# US 2013/0156747 A1 · PEGylated Mutated Clostridium botulinum Toxin > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0156747 A1 - Document ID: US20130156747A1 - Status: Published application - Kind: A1 - Application number: 13/624,493 - Filed: 2012-09-21 - Published: 2013-06-20 - Earliest claimed: 2006-03-15 - Assignees: MERZ PHARMA GmbH & CO. KGaA - Inventors: Jürgen FREVERT; Volker Specht - Web page: https://patentgrep.com/patent/US20130156747A1 ## CPC - A61K 39/08: Clostridium, e.g. Clostridium tetani - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis - A61P 1/06: Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia - A61P 17/00: Drugs for dermatological disorders - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia - A61P 27/02: Ophthalmic agents - C07K 14/33: from Clostridium (G) - C12N 9/96: Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## 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. ## Claims ### Claim at position 1 1-22. (canceled) ### Claim 23 A pharmaceutical composition comprising a modified botulinum toxin, the modified botulinum toxin comprising a natural heavy chain and a modified light chain, wherein the light chain comprises at least one and at most 20 amino acid residues occurring naturally at its N-terminus being mutated to a cysteine residue, and at least one chain of PEG coupled to at least one cysteine residue in said 20 amino acid residues at said N-terminus. ### Claim 24 (depends on 23) The pharmaceutical composition according to claim 23, wherein the composition is stabilized without addition of human serum albumin (HSA). ### Claim 25 (depends on 23) The pharmaceutical composition according to claim 23, wherein the composition is in lyophilized form. ### Claim 26 (depends on 23) The pharmaceutical composition according to claim 23, wherein the composition is in liquid form. ### Claim 27 (depends on 23) The pharmaceutical composition according to claim 23, wherein the composition is formulated for intramuscular injection. ### Claim 28 (depends on 24) The pharmaceutical composition according to claim 24, wherein the composition is in lyophilized form. ### Claim 29 (depends on 24) The pharmaceutical composition according to claim 24, wherein the composition is in liquid form. ### Claim 30 (depends on 24) The pharmaceutical composition according to claim 24, wherein the composition is formulated for intramuscular injection. ### Claim 31 A method of treating dystonia or for removing facial wrinkles, the method comprising treatment of a subject with a modified botulinum toxin, the modified botulinum toxin comprising a natural heavy chain and a modified light chain, characterized in that the modification of the light chain (i) comprises 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. ### Claim 32 (depends on 31) The method according to claim 31, wherein the dystonia is a spasmodic dysphonia, a laryngeal dystonia, a cervical dystonia, a focal hand dystonia, a blepharospasm, a strabism, a cerebral paresis, a hemifacial spasm, spasticity, a spasmodic colitis, animus, TICS, tremor, bruxism, an anal fissure, an achalasia, a dysphagia, or a hyperhidrosis.