JP2008525460A5 - - Google Patents
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- Publication number
- JP2008525460A5 JP2008525460A5 JP2007548380A JP2007548380A JP2008525460A5 JP 2008525460 A5 JP2008525460 A5 JP 2008525460A5 JP 2007548380 A JP2007548380 A JP 2007548380A JP 2007548380 A JP2007548380 A JP 2007548380A JP 2008525460 A5 JP2008525460 A5 JP 2008525460A5
- Authority
- JP
- Japan
- Prior art keywords
- seq
- composition
- nucleotides
- interfering rna
- sequence
- 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
- 239000002773 nucleotide Substances 0.000 claims 48
- 125000003729 nucleotide group Chemical group 0.000 claims 48
- 230000000692 anti-sense effect Effects 0.000 claims 32
- 239000000203 mixture Substances 0.000 claims 32
- 108020004999 messenger RNA Proteins 0.000 claims 26
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 22
- 230000002452 interceptive effect Effects 0.000 claims 22
- 230000000295 complement effect Effects 0.000 claims 12
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 claims 10
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 claims 10
- 230000004962 physiological condition Effects 0.000 claims 6
- 239000003937 drug carrier Substances 0.000 claims 4
- 208000030533 eye disease Diseases 0.000 claims 4
- 208000005590 Choroidal Neovascularization Diseases 0.000 claims 2
- 206010060823 Choroidal neovascularisation Diseases 0.000 claims 2
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 2
- 208000010412 Glaucoma Diseases 0.000 claims 2
- 208000022873 Ocular disease Diseases 0.000 claims 2
- 230000002238 attenuated effect Effects 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 208000002780 macular degeneration Diseases 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000029663 wound healing Effects 0.000 claims 2
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 claims 1
- 206010038934 Retinopathy proliferative Diseases 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 claims 1
- 230000037361 pathway Effects 0.000 claims 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 claims 1
- 230000000699 topical effect Effects 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63870504P | 2004-12-23 | 2004-12-23 | |
| US60/638,705 | 2004-12-23 | ||
| PCT/US2005/046064 WO2006069037A1 (en) | 2004-12-23 | 2005-12-19 | Rnai inhibition of ctgf for treatment of ocular disorders |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012029499A Division JP2012097119A (ja) | 2004-12-23 | 2012-02-14 | 眼の障害を処置するためのCTGFのRNAi阻害 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008525460A JP2008525460A (ja) | 2008-07-17 |
| JP2008525460A5 true JP2008525460A5 (enExample) | 2009-02-12 |
| JP5095414B2 JP5095414B2 (ja) | 2012-12-12 |
Family
ID=36218404
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007548380A Expired - Fee Related JP5095414B2 (ja) | 2004-12-23 | 2005-12-19 | 眼の障害を処置するためのCTGFのRNAi阻害 |
| JP2012029499A Withdrawn JP2012097119A (ja) | 2004-12-23 | 2012-02-14 | 眼の障害を処置するためのCTGFのRNAi阻害 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012029499A Withdrawn JP2012097119A (ja) | 2004-12-23 | 2012-02-14 | 眼の障害を処置するためのCTGFのRNAi阻害 |
Country Status (13)
| Country | Link |
|---|---|
| US (4) | US7622454B2 (enExample) |
| EP (2) | EP1827503A1 (enExample) |
| JP (2) | JP5095414B2 (enExample) |
| KR (1) | KR20070091337A (enExample) |
| CN (1) | CN101160138B (enExample) |
| AR (1) | AR052172A1 (enExample) |
| AU (1) | AU2005319279B2 (enExample) |
| BR (1) | BRPI0516377A (enExample) |
| CA (1) | CA2591611A1 (enExample) |
| MX (1) | MX2007007654A (enExample) |
| TW (1) | TWI386225B (enExample) |
| WO (1) | WO2006069037A1 (enExample) |
| ZA (1) | ZA200704932B (enExample) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2598234A1 (en) | 2005-03-11 | 2006-09-21 | Alcon, Inc. | Rnai-mediated inhibition of frizzled related protein-1 for treatment of glaucoma |
| US20060275797A1 (en) * | 2005-03-21 | 2006-12-07 | Alcon Manufacturing, Ltd. | Use of agents which inhibit connective tissue growth factor (CTGF) binding and signaling via the TrkA/p75NTR receptor complex for the prevention and treatment of CTGF-mediated ocular disorders |
| AU2008308784B2 (en) * | 2007-10-01 | 2013-07-18 | Arrowhead Research Corporation | Self complementary AAV-mediated delivery of interfering RNA molecules to treat or prevent ocular disorders |
| US7973019B1 (en) | 2007-10-03 | 2011-07-05 | Alcon Research, Ltd. | Transferrin/transferrin receptor-mediated siRNA delivery |
| US20090131358A1 (en) * | 2007-11-15 | 2009-05-21 | Alcon Research, Ltd. | LOW DENSITY LIPOPROTEIN RECEPTOR-MEDIATED siRNA DELIVERY |
| TW200932274A (en) | 2007-12-18 | 2009-08-01 | Alcon Res Ltd | Interfering RNA delivery system and uses thereof |
| US8446125B2 (en) | 2008-06-20 | 2013-05-21 | Superior Communications, Inc. | Vehicle power charger |
| US8946172B2 (en) | 2008-08-25 | 2015-02-03 | Excaliard Pharmaceuticals, Inc. | Method for reducing scarring during wound healing using antisense compounds directed to CTGF |
| EP2334319B1 (en) * | 2008-08-25 | 2017-12-06 | Excaliard Pharmaceuticals, Inc. | Method for reducing scarring during wound healing using antisense compounds directed to ctgf |
| CN107083386A (zh) * | 2008-08-25 | 2017-08-22 | 埃克斯雷德制药有限公司 | 阻止结缔组织生长因子的反义核苷酸及其用途 |
| EP2342340A1 (en) | 2008-09-22 | 2011-07-13 | Rxi Pharmaceuticals Corporation | Rna interference in skin indications |
| WO2010090762A1 (en) | 2009-02-04 | 2010-08-12 | Rxi Pharmaceuticals Corporation | Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| JP2012520683A (ja) * | 2009-03-19 | 2012-09-10 | メルク・シャープ・エンド・ドーム・コーポレイション | 低分子干渉核酸(siNA)を用いた結合組織増殖因子(CTGF)遺伝子発現のRNA干渉媒介性阻害 |
| CA2794189C (en) | 2010-03-24 | 2022-01-11 | Rxi Pharmaceuticals Corporation | Rna interference in dermal and fibrotic indications |
| US9095504B2 (en) | 2010-03-24 | 2015-08-04 | Rxi Pharmaceuticals Corporation | RNA interference in ocular indications |
| KR101249041B1 (ko) * | 2010-04-28 | 2013-03-29 | 포항공과대학교 산학협력단 | 결합조직 성장인자를 이용한 약학적 조성물 |
| EP2582365B1 (en) * | 2010-06-16 | 2019-03-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compositions for stimulating reepithelialisation during wound healing |
| CN103328633B (zh) | 2010-10-22 | 2018-07-10 | 成均馆大学校产学协力团 | 诱导rna干扰的核酸分子及其用途 |
| JP2014505666A (ja) | 2010-11-18 | 2014-03-06 | ザ ジェネラル ホスピタル コーポレイション | 癌治療のための降圧剤の組成物および使用 |
| DK2670411T3 (da) * | 2011-02-02 | 2019-05-13 | Excaliard Pharmaceuticals Inc | Antisense-forbindelser rettet mod bindevævsvækstfaktor (CTGF) til anvendelse i en fremgangsmåde til behandling af keloider eller hypertrofiske ar |
| CN102727513B (zh) * | 2011-04-15 | 2014-07-09 | 百奥迈科生物技术有限公司 | 靶向于组织因子基因的小核酸及其用途 |
| WO2012161677A1 (en) | 2011-05-20 | 2012-11-29 | Alcon Research, Ltd. | TRANSFERRIN/TRANSFERRIN RECEPTOR-MEDIATED siRNA DELIVERY |
| US8802839B2 (en) * | 2011-07-15 | 2014-08-12 | Fibrogen, Inc. | Connective tissue growth factor antisense oligonucleotides |
| US20130178421A1 (en) | 2012-01-06 | 2013-07-11 | Alcon Research, Ltd. | Interfering rna delivery system and uses thereof |
