Methods of using a fixed dose of a clotting factor

Abstract

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 providing a clotting factor, comprising administering a fixed dose of a clotting factor to a subject in need thereof. 
     
     
         2 . A method of reducing, ameliorating, or preventing one or more symptoms of a bleeding disease or disorder in a subject comprising administering a fixed dose of a clotting factor to a subject in need thereof. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1  wherein the clotting factor is a modified clotting factor comprising a clotting factor and a heterologous moiety. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 4 , wherein the heterologous moiety comprises albumin, albumin binding polypeptide, an FcRn binding partner, PAS, the β subunit of the C-terminal peptide (CTP) of human chorionic gonadotropin, polyethylene glycol (PEG), hydroxyethyl starch (HES), albumin-binding small molecules, or combinations thereof. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the fixed dose is administered at regular intervals of every day, every two days, every three days, twice a week, every four days, every five days, every six days, every week, every eight days, every nine days, every 10 days, every 11 days, every 12 days, every 13 days, every two weeks, every three weeks, or every four weeks. 
     
     
         10 - 41 . (canceled) 
     
     
         42 . The method of  claim 1 , wherein the fixed dose is standard across all body weights. 
     
     
         43 - 46 . (canceled) 
     
     
         47 . The method of  claim 1 , wherein the fixed dose is stratified into two or more fixed dose amounts based on specified weight categories. 
     
     
         48 - 59 . (canceled) 
     
     
         60 . The method of  claim 1 , wherein the clotting factor is a long-acting FVIII polypeptide, wherein the long-acting FVIII polypeptide comprises a FVIII polypeptide and a first FcRn binding partner. 
     
     
         61 . (canceled) 
     
     
         62 . (canceled) 
     
     
         63 . The method of  claim 60 , wherein the long-acting FVIII polypeptide further comprises a second FcRn binding partner. 
     
     
         64 - 70 . (canceled) 
     
     
         71 . The method of  claim 1 , wherein the clotting factor comprises FVIII polypeptide in the long acting polypeptide is a full-length FVIII or a B-domain deleted FVIII. 
     
     
         72 . (canceled) 
     
     
         73 . The method of  claim 1 , wherein the clotting factor comprises a FVIII polypeptide comprising an amino acid sequence that is at least 90% or 95% identical to a FVIII amino acid sequence shown in Table 7A or 7B without a signal sequence (amino acids 20 to 1457 of SEQ ID NO: 6 or amino acids 20 to 2351 of SEQ ID NO: 8). 
     
     
         74 . (canceled) 
     
     
         75 . The method of  claim 60 , wherein the first FcRn binding partner is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a Fc amino acid sequence shown in Table 5B without a signal sequence (amino acids 1 to 227 SEQ ID NO:4). 
     
     
         76 . (canceled) 
     
     
         77 . The method of  claim 63 , wherein the second FcRn binding partner is at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a Fc amino acid sequence shown in Table 5B without a signal sequence (amino acids 1 to 227 SEQ ID NO:4). 
     
     
         78 . The method of  claim 60 , wherein the long-acting FVIII polypeptide comprises a sequence at least 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the FVIII and Fc amino acid sequence shown in Table 7A or 7B without a signal sequence (amino acids 1 to 1665 of SEQ ID NO: 6 or amino acids 1 to 2559 of SEQ ID NO: 8). 
     
     
         79 . The method of  claim 63 , wherein the fixed dose is standard across all body weights. 
     
     
         80 . (canceled) 
     
     
         81 . (canceled) 
     
     
         82 . The method of  claim 63 , wherein the fixed dose is stratified into two or more dose amounts based on specified weight categories. 
     
     
         83 - 92 . (canceled) 
     
     
         93 . The method of  claim 1 , wherein the fixed dose of the clotting factor is to prevent one or more bleeding episodes. 
     
     
         94 . (canceled) 
     
     
         95 . (canceled) 
     
     
         96 . The method of  claim 1 , wherein the fixed dose of the clotting factor is for perioperative management of a bleeding episode. 
     
     
         97 - 104 . (canceled) 
     
     
         105 . The method of  claim 1 , wherein the subject is in need of on-demand treatment. 
     
     
         106 . (canceled) 
     
     
         107 . (canceled) 
     
     
         108 . The method of  claim 1 , wherein the subject is in need of surgical prophylaxis, peri-operative management, or treatment for surgery. 
     
     
         109 - 119 . (canceled) 
     
     
         120 . A pharmaceutical composition comprising a fixed dose of a modified clotting factor and a pharmaceutically acceptable carrier for use to reduce, ameliorate, or prevent one or more symptoms of a bleeding disease or disorder in a subject in need thereof 
     
     
         121 . (canceled) 
     
     
         122 . A kit comprising the pharmaceutical composition of  claim 120  and instructions to administer the fixed dose of the modified clotting factor to the subject. 
     
     
         123 - 128 . (canceled)