RU2015144026A - Антитела против cd25 и их применения - Google Patents
Антитела против cd25 и их применения Download PDFInfo
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- RU2015144026A RU2015144026A RU2015144026A RU2015144026A RU2015144026A RU 2015144026 A RU2015144026 A RU 2015144026A RU 2015144026 A RU2015144026 A RU 2015144026A RU 2015144026 A RU2015144026 A RU 2015144026A RU 2015144026 A RU2015144026 A RU 2015144026A
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- Prior art keywords
- antibody
- sequence
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- heavy chain
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Links
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 title claims 7
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 title claims 7
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 title claims 7
- 239000012634 fragment Substances 0.000 claims 12
- 210000004027 cell Anatomy 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 238000006467 substitution reaction Methods 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 0.000 claims 2
- 102220104394 rs879253878 Human genes 0.000 claims 2
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 208000000389 T-cell leukemia Diseases 0.000 claims 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims 1
- 206010052779 Transplant rejections Diseases 0.000 claims 1
- 206010046851 Uveitis Diseases 0.000 claims 1
- 229940125644 antibody drug Drugs 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 230000035772 mutation Effects 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 102220134332 rs142032681 Human genes 0.000 claims 1
- 102220061206 rs786203134 Human genes 0.000 claims 1
- 102220119395 rs886042306 Human genes 0.000 claims 1
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
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- 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
- 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
- A61K47/51—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 non-active ingredient being a modifying agent
- A61K47/68—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 non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—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 non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—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 non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/005—Glycopeptides, glycoproteins
-
- 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
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/524—CH2 domain
-
- 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
-
- 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
- C07K2317/50—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
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/71—Decreased effector function due to an Fc-modification
-
- 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
- C07K2317/72—Increased effector function due to an Fc-modification
-
- 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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Pulmonology (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Endocrinology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Ophthalmology & Optometry (AREA)
- Transplantation (AREA)
- Oncology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361798235P | 2013-03-15 | 2013-03-15 | |
| US61/798,235 | 2013-03-15 | ||
| PCT/US2014/029634 WO2014145000A2 (en) | 2013-03-15 | 2014-03-14 | Anti-cd25 antibodies and their uses |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2015144026A true RU2015144026A (ru) | 2017-04-20 |
Family
ID=50897881
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2015144026A RU2015144026A (ru) | 2013-03-15 | 2014-03-14 | Антитела против cd25 и их применения |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US20150010539A1 (enExample) |
| EP (2) | EP3216804A3 (enExample) |
| JP (1) | JP2016515524A (enExample) |
| CN (1) | CN105377892A (enExample) |
| AU (1) | AU2014233478A1 (enExample) |
| BR (1) | BR112015023084A2 (enExample) |
| CA (1) | CA2904532A1 (enExample) |
| HK (1) | HK1220470A1 (enExample) |
| MX (1) | MX2015012551A (enExample) |