| JP5906327B2 (ja) | 2012-01-18 | 2016-04-20 | バイオニア コーポレーションBioneer Corporation | 磁性ナノ粒子−SAMiRNA複合体およびその製造方法 |
| CN108148838B (zh) * | 2012-05-22 | 2026-07-31 | 奥利克斯医药有限公司 | 具有细胞内穿透能力的诱导rna干扰的核酸分子及用途 |
| US9695421B2 (en) | 2013-07-05 | 2017-07-04 | Bioneer Corporation | Dengue virus-specific siRNA, double helix oligo-RNA structure comprising siRNA, and composition for suppressing proliferation of dengue virus comprising RNA structure |
| RU2656154C2 (ru) * | 2013-07-05 | 2018-05-31 | Байонир Корпорейшн | СВЯЗАННАЯ С РЕСПИРАТОРНЫМ ЗАБОЛЕВАНИЕМ ГЕН-СПЕЦИФИЧЕСКАЯ миРНК, ДВУСПИРАЛЬНАЯ КОНСТРУКЦИЯ ОЛИГО-РНК, СОДЕРЖАЩАЯ миРНК, И СОДЕРЖАЩАЯ ЕЕ КОМПОЗИЦИЯ ДЛЯ ПРЕДУПРЕЖДЕНИЯ ИЛИ ЛЕЧЕНИЯ РЕСПИРАТОРНОГО ЗАБОЛЕВАНИЯ |
| CA2917299C (en) | 2013-07-05 | 2020-07-21 | Bioneer Corporation | Improved nanoparticle type oligonucleotide structure having high efficiency and method for preparing same |
| WO2015085113A1 (en) * | 2013-12-04 | 2015-06-11 | Rxi Pharmaceuticals Corporation | Methods for treatment of wound healing utilizing chemically modified oligonucleotides |
| WO2015152693A2 (ko) | 2014-04-04 | 2015-10-08 | (주)바이오니아 | 신규 이중 나선 올리고 rna 및 이를 포함하는 섬유증 또는 호흡기 질환의 예방 또는 치료용 약학조성물 |
| CA2947270A1 (en) | 2014-04-28 | 2015-11-05 | Rxi Pharmaceuticals Corporation | Methods for treating cancer using nucleic acids targeting mdm2 or mycn |
| US10314690B1 (en) * | 2014-05-12 | 2019-06-11 | Gholam A. Peyman | Method of corneal transplantation or corneal inlay implantation with cross-linking |
| US11648261B2 (en) | 2014-05-12 | 2023-05-16 | Gholam A. Peyman | Method of treating, reducing, or alleviating a medical condition in a patient |
| US11565023B2 (en) | 2014-05-12 | 2023-01-31 | Gholam A. Peyman | Method of corneal transplantation or corneal inlay implantation with cross-linking |
| US10881503B2 (en) | 2014-05-12 | 2021-01-05 | Gholam A. Peyman | Method of corneal transplantation or corneal inlay implantation with cross-linking |
| US11338059B2 (en) | 2014-05-12 | 2022-05-24 | Gholam A. Peyman | Method of corneal and scleral inlay crosslinking and preservation |
| US11045352B2 (en) | 2014-05-12 | 2021-06-29 | Gholam A. Peyman | Methods for treatment of dry eye and other acute or chronic inflammatory processes |
| US10925889B2 (en) | 2014-05-12 | 2021-02-23 | Gholam A. Peyman | Method of treating, reducing, or alleviating a medical condition in a patient |
| US10583221B2 (en) | 2014-05-12 | 2020-03-10 | Gholam A. Peyman | Method of corneal transplantation or corneal inlay implantation with cross-linking |
| US11666777B2 (en) | 2014-05-12 | 2023-06-06 | Gholam A. Peyman | Photodynamic therapy technique for preventing damage to the fovea of the eye or another body portion of a patient |
| US12396889B2 (en) | 2014-05-12 | 2025-08-26 | Gholam A. Peyman | Lamellar corneal autologous or homologous graft in refractive surgery |
| WO2016179329A1 (en) | 2015-05-04 | 2016-11-10 | The Regents Of The University Of Colorado, A Body Corporate | Wireless power transfer |
| JP7027311B2 (ja) | 2015-11-16 | 2022-03-01 | オリックス ファーマシューティカルズ,インコーポレーテッド | MyD88又はTLR3を標的とするRNA複合体を使用した加齢黄斑変性の治療 |
| EP3389720A1 (en) | 2015-12-18 | 2018-10-24 | The General Hospital Corporation | Polyacetal polymers, conjugates, particles and uses thereof |
| KR102825945B1 (ko) | 2016-02-02 | 2025-06-30 | 올릭스 주식회사 | Angpt2 및 pdgfb를 표적화하는 rna 복합체를 사용하는 혈관신생 관련 질환의 치료 |
| WO2017134525A1 (en) | 2016-02-02 | 2017-08-10 | Olix Pharmaceuticals, Inc. | TREATMENT OF ATOPIC DERMATITIS AND ASTHMA USING RNA COMPLEXES THAT TARGET lL4Rα, TRPA1, OR F2RL1 |
