Novel Anti-Human Transferrin Receptor Antibody Capable of Penetrating Blood-Brain Barrier

Patent metadata

Field	Value
Publication number	US-2020317798-A1
Application number	US-202016909398-A
Country	US
Kind code	A1
Filing date	Jun 23, 2020
Priority date	Dec 26, 2016
Publication date	Oct 8, 2020
Grant date	—

Abstract

Provided is an anti-human transferrin receptor antibody or an analog thereof, wherein in the heavy chain variable region of the antibody, (a) CDR1 comprises the amino acid sequence set forth as SEQ ID NO: 62 or SEQ ID NO: 63, (b) CDR2 comprises the amino acid sequence set forth as SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 comprises the amino acid sequence set forth as SEQ ID NO: 15 or SEQ ID NO: 16, and an analogue thereof.

First claim

1 . An anti-human transferrin receptor antibody, wherein in the heavy chain variable region of the antibody, wherein
(a) CDR1 comprises the amino acid sequence of SEQ ID NO: 62 or SEQ ID NO: 63, (b) CDR2 comprises the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 14, and (c) CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO: 16.

2 - 79 . (canceled)

80 . The antibody according to claim 1 , wherein the framework region 3 of the heavy chain comprises the amino acid sequence of SEQ ID NO: 64.

81 . The antibody according to claim 1 , wherein in the heavy chain variable region,
the CDR2 comprises an amino acid sequence having sequence identity not lower than 80% to the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 14, in place thereof, and the CDR3 comprises an amino acid sequence having sequence identity not lower than 80% to the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO: 16, in place thereof.

82 . The antibody according to claim 1 , wherein in the heavy chain variable region,
the CDR2 comprises an amino acid sequence having sequence identity not lower than 90% to the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 14, in place thereof, and the CDR3 comprises an amino acid sequence having sequence identity not lower than 90% to the amino acid sequence of SEQ ID NO: 15 or SEQ ID NO: 16, in place thereof.

83 . The antibody according to claim 1 , wherein the heavy chain variable region comprises an amino acid sequence modified from at least one amino acid sequence of
(a) SEQ ID NO: 62 or SEQ ID NO: 63 as to the CDR1, (b) SEQ ID NO: 13 or SEQ ID NO: 14 as to the CDR2, (c) SEQ ID NO: 15 or SEQ ID NO: 16 as to the CDR3, and (d) SEQ ID NO: 64 as to the framework region 3,
by the substitution, deletion or addition of 1 to 5 amino acids, in place thereof,
wherein in the CDR1, methionine positioned at position 5 from the N-terminal side of the amino acid sequence of SEQ ID NO: 62 or SEQ ID NO: 63 is also located at the same position in the amino acid sequence thus modified, and
in the framework region 3, leucine positioned at position 17 from the N-terminal side of SEQ ID NO: 64 is also located at the same position in the amino acid sequence thus modified.

84 . The antibody according to claim 1 , wherein the heavy chain variable region comprises an amino acid sequence modified from at least one amino acid sequence of
(a) SEQ ID NO: 62 or SEQ ID NO: 63 as to the CDR1, (b) SEQ ID NO: 13 or SEQ ID NO: 14 as to the CDR2, (c) SEQ ID NO: 15 or SEQ ID NO: 16 as to the CDR3, and (d) SEQ ID NO: 64 as to the framework region 3,
by the substitution, deletion or addition of 1 to 3 amino acids, in place thereof,
wherein in the CDR1, methionine positioned at position 5 from the N-terminal side of the amino acid sequence of SEQ ID NO: 62 or SEQ ID NO: 63 is also located at the same position in the amino acid sequence thus modified, and
in the framework region 3, leucine positioned at position 17 from the N-terminal side of SEQ ID NO: 64 is also located at the same position in the amino acid sequence thus modified.

85 . The antibody according to claim 80 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 65.

86 . The antibody according to claim 85 , wherein the heavy chain variable region comprises, in a portion except for the amino acid sequences of SEQ ID NO: 62 or SEQ ID NO: 63 of the CDR1 and SEQ ID NO: 64 of the framework region 3, an amino acid sequence having sequence identity not lower than 80% to the portion in place of the portion.

