Methods of using a fixed dose of a clotting factor
View Patent ↗The present invention provides methods of administering a clotting factor by a fixed dosing regimen; methods of reducing, ameliorating, or preventing one or more symptoms of a bleeding disease or disorder; and a kit comprising a dotting factor useful for a fixed dosing regimen. While plasma-derived and recombinant clotting factor products allow hemophilia patients to live longer and healthier, hemophilia still remains one of the most costly and complex conditions to manage.
1. A method of treating hemophilia B in a subject in need thereof, comprising administering a fixed dose of chimeric Factor IX (FIX) polypeptide to the subject,
wherein the fixed dose is standard across all body weight,
wherein the fixed dose is administered weekly at a dose between about 3,000 IU and about 4,000 IU, and
wherein the chimeric FIX polypeptide comprises:
(i) a first polypeptide chain comprising a FIX-Fc amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to SEQ ID NO: 2, and
(ii) a second polypeptide chain comprising an Fc amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity sequence identity to the amino acid sequence according to SEQ ID NO: 4.
2. The method of claim 1 , wherein the administering reduces or ameliorates one or more symptoms of hemophilia B.
3. The method of claim 1 , wherein a body weight effect on clearance (θ BW _ CL ) of the chimeric FIX polypeptide is equal to or less than about 0.500.
4. The method of claim 1 , wherein a body weight effect on the central volume of distribution (θ BW _ V1 ) of the chimeric FIX polypeptide is equal to or less than about 0.467.
5. The method of claim 1 , wherein the fixed dose is administered intravenously.
6. The method of claim 1 , wherein the the fixed dose amount is about 3,000 IU per dose and wherein the fixed dose is administered weekly.
7. The method of claim 1 , wherein the the fixed dose amount is about 4,000 IU per dose and wherein the fixed dose is administered weekly.
8. The method of claim 1 , wherein the chimeric FIX polypeptide comprises:
(i) a first polypeptide chain comprising a FIX-Fc amino acid sequence according to SEQ ID NO: 2; and
(ii) a second polypeptide chain comprising a Fc amino acid sequence according to SEQ ID NO: 4.
9. A method of treating hemophilia B in a subject in need thereof, comprising administering a fixed dose of a chimeric FIX polypeptide to the subject,
wherein the fixed dose is standard across all body weight,
wherein the fixed dose is administered every 10 days at a dose between about 6,000 IU and about 8,000 IU, and
wherein the chimeric FIX polypeptide comprises:
(i) a first polypeptide chain comprising a FIX-Fc amino acids sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to SEQ ID NO: 2; and
(ii) a second polypeptide chain comprising an Fc amino acid sequence having at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity sequence identity to the amino acid sequence according to SEQ ID NO: 4.
10. The method of claim 9 , wherein the fixed dose is administered intravenously.
11. The method of claim 9 , wherein the fixed dose is about 6,000 IU per dose and wherein the fixed dose is administered every 10 days. intravaneously.
12. The method of claim 9 , wherein the fixed dose amount is about 7,500 IU per dose and wherein the fixed dose is administered every 10 days.
13. The method of claim 9 , wherein the fixed dose amount is about 8,000 IU per dose and wherein the fixed dose is administered every 10 days.
14. The method of claim 9 , wherein the chimeric FIX polypeptide comprises:
(i) a first polypeptide chain comprising a FIX-Fc amino acid sequence according to SEQ ID NO: 2; and
(ii) a second polypeptide chain comprising a Fc amino acid sequence according to SEQ ID NO: 4.