JP2005500300A5 - - Google Patents
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- Publication number
- JP2005500300A5 JP2005500300A5 JP2003506277A JP2003506277A JP2005500300A5 JP 2005500300 A5 JP2005500300 A5 JP 2005500300A5 JP 2003506277 A JP2003506277 A JP 2003506277A JP 2003506277 A JP2003506277 A JP 2003506277A JP 2005500300 A5 JP2005500300 A5 JP 2005500300A5
- Authority
- JP
- Japan
- Prior art keywords
- medicament
- preparation
- compound
- treatment
- use according
- 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
- 150000001875 compounds Chemical class 0.000 claims 15
- 239000003814 drug Substances 0.000 claims 12
- 230000002265 prevention Effects 0.000 claims 8
- 206010028980 Neoplasm Diseases 0.000 claims 6
- 201000011510 cancer Diseases 0.000 claims 4
- 150000002596 lactones Chemical class 0.000 claims 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 3
- 125000001033 ether group Chemical group 0.000 claims 3
- 230000036470 plasma concentration Effects 0.000 claims 3
- 108010001127 Insulin Receptor Proteins 0.000 claims 2
- 102100036721 Insulin receptor Human genes 0.000 claims 2
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 claims 2
- 238000001802 infusion Methods 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- YJGVMLPVUAXIQN-HAEOHBJNSA-N picropodophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-HAEOHBJNSA-N 0.000 claims 2
- NOVZFMNCTCKLPF-UHFFFAOYSA-N 2,5-bis(aziridin-1-yl)-3,6-dipropoxycyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C(OCCC)=C(N2CC2)C(=O)C(OCCC)=C1N1CC1 NOVZFMNCTCKLPF-UHFFFAOYSA-N 0.000 claims 1
- 206010000599 Acromegaly Diseases 0.000 claims 1
- 206010003210 Arteriosclerosis Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- ZGLXUQQMLLIKAN-UHFFFAOYSA-N Deoxypicropodophyllin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3CC3C2C(OC3)=O)=C1 ZGLXUQQMLLIKAN-UHFFFAOYSA-N 0.000 claims 1
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 claims 1
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 claims 1
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 claims 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 claims 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 208000011775 arteriosclerosis disease Diseases 0.000 claims 1
- 238000007887 coronary angioplasty Methods 0.000 claims 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims 1
- 239000000824 cytostatic agent Substances 0.000 claims 1
- ZGLXUQQMLLIKAN-SVIJTADQSA-N deoxypodophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3C[C@@H]3[C@@H]2C(OC3)=O)=C1 ZGLXUQQMLLIKAN-SVIJTADQSA-N 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 230000026731 phosphorylation Effects 0.000 claims 1
- 238000006366 phosphorylation reaction Methods 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0102168-2 | 2001-06-19 | ||
| SE0102168A SE0102168D0 (sv) | 2001-06-19 | 2001-06-19 | New use and new compounds |
| US30043101P | 2001-06-26 | 2001-06-26 | |
| US60/300,431 | 2001-06-26 | ||
| PCT/SE2002/001202 WO2002102804A1 (en) | 2001-06-19 | 2002-06-19 | New use of specific cyclolignans |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009134006A Division JP2009242406A (ja) | 2001-06-19 | 2009-06-03 | 特定のシクロリグナン類の新しい使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005500300A JP2005500300A (ja) | 2005-01-06 |
| JP2005500300A5 true JP2005500300A5 (https=) | 2006-01-05 |
| JP5071910B2 JP5071910B2 (ja) | 2012-11-14 |
Family
ID=20284528
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003506278A Pending JP2004534078A (ja) | 2001-06-19 | 2002-06-19 | シクロリグナン類の新規の使用および新規のシクロリグナン類 |
| JP2003506277A Expired - Fee Related JP5071910B2 (ja) | 2001-06-19 | 2002-06-19 | 特定のシクロリグナン類の新しい使用 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003506278A Pending JP2004534078A (ja) | 2001-06-19 | 2002-06-19 | シクロリグナン類の新規の使用および新規のシクロリグナン類 |
