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Salts Of Methyl 6 (2,4 Dichlorophenyl) 5 [4 [(3 S) 1 (3 Fluoropropyl)pyrrolidin 3 Yl]Oxyphenyl] 8,9 Dihydro 7 H Benzo[7]Annulene 2 Carboxylate And Preparation Process Thereof

Abstract: Herein are provided novel salts of methyl 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylate namely the oxalate salt (I) and the dibenzoyltartrate salt (II).

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Patent Information

Application #
Filing Date
03 April 2021
Publication Number
22/2021
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
PATENTS@DPAHAUJA.COM
Parent Application
Patent Number
Legal Status
Grant Date
2023-03-08
Renewal Date

Applicants

SANOFI
54, rue La Boétie 75008 PARIS

Inventors

1. MALPART, Joël
Sanofi - Patent Department 54 rue La Boétie 75008 Paris
2. RUIZ MONTES, José
Sanofi - Patent Department 54 rue La Boétie 75008 Paris

Specification

SALTS OF METHYL 6-(2,4-DICHLOROPHENYL)-5-[4-[(3S)-1-(3- FLUOROPROPYL)PYRROLIDIN-3-YL]OXYPHENYL]-8,9-DIHYDRO-7H- B ENZO[7]AN N U LE N E-2-CARBOXYLATE AND PREPARATION PROCESS THEREOF Herein are provided novel salts of methyl 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylate. Methyl 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylate, also named as 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid methyl ester and hereafter designated as “compound (2)”, is the N-1 intermediate in the synthesis of 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (hereafter “compound (1 )”). Indeed, compound (1 ) can be obtained by saponification of compound (2). Compound (1 ), depicted below, is a selective estrogen receptor degrader (SERD) which has estrogen receptor antagonist properties and accelerates the proteasomal degradation of the estrogen receptor. It may be used in particular as anticancer agent. This compound is disclosed in the patent application WO 2017/140669. For active ingredients in medicinal products and their synthesis intermediates there is always a need to find new synthesis routes more adapted for industrial implementation. Herein are provided novel salt forms of compounds (2), namely an oxalate salt of said compound: and a dibenzoyltartrate salt: Herein are further provided processes for the preparation of the above-mentioned salt forms of compounds (2), namely: a process for the preparation of an oxalate salt of compound (2), comprising the step of adding oxalic acid to said compound (2) in a solvent chosen from ester-type solvent, ether-type solvent and toluene; and - a process for the preparation of a dibenzoyltartrate salt of compound (2), comprising the step of adding dibenzoyl tartaric acid to said compound in a mixture of toluene and heptane. Said salts according to the present invention are particularly useful in the framework of the preparation of compound (1 ) as defined above. The advantages of said salts will be apparent from the detailed description of said process. The salts according to the invention may be obtained according to the preparation processes detailed herein after. In particular, the salts according to the invention may be obtained following the route of synthesis as described in the patent application WO 2017/140669 as represented in Scheme 3 and 4 herein after. The step before obtaining the salt is represented by the scheme below. Intermediate (D5) Compound (2) Said step may be followed by a salification step as detailed herein after. Example 5 of the present application starts from intermediate (D5) for forming via a Suzuki coupling a compound (2) as defined herein above, which is itself used for forming a salt of compound (2). Alternatively, the salts according to the invention may be obtained by a salification step following a Suzuki coupling in the framework of the preparation of compound (2) as an improved process which is detailed hereinafter. Improved process The present text describes a process for the preparation of compound (2) (methyl ester of compound (1 )) implementing the salt forms described above: in salts forms, characterized in that compound (2) may be obtained by a Suzuki coupling of compound (3), wherein LG represents a leaving group, with an organoboron reagent: followed by a salification reaction. Compound (3) as described above may be obtained by activation of compound (4) with a leaving group LG: Compound (4) as described above may be obtained by alpha-arylation of methyl 5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-carboxylate (represented as compound (5) below) with 1-LG’-2, 4-dichlorobenzene as defined herein after: LG’ represents any leaving group. LG’ may represents a leaving group of the formula -0-S02-CnF(2n+i) with n = 1 to 4, more particularly a triflate (wherein n = 1 ) or a nonaflate (wherein n = 4), or a halogen atom selected from bromine or iodine. 