IP Library › Granted Patent US 12,545,746
Granted Patent B2
US 12,545,746 · App. 17/785,537 · Granted Feb 10, 2026

Anti-BCMA car antibodies, conjugates, and methods of use

Inventors: Kevin Friedman (Melrose, MA); Molly Reed Perkins (Milton, MA)
Assignee: 2seventy bio, Inc.
C07K16/4266G01N33/505C07K2317/21C07K2317/24C07K2317/622
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Quick Facts
Patent No.
US 12,545,746
App. No.
17/785,537
Granted
Feb 10, 2026
Kind
B2
Abstract

The invention provides improved methods for detecting anti-BCMA CAR expression on T cells. The invention generally provides antibodies and antigen binding fragments thereof, conjugates thereof, and methods of using the same to detect, determine, or measure CAR T cells and/or CAR expression on one or more T cells.

Claims (20)

1 . An antibody or antigen binding fragment thereof comprising a variable light chain sequence set forth in SEQ ID NO: 7 and a variable heavy chain sequence set forth in SEQ ID NO: 8.

2 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is an scFv.

3 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof comprises a light chain sequence set forth in SEQ ID NO: 11 and a heavy chain sequence set forth in SEQ ID NO: 12 or SEQ ID NO: 13.

4 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof binds one or more epitopes of an anti-BCMA CAR sequence set forth in SEQ ID NO: 9 and/or SEQ ID NO: 10.

5 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment is murine or chimeric.

6 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment comprises an IgG1, IgG2, IgG3, or IgG4 constant domain.

7 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment comprises an IgG1 constant domain.

8 . A conjugate, comprising the antibody or antigen binding fragment thereof of claim 1 ; and a detectable label.

9 . The conjugate of claim 8 , wherein the detectable label is selected from the group consisting of: a hapten, a fluorescent dye, a fluorescent protein, a chromophore, a metal ion, a gold particle, a silver particle, a magnetic particle, a polypeptide, an enzyme, a luminescent compound, or an oligonucleotide.

10 . The conjugate of claim 8 , wherein the detectable label is an AlexaFluor® (AF) dye selected from the group consisting of: AF350, AF405, AF488, AF500, AF514, AF532, AF546, AF555, AF568, AF594, AF610, AF633, AF635, AF647, AF680, AF700, AF710, AF750, AF790, and AF800.

11 . The conjugate of claim 10 , wherein the detectable label is the AlexaFluor® (AF) dye AF488.

12 . The conjugate of claim 8 , wherein the detectable label is an enzyme selected from the group consisting of: alkaline phosphatase, horseradish peroxidase, luciferase, and β-galactosidase.

13 . A polynucleotide encoding the antibody or antigen-binding fragment thereof of claim 1 .

14 . A host cell comprising the or the polynucleotide of claim 13 .

15 . A composition comprising the antibody or antigen-binding fragment thereof of claim 1 .

16 . A method of producing an antibody or antigen-binding fragment thereof, comprising expressing the antibody or antigen-binding fragment thereof of claim 1 , in a host cell and recovering or isolating the antibody.

17 . A kit comprising the antibody or antigen-binding fragment thereof of claim 1 and instructions for use.

18 . A method of detecting expression of an anti-BCMA CAR on a T cell, comprising: contacting a T cell with the antibody or antigen-binding fragment thereof of claim 1 and detecting the formation of an antibody:anti-BCMA CAR complex.

19 . A method of determining the expression of an anti-BCMA CAR on a T cell comprising: contacting a T cell with the antibody or antigen-binding fragment thereof of claim 1 ; detecting the formation of an antibody:anti-BCMA CAR complex; and measuring the amount of the complex to determine the expression of the anti-BCMA CAR on the T cell.

