JP2022524018A - Il-10バリアント分子ならびに炎症性疾患および腫瘍を処置する方法 - Google Patents
Il-10バリアント分子ならびに炎症性疾患および腫瘍を処置する方法 Download PDFInfo
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- JP2022524018A JP2022524018A JP2021552750A JP2021552750A JP2022524018A JP 2022524018 A JP2022524018 A JP 2022524018A JP 2021552750 A JP2021552750 A JP 2021552750A JP 2021552750 A JP2021552750 A JP 2021552750A JP 2022524018 A JP2022524018 A JP 2022524018A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5428—IL-10
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—RNA viruses
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—RNA viruses
- C07K16/112—Retroviridae (F), e.g. leukemia viruses
- C07K16/114—Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
-
- 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
- C07K2317/60—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
- C07K2317/626—Diabody or triabody
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2025176328A JP2026016505A (ja) | 2019-03-06 | 2025-10-20 | Il-10バリアント分子ならびに炎症性疾患および腫瘍を処置する方法 |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962814669P | 2019-03-06 | 2019-03-06 | |
| US62/814,669 | 2019-03-06 | ||
| US201962899504P | 2019-09-12 | 2019-09-12 | |
| US62/899,504 | 2019-09-12 | ||
| US202062962332P | 2020-01-17 | 2020-01-17 | |
| US62/962,332 | 2020-01-17 | ||
| PCT/US2020/021498 WO2020181235A1 (en) | 2019-03-06 | 2020-03-06 | Il-10 variant molecules and methods of treating inflammatory disease and oncology |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2025176328A Division JP2026016505A (ja) | 2019-03-06 | 2025-10-20 | Il-10バリアント分子ならびに炎症性疾患および腫瘍を処置する方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2022524018A true JP2022524018A (ja) | 2022-04-27 |
| JP2022524018A5 JP2022524018A5 (https=) | 2023-04-26 |
| JPWO2020181235A5 JPWO2020181235A5 (https=) | 2023-04-26 |
Family
ID=72334859
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021552750A Withdrawn JP2022524018A (ja) | 2019-03-06 | 2020-03-06 | Il-10バリアント分子ならびに炎症性疾患および腫瘍を処置する方法 |
| JP2025176328A Pending JP2026016505A (ja) | 2019-03-06 | 2025-10-20 | Il-10バリアント分子ならびに炎症性疾患および腫瘍を処置する方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2025176328A Pending JP2026016505A (ja) | 2019-03-06 | 2025-10-20 | Il-10バリアント分子ならびに炎症性疾患および腫瘍を処置する方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (8) | US10858412B2 (https=) |
| EP (1) | EP3934681A4 (https=) |
| JP (2) | JP2022524018A (https=) |
| KR (1) | KR20210139312A (https=) |
| CN (2) | CN114072164A (https=) |
| CA (1) | CA3132385A1 (https=) |
| WO (1) | WO2020181235A1 (https=) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10017739B2 (en) * | 2012-09-06 | 2018-07-10 | Duke University | Methods of expanding and assessing B cells and using expanded B cells to treat disease |
| JP7641912B2 (ja) | 2019-04-19 | 2025-03-07 | シナーキン・ファーマ・ベスローテン・フエンノートシャップ | Il13を含む融合タンパク質 |
| WO2021231773A1 (en) | 2020-05-13 | 2021-11-18 | Good Therapeutics, Inc. | Compositions of protein complexes and methods of use thereof |
| CA3186753A1 (en) | 2020-07-20 | 2022-01-27 | John Mumm | Dual cytokine fusion proteins comprising il-10 |
| CN112898436A (zh) * | 2020-10-23 | 2021-06-04 | 广州医科大学附属肿瘤医院 | 一种具有靶向功能的鼠pd1和鼠il-15基因融合蛋白的表达及其应用 |
| KR102792982B1 (ko) * | 2021-05-28 | 2025-04-14 | 한양대학교 산학협력단 | 세포투과성 펩티드 및 이의 용도 |
| WO2023078245A1 (zh) * | 2021-11-02 | 2023-05-11 | 广东菲鹏制药股份有限公司 | Il10单体融合蛋白及其应用 |
