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

Patent metadata

Field	Value
Publication number	US-2020299666-A1
Application number	US-202016862706-A
Country	US
Kind code	A1
Filing date	Apr 30, 2020
Priority date	Jan 7, 2015
Publication date	Sep 24, 2020
Grant date	—

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 wherein the heavy chain comprises at least one mutation selected from the group consisting of:
the mutation which consists of the substitution of the glutamic acid residue (E) at position 215 by a glutamine residue (Q), an asparagine residue (N), a serine residue (S), an alanine residue (A), or a tyrosine residue (Y); the mutation which consists of the substitution of the glutamic acid residue (E) at position 216 by a glutamine residue (Q); and the mutation which consists of the substitution of the glutamic acid residue (E) at position 218 by a glutamine residue (Q);

First claim

1 - 9 . (canceled)

10 . A nucleic acid molecule which encodes for a mutated factor X (FX) polypeptide comprising the amino acid sequence of SEQ ID NO. 1 from the amino acid residue at position 235 to the amino acid residue at position 488 of SEQ ID NO: 1, wherein the heavy chain comprises at least one mutation selected from the group consisting of:
a mutation comprising substitution of a glutamic acid residue (E) at position 255 by a glutamine residue (Q), a serine residue (S), an alanine residue (A), or a tyrosine residue (Y); a mutation comprising substitution of a glutamic acid residue (E) at position 256 by a glutamine residue (Q); and a mutation comprising substitution of a glutamic acid residue (E) at position 258 by a glutamine residue (Q).

11 . A vector which comprises the nucleic acid molecule of claim 10 .

12 . A host cell which is transformed with the nucleic acid molecule of claim 10 or a vector comprising the nucleic acid.

13 . (canceled)

14 . A method of treating haemophilia in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a mutated factor X (FX) polypeptide comprising the amino acid sequence of SEQ ID NO. 1 from the amino acid residue at position 235 to the amino acid residue at position 488 of SEQ ID NO: 1, wherein the heavy chain comprises at least one mutation selected from the group consisting of:
a mutation comprising substitution of a glutamic acid residue (E) at position 255 by a glutamine residue (Q), a serine residue (S), an alanine residue (A), or a tyrosine residue (Y); a mutation comprising substitution of a glutamic acid residue (E) at position 256 by a glutamine residue (Q); and a mutation comprising substitution of a glutamic acid residue (E) at position 258 by a glutamine residue (Q),
or a nucleic acid molecule encoding the mutated factor X (FX) polypeptide.

15 . A pharmaceutical composition which comprises the nucleic acid molecule of claim 10 .

16 . The method of claim 14 , wherein the nucleic acid molecule is present in a vector.

17 . The method of claim 14 , wherein the nucleic acid molecule is not present in a vector.

18 . The nucleic acid of claim 10 wherein the at least one mutation is a glutamine residue at position 255, 256, or 289.

19 . The nucleic acid of claim 10 wherein the mutated FX polypeptide comprises an activation peptide and where a fibrinopeptide A is inserted between the activation peptide and the heavy chain.

20 . A pharmaceutical composition which comprises the nucleic acid molecule of claim 18 .

21 . A pharmaceutical composition which comprises the nucleic acid molecule of claim 19 .

Assignees

• Inst Nat Sante Rech Med
• Univ Paris Sud

Inventors

• Christophe Olivier
• Lenting Petrus
• DENIS Cécile

Classifications

• 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

• C07K14/75

  Fibrinogen · CPC title

• C12Y304/21006

  Coagulation factor Xa (3.4.21.6) · CPC title

• C07K14/745

  Blood coagulation or fibrinolysis factors · CPC title

• C12N9/6432 Primary

  Coagulation factor Xa (3.4.21.6) · CPC title