AU2003238370B2 - Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same - Google Patents
Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same Download PDFInfo
- Publication number
- AU2003238370B2 AU2003238370B2 AU2003238370A AU2003238370A AU2003238370B2 AU 2003238370 B2 AU2003238370 B2 AU 2003238370B2 AU 2003238370 A AU2003238370 A AU 2003238370A AU 2003238370 A AU2003238370 A AU 2003238370A AU 2003238370 B2 AU2003238370 B2 AU 2003238370B2
- Authority
- AU
- Australia
- Prior art keywords
- framework
- single chain
- antibody
- sequence
- sequences
- 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.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
- G01N33/6857—Antibody fragments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/567—Framework region [FR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/80—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/80—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies
- C07K2317/82—Immunoglobulins specific features remaining in the (producing) cell, i.e. intracellular antibodies or intrabodies functional in the cytoplasm, the inner aspect of the cell membrane, the nucleus or the mitochondria
-
- 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
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2010202634A AU2010202634B2 (en) | 2002-05-22 | 2010-06-24 | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| AU2012211497A AU2012211497C1 (en) | 2002-05-22 | 2012-08-01 | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38264902P | 2002-05-22 | 2002-05-22 | |
| US60/382,649 | 2002-05-22 | ||
| US43825603P | 2003-01-03 | 2003-01-03 | |
| US60/438,256 | 2003-01-03 | ||
| PCT/EP2003/005324 WO2003097697A2 (en) | 2002-05-22 | 2003-05-21 | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2010202634A Division AU2010202634B2 (en) | 2002-05-22 | 2010-06-24 | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2003238370A1 AU2003238370A1 (en) | 2003-12-02 |
| AU2003238370B2 true AU2003238370B2 (en) | 2010-04-29 |
Family
ID=29553590
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003238370A Expired AU2003238370B2 (en) | 2002-05-22 | 2003-05-21 | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| AU2010202634A Expired AU2010202634B2 (en) | 2002-05-22 | 2010-06-24 | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2010202634A Expired AU2010202634B2 (en) | 2002-05-22 | 2010-06-24 | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
Country Status (14)
| Country | Link |
|---|---|
| US (5) | US8853362B2 (enExample) |
| EP (5) | EP3656787A1 (enExample) |
| JP (10) | JP2006508638A (enExample) |
| CN (4) | CN105175535A (enExample) |
| AU (2) | AU2003238370B2 (enExample) |
| CA (2) | CA2867542C (enExample) |
| CY (1) | CY1114225T1 (enExample) |
| DK (2) | DK2332989T3 (enExample) |
| ES (3) | ES2656427T3 (enExample) |
| HU (1) | HUE048922T2 (enExample) |
| NZ (1) | NZ536412A (enExample) |
| PT (2) | PT2332989E (enExample) |
| SI (2) | SI2332989T1 (enExample) |
| WO (1) | WO2003097697A2 (enExample) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0226727D0 (en) * | 2002-11-15 | 2002-12-24 | Medical Res Council | Intrabodies |
| WO2006099747A1 (en) | 2005-03-25 | 2006-09-28 | National Research Council Of Canada | Method for isolation of soluble polypeptides |
| AU2011265593B2 (en) * | 2005-06-07 | 2013-08-15 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| DK2390267T3 (da) | 2005-06-07 | 2013-08-26 | Esbatech A Novartis Co Llc | Stabile og opløselige antistoffer, der hæmmer TNF(alfa) |
| AU2016204739C1 (en) * | 2005-06-07 | 2017-10-19 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| AU2013207650B2 (en) * | 2005-06-07 | 2016-04-21 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting TNFalpha |
| EP2013236B1 (en) * | 2006-04-28 | 2015-06-17 | Delenex Therapeutics AG | Antibodies binding to the extracellular domain of the receptor tyrosine kinase alk |
| AU2007272224B2 (en) | 2006-07-10 | 2013-05-02 | Novartis Ag | scFv antibodies which pass epithelial and/or endothelial layers |
