	US 12,247,072 B2
	IL-21 polypeptides and targeted constructs
Yik Andy Yeung, South San Francisco, CA (US); Renee L. Greer, Pacifica, CA (US); Henry C. Nguyen, San Francisco, CA (US); David Liu, Pacifica, CA (US); Byong Kang, San Francisco, CA (US); and Ivana Djuretic, Pacifica, CA (US)
Assigned to ASHER BIOTHERAPEUTICS, INC., South San Francisco, CA (US)
Filed by Asher Biotherapeutics, Inc., South San Francisco, CA (US)
Filed on Apr. 27, 2023, as Appl. No. 18/308,338.
Application 18/308,338 is a continuation of application No. PCT/US2022/026584, filed on Apr. 27, 2022.
Application PCT/US2022/026584 is a continuation in part of application No. PCT/US2021/062485, filed on Dec. 8, 2021.
Application PCT/US2022/026584 is a continuation in part of application No. PCT/US2021/056312, filed on Oct. 22, 2021.
Claims priority of provisional application 63/297,631, filed on Jan. 7, 2022.
Claims priority of provisional application 63/223,684, filed on Jul. 20, 2021.
Claims priority of provisional application 63/190,669, filed on May 19, 2021.
Prior Publication US 2023/0340104 A1, Oct. 26, 2023
Int. Cl. C07K 16/24 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 14/54 (2006.01); C07K 16/28 (2006.01); C07K 16/40 (2006.01)

CPC C07K 16/244 (2013.01) [A61P 35/00 (2018.01); C07K 14/54 (2013.01); C07K 16/2815 (2013.01); C07K 16/40 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/51 (2013.01); C07K 2317/515 (2013.01); C07K 2317/522 (2013.01); C07K 2317/524 (2013.01); C07K 2317/526 (2013.01); C07K 2317/565 (2013.01); C07K 2317/64 (2013.01); C07K 2317/92 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01); C07K 2319/74 (2013.01)]

30 Claims

1. A fusion protein comprising:

a) an IL-21 polypeptide comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 16-21, 41-98 and 374-379; and

b) an antibody or an antigen binding fragment thereof that specifically binds to at least one of CD8α, CD8αα, or CDaβ, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain; and wherein:

(1) the VH domain comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO:226, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:227, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:151; and the VL domain comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 152, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 153, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 154;

(2) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 228, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:227, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 157; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:158, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 159, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:160;

(3) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 223, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:227, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 164, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 165, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:166;

(4) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 229, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:227, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 169; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 170, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:171, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:172;

(5) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 230, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:231, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 175; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 176, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 177, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:178;

(6) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 230, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:232, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 181; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 182, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 183, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:184;

(7) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 223, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:224, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:225; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 140, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 141, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:142;

(8) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 233, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:234, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 145; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 146, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 147, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 148;

(9) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:241, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:242, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:204; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 152, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 153, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:202;

(10) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:241, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:243, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:204; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:205, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:206, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:207;

(11) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:241, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:243, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:204; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 152, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 153, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:202;

(12) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:250, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:251, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:288; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQSVSSNLA (SEQ ID NO: 176), a CDR-L2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 177), and a CDR-L3 comprising the amino acid sequence of QQYGSSPPVT (SEQ ID NO: 178);

(13) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:250, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:261, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:288; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of RASQSVSSNLA (SEQ ID NO: 176), a CDR-L2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 177), and a CDR-L3 comprising the amino acid sequence of QQYGSSPPVT (SEQ ID NO:178); or

(14) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:223, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:224, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:284; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:285, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:286, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:287.