CA2765989C - Anti notch-1 antibodies - Google Patents
Anti notch-1 antibodies Download PDFInfo
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- CA2765989C CA2765989C CA2765989A CA2765989A CA2765989C CA 2765989 C CA2765989 C CA 2765989C CA 2765989 A CA2765989 A CA 2765989A CA 2765989 A CA2765989 A CA 2765989A CA 2765989 C CA2765989 C CA 2765989C
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- antibody
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- human
- amino acid
- notch
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21819309P | 2009-06-18 | 2009-06-18 | |
| US61/218,193 | 2009-06-18 | ||
| PCT/IB2010/052711 WO2010146550A1 (en) | 2009-06-18 | 2010-06-16 | Anti notch-1 antibodies |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2765989A1 CA2765989A1 (en) | 2010-12-23 |
| CA2765989C true CA2765989C (en) | 2016-11-29 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2765989A Expired - Fee Related CA2765989C (en) | 2009-06-18 | 2010-06-16 | Anti notch-1 antibodies |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US9090690B2 (OSRAM) |
| EP (2) | EP2443151A1 (OSRAM) |
| JP (2) | JP6059985B2 (OSRAM) |
| KR (1) | KR101570898B1 (OSRAM) |
| CN (1) | CN102686610A (OSRAM) |
| AU (1) | AU2010261364B2 (OSRAM) |
| BR (1) | BRPI1011805A2 (OSRAM) |
| CA (1) | CA2765989C (OSRAM) |
| CO (1) | CO6480924A2 (OSRAM) |
| IL (1) | IL217066A0 (OSRAM) |
| MX (1) | MX337468B (OSRAM) |
| NZ (1) | NZ597611A (OSRAM) |
| PE (1) | PE20121494A1 (OSRAM) |
| PH (1) | PH12011502609B1 (OSRAM) |
| RU (1) | RU2011151287A (OSRAM) |
| SG (1) | SG176731A1 (OSRAM) |
| WO (1) | WO2010146550A1 (OSRAM) |
| ZA (1) | ZA201109282B (OSRAM) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20120080A1 (es) * | 2008-10-01 | 2012-02-17 | Genentech Inc | Anticuerpos anti-notch2 y metodos de uso |
| WO2010146550A1 (en) * | 2009-06-18 | 2010-12-23 | Pfizer Inc. | Anti notch-1 antibodies |
| RU2012117619A (ru) * | 2009-09-30 | 2013-11-10 | Дженентек, Инк. | ЛЕЧЕНИЕ ЗЛОКАЧЕСТВЕННЫХ ОПУХОЛЕЙ, УСТОЙЧИВЫХ К ДЕЙСТВИЮ АНТАГОНИСТА Notch1, С ПОМОЩЬЮ АНТАГОНИСТА Notch3 |
| WO2012080926A2 (en) * | 2010-12-15 | 2012-06-21 | Wyeth Llc | Anti-notch1 antibodies |
| WO2012080891A1 (en) * | 2010-12-15 | 2012-06-21 | Rinat Neuroscience Corp. | Anti-notch-1 antibodies |
| BR112015010436A2 (pt) | 2012-11-07 | 2017-08-22 | Pfizer | Anticorpos anti-notch3 e conjugados anticorpo-fármaco |
| WO2015134627A1 (en) * | 2014-03-07 | 2015-09-11 | Oncomed Pharmaceuticals, Inc. | Methods for treating cancer with notch1 antibodies |
| MX2017000363A (es) | 2014-07-11 | 2017-04-27 | Genentech Inc | Inhibicion de la via de notch. |
| US11026996B2 (en) * | 2016-05-25 | 2021-06-08 | The Trustees Of Columbia University In The City Of New York | Human Notch1 based fusion proteins as decoy inhibitors of jagged-notch signaling and DLL-notch signaling |
| JP2019535250A (ja) * | 2016-10-29 | 2019-12-12 | ジェネンテック， インコーポレイテッド | 抗ｍｉｃ抗体及び使用方法 |
| WO2020045646A1 (ja) | 2018-08-31 | 2020-03-05 | Ｂｌｏｏｍ Ｔｅｃｈｎｏｌｏｇｙ 株式会社 | 終末糖化産物に対する抗体およびその使用 |
| WO2024053742A1 (ja) | 2022-09-09 | 2024-03-14 | 国立大学法人 東京医科歯科大学 | コロナウイルス感染症の治療薬 |