| JP7049262B2 (ja) | 2016-04-11 | 2022-04-06 | オリックス ファーマシューティカルズ,インコーポレーテッド | 結合組織成長因子を標的とするrna複合体を用いた特発性肺胞線維症の治療 |
| KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| WO2018146557A2 (en) | 2017-02-10 | 2018-08-16 | Dong Ki Lee | Long double-stranded rna for rna interference |
| US10363833B2 (en) * | 2017-03-15 | 2019-07-30 | Ford Global Technologies, Llc | Inductive charging active suspension |
| KR20190037166A (ko) * | 2017-09-28 | 2019-04-05 | 올릭스 주식회사 | 결합 조직 성장 인자를 표적으로 하는 rna 복합체를 함유하는 노인성 황반변성의 예방 또는 치료용 약학 조성물 |
| CN112512532B (zh) * | 2018-07-31 | 2024-11-08 | 雷莫内克斯生物制药有限公司 | 用于抑制ctgf表达的组合物 |
| US11707518B2 (en) | 2019-04-28 | 2023-07-25 | Gholam A. Peyman | Method of treating, reducing, or alleviating a medical condition in a patient |
| US12226478B2 (en) | 2019-04-28 | 2025-02-18 | Gholam A. Peyman | Method of treating, reducing, or alleviating a medical condition in a patient |
| CN110144350A (zh) * | 2019-05-15 | 2019-08-20 | 基诺泰康生物科技(北京)有限公司 | 一种特异性抑制CTGF基因表达的siRNA及其在抑制癜痕形成中的应用 |
| KR102757180B1 (ko) | 2019-11-22 | 2025-01-21 | (주)바이오니아 | Ctgf 유전자 특이적 이중가닥 올리고뉴클레오티드 및 이를 포함하는 섬유증 관련 질환 및 호흡기 관련 질환 예방 및 치료용 조성물 |
| KR102421750B1 (ko) * | 2020-05-26 | 2022-07-19 | 올릭스 주식회사 | MyD88을 표적으로 하는 RNAi 제제 및 이의 용도 |
| CN114807127A (zh) * | 2021-01-19 | 2022-07-29 | 陈璞 | 用于结缔组织生长因子的小干扰rna及其应用 |
| WO2023239756A1 (en) | 2022-06-07 | 2023-12-14 | Generation Bio Co. | Lipid nanoparticle compositions and uses thereof |
| WO2025147949A1 (zh) * | 2024-01-11 | 2025-07-17 | 广州瑞风生物科技有限公司 | 基因编辑系统及其应用 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5408040A (en) | 1991-08-30 | 1995-04-18 | University Of South Florida | Connective tissue growth factor(CTGF) |
| US5770209A (en) * | 1991-08-30 | 1998-06-23 | University Of South Florida | Acceleration of wound healing using connective tissue growth factor |
| US7384634B2 (en) * | 1991-08-30 | 2008-06-10 | University Of South Florida | Connective tissue growth factor |
| WO1994001550A1 (en) * | 1992-07-02 | 1994-01-20 | Hybridon, Inc. | Self-stabilized oligonucleotides as therapeutic agents |
| US5734039A (en) * | 1994-09-15 | 1998-03-31 | Thomas Jefferson University | Antisense oligonucleotides targeting cooperating oncogenes |
| US7041548B1 (en) * | 1996-07-16 | 2006-05-09 | Micron Technology, Inc. | Methods of forming a gate stack that is void of silicon clusters within a metallic silicide film thereof |
| US6506559B1 (en) * | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US6348329B1 (en) * | 1998-11-06 | 2002-02-19 | Fibrogen, Inc. | Nucleic acids encoding rat connective tissue growth factor (CTGF) and methods of use |
| US7115390B1 (en) * | 1998-12-14 | 2006-10-03 | Fibrogen, Inc. | Connective tissue growth factor fragments and methods and uses thereof |
| AU776150B2 (en) * | 1999-01-28 | 2004-08-26 | Medical College Of Georgia Research Institute, Inc. | Composition and method for (in vivo) and (in vitro) attenuation of gene expression using double stranded RNA |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| US6326193B1 (en) * | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
| GB9927444D0 (en) * | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
| JP2003526367A (ja) | 2000-03-16 | 2003-09-09 | ジェネティカ インコーポレイテッド | Rna干渉の方法とrna干渉組成物 |
| KR20080023768A (ko) * | 2000-03-30 | 2008-03-14 | 화이트헤드 인스티튜트 포 바이오메디칼 리서치 | Rna 간섭의 rna 서열 특이적인 매개체 |
| CN100523215C (zh) | 2000-12-01 | 2009-08-05 | 马普科技促进协会 | 介导rna干涉的小rna分子 |
| JP4779255B2 (ja) | 2001-07-16 | 2011-09-28 | パナソニック株式会社 | レーザ光源 |