Country Status (15)
| Country | Link |
|---|---|
| US (7) | US7348358B2 (https=) |
| EP (5) | EP1397369A1 (https=) |
| JP (2) | JP2004534078A (https=) |
| KR (1) | KR100940055B1 (https=) |
| CN (3) | CN1659171A (https=) |
| AT (1) | ATE441411T1 (https=) |
| AU (2) | AU2002311731B8 (https=) |
| CA (2) | CA2451047C (https=) |
| DK (1) | DK1498121T3 (https=) |
| ES (1) | ES2333014T3 (https=) |
| NO (1) | NO332642B1 (https=) |
| NZ (2) | NZ530172A (https=) |
| PT (1) | PT1498121E (https=) |
| SE (1) | SE0102168D0 (https=) |
| WO (2) | WO2002102805A1 (https=) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0102168D0 (sv) * | 2001-06-19 | 2001-06-19 | Karolinska Innovations Ab | New use and new compounds |
| SE0203747D0 (sv) * | 2002-12-18 | 2002-12-18 | Karolinska Innovations Ab | New use |
| SE0203746D0 (sv) * | 2002-12-18 | 2002-12-18 | Karolinska Innovations Ab | New compounds |
| SE0301202D0 (sv) * | 2003-04-24 | 2003-04-24 | Orteca Ab C O Karolinska Innov | New use and new compounds |
| US7342114B2 (en) | 2003-07-01 | 2008-03-11 | California Pacific Medical Center | Podophyllotoxin derivatives |
| US20050075358A1 (en) * | 2003-10-06 | 2005-04-07 | Carboni Joan M. | Methods for treating IGF1R-inhibitor induced hyperglycemia |
| KR100872204B1 (ko) * | 2003-10-15 | 2008-12-09 | 오에스아이 파마슈티컬스, 인코포레이티드 | 이미다조피라진 티로신 키나제 억제제 |
| ATE514434T1 (de) | 2004-02-25 | 2011-07-15 | Dana Farber Cancer Inst Inc | Hemmer des insulinartigen wachstumsfaktor- rezeptors-1 zur hemmung von tumorzellwachstum |
| ATE384700T1 (de) | 2004-03-12 | 2008-02-15 | Analytecon Sa | Tetrahydroisochinolin- und tetrahydrobenzazepin derivative als igf-1r inhibitoren |
| TWI378934B (en) * | 2004-04-02 | 2012-12-11 | Osi Pharm Inc | 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors |
| TW200613306A (en) | 2004-07-20 | 2006-05-01 | Osi Pharm Inc | Imidazotriazines as protein kinase inhibitors |
| US7566721B2 (en) * | 2005-08-08 | 2009-07-28 | Osi Pharmaceuticals, Inc. | Substituted thienol[2,3-d]pyrimidines as kinase inhibitors |
| AU2006292278B2 (en) | 2005-09-20 | 2012-03-08 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| US8575164B2 (en) * | 2005-12-19 | 2013-11-05 | OSI Pharmaceuticals, LLC | Combination cancer therapy |
| AU2007218217A1 (en) * | 2006-02-24 | 2007-08-30 | Axelar Ab | Use of cyclolignans for the treatment of type 2 diabetes and as contraceptives |
| EP2056808A4 (en) * | 2006-08-28 | 2009-12-23 | Univ California | Small molecule potentiator of hormonal therapy for breast cancer |
| JP2011510018A (ja) * | 2008-01-18 | 2011-03-31 | オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド | 癌治療のためのイミダゾピラジノール誘導体 |
| WO2009100349A1 (en) * | 2008-02-09 | 2009-08-13 | The Trustees Of Columbia University In The City Of New York | Analogues of (-)-picropodophyllin, synthesis and uses thereof |
| WO2009108857A2 (en) * | 2008-02-27 | 2009-09-03 | Combithera, Inc. | Combination therapy for prostate cancer |
| EP2274617A4 (en) * | 2008-04-10 | 2011-11-09 | Massachusetts Inst Technology | METHOD OF DETECTING AND USING MEDIUM-TREATMENT AID ON CANCER STEM CELLS |
| EP2283020B8 (en) * | 2008-05-19 | 2012-12-12 | OSI Pharmaceuticals, LLC | Substituted imidazopyr-and imidazotri-azines |
| WO2010054264A1 (en) | 2008-11-07 | 2010-05-14 | Triact Therapeutics, Inc. | Use of catecholic butane derivatives in cancer therapy |
| WO2010099139A2 (en) | 2009-02-25 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Combination anti-cancer therapy |
| US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| EP2401614A1 (en) | 2009-02-27 | 2012-01-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| WO2010123792A1 (en) | 2009-04-20 | 2010-10-28 | Osi Pharmaceuticals, Inc. | Preparation of c-pyrazine-methylamines |
