US 12,351,640 B2
Chimeric antigen receptor and CAR-T cells that bind BCMA
Armin Rehm, Berlin (DE); Uta Elisabeth Höpken, Berlin (DE); Julia Bluhm, Berlin (DE); Wolfgang Uckert, Berlin (DE); Elisa Kieback, Berlin (DE); and Stephen Marino, Berlin (DE)
Assigned to Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, Berlin (DE)
Filed by Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft, Berlin (DE)
Filed on May 17, 2024, as Appl. No. 18/667,995.
Application 18/667,995 is a division of application No. 16/307,854, granted, now 12,048,718, previously published as PCT/EP2017/063862, filed on Jun. 7, 2017.
Claims priority of application No. 16173401 (EP), filed on Jun. 7, 2016.
Prior Publication US 2024/0382522 A1, Nov. 21, 2024
Int. Cl. C07K 16/28 (2006.01); A61K 35/17 (2025.01); A61K 39/00 (2006.01); A61K 40/11 (2025.01); A61K 40/22 (2025.01); A61K 40/31 (2025.01); A61K 40/41 (2025.01); A61K 40/42 (2025.01); A61K 47/65 (2017.01); C07K 14/705 (2006.01); C12N 5/0783 (2010.01); C12N 15/62 (2006.01); C12N 15/85 (2006.01)
CPC C07K 16/2878 (2013.01) [A61K 35/17 (2013.01); A61K 40/11 (2025.01); A61K 40/22 (2025.01); A61K 40/31 (2025.01); A61K 40/418 (2025.01); A61K 40/4211 (2025.01); A61K 40/4215 (2025.01); A61K 47/65 (2017.08); C07K 14/70596 (2013.01); C12N 5/0636 (2013.01); C12N 15/62 (2013.01); C12N 15/85 (2013.01); A61K 2039/505 (2013.01); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/48 (2023.05); C07K 2317/24 (2013.01); C07K 2317/33 (2013.01); C07K 2317/34 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2319/03 (2013.01)] 20 Claims
 
1. A nucleic acid molecule encoding a chimeric antigen receptor (CAR) polypeptide, wherein the CAR polypeptide comprises:
i. an extracellular antigen-binding domain, comprising an antibody or antibody fragment that binds a human B Cell Maturation Antigen (BCMA) polypeptide;
ii. a transmembrane domain; and
iii. an intracellular domain;
wherein the extracellular antigen-binding domain comprises:
(I) a variable heavy chain (VH) domain comprising:
(a) a heavy chain complementary determining region 1 (H-CDR1) comprising SEQ ID NO: 34 (RYWX1S), wherein X1 is I, F, L, V, Y, C, G, A, or M;
(b) a heavy chain complementary determining region 2 (H-CDR2) comprising amino acids 50-67 of SEQ ID NO: 53 (EINPZ2SSTINYAPSLKX11X12), wherein Z2 is S, N, T, G, or D; X11 is D; and X12 is K or R; and
(c) a heavy chain complementary determining region 3 (H-CDR3) comprising SEQ ID NO: 36 (SLYX4DYGDAX5DYW), wherein X4 is Y, and X5 is Y, L, F, I, V, A, C, or M; and
(II) a variable light chain (VL) domain comprising:
(a) a light chain complementary determining region 1 (L-CDR1) comprising SEQ ID NO: 37 (KASQSVX1X2NVA), wherein X1X2 is ES or DS;
(b) a light chain complementary determining region 2 (L-CDR2) comprising SEQ ID NO: 29 (SASLRFS), and
(c) a light chain complementary determining region 3 (L-CDR3) comprising SEQ ID NO: 30 (QQYNNYPLTFG);
wherein expression of the CAR polypeptide in an immune effector cell is effective to increase cytotoxicity of the immune effector cell to both (i) multiple myeloma cells, and (ii) mantle cell lymphoma cells.