JP2010539153A5 - - Google Patents
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- Publication number
- JP2010539153A5 JP2010539153A5 JP2010524589A JP2010524589A JP2010539153A5 JP 2010539153 A5 JP2010539153 A5 JP 2010539153A5 JP 2010524589 A JP2010524589 A JP 2010524589A JP 2010524589 A JP2010524589 A JP 2010524589A JP 2010539153 A5 JP2010539153 A5 JP 2010539153A5
- Authority
- JP
- Japan
- Prior art keywords
- group
- progestin
- ethinylestradiol
- agonist
- gnrh
- 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.)
- Granted
Links
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims 12
- 239000000583 progesterone congener Substances 0.000 claims 9
- 239000000556 agonist Substances 0.000 claims 8
- 239000002207 metabolite Substances 0.000 claims 6
- 239000002379 progesterone receptor modulator Substances 0.000 claims 6
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 claims 5
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims 5
- 150000001875 compounds Chemical class 0.000 claims 5
- -1 chromanomate Chemical compound 0.000 claims 4
- 239000002474 gonadorelin antagonist Substances 0.000 claims 4
- 229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 claims 3
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 claims 3
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims 3
- 229940123142 Steroid sulfatase inhibitor Drugs 0.000 claims 3
- 229960002568 ethinylestradiol Drugs 0.000 claims 3
- 229960004400 levonorgestrel Drugs 0.000 claims 3
- 229940127234 oral contraceptive Drugs 0.000 claims 3
- 239000003539 oral contraceptive agent Substances 0.000 claims 3
- 229960003387 progesterone Drugs 0.000 claims 3
- 239000000186 progesterone Substances 0.000 claims 3
- VTHUYJIXSMGYOQ-KOORYGTMSA-N 17-hydroxyprogesterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 VTHUYJIXSMGYOQ-KOORYGTMSA-N 0.000 claims 2
- 150000000319 19-nortestosterones Chemical class 0.000 claims 2
- FPYZYVOKXDWGRZ-UHFFFAOYSA-N S(=O)(=O)=NC(=O)N.N1CCCCC1 Chemical compound S(=O)(=O)=NC(=O)N.N1CCCCC1 FPYZYVOKXDWGRZ-UHFFFAOYSA-N 0.000 claims 2
- METQSPRSQINEEU-UHFFFAOYSA-N dihydrospirorenone Natural products CC12CCC(C3(CCC(=O)C=C3C3CC33)C)C3C1C1CC1C21CCC(=O)O1 METQSPRSQINEEU-UHFFFAOYSA-N 0.000 claims 2
- 229960004845 drospirenone Drugs 0.000 claims 2
- METQSPRSQINEEU-HXCATZOESA-N drospirenone Chemical compound C([C@]12[C@H]3C[C@H]3[C@H]3[C@H]4[C@@H]([C@]5(CCC(=O)C=C5[C@@H]5C[C@@H]54)C)CC[C@@]31C)CC(=O)O2 METQSPRSQINEEU-HXCATZOESA-N 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229940011871 estrogen Drugs 0.000 claims 2
- 239000000262 estrogen Substances 0.000 claims 2
- 229940053934 norethindrone Drugs 0.000 claims 2
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 claims 2
- 210000001672 ovary Anatomy 0.000 claims 2
- 150000003128 pregnanes Chemical class 0.000 claims 2
- ZEXMYIFTZVZUMU-UHFFFAOYSA-N (2-phenylphenyl)sulfamic acid Chemical compound OS(=O)(=O)NC1=CC=CC=C1C1=CC=CC=C1 ZEXMYIFTZVZUMU-UHFFFAOYSA-N 0.000 claims 1
- ORKBYCQJWQBPFG-WOMZHKBXSA-N (8r,9s,10r,13s,14s,17r)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one;(8r,9s,13s,14s,17r)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1.O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 ORKBYCQJWQBPFG-WOMZHKBXSA-N 0.000 claims 1
- IEXUMDBQLIVNHZ-YOUGDJEHSA-N (8s,11r,13r,14s,17s)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(O)CCCO)[C@@]2(C)C1 IEXUMDBQLIVNHZ-YOUGDJEHSA-N 0.000 claims 1
- MXBCYQUALCBQIJ-RYVPXURESA-N (8s,9s,10r,13s,14s,17r)-13-ethyl-17-ethynyl-11-methylidene-1,2,3,6,7,8,9,10,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol;(8r,9s,13s,14s,17r)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1.C1CC[C@@H]2[C@H]3C(=C)C[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 MXBCYQUALCBQIJ-RYVPXURESA-N 0.000 claims 1
- 108010037003 Buserelin Proteins 0.000 claims 1
- 201000009273 Endometriosis Diseases 0.000 claims 1
- 208000000571 Fibrocystic breast disease Diseases 0.000 claims 1
- 108010069236 Goserelin Proteins 0.000 claims 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims 1
