Carrier for targeting nerve cells
AssigneeIpsen Bioinnovation Limited
InventorsAndreas Rummel, Tanja Weil, Aleksandrs Gutcaits
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Abstract
The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragm assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.
Claims8
An expression vector comprising a nucleic acid sequence that encodes a transport protein comprising a modified clostridial neurotoxin, wherein:
- (a) the modified clostridial neurotoxin comprises a heavy chain comprising:
- (i) an HN-fragment;
- and (ii) an HC-fragment comprising a HCC-fragment and a HCN-fragment, wherein the HCC-fragment binds to a nerve cell with a higher or lower affinity than the corresponding native neurotoxin;
- and
- (b) the modified clostridial neurotoxin is a Clostridium botulinum neurotoxin serotype A selected from SEQ ID NO:
- 2, 3, 4, and 5, modified by the substitution of at least one amino acid at any one of positions 1195, 1196, 1199, 1204, 1205, 1206, 1207, 1209, 1213, 1217, 1255, 1256, 1258, and/or 1260 with either a naturally occurring or a non-naturally occurring amino acid.
Dependencies are inferred from the claim text.