1 -LG’-2, 4-dichlorobenzene may be 1 -Hal-2, 4-dichlorobenzene, wherein Hal represents a halogen atom selected from bromine or iodine: The leaving groups LG and LG’ are defined as a chemical moiety displaying leaving group properties and allowing further substitution in a subsequent chemical reaction. More particularly, the leaving group LG in compound (3) may be obtained by activating the carbonyl function in compound (4). Conventional activation reactions of the carbonyl function in compound (4) may be used as known to one of skill in the Art. For example, the leaving group LG in compound (3) may be a halogen atom or an alkyl or aryl sulfamate, an alkyl or aryl phosphate or an alkyl or aryl sulfonate, in particular a halogen atom or an alkyl or aryl sulfonate. The leaving group LG may be a halogen atom or a mesylate, tosylate, sulfamate, phosphate, triflate or nonaflate group. The leaving group in compound (3) may be a halogen atom or a mesylate, tosylate, sulfamate, phosphate or triflate group. The leaving group LG may be a triflate or a nonaflate group. Advantageously, the leaving group LG is the triflate group (trifluoromethanesulfonyl, corresponding to the formula -0-S(0)2-CF3). In the context of the present specification, the terms below have the following definitions unless otherwise mentioned throughout the instant specification: - an alkyl group: a linear or branched saturated hydrocarbon-based aliphatic group comprising, unless otherwise mentioned, from 1 to 6 carbon atoms (noted“(Ci-C6)-alkyl”). By way of examples, mention may be made of, but not limited to: methyl, ethyl, propyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl and isohexyl groups, and the like. Said groups may be partially or fully substituted by fluorine atoms and include but not be limited to perfluoromethyl, perfluoroethyl, perfluoropropyl, perfluorobutyl, and the like; - an aryl group: phenyl, naphtyl or substituted phenyl, wherein a substituted phenyl is defined as a phenyl group in which one or more of the hydrogens has been replaced by the same or different substituents including, but not limited to: halogen atom, alkyl, nitro, cyano, alkoxy, aryl, heteroaryl and trifluoromethyl groups, and the like. Compound (4) may be activated into compound (3’), wherein compound (3’) is defined as compound (3) wherein LG represents the triflate group. The activation of compound (4) into compound (3’) is a triflation reaction: In such a reaction a triflation reagent is used, such as N-phenylbistriflimide or triflic anhydride. Advantageously, N-phenylbistriflimide, also known as N,N-bis(trifluoromethylsulfonyl)aniline, is used as the triflation reagent. This reagent is advantageously used in a slight excess amount relative to compound (4), such as about 1 .3 eq. (equivalent). Suitable triflation media depend on the triflation reagent used, as known to one of skill in the Art. The triflation reaction is carried out is an appropriate organic solvent, for example THF (tetrahydrofuran), Me-THF (methyl-tetrahydrofuran), acetonitrile, dioxane, or a mixture of toluene with Me-THF. Advantageously, Me-THF is used as organic solvent. The triflation reaction is advantageously carried out with N-phenylbistriflimide as triflation reagent, in Me-THF as organic solvent. The temperature for the triflation reaction is advantageously chosen between 0°C and room temperature. The triflation reaction is carried out with a strong base, for example sodium hydride (NaH), potassium bis(trimethylsilyl)amide (KHMDS) or a phosphazene base such as BEMP (2-tert-butylimino-2-diethylamino-1 ,3-dimethylperhydro-1 ,3,2-diazaphosphorine) or BTPP (tert-butylimino-tri(pyrrolidino) phosphorane). Advantageously, sodium hydride is used as a strong base. When NaH is used as strong base, the triflation reaction is carried out with a catalyst, for example DBU (1 ,8-diazabicyclo[5.4.0]undec-7-ene) or DBN (1 ,5-diazabicyclo(4.3.0)non-5-ene). Advantageously, DBU is used