Monoclonal antibody inhibitor of factor XIIA

Patent metadata

Field	Value
Publication number	US-10913802-B2
Application number	US-201615746048-A
Country	US
Kind code	B2
Filing date	Jul 21, 2016
Priority date	Jul 21, 2015
Publication date	Feb 9, 2021
Grant date	Feb 9, 2021

Abstract

Disclosed herein are anti-Factor XIIa antibodies and methods of using such for treating diseases associated with Factor XII, including diseases associated with contact system activation, plasma prekallikrein signaling (e.g., hereditary angioedema), and ocular diseases.

First claim

What is claimed is:

1. A monoclonal antibody that binds to Factor XIIa (FXIIa) wherein the antibody comprises a heavy chain comprising a heavy chain variable region that comprises a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2), and a heavy chain complementarity determining region 3 (HC CDR3), and a light chain comprising a light chain variable region that comprises a light chain CDR1 (LC CDR1), a light chain CDR2 (LC CDR2), and a light chain CDR3 (LC CDR3), wherein:
(i) the HC CDR1 comprises QYVMH (SEQ ID NO: 58), the HC CDR2 comprises SIWPSGGHTRYADSVKG (SEQ ID NO: 75), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(ii) the HC CDR1 comprises WYSMH (SEQ ID NO: 41), the HC CDR2 comprises VIYPSGGKTRYADSVKG (SEQ ID NO: 74), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(iii) the HC CDR1 comprises QYVMH (SEQ ID NO: 42), the HC CDR2 comprises SIWPSGGHTRYADSVKG (SEQ ID NO: 75), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(iv) the HC CDR1 comprises WYVMH (SEQ ID NO: 43), the HC CDR2 comprises GIWPSGGRTKYADSVKG (SEQ ID NO: 76), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(v) the HC CDR1 comprises NYVMH (SEQ ID NO: 44), the HC CDR2 comprises SIWPSGGKTKYADSVKG (SEQ ID NO: 77), and the HC CDR3 comprises QRYRGPKYYYYMDA (SEQ ID NO: 112);
(vi) the HC CDR1 comprises MYTMN (SEQ ID NO: 45), the HC CDR2 comprises RIYPSGGKTLYADSVKG (SEQ ID NO: 78), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(vii) the HC CDR1 comprises QYVMS (SEQ ID NO: 46), the HC CDR2 comprises RIYPSGGVTKYADSVKG (SEQ ID NO: 79), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(viii) the HC CDR1 comprises WYNMH (SEQ ID NO: 47), the HC CDR2 comprises YISPSGGKTKYTDSVKG (SEQ ID NO: 80), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(ix) the HC CDR1 comprises RYIMH (SEQ ID NO: 48), the HC CDR2 comprises SIYPSGGVTKYADSVKG (SEQ ID NO: 81), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(x) the HC CDR1 comprises RYIMG (SEQ ID NO: 49), the HC CDR2 comprises SIYPSGGVTRYADSVKG (SEQ ID NO: 82), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xi) the HC CDR1 comprises QYNMV (SEQ ID NO: 50), the HC CDR2 comprises RIWPSGGKTTYADSVKG (SEQ ID NO: 83), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xii) the HC CDR1 comprises RYVMV (SEQ ID NO: 51), the HC CDR2 comprises RIYPSGGMTQYADSVKG (SEQ ID NO: 84), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xiii) the HC CDR1 comprises WYNMA (SEQ ID NO: 52), the HC CDR2 comprises RIYPSGGMTQYADSVKG (SEQ ID NO: 84), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xiv) the HC CDR1 comprises QYIMH (SEQ ID NO: 53), the HC CDR2 comprises SIYPSGGNTKYADSVKG (SEQ ID NO: 85), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xv) the HC CDR1 comprises HYVMH (SEQ ID NO: 54), the HC CDR2 comprises SIYPSGGLTKYADSVKG (SEQ ID NO: 86), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xvi) the HC CDR1 comprises WYTMH (SEQ ID NO: 55), the HC CDR2 comprises SIYPSGGFTRYADSVKG (SEQ ID NO: 87), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xvii) the HC CDR1 comprises FYHMH (SEQ ID NO: 56), the HC CDR2 comprises RIVPSGGMTRYADSVKG (SEQ ID NO: 88), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xviii) the HC CDR1 comprises FYSMH (SEQ ID NO: 57), the HC CDR2 comprises RIYPSGGVTKYADSVKG (SEQ ID NO: 89), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xix) the HC CDR1 comprises QYVMH (SEQ ID NO: 58), the HC CDR2 comprises SIWPSGGKTTYADSVKG (SEQ ID NO: 90), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xx) the HC CDR1 comprises QYVMH (SEQ ID NO: 58), the HC CDR2 comprises SIWPSGGFTKYADSVKG (SEQ ID NO: 91), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxi) the HC CDR1 comprises FYNMH (SEQ ID NO: 59), the HC CDR2 comprises SIYPSGGVTRYADSVKG (SEQ ID NO: 92), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxii) the HC CDR1 comprises WYVMH (SEQ ID NO: 43), the HC CDR2 comprises SIYPSGGKTSYADSVKG (SEQ ID NO: 93), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxiii) the HC CDR1 comprises PYIMH (SEQ ID NO: 60), the HC CDR2 comprises VIYPSGSKTNYADSVKG (SEQ ID NO: 94), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxiv) the HC CDR1 comprises RYTMR (SEQ ID NO: 61), the HC CDR2 comprises SIWPSGGMTRYADSVKG (SEQ ID NO: 95), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxv) the HC CDR1 comprises QYVMH (SEQ ID NO: 58), the HC CDR2 comprises SIYPSGGLTRYADSVKG (SEQ ID NO: 96), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxvi) the HC CDR1 comprises WYIMG (SEQ ID NO: 62), the HC CDR2 comprises YIYPSGGNTRYADSVKG (SEQ ID NO: 97), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxvii) the HC CDR1 comprises RYVMH (SEQ ID NO: 63), the HC CDR2 comprises SIWPSGGMTKYADSVKG (SEQ ID NO: 98), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxviii) the HC CDR1 comprises FYIMG (SEQ ID NO: 64), the HC CDR2 comprises RIYPSGGATQYADSVKG (SEQ ID NO: 99), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxix) the HC CDR1 comprises FYVMG (SEQ ID NO: 65), the HC CDR2 comprises RIYPSGGLTQYADSVKG (SEQ ID NO: 100), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxx) the HC CDR1 comprises FYSMH (SEQ ID NO: 66), the HC CDR2 comprises RIYPSGGITSYADSVKG (SEQ ID NO: 101), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxi) the HC CDR1 comprises MYIMH (SEQ ID NO: 67), the HC CDR2 comprises SIYPSGGMTKYADSVKG (SEQ ID NO: 102), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxii) the HC CDR1 comprises MYVMH (SEQ ID NO: 68), the HC CDR2 comprises SIYPSGGLTKYADSVKG (SEQ ID NO: 103), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxiii) the HC CDR1 comprises QYVMH (SEQ ID NO: 58), the HC CDR2 comprises RIYPSGGLTNYADSVKG (SEQ ID NO: 104), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxiv) the HC CDR1 comprises WYVMQ (SEQ ID NO: 69), the HC CDR2 comprises SIYPSGGMTKYADSVKG (SEQ ID NO: 102), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxv) the HC CDR1 comprises WYIMG (SEQ ID NO: 62), the HC CDR2 comprises RIYPSGGSTHYADSVKG (SEQ ID NO: 105), and the HC CDR3 comprises QRYRGPRYYYYIDA (SEQ ID NO: 113);
(xxxvi) the HC CDR1 comprises QYTMV (SEQ ID NO: 70), the HC CDR2 comprises RIYPSGGVTQYADSVKG (SEQ ID NO: 106), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxvii) the HC CDR1 comprises WYVMY (SEQ ID NO: 71), the HC CDR2 comprises RIYPSGGITHYADSVKG (SEQ ID NO: 107), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxviii) the HC CDR1 comprises FYVML (SEQ ID NO: 72), the HC CDR2 comprises SIWPSGGVTKYADSVKG (SEQ ID NO: 108), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxix) the HC CDR1 comprises WYVMQ (SEQ ID NO: 69), the HC CDR2 comprises YIYPSGGHTKYADSVKG (SEQ ID NO: 109), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111);
(xxxx) the HC CDR1 comprises RYSMN (SEQ ID NO: 73), the HC CDR2 comprises GIYPSGGKTKYADSVKG (SEQ ID NO: 110), and the HC CDR3 comprises QRYRGPKYYYYMDV (SEQ ID NO: 111); and
the LC CDR1 comprises RSSQSLLHSNGYNYLD (SEQ ID NO: 114), the LC CDR2 comprises LGSNRAS (SEQ ID NO: 115), and the LC CDR3 comprises MQALQTPWT (SEQ ID NO: 116).

2. The antibody of claim 1 , wherein the antibody is a full length antibody or an antigen-binding fragment thereof.

3. The antibody of claim 2 , wherein the antibody is a Fab.

4. The antibody of claim 1 , wherein the antibody is a human antibody or a humanized antibody.

5. The antibody of claim 1 , wherein the heavy chain further comprises a heavy chain constant region.

Assignees

• Dyax Corp

Inventors

• Mason Shauna
• Kenniston Jon A
• Nixon Andrew
• Sexton Daniel J
• Comeau Stephen R
• Adelman Burt

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P27/02

  Ophthalmic agents · CPC title