US 2025/0026841 A1Published application

Bispecific antibodies targeting cd137 and uses thereof for anti-cancer immunotherapy

AssigneeAP Biosciences, Inc.

InventorsJeng-Horng Her, Po-Lin Huang, Hsin-Ta Hsieh, Ching-Hsuan Hsu, Jhong-Jhe You

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Abstract

Provided herein are antibodies or antigen binding fragments thereof having a binding specificity for p95HER2 or for CD73, bispecific antibodies comprising a first antigen binding region that binds to p95HER2 or CD73 and a second antigen binding region that binds to an immune checkpoint molecule or an immune stimulatory molecule, and antibody-drug conjugates thereof. Also provided herein are pharmaceutical compositions comprising the antibodies, antigen binding fragments thereof, bispecific antibodies or antibody drug conjugates thereof, and methods of use thereof. The methods of use include method of treating cancer.

Claims33

Dependent claims

An antibody or antigen binding fragment thereof comprising:

(i) a VH region comprising complementarity-determining region (CDR)-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:3, CDR-H2 is set forth in SEQ ID NO:4, and CDR-H3 is set forth in SEQ ID NO:5 or sequences having 90% identity to SEQ ID NO:3, 4 or 5 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:6, CDR-L2 is set forth in SEQ ID NO:7, and CDR-L3 is set forth in SEQ ID NO:
8 or sequences having 90% identity to SEQ ID NO:6, 7 or 8 and the antigen binding specificity thereof;
(ii) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:11, CDR-H2 is set forth in SEQ ID NO:12, and CDR-H3 is set forth in SEQ ID NO:13 or sequences having 90% identity to SEQ ID NO:11, 12 or 13 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:14, CDR-L2 is set forth in SEQ ID NO:
15, and CDR-L3 is set forth in SEQ ID NO:16 or sequences having 90% identity to SEQ ID NO:14, 15 or 16 and the antigen binding specificity thereof;
(iii) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:19, CDR-H2 is set forth in SEQ ID NO:20, and CDR-H3 is set forth in SEQ ID NO:21 or sequences having 90% identity to SEQ ID NO:19, 20 or 21 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:22, CDR-L2 is set forth in SEQ ID NO:23, and CDR-L3 is set forth in SEQ ID NO:24 or sequences having 90% identity to SEQ ID NO:22, 23 or 24 and the antigen binding specificity thereof;
(iv) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:27, CDR-H2 is set forth in SEQ ID NO:28, and CDR-H3 is set forth in SEQ ID NO:29 or sequences having 90% identity to SEQ ID NO:27, 28 or 29 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:30, CDR-L2 is set forth in SEQ ID NO:31, and CDR-L3 is set forth in SEQ ID NO:32 or sequences having 90% identity to SEQ ID NO:30, 31 or 32 and the antigen binding specificity thereof, or
(v) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:35, CDR-H2 is set forth in SEQ ID NO:36, and CDR-H3 is set forth in SEQ ID NO:37 or sequences having 90% identity to SEQ ID NO:35, 36 or 37 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:38, CDR-L2 is set forth in SEQ ID NO:39, and CDR-L3 is set forth in SEQ ID NO:40 or sequences having 90% identity to SEQ ID NO:38, 39 or 40 and the antigen binding specificity thereof, wherein the antibody or antigen binding fragment binds to p95HER2.

9 more elements

An antibody or antigen binding fragment thereof comprising:

