Factor ix polypeptides and methods of use thereof

Abstract

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 on-demand treatment of bleeding, comprising intravenously administering to a hemophilia B human subject in need thereof a dose of about 25 IU/kg to about 100 IU/kg of a chimeric factor IX (FIX) polypeptide comprising human FIX having an amino acid sequence identical to amino acids 1 to 415 of SEQ ID NO: 2 and a FcRn binding partner (FcRn BP), wherein the FcRn BP is human Fc or human albumin. 
     
     
         123 . The method of  claim 122 , wherein the human subject exhibits a plasma FIX level of about 30 IU/dL to about 60 IU/dL following a dose of the chimeric FIX polypeptide. 
     
     
         124 . The method of  claim 122 , wherein the human subject exhibits a plasma FIX level of about 80 IU/dL to about 100 IU/dL following a dose of the chimeric FIX polypeptide. 
     
     
         125 . The method of  claim 122 , wherein the human subject exhibits a plasma FIX level about 20% to about 50% of normal following a dose of the chimeric FIX polypeptide. 
     
     
         126 . The method of  claim 122 , wherein the human subject exhibits a plasma FIX level about 50% to about 100% of normal following a dose of the chimeric FIX polypeptide. 
     
     
         127 . The method of  claim 123 , wherein the plasma FIX level is measured 8-12 hours following a dose of the chimeric FIX polypeptide. 
     
     
         128 . The method of  claim 124 , wherein the plasma FIX level is measured 8-12 hours following a dose of the chimeric FIX polypeptide. 
     
     
         129 . The method of  claim 125 , wherein the plasma FIX level is measured 8-12 hours following a dose of the chimeric FIX polypeptide. 
     
     
         130 . The method of  claim 126 , wherein the plasma FIX level is measured 8-12 hours following a dose of the chimeric FIX polypeptide. 
     
     
         131 . The method of  claim 122 , wherein the dose is 50 IU/kg to 60 IU/kg, 70 IU/kg to 80 IU/kg, or 90 IU/kg to 100 IU/kg. 
     
     
         132 . The method of  claim 122 , wherein the chimeric FIX polypeptide is administered at a dosing interval of about 24-48 hours between two doses. 
     
     
         133 . The method of  claim 122 , wherein the chimeric FIX polypeptide is administered at a dosing interval of about 7 days between two doses. 
     
     
         134 . The method of  claim 122 , wherein the FcRn BP is human Fc. 
     
     
         135 . The method of  claim 134 , wherein the human Fc comprises amino acids 1 to 227 of SEQ ID NO: 4. 
     
     
         136 . The method of  claim 122 , wherein the FcRn BP is human albumin. 
     
     
         137 . The method of  claim 122 , wherein the chimeric polypeptide further comprises a linker joining the human FIX and the human Fc or the human albumin. 
     
     
         138 . The method of  claim 122 , wherein the human subject is in need of management of bleeding associated with surgery. 
     
     
         139 . The method of  claim 138 , wherein the surgery is minor surgery, major surgery, tooth extraction, tonsillectomy, inguinal herniotomy, synovectomy, total knee replacement, craniotomy, osteosynthesis, trauma surgery, intracranial surgery, intra-abdominal surgery, intrathoracic surgery, or joint replacement surgery. 
     
     
         140 . The method of  claim 138 , wherein the human subject will undergo major surgery. 
     
     
         141 . The method of  claim 138 , wherein the human subject is undergoing major surgery. 
     
     
         142 . The method of  claim 138 , wherein the human subject has undergone major surgery. 
     
     
         143 . The method of  claim 140 , wherein the major surgery is orthopedic surgery, extensive oral surgery, urologic surgery, or hernia surgery. 
     
     
         144 . The method of  claim 122 , wherein the human subject has hemarthrosis, a muscle bleed, an oral bleed, a hemorrhage, a hemorrhage into muscles, an oral hemorrhage, trauma, trauma capitis, gastrointestinal bleeding, an intracranial hemorrhage, an intra-abdominal hemorrhage, an intrathoracic hemorrhage, a bone fracture, central nervous system bleeding, bleeding in the retropharyngeal space, bleeding in the retroperitoneal space, or bleeding in the iliopsoas sheath.