Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting an increased duration of effect without a delayed onset of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a domain consisting of proline, alanine, serine, threonine, glycine and glutamate residues, and the methods comprise the steps of inserting a nucleic acid sequence coding for said domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising said domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with an increased duration of effect without a delayed onset of effect.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a random coil domain, and the methods comprise the steps of inserting a nucleic acid sequence coding for a random coil domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising the random coil domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with increased duration of effect.

Abstract: This invention relates to novel recombinant botulinum neurotoxins serotype A exhibiting both (i) an increased duration of effect and (ii) a high specific biological activity. These novel recombinant botulinum neurotoxins comprise at least two additional domains consisting of proline, alanine and an additional amino acid residue and at least one amino acid modification which is located at the alpha-exosite or at the beta-exosite of the light chain of the neurotoxin. The invention further relates to novel recombinant single-chain precursor botulinum neurotoxins and compositions comprising the recombinant botulinum neurotoxin with an increased duration of effect and a high specific biological activity.

Abstract: This invention relates to novel recombinant botulinum neurotoxins serotype A exhibiting both (i) an increased duration of effect and (ii) a high specific biological activity. These novel recombinant botulinum neurotoxins comprise at least two additional domains consisting of proline, alanine and an additional amino acid residue and at least one amino acid modification which is located at the alpha-exosite or at the beta-exosite of the light chain of the neurotoxin. The invention further relates to novel recombinant single-chain precursor botulinum neurotoxins and compositions comprising the recombinant botulinum neurotoxin with an increased duration of effect and a high specific biological activity.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise (i) at least two random coil domains, or (ii) at least two domains having a polyproline II helix conformation, and the methods comprise the steps of inserting at least two nucleic acid sequences each coding for (i) a random coil domain, or (ii) a domain having a polyproline II helix conformation, into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising (i) the random coil domain-coding sequences, or (ii) the sequences encoding the domains having a polyproline II helix conformation in a host cell.

Abstract: The invention relates to novel recombinant single-chain precursor botulinum neurotoxins serotype A comprising at least one additional domain and least one amino acid modification of the heavy chain of the neurotoxin. The novel recombinant single-chain precursor botulinum neurotoxins further comprises at least one cleavage site for a protease selected from the group consisting of thrombin, HRV3C, Tobacco Etch Vims protease, enterokinase and factor Xa. The invention further relates to novel recombinant botulinum neurotoxins serotype A exhibiting an increased duration of effect.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting an increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise at least one domain wherein said domain comprises an amino acid sequence consisting of at least 50 amino acid residues, wherein said amino acid sequence consists of at least one proline and at least one alanine residue. The invention relates also to novel recombinant clostridial neurotoxins comprising at least one domain wherein said domain comprises an amino acid sequence consisting of at least 50 amino acid residues, wherein said domain comprises a plurality of specific amino acid repeats consisting of proline, alanine and tyrosine residues, or proline, alanine and glutamine residues, or proline, alanine and threonine residues.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a random coil domain, and the methods comprise the steps of inserting a nucleic acid sequence coding for a random coil domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising the random coil domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with increased duration of effect.

Abstract: This invention relates to novel recombinant botulinum neurotoxins serotype A exhibiting both (i) an increased duration of effect and (ii) a high specific biological activity. These novel recombinant botulinum neurotoxins comprise at least two additional domains consisting of proline, alanine and an additional amino acid residue and at least one amino acid modification which is located at the alpha-exosite or at the beta-exosite of the light chain of the neurotoxin. The invention further relates to novel recombinant single-chain precursor botulinum neurotoxins and compositions comprising the recombinant botulinum neurotoxin with an increased duration of effect and a high specific biological activity.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a random coil domain, and the methods comprise the steps of inserting a nucleic acid sequence coding for a random coil domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising the random coil domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with increased duration of effect.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting an increased duration of effect without a delayed onset of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a domain consisting of proline, alanine, serine, threonine, glycine and glutamate residues, and the methods comprise the steps of inserting a nucleic acid sequence coding for said domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising said domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with an increased duration of effect without a delayed onset of effect.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise (i) at least two random coil domains, or (ii) at least two domains having a polyproline II helix conformation, and the methods comprise the steps of inserting at least two nucleic acid sequences each coding for (i) a random coil domain, or (ii) a domain having a polyproline II helix conformation, into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising (i) the random coil domain-coding sequences, or (ii) the sequences encoding the domains having a polyproline II helix conformation in a host cell.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a random coil domain, and the methods comprise the steps of inserting a nucleic acid sequence coding for a random coil domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising the random coil domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with increased duration of effect.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a random coil domain, and the methods comprise the steps of inserting a nucleic acid sequence coding for a random coil domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising the random coil domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with increased duration of effect.

