JP5960061B2 - 末梢血管疾患を治療するための方法および組成物 - Google Patents

末梢血管疾患を治療するための方法および組成物 Download PDF

Info

Publication number
JP5960061B2
JP5960061B2 JP2012544900A JP2012544900A JP5960061B2 JP 5960061 B2 JP5960061 B2 JP 5960061B2 JP 2012544900 A JP2012544900 A JP 2012544900A JP 2012544900 A JP2012544900 A JP 2012544900A JP 5960061 B2 JP5960061 B2 JP 5960061B2
Authority
JP
Japan
Prior art keywords
composition
arginine
acid
salt
raynaud
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.)
Expired - Fee Related
Application number
JP2012544900A
Other languages
English (en)
Japanese (ja)
Other versions
JP2013514995A5 (https=
JP2013514995A (ja
Inventor
フランガキス,クリスト,ジェー.
レイトン,ハリー,ジェー.
Original Assignee
エクソドス ライフ サイエンシーズ リミテッド パートナーシップ
エクソドス ライフ サイエンシーズ リミテッド パートナーシップ
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by エクソドス ライフ サイエンシーズ リミテッド パートナーシップ, エクソドス ライフ サイエンシーズ リミテッド パートナーシップ filed Critical エクソドス ライフ サイエンシーズ リミテッド パートナーシップ
Publication of JP2013514995A publication Critical patent/JP2013514995A/ja
Publication of JP2013514995A5 publication Critical patent/JP2013514995A5/ja
Application granted granted Critical
Publication of JP5960061B2 publication Critical patent/JP5960061B2/ja
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • A61K31/497Non-condensed pyrazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/04Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/02Drugs for disorders of the nervous system for peripheral neuropathies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Cardiology (AREA)
  • Rheumatology (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Pain & Pain Management (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
JP2012544900A 2009-12-18 2010-12-17 末梢血管疾患を治療するための方法および組成物 Expired - Fee Related JP5960061B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US28796709P 2009-12-18 2009-12-18
US61/287,967 2009-12-18
PCT/US2010/061054 WO2011075655A1 (en) 2009-12-18 2010-12-17 Methods and compositions for treating peripheral vascular disease

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2016029675A Division JP2016166178A (ja) 2009-12-18 2016-02-19 末梢血管疾患を治療するための方法および組成物

Publications (3)

Publication Number Publication Date
JP2013514995A JP2013514995A (ja) 2013-05-02
JP2013514995A5 JP2013514995A5 (https=) 2014-02-06
JP5960061B2 true JP5960061B2 (ja) 2016-08-02

Family

ID=44167718

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2012544900A Expired - Fee Related JP5960061B2 (ja) 2009-12-18 2010-12-17 末梢血管疾患を治療するための方法および組成物
JP2016029675A Pending JP2016166178A (ja) 2009-12-18 2016-02-19 末梢血管疾患を治療するための方法および組成物

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2016029675A Pending JP2016166178A (ja) 2009-12-18 2016-02-19 末梢血管疾患を治療するための方法および組成物

Country Status (7)