(i) a VH region comprising complementarity-determining region (CDR)-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:51, CDR-H2 is set forth in SEQ ID NO:52, and CDR-H3 is set forth in SEQ ID NO:53 or sequences having 90% identity to SEQ ID NO:51, 52 or 53 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:54, CDR-L2 is set forth in SEQ ID NO:55, and CDR-L3 is set forth in SEQ ID NO:
56 or sequences having 90% identity to SEQ ID NO:55, 56 or 57 and the antigen binding specificity thereof;
(ii) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:59, CDR-H2 is set forth in SEQ ID NO:60, and CDR-H3 is set forth in SEQ ID NO:61 or sequences having 90% identity to SEQ ID NO:59, 60 or 61 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:62, CDR-L2 is set forth in SEQ ID NO:63, and CDR-L3 is set forth in SEQ ID NO:64 or sequences having 90% identity to SEQ ID NO:62, 63 or 64 and the antigen binding specificity thereof;
(iii) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:67, CDR-H2 is set forth in SEQ ID NO:68, and CDR-H3 is set forth in SEQ ID NO:69 or sequences having 90% identity to SEQ ID NO:67, 68 or 69 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:70, CDR-L2 is set forth in SEQ ID NO:71, and CDR-L3 is set forth in SEQ ID NO:
72 or sequences having 90% identity to SEQ ID NO:70, 71 or 72 and the antigen binding specificity thereof;
(iv) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:75, CDR-H2 is set forth in SEQ ID NO:76, and CDR-H3 is set forth in SEQ ID NO:77 or sequences having 90% identity to SEQ ID NO:75, 76 or 77 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:78, CDR-L2 is set forth in SEQ ID NO:
79, and CDR-L3 is set forth in SEQ ID NO:80 or sequences having 90% identity to SEQ ID NO:78, 79 or 80 and the antigen binding specificity thereof;
(v) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:67, CDR-H2 is set forth in SEQ ID NO:68, and CDR-H3 is set forth in SEQ ID NO:69 or sequences having 90% identity to SEQ ID NO:67, 68 or 69 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:70, CDR-L2 is set forth in SEQ ID NO:82, and CDR-L3 is set forth in SEQ ID NO:72 or sequences having 90% identity to SEQ ID NO:70, 82 or 72 and the antigen binding specificity thereof;
(vi) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:67, CDR-H2 is set forth in SEQ ID NO:68, and CDR-H3 is set forth in SEQ ID NO:69 or sequences having 90% identity to SEQ ID NO:67, 68 or 69 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:70, CDR-L2 is set forth in SEQ ID NO:84, and CDR-L3 is set forth in SEQ ID NO:
72 or sequences having 90% identity to SEQ ID NO:70, 84 or 72 and the antigen binding specificity thereof;
or
(vii) a VH region comprising CDR-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:67, CDR-H2 is set forth in SEQ ID NO:68, and CDR-H3 is set forth in SEQ ID NO:69 or sequences having 90% identity to SEQ ID NO:67, 68 or 69 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:70, CDR-L2 is set forth in SEQ ID NO:86, and CDR-L3 is set forth in SEQ ID NO:
72 or sequences having 90% identity to SEQ ID NO:70, 86 or 72 and the antigen binding specificity thereof;
wherein the antibody or antigen binding fragment binds to CD73.

18 more elements

A bispecific antibody comprising a first antigen binding region and a second antigen binding region, wherein the first antigen binding region binds to CD73, wherein the antibody comprises:

(i) a VH region comprising complementarity-determining region (CDR)-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:67, CDR-H2 is set forth in SEQ ID NO:
68, and CDR-H3 is set forth in SEQ ID NO:69 or sequences having 90% identity to SEQ ID NO:
67, 68 or 69 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:70, CDR-L2 is set forth in SEQ ID NO:71, and CDR-L3 is set forth in SEQ ID NO:72 or sequences having 90% identity to SEQ ID NO:70, 71 or 72 and the antigen binding specificity thereof;
(ii) a VH region comprising complementarity-determining region (CDR)-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:67, CDR-H2 is set forth in SEQ ID NO:
68, and CDR-H3 is set forth in SEQ ID NO:69 or sequences having 90% identity to SEQ ID NO:
67, 68 or 69 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:70, CDR-L2 is set forth in SEQ ID NO:82, and CDR-L3 is set forth in SEQ ID NO:72 or sequences having 90% identity to SEQ ID NO:
70, 82 or 72 and the antigen binding specificity thereof;
(iii) a VH region comprising complementarity-determining region (CDR)-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:67, CDR-H2 is set forth in SEQ ID NO:
68, and CDR-H3 is set forth in SEQ ID NO:69 or sequences having 90% identity to SEQ ID NO:
67, 68 or 69 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:70, CDR-L2 is set forth in SEQ ID NO:84, and CDR-L3 is set forth in SEQ ID NO:
72 or sequences having 90% identity to SEQ ID NO:
70, 84 or 72 and the antigen binding specificity thereof;
or
(iv) a VH region comprising complementarity-determining region (CDR)-H1, CDR-H2, and CDR-H3, wherein CDR-H1 is set forth in SEQ ID NO:67, CDR-H2 is set forth in SEQ ID NO:
68, and CDR-H3 is set forth in SEQ ID NO:69 or sequences having 90% identity to SEQ ID NO:
67, 68 or 69 and the antigen binding specificity thereof;
and a VL region comprising CDR-L1, CDR-L2, and CDR-L3, wherein CDR-L1 is set forth in SEQ ID NO:70, CDR-L2 is set forth in SEQ ID NO:86, and CDR-L3 is set forth in SEQ ID NO:72 or sequences having 90% identity to SEQ ID NO:70, 86 or 72 and the antigen binding specificity thereof.

17 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/708,551Filed 18 Nov 2022
Priority: 19 Nov 2021
Published: 23 Jan 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

A61P 35/00
Antineoplastic agents
C07K 16/2878
Against receptors, cell surface antigens or cell surface determinants: against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
A61K 47/6801
The modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment: drug-antibody or immunoglobulin conjugates…
C07K 16/2896
Against receptors, cell surface antigens or cell surface determinants: against molecules with a "CD"-designation, not provided for elsewhere