| RU (1) | RU2015144026A (enExample) |
| WO (1) | WO2014145000A2 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3551047A1 (en) | 2016-12-07 | 2019-10-16 | Progenity, Inc. | Gastrointestinal tract detection methods, devices and systems |
| US11879014B2 (en) | 2017-03-17 | 2024-01-23 | Tusk Therapeutics Ltd. | Method of treating cancer or depleting regulatory T cells in a subject by administering a human IGG1 anti-CD25 antibody |
| CN113336849A (zh) * | 2017-03-28 | 2021-09-03 | 礼进生物医药科技（上海）有限公司 | 用于增强肿瘤微环境中免疫应答的治疗剂和方法 |
| US20210138213A1 (en) | 2017-03-30 | 2021-05-13 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an immune modulatory agent released using an ingestible device |
| AU2019233581B2 (en) | 2018-03-13 | 2025-08-28 | Cancer Research Technology Limited | Anti-CD25 for tumour specific cell depletion |
| WO2019246317A1 (en) | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease or condition in a tissue originating from the endoderm |
| US20230041197A1 (en) | 2018-06-20 | 2023-02-09 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an immunomodulator |
| CN116726362A (zh) | 2018-11-19 | 2023-09-12 | 比奥拉治疗股份有限公司 | 用生物治疗剂治疗疾病的方法和装置 |
| CN115666704B (zh) | 2019-12-13 | 2025-09-26 | 比特比德科有限责任公司 | 用于将治疗剂递送至胃肠道的可摄取装置 |
| CA3182362A1 (en) * | 2020-05-14 | 2021-11-18 | Jiangsu Hengrui Medicine Co., Ltd. | Anti-cd25 antibodies, antigen-binding fragments thereof, and medical uses thereof |
| JP7773172B2 (ja) * | 2021-06-11 | 2025-11-19 | 国立大学法人 新潟大学 | Ｔ細胞増殖促進ペプチド |
| EP4380604A1 (en) | 2021-08-05 | 2024-06-12 | Go Therapeutics, Inc. | Anti-glyco-muc4 antibodies and their uses |
| EP4386000A1 (en) * | 2021-08-09 | 2024-06-19 | Nanjing Novoacine Bio-Technology Co., Ltd. | Recombinant anti-human-cd25 antibody and use thereof |
| CA3230934A1 (en) | 2021-09-03 | 2023-03-09 | Go Therapeutics, Inc. | Anti-glyco-cmet antibodies and their uses |
| JP2024534910A (ja) | 2021-09-03 | 2024-09-26 | ジーオー セラピューティクス，インコーポレイテッド | 抗グリコｌａｍｐ１抗体およびその使用 |
| CN115181182B (zh) * | 2022-06-13 | 2024-03-29 | 南京融捷康生物科技有限公司 | 一种人源化的抗cd25的单域抗体及其应用 |
| CN115181181B (zh) * | 2022-06-13 | 2024-03-29 | 南京融捷康生物科技有限公司 | 一种抗cd25的单域抗体及其应用 |
| EP4572772A1 (en) | 2022-08-17 | 2025-06-25 | Capstan Therapeutics, Inc. | Conditioning for in vivo immune cell engineering |
| WO2024194605A1 (en) | 2023-03-17 | 2024-09-26 | Quell Therapeutics Limited | Treg therapy |
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| US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
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-
2014
- 2014-03-14 CN CN201480021398.5A patent/CN105377892A/zh active Pending
- 2014-03-14 CA CA2904532A patent/CA2904532A1/en not_active Abandoned
- 2014-03-14 BR BR112015023084A patent/BR112015023084A2/pt active Search and Examination
- 2014-03-14 EP EP17157958.4A patent/EP3216804A3/en not_active Withdrawn
- 2014-03-14 RU RU2015144026A patent/RU2015144026A/ru not_active Application Discontinuation
- 2014-03-14 MX MX2015012551A patent/MX2015012551A/es unknown
- 2014-03-14 US US14/214,089 patent/US20150010539A1/en not_active Abandoned
- 2014-03-14 JP JP2016503174A patent/JP2016515524A/ja active Pending
- 2014-03-14 EP EP14729110.8A patent/EP2970488A2/en not_active Withdrawn
- 2014-03-14 AU AU2014233478A patent/AU2014233478A1/en not_active Abandoned
- 2014-03-14 WO PCT/US2014/029634 patent/WO2014145000A2/en not_active Ceased
- 2014-03-14 HK HK16108469.7A patent/HK1220470A1/zh unknown
-
2017
- 2017-05-03 US US15/585,404 patent/US20170233481A1/en not_active Abandoned
-
2020
- 2020-06-11 US US16/899,399 patent/US20200308290A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| HK1220470A1 (zh) | 2017-05-05 |
| BR112015023084A2 (pt) | 2017-11-21 |
| US20170233481A1 (en) | 2017-08-17 |
| JP2016515524A (ja) | 2016-05-30 |
| US20200308290A1 (en) | 2020-10-01 |
| EP2970488A2 (en) | 2016-01-20 |
| CA2904532A1 (en) | 2014-09-18 |
| WO2014145000A3 (en) | 2015-03-19 |
| AU2014233478A1 (en) | 2015-09-24 |
| US20150010539A1 (en) | 2015-01-08 |
| EP3216804A2 (en) | 2017-09-13 |
| MX2015012551A (es) | 2016-10-26 |
| AU2014233478A8 (en) | 2015-10-22 |
| EP3216804A3 (en) | 2017-12-20 |
| CN105377892A (zh) | 2016-03-02 |
| WO2014145000A2 (en) | 2014-09-18 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20181206 |