Abstract: The present invention relates to the pharmaceutical field. Specifically, it contemplates a polynucleotide encoding a Neurotoxin polypeptide exhibiting a reduced duration of biological effect in a subject, wherein the polypeptide comprises at feast one degradation signal in the light chain as well as vectors and host calls comprising the polynucleotide, polypeptides encoded thereby and antibodies specifically binding to the polypeptides. Moreover, the invention relates to medicaments comprising the polynucleotides and polypeptides as well as specific therapeutic applications thereof. Furthermore, the present invention contemplates methods for the manufacture of the polypeptides and medicaments.

Abstract: The present invention relates to the pharmaceutical field. Specifically, it contemplates a polynucleotide encoding a Neurotoxin polypeptide exhibiting a reduced duration of biological effect in a subject, wherein the polypeptide comprises at feast one degradation signal in the light chain as well as vectors and host calls comprising the polynucleotide, polypeptides encoded thereby and antibodies specifically binding to the polypeptides. Moreover, the invention relates to medicaments comprising the polynucleotides and polypeptides as well as specific therapeutic applications thereof. Furthermore, the present invention contemplates methods for the manufacture of the polypeptides and medicaments.

Abstract: This invention relates to novel recombinant clostridial neurotoxins exhibiting increased duration of effect and to methods for the manufacture of such recombinant clostridial neurotoxins. These novel recombinant clostridial neurotoxins comprise a random coil domain, and the methods comprise the steps of inserting a nucleic acid sequence coding for a random coil domain into a nucleic acid sequence coding for a parental clostridial neurotoxin and expression of the recombinant nucleic acid sequence comprising the random coil domain-coding sequence in a host cell. The invention further relates to novel recombinant single-chain precursor clostridial neurotoxins used in such methods, nucleic acid sequences encoding such recombinant single-chain precursor clostridial neurotoxins, and pharmaceutical compositions comprising the recombinant clostridial neurotoxin with increased duration of effect.

Abstract: The invention relates to a modified botulinum toxin comprising a natural heavy chain and a modified light chain, characterized in that the modification of the light chain resides in that it comprises (i) an extension of the chain on its N-terminus which has the structure -(C)n-(tag)m-(X)l- in the direction from the N- to the C-terminal end, wherein C represents a cysteine residue, tag represents any tag and X represents the residue of any naturally occurring amino acid, n represents an integer from 1 to 50, m represents 0 or 1, and l represents 0 or an integer from 1 to 50, and in that (ii) at least one of the cysteine residues in the extension of the chain is coupled to at least one chain of PEG.

Abstract: The invention relates to a modified botulinum toxin comprising a natural heavy chain and a modified light chain, characterized in that the modification of the light chain resides in that it comprises (i) an extension of the chain on its N-terminus which has the structure -(C)n-(tag)m-(X)l- in the direction from the N- to the C-terminal end, wherein C represents a cysteine residue, tag represents any tag and X represents the residue of any naturally occurring amino acid, n represents an integer from 1 to 50, m represents 0 or 1, and l represents 0 or an integer from 1 to 50, and in that (ii) at least one of the cysteine residues in the extension of the chain is coupled to at least one chain of PEG.

Abstract: The invention relates to a modified botulinum toxin comprising a natural heavy chain and a modified light chain, characterized in that the modification of the light chain resides in that it comprises (i) an extension of the chain on its N-terminus which has the structure —(C)n-(tag)m-(X)l— in the direction from the N- to the C-terminal end, wherein C represents a cysteine residue, tag represents any tag and X represents the residue of any naturally occurring amino acid, n represents an integer from 1 to 50, m represents 0 or 1, and l represents 0 or an integer from 1 to 50, and in that (ii) at least one of the cysteine residues in the extension of the chain is coupled to at least one chain of PEG.