IP Library › Patent Application 16634506

Patent Application

App. No. 16/634,506

ANTI-TIGIT ANTIBODIES

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Patent No.: US None
App. No.: 16/634,506

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Abstract

Anti-TIGIT antibodies and antigen binding fragments thereof that inhibit TIGIT-mediated signalling are provided, together with combinations comprising said antibodies or antigen binding fragments thereof and methods for their use.

Claims (118)

1 .- 52 . (canceled)

53 . A method of promoting a T cell activity comprising contacting a population of T cells with an antibody or antigen binding fragment thereof which binds to human TIGIT, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable domain (VH) comprising a HCDR1, a HCDR2, and a HCDR3, and a light chain variable domain (VL) comprising a LCDR1, a LCDR2 and a LCDR3, and:

(i) the HCDR1 comprises SEQ ID NO:16, the HCDR2 comprises SEQ ID NO:17, the HCDR3 comprises SEQ ID NO:18, the LCDR1 comprises SEQ ID NO:61, the LCDR2 comprises SEQ ID NO:62, and the LCDR3 comprises SEQ ID NO:63;

(ii) the HCDR1 comprises SEQ ID NO:4, the HCDR2 comprises SEQ ID NO:5, the HCDR3 comprises SEQ ID NO:6, the LCDR1 comprises SEQ ID NO:49, the LCDR2 comprises SEQ ID NO:50, and the LCDR3 comprises SEQ ID NO:51;

(iii) the HCDR1 comprises SEQ ID NO:7, the HCDR2 comprises SEQ ID NO:8, the HCDR3 comprises SEQ ID NO:9, the LCDR1 comprises SEQ ID NO:52, the LCDR2 comprises SEQ ID NO:53, and the LCDR3 comprises SEQ ID NO:54;

(iv) the HCDR1 comprises SEQ ID NO:10, the HCDR2 comprises SEQ ID NO:11, the HCDR3 comprises SEQ ID NO:12, the LCDR1 comprises SEQ ID NO:55, the LCDR2 comprises SEQ ID NO:56, and the LCDR3 comprises SEQ ID NO:57;

(v) the HCDR1 comprises SEQ ID NO:13, the HCDR2 comprises SEQ ID NO:14, the HCDR3 comprises SEQ ID NO:15, the LCDR1 comprises SEQ ID NO:58, the LCDR2 comprises SEQ ID NO:59, and the LCDR3 comprises SEQ ID NO:60;

(vi) the HCDR1 comprises SEQ ID NO:1, the HCDR2 comprises SEQ ID NO:2, the HCDR3 comprises SEQ ID NO:3, the LCDR1 comprises SEQ ID NO:46, the LCDR2 comprises SEQ ID NO:47, and the LCDR3 comprises SEQ ID NO:48;

(vii) the HCDR1 comprises SEQ ID NO:19, the HCDR2 comprises SEQ ID NO:20, the HCDR3 comprises SEQ ID NO:21, the LCDR1 comprises SEQ ID NO:64, the LCDR2 comprises SEQ ID NO:65, and the LCDR3 comprises SEQ ID NO:66;

(viii) the HCDR1 comprises SEQ ID NO:22, the HCDR2 comprises SEQ ID NO:23, the HCDR3 comprises SEQ ID NO:24, the LCDR1 comprises SEQ ID NO:67, the LCDR2 comprises SEQ ID NO:68, and the LCDR3 comprises SEQ ID NO:69;

(ix) the HCDR1 comprises SEQ ID NO:25, the HCDR2 comprises SEQ ID NO:26, the HCDR3 comprises SEQ ID NO:27, the LCDR1 comprises SEQ ID NO:70, the LCDR2 comprises SEQ ID NO:71, and the LCDR3 comprises SEQ ID NO:72;

(x) the HCDR1 comprises SEQ ID NO:28, the HCDR2 comprises SEQ ID NO:29, the HCDR3 comprises SEQ ID NO:30, the LCDR1 com comprises prising SEQ ID NO:73, the LCDR2 comprises SEQ ID NO:74, and the LCDR3 comprises SEQ ID NO:75;

(xi) the HCDR1 comprises SEQ ID NO:31, the HCDR2 comprises SEQ ID NO:32, the HCDR3 comprises SEQ ID NO:33, the LCDR1 comprises SEQ ID NO:76, the LCDR2 comprises SEQ ID NO:77, and the LCDR3 comprises SEQ ID NO:78;

(xii) the HCDR1 comprises SEQ ID NO:34, the HCDR2 comprises SEQ ID NO:35, the HCDR3 comprises SEQ ID NO:36, the LCDR1 comprises SEQ ID NO:79, the LCDR2 comprises SEQ ID NO:80, and the LCDR3 comprises SEQ ID NO:81;