as catalyst. Advantageously, the triflation reaction is carried out with sodium hydride as strong base, and with DBU as catalyst. Advantageously, a catalytic amount of DBU is used in the triflation reaction (such as about 0.2 eq.) and a stoichiometric amount of NaH (such as about 1.0-1.1 eq.), or a sub-stoichiometric amount of NaH (about 0.7-0.8 eq.) and a stoichiometric amount of DBU (about 1.0-1.2 eq.). The triflation reaction is advantageously followed by a crystallization of the product obtained, according to crystallization techniques known to one of skill, so as to obtain compound (3) in a high purity, such as a purity level equal to or greater than 99%, before having it undergo the next steps of the process. Such a crystallization step may be carried out for example in acetonitrile, tert-amyl alcohol, heptane or diisopropylether. Advantageously, the crystallization is carried out in acetonitrile. The crystallization in acetonitrile is advantageously carried out at 0°C and may be followed by drying at about 45°C. The alpha-arylation of compound (5) to produce compound (4) may be carried out with 1-iodo-2, 4-dichlorobenzene or with 1-bromo-2, 4-dichlorobenzene, which are both commercially available reactants. Advantageously, 1-bromo-2, 4-dichlorobenzene is used as alpha-arylation reactant. This alpha-arylation step may be carried out in an organic solvent, in presence of a palladium derivative as catalyst, of an appropriate ligand for the alpha-arylation reaction, and of a mineral base. Advantageously, the alpha-arylation step may be carried out in xylene, toluene, butyl acetate, isopropyl acetate or THF as organic solvent, using palladium(ll) acetate (Pd(OAc)2) or tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3) as catalyst, and Xantphos (4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) as ligand. Alternatively, when Pd2dba3 is used as catalyst, DPEPhos (bis[(2-diphenylphosphino)phenyl] ether) may be used as ligand. Another possible palladium derivative for use in the alpha-arylation step is [1 ,1 '-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(ll) (PdCl2(dtbpf)). Avantageously, the alpha-arylation step may be carried out in toluene as organic solvent and with Pd2dba3 as catalyst. Under these conditions, heating at reflux may be applied. Advantageously, the alpha-arylation step may be carried out in the presence of a mineral base, such as K2CO3, K3PO4, CS2CO3 and tBuONa. The mineral base is advantageously present in excess, such as 1.5 to 4 equivalent (eq.), more particularly 2.5 to 4 eq., in respect to the compound (5). The Suzuki reaction applied on compound (3) to produce compound (2) may be defined as a coupling reaction using an organoboron reagent and a transition metal-based catalyst, advantageously a palladium-based catalyst. Advantageously, the organoboron reagent for use in the Suzuki coupling step of the process described herein may be reagent (1 ), namely (3S)-1 -(3-fluoropropyl)-3-[4-(4, 4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenoxy]pyrrolidine, which is described in the patent application WO 2017/140669, or the corresponding acid (named reagent (2) as illustrated below), obtained by hydrolysis of the ester moiety of reagent (1 ), or a salt thereof such as the trifluoroborate potassium salt (named reagent (3) as illustrated below), obtained by salification of the boronic acid or ester moiety of reagent (2) or (1 ) by potassium hydrogen difluoride (KHF2): reagent (1 ) reagent (2) reagent (3) The content of patent application WO 2017/140669 for the preparation of (3S)-1-(3-fluoropropyl)-3-[4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenoxy]pyrrolidine (reagent (1 )) is herein incorporated by reference. The organoboron reagent for use in the Suzuki coupling step of the process described herein may advantageously be used in an equimolar amount (i.e. about 1 eq.) relative to the compound (3). The palladium-based catalyst for use in the Suzuki coupling step of the process described herein may advantageously be the palladium complex bis(triphenylphosphine)palladium(ll) dichloride, of formula PdCl2(PPh3)2. It is used in catalytic amount, for example at an amount of about 0.05 eq. Suitable reaction media for the Suzuki coupling step of the process described herein depend on the specific reagents used, as known to one of skill in the Art. When bis(triphenylphosphine)palladium(ll) dichloride