CA2757645C - Methods and materials for delivering molecules - Google Patents
Methods and materials for delivering molecules Download PDFInfo
- Publication number
- CA2757645C CA2757645C CA2757645A CA2757645A CA2757645C CA 2757645 C CA2757645 C CA 2757645C CA 2757645 A CA2757645 A CA 2757645A CA 2757645 A CA2757645 A CA 2757645A CA 2757645 C CA2757645 C CA 2757645C
- Authority
- CA
- Canada
- Prior art keywords
- polypeptide
- attached
- enzymatic
- polymeric nanoparticle
- nanoparticle
- 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.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6925—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a microcapsule, nanocapsule, microbubble or nanobubble
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
- A61K47/6931—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
- A61K47/6935—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
- A61K47/6931—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
- A61K47/6935—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
- A61K47/6937—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol the polymer being PLGA, PLA or polyglycolic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Crystallography & Structural Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16692909P | 2009-04-06 | 2009-04-06 | |
| US61/166,929 | 2009-04-06 | ||
| PCT/US2010/029985 WO2010117957A2 (en) | 2009-04-06 | 2010-04-05 | Methods and materials for delivering molecules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2757645A1 CA2757645A1 (en) | 2010-10-14 |
| CA2757645C true CA2757645C (en) | 2018-05-15 |
Family
ID=42936837
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2757645A Active CA2757645C (en) | 2009-04-06 | 2010-04-05 | Methods and materials for delivering molecules |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9636384B2 (cg-RX-API-DMAC10.html) |
| EP (1) | EP2416763B1 (cg-RX-API-DMAC10.html) |
| JP (2) | JP5866117B2 (cg-RX-API-DMAC10.html) |
| CA (1) | CA2757645C (cg-RX-API-DMAC10.html) |
| IL (1) | IL215455B (cg-RX-API-DMAC10.html) |
| WO (1) | WO2010117957A2 (cg-RX-API-DMAC10.html) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013524811A (ja) * | 2010-04-20 | 2013-06-20 | ユニバーシティ オブ フロリダ リサーチ ファンデーション インコーポレーティッド | ナノザイム、ナノザイムの製造方法、およびナノザイムの使用方法 |
| JP2014522649A (ja) * | 2011-07-06 | 2014-09-08 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 多酵素ナノ複合体 |
| US8871189B2 (en) * | 2011-11-30 | 2014-10-28 | Mallinckrodt Llc | MMP-targeted therapeutic and/or diagnostic nanocarriers |
| US20130323221A1 (en) * | 2012-05-30 | 2013-12-05 | Biostrategies LC | Plant lectins as carriers of associated drug substances into animal and human cells |
| US10413606B2 (en) | 2012-10-01 | 2019-09-17 | Mayo Foundation For Medical Education And Research | Methods for treating cancer with nanoparticle complexes of albumin-bound paclitaxel and anti-VEGF antibodies |
| EP2910632B1 (en) * | 2012-10-19 | 2017-07-05 | Tokushima University | Highly functional enzyme having modified substrate specificity of human beta-hexosaminidase b and exhibiting protease resistance |
| WO2015023715A1 (en) | 2013-08-14 | 2015-02-19 | The University Of Florida Research Foundation, Inc. | Nanozymes, methods of making nanozymes, and methods of using nanozymes |
| EP3154586B1 (en) | 2014-06-13 | 2020-05-27 | Mayo Foundation for Medical Education and Research | Treating lymphomas |
| US10213513B2 (en) | 2014-06-16 | 2019-02-26 | Mayo Foundation For Medical Education And Research | Treating myelomas |
| CN107073132B (zh) | 2014-10-06 | 2021-08-27 | 梅约医学教育与研究基金会 | 载体-抗体组合物及其制备和使用方法 |
| TW201707725A (zh) | 2015-08-18 | 2017-03-01 | 美國馬友醫藥教育研究基金會 | 載體-抗體組合物及其製造及使用方法 |
| TW201713360A (en) | 2015-10-06 | 2017-04-16 | Mayo Foundation | Methods of treating cancer using compositions of antibodies and carrier proteins |
| WO2017120501A1 (en) | 2016-01-07 | 2017-07-13 | Mayo Foundation For Medical Education And Research | Methods of treating cancer with interferon |
| US11351254B2 (en) | 2016-02-12 | 2022-06-07 | Mayo Foundation For Medical Education And Research | Hematologic cancer treatments |
| WO2017165440A1 (en) | 2016-03-21 | 2017-09-28 | Mayo Foundation For Medical Education And Research | Methods for reducing toxicity of a chemotherapeutic drug |
| EP3432928A4 (en) | 2016-03-21 | 2019-11-20 | Mayo Foundation for Medical Education and Research | PROCESS FOR IMPROVING THE THERAPEUTIC INDEX FOR CHEMOTHERAPEUTIC |
