US 11,970,525 B2
Treatment of cancer using GFR alpha-4 chimeric antigen receptor
Donald L. Siegel, Lansdale, PA (US); Michael C. Milone, Cherry Hill, NJ (US); Vijay Bhoj, Philadelphia, PA (US); and Christoph Rader, Jupiter, FL (US)
Assigned to The Trustees of the University of Pennsylvania, Philadelphia, PA (US); Novartis AG, Basel (CH); and The Scripps Research Institute, La Jolla, CA (US)
Filed by THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, Philadelphia, PA (US); NOVARTIS AG, Basel (CH); and THE SCRIPPS RESEARCH INSTITUTE, La Jolla, CA (US)
Filed on Oct. 23, 2020, as Appl. No. 17/078,903.
Application 17/078,903 is a division of application No. 15/503,971, granted, now 10,851,149, previously published as PCT/US2015/045349, filed on Aug. 14, 2015.
Claims priority of provisional application 62/037,383, filed on Aug. 14, 2014.
Prior Publication US 2021/0079059 A1, Mar. 18, 2021
Int. Cl. C07K 14/725 (2006.01); C07K 14/705 (2006.01); C07K 14/71 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01)
CPC C07K 14/7051 (2013.01) [C07K 14/70517 (2013.01); C07K 14/70578 (2013.01); C07K 14/71 (2013.01); C07K 16/2863 (2013.01); C07K 16/30 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5156 (2013.01); C07K 2317/24 (2013.01); C07K 2317/33 (2013.01); C07K 2317/55 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2319/00 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/50 (2013.01); C07K 2319/70 (2013.01)] 20 Claims
 
1. A chimeric antigen receptor (CAR) polypeptide comprising an antigen binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the antigen binding domain binds to isoform a or isoform b of human Glycosyl-phosphatidylinositol (GPI)-linked GDNF family α-receptor 4 (GFRα4) cell-surface receptor and comprises:
(a) (i) a heavy chain variable region comprising a heavy chain complementary determining region 1 (HC CDR1) comprising the amino acid sequence set forth in SEQ ID NO: 63, a heavy chain complementary determining region 2 (HC CDR2) comprising the amino acid sequence set forth in SEQ ID NO: 65, and a heavy chain complementary determining region 3 (HC CDR3) comprising the amino acid sequence set forth in SEQ ID NO: 67; and
(ii) a light chain complementary determining region 1 (LC CDR1) comprising the amino acid sequence set forth in SEQ ID NO: 71, a light chain complementary determining region 2 (LC CDR2) comprising the amino acid sequence set forth in SEQ ID NO: 73, and a light chain complementary determining region 3 (LC CDR3) comprising the amino acid sequence set forth in SEQ ID NO: 75; or
(b) (i) a heavy chain variable region comprising a heavy chain complementary determining region 1 (HC CDR1) comprising the amino acid sequence set forth in SEQ ID NO: 43, a heavy chain complementary determining region 2 (HC CDR2) comprising the amino acid sequence set forth in SEQ ID NO: 45, and a heavy chain complementary determining region 3 (HC CDR3) comprising the amino acid sequence set forth in SEQ ID NO: 47; and
(ii) a light chain complementary determining region 1 (LC CDR1) comprising the amino acid sequence set forth in SEQ ID NO: 51, a light chain complementary determining region 2 (LC CDR2) comprising the amino acid sequence set forth in SEQ ID NO: 53, and a light chain complementary determining region 3 (LC CDR3) comprising the amino acid sequence set forth in SEQ ID NO: 55.