WO2017208105A1 - Novel crystalline form of dolutegravir sodium - Google Patents
Novel crystalline form of dolutegravir sodium Download PDFInfo
- Publication number
- WO2017208105A1 WO2017208105A1 PCT/IB2017/052926 IB2017052926W WO2017208105A1 WO 2017208105 A1 WO2017208105 A1 WO 2017208105A1 IB 2017052926 W IB2017052926 W IB 2017052926W WO 2017208105 A1 WO2017208105 A1 WO 2017208105A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cmr
- solvent
- process according
- dol
- utegravi
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
Definitions
- the present invention provides novel crystalline form A of Dolutegravir sodium and process for preparation thereof.
- Dolutegravir is an integrase inhibitor. It is used against HIV infections as a single drug or fixed-dose combination with abacavir sulphate and lamivudine under the trade names Tivicay ⁇ andTriumeq ⁇ respectively.
- Dolutegravir sodium is disclosed in the patent US 8129385 and the patent US 9242986 mentions crystal form of a sodium salt of dolutegravir and crystal form of a hydrate of sodi um salt of dol utegravi r.
- Another patent US 9206197 mentions amorphous form of dolutegravir sodium and process for its preparation.
- the applications WO 2015118460 and WO 2015139591 provide various crystalline forms of dolutegravir sodium
- the applications WO 2015138933 and WO 2015092752 provide various crystalline forms of dolutegravir sodium solvates and WO 2016016279 mentions hydrates of dolutegravir sodium.
- the present invention provides novel crystalline form of dol utegravi r sodi urn designated as Form A and process for preparation thereof. DESCRIPTION OF DRAWING
- Figure 1 X-ray powder diffraction pattern of crystalline Form A of dol utegravi r sodium.
- Figure2 Infrared absorption spectrum of crystalline FormA of dol utegravi r sodium.
- Figure 3- DSC thermogram of crystalline FormA of dol utegravi r sodium
- the present invention provides novel crystalline form A of dol utegravi r sodium with characteristic diffraction peaks at 633 ⁇ 4 7.83 ⁇ 4 9.33 ⁇ 4 ⁇ Ae, 12.43 ⁇ 4 13.53 ⁇ 4 12.7e ⁇ 15.13 ⁇ 4 15.8e ⁇ 18.33 ⁇ 4 19.0 ⁇ 19.6 ⁇ 20.7e ⁇ 22.8e ⁇ 23.13 ⁇ 4 24.3e and 25.8e e 0.2 degree two theta in an X-ray diffraction pattern.
- the present invention further provides process for preparation of crystalline form A of dol utegravi r sodium
- the present invention relates to novel crystalline form A of dol utegravi r sodium and processes for its preparation.
- the present invention provides crystalline form A of dol utegravi r sodium.
- the crystalline form A of dolutegravir sodium is characterized by infrared absorption spectrum as depicted i n Figure 2.
- the crystalline form A of dolutegravir sodium is characterized by Differential Scanning Calorimetry (DSC) thermogram as depicted in Figure 3.
- the present invention provides a process for the preparation of crystal I i ne form A of dol utegravi r sodi um comprisi ng the steps of: a) dissolving dol utegravir sodium in a first solvent;
- step (b) addi ng the sol uti on of step (a) to a pre cool ed sol uti on of second solvent; and c) i sol ati ng form A of dol utegravi r sodi um
- the first solvent and second solvent can be selected from polar solvent non-polar solvents or mixtures thereof.
- Polar solvent can be selected from alcohols like methanol, ethanol, butanol, propanol; nitriles l ike acetonitrile, propionitrile, butyronitrile; ethers like tetrahydrofuran, dioxane, di methoxyethane; esters like ethyl acetate, ethyl acetoacetate, butyl acetate, propyl acetate; ketones like acetone, methyl ethyl ketone, methyl isobutyl ketone; other polar solvents li ke dimethylformamide, dimethyl sulfoxide, water and mixtures thereof.