is used as a catalyst, the reaction may advantageously be carried out with an inorganic base, such as cesium carbonate (CS2CO3), and in an organic solvent, such as a water/acetonitrile (CH3CN) mixture. Salification step The salification step as described herein after can be implemented for both routes of synthesis (WO 2017/140669 route and the improved route). Both routes contain a Suzuki coupling step before such salification step. Still in the framework of the preparation of compound (2), a salification reaction may be performed after the Suzuki coupling step so as to obtain compound (2) in a salt form according to the present invention, advantageously in the form of an oxalate salt or of a dibenzoyltartrate salt. The Suzuki coupling may thus be followed by a salification reaction, for example for obtaining an oxalate salt of compound (2) or a dibenzoyltartrate salt of compound (2). The oxalate salt of compound (2) provided herein may be obtained using oxalic acid in a solvent selected from an ester-type solvent, such as an acetate solvent (for example ethyl acetate or isopropyl acetate), an ether-type solvent, such as MTBE (methyl-tertbutyl ether) or diisopropyl ether, and toluene. Advantageously, the oxalate salt of compound (2) may be obtained using oxalic acid in isopropylacetate, under heating, for example between 60°C and 80°C, preferably at about 70°C. The said process forms part of the present invention. Thus, the present invention further provides a process for the preparation of an oxalate salt of compound (2), comprising the step of adding oxalic acid to a compound (2) in a solvent chosen from ester-type solvent, ether-type solvent and toluene. In a particular embodiment, the ester-type solvent is an acetate solvent, in particular ethyl acetate or isopropyl acetate, more particularly isopropyl acetate. In another embodiment, the ether-type solvent is chosen from methyl-tertbutyl and diisopropryl ether. In a particular embodiment, the process for the preparation of an oxalate salt of compound (2) is carried out in isopropyl acetate, under heating, in particular between 60°C and 80°C and more particularly at 70°C. The dibenzoyltartrate salt of compound (2) provided herein may be obtained using dibenzoyl tartaric acid (also named (2R,3R)-2,3-dibenzoyloxybutanedioic acid), in a mixture of toluene and heptane. The said process forms part of the present invention. Thus, the present invention further provides a process for the preparation of a dibenzoyltartrate salt of compound (2), comprising the step of adding dibenzoyl tartic acid to a compound (2) in a mixture of toluene and heptane. The term“salification” of compound (2) as described above refers to the formation of a salt, allowing to precipitate compound (2). Especially for the oxalate salt, such salification step allows to recover compound (2) from the reaction mixture in high purity. It also allows avoiding the use of a column chromatography for recovering the compound (2) from the reaction mixture in high purity. Such a route of synthesis with a salt formation is particularly convenient for the industrial scale and for the storage of compound (2). Example 6 of the present application illustrates the suitable solvents for various ways of obtaining the claimed salts. The dibenzoyl tartrate salt of compound (2) precipitates with a purity of about 93%, and the oxalate salt of compound (2) with a purity level equal to or greater than 98%. In view of the above description, the process described herein for the preparation of compound (2) is represented in scheme 1 below, wherein LG’ and LG are as defined above: Scheme 1 : The process described herein for the preparation of compound (2) is also represented in scheme 2 below, wherein LG’ is as defined above: Scheme 2 Compound (2) may undergo a saponification reaction, whereby the hydrolysis of the ester function will yield compound (1 ), bearing the corresponding acidic function. Such a saponification reaction may be carried out under conditions known to one of skill in the Art, namely in basic medium, advantageously using sodium hydroxide as a base, and in an organic solvent, advantageously an alcoholic solvent, such as methanol. Heating is applied during the saponification reaction so as to accelerate the hydrolysis of the ester moiety, for example at about 60°C. Such a saponification reaction is described in