| CN103275216B (zh) * | 2007-03-12 | 2015-05-06 | 艾斯巴技术-诺华有限责任公司 | 单链抗体的基于序列的工程改造和最优化 |
| WO2008131575A2 (en) * | 2007-04-27 | 2008-11-06 | Esbatech Ag | Anti-alk antibodies suitable for treating metastatic cancers or tumors |
| KR101530723B1 (ko) * | 2007-06-25 | 2015-06-22 | 에스바테크 - 어 노바티스 컴파니 엘엘씨 | 단일 쇄 항체의 서열에 기초한 공학처리 및 최적화 |
| DK2158315T3 (en) * | 2007-06-25 | 2016-06-06 | Esbatech Alcon Biomed Res Unit | Methods of modifying antibodies and modified antibodies with improved functional properties |
| CN101842388B (zh) | 2007-09-13 | 2013-09-04 | 德勒尼克斯治疗股份公司 | 针对β淀粉样肽的人源化抗体 |
| HUE038432T2 (hu) | 2008-06-25 | 2018-10-29 | Esbatech Alcon Biomed Res Unit | Nyúl antitestek humanizálása egy univerzális antitest keret alkalmazásával |
| ES2771150T3 (es) * | 2008-06-25 | 2020-07-06 | Novartis Ag | Humanización de anticuerpos de conejo usando un armazón de anticuerpo universal |
| ES2890405T3 (es) | 2008-06-25 | 2022-01-19 | Novartis Ag | Humanización de anticuerpos de conejo usando un armazón de anticuerpo universal |
| AU2013202997B2 (en) * | 2008-06-25 | 2015-01-22 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFalpha |
| AU2016273957C1 (en) * | 2008-06-25 | 2019-04-18 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFa |
| AU2015201794B2 (en) * | 2008-06-25 | 2017-01-19 | Novartis Ag | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFa |
| ES2687259T5 (es) * | 2008-06-25 | 2022-10-14 | Novartis Ag | Anticuerpos estables y solubles que inhiben TNF |
| HRP20241467T1 (hr) | 2008-06-25 | 2025-01-03 | Novartis Ag | Stabilna i topljiva protutijela koja inhibiraju vegf |
| US9556265B2 (en) | 2008-06-25 | 2017-01-31 | Esbatech, An Alcon Biomedical Research Unit Llc | Solubility optimization of immunobinders |
| CA2729185A1 (en) | 2008-06-30 | 2010-01-21 | Esbatech, An Alcon Biomedical Research Unit Llc | Methods and compositions for modifying immunobinders |
| EP2303230A2 (en) | 2008-07-10 | 2011-04-06 | ESBATech, an Alcon Biomedical Research Unit LLC | Methods and compositions for enhanced delivery of macromolecules |
| RU2577965C2 (ru) * | 2009-02-24 | 2016-03-20 | ИЭсБиЭйТЕК, ЭН АЛЬКОН БАЙОМЕДИКАЛ РИСЕРЧ ЮНИТ ЭлЭлСи | Способ идентификации иммунных связывающих веществ поверхностных антигенов клетки |
| CA2744103C (en) | 2009-02-24 | 2018-01-02 | Esbatech, An Alcon Biomedical Research Unit Llc | Methods for identifying immunobinders of cell-surface antigens |
| US8399625B1 (en) | 2009-06-25 | 2013-03-19 | ESBATech, an Alcon Biomedical Research Unit, LLC | Acceptor framework for CDR grafting |
| US8524220B1 (en) | 2010-02-09 | 2013-09-03 | David Gordon Bermudes | Protease inhibitor: protease sensitivity expression system composition and methods improving the therapeutic activity and specificity of proteins delivered by bacteria |
| US9597379B1 (en) | 2010-02-09 | 2017-03-21 | David Gordon Bermudes | Protease inhibitor combination with therapeutic proteins including antibodies |
| US8771669B1 (en) | 2010-02-09 | 2014-07-08 | David Gordon Bermudes | Immunization and/or treatment of parasites and infectious agents by live bacteria |
| UY33679A (es) | 2010-10-22 | 2012-03-30 | Esbatech | Anticuerpos estables y solubles |
| EP2476754A1 (en) * | 2011-01-14 | 2012-07-18 | Bundesrepublik Deutschland, Letztvertreten Durch Den Präsidenten Des Paul-Ehrlich-Instituts | Methods for the identification and repair of amino acid residues destabilizing single-chain variable fragments (scFv) |
| DK2744931T3 (en) | 2011-08-18 | 2018-08-06 | Affinity Biosciences Pty Ltd | SOLUBLE POLYPEPTIDES |
| AR088403A1 (es) | 2011-10-20 | 2014-05-28 | Esbatech A Novartis Co Llc | Anticuerpo de union a multiples antigenos estable |
| WO2014030780A1 (en) * | 2012-08-22 | 2014-02-27 | Mogam Biotechnology Research Institute | Screening and engineering method of super-stable immunoglobulin variable domains and their uses |
| US9404930B2 (en) | 2012-11-05 | 2016-08-02 | Delenex Therapeutics Ag | Antibody to human IL-1 beta |
| EP4001307A1 (en) | 2012-12-17 | 2022-05-25 | Cell Medica Inc. | Antibodies against il-1 beta |
