IP Library › Granted Patent US 12,637,509
Granted Patent B2
US 12,637,509 · App. 17/672,123 · Granted May 26, 2026

Trispecific antibody targeting BCMA, GPRC5D, and CD3

Inventors: Ricardo Marcos Attar (Spring House, PA); Scott Ronald Brodeur (New Hope, PA); Rajkumar Ganesan (Thousand Oaks, CA); Leopoldo Luistro (Lansdale, PA); Ulrike Philippar (Antwerp, BE); Kodandaram Pillarisetti (King of Prussia, PA); Sanjaya Singh (Blue Bell, PA); Danlin Dan Qing Yang (Philadelphia, PA)
Assignee: Janssen Biotech, Inc.
C07K16/2803A61P35/00C07K14/7051A61K2039/505A61K2039/545C07K2317/24C07K2317/33C07K2317/55C07K2317/565C07K2317/567C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,637,509
App. No.
17/672,123
Granted
May 26, 2026
Kind
B2
Abstract

Provided herein are multispecific antibodies that bind to BCMA, GPRC5D and CD3 and multispecific antigen-binding fragments thereof. Also described are related polynucleotides capable of encoding the provided multispecific antibodies or multispecific antigen-binding fragments, cells expressing the provided multispecific antibodies or multispecific antigen-binding fragments, as well as associated vectors and detectably labeled multispecific antibodies or multispecific antigen-binding fragments. In addition, methods of producing and using the provided multispecific antibodies and multispecific antigen-binding fragments are described. Further provided herein are antibodies that bind to BCMA and antigen-binding fragments thereof. Also described are related polynucleotides capable of encoding the provided BCMA-specific antibodies or antigen-binding fragments, cells expressing the provided BCMA-specific antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled BCMA-specific antibodies or antigen-binding fragments. In addition, methods of producing and using the provided BCMA-specific antibodies and antigen-binding fragments are described.

Claims (68)

1 . A trispecific antibody, comprising:

(a) a first antigen-binding arm comprising a first heavy chain variable domain (VH1) and a first light chain variable domain (VL1), wherein the VH1 comprises the heavy chain complementarity determining region 1 (HCDR1), the HCDR2, and the HCDR3 of the VH1 of SEQ ID NO: 8 and the VL1 comprises the light chain complementarity determining region 1 (LCDR1), the LCDR2, and the LCDR3 of the VL1 of SEQ ID NO: 7;

(b) a second antigen-binding arm comprising a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2), wherein the VH2 comprises the HCDR1, the HCDR2, and the HCDR3 of the VH2 of SEQ ID NO: 16 and the VL2 comprises the LCDR1, the LCDR2, and the LCDR3 of the VL2 of SEQ ID NO: 15;

(c) a third antigen-binding arm comprising a third heavy chain variable domain (VH3) and a third light chain variable domain (VL3), wherein the VH3 comprises the HCDR1, the HCDR2, and the HCDR3 of the VH3 of SEQ ID NO: 24 and the VL3 comprises the LCDR1, the LCDR2, and the LCDR3 of the VL3 of SEQ ID NO: 23;

wherein the first antigen-binding arm binds to an epitope on cluster of differentiation 3 (CD3), the second antigen-binding arm binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and the third antigen-binding arm binds to an epitope on B cell maturation antigen (BCMA).

2 . The trispecific antibody of claim 1 , wherein the first antigen-binding arm comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 4, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 5, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 6, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 1, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 2, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 3.

3 . The trispecific antibody of claim 2 , wherein the first antigen-binding arm comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7.

4 . The trispecific antibody of claim 1 , wherein the second antigen-binding arm comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 12, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 13, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 14, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 9, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 10, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 11.

5 . The trispecific antibody of claim 4 , wherein the second antigen-binding arm comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15.

6 . The trispecific antibody of claim 1 , wherein the third antigen-binding arm comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 20, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 21, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 22, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 17, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 18, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 19.

7 . The trispecific antibody of claim 6 , wherein the third antigen-binding arm comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.

