Novel anti-transferrin receptor antibody that passes through blood-brain barrier

Patent metadata

Field	Value
Publication number	US-2016369001-A1
Application number	US-201415107839-A
Country	US
Kind code	A1
Filing date	Dec 24, 2014
Priority date	Dec 25, 2013
Publication date	Dec 22, 2016
Grant date	—

Abstract

Disclosed are novel anti transferrin receptor antibody that can pass through the blood-brain barrier, a fusion protein comprising a protein necessary to be brought into function in the central nervous system and the antibody, and method of their production. The fusion protein comprises amino acid sequences of an anti-human transferrin receptor antibody that recognizes an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, and 3, and of other protein that is bound thereto on the C- terminal side.

First claim

1 . An anti-human transferrin receptor antibody that recognizes an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, and 3.

2 . The anti-human transferrin receptor antibody according to claim 1 that recognizes a partial sequence consisting of at least ten consecutive amino acid residues occurring in the amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, and 3.

3 . The anti-human transferrin receptor antibody according to claim 1 , wherein the anti-human transferrin receptor antibody is a single-chain antibody comprising
an amino acid sequence comprising the whole or part of the variable region of the light chain, an amino acid sequence that is bound thereto on the C-terminal side and consists of 15-25 amino acid residues as a first linker sequence, and further an amino acid sequence that is bound thereto on the C-terminal side and comprises the whole or part of the variable region of the heavy chain.

4 . The anti-human transferrin receptor antibody according to claim 3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 5, 6 and 7.

5 . A fusion protein comprising an anti-human transferrin receptor antibody according to claim 1 and an amino acid sequence of other protein that is bound thereto on the C-terminal side.

6 . A fusion protein comprising an anti-human transferrin receptor antibody according to one of claim 1 and an amino acid sequence that is bound thereto on the C-terminus and consists of 3-50 amino acid residues as a second linker sequence, and further
an amino acid sequence of the said other protein that is bound thereto on the C-terminus.

7 . The fusion protein according to claim 5 , wherein the said other protein is a lysosomal enzyme.

8 . The fusion protein according to claim 7 , wherein the lysosomal enzyme is human iduronate 2-sulfatase

9 . A DNA encoding an anti-human transferrin receptor antibody according to claim 1 .

10 . A DNA encoding the fusion protein according to claim 5 .

11 . A mammalian expression vector comprising the DNA according to claim 10 incorporated therein.

12 . A mammalian cell transformed with the mammalian expression vector according to claim 11 .

13 . The cell according to claim 12 , wherein the mammalian cell is a CHO cell.

Assignees

• Japan Chem Res

Inventors

• Sonoda Hiroyuki
• Morimoto Hideto
• Koshimura Yuri
• Kinoshita Masafumi
• Takagi Haruna
• Yoshii Yoshiko

Classifications

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K16/2881 Primary

  against CD71 · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C12Y301/06013

  Iduronate-2-sulfatase (3.1.6.13) · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title