| JP2024546938A (ja) * | 2021-12-13 | 2024-12-26 | デカ バイオサイエンシーズ, インコーポレイテッド | マルチサブユニットサイトカインを含む二重サイトカイン融合タンパク質 |
| JP2024546999A (ja) * | 2021-12-16 | 2024-12-26 | デカ バイオサイエンシーズ, インコーポレイテッド | Il-10を含む二重サイトカイン融合物およびがんを処置するための養子細胞療法または二重特異性t細胞エンゲージャー |
| CN118900697A (zh) | 2022-02-22 | 2024-11-05 | 德卡生物科学公司 | 使用白细胞介素减轻双特异性t细胞接合器或嵌合抗原受体t细胞介导的细胞因子释放综合征的方法 |
| CN114632156B (zh) * | 2022-05-17 | 2022-08-16 | 中国人民解放军军事科学院军事医学研究院 | Tim-3在预防、治疗或减轻疼痛中的应用 |
| WO2024097875A1 (en) * | 2022-11-02 | 2024-05-10 | Shattuck Labs, Inc. | Fusion proteins for the treatment of nonalcoholic steatohepatitis |
| WO2024123812A1 (en) | 2022-12-05 | 2024-06-13 | Shattuck Labs, Inc. | Fusion proteins for the treatment of cardiometabolic diseases |
| WO2024249568A1 (en) | 2023-05-30 | 2024-12-05 | Paragon Therapeutics, Inc. | Alpha4beta7 integrin antibody compositions and methods of use |
| CN121889424A (zh) | 2023-08-14 | 2026-04-17 | 派拉冈医疗公司 | α4β7整联蛋白结合蛋白及使用方法 |
| KR20250078792A (ko) * | 2023-11-24 | 2025-06-04 | 주식회사 메드팩토 | 피브로넥틴 엑스트라도메인 B (Extradomain B of Fibronectin, EDB-FN) 및 전환성장인자 베타(transforming growth factor β, TGFβ)에 특이적으로 결합하는 융합 단백질 및 이의 용도 |
| CN121108363A (zh) * | 2024-06-12 | 2025-12-12 | 广东菲鹏制药股份有限公司 | 一种融合蛋白及其用途 |
| CN119613546B (zh) * | 2025-02-10 | 2025-05-13 | 细胞生态海河实验室 | Il-10抗体及其应用 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011502137A (ja) * | 2007-10-30 | 2011-01-20 | フィロゲン エスピーエー | 関節リウマチと関連する抗原 |
| JP2012504425A (ja) * | 2008-10-02 | 2012-02-23 | エマージェント プロダクト デベロップメント シアトル, エルエルシー | Cd86アンタゴニストの多標的結合タンパク質 |
| JP2014519807A (ja) * | 2011-04-29 | 2014-08-21 | ロシュ グリクアート アーゲー | 新規なイムノコンジュゲート |
| JP2016500670A (ja) * | 2012-10-03 | 2016-01-14 | フィロゲン エスピーエー | 炎症性腸疾患に関連する抗原 |
| JP2017506075A (ja) * | 2014-02-06 | 2017-03-02 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | インターロイキン−10イムノコンジュゲート |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA200802289A1 (ru) * | 2006-05-08 | 2009-04-28 | Филоджен Спа | Направляемые к мишени антителами цитокины для терапии |
| ES2536772T3 (es) * | 2007-09-21 | 2015-05-28 | The Regents Of The University Of California | El interferón dirigido demuestra potentes actividades apoptóticas y antitumorales |
| WO2012045334A1 (en) * | 2010-10-05 | 2012-04-12 | Synthon Bv | Biologically active il-10 fusion proteins |
| CA2876285A1 (en) | 2012-08-08 | 2014-02-13 | Roche Glycart Ag | Interleukin-10 fusion proteins and uses thereof |
| KR20160043927A (ko) | 2013-03-14 | 2016-04-22 | 파카쉬 길 | 세포 표면 grp78에 결합하는 항체를 사용하는 암 치료 |
| CN104403004B (zh) * | 2014-11-24 | 2017-10-13 | 苏州丁孚靶点生物技术有限公司 | 抗体‑干扰素异二聚体的制备和用途 |
| AU2015364396B2 (en) * | 2014-12-19 | 2018-08-09 | Alkermes, Inc. | Single chain Fc fusion proteins |
| WO2017091611A1 (en) * | 2015-11-23 | 2017-06-01 | Immungene, Inc | Enhanced cancer immunotherapy using antibody-interferon fusion molecules |
| UY37003A (es) * | 2015-12-04 | 2017-06-30 | Novartis Ag | Composiciones de anticuerpo injertado con citoquina y métodos para su uso en inmunorregulacion |
-
2020
- 2020-03-06 JP JP2021552750A patent/JP2022524018A/ja not_active Withdrawn
- 2020-03-06 CA CA3132385A patent/CA3132385A1/en active Pending
- 2020-03-06 CN CN202080033670.7A patent/CN114072164A/zh active Pending
- 2020-03-06 EP EP20765677.8A patent/EP3934681A4/en active Pending
- 2020-03-06 CN CN202511790818.2A patent/CN121652287A/zh active Pending
