TW202012622A - 重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 - Google Patents
重組肉毒桿菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｏｔｕｌｉｎｕｍ）神經毒素 Download PDFInfo
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| KR102558892B1 (ko) | 2016-09-13 | 2023-07-21 | 알레간 인코포레이티드 | 안정화된 비단백질 클로스트리듐 독소 조성물 |
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| CN102481351B (zh) * | 2009-04-14 | 2015-05-13 | Mcw研究基金会股份有限公司 | 工程改造的肉毒杆菌神经毒素 |
| WO2011142783A2 (en) * | 2009-12-16 | 2011-11-17 | Allergan, Inc. | Modified clostridial toxins comprising an integrated protease cleavage site-binding domain |
| WO2012112434A1 (en) | 2011-02-14 | 2012-08-23 | Allergan, Inc. | Inhibiting aberrant blood vessel formation using retargeted endopeptidases |
| GB201219602D0 (en) * | 2012-10-31 | 2012-12-12 | Syntaxin Ltd | Recombinant clostridium botulinum neurotoxins |
| GB201407525D0 (en) * | 2014-04-29 | 2014-06-11 | Syntaxin Ltd | Manufacture of recombinant clostridium botulinum neurotoxins |
| WO2018039506A1 (en) * | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Engineered botulinum neurotoxin |
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2012
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