Country Link
US (3) US20130053393A1 (https=)
EP (1) EP2512479B1 (https=)
JP (2) JP5960061B2 (https=)
AU (1) AU2010330813B2 (https=)
CA (1) CA2784788A1 (https=)
DK (1) DK2512479T3 (https=)
WO (1) WO2011075655A1 (https=)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2512460A4 (en) 2009-12-18 2015-01-21 Exodos Life Sciences Ltd Partnership METHOD AND COMPOSITIONS FOR STABLE LIQUID ACTIVE FORMULATIONS
SI2576548T1 (sl) * 2010-05-26 2015-11-30 Adverio Pharma Gmbh Uporaba sGC stimulatorjev, sGC aktivatorjev, samih in v kombinacijah s PDE5 inhibitorji za zdravljenje sistemske skleroze
DE102010021637A1 (de) 2010-05-26 2011-12-01 Bayer Schering Pharma Aktiengesellschaft Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung
CN103826638B (zh) * 2011-09-09 2015-11-25 Sk化学公司 含有pde5 抑制剂的减少皮肤皱纹的组合物
EP3024455A1 (en) 2013-07-25 2016-06-01 Bayer Pharma Aktiengesellschaft Sgc stimulators or sgc activators and pde5 inhibitors in combination with additional treatment for the therapy of cystic fibrosis
CN104644579A (zh) * 2013-11-25 2015-05-27 天津市汉康医药生物技术有限公司 一种阿伐那非药物组合物
JP6211406B2 (ja) * 2013-12-04 2017-10-11 ライオン株式会社 ムスカリン受容体活性化剤及び唾液分泌促進剤
JP6236304B2 (ja) * 2013-12-04 2017-11-22 ライオン株式会社 涙液分泌促進剤
US20160317542A1 (en) 2013-12-09 2016-11-03 Respira Therapeutics, Inc. Pde5 inhibitor powder formulations and methods relating thereto
CA3128680C (en) 2014-08-12 2025-10-07 The Children's Hospital Of Philadelphia METHODS FOR IMPROVING MYOCARDIAL PERFORMANCE IN PATIENTS WHO HAVE UNDERGONE FONTAN SURGERY, USING UDENAFIL COMPOSITIONS
EP3226972A4 (en) 2014-12-01 2018-08-08 Achelios Therapeutics, Inc. Methods and compositions for treating migraine and conditions associated with pain
CN107580495A (zh) * 2015-05-06 2018-01-12 拜耳制药股份公司 单独和与PDE5抑制剂组合的sGC刺激剂、sGC活化剂用于治疗伴随系统性硬化症(SSc)的指溃疡(DU)的用途
US9993447B2 (en) * 2015-09-14 2018-06-12 JW Nutritional, LLC Systems and methods for increasing agmatine cellular uptake by oral administration
PL3377495T3 (pl) 2015-11-16 2022-05-16 Topadur Pharma Ag Pochodne 2-fenylo-3,4-dihydropirolo[2,1-f] [1,2,4]triazynonu jako inhibitory fosfodiesterazy i ich zastosowania
CA3055882A1 (en) 2017-03-14 2018-09-20 Atir Holding S.A. Topical formulation for the treatment of pigmented skin
CA3055881C (en) 2017-03-14 2021-04-06 Atir Holding S.A. Use of heterocyclic compounds in the treatment of pigmented skin
KR102670626B1 (ko) 2017-05-22 2024-05-29 토파두르 파마 아게 가용성 구아닐레이트 사이클라제 활성제 및 포스포디에스테라제 억제제의 신규한 이중 작용 방식 및 이의 용도
US11117808B2 (en) * 2017-08-01 2021-09-14 University Of Georgia Research Foundation, Inc. Mesoporous nitric oxide-releasing silica particles, methods of making, and uses thereof
KR20190043369A (ko) * 2017-10-18 2019-04-26 주식회사 코아팜바이오 유데나필의 신규한 반고형 제제
MX2017016930A (es) * 2017-12-19 2019-06-20 Malesil Research & Tech Llc Uso del maleato de sildenafil en el tratamiento de ulceras de pie diabetico.
US11197848B2 (en) 2018-06-01 2021-12-14 Tavanta Therapeutics Hungary Incorporated Topical amlodipine salts for the treatment of anorectal diseases
JP7596257B2 (ja) * 2018-08-06 2024-12-09 ニコックス エス.エー. 一酸化窒素放出性ホスホジエステラーゼ5型阻害薬
WO2020109354A1 (en) 2018-11-28 2020-06-04 Topadur Pharma Ag Novel dual mode of action soluble guanylate cyclase activators and phosphodiesterase inhibitors and uses thereof
WO2020123312A1 (en) 2018-12-09 2020-06-18 Weinberg Assa Method to prevent and treat macular degeneration by vasodilators
AU2020356193A1 (en) 2019-09-24 2022-05-19 Children's Hospital Of Philadelphia Methods of improving exercise performance, single ventricular performance, and myocardial performance index (MPI) in single ventricle heart disease, using udenafil compositions
WO2021245192A1 (en) 2020-06-04 2021-12-09 Topadur Pharma Ag Novel dual mode of action soluble guanylate cyclase activators and phosphodiesterase inhibitors and uses thereof
EP4251164A2 (en) * 2020-11-25 2023-10-04 Aisa Pharma, Inc. Treatment of raynaud's disease
US11185513B1 (en) * 2021-05-07 2021-11-30 King Abdulaziz University Transfersome-containing transdermal film formulations and methods of use
CA3228160A1 (en) 2021-09-29 2023-04-06 Topadur Pharma Ag Topical compositions of 2-phenyl-3,4-dihydropyrrolo[2,l-f] [1,2,4]triazinone derivatives and uses thereof
KR20230129639A (ko) 2022-03-02 2023-09-11 연세대학교 산학협력단 이중작용 pde5 억제제/질산유기에스터의 국소 혈류 증진을 위한 경피 투약 형태
JP2025506878A (ja) 2022-03-02 2025-03-13 トパデュール ファルマ アーゲー 局所組成物及びその使用

