IP Library › Granted Patent US 12,415,866
Granted Patent B2
US 12,415,866 · App. 17/136,483 · Granted Sep 16, 2025

Monoclonal antibody inhibitor of Factor XIIa

Inventors: Shauna Mason (Arlington, MA); Jon A. Kenniston (Hingham, MA); Andrew Nixon (Hanover, MA); Daniel J. Sexton (Melrose, MA); Stephen R. Comeau (Avon, NY); Burt Adelman (Concord, MA)
Assignee: Takeda Pharmaceutical Company Limited
C07K16/36A61K2039/505C07K2317/21C07K2317/24C07K2317/34C07K2317/55C07K2317/76C07K2317/90C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 12,415,866
App. No.
17/136,483
Granted
Sep 16, 2025
Kind
B2
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.

Claims (264)

1. A method of treating a disease associated with contact system activation, the method comprising administering to a subject in need thereof a monoclonal antibody that binds to active Factor XII (FXIIa) and does not bind to Factor XII (FXII); 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 CD3), 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;

and wherein the disease associated with the contact activation system is hereditary angioedema (HAE) or an ocular disease.

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

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

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

5. The method of claim 1 , wherein:

(i) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 125

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYVMHWVRQAPGKGLEWVS

SIWPSGGHTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(ii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 1

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYSMHWVRQAPGKGLEWVS

VIYPSGGKTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(iii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 2

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYVMHWVRQAPGKGLEWVS

SIWPSGGHTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(iv) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 3

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYVMHWVRQAPGKGLEWVS

GIWPSGGRTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(v) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 4

EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYVMHWVRQAPGKGLEWVS

SIWPSGGKTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDAWGQGTTVTVSS;

(vi) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 5

EVQLLESGGGLVQPGGSLRLSCAASGFTFSMYTMNWVRQAPGKGLEWVS

RIYPSGGKTLYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(vii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 6

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYVMSWVRQAPGKGLEWVS

RIYPSGGVTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(viii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 7

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYNMHWVRQAPGKGLEWVS

YISPSGGKTKYTDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(ix) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 8

EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYIMHWVRQAPGKGLEWVS

SIYPSGGVTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(x) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 9

EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYIMGWVRQAPGKGLEWVS

SIYPSGGVTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xi) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 10

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYNMVWVRQAPGKGLEWVS

RIWPSGGKTTYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 11;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYVMVWVRQAPGKGLEWVSR

IYPSGGMTQYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xiii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 12;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYNMAWVRQAPGKGLEWVSR

IYPSGGMTQYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xiv) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 13;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYIMHWVRQAPGKGLEWVSS

IYPSGGNTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xv) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 14;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYVMHWVRQAPGKGLEWVSS

IYPSGGLTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xvi) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 15;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYTMHWVRQAPGKGLEWVSS

IYPSGGFTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xvii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 16;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSFYHMHWVRQAPGKGLEWVSR

IVPSGGMTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xviii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 17;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSFYSMHWVRQAPGKGLEWVSR

IYPSGGVTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xix) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 18;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYVMHWVRQAPGKGLEWVSS

IWPSGGKTTYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xx) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 19;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYVMHWVRQAPGKGLEWVSS

IWPSGGFTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xxi) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 20;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSFYNMHWVRQAPGKGLEWVSS

IYPSGGVTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xxii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 21;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYVMHWVRQAPGKGLEWVSS

IYPSGGKTSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xxiii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 22;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSPYIMHWVRQAPGKGLEWVSV

IYPSGSKTNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xxiv) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 23;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYTMRWVRQAPGKGLEWVSS

IWPSGGMTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGQGTTVTVSS,

(xxv) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 24;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYVMHWVRQAPGKGLEWVSS

IYPSGGLTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGQGTTVTVSS,

(xxvi) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 25;

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYIMGWVRQAPGKGLEWVSY

IYPSGGNTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRQR

YRGPKYYYYMDVWGKGTTVTVSS,

(xxvii) the heavy chain variable region comprises the amino acid sequence

 SEQ ID NO: 26

EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYVMHWVRQAPGKGLEWVS

SIWPSGGMTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxviii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 27

