Ipsen Bioinnovation Limited

Sai Man Liu

Gavin Stephen Hackett

Dina Brady Anderson

Shilpa Palan

The present invention provides engineered clostridial toxins comprising at least one amino acid modification, wherein said at least one amino acid modification increases the isoelectric point (pi) of the engineered clostridial toxin to a value that is at least 0.2 pi units higher than the pi of an otherwise identical clostridial toxin lacking said at least one amino acid modification, and wherein said at least one amino acid modification is not located in the clostridial toxin binding domain (Hdomain). Also provided are medical uses of the engineered clostridial toxins.

Cationic neurotoxins

The invention provides methods for producing soluble di-chain BoNT/A protein.

Composition comprising recombinant clostridium neurotoxin

The present invention provides an engineered clostridial toxin comprising at least one amino acid modification, wherein said at least one amino acid modification increases the isoelectric point (pI) of the engineered clostridial toxin to a value that is at least 0.2 pI units higher than the pI of an otherwise identical clostridial toxin lacking said at least one amino acid modification. Also provided are corresponding uses of the engineered clostridial toxin in therapy.

Method for preventing or treating a condition or disease in a subject comprising administering to the subject an engineered clostridial toxin comprising at least one amino acid modification that increases the isoelectric point of the toxin to a value that is at least 0.2 pI units higher than the isoelectric point of an otherwise identical clostridial toxin lacking the modification.

Engineered clostridial toxins comprising an amino acid modification that increases the isoelectric point of the engineered clostridial toxin to a value that is at least 0.2 pI units higher than the isoelectric point of an otherwise identical clostridial toxin lacking the modification, wherein the modification is not located in the clostridial toxin binding domain (Hdomain).

Methods for producing di-chain BoNT/A from single chain BoNT/A using Lys-C followed by purification using a hydrophobic surface.

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Abingdon, United Kingdom

Sai Man Liu