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7914814B2 (en) * 1997-09-17 2011-03-29 Strategic Science & Technologies, Llc Topical delivery of arginine of cause beneficial effects
JP2002542147A (ja) * 1998-12-14 2002-12-10 セレジィ ファーマシューティカルス, インコーポレイテッド 肛門直腸障害の処置のための組成物および方法
US20040110843A1 (en) * 2000-01-10 2004-06-10 Nexmed (Holdings), Inc. Methods of treatment of male erectile dysfunction
US20030105108A1 (en) * 2002-12-19 2003-06-05 Wood Ralph E. Method of treating peripheral vascular diseases, peripheral neuropathies, and autonomic neuropathies
US7737147B2 (en) * 2000-07-27 2010-06-15 Thomas Nadackal Thomas Methods and compositions to enhance the efficacy of phosphodiesterase inhibitors
US6538033B2 (en) 2000-08-29 2003-03-25 Huntington Medical Research Institutes Nitric oxide donor compounds
JP2005530772A (ja) * 2002-05-09 2005-10-13 ミモトープス・プロプライエタリー・リミテッド アミノ酸類縁体
US20020168424A1 (en) * 2002-07-31 2002-11-14 Dr. Mohsen Shahinpoor Nitric oxide (NO) donor+cGMP-PDE5 inhibitor as a topical drug for glaucoma
US20020182162A1 (en) * 2002-08-07 2002-12-05 Mohsen Shahinpoor Nitric oxide (NO) donor+cGMP-PDE5 inhibitor as a topical drug for enhanced hair growth
AU2005218539A1 (en) * 2004-03-01 2005-09-15 Lumen Therapeutics, Llc Compositions and methods for treating diseases
HUP0401422A2 (en) * 2004-07-15 2006-04-28 G Laszlo Meszaros Use of l-arginine as vasoaktive ingredient absorbing through skin for external application
CN101300007A (zh) * 2005-06-29 2008-11-05 马尔斯公司 诱导周围血管的血管舒张
WO2010062366A1 (en) * 2008-10-31 2010-06-03 Arginetix, Inc. Compositions and methods of treating endothelial disorders

Also Published As

Publication number Publication date
AU2010330813B2 (en) 2016-04-28
EP2512479B1 (en) 2016-03-30
WO2011075655A1 (en) 2011-06-23
US20130053393A1 (en) 2013-02-28
EP2512479A1 (en) 2012-10-24
AU2010330813A1 (en) 2012-08-09
JP2016166178A (ja) 2016-09-15
EP2512479A4 (en) 2013-07-17
US20180036314A1 (en) 2018-02-08
CA2784788A1 (en) 2011-06-23
AU2010330813A2 (en) 2012-08-09
US20150031704A1 (en) 2015-01-29
JP2013514995A (ja) 2013-05-02
HK1169941A1 (zh) 2013-02-15
DK2512479T3 (en) 2016-06-06

Similar Documents

Publication Publication Date Title
JP5960061B2 (ja) 末梢血管疾患を治療するための方法および組成物
CA2323839C (en) Treatment of neuropathy
US7419981B2 (en) Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor
EP1536782B1 (en) Synergistic combination of an alpha-2-delta ligand and a pdev inhibitor for use in the treatment of pain
CA2359383A1 (en) Use of pdev inhibitors for improved fecundity in mammals
KR20240162167A (ko) 신장 질환 또는 장애의 치료를 위한 비페닐 설폰아미드 화합물
BRPI0620234A2 (pt) combinação farmacêutica para o tratamento de luts que compreende um inibidor da pde5 e um antagonista muscarìnico
JP2005523263A (ja) 瘢痕化及び繊維症の治療におけるpde5阻害剤の使用
KR102902972B1 (ko) Iv형 콜라겐 질환의 치료를 위한 비페닐 설폰아미드 화합물
CA2660939A1 (en) Pharmaceutical compositions for the treatment of fungal infections
US20040092522A1 (en) Synergistic combinations
US20050148585A1 (en) Treatment of wounds
WO2005042022A2 (en) Combination of an activator of solubleguanylate cyclase and an angiotensin ii receptor antagonist
HK1169941B (en) Compositions for treating peripheral vascular disease
KR20030097778A (ko) 상처 치료방법
AU2011221426A1 (en) Pharmaceutical compositions for the treatment of fungal infections

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20131213

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20131213

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20141202

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20150224

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150602

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20151020

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20160219

A911 Transfer to examiner for re-examination before appeal (zenchi)

Free format text: JAPANESE INTERMEDIATE CODE: A911

Effective date: 20160421

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20160524

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20160622

R150 Certificate of patent or registration of utility model

Ref document number: 5960061

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

LAPS Cancellation because of no payment of annual fees