029306-FER_SER_REPLY [09-09-2021(online)].pdf 2021-09-09
37 201641029306-2. Marked Copy under Rule 14(2) [09-09-2021(online)].pdf 2021-09-09
38 201641029306-2. Marked Copy under Rule 14(2) [09-09-2021(online)]-1.pdf 2021-09-09
39 201641029306-Correspondence_Copy of Online Submission_14-09-2021.pdf 2021-09-14
40 201641029306-FER.pdf 2021-10-17
41 201641029306-Written submissions and relevant documents [17-01-2023(online)].pdf 2023-01-17
42 201641029306-POA [17-01-2023(online)].pdf 2023-01-17
43 201641029306-FORM 13 [17-01-2023(online)].pdf 2023-01-17
44 201641029306-PreGrant-HearingNotice-(HearingDate-24-01-2024).pdf 2023-12-22
45 201641029306-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [21-01-2024(online)].pdf 2024-01-21
46 201641029306-PreGrant-ExtendedHearingNotice-(HearingDate-23-02-2024).pdf 2024-01-22
47 201641029306-Correspondence to notify the Controller [22-01-2024(online)].pdf 2024-01-22
48 201641029306-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [20-02-2024(online)].pdf 2024-02-20
49 201641029306-Correspondence to notify the Controller [22-02-2024(online)].pdf 2024-02-22
50 201641029306-PreGrant-ExtendedHearingNotice-(HearingDate-13-03-2024).pdf 2024-03-01
51 201641029306-Correspondence to notify the Controller [11-03-2024(online)].pdf 2024-03-11
52 201641029306-Correspondence to notify the Controller [12-03-2024(online)].pdf 2024-03-12
53 201641029306-Written submissions and relevant documents [27-03-2024(online)].pdf 2024-03-27
54 201641029306-Written submissions and relevant documents [27-03-2024(online)]-1.pdf 2024-03-27
55 201641029306-Retyped Pages under Rule 14(1) [31-07-2024(online)].pdf 2024-07-31
56 201641029306-PatentCertificate31-07-2024.pdf 2024-07-31
57 201641029306-IntimationOfGrant31-07-2024.pdf 2024-07-31
58 201641029306-2. Marked Copy under Rule 14(2) [31-07-2024(online)].pdf 2024-07-31
59 201641029306-Response to office action [26-09-2025(online)].pdf 2025-09-26

Search Strategy

1 IntellectualPropertyIndiaE_20-11-2020.pdf

ERegister / Renewals

3rd: 25 Oct 2024

From 29/08/2018 - To 29/08/2019

4th: 25 Oct 2024

From 29/08/2019 - To 29/08/2020

5th: 25 Oct 2024

From 29/08/2020 - To 29/08/2021

6th: 25 Oct 2024

From 29/08/2021 - To 29/08/2022

7th: 25 Oct 2024

From 29/08/2022 - To 29/08/2023

8th: 25 Oct 2024

From 29/08/2023 - To 29/08/2024

9th: 25 Oct 2024

From 29/08/2024 - To 29/08/2025

10th: 27 Aug 2025

From 29/08/2025 - To 29/08/2026