- 2020-03-06 KR KR1020217032047A patent/KR20210139312A/ko active Pending
- 2020-03-06 US US16/811,718 patent/US10858412B2/en active Active
- 2020-03-06 WO PCT/US2020/021498 patent/WO2020181235A1/en not_active Ceased
- 2020-08-24 US US17/001,264 patent/US10975133B2/en active Active
- 2020-08-25 US US17/002,531 patent/US10981965B2/en active Active
- 2020-08-25 US US17/002,388 patent/US10975134B2/en active Active
- 2020-08-25 US US17/002,537 patent/US20210040168A1/en not_active Abandoned
- 2020-09-04 US US17/012,841 patent/US10981966B2/en active Active
-
2021
- 2021-05-17 US US17/322,394 patent/US20220106373A1/en not_active Abandoned
-
2024
- 2024-05-07 US US18/657,437 patent/US20240294591A1/en active Pending
-
2025
- 2025-10-20 JP JP2025176328A patent/JP2026016505A/ja active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011502137A (ja) * | 2007-10-30 | 2011-01-20 | フィロゲン エスピーエー | 関節リウマチと関連する抗原 |
| JP2012504425A (ja) * | 2008-10-02 | 2012-02-23 | エマージェント プロダクト デベロップメント シアトル, エルエルシー | Cd86アンタゴニストの多標的結合タンパク質 |
| JP2014519807A (ja) * | 2011-04-29 | 2014-08-21 | ロシュ グリクアート アーゲー | 新規なイムノコンジュゲート |
| JP2016500670A (ja) * | 2012-10-03 | 2016-01-14 | フィロゲン エスピーエー | 炎症性腸疾患に関連する抗原 |
| JP2017506075A (ja) * | 2014-02-06 | 2017-03-02 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | インターロイキン−10イムノコンジュゲート |
Non-Patent Citations (5)
| Title |
|---|
| DING Y ET AL.: "A single amino acid determines the immunostimulatory activity of interleukin 10", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 191, no. 2, JPN6024003690, 17 January 2000 (2000-01-17), pages 213 - 224, ISSN: 0005621330 * |
| FERCHER CHRISTIAN ET AL.: ""Evolution of the magic bullet: Single chain antibody fragments for the targeted delivery of immuno", EXPERIMENTAL BIOLOGY AND MEDICINE, vol. 243, no. 2, JPN6024041277, 19 December 2017 (2017-12-19), pages 166 - 183, ISSN: 0005621327 * |
| JOG NR ET AL.: "Epstein Barr Virus Interleukin 10 Suppresses Anti-inflammatory Phenotype in Human Monocytes", FRONTIERS IN IMMUNOLOGY, vol. 9, no. 2198, JPN6024003688, 9 October 2018 (2018-10-09), pages 1 - 11, ISSN: 0005621328 * |
| SALEK-ARDAKANI S ET AL.: "Epstein-Barr virus encoded interleukin-10 inhibits HLA-class I, ICAM-1, and B7 expression on human m", VIROLOGY, vol. 304, no. 2, JPN6024003689, 2 December 2012 (2012-12-02), pages 342 - 351, ISSN: 0005621329 * |
| VAZQUEZ-LOMBARDI RODRIGO ET AL.: ""Molecular Engineering of Therapeutic Cytokines"", ANTIBODIES, vol. 2, no. 3, JPN6024041278, 3 July 2013 (2013-07-03), pages 426 - 451, ISSN: 0005437054 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US10975133B2 (en) | 2021-04-13 |
| US10981966B2 (en) | 2021-04-20 |
| CN114072164A (zh) | 2022-02-18 |
| US20200385435A1 (en) | 2020-12-10 |
| US20220106373A1 (en) | 2022-04-07 |
| US20200399337A1 (en) | 2020-12-24 |
| US20240294591A1 (en) | 2024-09-05 |
| KR20210139312A (ko) | 2021-11-22 |
| US20210040168A1 (en) | 2021-02-11 |
| CN121652287A (zh) | 2026-03-13 |
| US20200283488A1 (en) | 2020-09-10 |
| JP2026016505A (ja) | 2026-02-03 |
| US20200385436A1 (en) | 2020-12-10 |
| EP3934681A4 (en) | 2023-12-20 |
| US10981965B2 (en) | 2021-04-20 |
| US10975134B2 (en) | 2021-04-13 |
| CA3132385A1 (en) | 2020-09-10 |
| EP3934681A1 (en) | 2022-01-12 |
| WO2020181235A1 (en) | 2020-09-10 |
| US20200385437A1 (en) | 2020-12-10 |
| US10858412B2 (en) | 2020-12-08 |
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