Method of treating atherosclerosis

Patent metadata

Field	Value
Publication number	US-2022017638-A1
Application number	US-202117498112-A
Country	US
Kind code	A1
Filing date	Oct 11, 2021
Priority date	Apr 6, 2016
Publication date	Jan 20, 2022
Grant date	—

Abstract

The present disclosure relates to a method of treating or preventing atherosclerosis in a subject by administering an inhibitor of FXII.

First claim

1 . A method of treating atherosclerosis in a subject, comprising administering to the subject an effective amount of an anti-Factor XII (FXII) antibody or antigen binding fragment thereof comprising:
(i) a V H comprising:
(a) a sequence set forth in SEQ ID NO: 6; or
(b) a CDR1 comprising a sequence set forth in SEQ ID NO: 8; a CDR2 comprising a sequence set forth in SEQ ID NO: 10; and a CDR3 comprising a sequence set forth in SEQ ID NO: 12; or
(c) a CDR1 comprising a sequence set forth in SEQ ID NO: 8; a CDR2 comprising a sequence set forth in SEQ ID NO: 9; and a CDR3 comprising a sequence set forth in SEQ ID NO: 11; and/or
(ii) a V L comprising:
(a) a sequence set forth in SEQ ID NO: 7; or
(b) a CDR1 comprising a sequence set forth in SEQ ID NO: 13; a CDR2 comprising a sequence set forth in SEQ ID NO: 14; and a CDR3 comprising a sequence set forth in SEQ ID NO: 16; or
(c) a CDR1 comprising a sequence set forth in SEQ ID NO: 13; a CDR2 comprising a sequence set forth in SEQ ID NO: 14; and a CDR3 comprising a sequence set forth in SEQ ID NO: 15.

2 . The method of claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof comprises:
(i) a V H comprising a sequence set forth in SEQ ID NO: 18 and a V L comprising a sequence set forth in SEQ ID NO: 19 or (ii) a heavy chain comprising a sequence set forth in SEQ ID NO: 20 and a light chain comprising a sequence set forth in SEQ ID NO: 21.

3 . The method of claim 1 , wherein the anti-FXII antibody is an IgG antibody.

4 . The method of claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof is linked to a fusion partner, wherein the fusion partner comprises polyethylene glycol (PEG) or a half-life enhancing polypeptide, wherein the half-life enhancing polypeptide is selected from the group consisting of albumin, afamin, alpha-fetoprotein, vitamin D binding protein, human albumin, an immunoglobulin, and an Fc of an IgG.

5 . The method of claim 4 , wherein the half-life enhancing polypeptide is linked to the anti-FXII antibody or antigen binding fragment thereof 4via a linker.

6 . The method of claim 5 , wherein the anti-FXII antibody or antigen binding fragment thereof is a fusion protein comprising human albumin linked to the anti-FXII antibody or antigen binding fragment thereof via a linker peptide.

7 . The method of claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof is administered to the subject intravenously or subcutaneously or intrathecally.

8 . The method of claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof is administered to the subject:
(i) in a single dose; or (ii) in a plurality of doses; or (iii) as a continuous dose.

9 . The method of claim 1 , wherein the anti-FXII antibody or antigen binding fragment thereof is administered to the subject at a concentration from about 0.01 to about 100 mg/kg body weight.

10 . The method of claim 1 , wherein the subject is at risk of developing atherosclerosis and/or suffers from diabetes and/or obesity.

11 . A kit for use in the treatment or prevention of atherosclerosis in a subject, comprising:
(a) an anti-FXII antibody or antigen binding fragment thereof comprising
(i) a V H comprising:
(A) a sequence set forth in SEQ ID NO: 6; or
(B) a CDR1 comprising a sequence set forth in SEQ ID NO: 8; a CDR2 comprising a sequence set forth in SEQ ID NO: 10; and a CDR3 comprising a sequence set forth in SEQ ID NO: 12; or
(C) a CDR1 comprising a sequence set forth in SEQ ID NO: 8; a CDR2 comprising a sequence set forth in SEQ ID NO: 9; and a CDR3 comprising a sequence set forth in SEQ ID NO: 11; and/or

(ii) a V L comprising:
(A) a sequence set forth in SEQ ID NO: 7; or
(B) a CDR1 comprising a sequence set forth in SEQ ID NO: 13; a CDR2 comprising a sequence set forth in SEQ ID NO: 14; and a CDR3 comprising a sequence set forth in SEQ ID NO: 16; or
(c) a CDR1 comprising a sequence set forth in SEQ ID NO: 13; a CDR2 comprising a sequence set forth in SEQ ID NO: 14; and a CDR3 comprising a sequence set forth in SEQ ID NO: 15;

(b) instructions for using the kit in treating or preventing atherosclerosis in the subject; and (c) optionally, at least one further therapeutically active compound or drug.

12 . An anti-Factor XII (FXII) antibody or antigen binding fragment thereof, wherein the anti-FXII antibody comprises:
(i) a V H comprising a sequence set forth in SEQ ID NO: 18 and a V L comprising a sequence set forth in SEQ ID NO: 19; or (ii) a heavy chain comprising a sequence set forth in SEQ ID NO: 20 and a light chain comprising a sequence set forth in SEQ ID NO: 21.

Assignees

• Csl Ltd

Inventors

• Panousis Con
• Peter Karlheinz
• Hosseini Hamid
• Chen Yung-Chih

Classifications

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K14/81

  Protease inhibitors · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K2039/505

  comprising antibodies · CPC title