| AU2002366641A1 (en) * | 2001-12-11 | 2003-06-23 | Fibrogen, Inc. | Methods for inhibiting ocular processes |
| EP1497420A4 (en) | 2002-04-30 | 2005-04-27 | Alcon Inc | AGENTS THAT REGULATE, RESTRICT OR MODULATE THE ACTIVITY AND / OR EXPRESSION OF BIND WEAVE GROWTH FACTOR (CTGF) AS UNIQUE MEDICAMENTS BOTH TO REDUCE EYESPRINTS AND TREAT GLACCOMPETOSIS RETINOPATHIES / OPTIC NEUROPATHIES |
| CA2524569C (en) * | 2002-05-03 | 2013-10-22 | Duke University | A method of regulating gene expression |
| AU2003261449A1 (en) * | 2002-08-07 | 2004-02-25 | Compositions for rna interference and methods of use thereof | |
| EP1534832A2 (en) | 2002-09-04 | 2005-06-01 | Provost, Fellows and Scholars of the College of the Holy and Undivided Trinity of Queen Elizabeth near Dublin | Compositions and methods for tissue specific or inducible inhibition of gene expression |
| AU2003249012A1 (en) * | 2002-09-30 | 2004-04-23 | Japan As Represented By The President Of The University Of Tokyo | Genes and polypeptides relating to human myeloid leukemia |
| US20040175732A1 (en) * | 2002-11-15 | 2004-09-09 | Rana Tariq M. | Identification of micrornas and their targets |
| JP2007524349A (ja) | 2003-01-16 | 2007-08-30 | ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア | ICAM−1のsiRNA阻害のための組成物及び方法 |
| AU2003224132A1 (en) * | 2003-04-24 | 2004-11-19 | Galapagos Genomics N.V. | Effective sirna knock-down constructs |
| US7462602B2 (en) * | 2003-05-01 | 2008-12-09 | University Of Florida Research Foundation, Inc. | Anti-scarring ribozymes and methods |
| JPWO2004096277A1 (ja) * | 2003-05-01 | 2006-07-13 | 国立大学法人京都大学 | 眼内血管新生疾患の予防又は治療剤 |
| AU2004242586C1 (en) * | 2003-05-28 | 2011-02-24 | Regeneron Pharmaceuticals, Inc. | Method of treating corneal transplant rejection by using VEGF antagonists |
| GB0403600D0 (en) | 2004-02-18 | 2004-03-24 | Trinity College Dublin | Methods and reagents for treating disease |
| GB0404209D0 (en) | 2004-02-25 | 2004-03-31 | Uws Ventures Ltd | Materials and methods for treatment of allergic disease |
-
2005
- 2005-11-24 TW TW094141307A patent/TWI386225B/zh not_active IP Right Cessation
- 2005-12-19 CA CA002591611A patent/CA2591611A1/en not_active Abandoned
- 2005-12-19 EP EP05857141A patent/EP1827503A1/en not_active Withdrawn
- 2005-12-19 MX MX2007007654A patent/MX2007007654A/es active IP Right Grant
- 2005-12-19 AU AU2005319279A patent/AU2005319279B2/en not_active Ceased
- 2005-12-19 KR KR1020077016318A patent/KR20070091337A/ko not_active Ceased
- 2005-12-19 CN CN2005800479231A patent/CN101160138B/zh not_active Expired - Fee Related
- 2005-12-19 US US11/313,200 patent/US7622454B2/en not_active Expired - Fee Related
- 2005-12-19 WO PCT/US2005/046064 patent/WO2006069037A1/en not_active Ceased
- 2005-12-19 EP EP10010890A patent/EP2319543A1/en not_active Withdrawn
- 2005-12-19 JP JP2007548380A patent/JP5095414B2/ja not_active Expired - Fee Related
- 2005-12-19 ZA ZA200704932A patent/ZA200704932B/xx unknown
- 2005-12-19 BR BRPI0516377-3A patent/BRPI0516377A/pt not_active IP Right Cessation
- 2005-12-20 AR ARP050105371A patent/AR052172A1/es unknown
-
2009
- 2009-10-12 US US12/577,267 patent/US7838507B2/en not_active Expired - Fee Related
-
2010
- 2010-10-08 US US12/901,019 patent/US20110028534A1/en not_active Abandoned
-
2012
- 2012-02-14 JP JP2012029499A patent/JP2012097119A/ja not_active Withdrawn
-
2013
- 2013-12-05 US US14/097,928 patent/US20140094502A1/en not_active Abandoned
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