(xiii) the HCDR1 comprises SEQ ID NO:37, the HCDR2 comprises SEQ ID NO:38, the HCDR3 comprises SEQ ID NO:39, the LCDR1 comprises SEQ ID NO:82, the LCDR2 comprises SEQ ID NO:83, and the LCDR3 comprises SEQ ID NO:84;

(xiv) the HCDR1 comprises SEQ ID NO:40, the HCDR2 comprises SEQ ID NO:41, the HCDR3 comprises SEQ ID NO:42, the LCDR1 comprises SEQ ID NO:85, the LCDR2 comprises SEQ ID NO:86, and the LCDR3 comprises SEQ ID NO:87;

(xv) the HCDR1 comprises SEQ ID NO:43, the HCDR2 comprises SEQ ID NO:44, the HCDR3 comprises SEQ ID NO:45, the LCDR1 comprises SEQ ID NO:88, the LCDR2 comprises SEQ ID NO:89, and the LCDR3 comprises SEQ ID NO:90;

(xvi) the HCDR1 comprises SEQ ID NO:271, the HCDR2 comprises SEQ ID NO:272, the HCDR3 comprises SEQ ID NO:273, the LCDR1 comprises SEQ ID NO:283, the LCDR2 comprises SEQ ID NO:284, and the LCDR3 comprises SEQ ID NO:285;

(xvii) the HCDR1 comprises SEQ ID NO:274, the HCDR2 comprises SEQ ID NO:275, the HCDR3 comprises SEQ ID NO:276, the LCDR1 comprises SEQ ID NO:286, the LCDR2 comprises SEQ ID NO:287, and the LCDR3 comprises SEQ ID NO:288; or

(xviii) the HCDR1 comprises SEQ ID NO:277, the HCDR2 comprises SEQ ID NO:278, the HCDR3 comprises SEQ ID NO:279, the LCDR1 comprises SEQ ID NO:289, the LCDR2 comprises SEQ ID NO:290, and the LCDR3 comprises SEQ ID NO:291.

54 . The method of claim 53 , wherein:

(i) the VH comprises the amino acid sequence of SEQ ID NO:211 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:212 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(ii) the VH comprises the amino acid sequence of SEQ ID NO:213 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:214 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(iii) the VH comprises the amino acid sequence of SEQ ID NO:215 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:216 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(iv) the VH comprises the amino acid sequence of SEQ ID NO:217 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:218 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(v) the VH comprises the amino acid sequence of SEQ ID NO:219 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:220 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(vi) the VH comprises the amino acid sequence of SEQ ID NO:221 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:222 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(vii) the VH comprises the amino acid sequence of SEQ ID NO:223 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:224 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(viii) the VH comprises the amino acid sequence of SEQ ID NO:225 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:226 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(ix) the VH comprises the amino acid sequence of SEQ ID NO:227 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:228 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(x) the VH comprises the amino acid sequence of SEQ ID NO:229 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:230 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(xi) the VH comprises the amino acid sequence of SEQ ID NO:231 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:232 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(xii) the VH comprises the amino acid sequence of SEQ ID NO:233 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:234 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(xiii) the VH comprises the amino acid sequence of SEQ ID NO:235 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:236 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(xiv) the VH comprises the amino acid sequence of SEQ ID NO:237 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:238 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(xv) the VH comprises the amino acid sequence of SEQ ID NO:239 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:240 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(xvi) the VH comprises the amino acid sequence of SEQ ID NO:327 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:328 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL;

(xvii) the VH comprises the amino acid sequence of SEQ ID NO:329 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:330 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL; or

(xviii) the VH comprises the amino acid sequence of SEQ ID NO:331 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VH and the VL comprises the amino acid sequence of SEQ ID NO:332 or an amino acid sequence at least 90% identical thereto wherein all differences are located in a framework region of the VL.

55 . The method of promoting T cell activity according to claim 53 , wherein:

the HCDR1 comprises SEQ ID NO: 16

(YTFTSYYMH),

the HCDR2 comprises SEQ ID NO: 17

(VIGPSGASTSYAQKFQG),

the HCDR3 comprises SEQ ID NO: 18

(ARDHSDYWSGIMEV),

the LCDR1 comprises SEQ ID NO: 61

(RASQSVRSSYLA),

the LCDR2 comprises SEQ ID NO: 62

(GASSRAT),

and

the LCDR3 comprises SEQ ID NO: 63

(QQYFSPPWT).

56 . The method of promoting T cell activity according to claim 56 , wherein the VH comprises the amino acid sequence shown as SEQ ID NO: 221 or an amino acid sequence exhibiting at least 90%, 95%, 97%, 98% or 99% sequence identity thereto wherein all differences are located in a framework region of the VL, and the light chain variable domain comprises the amino acid sequence shown as SEQ ID NO: 222 or an amino acid sequence exhibiting at least 90%, 95%, 97%, 98% or 99% sequence identity thereto, wherein all differences are located in a framework regions of the VH.