| US10618969B2 (en) | 2016-04-06 | 2020-04-14 | Mayo Foundation For Medical Education And Research | Carrier-binding agent compositions and methods of making and using the same |
| CN109843336A (zh) | 2016-09-01 | 2019-06-04 | 梅约医学教育与研究基金会 | 用于靶向t细胞癌症的方法和组合物 |
| CN109890419A (zh) | 2016-09-01 | 2019-06-14 | 梅约医学教育与研究基金会 | 用于治疗癌症的载体-pd-l1结合剂组合物 |
| US11590098B2 (en) | 2016-09-06 | 2023-02-28 | Mayo Foundation For Medical Education And Research | Methods of treating triple-negative breast cancer using compositions of antibodies and carrier proteins |
| CN109843924A (zh) | 2016-09-06 | 2019-06-04 | 梅约医学教育与研究基金会 | 治疗表达pd-l1的癌症的方法 |
| AU2017324947A1 (en) | 2016-09-06 | 2019-03-28 | Mayo Foundation For Medical Education And Research | Paclitaxel-albumin-binding agent compositions and methods for using and making the same |
| WO2022006271A2 (en) * | 2020-06-30 | 2022-01-06 | Hillstream Biopharma Inc. | Nanoparticles and methods of manufacture thereof |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US5122614A (en) * | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| US5766897A (en) | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
| US5621039A (en) * | 1993-06-08 | 1997-04-15 | Hallahan; Terrence W. | Factor IX- polymeric conjugates |
| US5565215A (en) | 1993-07-23 | 1996-10-15 | Massachusettes Institute Of Technology | Biodegradable injectable particles for imaging |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| KR19990085365A (ko) * | 1998-05-16 | 1999-12-06 | 허영섭 | 지속적으로 약물 조절방출이 가능한 생분해성 고분자 미립구 및그 제조방법 |
| KR100566911B1 (ko) | 2001-06-25 | 2006-04-03 | 주식회사 삼양사 | 약물 전달체용 음이온기-함유 양친성 블록 공중합체 및 그의 양이온성 약물과의 복합체 |
| WO2003057179A2 (en) * | 2002-01-11 | 2003-07-17 | Biomarin Pharmaceutical, Inc. | Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes |
| US20080014188A1 (en) | 2004-02-06 | 2008-01-17 | Zankel Todd C | Manufacture of Highly Phosphorylated Lysosomal Enzymes and Uses Thereof |
| EP1794590B1 (en) | 2004-09-08 | 2014-02-26 | Rensselaer Polytechnic Institute | Enhanced stability of proteins immobilized on nanoparticles |
| JP2009501237A (ja) * | 2005-03-14 | 2009-01-15 | ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム | 生物活性fus1ペプチドおよびナノ粒子−ポリペプチド複合体 |
| US20070059775A1 (en) | 2005-03-29 | 2007-03-15 | The Trustees Of Columbia University In The City Of New York | Synthesis and conjugation of iron oxide nanoparticles to antibodies for targeting specific cells using fluorescence and MR imaging techniques |
| JP5137814B2 (ja) | 2005-04-06 | 2013-02-06 | ジェンザイム・コーポレーション | 治療ターゲティングのための酸不安定リンカーを介するpegおよびポリシアルリソソーム酵素のコンジュゲート |
| US8246995B2 (en) * | 2005-05-10 | 2012-08-21 | The Board Of Trustees Of The Leland Stanford Junior University | Hydrophobic nanotubes and nanoparticles as transporters for the delivery of drugs into cells |
| FR2889362B1 (fr) | 2005-08-01 | 2007-10-19 | Thomson Licensing Sas | Systeme d'antennes a diversite de type dipole |
| JP2009508936A (ja) * | 2005-09-20 | 2009-03-05 | イッサム リサーチ ディベロップメント カンパニー | 活性物質の標的化送達用ナノ粒子 |
| EP1818395A1 (en) * | 2006-02-08 | 2007-08-15 | Diatos | Compositions and methods for treating lysosomal storage diseases |
| WO2008105773A2 (en) | 2006-03-31 | 2008-09-04 | Massachusetts Institute Of Technology | System for targeted delivery of therapeutic agents |
| US20100015050A1 (en) | 2006-12-21 | 2010-01-21 | Wayne State University | Peg and targeting ligands on nanoparticle surface |
| ATE539089T1 (de) * | 2007-03-21 | 2012-01-15 | Raptor Pharmaceutical Inc | Cyclische rezeptor-assoziierte-proteine (rap)- peptide |
-
2010
- 2010-04-05 CA CA2757645A patent/CA2757645C/en active Active
- 2010-04-05 EP EP10762266.4A patent/EP2416763B1/en active Active
- 2010-04-05 WO PCT/US2010/029985 patent/WO2010117957A2/en not_active Ceased
- 2010-04-05 JP JP2012503772A patent/JP5866117B2/ja active Active
- 2010-04-05 US US13/263,052 patent/US9636384B2/en active Active
-
2011
- 2011-10-02 IL IL215455A patent/IL215455B/en active IP Right Grant
-
2015
- 2015-02-23 JP JP2015032550A patent/JP2015098484A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP2416763A2 (en) | 2012-02-15 |
| JP5866117B2 (ja) | 2016-02-17 |
| EP2416763A4 (en) | 2015-05-06 |
| EP2416763B1 (en) | 2026-06-10 |
| CA2757645A1 (en) | 2010-10-14 |
| JP2012522809A (ja) | 2012-09-27 |
| JP2015098484A (ja) | 2015-05-28 |
| WO2010117957A2 (en) | 2010-10-14 |
| US9636384B2 (en) | 2017-05-02 |
| US20120040432A1 (en) | 2012-02-16 |
| IL215455A0 (en) | 2011-12-29 |
| WO2010117957A3 (en) | 2011-03-03 |
| IL215455B (en) | 2019-03-31 |
| EP2416763C0 (en) | 2026-06-10 |
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