8 . The trispecific antibody of claim 1 , wherein:

the first antigen-binding arm comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 of SEQ ID NOs: 4, 5, 6, 1, 2, and 3, respectively;

the second antigen-binding arm comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 of SEQ ID NOs: 12, 13, 14, 9, 10, and 11, respectively; and

the third antigen-binding arm comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 of SEQ ID NOs: 20, 21, 22, 17, 18, and 19, respectively.

9 . The trispecific antibody of claim 8 , wherein:

the first antigen-binding arm comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7;

the second antigen-binding arm comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15; and

the third antigen-binding arm comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.

10 . The trispecific antibody of claim 1 , wherein the first antigen-binding arm comprises a Fragment crystallizable (Fc) domain comprising the amino acid sequence of SEQ ID NO: 158 wherein the Fc domain comprises one or more mutations selected from T366S, L368A, T366W, and Y407V according to EU numbering.

11 . The trispecific antibody of claim 10 , wherein the Fc domain further comprises one or more mutations selected from L234A, L235A, and D265S according to EU numbering.

12 . The trispecific antibody of claim 10 , wherein the Fc domain comprises mutations H435R and/or Y436F according to EU numbering.

13 . The trispecific antibody of claim 1 , wherein the first antigen-binding arm specifically binds to SEQ ID NO: 161.

14 . The trispecific antibody of claim 1 , wherein the third antigen-binding arm specifically binds to SEQ ID NO: 162.

15 . The trispecific antibody of claim 1 , wherein the first antigen-binding arm comprises a first heavy chain (HC1) comprising the amino acid sequence of SEQ ID NO: 26.

16 . The trispecific antibody of claim 15 , wherein the first antigen-binding arm comprises a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 27.

17 . The trispecific antibody of claim 1 , wherein a single polypeptide comprises the second antigen-binding arm and the third antigen-binding arm, the single polypeptide comprising the amino acid sequence of SEQ ID NO: 28.

18 . The trispecific antibody of claim 17 , wherein the first antigen-binding arm comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 26 and a LC comprising the amino acid sequence of SEQ ID NO: 27.

19 . A synthetic polynucleotide encoding the trispecific antibody or trispecific binding fragment of claim 1 .

20 . A pharmaceutical composition for treating multiple myeloma comprising the trispecific antibody of claim 1 and a pharmaceutically acceptable carrier.

21 . A cell expressing the trispecific antibody of claim 1 .

22 . The cell of claim 21 , wherein the cell is a hybridoma.

23 . The cell of claim 21 , wherein the trispecific antibody is recombinantly produced.

24 . A method for treating multiple myeloma in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 20 .

25 . The method of claim 24 , wherein the pharmaceutical composition is administered for a time sufficient to treat the multiple myeloma.

26 . The method of claim 24 , wherein the multiple myeloma expresses BCMA and/or GPRC5D.

27 . The method of claim 26 , wherein the multiple myeloma is smoldering multiple myeloma (SMM).

28 . The method of claim 24 , wherein the multiple myeloma is relapsed, refractory, or any combination thereof.

29 . The method of claim 28 , wherein the subject has received a prior treatment, wherein the prior treatment comprises a proteasome inhibitor, an immunomodulatory drug, a CD38 antibody, a bispecific agent, a CAR-T therapy, or a combination thereof.

30 . A method for generating a trispecific antibody, wherein the method comprises culturing the cell of claim 21 and isolating the trispecific antibody.

31 . A trispecific antibody, comprising:

a polypeptide comprising the amino acid sequence of SEQ 1 D NO: 29,

a polypeptide comprising the amino acid sequence of SEQ 1 D NO: 30, and

a polypeptide comprising the amino acid sequence of SEQ 11 ) NO: 31.

32 . A trispecific antibody, comprising:

a polypeptide comprising the amino acid sequence of SEQ 1 D NO: 26,

a polypeptide comprising the amino acid sequence of SEQ 1 D NO: 27, and

a polypeptide comprising the amino acid sequence of SEQ 11 ) NO: 28.