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 claims 1
- 108010000817 Leuprolide Proteins 0.000 claims 1
- 108010021717 Nafarelin Proteins 0.000 claims 1
- JVBGZFRPTRKSBB-MJBQOYBXSA-N Telapristone acetate Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(C(=O)COC)OC(C)=O)=CC=C(N(C)C)C=C1 JVBGZFRPTRKSBB-MJBQOYBXSA-N 0.000 claims 1
- 108010050144 Triptorelin Pamoate Proteins 0.000 claims 1
- 206010046798 Uterine leiomyoma Diseases 0.000 claims 1
- GYMWQLRSSDFGEQ-ADRAWKNSSA-N [(3e,8r,9s,10r,13s,14s,17r)-13-ethyl-17-ethynyl-3-hydroxyimino-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] acetate;(8r,9s,13s,14s,17r)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1.O/N=C/1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(OC(C)=O)C#C)[C@@H]4[C@@H]3CCC2=C\1 GYMWQLRSSDFGEQ-ADRAWKNSSA-N 0.000 claims 1
- 230000005856 abnormality Effects 0.000 claims 1
- 208000011803 breast fibrocystic disease Diseases 0.000 claims 1
- 229960002719 buserelin Drugs 0.000 claims 1
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000037416 cystogenesis Effects 0.000 claims 1
- 230000009977 dual effect Effects 0.000 claims 1
- 229960002913 goserelin Drugs 0.000 claims 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 201000010260 leiomyoma Diseases 0.000 claims 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 claims 1
- 229960004338 leuprorelin Drugs 0.000 claims 1
- 230000007774 longterm Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- IMSSROKUHAOUJS-MJCUULBUSA-N mestranol Chemical compound C1C[C@]2(C)[C@@](C#C)(O)CC[C@H]2[C@@H]2CCC3=CC(OC)=CC=C3[C@H]21 IMSSROKUHAOUJS-MJCUULBUSA-N 0.000 claims 1
- 229960001390 mestranol Drugs 0.000 claims 1
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 claims 1
- 229960003248 mifepristone Drugs 0.000 claims 1
- 229960002333 nafarelin Drugs 0.000 claims 1
- RWHUEXWOYVBUCI-ITQXDASVSA-N nafarelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 RWHUEXWOYVBUCI-ITQXDASVSA-N 0.000 claims 1
- 229950011093 onapristone Drugs 0.000 claims 1
- 239000003217 oral combined contraceptive Substances 0.000 claims 1
- 230000027758 ovulation cycle Effects 0.000 claims 1
- 239000006187 pill Substances 0.000 claims 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims 1
- 229960004824 triptorelin Drugs 0.000 claims 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96010907P | 2007-09-17 | 2007-09-17 | |
| US60/960,109 | 2007-09-17 | ||
| PCT/IB2008/002296 WO2009037539A2 (en) | 2007-09-17 | 2008-09-04 | Treatment of oestrogen dependant conditions in pre-menopausal women |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010539153A JP2010539153A (ja) | 2010-12-16 |
| JP2010539153A5 true JP2010539153A5 (enExample) | 2011-10-13 |
| JP5543920B2 JP5543920B2 (ja) | 2014-07-09 |
Family
ID=40468492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010524589A Expired - Fee Related JP5543920B2 (ja) | 2007-09-17 | 2008-09-04 | 閉経前の女性におけるエストロゲン依存症状の治療 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20100204146A1 (enExample) |
| EP (1) | EP2207544A2 (enExample) |
| JP (1) | JP5543920B2 (enExample) |
| KR (1) | KR20100068287A (enExample) |
| BR (1) | BRPI0817045A2 (enExample) |
| CA (1) | CA2698814A1 (enExample) |
| WO (1) | WO2009037539A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2647378A1 (en) | 2012-04-05 | 2013-10-09 | PregLem S.A. | Steroid sulfatase inhibitor regimen for the treatment of endometriosis |
| EP2647379A1 (en) | 2012-04-05 | 2013-10-09 | PregLem S.A. | Combined use of a steroid sulfatase inhibitor for the treatment of endometriosis |
| BR112015023273A2 (pt) * | 2013-03-14 | 2017-07-18 | Hra Pharma Lab | método para programar a ovulação. |
| KR101686986B1 (ko) * | 2014-07-28 | 2016-12-16 | 에스케이케미칼주식회사 | 류프로라이드를 포함하는 속효성과 지속성을 동시에 갖는 약제학적 조성물 |
| KR102397510B1 (ko) | 2014-12-23 | 2022-05-13 | 주식회사 젬백스앤카엘 | 난소 기능 보존용 펩티드 및 이를 포함하는 조성물 |
| AU2018243312B2 (en) | 2017-03-31 | 2023-02-02 | Bt Bidco, Inc. | Localization systems and methods for an ingestible device |
| CN110809473A (zh) * | 2017-06-01 | 2020-02-18 | 延世大学校产学协力团 | 用于预防或治疗骨相关疾病的药物组合物 |