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| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| DE3572982D1 (en) | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
| GB8421551D0 (en) | 1984-08-24 | 1984-09-26 | Ici Plc | Water-soluble dye |
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| US4754065A (en) | 1984-12-18 | 1988-06-28 | Cetus Corporation | Precursor to nucleic acid probe |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
| US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
| US5047335A (en) | 1988-12-21 | 1991-09-10 | The Regents Of The University Of Calif. | Process for controlling intracellular glycosylation of proteins |
| CA2006596C (en) | 1988-12-22 | 2000-09-05 | Rika Ishikawa | Chemically-modified g-csf |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| US5278299A (en) | 1991-03-18 | 1994-01-11 | Scripps Clinic And Research Foundation | Method and composition for synthesizing sialylated glycosyl compounds |
| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
| GB9115364D0 (en) | 1991-07-16 | 1991-08-28 | Wellcome Found | Antibody |
| AU669124B2 (en) | 1991-09-18 | 1996-05-30 | Kyowa Hakko Kirin Co., Ltd. | Process for producing humanized chimera antibody |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| AU665025B2 (en) | 1991-09-23 | 1995-12-14 | Cambridge Antibody Technology Limited | Production of chimeric antibodies - a combinatorial approach |
| WO1993010260A1 (en) | 1991-11-21 | 1993-05-27 | The Board Of Trustees Of The Leland Stanford Junior University | Controlling degradation of glycoprotein oligosaccharides by extracellular glycosisases |
| US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| AU4116793A (en) | 1992-04-24 | 1993-11-29 | Board Of Regents, The University Of Texas System | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
| US5786158A (en) | 1992-04-30 | 1998-07-28 | Yale University | Therapeutic and diagnostic methods and compositions based on notch proteins and nucleic acids |
| US6210671B1 (en) | 1992-12-01 | 2001-04-03 | Protein Design Labs, Inc. | Humanized antibodies reactive with L-selectin |
| JP2698529B2 (ja) | 1993-04-06 | 1998-01-19 | 浜松ホトニクス株式会社 | イメージインテンシファイア装置 |
| EP0714409A1 (en) | 1993-06-16 | 1996-06-05 | Celltech Therapeutics Limited | Antibodies |
| US6180377B1 (en) | 1993-06-16 | 2001-01-30 | Celltech Therapeutics Limited | Humanized antibodies |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US6265150B1 (en) | 1995-06-07 | 2001-07-24 | Becton Dickinson & Company | Phage antibodies |
| US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| PT2180007E (pt) | 1998-04-20 | 2013-11-25 | Roche Glycart Ag | Engenharia de glicosilação de anticorpos para melhorar a citotoxicidade celular dependente de anticorpos |
| GB9809951D0 (en) | 1998-05-08 | 1998-07-08 | Univ Cambridge Tech | Binding molecules |
| AU768269B2 (en) | 1998-10-02 | 2003-12-04 | Government of The United States of America, as represented by The Secretary Department of Health & Human Services, The National Institutes of Health, The | Apoptosis inducing agents and methods |
| US20030035798A1 (en) | 2000-08-16 | 2003-02-20 | Fang Fang | Humanized antibodies |
| KR101155191B1 (ko) | 1999-01-15 | 2012-06-13 | 제넨테크, 인크. | 효과기 기능이 변화된 폴리펩티드 변이체 |
| ES2568899T3 (es) | 1999-04-09 | 2016-05-05 | Kyowa Hakko Kirin Co., Ltd. | Procedimiento para controlar la actividad de una molécula inmunofuncional |
| US6849425B1 (en) | 1999-10-14 | 2005-02-01 | Ixsys, Inc. | Methods of optimizing antibody variable region binding affinity |
| US7399633B2 (en) | 2000-10-27 | 2008-07-15 | Fred Hutchinson Cancer Research Center | Methods for immortalizing cells |
| ES2326964T3 (es) | 2001-10-25 | 2009-10-22 | Genentech, Inc. | Composiciones de glicoproteina. |
| US20030148954A1 (en) | 2001-11-02 | 2003-08-07 | Wisconsin Alumni Research Foundation | Agents and methods for modulating activator protein-1-mediated cellular processes |
| WO2003042246A2 (en) | 2001-11-14 | 2003-05-22 | Lorantis Limited | Inhibitors of the notch signalling pathway for use in the treatment of cancer |
| BR0309145A (pt) | 2002-04-09 | 2005-02-01 | Kyowa Hakko Kogyo Kk | Células das quais o genoma é modificado |
| US7666982B2 (en) | 2002-07-18 | 2010-02-23 | Masayasu Okochi | Notch-origin polypeptides and biomarkers and reagents using the same |
| CA2921578C (en) | 2002-12-24 | 2017-02-14 | Rinat Neuroscience Corp. | Anti-ngf antibodies and methods using same |
| WO2005054434A2 (en) | 2003-11-26 | 2005-06-16 | Health Research, Inc. | Use of notch pathway interfering agents for treatment of plasma cell disorders |
| WO2006001956A2 (en) | 2004-05-20 | 2006-01-05 | The Board Of Trustees Of The University Of Illinois | Compositions for inhibiting cell growth and inducing apoptosis in cancer cells and methods of use thereof |
| US20070077245A1 (en) | 2004-08-04 | 2007-04-05 | The Brigham And Women's Hospital, Inc. | NOTCH mutations leading to increased receptor signaling |
| WO2006053063A2 (en) | 2004-11-05 | 2006-05-18 | The Regents Of The University Of California | Notch-1 assay to detect neurodegenerative diseases |
| JP4884395B2 (ja) | 2004-12-21 | 2012-02-29 | アストラゼネカ エービー | アンジオポエチン−２に対する抗体およびそれらの使用 |
| CA2600908A1 (en) | 2005-03-04 | 2006-09-08 | The Hospital For Sick Children | Methods for cancer prognosis |
| US7100777B1 (en) * | 2005-07-07 | 2006-09-05 | Jui-Chien Kao | Hanger rack for hand tools |
| US20070072222A1 (en) | 2005-09-23 | 2007-03-29 | Franziska Boess | FABP4 as biomarker for toxic effect |
| WO2007061988A2 (en) | 2005-11-22 | 2007-05-31 | University Of Vermont And State Agricultural College | Methods for determining notch signaling and uses thereof |
| WO2008057144A2 (en) | 2006-05-15 | 2008-05-15 | The Brigham And Women's Hospital, Inc. | Functional negative regulatory domain sequences from human notch1 and 2 and isolated lnr domains from human notch1 |
| CA2655362A1 (en) | 2006-06-13 | 2007-12-21 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for diagnosing and treating cancer |
| JP2010520280A (ja) | 2007-03-05 | 2010-06-10 | ボード オブ リージェンツ， ザ ユニバーシティ オブ テキサス システム | ＮｏｔｃｈまたはＮｕｍｂ特異的免疫療法との相乗効果を有する、癌細胞の再生のネガティブな遺伝的制御 |
| PE20090321A1 (es) * | 2007-06-04 | 2009-04-20 | Genentech Inc | Anticuerpos anti-notch1 nrr, metodo de preparacion y composicion farmaceutica |
| US8119366B2 (en) | 2007-10-05 | 2012-02-21 | Trojan Technologies, Ltd. | Antennapedia-dominant negative mastermind-like construct |
| JO3076B1 (ar) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
| US8834875B2 (en) | 2010-01-13 | 2014-09-16 | Oncomed Pharmaceuticals, Inc. | Notch1 binding agents and methods of use thereof |
| NZ590127A (en) | 2008-07-08 | 2012-11-30 | Oncomed Pharm Inc | Notch1 receptor binding agents and methods of use thereof |
| US20110286916A1 (en) | 2008-11-20 | 2011-11-24 | Jose Miguel Aste-Amezaga | Generation and characterization of anti-notch antibodies for therapeutic and diagnostic use |
| WO2010146550A1 (en) * | 2009-06-18 | 2010-12-23 | Pfizer Inc. | Anti notch-1 antibodies |
| RU2012117619A (ru) | 2009-09-30 | 2013-11-10 | Дженентек, Инк. | ЛЕЧЕНИЕ ЗЛОКАЧЕСТВЕННЫХ ОПУХОЛЕЙ, УСТОЙЧИВЫХ К ДЕЙСТВИЮ АНТАГОНИСТА Notch1, С ПОМОЩЬЮ АНТАГОНИСТА Notch3 |
| WO2012080926A2 (en) | 2010-12-15 | 2012-06-21 | Wyeth Llc | Anti-notch1 antibodies |
| WO2012080891A1 (en) | 2010-12-15 | 2012-06-21 | Rinat Neuroscience Corp. | Anti-notch-1 antibodies |
-
2010
- 2010-06-16 WO PCT/IB2010/052711 patent/WO2010146550A1/en not_active Ceased
- 2010-06-16 BR BRPI1011805A patent/BRPI1011805A2/pt not_active IP Right Cessation
- 2010-06-16 JP JP2012515616A patent/JP6059985B2/ja not_active Expired - Fee Related
- 2010-06-16 SG SG2011090800A patent/SG176731A1/en unknown
- 2010-06-16 AU AU2010261364A patent/AU2010261364B2/en not_active Ceased
- 2010-06-16 MX MX2011013717A patent/MX337468B/es active IP Right Grant
- 2010-06-16 KR KR1020127001293A patent/KR101570898B1/ko not_active Expired - Fee Related
- 2010-06-16 EP EP10730230A patent/EP2443151A1/en not_active Withdrawn
- 2010-06-16 EP EP18172657.1A patent/EP3431501A1/en not_active Withdrawn
- 2010-06-16 PH PH1/2011/502609A patent/PH12011502609B1/en unknown
- 2010-06-16 RU RU2011151287/10A patent/RU2011151287A/ru not_active Application Discontinuation
- 2010-06-16 CN CN2010800367326A patent/CN102686610A/zh active Pending
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- 2010-06-16 US US13/378,791 patent/US9090690B2/en active Active
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Also Published As
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| PE20121494A1 (es) | 2012-11-01 |
| BRPI1011805A2 (pt) | 2016-10-11 |
| US9090690B2 (en) | 2015-07-28 |
| PH12011502609A1 (en) | 2012-11-12 |
| RU2011151287A (ru) | 2013-07-27 |
| US20120093813A1 (en) | 2012-04-19 |
| EP3431501A1 (en) | 2019-01-23 |
| AU2010261364B2 (en) | 2015-05-07 |
| JP2012530487A (ja) | 2012-12-06 |
| MX337468B (es) | 2016-03-02 |
| NZ597611A (en) | 2014-03-28 |
| KR101570898B1 (ko) | 2015-11-23 |
| CO6480924A2 (es) | 2012-07-16 |
| CA2765989A1 (en) | 2010-12-23 |
| WO2010146550A1 (en) | 2010-12-23 |
| JP6059985B2 (ja) | 2017-01-11 |
| SG176731A1 (en) | 2012-01-30 |
| AU2010261364A1 (en) | 2012-01-19 |
| CN102686610A (zh) | 2012-09-19 |
| KR20120071379A (ko) | 2012-07-02 |
| IL217066A0 (en) | 2012-02-29 |
| EP2443151A1 (en) | 2012-04-25 |
| PH12011502609B1 (en) | 2018-11-07 |
| MX2011013717A (es) | 2012-05-29 |
| ZA201109282B (en) | 2012-08-29 |
| JP2016121162A (ja) | 2016-07-07 |
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