US 12,139,526 B2
Modified chimeric receptors and related compositions and methods
Lucas James Thompson, Seattle, WA (US); Robert F. Dubose, Bellevue, WA (US); and Archana Brahmandam, Seattle, WA (US)
Assigned to Juno Therapeutics, Inc., Seattle, WA (US)
Appl. No. 15/780,623
Filed by Juno Therapeutics, Inc., Seattle, WA (US)
PCT Filed Dec. 2, 2016, PCT No. PCT/US2016/064861
§ 371(c)(1), (2) Date May 31, 2018,
PCT Pub. No. WO2017/096329, PCT Pub. Date Jun. 8, 2017.
Claims priority of provisional application 62/348,130, filed on Jun. 9, 2016.
Claims priority of provisional application 62/262,911, filed on Dec. 3, 2015.
Prior Publication US 2018/0355014 A1, Dec. 13, 2018
Int. Cl. A61K 39/00 (2006.01); A61K 35/17 (2015.01); C07K 14/705 (2006.01); C07K 14/74 (2006.01); C12N 5/0783 (2010.01); C12N 5/10 (2006.01); A61K 35/66 (2015.01); A61P 35/00 (2006.01); A61P 35/04 (2006.01); A61P 37/00 (2006.01); C07K 7/06 (2006.01); C07K 9/00 (2006.01); C07K 16/28 (2006.01); C12N 15/62 (2006.01); C12N 15/86 (2006.01)
CPC C07K 14/70539 (2013.01) [A61K 35/17 (2013.01); C07K 14/705 (2013.01); A61K 35/66 (2013.01); A61P 35/00 (2018.01); A61P 35/04 (2018.01); A61P 37/00 (2018.01); C07K 7/06 (2013.01); C07K 9/00 (2013.01); C07K 16/2812 (2013.01); C07K 16/2815 (2013.01); C07K 16/2818 (2013.01); C07K 2317/56 (2013.01); C07K 2317/622 (2013.01); C07K 2319/03 (2013.01); C07K 2319/033 (2013.01); C12N 5/10 (2013.01); C12N 15/62 (2013.01); C12N 15/86 (2013.01)] 20 Claims
 
1. An engineered T cell comprising a chimeric receptor, wherein the chimeric receptor comprises a CD28 transmembrane domain and a 4-1BB costimulatory signaling domain having one or more amino acid sequence modifications compared to a reference chimeric receptor comprising the sequence set forth in SEQ ID NO:5 wherein:
the CD28 transmembrane domain and the 4-1BB costimulatory signaling domain of the chimeric receptor together comprise a sequence of amino acids that exhibits at least 95% sequence identity to SEQ ID NO:5;
and wherein:
the one or more amino acid sequence modifications comprise an amino acid replacement(s) corresponding to replacement selected from among K28A, K28H, K28L, K28Q, K28L, K28Q, K28S, R31A, R31H, R31L, R31N, R31S, L34A and L34S, with reference to the numbering set forth in SEQ ID NO:5.