IP Library › Granted Patent US 12,747,298
Granted Patent B2
US 12,747,298 · App. 18/002,472 · Granted Sep 29, 2026

Multi-specific antibodies binding to BCMA

Inventors: Nathan Trinklein (Newark, CA); Katherine Harris (Newark, CA); Harbani Malik (Newark, CA); Ute Schellenberger (Newark, CA); Omid Vafa (Newark, CA); Shelley Force Aldred (Newark, CA)
Assignee: TeneoBio, Inc.
C07K16/2878C07K16/18C07K2317/21C07K2317/31C07K2317/35
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Quick Facts
Patent No.
US 12,747,298
App. No.
18/002,472
Granted
Sep 29, 2026
Kind
B2
Abstract

Multi-specific, human heavy chain antibodies (e.g., UniAbsm) binding to BCMA are disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat disorders that are characterized by the expression of BCMA.

Claims (65)

1 . A multi-specific antibody comprising:

(a) a first binding unit that binds to La protein, comprising:

(i) a heavy chain variable region comprising: a CDR1 sequence of SEQ ID NOs: 4 or 7, a CDR2 sequence of SEQ ID NO: 5, and a CDR3 sequence of SEQ ID NO: 6 or 8, in a human VH framework; and

(ii) a light chain variable region comprising: a CDR1 sequence of SEQ ID NO: 9, a CDR2 sequence of SEQ ID NO: 10, and a CDR3 sequence of SEQ ID NO: 11, in a human VL framework; and

(b) a second binding unit that binds to BCMA, comprising:

(i) an antigen-binding domain of an anti-BCMA heavy chain-only antibody, comprising a CDR1 sequence of SEQ ID NO: 1, a CDR2 sequence of SEQ ID NO: 2, and a CDR3 sequence of SEQ ID NO: 3, in a human VH framework, wherein the antigen-binding domain of the anti-BCMA heavy chain-only antibody is in a monovalent or bivalent configuration.

2 . The multi-specific antibody of claim 1 , wherein the heavy chain variable region and the light chain variable region of the first binding unit are on a common polypeptide subunit of the multi-specific antibody, and are connected by a linker sequence.

3 . The multi-specific antibody of claim 1 , wherein the heavy chain variable region and the light chain variable region of the first binding unit are on different polypeptide subunits of the multi-specific antibody.

4 . The multi-specific antibody of claim 1 , wherein the heavy chain variable region of the first binding unit comprises:

(i) a CDR1 sequence of SEQ ID NO: 4, a CDR2 sequence of SEQ ID NO: 5, and a CDR3 sequence of SEQ ID NO: 6; or

(ii) a CDR1 sequence of SEQ ID NO: 7, a CDR2 sequence of SEQ ID NO: 5, and a CDR3 sequence of SEQ ID NO: 8.

5 . The multi-specific antibody of claim 1 , wherein the human VL framework is a human Vkappa framework; or wherein the human VL framework is a human Vlambda framework.

6 . The multi-specific antibody of claim 1 , wherein the heavy chain variable region of the first binding unit comprises a sequence having at least 95% identity to SEQ ID NO: 14 or SEQ ID NO: 15; or wherein the heavy chain variable region of the first binding unit comprises the sequence of SEO ID NO: 14 or SEO ID NO: 15.

7 . The multi-specific antibody of claim 1 , wherein the light chain variable region of the first binding unit comprises a sequence having at least 95% identity to SEQ ID NO: 16 or SEQ ID NO: 17; or wherein the light chain variable region of the first binding unit comprises the sequence of SEQ ID NO: 16 or SEQ ID NO: 17.

8 . The multi-specific antibody of claim 1 , wherein the antigen-binding domain of the anti-BCMA heavy chain-only antibody comprises a variable region sequence having at least 95% identity to the sequence of SEQ ID NO: 12; or wherein the antigen-binding domain of the anti-BCMA heavy chain-only antibody comprises a variable region sequence comprising the sequence of SEQ ID NO: 12.

9 . The multi-specific antibody of claim 1 , wherein the antigen-binding domain of the anti-BCMA heavy chain-only antibody is in a bivalent configuration, and comprises a linker sequence.

10 . The multi-specific antibody of claim 9 , wherein the linker sequence comprises a G4S linker sequence.

11 . The multi-specific antibody of claim 1 , wherein the first binding unit further comprises a heavy chain constant region comprising a CH1 domain, a hinge region, a CH2 domain, and a CH3 domain.

12 . The multi-specific antibody of claim 11 , wherein the CH2 domain comprises the sequence of a wild type human IgG4 CH2 domain (SEQ ID NO: 36); or wherein the CH2 domain comprises a variant human IgG4 CH2 domain comprising an F234A mutation, an L235A mutation, or both an F234A mutation and an L235A mutation.

13 . The multi-specific antibody of claim 11 , wherein the CH3 domain comprises the sequence of a wild type human IgG4 CH3 domain (SEQ ID NO: 38); wherein the CH3 domain comprises a variant human IgG4 CH3 domain comprising a T366W mutation (SEQ ID NO: 39); or wherein the CH3 domain comprises a variant human IgG4 CH3 domain comprising a T366S mutation, an L368A mutation, and a Y407V mutation (SEQ ID NO: 40).

