US 12,234,292 B2
FN14 antibodies and uses thereof
Aihua Song, San Diego, CA (US); Andrew John McKnight, San Diego, CA (US); Rachel Soloff Nugent, San Diego, CA (US); John Lorca Laudenslager, La Mesa, CA (US); Giuseppe Destito, Encinitas, CA (US); Sarah Sunrise Bubeck, Livingston, TX (US); Shinya Ogawa, Tokyo (JP); Yuji Yamazaki, Tokyo (JP); David Mills, Seattle, WA (US); Aruna Bitra, La Jolla, CA (US); and Dirk Michael Zajonc, La Jolla, CA (US)
Assigned to KYOWA KIRIN CO., LTD., Tokyo (JP)
Appl. No. 17/416,148
Filed by KYOWA KIRIN CO., LTD., Tokyo (JP)
PCT Filed Dec. 19, 2019, PCT No. PCT/IB2019/061058
§ 371(c)(1), (2) Date Jun. 18, 2021,
PCT Pub. No. WO2020/128927, PCT Pub. Date Jun. 25, 2020.
Claims priority of provisional application 62/782,912, filed on Dec. 20, 2018.
Prior Publication US 2022/0289857 A1, Sep. 15, 2022
Int. Cl. C07K 16/28 (2006.01); A61P 35/00 (2006.01); A61P 37/00 (2006.01)
CPC C07K 16/2878 (2013.01) [A61P 35/00 (2018.01); A61P 37/00 (2018.01); C07K 2317/24 (2013.01); C07K 2317/524 (2013.01); C07K 2317/55 (2013.01); C07K 2317/565 (2013.01); C07K 2317/567 (2013.01); C07K 2317/76 (2013.01)] 16 Claims
 
1. An antibody or antigen binding fragment thereof that binds to Fn14, wherein the antibody or antigen binding fragment thereof is an antagonist of Fn14, wherein the antibody or antigen binding fragment thereof comprises:
(a) a heavy chain variable region (VH) comprising
(i) VH complementarity determining region 1 (CDR H1) comprising an amino acid sequence of GYX1FX2DYNMH (SEQ ID NO: 184), wherein X1 is T, I or R, and X2 is T or Q;
(ii) VH complementarity determining region 2 (CDR H2) comprising an amino acid sequence of X3INPX4NX5X6TNYNX9KFX10G (SEQ ID NO: 257), wherein X3 is Y or S, X4 is N or R, X5 is A or G, X6 is G or W, X9 is Q or D, and X10 is K, G, H, or D; and
(iii) VH complementarity determining region 3 (CDR H3) comprising an amino acid sequence of SGWFTY (SEQ ID NO: 121); and
(b) a light chain variable region (VL) comprising
(i) VL complementarity determining region 1 (CDR L1) comprising an amino acid sequence of KSSQSLLNSAGKTYLN (SEQ ID NO: 127);
(ii) VL complementarity determining region 2 (CDR L2) comprising an amino acid sequence of LVX11X12LDX13 (SEQ ID NO: 258), wherein X11 is S or A, X12 is Q or E, and X13 is S or D; and
(iii) VL complementarity determining region 3 (CDR L3) comprising an amino acid sequence of WQGTX7X8PWT (SEQ ID NO: 186), wherein X7 is H or F, and X8 is F or Y,
and wherein
(a) the antibody or antigen binding fragment thereof is not an agonist of Fn14;
(b) the antibody or antigen binding fragment thereof binds human, cynomolgus macaque, rat and mouse Fn14; and/or
(c) the antibody or antigen binding fragment thereof binds subdomain 1 comprising amino acids 30-50 of human Fn14 having an amino acid sequence of SEQ ID NO: 2.