BR112014000033A2 - compostos para o tratamento de dependência química - Google Patents
compostos para o tratamento de dependência químicaInfo
- Publication number
- BR112014000033A2 BR112014000033A2 BR112014000033A BR112014000033A BR112014000033A2 BR 112014000033 A2 BR112014000033 A2 BR 112014000033A2 BR 112014000033 A BR112014000033 A BR 112014000033A BR 112014000033 A BR112014000033 A BR 112014000033A BR 112014000033 A2 BR112014000033 A2 BR 112014000033A2
- Authority
- BR
- Brazil
- Prior art keywords
- compounds
- treatment
- chemical dependence
- dependence
- chemical
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title 1
- 206010013663 drug dependence Diseases 0.000 title 1
- 208000011117 substance-related disease Diseases 0.000 title 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Addiction (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161503923P | 2011-07-01 | 2011-07-01 | |
| PCT/US2012/044809 WO2013006400A1 (en) | 2011-07-01 | 2012-06-29 | Compounds for the treatment of addiction |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112014000033A2 true BR112014000033A2 (pt) | 2019-06-18 |
Family
ID=46513858
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112014000033A BR112014000033A2 (pt) | 2011-07-01 | 2012-06-29 | compostos para o tratamento de dependência química |
Country Status (32)
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012149106A1 (en) | 2011-04-29 | 2012-11-01 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for increasing proliferation of adult salivary stem cells |
| TWI510480B (zh) | 2011-05-10 | 2015-12-01 | Gilead Sciences Inc | 充當離子通道調節劑之稠合雜環化合物 |
| NO3175985T3 (enExample) | 2011-07-01 | 2018-04-28 | ||
| TWI549944B (zh) | 2011-07-01 | 2016-09-21 | 吉李德科學股份有限公司 | 作為離子通道調節劑之稠合雜環化合物 |
| TWI567061B (zh) | 2011-07-01 | 2017-01-21 | 吉李德科學股份有限公司 | 用於治療成癮之化合物 |
| KR20150135332A (ko) | 2013-03-14 | 2015-12-02 | 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 | 미토콘드리아 알데히드 탈수소효소-2 조절인자들 및 이들의 사용 방법 |
| LT3080134T (lt) * | 2013-12-13 | 2018-11-12 | Vertex Pharmaceuticals Incorporated | Piridono amidų provaistai, naudotini kaip natrio kanalų moduliatoriai |
| US10077669B2 (en) | 2014-11-26 | 2018-09-18 | United Technologies Corporation | Non-metallic engine case inlet compression seal for a gas turbine engine |
| US10289971B2 (en) | 2015-02-13 | 2019-05-14 | Atlassian Pty Ltd | Issue and trigger rebalancing in a ranked issue management system |
| HUE061016T2 (hu) | 2016-08-19 | 2023-05-28 | Univ Bristol | Citizin-származékok a szenvedélybetegségek kezelésére |
| JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
| KR20200070273A (ko) * | 2017-10-16 | 2020-06-17 | 아미그달라 뉴로사이언시즈, 인크. | 중독을 예방하기 위한 병용 요법 |
| SI3752501T1 (sl) | 2018-02-13 | 2023-08-31 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| CA3093130C (en) | 2018-04-19 | 2023-10-17 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| DK3793565T3 (en) | 2018-05-14 | 2022-03-07 | Gilead Sciences Inc | Mcl-1-inhibitorer |
| SI3820572T1 (sl) | 2018-07-13 | 2023-12-29 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| EP3829562A1 (en) * | 2018-07-27 | 2021-06-09 | Amygdala Neurosciences, Inc. | Combination therapy for nicotine addiction |
| WO2020076974A1 (en) * | 2018-10-12 | 2020-04-16 | Amygdala Neurosciences, Inc. | Addiction treatment of an alcohol-consuming patient population |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ, インコーポレイテッド | Pd-1/pd-l1阻害剤 |
| US12029718B2 (en) | 2021-11-09 | 2024-07-09 | Cct Sciences, Llc | Process for production of essentially pure delta-9-tetrahydrocannabinol |
| JP2025520426A (ja) | 2022-06-14 | 2025-07-03 | アミグダラ ニューロサイエンシーズ, インコーポレイテッド | Aldh-2阻害化合物及び使用方法 |
| US20230399299A1 (en) | 2022-06-14 | 2023-12-14 | Amygdala Neurosciences, Inc. | Aldh-2 inhibitor compounds and methods of use |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| US4326525A (en) | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