14 . The multi-specific antibody of claim 11 , wherein the hinge region comprises the sequence of a wild type human IgG4 hinge region (SEQ ID NO: 32); or wherein the hinge region comprises a variant human IgG4 hinge region sequence comprising an S228P mutation (SEO ID NO: 33).

15 . The multi-specific antibody of claim 14 , further comprising a variant human IgG4 CH2 domain comprising an F234A mutation and an L235A mutation; or further comprising a variant human IgG4 CH3 domain comprising a T366W mutation; or further comprising a variant human IgG4 CH3 domain comprising a T366S mutation, an L368A mutation, and a Y407V mutation.

16 . The multi-specific antibody of claim 1 , wherein the first binding unit further comprises a light chain constant region comprising a human Vkappa constant region sequence; or wherein the first binding unit further comprises a light chain constant region comprising a human Vlambda constant region sequence.

17 . The multi-specific antibody of claim 1 , wherein the second binding unit further comprises a heavy chain constant region sequence, in the absence of a CH1 sequence.

18 . The multi-specific antibody of claim 17 , wherein the heavy chain constant region sequence comprises a CH2 domain and a CH3 domain, but no CH1 domain.

19 . The multi-specific antibody of claim 18 , wherein the CH2 domain comprises the sequence of a wild type human IgG4 CH2 domain (SEQ ID NO: 36); or wherein the CH2 domain comprises a variant human IgG4 CH2 domain comprising an F234A mutation, an L235A mutation, or both an F234A mutation and an L235A mutation.

20 . The multi-specific antibody of claim 18 , wherein the CH3 domain comprises the sequence of a wild type human IgG4 CH3 domain (SEQ ID NO: 38); or wherein the CH3 domain comprises a variant human IgG4 CH3 domain comprising a T366W mutation (SEO ID NO: 39); or wherein the CH3 domain comprises a variant human IgG4 CH3 domain comprising a T366S mutation, an L368A mutation, and a Y407V mutation (SEO ID NO: 40).

21 . The multi-specific antibody of claim 18 , wherein the multi-specific antibody further comprises a hinge region, wherein the hinge region comprises a wild type human IgG4 hinge region sequence (SEQ ID NO: 32); or wherein the hinge region comprises a variant human IgG4 hinge region sequence comprising an S228P mutation (SEO ID NO: 33).

22 . The multi-specific antibody of claim 21 , further comprising a variant human IgG4 CH2 domain comprising an F234A mutation and an L235A mutation.

23 . The multi-specific antibody of claim 22 , further comprising a variant human IgG4 CH3 domain comprising a T366W mutation; or further comprising a variant human IgG4 CH3 domain comprising a T366S mutation, an L368A mutation, and a Y407V mutation.

24 . The multi-specific antibody of claim 1 , which is bispecific.

25 . A bispecific three-chain antibody-like molecule that binds to BCMA and La protein, comprising:

(i)

(a) a first heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 18;

(b) a second heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 24; and

(c) a first light chain polypeptide subunit comprising the sequence of SEQ ID NO: 20; or

(ii)

(a) a first heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 18;

(b) a second heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 26; and

(c) a first light chain polypeptide subunit comprising the sequence of SEQ ID NO: 20; or

(iii)

(a) a first heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 21;

(b) a second heavy chain polypeptide subunit comprising the sequence of SEO ID NO: 24; and

(c) a first light chain polypeptide subunit comprising the sequence of SEQ ID NO: 23; or

(iv)

(a) a first heavy chain polypeptide subunit comprising the sequence of SEO ID NO: 21;

(b) a second heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 26; and

(c) a first light chain polypeptide subunit comprising the sequence of SEQ ID NO: 23; or

(v)

(a) a first heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 19;

(b) a second heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 25; and

(c) a first light chain polypeptide subunit comprising the sequence of SEO ID NO: 20; or

(vi)

(a) a first heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 19;

(b) a second heavy chain polypeptide subunit comprising the sequence of SEO ID NO: 27; and

(c) a first light chain polypeptide subunit comprising the sequence of SEQ ID NO: 20; or

(vii)

(a) a first heavy chain polypeptide subunit comprising the sequence of SEO ID NO: 22;

(b) a second heavy chain polypeptide subunit comprising the sequence of SEO ID NO: 25; and

(c) a first light chain polypeptide subunit comprising the sequence of SEQ ID NO: 23; or

(viii)

(a) a first heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 22;

(b) a second heavy chain polypeptide subunit comprising the sequence of SEQ ID NO: 27; and

(c) a first light chain polypeptide subunit comprising the sequence of SEQ ID NO: 23.

26 . A method of treatment, comprising administering to an individual in need an effective dose of the antibody of claim 1 , or a pharmaceutical composition comprising the antibody of claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 30, 2023
From: TRINKLEIN, NATHAN; HARRIS, KATHERINE; MALIK, HARBANI; SCHELLENBERGER, UTE; VAFA, OMID; FORCE ALDRED, SHELLEY
To: TENEOBIO, INC.
Reel/Frame 064127/0714 →
Continuity (2)
Provisional Application 63046477 · Jun 30, 2020
Related Publication 20230257473A1 · Aug 17, 2023
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