US 12,435,328 B2
Therapeutic enzyme fusion protein having a novel structure and use thereof
Eui Joon Jung, Hwaseong-si (KR); Jin Young Kim, Hwaseong-si (KR); In Young Choi, Hwaseong-si (KR); and Sung Youb Jung, Hwaseong-si (KR)
Assigned to HANMI PHARM. CO., LTD., Hwaseong-si (KR)
Appl. No. 16/955,525
Filed by HANMI PHARM. CO., LTD., Hwaseong-si (KR)
PCT Filed Dec. 21, 2018, PCT No. PCT/KR2018/016487
§ 371(c)(1), (2) Date Jun. 18, 2020,
PCT Pub. No. WO2019/125059, PCT Pub. Date Jun. 27, 2019.
Claims priority of application No. 10-2017-0178378 (KR), filed on Dec. 22, 2017.
Prior Publication US 2021/0009984 A1, Jan. 14, 2021
Int. Cl. C12N 9/62 (2006.01); C12N 9/38 (2006.01); C12N 9/40 (2006.01); C12N 9/96 (2006.01); A61K 38/00 (2006.01); C12N 15/62 (2006.01)
CPC C12N 9/96 (2013.01) [C12N 9/2465 (2013.01); C12N 9/2471 (2013.01); A61K 38/00 (2013.01); C07K 2319/30 (2013.01); C12N 15/62 (2013.01); C12Y 302/01022 (2013.01); C12Y 302/01023 (2013.01)] 8 Claims
 
1. An enzyme fusion protein of the following Formula 1:

OG Complex Work Unit Chemistry
wherein X and X′ are the same each other and each independently an enzyme and the enzyme forms a dimer through a non-covalent bond;
L and L′ are the same or different from each other, and are a peptide linker consisting of 10 to 50 amino acid residues;
F is an immunoglobulin Fc region obtained from immunoglobulin G4 (IgG4) and the immunoglobulin Fc region is in a monomer form;
| is a covalent bond; and
: is a non-covalent bond,
wherein the enzyme is selected from the group consisting of beta-glucosidase, alpha-galactosidase, beta-galactosidase, iduronidase, iduronate-2-sulfatase, galactose-6-sulfatase, acid alpha-glucosidase, acid ceramidase, acid sphingomyelinase, galactocerebrosidase, arylsulfatase A, B, beta-hexosaminidase A, B, heparin N-sulfatase, alpha-D-mannosidase, beta-glucuronidase, N-acetylgalactosamine-6 sulfatase, lysosomal acid lipase, alpha-N-acetyl-glucosaminidase, glucocerebrosidase, butyrylcholinesterase, chitinase, glutamate decarboxylase, imiglucerase, lipase, uricase, platelet-activating factor acetylhydrolase, neutral endopeptidase, and myeloperoxidase,
wherein the immunoglobulin Fc region comprises the amino acid sequence of SEQ ID NO: 8, wherein serine at position 2 is substituted with proline; or asparagine at position 71 is substituted with glutamine; or serine at position 2 is substituted with proline and asparagine at position 71 is substituted with glutamine.