33 . A trispecific antibody, comprising:

a polypeptide comprising the amino acid sequence of SEQ 1 D NO: 29,

a polypeptide comprising the amino acid sequence of SEQ 1 D NO: 30, and

a polypeptide comprising the amino acid sequence of SEQ 11 ) NO: 31.

34 . A trispecific antibody, comprising:

a polypeptide comprising the amino acid sequence of SEQ 1 D NO: 26,

a polypeptide comprising the amino acid sequence of SEQ 1 D NO: 27, and

a polypeptide comprising the amino acid sequence of SEQ 11 ) NO: 28.

35 . A method for treating multiple myeloma in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the trispecific antibody of claim 31 .

36 . The method of claim 35 , wherein the trispecific antibody is administered for a time sufficient to treat the multiple myeloma.

37 . The method of claim 35 , wherein the multiple myeloma expresses BCMA and/or GPRC5D.

38 . The method of claim 37 , wherein the multiple myeloma is smoldering multiple myeloma (SMM).

39 . The method of claim 35 , wherein the multiple myeloma is relapsed, refractory, or any combination thereof.

40 . The method of claim 39 , wherein the subject has received a prior treatment, wherein the prior treatment comprises a proteasome inhibitor, an immunomodulatory drug, a CD38 antibody, a bispecific agent, a CAR-T therapy, or a combination thereof.

41 . A method for treating multiple myeloma in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the trispecific antibody of claim 33 .

42 . The method of claim 41 , wherein the trispecific antibody is administered for a time sufficient to treat the multiple myeloma.

43 . The method of claim 41 , wherein the multiple myeloma expresses BCMA and/or GPRC5D.

44 . The method of claim 43 , wherein the multiple myeloma is smoldering multiple myeloma (SMM).

45 . The method of claim 41 , wherein the multiple myeloma is relapsed, refractory, or any combination thereof.

46 . The method of claim 45 , wherein the subject has received a prior treatment, wherein the prior treatment comprises a proteasome inhibitor, an immunomodulatory drug, a CD38 antibody, a bispecific agent, a CAR-T therapy, or a combination thereof.

Assignments (8)
CORRECTIVE ASSIGNMENT TO CORRECT THE CONVEYING PARTY DATA IS JANSSEN RESEARCH & DEVELOPMENT, LLC PREVIOUSLY RECORDED ON REEL 60410 FRAME 702. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Mar 24, 2026
From: JANSSEN RESEARCH & DEVELOPMENT, LLC
To: JANSSEN PHARMACEUTICA NV
Reel/Frame 075219/0068 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 12, 2025
From: JANSSEN PHARMACEUTICA NV
To: JANSSEN BIOTECH, INC.
Reel/Frame 073951/0804 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 12, 2022
From: CENTOCOR RESEARCH & DEVELOPMENT, INC.
To: JANSSEN PHARMACEUTICA NV
Reel/Frame 060480/0608 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 6, 2022
From: JANSSEN RESEARCH & DEVELOPMENT, INC.
To: JANSSEN PHARMACEUTICA NV
Reel/Frame 060410/0702 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 6, 2022
From: ATTAR, RICARDO MARCOS
To: JANSSEN RESEARCH & DEVELOPMENT, LLC
Reel/Frame 060411/0009 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2022
From: PHILIPPAR, ULRIKE
To: JANSSEN PHARMACEUTICA NV
Reel/Frame 060284/0833 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2022
From: PILLARISETTI, KODANDARAM
To: CENTOCOR RESEARCH & DEVELOPMENT, INC.
Reel/Frame 060284/0983 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2022
From: BRODEUR, SCOTT RONALD; GANESAN, RAJKUMAR; LUISTRO, LEOPOLDO; SINGH, SANJAYA; YANG, DANLIN DAN QING
To: JANSSEN RESEARCH & DEVELOPMENT, LLC
Reel/Frame 060284/0766 →
Continuity (2)
Provisional Application 63149921 · Feb 16, 2021
Related Publication 20220267438A1 · Aug 25, 2022
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