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2. 发明授权

US07381802B2 Human antibodies that specifically recognize the toxin Cn2 from Centruroides noxius scorpion venom 有权
标题翻译：人类抗体，特异性识别毒素Cn2来自Centruroides noxius蝎子毒液
公开(公告)号：US07381802B2
公开(公告)日：2008-06-03
申请号：US11404879
申请日：2006-04-17
申请人： Lidia Riaño-Umbarila , Baltazar Becerril Lujan , Lourival Domingos Possani Postay
发明人： Lidia Riaño-Umbarila , Baltazar Becerril Lujan , Lourival Domingos Possani Postay
IPC分类号： C07K16/00 , C12P21/08 , A61K39/395 , A61K39/00
CPC分类号： C07K16/18 , A61K39/39591 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/76 , C07K2317/92
摘要： The present invention is directed to recombinant human antibodies specific for Cn2 toxin from C. noxius scorpion venom. The antibodies are able to recognize the toxin and preferably neutralize it as well as the whole venom of C. noxius scorpion. This invention is also directed to a human non-immune phage display library. One clone that specifically binds the Cn2 toxin was affinity matured by directed evolution. Three cycles of maturation were performed and several scFv clones were isolated which specifically recognize toxin Cn2 with increased Kd of 446 fold. All variants were monomeric and only variants 6009F, 6105F and 6103E showed to be capable of neutralizing toxin Cn2 and the whole venom. Variant 6009F recognizes a different epitope than that of BCF2, a murine monoclonal antibody raised against scorpion toxin Cn2 which is also capable of neutralizing both Cn2 toxin and the whole venom when tested in mice, as well as that of commercially available polyclonal antibody fragments antivenom from horse. The scFv 6009F is the first reported recombinant human antibody fragment capable of neutralizing a scorpion venom. These results pave the way for the generation of safer autologous recombinant neutralizing antivenom against scorpion stings. The antibodies of the present invention can be used as part of a composition to treat those in need of treatment including those already stung by one or more scorpions, particularly C. noxius scorpions.
摘要翻译：本发明涉及对来自C.noxius蝎毒素的Cn2毒素特异的重组人抗体。抗体能够识别毒素，并优选中和它以及C.noxius蝎子的全部毒液。本发明还涉及人类非免疫噬菌体展示文库。特异性结合Cn2毒素的一个克隆通过定向进化亲和成熟。进行三个成熟周期，分离出几个特异性识别毒素Cn2的scFv克隆，增加Kd 446倍。所有变体都是单体的，只有变体6009F，6105F和6103E才能够中和毒素Cn2和全毒液。变体6009F识别与BCF2不同的表位，BCF2是针对蝎毒素Cn2产生的鼠单克隆抗体，其在小鼠中测试时也能够中和Cn2毒素和全毒液，以及可商购的多克隆抗体片段抗蛇毒素马。 scFv 6009F是能够中和蝎毒液的首次报道的重组人抗体片段。这些结果为针对蝎子蜇产生更安全的自体重组中和抗蛇毒剂铺平了道路。本发明的抗体可以用作组合物的一部分，以治疗需要治疗的组合物，包括已经被一种或多种蝎子，特别是C.noxius蝎子刺伤的那些。

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