TWI694084B - Ｕｔｉ融合蛋白質 - Google Patents
Ｕｔｉ融合蛋白質 Download PDFInfo
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- TWI694084B TWI694084B TW104127393A TW104127393A TWI694084B TW I694084 B TWI694084 B TW I694084B TW 104127393 A TW104127393 A TW 104127393A TW 104127393 A TW104127393 A TW 104127393A TW I694084 B TWI694084 B TW I694084B
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| CA2834626A1 (en) * | 2011-04-29 | 2012-11-01 | University Of Washington | Therapeutic nuclease compositions and methods |
| US8619331B2 (en) | 2011-07-19 | 2013-12-31 | Xerox Corporation | Simulated paper texture using clear toner and glossmark on texture-less stock |
| BR112014013205A2 (pt) * | 2011-12-01 | 2020-10-27 | Protevobio, Inc. | proteína de fusão, seu uso e seu método de produção, composição farmacêutica, ácido nucleico, e kit |
| JP5855239B2 (ja) * | 2012-04-23 | 2016-02-09 | 株式会社Ｎｒｌファーマ | ラクトフェリン融合タンパク質及びその製造方法 |
| JP2013253079A (ja) * | 2012-05-14 | 2013-12-19 | Xuhua (Shanghai) Biological Research & Development Center Co Ltd | 生物学的に活性なヒト尿中トリプシンインヒビターのＦｃ融合タンパク質並びにその調製および使用 |
| CA2939639C (en) * | 2014-02-24 | 2023-01-24 | Takeda Gmbh | Uti fusion proteins |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103044554A (zh) * | 2012-05-14 | 2013-04-17 | 旭华（上海）生物研发中心有限公司 | 重组二聚化人尿胰蛋白酶抑制剂、其制备方法及其应用 |
Non-Patent Citations (1)
| Title |
|---|
| NCBI GenBank accession no. 1BIK_A (公開日2012.11.12) * |
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