- Non-polar solvents can be selected from hydrocarbon like hexane, cyclohexane, n-heptane, pentane, cyclopentane, toluene; chlori nated hydrocarbon solvent like methylene chloride, ethylene chloride, chloroform, carbon tetrachloride and mixtures thereof.
- the first solvent is preferably dimethyl sulfoxide and second solvent is preferably methanol.
- step (b) the second solvent can be pre cooled to a temperature of less than 30eC, preferably less than 20eC, more preferably less than 10eC.
- step (c) form A of dolutegravir sodium can be isolated by techniques known in art like filtration, concentration, evaporation of solvents etc.
- the form A of dolutegravir sodium of the present invention was found to be stable at 40eC/ 75% RH; 25eC/ 60% RH and 5eC.
- the total impurity content in form A of dolutegravir sodium was found to be not more than 0.1% by H PLC, in stabil ity.
- Dolutegravir sodium which is used for preparation of form A of dol utegravir sodium can be prepared by methods as described in application WO 2010068253 or by preparations known in the literature.
- the infrared absorption spectrum was obtained using a Perkin Elmer Precisely Spectrum 400 i nstrument usi ng K B r pel I et method.
- E xampl e 1 Preparati on of crystal I i ne form A of dol utegravi r sodi um: A mixture of dolutegravir sodium (1 g) and dimethyl sulfoxide (250 ml) was heated at 130eC. The solution was cooled to 25-30eC. This solution was added dropwise to methanol (75 ml) at -10eC. Methanol (25 ml) was added to this mixture at -10eC and stirred for 6-7 hours. The mixture was then stirred for 15 minutes at 25eC. The solid filtered and dried under vacuum Y ield 0.8 g.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides novel crystalline form A of dolutegravir sodium with characteristic diffraction peaks at 6.3, 7.8, 9.3, 11.4, 12.4, 13.5, 12.7, 15.1, 15.8, 18.3, 19.0, 19.6, 20.7, 22.8, 23.1, 24.3 and 25.8 ± 0.2 degree two theta in an X-ray diffraction pattern. The present invention further provides process for preparation of crystalline form A of dolutegravir sodium.
Description
NOVEL CRYSTALLINE FORM OF DOLUTEGRAVIR SODIUM
FIELD OF INVENTION The present invention provides novel crystalline form A of Dolutegravir sodium and process for preparation thereof.
BACKGROUND OF THE INVENTION Dolutegravir is an integrase inhibitor. It is used against HIV infections as a single drug or fixed-dose combination with abacavir sulphate and lamivudine under the trade names Tivicay÷ andTriumeq÷ respectively. These commercial products contain dolutegravir as its sodium salt It is chemically known as sodium (4R,12aS)-9-{[(2,4- difl uoropheny I) methyl] carbamoyl} -4- methyl -6,8- di oxo-3,4,6,8,12,12a-hexahydro-2H- pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate (I) having following chemical structure.
(I)
Dolutegravir sodium is disclosed in the patent US 8129385 and the patent US 9242986 mentions crystal form of a sodium salt of dolutegravir and crystal form of a hydrate of sodi um salt of dol utegravi r.
Another patent US 9206197 mentions amorphous form of dolutegravir sodium and process for its preparation. The applications WO 2015118460 and WO 2015139591 provide various crystalline forms of dolutegravir sodium The applications WO 2015138933 and WO 2015092752 provide various crystalline forms of dolutegravir sodium solvates and WO 2016016279 mentions hydrates of dolutegravir sodium.
