Mutated factor X polypeptides and uses thereof for the treatment of haemophilia

Patent metadata

Field	Value
Publication number	US-10655119-B2
Application number	US-201615746970-A
Country	US
Kind code	B2
Filing date	Jul 26, 2016
Priority date	Jul 25, 2015
Publication date	May 19, 2020
Grant date	May 19, 2020

Abstract

The present invention relates to mutated factor (FX) polypeptides and uses thereof for the treatment of haemophilia. In particular, the present invention relates to a mutated factor X (FX) polypeptide which comprises a heavy chain wherein at least one amino acid residue at position 441 and/or 448 of SEQ ID NO: 1 is mutated.

First claim

The invention claimed is:

1. A mammalian mutated factor X polypeptide, having the amino acid sequence set forth in SEQ ID NO: 1, which comprises a heavy chain, wherein at least one amino acid residue at position 441 and/or position 448 is mutated, and wherein said factor X polypeptide is not inactivated by a factor X inhibitor selected from the group consisting of antithrombin (AT), tissue pathway inhibitor (TFPI) and alloantibodies to factor X.

2. The mutated factor X polypeptide of claim 1 , wherein the glutamic acid residue (E) at position 441 of SEQ ID NO: 1 is substituted by an amino acid residue selected from the group consisting of glutamine (Q), alanine (A), lysine (K) and arginine (R).

3. The mutated factor X polypeptide of claim 1 , wherein the lysine residue (K) at position 448 of SEQ ID NO: 1 is substituted by an amino acid residue selected from the group consisting of asparagine (N), alanine (A), glutamic acid (E) and aspartic acid (D).

4. The mutated factor X (FX) polypeptide of claim 1 further comprising a fibrinopeptide A that is inserted between an activation peptide having the amino acid sequence set forth in SEQ ID NO: 1 at positions 182 to 183, and the heavy chain.

5. The mutated factor X polypeptide of claim 4 , wherein the fibrinopeptide A has the amino acid sequence set forth in SEQ ID NO: 2.

6. A pharmaceutical composition which comprises the mutated factor X (FX) polypeptide of claim 1 , in a pharmaceutically acceptable carrier.

7. The mutated factor X polypeptide of claim 1 , wherein said mutated factor X polypeptide is able to bypass factor VIII and/or factor IX and restore coagulation.

Assignees

• Inst Nat Sante Rech Med
• Univ Paris Sud
• Univ Paris—Sud

Inventors

• Christophe Olivier
• Denis Cecile
• Lenting Peter

Classifications

• C12N9/6432 Primary

  Coagulation factor Xa (3.4.21.6) · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12Y304/21006

  Coagulation factor Xa (3.4.21.6) · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title