Treatment with factor ix-albumin fusion protein
The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.
1. A method of treating a patient in need of a Factor IX polypeptide, comprising the step of administering an effective amount of an albumin fusion protein comprising a Factor IX polypeptide fused to an albumin polypeptide, wherein the albumin polypeptide has the ability to prolong the serum half-life of the fused Factor IX polypeptide compared to the unfused Factor IX polypeptide, wherein the fused Factor IX polypeptide has Factor IX coagulant activity, wherein the Factor IX polypeptide is fused at the N-terminus of the albumin polypeptide, and wherein the albumin polypeptide is selected from:
a) a full-length albumin;
b) a mature albumin;
c) a fragment of albumin;
d) a polypeptide consisting of an amino acid sequence at least 95% identical to SEQ ID NO:18; and
e) amino acids 1 to 387 of SEQ ID NO:18;
and wherein the Factor IX polypeptide is selected from:
i) a full-length Factor IX;
ii) an activated Factor IX (Factor IXa);
iii) a fragment of Factor IX having a deletion that consists of 1-50 amino acid residues as compared to the sequence of amino acids 1 (Tyr) to 416 (Thr) of SEQ ID NO:46;
iv) a polypeptide consisting of an amino acid sequence at least 90% identical to the sequence of amino acids 1 (Tyr) to 416 (Thr) of SEQ ID NO: 46; and
v) a mature Factor IX.
2. The method of claim 1 , wherein the administration comprises subcutaneous administration.
3. The method of claim 2 , wherein the subcutaneous administration comprises one or more injections.
4. The method of claim 2 , wherein the effective amount of the albumin fusion protein is in the range of 1 μg/kg/day to 10 mg/kg/day of patient body weight.
5. The method of claim 4 , wherein the effective amount of the albumin fusion protein is at least 0.01 mg/kg/day.
6. The method of claim 2 , wherein the albumin fusion protein is administered continuously.
7. The method of claim 2 , wherein the subcutaneous administration comprises between 1 and 4 injections per day.
8. The method of claim 6 , wherein the continuous administration comprises continuous subcutaneous infusions.
9. The method of claim 2 , wherein the subcutaneous administration uses a sustained-release system.
10. The method of claim 1 , wherein said fragment of Factor IX has a deletion that consists of 1-25 amino acid residues as compared to the sequence of amino acids 1 (Tyr) to 416 (Thr) of SEQ ID NO:46.
11. The method of claim 1 , wherein said fragment of Factor IX has a deletion that consists of 1-10 amino acid residues as compared to the sequence of amino acids 1 (Tyr) to 416 (Thr) of SEQ ID NO:46.
12. The method of claim 1 , wherein said Factor IX polypeptide is derived from a human Factor IX.