US 11,912,776 B2
Chimeric antigen receptors targeting B-cell maturation antigen
Tracy Chia-Chien Kuo, San Mateo, CA (US); Bijan Andre Boldajipour, San Francisco, CA (US); Javier Fernando Chaparro Riggers, San Mateo, CA (US); Philippe Duchateau, Draveil (FR); Roman Galetto, Paris (FR); Alexandre Juillerat, New York, NY (US); Thomas Charles Pertel, San Mateo, CA (US); Arvind Rajpal, San Francisco, CA (US); Barbra Johnson Sasu, San Francisco, CA (US); Cesar Adolfo Sommer, San Mateo, CA (US); Julien Valton, Charenton le Pont (FR); and Thomas John Van Blarcom, Oakland, CA (US)
Assigned to PFIZER INC., New York, NY (US)
Filed by Pfizer Inc., New York, NY (US)
Filed on Mar. 15, 2022, as Appl. No. 17/695,769.
Application 17/695,769 is a division of application No. 16/384,719, filed on Apr. 15, 2019, granted, now 11,312,782.
Application 16/384,719 is a division of application No. 15/085,317, filed on Mar. 30, 2016, granted, now 10,294,304.
Claims priority of provisional application 62/301,177, filed on Feb. 29, 2016.
Claims priority of provisional application 62/286,473, filed on Jan. 25, 2016.
Claims priority of provisional application 62/146,825, filed on Apr. 13, 2015.
Prior Publication US 2022/0340671 A1, Oct. 27, 2022
Int. Cl. C07K 14/705 (2006.01); C07K 16/28 (2006.01); A61K 39/395 (2006.01); A61K 39/00 (2006.01); C12N 5/10 (2006.01); C07K 14/725 (2006.01); A61K 31/7076 (2006.01); C12N 15/63 (2006.01); A61K 35/17 (2015.01); C12N 5/0783 (2010.01); A61K 38/00 (2006.01)
CPC C07K 16/2878 (2013.01) [A61K 31/7076 (2013.01); A61K 35/17 (2013.01); A61K 39/0011 (2013.01); A61K 39/46 (2023.05); A61K 39/4631 (2023.05); A61K 39/464417 (2023.05); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70578 (2013.01); C07K 16/2896 (2013.01); C12N 5/0636 (2013.01); C12N 5/10 (2013.01); C12N 15/63 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5156 (2013.01); C07K 16/2863 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/569 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/92 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/33 (2013.01); C12N 2510/02 (2013.01)] 24 Claims
 
1. A method of treating a condition associated with malignant cells expressing B-cell maturation antigen (BCMA) in a subject comprising:
administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising an engineered immune cell expressing at the surface a BCMA-specific chimeric antigen receptor (CAR) comprising an extracellular ligand-binding domain, a first transmembrane domain, and an intracellular signaling domain and wherein the extracellular ligand-binding domain comprises a single chain Fv fragment (scFv) comprising
(i) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 33 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 34;
(ii) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 112 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 38;
(iii) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 72 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 73;
(iv) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 39 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 40;
(v) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 76 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 77;
(vi) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 83 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 84;
(vii) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 92 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 93;
(viii) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 25 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 18; or
(ix) a heavy chain variable (VH) region comprising the amino acid sequence shown in SEQ ID NO: 8 and a light chain variable (VL) region comprising the amino acid sequence shown in SEQ ID NO: 80,
wherein the transmembrane domain comprises a CD8α chain transmembrane domain, and wherein the intracellular signaling domain comprises a CD3ξ signaling domain and/or a 4-1BB signaling domain.