| JP2016506974A (ja) * | 2013-02-15 | 2016-03-07 | エスバテック − ア ノバルティスカンパニー エルエルシー | Cdrグラフトのためのアクセプターフレームワーク |
| HK1219485A1 (zh) | 2013-02-20 | 2017-04-07 | Esbatech - A Novartis Company Llc | 用於cdr移植的受体框架 |
| HUE052232T2 (hu) | 2013-05-06 | 2021-04-28 | Scholar Rock Inc | Készítmények és eljárások növekedési faktor modulálására |
| US9737592B1 (en) | 2014-02-14 | 2017-08-22 | David Gordon Bermudes | Topical and orally administered protease inhibitors and bacterial vectors for the treatment of disorders and methods of treatment |
| US9879087B2 (en) | 2014-11-12 | 2018-01-30 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| US20170306046A1 (en) | 2014-11-12 | 2017-10-26 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| MX2018004515A (es) * | 2015-10-13 | 2019-04-15 | Eureka Therapeutics Inc | Agentes de anticuerpo especificos para cd19 humano y usos de los mismos. |
| CN116059316A (zh) | 2015-10-23 | 2023-05-05 | 优瑞科生物技术公司 | 抗体/t细胞受体嵌合构建体及其用途 |
| CN108463248B (zh) | 2015-11-12 | 2022-10-21 | 西雅图基因公司 | 聚糖相互作用化合物及使用方法 |
| EP4086285A1 (en) | 2016-02-25 | 2022-11-09 | Cell Medica Switzerland AG | Binding members to pd-l1 |
| AU2017331256B2 (en) | 2016-09-21 | 2024-11-07 | Aptevo Research And Development Llc | CD123 binding proteins and related compositions and methods |
| EP3541847A4 (en) | 2016-11-17 | 2020-07-08 | Seattle Genetics, Inc. | COMPOUNDS INTERACTING WITH GLYCANE AND METHODS OF USE |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| EP3589319A4 (en) | 2017-03-03 | 2021-07-14 | Seagen Inc. | GLYCAN INTERACTING COMPOUNDS AND METHOD OF USE |
| CN112218621A (zh) * | 2018-04-10 | 2021-01-12 | 西北大学 | 包含基于靶向亲和域的膜蛋白的胞外囊泡 |
| WO2020069349A1 (en) * | 2018-09-27 | 2020-04-02 | Colorado State University Research Foundation | Scfv's for live cell imaging and other uses |
| US12285437B2 (en) | 2019-10-30 | 2025-04-29 | The Research Foundation For The State University Of New York | Reversing the undesirable pH-profile of doxorubicin via activation of a disubstituted maleamic acid prodrug at tumor acidity |
| US11524998B2 (en) | 2020-07-16 | 2022-12-13 | Novartis Ag | Anti-betacellulin antibodies, fragments thereof, and multi-specific binding molecules |
| CA3172265A1 (en) | 2021-03-10 | 2022-09-15 | Dimitri BIELI | Antibodies against tdp-43 and methods of using the same |
| WO2023139292A1 (en) | 2022-01-24 | 2023-07-27 | Cambridge Enterprise Limited | Tau therapy |
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| ES2052027T5 (es) | 1988-11-11 | 2005-04-16 | Medical Research Council | Clonacion de secuencias de dominio variable de inmunoglobulina. |
| US5817311A (en) * | 1993-03-05 | 1998-10-06 | Universite Catholique De Louvain | Methods of inhibiting T-cell medicated immune responses with LO-CD2a-specific antibodies |
| DE4425115A1 (de) | 1994-07-15 | 1996-01-18 | Boehringer Mannheim Gmbh | Verfahren zur Modifizierung der Stabilität von Antikörpern |
| US6696248B1 (en) * | 1995-08-18 | 2004-02-24 | Morphosys Ag | Protein/(poly)peptide libraries |
| ATE219517T1 (de) | 1995-08-18 | 2002-07-15 | Morphosys Ag | Protein-/(poly)peptidbibliotheken |
| US6262238B1 (en) | 1997-01-14 | 2001-07-17 | Roche Diagnostic, Gmbh | Process for modifying the stability of antibodies |
| AU3587599A (en) | 1997-11-28 | 1999-06-16 | Invitrogen Corporation | Single chain monoclonal antibody fusion reagents that regulate transcript ion in vivo |
| GB2344886B (en) | 1999-03-10 | 2000-11-01 | Medical Res Council | Selection of intracellular immunoglobulins |
| ATE273323T1 (de) | 1999-12-28 | 2004-08-15 | Esbatech Ag | INTRAKÖRPER MIT DEFINIERTER STRUKTUR (ßFRAMEWORKß), DIE IN EINER REDUZIERENDEN UMGEBUNG STABIL IST, UND IHRE VERWENDUNGEN |
| GB0008419D0 (en) | 2000-04-05 | 2000-05-24 | Bioinvent Int Ab | A method for invitro molecular evolution of antibody function |
| EP1156062A1 (en) | 2000-05-12 | 2001-11-21 | GPC Biotech AG | Immunomodulatory human MHC class II antigen-binding peptides/proteins |