The present invention provides novel crystalline form of dol utegravi r sodi urn designated as Form A and process for preparation thereof. DESCRIPTION OF DRAWING
Figure 1 " X-ray powder diffraction pattern of crystalline Form A of dol utegravi r sodium. Figure2 " Infrared absorption spectrum of crystalline FormA of dol utegravi r sodium. Figure 3- DSC thermogram of crystalline FormA of dol utegravi r sodium
SUMMARY OF THE INVENTION
The present invention provides novel crystalline form A of dol utegravi r sodium with characteristic diffraction peaks at 63¾ 7.8¾ 9.3¾ \\Ae, 12.4¾ 13.5¾ 12.7e\ 15.1¾ 15.8e\ 18.3¾ 19.0ή 19.6ζ 20.7e\ 22.8e\ 23.1¾ 24.3e and 25.8e e 0.2 degree two theta in an X-ray diffraction pattern.
The present invention further provides process for preparation of crystalline form A of dol utegravi r sodium
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to novel crystalline form A of dol utegravi r sodium and processes for its preparation.
In one embodiment, the present invention provides crystalline form A of dol utegravi r sodium.
The crystalline form A of dolutegravir sodium having characteristic diffraction peaks at 6.3¾ 7.8e\ 9.3¾ 11.4e\ 12.4¾ 13.¾ 12.7e\ 15.1¾ 15.8¾ 18.3¾ 19.0¾ 19.6¾ 20.7e; 22.8e\ 23.1 e, 24.3e and 25.8e e 0.2 degree two theta i n an X - ray diff racti on pattern.
T he crystal I i ne form A of dol utegravi r sodi um of the present i nventi on i s characterized by X -ray powder diffraction pattern as depicted in Figure 1.
T he crystal I i ne form A of dol utegravi r sodi um havi ng character! sti c i nf rared absorpti on at 3431 e 2 cm1, 1643e 2 cmr1, 1538e 2 cm1, 1504e 2 cm1, 1424e 2 cmr1, 1320e 2 cmr1, 1278e 2 cm1, 1096e 2 cm1, 964 e 2 cmr1.
The crystalline form A of dolutegravir sodium is characterized by infrared absorption spectrum as depicted i n Figure 2.
The crystalline form A of dolutegravir sodium is characterized by Differential Scanning Calorimetry (DSC) thermogram as depicted in Figure 3.
T he present i nventi on provi des crystal I i ne form A of dol utegravi r sodi um comprisi ng: i ) X -ray powder di ff racti on pattern as depi cted i n F i gure 1 ,
ii) Infrared absorption spectrum as depicted in Figure 2, and
ii i) DSC thermogram as depicted in Figure 3. In another embodiment, the present invention provides a process for the preparation of crystal I i ne form A of dol utegravi r sodi um comprisi ng the steps of: a) dissolving dol utegravir sodium in a first solvent;
b) addi ng the sol uti on of step (a) to a pre cool ed sol uti on of second solvent; and c) i sol ati ng form A of dol utegravi r sodi um
The first solvent and second solvent can be selected from polar solvent non-polar solvents or mixtures thereof. Polar solvent can be selected from alcohols like methanol, ethanol, butanol, propanol; nitriles l ike acetonitrile, propionitrile, butyronitrile; ethers like tetrahydrofuran, dioxane, di methoxyethane; esters like ethyl acetate, ethyl acetoacetate, butyl acetate, propyl acetate; ketones like acetone, methyl ethyl ketone, methyl isobutyl ketone; other polar solvents li ke dimethylformamide, dimethyl sulfoxide, water and
mixtures thereof. Non-polar solvents can be selected from hydrocarbon like hexane, cyclohexane, n-heptane, pentane, cyclopentane, toluene; chlori nated hydrocarbon solvent like methylene chloride, ethylene chloride, chloroform, carbon tetrachloride and mixtures thereof. The first solvent is preferably dimethyl sulfoxide and second solvent is preferably methanol.
In step (b) the second solvent can be pre cooled to a temperature of less than 30eC, preferably less than 20eC, more preferably less than 10eC. In step (c) form A of dolutegravir sodium can be isolated by techniques known in art like filtration, concentration, evaporation of solvents etc.
