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1. 发明申请

WO2016180533A1 NOVEL RECOMBINANT CLOSTRIDIAL NEUROTOXINS WITH INCREASED DURATION OF EFFECT 审中-公开
标题翻译：新的重组离子神经毒素具有增加的作用时间
公开(公告)号：WO2016180533A1
公开(公告)日：2016-11-17
申请号：PCT/EP2016/000772
申请日：2016-05-11
申请人： MERZ PHARMA GMBH & CO. KGAA
发明人： FREVERT, Juergen , HOFMANN, Fred , SCHMIDT, Michael , LÓPEZ DE LA PAZ, Manuela
IPC分类号： C07K14/33
CPC分类号： C07K14/33
摘要： This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a SNARE complex-binding sequence, and the methods comprise the steps of inserting a nucleic acid sequence coding for a SNARE complex-binding sequence into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising the SNARE complex-binding sequence in a host cell. The invention further relates to novel recombinant single- chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with increased duration of effect.
摘要翻译：本发明涉及显示出增加的作用持续时间的新型重组梭菌神经毒素和制备这种重组梭菌神经毒素的方法。这些新型重组梭菌神经毒素包含SNARE复合物结合序列，并且所述方法包括以下步骤：将编码SNARE复合物结合序列的核酸序列插入到编码亲本梭菌神经毒素的核酸序列中，并重组核酸的表达酸序列在宿主细胞中包含SNARE复合物结合序列。本发明还涉及用于这些方法的新型重组单链前体梭菌神经毒素，编码这种重组单链前体梭菌神经毒素的核酸序列，以及包含具有增加的作用持续时间的重组梭菌神经毒素的药物组合物。

2. 发明申请

WO2019007509A1 NOVEL RECOMBINANT BOTULINUM NEUROTOXINS WITH INCREASED DURATION OF EFFECT 审中-公开
公开(公告)号：WO2019007509A1
公开(公告)日：2019-01-10
申请号：PCT/EP2017/066891
申请日：2017-07-06
申请人： MERZ PHARMA GMBH & CO. KGAA
发明人： FREVERT, Jürgen , HOFMANN, Fred , JURK, Marcel , LÓPEZ DE LA PAZ, Manuela , SCHEPS, Daniel
IPC分类号： C07K14/33 , A61K38/48
摘要： This invention relates to novel recombinant botulinum neurotoxins serotype A exhibiting both (i) an increased duration of effect and (ii) a high specific biological activity. These novel recombinant botulinum neurotoxins comprise at least two additional domains consisting of proline, alanine and an additional amino acid residue and at least one amino acid modification which is located at the alpha-exosite or at the beta-exosite of the light chain of the neurotoxin. The invention further relates to novel recombinant single-chain precursor botulinum neurotoxins and compositions comprising the recombinant botulinum neurotoxin with an increased duration of effect and a high specific biological activity.

3. 发明申请

WO2018233813A1 NOVEL RECOMBINANT BOTULINUM TOXIN WITH INCREASED DURATION OF EFFECT 审中-公开
公开(公告)号：WO2018233813A1
公开(公告)日：2018-12-27
申请号：PCT/EP2017/065096
申请日：2017-06-20
申请人： MERZ PHARMA GMBH & CO. KGAA
发明人： HOFMANN, Fred , JURK, Marcel , LÓPEZ DE LA PAZ, Manuela , SCHEPS, Daniel , FREVERT, Jürgen
IPC分类号： C07K14/33 , A61K8/64 , A61K8/99 , A61K38/16 , C12N15/62
摘要： This invention relates to novel recombinant clostridial neurotoxins exhibiting an increased duration of effect without a delayed onset of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a domain consisting of proline, alanine, serine, threonine, glycine and glutamate residues, and the methods comprise the steps of inserting a nucleic acid sequence coding for said domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising said domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with an increased duration of effect without a delayed onset of effect.

4. 发明申请

WO2019101308A1 NOVEL RECOMBINANT BOTULINUM TOXIN WITH INCREASED DURATION OF EFFECT 审中-公开
公开(公告)号：WO2019101308A1
公开(公告)日：2019-05-31
申请号：PCT/EP2017/080117
申请日：2017-11-22
申请人： MERZ PHARMA GMBH & CO. KGAA
发明人： FREVERT, Jürgen , HOFMANN, Fred , JURK, Marcel , LÓPEZ DE LA PAZ, Manuela , SCHEPS, Daniel
IPC分类号： A61K38/48 , C07K14/33
CPC分类号： C12N9/52 , A61K8/64 , A61K8/99 , A61K38/00 , A61Q19/08 , C07K14/33 , C07K2319/31 , C07K2319/50 , C12Y304/24069
摘要： This invention relates to novel recombinant clostridial neurotoxins exhibiting an increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise at least one domain wherein said domain comprises an amino acid sequence consisting of at least 50 amino acid residues, wherein said amino acid sequence consists of at least one proline and at least one alanine residue. The invention relates also to novel recombinant clostridial neurotoxins comprising at least one domain wherein said domain comprises an amino acid sequence consisting of at least 50 amino acid residues, wherein said domain comprises a plurality of specific amino acid repeats consisting of proline, alanine and tyrosine residues, or proline, alanine and glutamine residues, or proline, alanine and threonine residues.

5. 发明申请

WO2017125487A1 NOVEL RECOMBINANT CLOSTRIDIAL NEUROTOXINS WITH INCREASED DURATION OF EFFECT 审中-公开
标题翻译：具有增加的作用持续时间的新型重组菌丝体神经毒素
公开(公告)号：WO2017125487A1
公开(公告)日：2017-07-27
申请号：PCT/EP2017/051074
申请日：2017-01-19
申请人： MERZ PHARMA GMBH & CO. KGAA
发明人： HOFMANN, Fred , JURK, Marcel , LÓPEZ DE LA PAZ, Manuela , SCHEPS, Daniel , FREVERT, Jürgen
IPC分类号： C07K14/33 , A61K38/00
CPC分类号： C07K14/33
摘要： This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise (i) at least two random coil domains, or (ii) at least two domains having a polyproline II helix conformation, and the methods comprise the steps of inserting at least two nucleic acid sequences each coding for (i) a random coil domain, or (ii) a domain having a polyproline II helix conformation, into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising (i) the random coil domain-coding sequences, or (ii) the sequences encoding the domains having a polyproline II helix conformation in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with increased duration of effect.
摘要翻译：本发明涉及显示出增加的作用持续时间的新的重组梭菌神经毒素以及制备这种重组梭菌神经毒素的方法。这些新的重组梭菌神经毒素包含（i）至少两个无规卷曲结构域，或（ii）至少两个具有聚脯氨酸II螺旋构象的结构域，并且所述方法包括以下步骤：插入至少两个核酸序列，每个核酸序列编码）无规卷曲结构域或（ii）具有聚脯氨酸II螺旋构象的结构域整合到编码亲本梭菌神经毒素的核酸序列中并表达重组核酸序列，所述重组核酸序列包含（i）无规卷曲结构域编码序列，或（ii）编码宿主细胞中具有聚脯氨酸II螺旋构象的结构域的序列。本发明进一步涉及在这些方法中使用的新型重组单链前体梭菌神经毒素，编码此类重组单链前体梭菌神经毒素的核酸序列，以及包含具有增加的作用持续时间的重组梭菌神经毒素的药物组合物。

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