US 10,882,906 B2Granted

Claudin 5 antibody, and medicine containing said antibody

AssigneeOsaka University

InventorsYoshiaki Okada, Masuo Kondoh, Yosuke Hashimoto, Keisuke Shirakura, Takefumi Doi, Kiyohito Yagi, Hiroyuki Takeda, Tatsuya Sawasaki

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Abstract

Provided is a novel technique for controlling the blood-brain barrier. An antibody whose epitope is a region within an extracellular domain of Claudin 5 protein.

Claims15

Dependent claims

An antibody whose epitope is a region within an extracellular domain of Claudin 5 protein and wherein the antibody is selected from the group consisting of the following antibodies A to I:

(A) antibody A comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
1,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
2, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
3;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
5,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
6, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
7;
(B) antibody B comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO;
9,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
10, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
11, and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
13,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
14, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
15;
(C) antibody C comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
17,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
18, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
19;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
21,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
22, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
23;
(D) antibody D comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
25,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
26, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
27;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
29,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
30, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
31;
(E) antibody E comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
33,
heavy-chain CDR2 comprising the amino add sequence represented by SEQ ID NO:
34, and
heavy-chain CDR3 comprising the amino add sequence represented by SEQ ID NO:
35;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino add sequence represented by SEQ ID NO:
37,
light-chain CDR2 comprising the amino add sequence represented by SEQ ID NO:
38, and
light-chain CDR3 comprising the amino add sequence represented by SEQ ID NO:
39;
(F) antibody F comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
41,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
42, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
43;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
45,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
46, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
47;
(G) antibody G comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
49,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
50, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
51;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
53,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
54, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
55;
(H) antibody H comprising:
a heavy chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
57,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
58, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
59;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
61,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
62, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
63;
and
(I) antibody I comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
65,
heavy chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
66, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
67;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
69,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
70, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
71.

141 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/467,751Filed 4 Dec 2017
Priority: JP 2016-2373707 Dec 2016
Published: US 2020/0223915 A116 Jul 2020
Granted: 5 Jan 2021
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

A61P 35/00
Antineoplastic agents
C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
A61K 39/395
Medicinal preparations containing antigens or antibodies: antibodies ; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines

Family

US 2020/0223915 A1Pre-grant publication · published 16 Jul 2020
US 10,882,906 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Provided is a novel technique for controlling the blood-brain barrier. An antibody whose epitope is a region within an extracellular domain of Claudin 5 protein.

An antibody whose epitope is a region within an extracellular domain of Claudin 5 protein and wherein the antibody is selected from the group consisting of the following antibodies A to I:

(A) antibody A comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
1,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
2, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
3;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
5,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
6, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
7;
(B) antibody B comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO;
9,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
10, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
11, and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
13,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
14, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
15;
(C) antibody C comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
17,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
18, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
19;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
21,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
22, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
23;
(D) antibody D comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
25,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
26, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
27;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
29,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
30, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
31;
(E) antibody E comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
33,
heavy-chain CDR2 comprising the amino add sequence represented by SEQ ID NO:
34, and
heavy-chain CDR3 comprising the amino add sequence represented by SEQ ID NO:
35;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino add sequence represented by SEQ ID NO:
37,
light-chain CDR2 comprising the amino add sequence represented by SEQ ID NO:
38, and
light-chain CDR3 comprising the amino add sequence represented by SEQ ID NO:
39;
(F) antibody F comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
41,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
42, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
43;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
45,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
46, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
47;
(G) antibody G comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
49,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
50, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
51;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
53,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
54, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
55;
(H) antibody H comprising:
a heavy chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
57,
heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
58, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
59;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
61,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
62, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
63;
and
(I) antibody I comprising:
a heavy-chain variable region comprising:
heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
65,
heavy chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
66, and
heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
67;
and
a light-chain variable region comprising:
light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO:
69,
light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO:
70, and
light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO:
71.

141 more elements

Facts

Application

16/467,751Filed 4 Dec 2017

Priority

JP 2016-2373707 Dec 2016

Published

US 2020/0223915 A116 Jul 2020

Granted

5 Jan 2021

Term ends

Not estimatedThe source records don’t support an estimate.

Classification17 codes

A61P 35/00
Antineoplastic agents
C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
A61K 39/395
Medicinal preparations containing antigens or antibodies: antibodies ; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines