JP2020530296A5 - - Google Patents
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- JP2020530296A5 JP2020530296A5 JP2020507074A JP2020507074A JP2020530296A5 JP 2020530296 A5 JP2020530296 A5 JP 2020530296A5 JP 2020507074 A JP2020507074 A JP 2020507074A JP 2020507074 A JP2020507074 A JP 2020507074A JP 2020530296 A5 JP2020530296 A5 JP 2020530296A5
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- JP
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- Prior art keywords
- polypeptide
- domain
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- fcrn
- antibody
- 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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- 229920001184 polypeptide Polymers 0.000 claims description 83
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 83
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 83
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 claims description 14
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 claims description 14
- 238000006467 substitution reaction Methods 0.000 claims description 12
- 108010068617 neonatal Fc receptor Proteins 0.000 claims description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 235000018102 proteins Nutrition 0.000 claims description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Chemical group OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 2
- 102000008096 B7-H1 Antigen Human genes 0.000 claims description 2
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 2
- 101150013553 CD40 gene Proteins 0.000 claims description 2
- 101150029707 ERBB2 gene Proteins 0.000 claims description 2
- 108010087819 Fc receptors Proteins 0.000 claims description 2
- 102000009109 Fc receptors Human genes 0.000 claims description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 2
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 claims description 2
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 2
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 claims description 2
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 2
- 108010073807 IgG Receptors Proteins 0.000 claims description 2
- 102100032818 Integrin alpha-4 Human genes 0.000 claims description 2
- 108010041012 Integrin alpha4 Proteins 0.000 claims description 2
- 108010002352 Interleukin-1 Proteins 0.000 claims description 2
- 102000000589 Interleukin-1 Human genes 0.000 claims description 2
- 102000003814 Interleukin-10 Human genes 0.000 claims description 2
- 108090000174 Interleukin-10 Proteins 0.000 claims description 2
- 108090001005 Interleukin-6 Proteins 0.000 claims description 2
- 102000004889 Interleukin-6 Human genes 0.000 claims description 2
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 claims description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims description 2
- 108010052285 Membrane Proteins Proteins 0.000 claims description 2
- 102000018697 Membrane Proteins Human genes 0.000 claims description 2
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 2
- 102000014128 RANK Ligand Human genes 0.000 claims description 2
- 108010025832 RANK Ligand Proteins 0.000 claims description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 2
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 claims description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 2
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 claims description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 2
- 239000000556 agonist Substances 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 235000003704 aspartic acid Nutrition 0.000 claims description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 239000003053 toxin Substances 0.000 claims description 2
- 231100000765 toxin Toxicity 0.000 claims description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical group OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 claims 1
- 150000001413 amino acids Chemical group 0.000 claims 1
- 229930195712 glutamate Natural products 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 claims 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- 238000000034 method Methods 0.000 description 19
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 7
- 230000035772 mutation Effects 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 208000035143 Bacterial infection Diseases 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 238000011319 anticancer therapy Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022126967A JP7583767B2 (ja) | 2017-08-11 | 2022-08-09 | 血清中半減期の増強のための操作された抗体ｆｃバリアント |
