Fn14 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2022289857-A1
Application number	US-201917416148-A
Country	US
Kind code	A1
Filing date	Dec 19, 2019
Priority date	Dec 20, 2018
Publication date	Sep 15, 2022
Grant date	—

Abstract

An antibody or antigen binding fragment thereof that binds to a Fn14, wherein the antibody or antigen binding fragment thereof is an antagonist and non-agonist of Fn14.

First claim

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, 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.

2 .- 14 . (canceled)

15 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antigen binding fragment is selected from a group consisting of a Fab, a Fab′, a F(ab′)2, a Fv, a scFv, a dsFv, a diabody, a triabody, a tetrabody, and a multispecific antibody formed from antibody fragments.

16 . The antibody or antigen binding fragment thereof of claim 1 , wherein: (i) the antibody is a mouse antibody; (ii) the antibody is a chimeric antibody; (iii) the antibody is a fully human antibody or antigen binding fragment thereof; or (iv) the antibody or antigen binding fragment is a humanized antibody or antigen binding fragment thereof.

17 .- 21 . (canceled)

22 . The antibody or antigen binding fragment thereof of claim 1 , 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 GYX 1 FX 2 DYNMH (SEQ ID NO: 184), wherein X 1 is T, I or R, and X 2 is T or Q; (ii) VH complementarity determining region 2 (CDR H2) comprising an amino acid sequence of X 3 INPX 4 NX 5 X 6 TNYNX 9 KFX 10 G (SEQ ID NO: 257), wherein X 3 is Y or S, X 4 is N or R, X 5 is A or G, X 6 is G or W, X 9 is Q or D, and X 10 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 LVX 11 X 12 LDX 13 (SEQ ID NO: 258), wherein X 11 is S or A, X 12 is Q or E, and X 13 is S or D; and (iii) VL complementarity determining region 3 (CDR L3) comprising an amino acid sequence of WQGTX 7 X 8 PWT (SEQ ID NO: 186), wherein X 7 is H or F, and X 8 is F or Y.

23 . The antibody or antigen binding fragment thereof of claim 22 , 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 selected from a group consisting of SEQ ID NO: 119 and SEQ ID NO: 122; (ii) VH complementarity determining region 2 (CDR H2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 149; SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, and SEQ ID NO: 250; and (iii) VH complementarity determining region 3 (CDR H3) comprising an amino acid sequence of 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 SEQ ID NO: 127; (ii) VL complementarity determining region 2 (CDR L2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 128, SEQ ID NO: 254, SEQ ID NO: 255, and SEQ ID NO: 256; and (iii) VL complementarity determining region 3 (CDR L3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 129, SEQ ID NO: 130, and SEQ ID NO: 131.

24 .- 25 . (canceled)

26 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof comprises:
(i) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 123, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 130; (ii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 124, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 130; (iii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 125, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 130; (iv) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 126, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 130; (v) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 149, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 130; (vi) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 123, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 131; (vii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 124, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 131; (viii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 125, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 131; (ix) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 126, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 131; (x) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 149, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 131; (xi) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 124, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 254, and a CDR L3 of SEQ ID NO: 130; (xii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 124, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 255, and a CDR L3 of SEQ ID NO: 130; (xiii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 124, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 256, and a CDR L3 of SEQ ID NO: 130; (xiv) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 247, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 130; (xv) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 247, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 254, and a CDR L3 of SEQ ID NO: 130; (xvi) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 247, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 255, and a CDR L3 of SEQ ID NO: 130; (xvii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 247, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 256, and a CDR L3 of SEQ ID NO: 130; (xviii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 248, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 128, and a CDR L3 of SEQ ID NO: 130; (xix) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 248, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 254, and a CDR L3 of SEQ ID NO: 130; (xx) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 248, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 255, and a CDR L3 of SEQ ID NO: 130; (xxi) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 248, a CDR H3 of SEQ ID NO: 121, a CDR L1 of SEQ ID NO: 127, a CDR L2 of SEQ ID NO: 256, and a CDR L3 of SEQ ID NO: 130; (xxii) a CDR H1 of SEQ ID NO: 122, a CDR H2 of SEQ ID NO: 249, a CDR H3 of SEQ ID NO:

Assignees

• Kyowa Kirin Co Ltd

Inventors

• Song Aihua
• Mcknight Andrew John
• Nugent Rachel Soloff
• Laudenslager John Lorca
• Destito Giuseppe
• Bubeck Sarah Sunrise
• Ogawa Shinya
• Yamazaki Yuji
• Mills David
• Bitra Aruna
• Zajonc Dirk Michael

Classifications

• C07K16/2878 Primary

  against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/524

  CH2 domain · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/71

  Decreased effector function due to an Fc-modification · CPC title