Ipsen Bioinnovation Limited

Ipsen Biopharm Limited

Gavin Stephen Hackett

Sai Man Liu

Dina Brady Anderson

Shilpa Palan

Sai Man Lui

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

A method for purifying a clostridial neurotoxin comprising contacting a cation exchange resin with a composition comprising a clostridial neurotoxin, wherein the contacting step is performed at at least pH 7.3, wherein the step of contacting a cation exchange resin with a composition comprising said clostridial neurotoxin occurs prior to conversion of the clostridial neurotoxin from a single chain form into a dichain form. Also provided are uses of a buffer having a pH value that is &#x2212;1 pH unit or higher than the calculated pi of a clostridial neurotoxin, purification intermediates and clostridial neurotoxins obtainable by the invention, wherein the clostridial neurotoxin is in a single chain form.

Methods for purifying clostridial 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.

Growing community of inventors

Abingdon, United Kingdom

Gavin Stephen Hackett