The form A of dolutegravir sodium of the present invention was found to be stable at 40eC/ 75% RH; 25eC/ 60% RH and 5eC. The total impurity content in form A of dolutegravir sodium was found to be not more than 0.1% by H PLC, in stabil ity.
Dolutegravir sodium which is used for preparation of form A of dol utegravir sodium can be prepared by methods as described in application WO 2010068253 or by preparations known in the literature.
The X -ray powder diffraction pattern was recorded at room temperature using PA Nalytical X Tert PRO diffractogram with Cu K radiation (≡ = 1.54060 j ), running at 45 kV and 40 mA. The infrared absorption spectrum was obtained using a Perkin Elmer Precisely Spectrum 400 i nstrument usi ng K B r pel I et method.
The present invention is further illustrated by the following representative examples and does not I i mi t the scope of the i nventi on.
EXAM PL E S
E xampl e 1 : Preparati on of crystal I i ne form A of dol utegravi r sodi um: A mixture of dolutegravir sodium (1 g) and dimethyl sulfoxide (250 ml) was heated at 130eC. The solution was cooled to 25-30eC. This solution was added dropwise to methanol (75 ml) at -10eC. Methanol (25 ml) was added to this mixture at -10eC and stirred for 6-7 hours. The mixture was then stirred for 15 minutes at 25eC. The solid filtered and dried under vacuum Y ield 0.8 g.
E xampl e 2: Preparati on of crystal I i ne form A of dol utegravi r sodi um:
A mixture of dolutegravir (13 g) and dimethyl sulfoxide (104 ml) was heated to 70eC and then cooled to 25eC and filtered through micron filter. The filtrate was added dropwise to a pre-cooled solution of methanol (650 ml) and sodium hydroxide (2.65 g) at -10 to -7eC. T he mixture was sti rred at about -7eC for 40 mi nutes. T he sol id was fi Itered, washed with methanol and dried under vacuum Y ield 12.0 g.
Claims
C LAIMS
Crystal line form A of dolutegravir sodium having characteristic diffraction peaks at 6.3¾ 7.8¾ 9.3¾ 11.4e 12.4e\ 13.5¾ 12.7¾ 15.1e\ 15.8¾ 18.3¾ 19.0ή 19.6¾ 20.7£ 22.8e; 23.1 £ 24.3e and 25.8e e 0.2 degree two theta in an X -ray diffraction pattern.
The crystalli ne form A of claim 1, having characteristic infrared absorption at 3431 e 2 cmr1, 1643e 2 cmr1, 1538e 2 cmr1, 1504e 2 cm"1, 1424e 2 cm1, 1320e 2 cmr1, 1278e 2 cmr1, 1096e 2 cmr1 and 964 e 2 cmr1.
C rystal I i ne form A of dol utegravi r sodi um comprisi ng: i) X -ray powder diffraction pattern as depicted in figure 1,
i i ) I nf rared absorpti on spectrum as depi cted i n f i gure 2, and
i i i) DSC thermogram as depicted i n figure 3.
A process for the preparation of crystalline form A of dolutegravir sodium of claim 1, comprising:
i ) di ssolvi ng dol utegravi r sodi um i n a f i rst solvent;
ii) adding the solution of step (a) to a pre cooled solution of second solvent; and
i i i ) i sol ati ng form A of dol utegravi r sodi um
The process according to claim 4, wherein the solvent is polar solvent non-polar solvent or mixture thereof.
The process according to claim 5, wherein polar solvent is alcohol, ether, ester, ketone, di methyl formamide, dimethyl sulfoxide or water.
The process according to claim 6, wherein alcohol is methanol, ethanol, butanol or propanol; nitrile is acetonitrile, propionitrile or butyronitrile; ether is tetrahydrofuran, dioxane or di methoxyethane; ester is ethyl acetate, ethyl acetoacetate, butyl acetate or propyl acetate; ketones is acetone, methyl ethyl ketone or methyl isobutyl ketone.
