US 2026/0062484 A1 · BISPECIFIC ANTIGEN-BINDING MOLECULES AND METHODS OF USE

Abstract

The present invention provides bispecific antigen-binding molecules having a monovalent arm specific to a first target antigen (e.g., a T cell antigen, such as CD3) and a bivalent arm specific for a second target antigen (e.g., a tumor antigen, such as HER2). Bispecific antigen-binding molecules are useful in the treatment of disorders, such as cancer (e.g., HER2-positive cancer). The invention also features methods of producing bispecific antigen-binding molecules, methods of treating disorders using bispecific antigen-binding molecules, and compositions including bispecific antigen-binding molecules.

Claims29

Dependent claims

1-237. (canceled)

A method of:

(a) treating or delaying the progression of a HER2-positive cancer in a subject in need thereof;
or
(b) enhancing immune function in a subject having a HER2-positive cancer,
wherein the method comprises administering to the subject a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:
(a) the monovalent arm comprises a FabA that specifically binds CD3, wherein the C-terminus of the FabA is fused to an N-terminus of a first Fc subunit, and wherein the FabA comprises the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
3,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
(b) the bivalent arm comprises a FabB1 and a FabB2 that each specifically binds HER2, wherein the C-terminus of the FabB2 is fused to the N-terminus of the FabB1, and the C-terminus of the FabB1 is fused to an N-terminus of a second Fc subunit, wherein the FabB1 and the FabB2 each comprise the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
11,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
36,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
37,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
38,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
29, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
26;
and
(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.

29 more elements

A method of:

(a) treating or delaying the progression of a HER2-positive cancer in a subject in need thereof;
or
(b) enhancing immune function in a subject having a HER2-positive cancer,
wherein the method comprises administering to the subject a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:
(a) the monovalent arm comprises a FabA that specifically binds CD3, wherein the C-terminus of the FabA is fused to an N-terminus of a first Fc subunit, and wherein the FabA comprises the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
3,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
(b) the bivalent arm comprises a FabB1 and a FabB2 that each specifically binds HER2, wherein the C-terminus of the FabB2 is fused to the N-terminus of the FabB1, and the C-terminus of the FabB1 is fused to an N-terminus of a second Fc subunit, wherein the FabB1 and the FabB2 each comprise the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
11,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
19,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
20,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
21,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
22, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
26;
and
(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.

29 more elements

A method of:

(a) treating or delaying the progression of a HER2-positive cancer in a subject in need thereof;
or
(b) enhancing immune function in a subject having a HER2-positive cancer,
wherein the method comprises administering to the subject a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:
(a) the monovalent arm comprises a FabA that specifically binds CD3, wherein the C-terminus of the FabA is fused to an N-terminus of a first Fc subunit, and wherein the FabA comprises the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
3,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
(b) the bivalent arm comprises a FabB1 and a FabB2 that each specifically binds HER2, wherein the C-terminus of the FabB2 is fused to the N-terminus of the FabB1, and the C-terminus of the FabB1 is fused to an N-terminus of a second Fc subunit, wherein the FabB1 and the FabB2 each comprise the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
11,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
19,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
32,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
21,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
22, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
23;
and
(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.

29 more elements

A method of:

(a) treating or delaying the progression of a HER2-positive cancer in a subject in need thereof;
or
(b) enhancing immune function in a subject having a HER2-positive cancer,
wherein the method comprises administering to the subject a bispecific antigen-binding molecule that specifically binds CD3 and HER2 comprising a monovalent arm and a bivalent arm, wherein:
(a) the monovalent arm comprises a FabA that specifically binds CD3, wherein the C-terminus of the FabA is fused to an N-terminus of a first Fc subunit, and wherein the FabA comprises the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
1,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
2,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
3,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
4,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
5, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
6;
(b) the bivalent arm comprises a FabB1 and a FabB2 that each specifically binds HER2, wherein the C-terminus of the FabB2 is fused to the N-terminus of the FabB1, and the C-terminus of the FabB1 is fused to an N-terminus of a second Fc subunit, wherein the FabB1 and the FabB2 each comprise the following HVRs:
(i) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:
11,
(ii) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:
36,
(iii) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:
43,
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:
21,
(v) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:
29, and
(vi) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:
26;
and
(c) the first Fc subunit is associated with the second Fc subunit to form an Fc domain.

29 more elements

Dependencies are inferred from the claim text.

Facts

Application

19/176,544Filed 11 Apr 2025

Priority

8 Feb 2018

Published

5 Mar 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07K 16/2809
Against the immunoglobulin superfamily: against the T-cell receptor -CD3 complex
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines
A61K 47/65
The modifying agent being a protein, peptide or polyamino acid: peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers

Family

Application62/628,088Us provisional application · filed 8 Feb 2018

Application16/271,410Division · filed 8 Feb 2019

Application18/517,327Division · filed 22 Nov 2023

Application19/176,544Division

US 11,866,498 B2Related patent

US 12,297,270 B2Related patent

US 2019/0270814 A1Published application

US 2024/0092906 A1Published application

US 2026/0062484 A1This patent

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

Bispecific antigen-binding molecules and methods of use

Life of this patent

Bispecific antigen-binding molecules and methods of use

Life of this patent

Abstract

Claims29