	US 12,215,142 B2
	Antibody fragment degrading and removing abnormal TDP-43
Makoto Urushitani, Otsu (JP); and Yoshitaka Tamaki, Otsu (JP)
Assigned to NATIONAL UNIVERSITY CORPORATION SHIGA UNIVERSITY OF MEDICAL SCIENCE, Otsu (JP)
Appl. No. 16/980,667
Filed by NATIONAL UNIVERSITY CORPORATION SHIGA UNIVERSITY OF MEDICAL SCIENCE, Otsu (JP)
PCT Filed Mar. 15, 2019, PCT No. PCT/JP2019/010771 § 371(c)(1), (2) Date Sep. 14, 2020, PCT Pub. No. WO2019/177138, PCT Pub. Date Sep. 19, 2019.
Claims priority of application No. 2018-049752 (JP), filed on Mar. 16, 2018.
Prior Publication US 2021/0024621 A1, Jan. 28, 2021
Int. Cl. C07K 16/18 (2006.01); A61P 25/28 (2006.01); A61K 39/00 (2006.01); A61K 48/00 (2006.01)

CPC C07K 16/18 (2013.01) [A61P 25/28 (2018.01); A61K 2039/505 (2013.01); A61K 48/00 (2013.01); C07K 2317/24 (2013.01); C07K 2317/565 (2013.01); C07K 2317/567 (2013.01); C07K 2317/622 (2013.01); C07K 2317/76 (2013.01); C07K 2317/94 (2013.01)]

6 Claims

1. A modified antibody fragment that binds to misfolded TAR DNA-binding protein of 43 kDa, wherein the modified antibody fragment comprises an antibody fragment and a chaperone-mediated autophagy localizing signal peptide comprising KFREQ (SEQ ID NO: 8) and linked to the C-terminus of the antibody fragment;

the antibody fragment comprising:

a heavy-chain variable region comprising a heavy-chain CDR 1 consisting of an amino acid sequence GFNIKDYY (SEQ ID NO: 1), a heavy-chain CDR 2 consisting of an amino acid sequence IDPEDGET (SEQ ID NO: 2), and a heavy-chain CDR 3 consisting of an amino acid sequence TIIYYYGSRYVDY (SEQ ID NO: 3); and

a light-chain variable region comprising a light-chain CDR 1 consisting of an amino acid sequence SSISSSY (SEQ ID NO: 4), a light-chain CDR 2 consisting of an amino acid sequence RTS, and a light-chain CDR 3 consisting of an amino acid sequence QQGSSIPLT (SEQ ID NO: 5); and

wherein the antibody fragment is a scFv; and

wherein the antibody fragment and the chaperone-mediated autophagy localizing signal peptide are directly bonded, or an amino acid sequence exists between them.