US 11,530,266 B2Granted

Anti-podoplanin antibody

AssigneeJapanese Foundation for Cancer Research

InventorsNobuhiko Gyobu, Naoya Fujita, Mamoru Kakino, Ai Kawashima, Shinya Fujihara, Naoki Goda

Life of this patent

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Abstract

The object of the present invention is to provide a humanized or mouse-human chimeric anti-podoplanin antibody or an antibody fragment containing the antigen-binding region thereof, and the object is achieved by providing an isolated humanized or mouse-human chimeric anti-podoplanin antibody which comprises a predetermined amino acid sequence, or an antibody fragment containing the antigen-binding region thereof.

Claims12

Dependent claims

An isolated humanized anti-podoplanin antibody, or an antibody fragment thereof, comprising an antigen-binding region, which comprises a variable region comprising the amino acid sequence I or II below,

the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 in the following amino acid sequence I optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NOs:
7 to 14 below, respectively, and
the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 in the following amino acid sequence II optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NOs:
7, 15, 16, 10 to 14 below, respectively;
wherein, in the amino acid sequence I,
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
7,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
8,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
9,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
10,
the amino acid sequence of the light-chain FR1 is the amino acid sequence represented by SEQ ID NO:
11,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
12,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
13, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
14;
and
wherein, in the amino acid sequence II
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
7,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
15,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
16,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
10,
the amino acid sequence of the light-chain FR1 is the amino acid sequence represented by SEQ ID NO:
11,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
12,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
13, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
14,
wherein said anti-podoplanin antibody and antigen-binding region thereof specifically bind to the PLAG4 domain of human podoplanin.

61 more elements

An isolated mouse-human chimeric anti-podoplanin antibody, or an antibody fragment thereof, comprising an antigen-binding region, which comprises variable regions comprising the following amino acid sequences,

the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NO:
17 to 24 below, respectively,
wherein
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
17,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
18,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
19,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
20,
the amino acid sequence of the light-chain FR1 is the amino acid sequence represented by SEQ ID NO:
21,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
22,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
23, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
24,
wherein said anti-podoplanin antibody and antigen-binding region thereof specifically bind to the PLAG4 domain of human podoplanin.

29 more elements

A method of inhibiting the binding between podoplanin and CLEC-2, the method comprising the step of administering

an isolated humanized anti-podoplanin antibody, or an antibody fragment thereof, comprising an antigen-binding region which comprises a variable region comprising the amino acid sequence I or II below,
the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 in the following amino acid sequence I optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NOs:
7 to 14 below, respectively, and
the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 in the following amino acid sequence II optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NOs:
7, 15, 16, 10 to 14 below, respectively;
wherein in the amino acid sequence I,
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
7,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
8,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
9,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
10,
the amino acid sequence of the light-chain FR1 is the amino acid sequence represented by SEQ ID NO:
11,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
12,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
13, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
14;
and
wherein, in the amino acid sequence II,
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
7,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
15,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
16,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
10,
the amino acid sequence of the light-chain FRI is the amino acid sequence represented by SEQ ID NO:
11,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
12,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
13, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
14,
to a human subject,
wherein said anti-podoplanin antibody and antigen-binding region thereof specifically bind to the PLAG4 domain of human podoplanin.

63 more elements

A pharmaceutical composition, comprising, an effective amount for specifically binding to podoplanin of an isolated humanized anti-podoplanin antibody or an antibody fragment thereof, containing an antigen-binding region which comprises a variable region comprising the amino acid sequence I or II below,

the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 in the following amino acid sequence I optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NOs:
7 to 14 below, respectively, and
the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 in the following amino acid sequence II optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NOs:
7, 15, 16, 10 to 14 below, respectively;
wherein in the amino acid sequence I,
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
7,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
8,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
9,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
10,
the amino acid sequence of the light-chain FRI is the amino acid sequence represented by SEQ ID NO:
11,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
12,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
13, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
14;
and
wherein, in the amino acid sequence II,
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
7,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
15,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
16,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
10,
the amino acid sequence of the light-chain FRI is the amino acid sequence represented by SEQ ID NO:
11,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
12,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
13, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
14;
and a pharmaceutically acceptable carrier,
wherein said anti-podoplanin antibody and antigen-binding region thereof specifically bind to the PLAG4 domain of human podoplanin.

