JP6353159B2 - Ｔｌｒ非依存性低分子アジュバント - Google Patents

Ｔｌｒ非依存性低分子アジュバント Download PDF

Info

Publication number
JP6353159B2
JP6353159B2 JP2017506931A JP2017506931A JP6353159B2 JP 6353159 B2 JP6353159 B2 JP 6353159B2 JP 2017506931 A JP2017506931 A JP 2017506931A JP 2017506931 A JP2017506931 A JP 2017506931A JP 6353159 B2 JP6353159 B2 JP 6353159B2
Authority
JP
Japan
Prior art keywords
esi
found
sample mass
calculated
group
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.)
Active
Application number
JP2017506931A
Other languages
English (en)
Japanese (ja)
Other versions
JP2017530943A5 (cg-RX-API-DMAC7.html
JP2017530943A (ja
Inventor
ブルース ボイトラー
ブルース ボイトラー
Original Assignee
ザ スクリプス リサーチ インスティテュート
ザ スクリプス リサーチ インスティテュート
ボード オブ リージェンツ オブ ザ ユニヴァーシティ オブ テキサス システム， オースティン
ボード オブ リージェンツ オブ ザ ユニヴァーシティ オブ テキサス システム， オースティン
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 ザ スクリプス リサーチ インスティテュート, ザ スクリプス リサーチ インスティテュート, ボード オブ リージェンツ オブ ザ ユニヴァーシティ オブ テキサス システム， オースティン, ボード オブ リージェンツ オブ ザ ユニヴァーシティ オブ テキサス システム， オースティン filed Critical ザ スクリプス リサーチ インスティテュート
Publication of JP2017530943A publication Critical patent/JP2017530943A/ja
Publication of JP2017530943A5 publication Critical patent/JP2017530943A5/ja
Application granted granted Critical
Publication of JP6353159B2 publication Critical patent/JP6353159B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
    • C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D307/85—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pain & Pain Management (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Indole Compounds (AREA)
  • Furan Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
JP2017506931A 2014-08-06 2015-08-05 Ｔｌｒ非依存性低分子アジュバント Active JP6353159B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462033918P 2014-08-06 2014-08-06
US62/033,918 2014-08-06
PCT/US2015/043830 WO2016022700A2 (en) 2014-08-06 2015-08-05 Tlr-independent small molecule adjuvants

Publications (3)

Publication Number Publication Date
JP2017530943A JP2017530943A (ja) 2017-10-19
JP2017530943A5 JP2017530943A5 (cg-RX-API-DMAC7.html) 2017-12-14
JP6353159B2 true JP6353159B2 (ja) 2018-07-04

Family

ID=55264758

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2017506931A Active JP6353159B2 (ja) 2014-08-06 2015-08-05 Ｔｌｒ非依存性低分子アジュバント

Country Status (7)

Country Link
US (1) US9918959B2 (cg-RX-API-DMAC7.html)
EP (1) EP3177601B1 (cg-RX-API-DMAC7.html)
JP (1) JP6353159B2 (cg-RX-API-DMAC7.html)
AU (1) AU2015301100B2 (cg-RX-API-DMAC7.html)
CA (1) CA2957372C (cg-RX-API-DMAC7.html)
ES (1) ES2944541T3 (cg-RX-API-DMAC7.html)
WO (1) WO2016022700A2 (cg-RX-API-DMAC7.html)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102522730B1 (ko) * 2016-06-29 2023-04-19 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 디프로보심: 새로운 강력한 부류의 tlr 작용제
AU2019315952A1 (en) * 2018-08-02 2021-03-04 The Board Of Regents Of The University Of Texas System Adjuvant effect of the TLR1/2 agonist diprovocim synergizes with checkpoint-inhibiting antibodies to eliminate disease