| EP2427192A1 (en) * | 2009-05-07 | 2012-03-14 | OSI Pharmaceuticals, LLC | Use of osi-906 for treating adrenocortical carcinoma |
| WO2010138686A1 (en) * | 2009-05-29 | 2010-12-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Mdri-inverse agents |
| US7924203B2 (en) * | 2009-06-12 | 2011-04-12 | Analog Devices, Inc. | Most significant bits analog to digital converter, and an analog to digital converter including a most significant bits analog to digital converter |
| WO2010146059A2 (en) | 2009-06-16 | 2010-12-23 | F. Hoffmann-La Roche Ag | Biomarkers for igf-1r inhibitor therapy |
| CA2783656A1 (en) | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| CA2783665A1 (en) | 2010-03-03 | 2011-09-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| EP2544672A1 (en) | 2010-03-09 | 2013-01-16 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| CN103189381B (zh) | 2010-08-31 | 2016-06-08 | 阿克塞拉公司 | 制备环木脂体的新方法 |
| EP2624827A4 (en) | 2010-10-08 | 2014-05-28 | Axelar Ab | PICROPODOPHYLLINE B OR C POLYMORPHIC FOR USE IN ANTICANCER THERAPY |
| US20120214830A1 (en) | 2011-02-22 | 2012-08-23 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| JP5892508B2 (ja) * | 2011-05-23 | 2016-03-23 | 国立大学法人 鹿児島大学 | 抗腫瘍剤及びその製造方法 |
| WO2013124382A1 (en) * | 2012-02-24 | 2013-08-29 | Nestec S.A. | Peltatin for use in the treatment of cardiovascular disorders |
| WO2013132262A1 (en) | 2012-03-09 | 2013-09-12 | Axelar Ab | Picropodophyllin derivatives |
| WO2013132263A1 (en) | 2012-03-09 | 2013-09-12 | Axelar Ab | Picropodophyllin derivatives for use in therapy |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| JP5923375B2 (ja) * | 2012-04-24 | 2016-05-24 | 花王株式会社 | Ｃｇｒｐ応答性促進剤 |
| WO2014102889A1 (ja) * | 2012-12-25 | 2014-07-03 | 国立大学法人鹿児島大学 | 抗腫瘍剤及びその製造方法 |
| JP6255038B2 (ja) | 2013-02-26 | 2017-12-27 | トリアクト セラピューティクス，インク． | 癌治療 |
| CA2912254C (en) | 2013-05-10 | 2021-06-08 | M. Alphabet 2, L.L.C. | Methods of treating skin conditions using cyclolignan compounds |
| US9381246B2 (en) | 2013-09-09 | 2016-07-05 | Triact Therapeutics, Inc. | Cancer therapy |
| CN104434909A (zh) * | 2013-09-12 | 2015-03-25 | 中国药科大学 | 一种去氧鬼臼毒素作为胰岛素样生长因子受体拮抗剂用途 |
| WO2015168255A1 (en) | 2014-04-29 | 2015-11-05 | Whitehead Institute For Biomedical Research | Methods and compositions for targeting cancer stem cells |
| JP6550538B2 (ja) | 2015-10-27 | 2019-07-24 | カリフォルニア パシフィック メディカル センター | ポドフィロトキシン誘導体およびそれらの使用 |
| US10087194B2 (en) | 2015-10-27 | 2018-10-02 | California Pacific Medical Center | Podophyllotoxin derivatives and their use |
| CN110669054B (zh) * | 2018-07-03 | 2022-04-26 | 南京药石科技股份有限公司 | 胰岛素样生长因子-1受体酪氨酸激酶抑制剂及其用途 |
| KR102378151B1 (ko) * | 2020-05-11 | 2022-03-24 | 주식회사 제이앤씨사이언스 | 베타-아포피크로포도필린의 신규한 유도체 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2825730A (en) * | 1953-02-04 | 1958-03-04 | Thompson Boyce Plant Res | Organic compounds |
| US4342777A (en) * | 1979-03-29 | 1982-08-03 | The United States Of America As Represented By The Secretary Of Agriculture | Polybutylbenzylphenols and benzyl-3,4-methylenedioxybenzenes in insect population control |
| HU201672B (en) | 1984-12-28 | 1990-12-28 | Conpharm Ab | Process for producing pharmaceutical compositions comprising podophyllotoxin |
| US4771072A (en) * | 1985-01-10 | 1988-09-13 | Tanabe Seiyaku Co., Ltd. | Alkoxynaphthalene derivatives |
| SE468213B (sv) * | 1986-06-27 | 1992-11-23 | Conpharm Ab | Anvaendning av podophyllotoxin eller ett derivat daerav till framstaellning av en farmakologisk beredning foer behandling av kollagenoser, saerskilt reumatoid artrit |
| WO1988003800A1 (en) * | 1986-11-19 | 1988-06-02 | Chemex Pharmaceuticals, Inc. | Lipoxygenase inhibitors |
| SE464167B (sv) * | 1989-07-31 | 1991-03-18 | Analytecon Sa | Topisk farmaceutisk beredning av podophyllotoxin |
| CN1075316A (zh) | 1992-10-22 | 1993-08-18 | 布里斯托尔-米尔斯·斯奎布公司 | 表鬼臼毒中间体的制备方法 |
