US 12,006,354 B2
Antibody-IL2 engrafted proteins and methods of use in the treatment of cancer
Jonathan Deane, San Diego, CA (US); Yaiza Diaz-De-Durana, San Diego, CA (US); Michael DiDonato, San Diego, CA (US); Christophe Filippi, Studio City, CA (US); and Glen Spraggon, San Diego, CA (US)
Assigned to NOVARTIS AG, Basel (CH)
Appl. No. 16/616,318
Filed by NOVARTIS AG, Basel (CH)
PCT Filed May 22, 2018, PCT No. PCT/IB2018/053623
§ 371(c)(1), (2) Date Nov. 22, 2019,
PCT Pub. No. WO2018/215936, PCT Pub. Date Nov. 29, 2018.
Claims priority of provisional application 62/510,533, filed on May 24, 2017.
Prior Publication US 2020/0270334 A1, Aug. 27, 2020
Int. Cl. C07K 14/55 (2006.01); A61K 38/20 (2006.01); A61K 39/395 (2006.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01); C07K 16/08 (2006.01); C07K 16/10 (2006.01); C07K 19/00 (2006.01); C12N 5/071 (2010.01); C12N 5/0783 (2010.01); A61K 39/00 (2006.01); A61K 45/06 (2006.01)
CPC C07K 16/1027 (2013.01) [A61K 38/2013 (2013.01); A61K 39/3955 (2013.01); A61K 47/6801 (2017.08); A61P 35/00 (2018.01); C07K 14/55 (2013.01); C07K 19/00 (2013.01); C12N 5/0636 (2013.01); C12N 5/0682 (2013.01); A61K 2039/505 (2013.01); A61K 45/06 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/94 (2013.01); C07K 2319/30 (2013.01)] 27 Claims
 
1. An antibody cytokine engrafted protein comprising:
(a) an IgG class heavy chain comprising an IgG class heavy chain variable region (VH), comprising Complementarity Determining Regions (CDR) HCDR1 comprising SEQ ID NO: 7, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 16, SEQ ID NO: 39, SEQ ID NO: 42, SEQ ID NO: 45, or SEQ ID NO: 48, HCDR2 comprising SEQ ID NO: 8, SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 40, SEQ ID NO: 46 or SEQ ID NO: 49, and HCDR3 comprising SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 41, SEQ ID NO: 44, SEQ ID NO: 47 or SEQ ID NO: 50, and wherein the HCDRs individually comprise between 0 to 1 substitution; and
(b) an IgG class light chain comprising an IgG class light chain variable region (VL), comprising LCDR1 comprising SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 55, SEQ ID NO: 58, SEQ ID NO: 61 or SEQ ID NO: 64, LCDR2 comprising SEQ ID NO: SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30, SEQ ID NO: 33, SEQ ID NO: 56, SEQ ID NO: 59, SEQ ID NO: 62 or SEQ ID NO: 65, and LCDR3 comprising SEQ ID NO: 25, SEQ ID NO: 28, SEQ ID NO: 31, SEQ ID NO: 34, SEQ ID NO: 57, SEQ ID NO: 60, SEQ ID NO: 63 or SEQ ID NO: 66, and wherein the LCDRs individually comprise between 0 to 1 substitution; and
(c) a mutated Interleukin 2 (IL2) molecule engrafted into HCDR1, wherein the HCDR1 comprises SEQ ID NO: 7, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 16, SEQ ID NO: 39, SEQ ID NO: 42, SEQ ID NO: 45, or SEQ ID NO: 48, and wherein the mutated IL2 molecule contains a mutation that reduces the affinity of the mutated IL2 molecule to a high affinity IL2 receptor.