| JP2024193182A JP2025013474A (ja) | 2017-08-11 | 2024-11-01 | 血清中半減期の増強のための操作された抗体ｆｃバリアント |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762544622P | 2017-08-11 | 2017-08-11 | |
| US62/544,622 | 2017-08-11 | ||
| PCT/US2018/046398 WO2019033087A1 (en) | 2017-08-11 | 2018-08-11 | MODIFIED FC ANTIBODY VARIANTS FOR ENHANCED SERIAL HALF LIFE |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022126967A Division JP7583767B2 (ja) | 2017-08-11 | 2022-08-09 | 血清中半減期の増強のための操作された抗体ｆｃバリアント |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020530296A JP2020530296A (ja) | 2020-10-22 |
| JP2020530296A5 true JP2020530296A5 (enExample) | 2021-10-21 |
| JP7191087B2 JP7191087B2 (ja) | 2022-12-16 |
Family
ID=65272701
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020507074A Active JP7191087B2 (ja) | 2017-08-11 | 2018-08-11 | 血清中半減期の増強のための操作された抗体ｆｃバリアント |
| JP2022126967A Active JP7583767B2 (ja) | 2017-08-11 | 2022-08-09 | 血清中半減期の増強のための操作された抗体ｆｃバリアント |
| JP2024193182A Pending JP2025013474A (ja) | 2017-08-11 | 2024-11-01 | 血清中半減期の増強のための操作された抗体ｆｃバリアント |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022126967A Active JP7583767B2 (ja) | 2017-08-11 | 2022-08-09 | 血清中半減期の増強のための操作された抗体ｆｃバリアント |
| JP2024193182A Pending JP2025013474A (ja) | 2017-08-11 | 2024-11-01 | 血清中半減期の増強のための操作された抗体ｆｃバリアント |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US11059892B2 (enExample) |
| EP (1) | EP3665195A4 (enExample) |
| JP (3) | JP7191087B2 (enExample) |
| KR (1) | KR102867311B1 (enExample) |
| CN (1) | CN111032688A (enExample) |
| AU (1) | AU2018314257B2 (enExample) |
| CA (1) | CA3072099A1 (enExample) |
| IL (1) | IL272561B2 (enExample) |
| WO (1) | WO2019033087A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7762645B2 (ja) * | 2019-08-22 | 2025-10-30 | シダラ セラピューティクス インコーポレーテッド | バリアントｆｃドメイン及びその使用 |
| CN115515975A (zh) * | 2020-05-21 | 2022-12-23 | 兹杜斯生命科学有限公司 | Fc变体及其制备 |
| CN116437958A (zh) * | 2020-11-11 | 2023-07-14 | 吉利德科学公司 | 鉴定对采用gp120 CD4结合位点导向的抗体的疗法敏感的HIV患者的方法 |
| AU2022218137A1 (en) | 2021-02-03 | 2023-08-24 | Mozart Therapeutics, Inc. | Binding agents and methods of using the same |
| WO2022217022A1 (en) | 2021-04-10 | 2022-10-13 | Profoundbio Us Co. | Folr1 binding agents, conjugates thereof and methods of using the same |
| CA3216459A1 (en) | 2021-04-23 | 2022-10-27 | Profoundbio Us Co. | Anti-cd70 antibodies, conjugates thereof and methods of using the same |
| TW202320857A (zh) | 2021-07-06 | 2023-06-01 | 美商普方生物製藥美國公司 | 連接子、藥物連接子及其結合物及其使用方法 |
| WO2023076876A1 (en) | 2021-10-26 | 2023-05-04 | Mozart Therapeutics, Inc. | Modulation of immune responses to viral vectors |
| WO2023108115A1 (en) * | 2021-12-10 | 2023-06-15 | Board Of Regents, The University Of Texas System | Ph-selective antibody fc domains |
| WO2024030956A2 (en) | 2022-08-03 | 2024-02-08 | Mozart Therapeutics, Inc. | Cd39-specific binding agents and methods of using the same |
| CN119768183A (zh) | 2022-08-26 | 2025-04-04 | 吉利德科学公司 | 用于广泛中和抗体的给药和安排方案 |
| EP4720124A1 (en) | 2023-05-24 | 2026-04-08 | Mozart Therapeutics, Inc. | Cd8-specific binding proteins and methods of using the same |
| CN122003247A (zh) | 2023-07-07 | 2026-05-08 | 维里迪安治疗公司 | 治疗活动性和慢性甲状腺眼病的方法 |
| AR133955A1 (es) | 2023-09-26 | 2025-11-19 | Profoundbio Us Co | Agentes de unión a ptk7, conjugados de éstos y métodos de uso de los mismos |
| AU2024388998A1 (en) | 2023-11-27 | 2026-05-28 | Genmab A/S | Antibodies and methods for ptk7 detection |
| TW202547866A (zh) | 2024-01-10 | 2025-12-16 | 丹麥商珍美寶股份有限公司 | Ｓｌｉｔｒｋ６結合劑、其共軛物及使用彼之方法 |
| WO2025171006A1 (en) | 2024-02-06 | 2025-08-14 | Paragon Therapeutics, Inc. | Il-23 binding protein compositions and methods of use |
| AU2025218720A1 (en) | 2024-02-06 | 2026-05-21 | Paragon Therapeutics, Inc. | Il-23 antibody compositions and methods of use |
| WO2025181219A1 (en) | 2024-02-29 | 2025-09-04 | Genmab A/S | Egfr and c-met bispecific binding agents, conjugates thereof and methods of using the same |
| WO2025222129A2 (en) | 2024-04-19 | 2025-10-23 | Mozart Therapeutics, Inc. | Engineered cytokines and targeted cytokine delivery |
| US20260109746A1 (en) | 2024-10-22 | 2026-04-23 | Gilead Sciences, Inc. | Cd4-targeted il-15 molecules and methods of use |
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| US4554101A (en) | 1981-01-09 | 1985-11-19 | New York Blood Center, Inc. | Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity |
| US5824311A (en) | 1987-11-30 | 1998-10-20 | Trustees Of The University Of Pennsylvania | Treatment of tumors with monoclonal antibodies against oncogene antigens |
| US4870287A (en) | 1988-03-03 | 1989-09-26 | Loma Linda University Medical Center | Multi-station proton beam therapy system |
| US5846945A (en) | 1993-02-16 | 1998-12-08 | Onyx Pharmaceuticals, Inc. | Cytopathic viruses for therapy and prophylaxis of neoplasia |
| US5801005A (en) | 1993-03-17 | 1998-09-01 | University Of Washington | Immune reactivity to HER-2/neu protein for diagnosis of malignancies in which the HER-2/neu oncogene is associated |
| GB9506466D0 (en) | 1994-08-26 | 1995-05-17 | Prolifix Ltd | Cell cycle regulated repressor and dna element |
| US5702892A (en) | 1995-05-09 | 1997-12-30 | The United States Of America As Represented By The Department Of Health And Human Services | Phage-display of immunoglobulin heavy chain libraries |
| US5760395A (en) | 1996-04-18 | 1998-06-02 | Universities Research Assoc., Inc. | Method and apparatus for laser-controlled proton beam radiology |
| US5739169A (en) | 1996-05-31 | 1998-04-14 | Procept, Incorporated | Aromatic compounds for inhibiting immune response |
| US6737056B1 (en) * | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| US7094571B2 (en) | 2000-10-27 | 2006-08-22 | The Board Of Regents Of The University Of Texas System | Combinatorial protein library screening by periplasmic expression |
| US7419783B2 (en) | 2001-11-05 | 2008-09-02 | Research Development Foundation | Engineering of leader peptides for the secretion of recombinant proteins in bacteria |
| US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
| CA2480159A1 (en) | 2002-03-23 | 2003-10-09 | Research Development Foundation | Secretion of proteins with multiple disulfide bonds in bacteria and uses thereof |
| US7611866B2 (en) | 2002-07-15 | 2009-11-03 | Board Of Regents, The University Of Texas System | Selection of bacterial inner-membrane anchor polypeptides |
| US9051373B2 (en) * | 2003-05-02 | 2015-06-09 | Xencor, Inc. | Optimized Fc variants |
| WO2005047327A2 (en) | 2003-11-12 | 2005-05-26 | Biogen Idec Ma Inc. | NEONATAL Fc RECEPTOR (FcRn)-BINDING POLYPEPTIDE VARIANTS, DIMERIC Fc BINDING PROTEINS AND METHODS RELATED THERETO |
| AU2005335714B2 (en) | 2004-11-10 | 2012-07-26 | Macrogenics, Inc. | Engineering Fc antibody regions to confer effector function |
| US9200079B2 (en) | 2004-11-12 | 2015-12-01 | Xencor, Inc. | Fc variants with altered binding to FcRn |
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| CN102549016B (zh) | 2009-06-30 | 2015-05-06 | 研究发展基金会 | 免疫球蛋白fc多肽 |
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| JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
| TW201817745A (zh) | 2011-09-30 | 2018-05-16 | 日商中外製藥股份有限公司 | 具有促進抗原清除之ＦｃＲｎ結合域的治療性抗原結合分子 |
| EA201892339A3 (ru) * | 2011-12-19 | 2019-06-28 | Дзе Рокфеллер Юниверсити | Несиалированный выделенный полипептид, способ получения указанного полипептида и фармацевтическая композиция для лечения воспалительного заболевания |
| JPWO2013180201A1 (ja) * | 2012-05-30 | 2016-01-21 | 中外製薬株式会社 | 会合化した抗原を消失させる抗原結合分子 |
| JP6832709B2 (ja) * | 2014-05-16 | 2021-02-24 | メディミューン，エルエルシー | 新生児Ｆｃ受容体結合が改変されて治療および診断特性が強化された分子 |
| JP6034332B2 (ja) | 2014-05-30 | 2016-11-30 | トヨタ自動車株式会社 | 組換え微生物及び当該組換え微生物を用いた物質製造方法 |
| PT3215528T (pt) * | 2014-11-06 | 2019-10-11 | Hoffmann La Roche | Variantes da região fc com ligação modificada ao fcrn e métodos de utilização |
| CN118126157A (zh) | 2017-08-03 | 2024-06-04 | 美国安进公司 | 白介素-21突变蛋白和治疗方法 |
-
2018
- 2018-08-11 EP EP18844094.5A patent/EP3665195A4/en active Pending
- 2018-08-11 WO PCT/US2018/046398 patent/WO2019033087A1/en not_active Ceased
- 2018-08-11 CN CN201880051999.9A patent/CN111032688A/zh active Pending
- 2018-08-11 US US16/101,421 patent/US11059892B2/en active Active
- 2018-08-11 IL IL272561A patent/IL272561B2/en unknown
- 2018-08-11 JP JP2020507074A patent/JP7191087B2/ja active Active
- 2018-08-11 AU AU2018314257A patent/AU2018314257B2/en active Active
- 2018-08-11 CA CA3072099A patent/CA3072099A1/en active Pending
- 2018-08-11 KR KR1020207004453A patent/KR102867311B1/ko active Active
-
2021
- 2021-06-14 US US17/346,648 patent/US11958904B2/en active Active
-
2022
- 2022-08-09 JP JP2022126967A patent/JP7583767B2/ja active Active
-
2024
- 2024-04-05 US US18/628,078 patent/US20240270852A1/en active Pending
- 2024-11-01 JP JP2024193182A patent/JP2025013474A/ja active Pending
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