the patent application WO 2017/140669. As a salt form of compound (2) is used, a free base of compound (2) is prepared before carrying out the saponification reaction, for example using an aqueous solution of potassium carbonate. Described herein is also a process for the preparation of compound (1 ): by saponification of compound (2): wherein compound (2) is obtained by the process described above. Disclosed herein are also compounds (4), (3) and (3’), wherein LG represents a leaving group as described above: Compounds (4), (3) and (3’) are useful as novel intermediates in the preparation of compound (2). The process for the preparation of compound (2) described herein is particularly advantageous for industrial implementation as it comprises fewer reaction steps than other processes of synthesis of compound (2) known to date, which are described in the patent application WO 2017/140669. Scheme 3 below illustrates the shortest process for the synthesis of compound (2) described in WO 2017/140669. In scheme 3, each intermediate is designated under the same name as provided in said international patent application. This process as illustrated in scheme 3, starting from the commercially available intermediate 2-methoxy-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one, is hereafter designated as“route A”. Scheme 3: Route A Under route A illustrated in scheme 3, compound (2) is obtained in 4 steps starting from methyl 5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-carboxylate (same compound designated as“compound (5)” herein and as“intermediate (A5)” in WO 2017/140669). The process for the preparation of compound (2) described herein therefore allows to obtain this compound in only 3 steps starting from methyl 5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-carboxylate, compared to route A. A second process of synthesis of compound (2) is described in WO 2017/140669, starting from the same intermediates 2-methoxy-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one and intermediate (A2) as in scheme 3 above. This second process of synthesis of compound (2) is illustrated in scheme 4 below, wherein each intermediate is designated under the same name as provided in patent application WO 2017/140669. This process under scheme 4 is hereafter designated as“route B”. Scheme 4: Route B It therefore appears that the process for the preparation of compound (2) under scheme 4 entails many more reaction steps than the one under scheme 3. Hence the process for the synthesis of compound (2) as described herein is shorter in terms of number of steps compared to both routes A and B as described in WO 2017/140669. Below are described examples of protocols for the synthesis of salts of compound (2), according to the processes of synthesis described herein. Example 1 : Preparation of the organoboron derivative“reagent (1)” The preparation of reagent (1 ), useful in the Suzuki coupling step of the process for synthesis of compound (2) as described herein, is illustrated in scheme 5 below, reproduced from the patent application WO 2017/140669. SCHEME 5: STEP 1 Compound (d) Reagent (1) According to scheme 5, the commercially available compound (a) (4-(4, 4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenol) is condensed in tetrahydrofuran (THF) at room temperature on (R)-1-N-Boc-3-hydroxypyrrolidine, using N,N,N',N'-tetramethylazodicarboxamide as coupling agent. According to step 2, the compound (c) thus obtained is N-deprotected in methanol (MeOH) at room temperature using an acidic agent, for example a solution of HCI 4N in dioxane. Alkylation of the pyrrolidine nitrogen is then performed under step 3 by reacting compound (d) with the corresponding 1 , 1 -disubstituted 1-halogeno-3-fluoro propane, for example 1-iodo-3-fluoropropane, in acetonitrile in presence of potassium carbonate (K2CO3) at about 40°C. Steps 1 to 3 of scheme 5 are illustrated by the detailed protocols below. The 1H NMR spectra were performed on a Bruker Avance DRX-400 spectrometer, with the chemical shifts (d in ppm) in the solvent dimethyl sulfoxide-d6 (dDMSO-d6) referenced at 2.50 ppm at a temperature of 303 K. Coupling constants (J) are given in Hertz. The liquid chromatography/mass spectrography (LC/MS) data were obtained on a UPLC Acquity Waters instrument, light scattering detector Sedere and SQD Waters mass spectrometer using UV detection DAD 210