| GB9422947D0 (en) | 1994-11-14 | 1995-01-04 | Univ Salamanca | Immunosuppressive cyclolignan derivatives |
| JPH09194368A (ja) * | 1996-01-11 | 1997-07-29 | Pola Chem Ind Inc | ポドフィロトキシン誘導体及びそれからなる新規細胞分化誘導剤 |
| US5726027A (en) | 1996-03-08 | 1998-03-10 | The Regents Of The University Of California | Method for treatment of insulin resistance |
| DE69834828T2 (de) * | 1997-11-27 | 2007-01-04 | Commonwealth Scientific And Industrial Research Organisation | Verfahren zur konstruktion von agonisten und antagonisten des igf-rezeptors (1-462) |
| JP2002519335A (ja) | 1998-06-26 | 2002-07-02 | クアナム メディカル コーポレイション | 再狭窄の予防のためのトポイソメラーゼインヒビター |
| CA2397871A1 (en) | 2000-01-20 | 2001-07-26 | Supratek Pharma Inc. | Novel podophyllotoxin compositions |
| EP1335922B1 (en) * | 2000-11-20 | 2006-09-13 | Song-Bae Kim | Process for preparing 4'-demethyl-4'-O-substituted-1-deoxypodophyllotoxin derivatives and geometric isomers thereof and anti-cancer composition comprising the same |
| SE0102168D0 (sv) * | 2001-06-19 | 2001-06-19 | Karolinska Innovations Ab | New use and new compounds |
| WO2004094409A1 (en) * | 2003-03-27 | 2004-11-04 | Lankenau Institute For Medical Research | Novel ido inhibitors and methods of use |
| SE0301202D0 (sv) * | 2003-04-24 | 2003-04-24 | Orteca Ab C O Karolinska Innov | New use and new compounds |
-
2001
- 2001-06-19 SE SE0102168A patent/SE0102168D0/xx unknown
-
2002
- 2002-06-19 CN CN028162404A patent/CN1659171A/zh active Pending
- 2002-06-19 EP EP02741588A patent/EP1397369A1/en not_active Ceased
- 2002-06-19 WO PCT/SE2002/001223 patent/WO2002102805A1/en not_active Ceased
- 2002-06-19 NZ NZ53017202A patent/NZ530172A/xx unknown
- 2002-06-19 EP EP08150437A patent/EP1938819A3/en not_active Withdrawn
- 2002-06-19 EP EP10153209A patent/EP2186513A1/en not_active Withdrawn
- 2002-06-19 AU AU2002311731A patent/AU2002311731B8/en not_active Ceased
- 2002-06-19 ES ES04024370T patent/ES2333014T3/es not_active Expired - Lifetime
- 2002-06-19 NZ NZ530290A patent/NZ530290A/en not_active IP Right Cessation
- 2002-06-19 CN CNA2009101347598A patent/CN101606929A/zh active Pending
- 2002-06-19 DK DK04024370T patent/DK1498121T3/da active
- 2002-06-19 PT PT04024370T patent/PT1498121E/pt unknown
- 2002-06-19 CA CA2451047A patent/CA2451047C/en not_active Expired - Fee Related
- 2002-06-19 CA CA2455328A patent/CA2455328C/en not_active Expired - Fee Related
- 2002-06-19 AT AT04024370T patent/ATE441411T1/de active
- 2002-06-19 US US10/481,441 patent/US7348358B2/en not_active Expired - Fee Related
- 2002-06-19 KR KR1020037016630A patent/KR100940055B1/ko not_active Expired - Fee Related
- 2002-06-19 EP EP08150436A patent/EP1938818A3/en not_active Withdrawn
- 2002-06-19 JP JP2003506278A patent/JP2004534078A/ja active Pending
- 2002-06-19 EP EP04024370A patent/EP1498121B1/en not_active Expired - Lifetime
- 2002-06-19 CN CNB028161904A patent/CN100503611C/zh not_active Expired - Fee Related
- 2002-06-19 JP JP2003506277A patent/JP5071910B2/ja not_active Expired - Fee Related
- 2002-06-19 US US10/480,800 patent/US20040167208A1/en not_active Abandoned
- 2002-06-19 WO PCT/SE2002/001202 patent/WO2002102804A1/en not_active Ceased
- 2002-06-19 NO NO20035648A patent/NO332642B1/no not_active IP Right Cessation
- 2002-06-19 AU AU2002314671A patent/AU2002314671B2/en not_active Ceased
-
2006
- 2006-02-03 US US11/346,294 patent/US7709526B2/en not_active Expired - Fee Related
-
2008
- 2008-01-29 US US12/021,530 patent/US7629381B2/en not_active Expired - Fee Related
- 2008-01-29 US US12/021,578 patent/US7662851B2/en not_active Expired - Fee Related
-
2009
- 2009-07-23 US US12/508,218 patent/US8389747B2/en not_active Expired - Fee Related
-
2010
- 2010-02-26 US US12/714,107 patent/US20100216728A1/en not_active Abandoned
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