Carrier for targeting nerve cells
AssigneeSyntaxin Limited
InventorsAndreas Rummel, Tanja Weil, Aleksandrs Gutcaits
Life of this patent
Estimating the term…
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.
Claims26
A transport protein comprising a modified clostridial neurotoxin heavy chain, said heavy chain comprising a HN-fragment and a HC-fragment, wherein said HC-fragment includes a HCC-fragment and a HCN-fragment, wherein said HCC-fragment binds to a nerve cell with a higher or lower affinity than the corresponding native neurotoxin, and wherein said HCC-fragment comprises the substitution of at least one amino acid by either a naturally or not naturally occurring amino acid in the amino acid positions selected from the group consisting of:
- a) amino acid positions corresponding to threonine 1195, asparagine 1196, glutamine 1199, lysine 1204, isoleucine 1205, leucine 1206, serine 1207, leucine 1209, aspartate 1213, leucine 1217, phenylalanine 1255, asparagine 1256, isoleucine 1258 and/or lysine 1260 of Clostridium botulinum serotype A (SEQ ID NO.:
- 2, 3, 4 or 5);
- b) amino acid positions corresponding to lysine 1113, aspartate 1114, serine 1116, proline 1117, valine 1118, threonine 1182, tyrosine 1183, phenylalanine 1186, lysine 1188, glutamate 1191, lysine 1192, leucine 1193, phenylalanine 1194, phenylalanine 1204, phenylalanine 1243, glutamate 1245, lysine 1254, aspartate 1255 and tyrosine 1256 of Clostridium botulinum serotype B (SEQ ID NO.:
- 6, 7, 8, 9, 10 or 11);
- c) amino acid positions corresponding to positions 1084-1280 or 1093-1291 of Clostridium botulinum serotype C1 (SEQ ID NO.:
- 12, 13, 14, 15 or 16);
- d) amino acid positions corresponding to positions 1080-1276 or 1089-1285 of Clostridium botulinum serotype D (SEQ ID NO.:
- 17, 18, 19 or 20);
- e) amino acid positions corresponding to positions 1067-1252 or 1067-1251 of Clostridium botulinum serotype E (SEQ ID NO.:
- 21, 22 or 23);
- f) amino acid positions corresponding to positions 1087-1274 or 1088-1280 or 1085-1278 or 1076-1268 of Clostridium botulinum serotype F (SEQ ID NO.:
- 24, 25, 26 or 27);
- or
- g) amino acid positions corresponding to phenylalanine 1121, lysine 1123, alanine 1124, serine 1125, methionine 1126, valine 1190, leucine 1191, serine 1194, glutamate 1196, threonine 1199, glutamine 1200, leucine 1201, phenylalanine 1202, phenylalanine 1212, phenylalanine 1248, lysine 1250, aspartate 1251 and tyrosine 1262 of Clostridium botulinum serotype G (SEQ ID NO.:
- 28 or 29).
Dependencies are inferred from the claim text.