EVQLLESGGGLVQPGGSLRLSCAASGFTFSFYIMGWVRQAPGKGLEWVS

RIYPSGGATQYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxix) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 28

EVQLLESGGGLVQPGGSLRLSCAASGFTFSFYVMGWVRQAPGKGLEWVS

RIYPSGGLTQYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxx) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 29

EVQLLESGGGLVQPGGSLRLSCAASGFTFSFYSMHWVRQAPGKGLEWVS

RIYPSGGITSYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxxi) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 30

EVQLLESGGGLVQPGGSLRLSCAASGFTFSMYIMHWVRQAPGKGLEWVS

SIYPSGGMTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxxii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 31

EVQLLESGGGLVQPGGSLRLSCAASGFTFSMYVMHWVRQAPGKGLEWVS

SIYPSGGLTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxxiii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 32

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYVMHWVRQAPGKGLEWVS

RIYPSGGLTNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxxiv) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 33

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYVMQWVRQAPGKGLEWVS

SIYPSGGMTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxxv) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 34

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYIMGWVRQAPGKGLEWVS

RIYPSGGSTHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPRYYYYIDAWGQGTTVTVSS;

(xxxvi) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 35

EVQLLESGGGLVQPGGSLRLSCAASGFTFSQYTMVWVRQAPGKGLEWVS

RIYPSGGVTQYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxxvii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 36

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYVMYWVRQAPGKGLEWVS

RIYPSGGITHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxxviii) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 37

EVQLLESGGGLVQPGGSLRLSCAASGFTFSFYVMLWVRQAPGKGLEWVS

SIWPSGGVTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS;

(xxxix) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 38

EVQLLESGGGLVQPGGSLRLSCAASGFTFSWYVMQWVRQAPGKGLEWVS

YIYPSGGHTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS; or

(xxxx) the heavy chain variable region comprises the amino acid sequence

SEQ ID NO: 39

EVQLLESGGGLVQPGGSLRLSCAASGFTFSRYSMNWVRQAPGKGLEWVS

GIYPSGGKTKYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTR

QRYRGPKYYYYMDVWGKGTTVTVSS; and

the light chain variable region comprises the amino acid sequence

SEQ ID NO: 126 

DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSP

QLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQ

TPWTFGQGTKVEIK or the amino acid sequence

SEQ ID NO: 40

DIQMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSP

QLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQ

TPWTFGQGTKVEIK.

6. The method of claim 1 , wherein the heavy chain further comprises a heavy chain constant region.

7. The method of claim 6 , wherein the heavy chain constant region comprises at least one or more mutations mutation that enhance enhances half-life of the antibody as compared to the wild-type counterpart.

8. The method of claim 7 , wherein the one or more mutations are at one or more positions corresponding to position 145, 147, and/or 149 of SEQ ID NO:119, optionally wherein the one or more mutations are one or more amino acid substitutions of M145Y, S147T, and/or T149E.

9. The method of claim 6 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 120.

10. The method of claim 1 , further comprising evaluating the activity or quantity of FXIIa after administration of the antibody.

11. The method of claim 1 , wherein the subject has, is suspected of having, or is at risk for a disease associated with pKal signaling.

12. The method of claim 1 , wherein the HAE is Type 1, Type 2, or Type 3 HAE.

13. The method of claim 1 , wherein the ocular disease is macular edema, diabetic retinopathy, hypertensive retinopathy, age-related macular degeneration, or retinal vein occlusion.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 17, 2025
From: DYAX CORP.
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 069909/0120 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 9, 2021
From: MASON, SHAUNA; KENNISTON, JON A.; SEXTON, DANIEL J.; COMEAU, STEPHEN R.; NIXON, ANDREW; ADELMAN, BURT
To: DYAX CORP.
Reel/Frame 058059/0388 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 30, 2021
From: DYAX CORP.
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 055772/0327 →
Continuity (5)
Division 15746048
Provisional Application 62194957 · Jul 21, 2015
Provisional Application 62273657 · Dec 31, 2015
Provisional Application 62316310 · Mar 31, 2016
Related Publication 20210230299A1 · Jul 29, 2021
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