57 . The method of claim 53 , wherein the method promotes αβ T cell activity.

58 . The method of claim 53 , wherein the method promotes γδ T cell activity.

59 . The method of claim 53 , wherein the method is performed in vitro.

60 . The method of claim 53 , wherein the method is performed in vivo in a human subject.

61 . The method of claim 60 , wherein the human subject has a cancer.

62 . The method of claim 60 , wherein the human subject has a viral infection.

63 . The method of claim 62 , wherein the viral infection is a CMV infection.

64 . The method of claim 53 , wherein the method further comprises contacting the population of T cells with one or more of an anti-PD1 antibody, an anti-PD-L1 antibody, an anti-41BB antibody, an anti-OX40 antibody, an anti-GITR antibody, and an anti-ICOS antibody.

65 . A method of treating a viral infection in a subject comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof which binds to human TIGIT, wherein the antibody or antigen binding fragment thereof comprises a VH comprising a HCDR1, a HCDR2, and a HCDR3, and a VL comprising a LCDR1, a LCDR2 and a LCDR3, wherein:

(i) the HDCR1 comprises SEQ ID NO:16, the HDCR2 comprises SEQ ID NO:17, the HDCR3 comprises SEQ ID NO:18, the LCDR1 comprises SEQ ID NO:61, the LCDR2 comprises SEQ ID NO:62, and the LCDR3 comprises SEQ ID NO:63;

(ii) the HDCR1 comprises SEQ ID NO:4, the HDCR2 comprises SEQ ID NO:5, the HDCR3 comprises SEQ ID NO:6, the LCDR1 comprises SEQ ID NO:49, the LCDR2 comprises SEQ ID NO:50, and the LCDR3 comprises SEQ ID NO:51;

(iii) the HDCR1 comprises SEQ ID NO:7, the HDCR2 comprises SEQ ID NO:8, the HDCR3 comprises SEQ ID NO:9, the LCDR1 comprises SEQ ID NO:52, the LCDR2 comprises SEQ ID NO:53, and the LCDR3 comprises SEQ ID NO:54;

(iv) the HCDR1 comprising SEQ ID NO:10, the HDCR2 comprises SEQ ID NO:11, the HDCR3 comprises SEQ ID NO:12, the LCDR1 comprises SEQ ID NO:55, the LCDR2 comprises SEQ ID NO:56, and the LCDR3 comprises SEQ ID NO:57;

(v) the HDCR1 comprises SEQ ID NO:13, the HDCR2 comprises SEQ ID NO:14, the HDCR3 comprises SEQ ID NO:15, the LCDR1 comprises SEQ ID NO:58, the LCDR2 comprises SEQ ID NO:59, and the LCDR3 comprises SEQ ID NO:60;

(vi) the HDCR1 comprises SEQ ID NO:1, the HDCR2 comprises SEQ ID NO:2, the HDCR3 comprises SEQ ID NO:3, the LCDR1 comprises SEQ ID NO:46, the LCDR2 comprises SEQ ID NO:47, and the LCDR3 comprises SEQ ID NO:48;

(vii) the HDCR1 comprises SEQ ID NO:19, the HDCR2 comprises SEQ ID NO:20, the HDCR3 comprises SEQ ID NO:21, the LCDR1 comprises SEQ ID NO:64, the LCDR2 comprises SEQ ID NO:65, and the LCDR3 comprises SEQ ID NO:66;

(viii) the HDCR1 comprises SEQ ID NO:22, the HDCR2 comprises SEQ ID NO:23, the HDCR3 comprises SEQ ID NO:24, the LCDR1 comprises SEQ ID NO:67, the LCDR2 comprises SEQ ID NO:68, and the LCDR3 comprises SEQ ID NO:69;

(ix) the HDCR1 comprises SEQ ID NO:25, the HDCR2 comprises SEQ ID NO:26, the HDCR3 comprises SEQ ID NO:27, the LCDR1 comprises SEQ ID NO:70, the LCDR2 comprises SEQ ID NO:71, and the LCDR3 comprises SEQ ID NO:72;

(x) the HDCR1 comprises SEQ ID NO:28, the HDCR2 comprises SEQ ID NO:29, the HDCR3 comprises SEQ ID NO:30, the LCDR1 comprises SEQ ID NO:73, the LCDR2 comprises SEQ ID NO:74, and the LCDR3 comprises SEQ ID NO:75;

(xi) the HDCR1 comprises SEQ ID NO:31, the HDCR2 comprises SEQ ID NO:32, the HDCR3 comprises SEQ ID NO:33, the LCDR1 comprises SEQ ID NO:76, the LCDR2 comprises SEQ ID NO:77, and the LCDR3 comprises SEQ ID NO:78;

