	US 11,814,440 B2
	Glypican 2 as a cancer marker and therapeutic target
John M. Maris, Philadelphia, PA (US); Kristopher R. Bosse, Philadelphia, PA (US); Dimiter Dimitrov, Frederick, MD (US); Zhongyu Zhu, Frederick, MD (US); and Dontcho V. Jelev, Rockville, MD (US)
Assigned to The Children's Hospital of Philadelphia, Philadelphia, PA (US); and The United States of America, as Represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US)
Appl. No. 15/773,256
Filed by THE CHILDREN'S HOSPITAL OF PHILADELPHIA, Philadelphia, PA (US); and THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF THE HEALTH AND HUMAN SERVICES, Rockville, MD (US)
PCT Filed Nov. 8, 2016, PCT No. PCT/US2016/060974 § 371(c)(1), (2) Date May 3, 2018, PCT Pub. No. WO2017/083296, PCT Pub. Date May 18, 2017.
Claims priority of provisional application 62/350,976, filed on Jun. 16, 2016.
Claims priority of provisional application 62/253,000, filed on Nov. 9, 2015.
Prior Publication US 2018/0318444 A1, Nov. 8, 2018
Int. Cl. C07K 16/30 (2006.01); C07K 14/725 (2006.01); A61K 39/395 (2006.01); C07K 16/18 (2006.01); A61K 47/68 (2017.01); A61K 47/69 (2017.01); A61P 35/00 (2006.01); A61K 35/17 (2015.01); A61K 45/06 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/30 (2013.01) [A61K 35/17 (2013.01); A61K 39/39558 (2013.01); A61K 45/06 (2013.01); A61K 47/6889 (2017.08); A61K 47/6929 (2017.08); A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 16/18 (2013.01); A61K 2039/572 (2013.01); A61K 2300/00 (2013.01)]

14 Claims

1. A chimeric antigen receptor comprising:

(i) an ectodomain comprising a single chain antibody variable region derived from a monoclonal antibody that binds to a cancer cell-associated Glypican 2 on a Glypican-2 positive cancer cell, wherein said monoclonal antibody:

(a) is an IgG antibody;

(b) inhibits cancer cell growth; and

and said ectodomain has a flexible hinge attached at the C-terminus of said single chain antibody variable region;

(ii) a transmembrane domain; and

(iii) an endodomain;

wherein said endodomain comprises a signal transduction function when said single chain antibody variable region is engaged with the cancer cell-associated Glypican 2; and

wherein said single chain antibody variable region comprises:

(a) a heavy chain variable domain including a CDR1comprising the amino acid sequence of SEQ ID NO: 5, a CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain variable domain including a CDR1 comprising the amino acid sequence of SEQ ID NO: 8, a CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 10; or

(b) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 2 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 4.