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Method for producing di-chain clostridial neurotoxins

A neurotoxin, Clostridium technology, applied in nervous system diseases, chemical instruments and methods, pharmaceutical formulations, etc.

Inactive Publication Date: 2019-05-03
IPSEN BIOPHARM LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in particular the data presented in Figures 10 and 11 of US2006 / 0024794 A1 show that while a small fraction of double-chain neurotoxins are formed, the vast majority of Clostridial neurotoxins remain as free light and heavy chains

Method used

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  • Method for producing di-chain clostridial neurotoxins
  • Method for producing di-chain clostridial neurotoxins
  • Method for producing di-chain clostridial neurotoxins

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Embodiment Construction

[0028] The present invention is based on the inventors' discovery that separate co-expression of the Clostridial neurotoxin light and heavy chains in the oxidative environment of a heterologous host cell allows the two domains to fold together with significantly improved efficiency to form a double-stranded Clostridial neurotoxin .

[0029] In a first aspect, the present invention provides a method for producing a double-strand Clostridial neurotoxin comprising expressing in a heterologous host cell a first gene encoding a Clostridial neurotoxin light chain and a first gene encoding a Clostridial neurotoxin heavy chain a second gene, wherein the first and second genes are expressed in the oxidative environment of the host cell.

[0030] The term "oxidative environment" as used herein means a cellular environment that promotes the formation of cystine (oxidized dimer of cysteine). This is usually achieved through the balance of different redox proteins such as, but not limited...

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Abstract

The present invention provides methods, cells and kits suitable for recombinant production of di-chain clostridial neurotoxins, which avoid the requirement of an activation step, as well as di-chain clostridial neurotoxins thereby obtained which are suitable for use in therapy.

Description

technical field [0001] The present invention provides methods for the recombinant production of double-strand Clostridium neurotoxins that circumvent the need for an activation step. Background technique [0002] Clostridia bacteria produce highly potent and specific protein toxins that are toxic to neurons and other cells to which they are delivered. Examples of such Clostridial toxins include neurotoxins produced by Clostridium tetani (C. tetani) (TeNT) and by Clostridium botulinum (BoNT) serotypes A-G, and by Clostridium pasteuriani ( C. baratii) and those produced by Clostridium butyricum (C. butyricum). [0003] Some of the most potent toxins are known among the Clostridial toxins. As an example, the median lethal dose of botulinum neurotoxin in mice ranges from 0.5 to 5 ng / kg depending on the serotype. Both tetanus and botulinum toxin work by inhibiting the function of the affected neurons, especially the release of neurotransmitters. Botulinum toxin acts at the ne...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P21/02C07K14/33
CPCC07K14/33C12P21/02A61P13/10A61P25/00A61P25/08A61P25/14A61P27/02A61K38/00C12N15/70
Inventor D·克万
Owner IPSEN BIOPHARM LTD