Carrier for targeting nerve cells
AssigneeSyntaxin Limited
InventorsAndreas Rummel, Tanja Weil, Aleksandrs Gutcaits
Life of this patent
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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.
Claims22
A transport protein comprising a modified Clostridium botulinum serotype B neurotoxin Hcc domain that binds to a nerve cell with a higher or lower affinity than the native Clostridium botulinum serotype B neurotoxin from which said Hcc domain is derived, said transport protein comprises substitution by a non-polar amino acid of at least one amino acid in the amino acid positions selected from the group consisting of:
- amino acid positions corresponding to aspartate 1114, serine 1116, proline 1117, valine 1118, 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 neurotoxin of SEQ ID NO.:
- 6, 7, 8, 9, 10 or 11, wherein the transport protein binds to synaptotagmin I or II, and wherein the transport protein is covalently linked to a Clostridium botulinum serotype B protease.
A transport protein comprising a modified clostridial neurotoxin Hcc domain that binds to a nerve cell with a higher affinity than the native Clostridium botulinum serotype B neurotoxin from which said Hcc domain is derived, comprising substitution by a non-polar amino acid of at least one amino acid in the amino acid positions selected from the group consisting of:
- amino acid positions corresponding to aspartate 1114, serine 1116, proline 1117, valine 1118, 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 neurotoxin of SEQ ID NO.:
- 6, 7, 8, 9, 10 or 11;
- wherein the transport protein binds to synaptotagmin I or II.
A transport protein comprising a modified clostridial neurotoxin Hcc domain that binds to a nerve cell with a higher or lower affinity than the native Clostridium botulinum serotype B neurotoxin from which said Hcc domain is derived, comprising a substitution by a non-polar amino acid in the amino acid position corresponding to glutamate 1191 of Clostridium botulinum serotype B neurotoxin of SEQ ID NO.:
- 6, 7, 8, 9, 10 or 11;
- wherein the transport protein binds to synaptotagmin I or II, and wherein the transport protein is covalently linked to a Clostridium botulinum serotype B protease.
A transport protein comprising a modified clostridial neurotoxin Hcc domain that binds to a nerve cell with a higher affinity than the native Clostridium botulinum serotype B neurotoxin from which said Hcc domain is derived, comprising a substitution by a non-polar amino acid in the amino acid position corresponding to glutamate 1191 of Clostridium botulinum serotype B neurotoxin of SEQ ID NO.:
- 6, 7, 8, 9, 10 or 11;
- wherein the transport protein binds to synaptotagmin I or II.
Dependencies are inferred from the claim text.