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Application Documents

# Name Date
1 202137015849-IntimationOfGrant08-03-2023.pdf 2023-03-08
1 202137015849-TRANSLATIOIN OF PRIOIRTY DOCUMENTS ETC. [03-04-2021(online)].pdf 2021-04-03
2 202137015849-PatentCertificate08-03-2023.pdf 2023-03-08
2 202137015849-STATEMENT OF UNDERTAKING (FORM 3) [03-04-2021(online)].pdf 2021-04-03
3 202137015849-Response to office action [15-02-2023(online)].pdf 2023-02-15
3 202137015849-POWER OF AUTHORITY [03-04-2021(online)].pdf 2021-04-03
4 202137015849-FORM 1 [03-04-2021(online)].pdf 2021-04-03
4 202137015849-Correspondence to notify the Controller [03-02-2023(online)].pdf 2023-02-03
5 202137015849-US(14)-ExtendedHearingNotice-(HearingDate-08-02-2023).pdf 2022-12-06
5 202137015849-DECLARATION OF INVENTORSHIP (FORM 5) [03-04-2021(online)].pdf 2021-04-03
6 202137015849-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [05-12-2022(online)].pdf 2022-12-05
6 202137015849-COMPLETE SPECIFICATION [03-04-2021(online)].pdf 2021-04-03
7 202137015849-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [01-11-2022(online)].pdf 2022-11-01
7 202137015849-Proof of Right [07-09-2021(online)].pdf 2021-09-07
8 202137015849-US(14)-ExtendedHearingNotice-(HearingDate-21-12-2022).pdf 2022-11-01
8 202137015849-FORM 3 [07-09-2021(online)].pdf 2021-09-07
9 202137015849-Response to office action [19-10-2022(online)].pdf 2022-10-19
9 202137015849.pdf 2021-10-18
10 202137015849-FORM 18 [11-07-2022(online)].pdf 2022-07-11
10 202137015849-US(14)-HearingNotice-(HearingDate-14-11-2022).pdf 2022-10-03
11 202137015849-ABSTRACT [01-09-2022(online)].pdf 2022-09-01
11 202137015849-FER.pdf 2022-08-02
12 202137015849-CLAIMS [01-09-2022(online)].pdf 2022-09-01
12 202137015849-OTHERS [01-09-2022(online)].pdf 2022-09-01
13 202137015849-CORRESPONDENCE [01-09-2022(online)].pdf 2022-09-01
13 202137015849-FER_SER_REPLY [01-09-2022(online)].pdf 2022-09-01
14 202137015849-CORRESPONDENCE [01-09-2022(online)].pdf 2022-09-01
14 202137015849-FER_SER_REPLY [01-09-2022(online)].pdf 2022-09-01
15 202137015849-CLAIMS [01-09-2022(online)].pdf 2022-09-01
15 202137015849-OTHERS [01-09-2022(online)].pdf 2022-09-01
16 202137015849-ABSTRACT [01-09-2022(online)].pdf 2022-09-01
16 202137015849-FER.pdf 2022-08-02
17 202137015849-US(14)-HearingNotice-(HearingDate-14-11-2022).pdf 2022-10-03
17 202137015849-FORM 18 [11-07-2022(online)].pdf 2022-07-11
18 202137015849-Response to office action [19-10-2022(online)].pdf 2022-10-19
18 202137015849.pdf 2021-10-18
19 202137015849-FORM 3 [07-09-2021(online)].pdf 2021-09-07
19 202137015849-US(14)-ExtendedHearingNotice-(HearingDate-21-12-2022).pdf 2022-11-01
20 202137015849-Proof of Right [07-09-2021(online)].pdf 2021-09-07
20 202137015849-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [01-11-2022(online)].pdf 2022-11-01
21 202137015849-COMPLETE SPECIFICATION [03-04-2021(online)].pdf 2021-04-03
21 202137015849-REQUEST FOR ADJOURNMENT OF HEARING UNDER RULE 129A [05-12-2022(online)].pdf 2022-12-05
22 202137015849-DECLARATION OF INVENTORSHIP (FORM 5) [03-04-2021(online)].pdf 2021-04-03
22 202137015849-US(14)-ExtendedHearingNotice-(HearingDate-08-02-2023).pdf 2022-12-06
23 202137015849-Correspondence to notify the Controller [03-02-2023(online)].pdf 2023-02-03
23 202137015849-FORM 1 [03-04-2021(online)].pdf 2021-04-03
24 202137015849-POWER OF AUTHORITY [03-04-2021(online)].pdf 2021-04-03
24 202137015849-Response to office action [15-02-2023(online)].pdf 2023-02-15
25 202137015849-STATEMENT OF UNDERTAKING (FORM 3) [03-04-2021(online)].pdf 2021-04-03
25 202137015849-PatentCertificate08-03-2023.pdf 2023-03-08
26 202137015849-TRANSLATIOIN OF PRIOIRTY DOCUMENTS ETC. [03-04-2021(online)].pdf 2021-04-03
26 202137015849-IntimationOfGrant08-03-2023.pdf 2023-03-08

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