Factor IX Polypeptides and Methods of Use Thereof
The present invention provides methods of administering Factor IX; methods of administering chimeric and hybrid polypeptides comprising Factor IX; polynucleotides encoding such chimeric and hybrid polypeptides; cells comprising such polynucleotides; and methods of producing such chimeric and hybrid polypeptides using such cells.
1 - 121 . (canceled)
122 . A method of prophylactic treatment of hemophilia B in a human subject in need thereof, comprising intravenously administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric polypeptide comprising human Factor IX (FIX) and a FcRn binding partner (FcRn BP) at a dosing interval of about 7 days between doses, wherein the FcRn BP is a human Fc or a human albumin, wherein the subject exhibits a baseline-subtracted plasma FIX activity trough level of at least 1 IU/dL, and wherein the baseline is the lowest measured plasma Factor IX level in the subject prior to administering the first dose of the chimeric polypeptide.
123 . The method of claim 122 , wherein the dosing interval is 7 days.
124 . The method of claim 122 , wherein each of the multiple doses is 25 IU/kg to 40 IU/kg.
125 . The method of claim 124 , wherein the dosing interval is 7 days.
126 . The method of claim 122 , wherein each of the multiple doses is 25 IU/kg, 30 IU/kg, 35 IU/kg, 40 IU/kg, 45 IU/kg, or 50 IU/kg.
127 . The method of claim 122 , wherein each of the multiple doses is 25 IU/kg.
128 . The method of claim 122 , wherein each of the multiple doses is 30 IU/kg.
129 . The method of claim 122 , wherein each of the multiple doses is 35 IU/kg.
130 . The method of claim 122 , wherein each of the multiple doses is 40 IU/kg.
131 . The method of claim 122 , wherein each of the multiple doses is 45 IU/kg.
132 . The method of claim 122 , wherein each of the multiple doses is 50 IU/kg.
133 . The method of claim 122 , wherein the human FIX comprises amino acids 1 to 415 of SEQ ID NO: 2.
134 . The method of claim 122 , wherein the FcRn BP is human Fc.
135 . the method of claim 122 , wherein the FcRn BP is human albumin.
136 . The method of claim 134 , wherein the human Fc comprises amino acids 1 to 227 of SEQ ID NO: 4.
137 . The method of claim 122 , wherein the chimeric polypeptide further comprises a linker joining the human FIX and the FcRn BP.
138 . The method of claim 122 , wherein the subject exhibits a baseline-subtracted plasma FIX activity trough level above 2 IU/dL.
139 . The method of claim 122 , wherein the subject exhibits a baseline-subtracted plasma FIX activity trough level above 3 IU/dL.
140 . The method of claim 122 , wherein the subject exhibits a baseline-subtracted plasma FIX activity trough level above 4 IU/dL.
141 . The method of claim 122 , wherein the subject exhibits a baseline-subtracted plasma FIX activity trough level above 5 IU/dL.
142 . A method of prophylactic treatment of hemophilia B in a human subject in need thereof, comprising intravenously administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric polypeptide comprising human Factor IX (FIX) and a FcRn binding partner (FcRn BP) at a dosing interval of 7 days between doses, wherein the FcRn BP is a human Fc, wherein the subject exhibits a baseline-subtracted plasma FIX activity trough level of at least 1 IU/dL, and wherein the baseline is the lowest measured plasma Factor IX level in the subject prior to administering the first dose of the chimeric polypeptide.
143 . A method of prophylactic treatment of hemophilia B in a human subject in need thereof, comprising intravenously administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric polypeptide comprising human Factor IX (FIX) and a FcRn binding partner (FcRn BP) at a dosing interval of 7 days between doses, wherein the FcRn BP is a human albumin, wherein the subject exhibits a baseline-subtracted plasma FIX activity trough level of at least 1 IU/dL, and wherein the baseline is the lowest measured plasma Factor IX level in the subject prior to administering the first dose of the chimeric polypeptide.