The process according to claim 5, wherein non-polar solvent is hydrocarbon solvent or chlorinated hydrocarbon solvent.
The process according to claim 8, wherein hydrocarbon solvent is hexane, cyclohexane, n-heptane, pentane, cyclopentane or toluene.
The process according to claim 8, wherein chlorinated hydrocarbon solvent is methylene chloride, ethylene chloride, chloroform or carbon tetrachloride.
The process accordi ng to claim 4, wherein in step (ii) the solution is precooled to a temperature of less than 30eC.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN201621018583 | 2016-05-30 | ||
| IN201621018583 | 2016-05-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2017208105A1 true WO2017208105A1 (en) | 2017-12-07 |
Family
ID=59101521
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2017/052926 Ceased WO2017208105A1 (en) | 2016-05-30 | 2017-05-18 | Novel crystalline form of dolutegravir sodium |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2017208105A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116284047A (en) * | 2023-03-24 | 2023-06-23 | 天津大学 | A kind of dolutegravir-m-hydroxybenzoic acid co-crystal and its preparation method and application |
| CN116496297A (en) * | 2023-03-24 | 2023-07-28 | 天津大学 | A kind of dolutegravir oxalic acid co-crystal and its preparation method and application |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010068253A1 (en) | 2008-12-11 | 2010-06-17 | Shionogi & Co., Ltd. | Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates |
| US8129385B2 (en) | 2005-04-28 | 2012-03-06 | Shionogi & Co., Ltd. | Substituted 5-hydroxy-3,4,6,9,9a, 10-hexanhydro-2h-1-oxa04a,8a-diaza-anthracene-6,10-dioness |
| WO2015092752A1 (en) | 2013-12-20 | 2015-06-25 | Mylan Laboratories Ltd. | Novel crystalline form of dolutegravir sodium |
| WO2015118460A1 (en) | 2014-02-07 | 2015-08-13 | Mylan Laboratories Ltd. | Crystalline forms of dolutegravir sodium |
| WO2015138933A1 (en) | 2014-03-13 | 2015-09-17 | Assia Chemical Industries Ltd. | Solid state forms of dolutegravir sodium |
| WO2015139591A1 (en) | 2014-03-19 | 2015-09-24 | 杭州普晒医药科技有限公司 | Crystalline form of dolutegravir sodium salt and preparation method therefor |
| US9206197B2 (en) | 2011-09-14 | 2015-12-08 | Mapi Pharma Ltd. | Amorphous form of dolutegravir |
| WO2016016279A1 (en) | 2014-07-29 | 2016-02-04 | Lek Pharmaceuticals D.D. | Novel hydrates of dolutegravir sodium |
-
2017
- 2017-05-18 WO PCT/IB2017/052926 patent/WO2017208105A1/en not_active Ceased
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8129385B2 (en) | 2005-04-28 | 2012-03-06 | Shionogi & Co., Ltd. | Substituted 5-hydroxy-3,4,6,9,9a, 10-hexanhydro-2h-1-oxa04a,8a-diaza-anthracene-6,10-dioness |
| WO2010068253A1 (en) | 2008-12-11 | 2010-06-17 | Shionogi & Co., Ltd. | Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates |
| US9242986B2 (en) | 2008-12-11 | 2016-01-26 | Shionogi & Co., Ltd. | Synthesis of carbamoylpyridone HIV integrase inhibitors and intermediates |
| US9206197B2 (en) | 2011-09-14 | 2015-12-08 | Mapi Pharma Ltd. | Amorphous form of dolutegravir |
| WO2015092752A1 (en) | 2013-12-20 | 2015-06-25 | Mylan Laboratories Ltd. | Novel crystalline form of dolutegravir sodium |
| WO2015118460A1 (en) | 2014-02-07 | 2015-08-13 | Mylan Laboratories Ltd. | Crystalline forms of dolutegravir sodium |
| WO2015138933A1 (en) | 2014-03-13 | 2015-09-17 | Assia Chemical Industries Ltd. | Solid state forms of dolutegravir sodium |
