US 11,952,601 B2
Recombinant botulinum toxin with increased duration of effect
Fred Hofmann, Potsdam (DE); Marcel Jurk, Berlin (DE); Manuela López De La Paz, Liederbach am Taunus (DE); Daniel Scheps, Potsdam (DE); and Jürgen Frevert, Berlin (DE)
Assigned to MERZ PHARMA GMBH & CO. KGAA, Frankfurt am Main (DE)
Appl. No. 16/498,193
Filed by MERZ PHARMA GMBH & CO. KGAA, Frankfurt am Main (DE)
PCT Filed Jun. 20, 2017, PCT No. PCT/EP2017/065096
§ 371(c)(1), (2) Date Sep. 26, 2019,
PCT Pub. No. WO2018/233813, PCT Pub. Date Dec. 27, 2018.
Prior Publication US 2020/0048624 A1, Feb. 13, 2020
Int. Cl. C07K 14/33 (2006.01); A61K 8/66 (2006.01); A61K 38/16 (2006.01); C12N 9/52 (2006.01); C12N 15/52 (2006.01); C12N 15/70 (2006.01); A61K 38/00 (2006.01)
CPC C12N 9/52 (2013.01) [A61K 8/66 (2013.01); C12Y 304/24069 (2013.01); A61K 38/00 (2013.01); C07K 2319/31 (2013.01)] 16 Claims
OG exemplary drawing
 
1. A recombinant botulinum neurotoxin comprising: a functionally active botulinum neurotoxin light chain, a functionally active botulinum neurotoxin heavy chain, and at least one domain, wherein the botulinum neurotoxin is selected from Clostridium botulinum neurotoxin serotype A, E, and C; wherein said at least one domain consists of 100-500 amino acid residues consisting of a plurality of amino acid repeats consisting of proline, alanine, serine, threonine, glycine and glutamate residues, wherein no more than six consecutive amino acid residues are identical, and wherein said at least one domain comprises the amino acid sequence of SEQ ID NO: 1, wherein said at least one domain is inserted at a position selected from (i) the N-terminus of the functionally active botulinum neurotoxin light chain, (ii) the C-terminus of the functionally active botulinum neurotoxin light chain, (iii) the N-terminus of the functionally active botulinum neurotoxin heavy chain, or (iv) the C-terminus of the functionally active botulinum neurotoxin heavy chain, and wherein the recombinant botulinum neurotoxin exhibits an increased duration of effect without a delayed onset of effect relative to a wild type botulinum neurotoxin without said at least one domain.