62 more elements

A method of inhibiting the binding between podoplanin and CLEC-2, the method comprising the step of administering

an isolated mouse-human chimeric anti-podoplanin antibody, or an antibody fragment thereof, comprising an antigen-binding region, which comprises variable regions comprising the following amino acid sequences,
the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NO:
17 to 24 below, respectively,
wherein
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
17,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
18,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
19,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
20,
the amino acid sequence of the light-chain FRI is the amino acid sequence represented by SEQ ID NO:
21,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
22,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
23, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
24, to a human subject,
wherein said anti-podoplanin antibody and antigen-binding region thereof specifically bind to the PLAG4 domain of human podoplanin.

30 more elements

A pharmaceutical composition, comprising:

an effective amount for specifically binding to podoplanin of an isolated mouse-human chimeric anti-podoplanin antibody, or an antibody fragment thereof, comprising an antigen-binding region, which comprises variable regions comprising the following amino acid sequences,
the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NO:
17 to 24 below, respectively,
wherein
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
17,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
18,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
19,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
20,
the amino acid sequence of the light-chain FR1 is the amino acid sequence represented by SEQ ID NO:
21,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
22,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
23, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
24,
and a pharmaceutically acceptable carrier,
wherein said anti-podoplanin antibody and antigen-binding region thereof specifically bind to the PLAG4 domain of human podoplanin.

31 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/626,162Filed 14 Jun 2019
Priority: JP JP2019-04886115 Mar 2019
Published: US 2021/0403555 A130 Dec 2021
Granted: 20 Dec 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
C07K 16/2803
Against receptors, cell surface antigens or cell surface determinants: against the immunoglobulin superfamily
A61K 39/395
Medicinal preparations containing antigens or antibodies: antibodies ; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Family

US 2021/0403555 A1Pre-grant publication · published 30 Dec 2021
US 11,530,266 B2This patent

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

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Abstract

the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 in the following amino acid sequence I optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NOs:
7 to 14 below, respectively, and
the amino acid sequences of the heavy-chain FRs 1 to 4 and the light-chain FRs 1 to 4 in the following amino acid sequence II optionally have a sequence identity of not less than 90% to the amino acid sequences represented by SEQ ID NOs:
7, 15, 16, 10 to 14 below, respectively;
wherein, in the amino acid sequence I,
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
7,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
8,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
9,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
10,
the amino acid sequence of the light-chain FR1 is the amino acid sequence represented by SEQ ID NO:
11,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
12,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
13, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
14;
and
wherein, in the amino acid sequence II
the amino acid sequence of the heavy-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
1,
the amino acid sequence of the heavy-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
2,
the amino acid sequence of the heavy-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
3,
the amino acid sequence of the light-chain CDR1 is the amino acid sequence represented by SEQ ID NO:
4,
the amino acid sequence of the light-chain CDR2 is the amino acid sequence represented by SEQ ID NO:
5,
the amino acid sequence of the light-chain CDR3 is the amino acid sequence represented by SEQ ID NO:
6,
the amino acid sequence of the heavy-chain FR1 is the amino acid sequence represented by SEQ ID NO:
7,
the amino acid sequence of the heavy-chain FR2 is the amino acid sequence represented by SEQ ID NO:
15,
the amino acid sequence of the heavy-chain FR3 is the amino acid sequence represented by SEQ ID NO:
16,
the amino acid sequence of the heavy-chain FR4 is the amino acid sequence represented by SEQ ID NO:
10,
the amino acid sequence of the light-chain FR1 is the amino acid sequence represented by SEQ ID NO:
11,
the amino acid sequence of the light-chain FR2 is the amino acid sequence represented by SEQ ID NO:
12,
the amino acid sequence of the light-chain FR3 is the amino acid sequence represented by SEQ ID NO:
13, and
the amino acid sequence of the light-chain FR4 is the amino acid sequence represented by SEQ ID NO:
14,
wherein said anti-podoplanin antibody and antigen-binding region thereof specifically bind to the PLAG4 domain of human podoplanin.

61 more elements

Facts

Application

16/626,162Filed 14 Jun 2019

Priority

JP JP2019-04886115 Mar 2019

Published

US 2021/0403555 A130 Dec 2021

Granted

20 Dec 2022

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
C07K 16/2803
Against receptors, cell surface antigens or cell surface determinants: against the immunoglobulin superfamily
A61K 39/395
Medicinal preparations containing antigens or antibodies: antibodies ; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors