Optimised coding sequence and promoter

Patent metadata

Field	Value
Publication number	US-9393323-B2
Application number	US-201013382953-A
Country	US
Kind code	B2
Filing date	Jul 8, 2010
Priority date	Jul 8, 2009
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes are alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.

First claim

The invention claimed is:

1. An isolated nucleic acid molecule comprising a nucleotide sequence having at least 80% homology to the nucleotide sequence of SEQ ID NO: 1 and which encodes functional factor VIII protein and wherein with respect to the amino acid sequence encoded by SEQ ID NO: 1 any amino acid change encoded by the isolated nucleic acid molecule is in the portion of the amino acid sequence which replaced the B domain of the factor VIII protein.

2. The nucleic acid molecule of claim 1 having at least 85% homology to the nucleotide sequence of SEQ ID NO: 1.

3. The nucleic acid molecule of claim 1 comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO: 7.

4. The nucleic acid molecule of claim 1 further comprising the nucleotide sequence of SEQ ID NO: 3.

5. A vector comprising the nucleic acid molecule of claim 1 .

6. An isolated host cell comprising the nucleic acid molecule of claim 1 or the vector of claim 5 .

7. A method of treating haemophilia comprising administering the vector of claim 5 to a patient suffering from haemophilia.

8. A method for delivery of a nucleotide sequence encoding a functional factor VIII protein to a subject, which method comprises administering to said subject the nucleic acid molecule of claim 1 .

Assignees

• Nathwani Amit
• Ward Natalie
• Thrasher Adrian
• Tuddenham Edward
• Mcvey John
• Gray John
• Davidoff Andrew
• Ucl Business Plc
• Thrombosis Res Inst
• St Jude Childrens Res Hospital

Inventors

• Nathwani Amit
• Ward Natalie
• Thrasher Adrian
• Tuddenham Edward
• Mcvey John
• Gray John
• Davidoff Andrew

Classifications

• A61P7/04

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

• C12N2710/10041

  Use of virus, viral particle or viral elements as a vector · 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

• C12N15/86

  Viral vectors · CPC title

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title