| US5364620A (en) | 1983-12-22 | 1994-11-15 | Elan Corporation, Plc | Controlled absorption diltiazem formulation for once daily administration |
| US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
| US4992445A (en) | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
| US5001139A (en) | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
| US4902514A (en) | 1988-07-21 | 1990-02-20 | Alza Corporation | Dosage form for administering nilvadipine for treating cardiovascular symptoms |
| US5204369A (en) | 1991-07-01 | 1993-04-20 | The Endowment For Research In Human Biology | Method for the inhibition of aldh-i useful in the treatment of alcohol dependence or alcohol abuse |
| AU3899199A (en) | 1998-05-12 | 1999-11-29 | Endowment for Research in Human Biology, Inc., The | Methods and assays useful in the treatment of alcohol dependence or alcohol abuse |
| MXPA05000122A (es) | 2002-06-27 | 2005-12-14 | Endowment For Res In Human Bio | Compuestos utiles para la inhibicion de aldehido-deshidrogenasa. |
| JP2004182657A (ja) * | 2002-12-04 | 2004-07-02 | Eisai Co Ltd | Hdlレベル上昇促進剤 |
| US20080004260A1 (en) | 2006-06-29 | 2008-01-03 | Transcept Pharmaceuticals, Inc. | Compositions of 5-HT3 antagonists and dopamine D2 antagonists for treatment of dopamine-associated chronic conditions |
| WO2008014497A2 (en) | 2006-07-27 | 2008-01-31 | Cv Therapeutics, Inc. | Aldh-2 inhibitors in the treatment of addiction |
| US20080207610A1 (en) | 2006-07-27 | 2008-08-28 | Jeff Zablocki | Aldh-2 inhibitors in the treatment of addiction |
| US8158810B2 (en) | 2006-07-27 | 2012-04-17 | Gilead Sciences, Inc. | ALDH-2 inhibitors in the treatment of addiction |
| EP2126574B1 (en) | 2007-03-08 | 2015-12-23 | The Board of Trustees of the Leland Stanford Junior University | Mitochondrial aldehyde dehydrogenase-2 modulators and methods of use thereof |
| CN101925590A (zh) | 2008-01-24 | 2010-12-22 | 吉利德帕洛阿尔托股份有限公司 | 治疗成瘾的aldh-2抑制剂 |
| JP5301563B2 (ja) | 2008-05-01 | 2013-09-25 | ヴァイティー ファーマシューティカルズ,インコーポレイテッド | 11β−ヒドロキシステロイドデヒドロゲナーゼ1の環状インヒビター |
| ES2477552T3 (es) | 2008-09-08 | 2014-07-17 | The Board Of Trustees Of The Leland Stanford Junior University | Moduladores de la actividad de la aldehidodeshidrogenasa y métodos de uso de los mismos |
| KR20110082180A (ko) * | 2008-10-28 | 2011-07-18 | 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 | 알데히드 탈수소효소의 조절자 및 그것의 사용방법 |
| UY33469A (es) * | 2010-06-29 | 2012-01-31 | Irm Llc Y Novartis Ag | Composiciones y metodos para modular la via de señalizacion de wnt |
| TWI567061B (zh) | 2011-07-01 | 2017-01-21 | 吉李德科學股份有限公司 | 用於治療成癮之化合物 |
-
2012
- 2012-06-26 TW TW101122794A patent/TWI567061B/zh not_active IP Right Cessation
- 2012-06-27 UY UY0001034165A patent/UY34165A/es not_active Application Discontinuation
- 2012-06-28 AR ARP120102331A patent/AR086792A1/es not_active Application Discontinuation
- 2012-06-29 EA EA201391635A patent/EA025573B1/ru not_active IP Right Cessation
- 2012-06-29 MX MX2013014938A patent/MX337611B/es active IP Right Grant
- 2012-06-29 CN CN201280032944.6A patent/CN103635460B/zh not_active Expired - Fee Related
- 2012-06-29 KR KR1020167023967A patent/KR20160106207A/ko not_active Withdrawn
- 2012-06-29 BR BR112014000033A patent/BR112014000033A2/pt active Search and Examination
- 2012-06-29 EP EP15184883.5A patent/EP2993170B1/en active Active
- 2012-06-29 US US13/537,536 patent/US8558001B2/en active Active
- 2012-06-29 CA CA2840763A patent/CA2840763C/en active Active
- 2012-06-29 EP EP12735394.4A patent/EP2726460B1/en active Active
- 2012-06-29 ES ES12735394.4T patent/ES2553829T3/es active Active
- 2012-06-29 PE PE2013002811A patent/PE20141067A1/es not_active Application Discontinuation
- 2012-06-29 UA UAA201314148A patent/UA109199C2/ru unknown
- 2012-06-29 ES ES15184883.5T patent/ES2656716T3/es active Active
- 2012-06-29 WO PCT/US2012/044809 patent/WO2013006400A1/en not_active Ceased
- 2012-06-29 PL PL12735394T patent/PL2726460T3/pl unknown
- 2012-06-29 PT PT127353944T patent/PT2726460E/pt unknown
- 2012-06-29 KR KR1020147002302A patent/KR101664915B1/ko not_active Expired - Fee Related