20 . A method of determining a number of anti-BCMA CAR+ T cells in a population of T cells, comprising: contacting a population of T cells with the antibody or antigen-binding fragment thereof of claim 1 ; detecting the formation of an antibody:anti-BCMA CAR complex on one or more T cells; and enumerating the T cells that express the anti-BCMA CAR.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 24, 2022
From: FRIEDMAN, KEVIN; PERKINS, MOLLY REED
To: 2SEVENTY BIO, INC.
Reel/Frame 060889/0858 →
Continuity (2)
Provisional Application 62948488 · Dec 16, 2019
Related Publication 20230030085A1 · Feb 2, 2023
References Cited (67)
US 4671958A · Rodwell et al. · 1987 [cited by applicant]
US 5585089A · Queen et al. · 1996 [cited by applicant]
US 5665357A · Rose et al. · 1997 [cited by applicant]
US 12247084B2 · Friedman et al. · 2025 [cited by applicant]
US 20160046724A1 · Brogdon et al. · 2016 [cited by applicant]
US 20170051068A1 · Pillarisetti et al. · 2017 [cited by applicant]
US 20180162952A1 · Foord et al. · 2018 [cited by applicant]
US 20210261689A1 · Friedman et al. · 2021 [cited by applicant]
US 20250197523A1 · Friedman et al. · 2025 [cited by applicant]
EP 0404097A2 · 1990 [cited by applicant]
WO WO9301161A1 · 1993 [cited by applicant]
WO WO9306213A1 · 1993 [cited by applicant]
WO WO2012030982A1 · 2012 [cited by applicant]
WO WO2014190273A1 · 2014 [cited by applicant]
WO WO2016014565A2 · 2016 [cited by applicant]
WO WO2016014789A2 · 2016 [cited by applicant]
WO WO2016094304A2 · 2016 [cited by applicant]
WO WO2017031104A1 · 2017 [cited by applicant]
WO WO2018022786A1 · 2018 [cited by applicant]
WO WO2018156791A1 · 2018 [cited by applicant]
WO WO2018231759A1 · 2018 [cited by applicant]
WO WO2019118892A1 · 2019 [cited by applicant]
WO WO2019161035A1 · 2019 [cited by applicant]
Immunoglobulin kappa light chain variable region gene complex organization and immunoglobulin genes encoding anti-DNA autoantibodies in lupus mice, J. Clin. Invest.82, 852-860, 1988. [cited by examiner]
GenBank: CAH69220.1 (downloaded on May 20, 2025; published Apr. 27, 2010. [cited by examiner]
Proteins, Mar. 2012;80(3):896-912. [cited by examiner]
Extended European Search Report for Application No. 20902960.2 dated Mar. 7, 2024. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 16/973,877 dated Nov. 6, 2024. [cited by applicant]
Extended European Search Report for EP Application No. 19820088.3 dated Feb. 16, 2022, 9 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2020/065352, dated Mar. 15, 2021, 10 pages. [cited by applicant]
Bellucci, et al., “Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor.” Blood (2005); 105(10): 3945-3950. [cited by applicant]
Boerner P., et al., “Production of Antigen-Specific Human Monoclonal Antibodies From in Vitro-primed Human Splenocytes,” Journal of Immunology, Jul. 1991, vol. 147, No. 1, pp. 86-95. [cited by applicant]
Borden and Kabat, “Nucleotide sequence of the cDNAs encoding the variableregion heavy and light chains of a myeloma protein specific for the terminalnonreducing end of alpha(1-6)dextran”, Proc Natl Acad Sci U S A (1987)… [cited by applicant]
Brodeur et al., “Mouse-Human Myeloma Partners for the Production of Heterohybridomas,” Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., Mar. 1987, pp. 51-63. [cited by applicant]
Bruggemann, M. et al. (1993). “Designer Mice: The Production of Human Antibody Repertoires in Transgenic Animals,” Year in Immuno., vol. 7, pp. 33-40. [cited by applicant]
Chothia C., et al., “Canonical Structures for the Hypervariable Regions of Immunoglobulins,” Journal of Molecular Biology, Aug. 20, 1987, vol. 196, No. 4, pp. 901-917. [cited by applicant]
Chothia C., et al., “Conformations of Immunoglobulin Hypervariable Regions,” Nature, Dec. 1989, vol. 342, pp. 877-883. [cited by applicant]
Conde et al., “Revisiting 30 years of biofunctionalization and surface chemistry of inorganic nanoparticles for nanomedicine ” Frontiers in Chemistry, Jul. 15, 2014, vol. 2, article 48, 27 pages. [cited by applicant]
Holliger et al., ““Diabodies”: small bivalent and bispecific antibody fragments,” Proc. Natl. Acad. Sci. USA 90(14): 6444-6448 (1993). [cited by applicant]
Holt et al., “Domain antibodies: proteins for therapy”, Trends in Biotechnology, Nov. 2003, 21(11): 484-490. [cited by applicant]
Hu et. al., “The Chimeric Antigen Receptor Detection Toolkit,” Frontiers in Immunology, Aug. 11, 2020, vol. 11, pp. 1-16. [cited by applicant]