| WO2015139591A1 (en) | 2014-03-19 | 2015-09-24 | 杭州普晒医药科技有限公司 | Crystalline form of dolutegravir sodium salt and preparation method therefor |
| WO2016016279A1 (en) | 2014-07-29 | 2016-02-04 | Lek Pharmaceuticals D.D. | Novel hydrates of dolutegravir sodium |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116284047A (en) * | 2023-03-24 | 2023-06-23 | 天津大学 | A kind of dolutegravir-m-hydroxybenzoic acid co-crystal and its preparation method and application |
| CN116496297A (en) * | 2023-03-24 | 2023-07-28 | 天津大学 | A kind of dolutegravir oxalic acid co-crystal and its preparation method and application |
| CN116284047B (en) * | 2023-03-24 | 2024-05-24 | 天津大学 | A dolutegravir-m-hydroxybenzoic acid cocrystal and its preparation method and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2017208105A1 (en) | Novel crystalline form of dolutegravir sodium | |
| TWI491356B (en) | Synthesis of 2-ethyl-3,7-dimethyl-6-(4-(trifluoromethoxy)phenoxy) quinolin-4-ylmethyl carbonate and a method for producing the same Crystallization of the pesticide composition | |
| SE453195B (en) | CEFUROXIMAXETIL IN AMORF FORM, PROCEDURE FOR PREPARING IT AND COMPOSITION CONTAINING THIS | |
| CN109311891A (en) | The crystallization of Pyrrolopyrimidine compounds as JAK inhibitor | |
| US20180170958A1 (en) | Crystalline form a of obeticholic acid and preparation method thereof | |
| RU2009104959A (en) | CRYSTALLINE ANTI-FUNGAL COMPOUNDS | |
| JP2015522042A (en) | Form I crystals of tyrosine kinase inhibitor dimaleate salt and method for producing same | |
| CN113905741A (en) | Solid forms of orally delivered beta-lactamase inhibitors and uses thereof | |
| WO1997031000A1 (en) | Quinolones and their therapeutic use | |
| JP2019527724A5 (en) | ||
| CA2929559A1 (en) | Biscationic and triscationic amphiphiles as antimicrobial agents | |
| WO2015087245A1 (en) | Process for preparation of ertapenem and salts thereof | |
| CN103755723B (en) | A kind of preparation method of rifampicin I crystal form | |
| WO2018015974A1 (en) | Polymorphic forms and amorphous solid dispersion of selexipag | |
| CN103965185B (en) | 1,5-benzodiazepine compound containing thiazolyl and ester group and application thereof | |
| CA2920080A1 (en) | A process for preparing rifaximin .kappa. | |
| CN102464669A (en) | Amorphous everolimus and preparation method thereof | |
| US10300044B2 (en) | Polymorphic forms of methyl((1S)-1-(((2S)-2-(5-(4′-(2-((2S)-1-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-5-yl)-4-biphenylyl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamate and salts thereof | |
| WO2009113087A1 (en) | Montelukast benzhydryl piperazine salts and process for preparation thereof | |
| CN108440626B (en) | Crystal form of cytarabine 5' -O-L-valine ester hydrochloride and preparation method thereof | |
| JPWO2020099923A5 (en) | ||
| EP2899193B1 (en) | Crystalline form of abacavir that is essentially free of solvent | |
| WO2016107331A1 (en) | New crystal form of cefathiamidine compound and preparation method therefor | |
| WO2014189308A1 (en) | Novel crystal form of cefditoren pivoxil, and preparation method therefor | |
| WO2016067054A1 (en) | Processs for the formation of hydrocodone bitatrate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 17732219 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 17732219 Country of ref document: EP Kind code of ref document: A1 |