(xii) the HDCR1 comprises SEQ ID NO:34, the HDCR2 comprises SEQ ID NO:35, the HDCR3 comprises SEQ ID NO:36, the LCDR1 comprises SEQ ID NO:79, the LCDR2 comprises SEQ ID NO:80, and the LCDR3 comprises SEQ ID NO:81;

(xiii) the HDCR1 comprises SEQ ID NO:37, the HDCR2 comprises SEQ ID NO:38, the HDCR3 comprises SEQ ID NO:39, the LCDR1 comprises SEQ ID NO:82, the LCDR2 comprises SEQ ID NO:83, and the LCDR3 comprises SEQ ID NO:84;

(xiv) the HDCR1 comprises SEQ ID NO:40, the HDCR2 comprises SEQ ID NO:41, the HDCR3 comprises SEQ ID NO:42, the LCDR1 comprises SEQ ID NO:85, the LCDR2 comprises SEQ ID NO:86, and the LCDR3 comprises SEQ ID NO:87;

(xv) the HDCR1 comprises SEQ ID NO:43, the HDCR2 comprises SEQ ID NO:44, the HDCR3 comprises SEQ ID NO:45, the LCDR1 comprises SEQ ID NO:88, the LCDR2 comprises SEQ ID NO:89, and the LCDR3 comprises SEQ ID NO:90;

(xvi) the HDCR1 comprises SEQ ID NO:271, the HDCR2 comprises SEQ ID NO:272, the HDCR3 comprises SEQ ID NO:273, the LCDR1 comprises SEQ ID NO:283, the LCDR2 comprises SEQ ID NO:284, and the LCDR3 comprises SEQ ID NO:285;

(xvii) the HDCR1 comprises SEQ ID NO:274, the HDCR2 comprises SEQ ID NO:275, the HDCR3 comprises SEQ ID NO:276, the LCDR1 comprises SEQ ID NO:286, the LCDR2 comprises SEQ ID NO:287, and the LCDR3 comprises SEQ ID NO:288; or

(xviii) the HDCR1 comprises SEQ ID NO:277, the HDCR2 comprises SEQ ID NO:278, the HDCR3 comprises SEQ ID NO:279, the LCDR1 comprises SEQ ID NO:289, the LCDR2 comprises SEQ ID NO:290, and the LCDR3 comprises SEQ ID NO:291.

66 . The method of claim 65 , wherein:

67 . The method of claim 65 , wherein:

the HCDR1 comprises SEQ ID NO: 16

(YTFTSYYMH),

the HCDR2 comprises SEQ ID NO: 17

(VIGPSGASTSYAQKFQG),

the HCDR3 comprises SEQ ID NO: 18

(ARDHSDYWSGIMEV),

the LCDR1 comprises SEQ ID NO: 61

(RASQSVRSSYLA),

the LCDR2 comprises SEQ ID NO: 62

(GASSRAT),

and

the LCDR3 comprises SEQ ID NO: 63

(QQYFSPPWT).

68 . The method of claim 67 , wherein the VH comprises the amino acid sequence shown as SEQ ID NO: 221 or an amino acid sequence exhibiting at least 90%, 95%, 97%, 98% or 99% sequence identity thereto wherein all the differences are located in a framework region of the VH, and the VL comprises the amino acid sequence shown as SEQ ID NO: 222 or an amino acid sequence exhibiting at least 90%, 95%, 97%, 98% or 99% sequence identity thereto wherein all the differences are located in the framework region of the VL.

69 . The method of claim 65 , wherein the method further comprises administration of one or more additional therapeutic agent.

70 . The method of claim 69 , wherein the one or more therapeutic agent is selected from: a chemotherapeutic agent, an anti-PD1 antibody, an anti-PD-L1 antibody, an anti-41BB antibody, an anti-OX40 antibody, an anti-GITR antibody, and an anti-ICOS antibody.

71 . The method of claim 65 , wherein the viral infection is a CMV infection.

Assignments (4)

CHANGE OF NAME Recorded Dec 10, 2020

From: ITEOS THERAPEUTICS SA

To: ITEOS BELGIUM SA

Reel/Frame 054677/0908 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2020

From: QUEVA, CHRISTOPHE; DENIES, SOFIE; HOOFD, CATHERINE; CUENDE, JULIA; DRIESSENS, GREGORY; LAMBOLEZ, FLORENCE

To: ITEOS THERAPEUTICS SA

Reel/Frame 052059/0119 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2020

From: COOPER, ANTHONY

To: ADIMAB LLC

Reel/Frame 052059/0126 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2020

From: ADIMAB, LLC

To: ITEOS THERAPEUTICS SA

Reel/Frame 052059/0129 →