- 2012-06-29 PH PH1/2013/502674A patent/PH12013502674A1/en unknown
- 2012-06-29 MD MDA20140009A patent/MD4436B1/ro not_active IP Right Cessation
- 2012-06-29 SI SI201230340T patent/SI2726460T1/sl unknown
- 2012-06-29 SG SG10201605355RA patent/SG10201605355RA/en unknown
- 2012-06-29 AP AP2013007282A patent/AP3544A/xx active
- 2012-06-29 JP JP2014519122A patent/JP5943998B2/ja not_active Expired - Fee Related
- 2012-06-29 DK DK15184883.5T patent/DK2993170T3/da active
- 2012-06-29 AU AU2012279332A patent/AU2012279332B2/en not_active Ceased
-
2013
- 2013-03-08 US US13/791,422 patent/US8575353B2/en active Active
- 2013-08-13 US US13/966,029 patent/US9000015B2/en active Active
- 2013-11-28 ZA ZA2013/08977A patent/ZA201308977B/en unknown
- 2013-12-13 CR CR20130659A patent/CR20130659A/es unknown
- 2013-12-16 CL CL2013003597A patent/CL2013003597A1/es unknown
- 2013-12-18 EC ECSP13013087 patent/ECSP13013087A/es unknown
- 2013-12-18 CO CO13295408A patent/CO6821964A2/es active IP Right Grant
- 2013-12-30 MA MA36629A patent/MA35404B1/fr unknown
-
2014
- 2014-01-26 IL IL230657A patent/IL230657B/en active IP Right Grant
-
2015
- 2015-03-16 US US14/659,042 patent/US9610299B2/en not_active Expired - Fee Related
-
2017
- 2017-03-31 US US15/476,569 patent/US9987295B2/en active Active
-
2018
- 2018-05-08 US US15/974,171 patent/US10507215B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BR112014000033A2 (pt) | compostos para o tratamento de dependência química | |
| LTPA2020510I1 (lt) | Pakeistieji 4-fenil-piridinai, skirti su NK-receptoriumi susijusių ligų gydymui | |
| CO6940432A2 (es) | Compuestos de 1-arilcarbonilo-4-oxi-piperidina útiles para el tratamiento de enfermedades neurodegenerativas | |
| BR112013014943A2 (pt) | compostos úteis para o tratamento de aids | |
| PT2523661T (pt) | Inibidores de nkcc para o tratamento de autismo | |
| SMT201600293B (it) | Composti chimici | |
| HUE041891T2 (hu) | Berendezés ipari célokra használt víz kezelésére | |
| CO6791604A2 (es) | Compuesto para liberación controlada de agentes de tratamiento de pozos | |
| CO6801733A2 (es) | Silicato de zirconio microporoso para el tratamiento de la hipercalemia | |
| CO6960110A1 (es) | Composición aditiva para fluidos de tratamiento de pozos | |
| PT2753334T (pt) | Inibidores de proteassoma ativados por fap utilizados para o tratamento de tumores sólidos | |
| BR112014028424A2 (pt) | compostos de pirimidina para o tratamento de câncer | |
| PT2709604T (pt) | Canabidivarina para utilização no tratamento de dor neuropática | |
| BR112015004548A2 (pt) | inibidores de serina/treonina para tratamento de doenças hiperproliferativas | |
| BR112014013843A2 (pt) | uso de dispositivos para o tratamento de doenças neurológicas | |
| BR112014012016A2 (pt) | compostos | |
| LT2928477T (lt) | Telomerazės inhibitoriaus imetelstato panaudojimas mielofibrozės gydymui | |
| EP2994460A4 (en) | Compounds for treatment of angiogenesis-mediated diseases | |
| BR112013022523A2 (pt) | uso de glicopirrolato para o tratamento de taquicardia | |
| HUE049383T2 (hu) | Eljárás ipari víz kezelésére | |
| CO6791617A2 (es) | Combinaciones de compuestos activos | |
| EP2718255A4 (en) | QUINONE COMPOUNDS FOR THE TREATMENT OF APE1 MEDIATION DISEASES | |
| CO6821965A2 (es) | 1-piperazino-3-fenil-indanos deuterados para el tratamiento de esquizofrenia | |
| LT2812013T (lt) | Kompozicija, skirta džs gydymui | |
| IL231907B (en) | Compounds and compositions for treatment of transthyretin-associated amyloidosis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] |
Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
|
| B25A | Requested transfer of rights approved |
Owner name: AMYGDALA NEUROSCIENCES, INC. (US) |
|
| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] | ||
| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B350 | Update of information on the portal [chapter 15.35 patent gazette] | ||
| B11D | Dismissal acc. art. 38, par 2 of ipl - failure to pay fee after grant in time |