US 2026/0265387 A1Published application

Anti-tshr antibodies and uses thereof

AssigneeEthyreal Bio, Inc.

InventorsLauren Pepper, Charles Gordon Grummitt, Alexey Alexandrovich Lugovskoy, Melissa Geddie

Life of this patent

Estimating the term…

Abstract

Provided herein are antigen binding proteins that bind to thyroid stimulating hormone receptor (TSHR) and methods of using the same.

Claims37

Dependent claims

An antigen binding protein or an antigen binding fragment thereof which specifically binds thyroid-stimulating hormone receptor (TSHR), wherein the antigen binding protein or an antigen binding fragment thereof comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein:

a. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
21, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
22, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
23;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
24, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
25, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
26;
b. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
1, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
2, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
3;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
4, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
5, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
6;
c. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
11, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
12, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
13;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
14, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
15, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
16;
d. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
31, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
32, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
33;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
34, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
35, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
36;
e. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
41, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
42, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
43;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
44, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
45, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
46;
or
f. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
51, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
52, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
53;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
54, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
55, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
56.

46 more elements

A method of treating or preventing a thyroid stimulating hormone receptor (TSHR)-related disease in a subject, comprising administering to a subject in need thereof an antigen binding protein or an antigen binding fragment thereof which specifically binds thyroid-stimulating hormone receptor (TSHR), wherein the antigen binding protein or an antigen binding fragment thereof comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein:

a. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
21, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
22, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
23;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
24, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
25, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
26;
b. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
1, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
2, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
3;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
4, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
5, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
6;
c. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
11, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
12, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
13;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
14, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
15, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
16;
d. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
31, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
32, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
33;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
34, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
35, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
36;
e. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
41, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
42, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
43;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
44, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
45, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
46;
or
f. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
51, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
52, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
53;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
54, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
55, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
56, thereby treating or preventing the TSHR-related disease in the subject.

46 more elements

A chimeric antigen receptor (CAR) comprising a TSHR-binding domain comprising an antigen binding protein or an antigen binding fragment thereof which specifically binds thyroid-stimulating hormone receptor (TSHR), wherein the antigen binding protein or an antigen binding fragment thereof comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein:

a. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
21, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
22, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
23;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
24, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
25, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
26;
b. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
1, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
2, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
3;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
4, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
5, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
6;
c. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
11, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
12, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
13;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
14, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
15, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
16;
d. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
31, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
32, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
33;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
34, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
35, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
36;
e. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
41, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
42, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
43;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
44, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
45, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
46;
or
f. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
51, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
52, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
53;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
54, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
55, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
56.

46 more elements

An antibody drug conjugate (ADC) comprising an antigen binding protein or an antigen binding fragment thereof which specifically binds thyroid-stimulating hormone receptor (TSHR), wherein the antigen binding protein or an antigen binding fragment thereof comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein:

a. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
21, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
22, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
23;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
24, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
25, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
26;
b. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
1, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
2, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
3;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
4, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
5, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
6;
c. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
11, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
12, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
13;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
14, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
15, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
16;
d. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
31, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
32, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
33;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
34, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
35, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
36;
e. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
41, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
42, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
43;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
44, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
45, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
46;
or
f. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
51, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
52, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
53;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
54, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
55, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
56, conjugated to a drug, optionally wherein the drug is a radioisotope or to a therapeutic small molecule.

46 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/558,850Filed 6 Mar 2026
Priority: EP 25166758.027 Mar 2025
Published: 10 Sep 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 16/2869
Against receptors, cell surface antigens or cell surface determinants: against hormone receptors
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…
A61K 47/6849
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a receptor, a cell…
A61K 51/1036
Against receptors, cell-surface antigens or cell-surface determinants: against hormone receptors

Family

Application63/768,482Us provisional application · filed 7 Mar 2025
Application63/964,648Us provisional application · filed 21 Jan 2026
US 2026/0265387 A1This patent

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

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a. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
21, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
22, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
23;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
24, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
25, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
26;
b. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
1, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
2, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
3;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
4, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
5, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
6;
c. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
11, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
12, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
13;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
14, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
15, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
16;
d. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
31, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
32, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
33;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
34, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
35, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
36;
e. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
41, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
42, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
43;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
44, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
45, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
46;
or
f. the VH domain comprises a HCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
51, a HCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
52, and a HCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
53;
and the VL domain comprises a LCDR1 sequence comprising the amino acid sequence of SEQ ID NO:
54, a LCDR2 sequence comprising the amino acid sequence of SEQ ID NO:
55, and a LCDR3 sequence comprising the amino acid sequence of SEQ ID NO:
56.

46 more elements

Facts

Application

19/558,850Filed 6 Mar 2026

Priority

EP 25166758.027 Mar 2025

Published

10 Sep 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07K 16/2869
Against receptors, cell surface antigens or cell surface determinants: against hormone receptors
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…
A61K 47/6849
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a receptor, a cell…
A61K 51/1036
Against receptors, cell-surface antigens or cell-surface determinants: against hormone receptors