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101304748A (zh) * 2005-08-22 2008-11-12 加利福尼亚大学董事会 Tlr激动剂
EA019151B1 (ru) * 2007-02-07 2014-01-30 Дзе Регентс Оф Дзе Юниверсити Оф Калифорния Конъюгаты синтетических агонистов tlr и их применение
WO2008112941A1 (en) * 2007-03-13 2008-09-18 Board Of Regents The University Of Texas System Composition and method for the treatment of diseases affected by a peptide receptor
KR101208778B1 (ko) * 2008-03-03 2012-12-05 노파르티스 아게 Ｔｌｒ 활성 조정제로서의 화합물 및 조성물

Also Published As

Publication number Publication date
EP3177601A2 (en) 2017-06-14
CA2957372C (en) 2019-07-23
AU2015301100B2 (en) 2017-10-19
WO2016022700A2 (en) 2016-02-11
EP3177601A4 (en) 2018-04-04
JP2017530943A (ja) 2017-10-19
WO2016022700A8 (en) 2017-08-10
ES2944541T3 (es) 2023-06-22
CA2957372A1 (en) 2016-02-11
AU2015301100A1 (en) 2017-03-02
WO2016022700A3 (en) 2016-07-28
US9918959B2 (en) 2018-03-20
AU2015301100A8 (en) 2017-08-24
US20170224653A1 (en) 2017-08-10
EP3177601B1 (en) 2023-03-01

Similar Documents

Publication Publication Date Title
Skwarczynski et al. Poly (amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines
JP6356160B2 (ja) ネオセプチン：低分子アジュバント
TWI465434B (zh) Ｃ５ａＲ拮抗劑
JP2020536106A (ja) Ｈｉｖの処置に有用なインターフェロン遺伝子の刺激物質（ｓｔｉｎｇ）の調節物質
EA028550B1 (ru) Ингибитор грелин-o-ацилтрансферазы
CA3064025A1 (en) 5-5 fused rings as c5a inhibitors
JP2021502986A (ja) 新規イミダゾピリミジン化合物およびそれらの使用
KR101432246B1 (ko) 메포민을 포함하는 자가면역질환 예방 및 치료용 조성물
CN116075513A (zh) Nek7激酶的抑制剂
JP6353159B2 (ja) Ｔｌｒ非依存性低分子アジュバント
KR20240046882A (ko) 면역 불내성의 감소 및 자가면역 장애의 치료를 위한 조성물 및 방법
JP2022525608A (ja) ワクチンアジュバントとしてのｔｌｒ４およびｔｌｒ７リガンド製剤
Yang et al. Next-generation diprovocims with potent human and murine TLR1/TLR2 agonist activity that activate the innate and adaptive immune response
CN102002049B (zh) 一种抗原及其制备方法与应用
MX2014012634A (es) Compuesto heterociclico aromatico biciclico nitrogenado.
JP2018530738A (ja) 緑膿菌阻害化合物
JP2020530005A (ja) Ｂリンパ球活性の調節及び臓器保護のためのピルフェニドン誘導体
WO2024046323A1 (zh) 一种苯并五元氮环类化合物、其制备方法及医药用途
CN120239694A (zh) 苯基氧基酰胺激酶抑制剂
KR20240145992A (ko) 비사이클릭 프탈라진-1(2h)-온 유도체 및 관련 용도
TW201934543A (zh) 以鋅結合劑為基礎的ｅｂｎａ１專一性化合物
TWI908811B (zh) Nek7激酶抑制劑
WO2025045124A1 (zh) Soat1抑制剂及其应用
WO2019003141A1 (en) MODULATORS OF INDOLAMINE 2,3-DIOXYGENASE

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20171102

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20171102

A871 Explanation of circumstances concerning accelerated examination

Free format text: JAPANESE INTERMEDIATE CODE: A871

Effective date: 20171102

A975 Report on accelerated examination

Free format text: JAPANESE INTERMEDIATE CODE: A971005

Effective date: 20180213

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20180219

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20180222

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20180521

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: 20180604

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20180607

R150 Certificate of patent or registration of utility model

Ref document number: 6353159

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250