IP Library › Granted Patent US 10,435,466
Granted Patent B2
US 10,435,466 · App. 15/521,514 · Granted Oct 8, 2019

Anti-TIM-3 antibodies

Inventors: Cheng-i Wang (Singapore, SG); Hsueh Ling Janice Oh (Singapore, SG); Siok Ping Yeo (Singapore, SG); Yun Pei Sharon Goh (Singapore, SG)
Assignee: Agency for Science, Technology and Research
C07K16/2803A61K39/395C07K16/2809C07K16/28C07K2317/31C07K2317/622
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Quick Facts
Patent No.
US 10,435,466
App. No.
15/521,514
Granted
Oct 8, 2019
Kind
B2
Abstract

Anti-TIM-3 antibodies are disclosed, as well as pharmaceutical compositions comprising such antibodies, and uses and methods using the same, such as in the treatment of cancer or infectious disease or T-cell dysfunctional disorders. Bispecific antibodies against TIM-3 and other targets are also disclosed, with a preferred embodiment of a bispecific antibody against TIM-3 and CD3.

Claims (261)

1. An antibody that binds to TIM-3 or an antigen binding fragment of the antibody having:

(i) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 12)

EAWDYYVAAGY;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 30)

GYVAGSDA;

OR

(ii) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 13)

DSWDSADASGV;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 33)

GYVAGFDD;

OR

(iii) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 14)

DSWDYDYAAGV;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 34)

GYVAGFDS;

OR

(iv) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 15)

DSWDSYLAAGV;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 35)

GYVAGYDY;

OR

(v) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 16)

ESWDYDYASGV;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 36)

GYVAGSDA;

OR

(vi) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 17)

DSWDSSDSSGV;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 37)

GYVAGFDS;

OR

(vii) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 18)

EAWDSAYAAGS;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 38)

GYYAGDDY;

OR

(viii) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 19)

DSWDAALSAGV;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 39)

GYVAGYDY;

OR

(ix) at least one light chain variable region incorporating the following CDRs:

LC-CDR1:

(SEQ ID NO: 10)

SGSSSNIGNNYVS

LC-CDR2:

(SEQ ID NO: 11)

GNNWRPS

LC-CDR3:

(SEQ ID NO: 20)

ESWADAAAAAGY;

and

at least one heavy chain variable region incorporating the following CDRs:

HC-CDR1:

(SEQ ID NO: 61)

GYYWS,

or

(SEQ ID NO: 30)

GGSFSGYYWS

HC-CDR2:

(SEQ ID NO: 31)

EINHSGSTNYNPSLKS

HC-CDR3:

(SEQ ID NO: 40)

GYVAGSDA.

2. The TIM-3 binding antibody or the antigen binding fragment of the antibody of claim 1 , comprising a heavy chain and a light chain variable region sequence, wherein:

the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of one of SEQ ID NOs: 21 to 29 ( FIG. 2 ), and

the light chain sequence has at least 85% sequence identity to the light chain sequence of one of: SEQ ID NO:1 to 9 ( FIG. 1 ).

3. The TIM-3 binding antibody or the antigen binding fragment of the antibody of claim 1 , which is a bispecific antibody or a bispecific antigen binding fragment of the antibody, further comprising an antigen binding domain which binds to a target protein other than TIM-3.

4. The TIM-3 binding antibody or the antigen binding fragment of the antibody of claim 3 , wherein the antigen binding domain which binds to a target protein other than TIM-3 binds to CD3 or a CD3 polypeptide.

5. The TIM-3 binding antibody or the antigen binding fragment of the antibody of claim 4 , wherein the antibody or the antigen binding fragment of the antibody is cytotoxic against TIM-3 expressing cells.

6. The TIM-3 binding antibody or the antigen binding fragment of the antibody of claim 1 , comprising a heavy chain and a light chain variable region sequence, wherein:

(i) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:21, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:1;

OR

(ii) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:22, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:2;

OR

(iii) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:23, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:3;

OR

(iv) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:24, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:4;

OR

(v) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:25, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:5;

OR

(vi) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:26, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:6;

OR

(vii) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:27, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:7;

OR

(viii) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:28, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:8;

OR

(ix) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence of SEQ ID NO:29, and

the light chain sequence has at least 85% sequence identity to the light chain sequence of SEQ ID NO:9.

7. The TIM-3 binding antibody or the antigen binding fragment of the antibody of claim 1 , wherein the antigen binding fragment is a Fab fragment or scFv fragment.

8. The TIM-3 binding antibody or the antigen binding fragment of the antibody of claim 1 , wherein the antibody comprises a human constant region selected from IgG1, IgG2, IgG3 and IgG4.

9. A chimeric antigen receptor (CAR) comprising the TIM-3 binding antibody or the antigen binding fragment of the antibody of claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 24, 2017
From: WANG, CHENG-I; OH, HSUEH LING JANICE; YEO, SIOK PING; GOH, YUN PEI SHARON
To: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH
Reel/Frame 042131/0295 →
Priority Claims (1)
GB 1419094.6 · Oct 27, 2014 · national
Continuity (1)
Related Publication 20170306016A1 · Oct 26, 2017