| US6410271B1 (en) | 2000-06-23 | 2002-06-25 | Genetastix Corporation | Generation of highly diverse library of expression vectors via homologous recombination in yeast |
| DE10039191C1 (de) | 2000-08-10 | 2002-01-17 | Infineon Technologies Ag | Hochfrequenz-Eingangsstufe |
-
2003
- 2003-05-21 PT PT100098573T patent/PT2332989E/pt unknown
- 2003-05-21 AU AU2003238370A patent/AU2003238370B2/en not_active Expired
- 2003-05-21 PT PT37324340T patent/PT1506236E/pt unknown
- 2003-05-21 US US10/515,241 patent/US8853362B2/en not_active Expired - Lifetime
- 2003-05-21 SI SI200332427T patent/SI2332989T1/sl unknown
- 2003-05-21 EP EP19200477.8A patent/EP3656787A1/en not_active Withdrawn
- 2003-05-21 JP JP2004506369A patent/JP2006508638A/ja not_active Withdrawn
- 2003-05-21 NZ NZ536412A patent/NZ536412A/en not_active IP Right Cessation
- 2003-05-21 EP EP15160739.7A patent/EP2947095B1/en not_active Expired - Lifetime
- 2003-05-21 SI SI200332610T patent/SI2947095T1/sl unknown
- 2003-05-21 DK DK10009857.3T patent/DK2332989T3/en active
- 2003-05-21 HU HUE15160739A patent/HUE048922T2/hu unknown
- 2003-05-21 WO PCT/EP2003/005324 patent/WO2003097697A2/en not_active Ceased
- 2003-05-21 EP EP10010455.3A patent/EP2314622B1/en not_active Expired - Lifetime
- 2003-05-21 EP EP10009857.3A patent/EP2332989B1/en not_active Expired - Lifetime
- 2003-05-21 CN CN201510685456.0A patent/CN105175535A/zh active Pending
- 2003-05-21 ES ES10010455.3T patent/ES2656427T3/es not_active Expired - Lifetime
- 2003-05-21 CA CA2867542A patent/CA2867542C/en not_active Expired - Lifetime
- 2003-05-21 ES ES03732434T patent/ES2399617T3/es not_active Expired - Lifetime
- 2003-05-21 CN CN201010575786.1A patent/CN102093477B/zh not_active Expired - Lifetime
- 2003-05-21 CA CA2483285A patent/CA2483285C/en not_active Expired - Lifetime
- 2003-05-21 CN CN201410031953.4A patent/CN103739706B/zh not_active Expired - Lifetime
- 2003-05-21 ES ES10009857.3T patent/ES2537104T3/es not_active Expired - Lifetime
- 2003-05-21 DK DK03732434.0T patent/DK1506236T3/da active
- 2003-05-21 EP EP03732434A patent/EP1506236B1/en not_active Expired - Lifetime
- 2003-05-21 CN CN038146266A patent/CN1662556B/zh not_active Expired - Lifetime
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2010
- 2010-03-17 JP JP2010060713A patent/JP2010187678A/ja not_active Withdrawn
- 2010-06-24 AU AU2010202634A patent/AU2010202634B2/en not_active Expired
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2012
- 2012-08-28 JP JP2012187518A patent/JP6075836B2/ja not_active Expired - Lifetime
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2013
- 2013-02-04 JP JP2013019425A patent/JP6100544B2/ja not_active Expired - Lifetime
- 2013-04-08 CY CY20131100292T patent/CY1114225T1/el unknown
- 2013-09-19 JP JP2013193935A patent/JP2013256533A/ja active Pending
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2014
- 2014-08-26 US US14/469,276 patent/US9518108B2/en not_active Expired - Fee Related
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2015
- 2015-08-19 JP JP2015161601A patent/JP2015214583A/ja active Pending
- 2015-08-19 JP JP2015161600A patent/JP6261136B2/ja not_active Expired - Lifetime
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2016
- 2016-11-01 US US15/340,195 patent/US10125186B2/en not_active Expired - Lifetime
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2017
- 2017-08-24 JP JP2017161036A patent/JP2017201990A/ja active Pending
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2018
- 2018-10-30 US US16/175,002 patent/US10570190B2/en not_active Expired - Fee Related
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2019
- 2019-01-23 JP JP2019009288A patent/JP6918033B2/ja not_active Expired - Lifetime
- 2019-12-16 US US16/716,137 patent/US20200165322A1/en not_active Abandoned
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2020
- 2020-05-14 JP JP2020085288A patent/JP2020171286A/ja active Pending
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| Visintin M. et al, Journal of Molecular Biology, 2002, Vol. 317, No. 1, pp. 73-83 * |
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