Hudson, P.J. et al. (Jan. 2003). “Engineered Antibodies,” Nat. Med., vol. 9, No. 1, pp. 129-134. [cited by applicant]
International Search Report and Written Opinion mailed on Oct. 1, 2019, for International Application No. PCT/US2019/037274, 8 pages. [cited by applicant]
Jakobovits, A. et al. (Mar. 18, 1993). “Germ-line Transmission and Expression of a Human-Derived Yeast Artificial Chromosome,” Nature, vol. 362, pp. 255-258. [cited by applicant]
Jakobovits, A. et al. (Mar. 1993). “Analysis of Homozygous Mutant Chimeric Mice: Deletion of the Immunoglobulin Heavy-Chain Joining Region Blocks B-Cell Development and Antibody Production,” Proc. Natl. Acad. Sci. USA, … [cited by applicant]
Jena et al., “Chimeric Antigen Receptor (CAR)-Specific Monoclonal Antibody to Detect CD19-Specific T Cells in Clinical Trials” PLoS One. vol. 8, No. 3, 12 pages. [cited by applicant]
Kalled, Susan L. “The role of BAFF in immune function and implications for autoimmunity.” Immunological Reviews (2005); 204.1: 43-54. [cited by applicant]
Kozbor et al., “A human hybrid myeloma for production of human monoclonal antibodies,” J Immunol. Dec. 1984;133(6):3001-5. [cited by applicant]
Laabi, Y., et al. “A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by at (4; 16)(q26; p13) translocation in a malignant T cell lymphoma.” The EMBO Journal (1992); 11.11: 3897-3904. [cited by applicant]
Laabi, Yacine, et al. “The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed.” Nucleic Acids Research (1994); 22.7: 1147-1154. [cited by applicant]
Mackay, Fabienne, et al. “BAFF and APRIL: a tutorial on B cell survival.” Annual Review of Immunology (2003); 21.1: 231-264. [cited by applicant]
Moreaux, Jrme, et al. “BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone.” Blood (2004); 103.8: 3148-3157. [cited by applicant]
Neri, Paola, et al. “Neutralizing B-Cell-Activating Factor Antibody Improves Survival and Inhibits Osteoclastogenesis in a Severe Combined Immunodeficient Human Multiple Myeloma Model.” Clinical Cancer Research (2007); … [cited by applicant]
Ng et al., “B Cell-Activating Factor Belonging to the TNF Family (BAFF)-R Is the Principal BAFF Receptor Facilitating BAFF Costimulation of Circulating T and B Cells.” Journal of Immunology (2004); 173(2): 807-817. [cited by applicant]
Novak, et al., “Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival.” Blood (2004); 103 (2): 689-694. [cited by applicant]
O'Connor, et al., “BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells”. Journal of Experimental Medicine (2004); 199(1): 91-97. [cited by applicant]
Orlandi, R. et al., “Cloning immunoglobulin variable domains for expression by the polymerase chain reaction”, Proc Natl Acad Sci USA (1989); 86(10):3833-3737. [cited by applicant]
Plockthun, , A. “Antibodies from [cited by applicant]
Reichman et al., “Comparison of FACS and PCR for Detection of BCMA-CAR-T Cells,” International Journal of Molecular Sciences, Jan. 14, 2022, vol. 23, No. 2, 14 pages. [cited by applicant]
Schiemann, Barbara, et al. “An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway.” Science (2001); 293.5537: 2111-2114. [cited by applicant]
Smith et al., “Development and Evaluation of an Optimal Human Single-Chain Variable Fragment-Derived BCMA-Targeted CAR T Cell Vector,” Mol Ther. Jun. 6, 2018;26(6):1447-1456. [cited by applicant]
Supplementary European Search Report for European Application No. EP20190820088, dated Mar. 9, 2022, 10 pages. [cited by applicant]
Thompson et al., “BAFF Binds to the Tumor Necrosis Factor Receptor-like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell Population,” J. Exp. Med., vol. 192, No. 1, Jul. 3, 2000,… [cited by applicant]
Whitelegg N & Rees AR, “Antibody variable regions: toward a unified modeling method,” Methods Mol Biol. 2004;248:51-91. [cited by applicant]
Whitelegg N & Rees AR, “WAM: an improved algorithm for modelling antibodies on the Web,” Protein Eng. Dec. 2000;13(12):819-24. [cited by applicant]
Wu et al., “An Analysis of the Sequences of the Variable Regions of Bence Jones Proteins and Myeloma Light Chains and Their Implications for Antibody Complementarity,” Journal of Experimental Medicine, Mar. 1970, vol. 1… [cited by applicant]
Xu, et al., “B-Cell Maturation Protein, Which Binds the Tumour Necrosis Factor Family Members BAFF and APRIL, Is Dispensable for Humoral Immune Responses.” Molecular and Cellular Biology (2001); 21 (12): 4067-4074. [cited by applicant]