US 2026/0242489 A1Published application

Ph-dependent anti-egfr antibodies for treatment of solid tumors

AssigneeHuahui Health Ltd.

InventorsJianhua SUI, Ximing LIU, Xinxin TIAN

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Abstract

The present disclosure provides monoclonal anti-human EGFR (hEGFR) antibodies with cross-reactivity to human EGFR and mouse EGFR, pH dependent binding and/or competitive binding to hEGFR with its ligand EGF. The present disclosure also provides a method of site-directed engineering of an antibody to increase the pH-dependent binding to antigen of said antibody.

Claims21

Dependent claims

An isolated antibody or an antigen-binding fragment thereof that specifically binds to human EGFR (hEGFR), which comprises any one of following (a) to (h):

(a) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
50, 61 and 52, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
62, 15 and 54;
(b) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
11, 12 and 13, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
14, 15 and 16;
(c) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
50, 51 and 52, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
53, 15 and 54;
(d) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
50, 61 and 52, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
69, 70 and 54;
(e) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
50, 61 and 52, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
77, 70 and 54;
(f) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
23, 24, and 25 respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
26, 27, and 28;
(g) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
31, 32, and 33, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
34, 35, and 36;
or
(h) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
11, 39 and 40, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
41, 42, and 43;
wherein the hEGFR has an amino acid sequence as shown in SEQ ID NO:
1.

32 more elements

Dependencies are inferred from the claim text.

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Abstract

An isolated antibody or an antigen-binding fragment thereof that specifically binds to human EGFR (hEGFR), which comprises any one of following (a) to (h):

(a) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
50, 61 and 52, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
62, 15 and 54;
(b) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
11, 12 and 13, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
14, 15 and 16;
(c) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
50, 51 and 52, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
53, 15 and 54;
(d) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
50, 61 and 52, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
69, 70 and 54;
(e) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
50, 61 and 52, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
77, 70 and 54;
(f) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
23, 24, and 25 respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
26, 27, and 28;
(g) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
31, 32, and 33, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
34, 35, and 36;
or
(h) HCDR1, HCDR2 and HCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
11, 39 and 40, respectively;
and LCDR1, LCDR2, LCDR3 comprising or consisting of an amino acid sequence of SEQ ID NOs:
41, 42, and 43;
wherein the hEGFR has an amino acid sequence as shown in SEQ ID NO:
1.

32 more elements