87 . The antibody according to claim 85 , wherein the heavy chain variable region comprises, in a portion except for the amino acid sequences of SEQ ID NO: 62 or SEQ ID NO: 63 of the CDR1 and SEQ ID NO: 64 of the framework region 3, an amino acid sequence having sequence identity not lower than 90% to the portion in place of the portion.

88 . The antibody according to claim 85 , wherein the antibody comprises an amino acid sequence modified from the amino acid sequence constituting the heavy chain variable region, by the substitution, deletion or addition of 1 to 5 amino acids, in place thereof,
wherein in the CDR1, methionine positioned at position 5 from the N-terminus of the amino acid sequence of SEQ ID NO: 63 is also located at the same position in the amino acid sequence thus modified, and in the framework region 3, leucine positioned at position 17 from the N-terminal side of SEQ ID NO: 64 is also located at the same position in the amino acid sequence thus modified.

89 . The antibody according to claim 85 , wherein the antibody comprises an amino acid sequence modified from the amino acid sequence constituting the heavy chain variable region, by the substitution, deletion or addition of 1 to 3 amino acids, in place thereof,
wherein in the CDR1, methionine positioned at position 5 from the N-terminus of the amino acid sequence of SEQ ID NO: 63 is also located at the same position in the amino acid sequence thus modified, and in the framework region 3, leucine positioned at position 17 from the N-terminal side of SEQ ID NO: 64 is also located at the same position in the amino acid sequence thus modified.

90 . The antibody according to claim 85 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 66 or SEQ ID NO: 68.

91 . The antibody according to claim 90 , wherein the heavy chain comprises an amino acid sequence having sequence identity not lower than 80% to a portion except for the amino acid sequences of SEQ ID NO: 62 or SEQ ID NO: 63 of the CDR1 and SEQ ID NO: 64 of the framework region 3, in place of the portion.

92 . The antibody according to claim 90 , wherein the heavy chain comprises an amino acid sequence having sequence identity not lower than 90% to a portion except for the amino acid sequences of SEQ ID NO: 62 or SEQ ID NO: 63 of the CDR1 and SEQ ID NO: 64 of the framework region 3, in place of the portion.

93 . The antibody according to claim 90 , wherein the antibody comprises an amino acid sequence modified from the amino acid sequence constituting the heavy chain, by the substitution, deletion or addition of 1 to 5 amino acids, in place thereof, wherein in the CDR1, methionine positioned at position 5 from the N-terminus of the amino acid sequence of SEQ ID NO: 63 is also located at the same position in the amino acid sequence thus modified, and in the framework region 3, leucine positioned at position 17 from the N-terminal side of SEQ ID NO: 64 is also located at the same position in the amino acid sequence thus modified.

94 . The antibody according to claim 90 , wherein the antibody comprises an amino acid sequence modified from the amino acid sequence constituting the heavy chain, by the substitution, deletion or addition of 1 to 3 amino acids, in place thereof, wherein in the CDR1, methionine positioned at position 5 from the N-terminus of the amino acid sequence of SEQ ID NO: 63 is also located at the same position in the amino acid sequence thus modified, and in the framework region 3, leucine positioned at position 17 from the N-terminal side of SEQ ID NO: 64 is also located at the same position in the amino acid sequence thus modified.

95 . The antibody according to claim 1 , wherein in the light chain variable region of the antibody,
(a) CDR1 comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7, (b) CDR2 comprises the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 9, or the amino acid sequence Lys-Val-Ser, and (c) CDR3 comprises the amino aci

Assignees

• Japan Chem Res

Inventors

• Sonoda Hiroyuki
• Takahashi Kenichi

Classifications

• C12Y310/01001

  N-Sulfoglucosamine sulfohydrolase (3.10.1.1) · CPC title

• C12N9/14

  Hydrolases (3) · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2319/33

  fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies · CPC title

• C07K16/2881 Primary

  against CD71 · CPC title