US 12,071,466 B2
Anti-human kallikrein-2 (hK2) chimeric antigen receptor (CAR) and methods of use thereof
Raymond Brittingham, Spring House, PA (US); Rajkumar Ganesan, Blue Bell, PA (US); Sherry La Porte, Horsham, PA (US); John T. Lee, North Wales, PA (US); Jinquan Luo, Malvern, PA (US); Theresa McDevitt, Warminster, PA (US); Fei Shen, Collegeville, PA (US); Sanjaya Singh, Blue Bell, PA (US); Degang Song, Wynnewood, PA (US); Sathyadevi Venkataramani, Blue Bell, PA (US); Fang Yi, Collegeville, PA (US); and Yonghong Zhao, Trooper, PA (US)
Assigned to Janssen Biotech, Inc., Horsham, PA (US)
Filed by Janssen Biotech, Inc., Horsham, PA (US)
Filed on Jul. 23, 2020, as Appl. No. 16/936,719.
Claims priority of provisional application 63/030,522, filed on May 27, 2020.
Claims priority of provisional application 62/910,645, filed on Oct. 4, 2019.
Claims priority of provisional application 62/898,635, filed on Sep. 11, 2019.
Claims priority of provisional application 62/878,958, filed on Jul. 26, 2019.
Prior Publication US 2022/0064254 A1, Mar. 3, 2022
Int. Cl. A61K 35/17 (2015.01); A61K 38/00 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 16/40 (2006.01)
CPC C07K 14/7051 (2013.01) [A61K 35/17 (2013.01); C07K 14/70517 (2013.01); C07K 14/70596 (2013.01); C07K 16/40 (2013.01); A61K 38/00 (2013.01); C07K 2317/53 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01)] 35 Claims
 
1. A chimeric antigen receptor (CAR) comprising:
(a) an extracellular domain that specifically binds to the human Kallikrein-2 (hK2) antigen, wherein the extracellular antigen-binding domain comprises:
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 63, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 64, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 66, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 67, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 69, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 71;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 63, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 65, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 66, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 68, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 70, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 71;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 63, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 65, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 66, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 67, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 126, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 71;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 63, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 65, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 66, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 67, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 69, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 71;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 63, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 65, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 66, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 67, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 126, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 71;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 314, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 315, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 311, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 312, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 313, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 91;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 102, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 103, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 104, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 128, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 129, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 130;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 107, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 108, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 109, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 125, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 131, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 132;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 102, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 112, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 113, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 133, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 134, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 135;
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 115, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 116, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 117, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 136, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 137, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 138; or
a heavy chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 120, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 121, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 122, and a light chain complementarity determining region 1 (CDR1) having the amino acid sequence of SEQ ID NO: 97, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 127, a light chain CDR3 having the amino acid sequence of SEQ ID NO: 138;
(b) a transmembrane domain, wherein the transmembrane domain comprises a CD8a transmembrane region (CD8a-TM) polypeptide, and
(c) an intracellular signaling domain optionally comprising at least one co-stimulatory domain comprising a TNF receptor superfamily member 9 (CD137) component and a primary signaling domain comprising a T-cell surface glycoprotein CD3 zeta chain (CD3z) component.