| WO2019110688A1 (en) * | 2017-12-05 | 2019-06-13 | Ferring B.V. | A composition comprising degarelix for use in the treatment of breast cancer |
| WO2023150267A1 (en) * | 2022-02-03 | 2023-08-10 | Maison Amori Oqvpo Llc | Methods, compositions and uses for treating cancer by providing medications that induce targeted tumor cell mitosis before providing chemotherapy or radiation and kits therefor |
| IT202400009064A1 (it) * | 2024-04-19 | 2025-10-19 | J Dental Care Srl | Composizione per uso nel trattamento della sintomatologia post-menopausale e nel trattamento contraccettivo ormonale combinato |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| GB9118478D0 (en) | 1991-08-29 | 1991-10-16 | Imperial College | Steroid sulphatase inhibitors |
| GB9625334D0 (en) | 1996-12-05 | 1997-01-22 | Imperial College | Compound |
| GB9603325D0 (en) | 1996-02-16 | 1996-04-17 | Imperial College | A compound |
| GB9118465D0 (en) | 1991-08-29 | 1991-10-16 | Imperial College | Steroid sulphatase inhibitors |
| WO1996015794A1 (en) * | 1994-11-22 | 1996-05-30 | Balance Pharmaceuticals, Inc. | Compositions and methods for contraception and for treatment of benign gynecological disorders |
| GB9807779D0 (en) | 1998-04-09 | 1998-06-10 | Ciba Geigy Ag | Organic compounds |
| JP4320089B2 (ja) * | 1999-07-06 | 2009-08-26 | あすか製薬株式会社 | フェニルスルファメート誘導体 |
| CO5261573A1 (es) | 1999-11-19 | 2003-03-31 | Novartis Ag | Derivados de benzoxa y bezotiazol, compuesto y composicion farmaceutica que los contiene y proceso para la preparacion de la mencionada composicion |
| GB0020498D0 (en) | 2000-08-18 | 2000-10-11 | Sterix Ltd | Compound |
| GB0025788D0 (en) | 2000-10-20 | 2000-12-06 | Sterix Ltd | Use |
| WO2003006027A1 (en) * | 2001-07-13 | 2003-01-23 | Schering Aktiengesellschaft | Combination of drospirenone and an estrogen sulphamate for hrt |
| AR037097A1 (es) | 2001-10-05 | 2004-10-20 | Novartis Ag | Compuestos acilsulfonamidas, composiciones farmaceuticas y el uso de dichos compuestos para la preparacion de un medicamento |
| ATE319734T1 (de) | 2001-10-18 | 2006-03-15 | Sterix Ltd | Steroidale verbindungen zur inhibierung von steroidsulfatasen |
| CN100473648C (zh) | 2001-11-21 | 2009-04-01 | 斯特里克斯有限公司 | 作为芳香化酶抑制剂的含氨基磺酸酯基的1,2,4-三唑衍生物 |
| AR039156A1 (es) | 2002-03-28 | 2005-02-09 | Novartis Ag | Amidas del acido piperidinilamino sulfamico o piperazinil sulfamico y su uso para la manufactura de un medicamento en enfermedades mediadas por la accion de la sulfatasa esteroide |
| AU2003272964A1 (en) * | 2002-10-09 | 2004-05-04 | Kyowa Hakko Kogyo Co., Ltd. | Remedy for hormone-dependent cancer |
| AR041952A1 (es) | 2002-11-14 | 2005-06-01 | Novartis Ag | N-sulfonilaminotiazol |
| MXPA05012300A (es) * | 2003-05-16 | 2006-01-30 | Theramex | Derivados de benzotiofeno de sulfamato como inhibidores de sulfatasa esteroidea. |
| PL1624878T3 (pl) * | 2003-05-22 | 2007-01-31 | Pantarhei Bioscience Bv | Zastosowanie kompozycji zawierającej estrogenowy składnik w celu leczenia i zapobiegania bólowi mięśniowo-szkieletowemu |
| RU2365586C2 (ru) | 2003-12-15 | 2009-08-27 | Лаборатуар Терамекс | Производные 1-n-фениламино-1н-имидазола и содержащие их фармацевтические композиции |
| GB0411562D0 (en) | 2004-05-24 | 2004-06-23 | Sterix Ltd | Compound |
| GB0412492D0 (en) | 2004-06-04 | 2004-07-07 | Sterix Ltd | Compound |
| GB0505541D0 (en) | 2005-03-17 | 2005-04-27 | Novartis Ag | Organic compounds |
| GB0525323D0 (en) | 2005-12-13 | 2006-01-18 | Sterix Ltd | Compound |
-
2008
- 2008-09-04 CA CA2698814A patent/CA2698814A1/en not_active Abandoned
- 2008-09-04 JP JP2010524589A patent/JP5543920B2/ja not_active Expired - Fee Related
- 2008-09-04 US US12/678,674 patent/US20100204146A1/en not_active Abandoned
- 2008-09-04 KR KR1020107008404A patent/KR20100068287A/ko not_active Ceased
- 2008-09-04 EP EP08806991A patent/EP2207544A2/en not_active Withdrawn
- 2008-09-04 BR BRPI0817045 patent/BRPI0817045A2/pt not_active IP Right Cessation
- 2008-09-04 WO PCT/IB2008/002296 patent/WO2009037539A2/en not_active Ceased
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