Fusion proteins comprising factor ix for prophylactic treatment of hemophilia and methods thereof

Patent metadata

Field	Value
Publication number	US-2016346366-A1
Application number	US-201415106911-A
Country	US
Kind code	A1
Filing date	Dec 1, 2014
Priority date	Dec 23, 2013
Publication date	Dec 1, 2016
Grant date	—

Abstract

The present invention relates to prophylactic dosing regimens with long-acting factor IX (FIX) in dosing intervals of 1 week or longer, including (but not limited to) 10 days or longer, such as two weeks, three weeks or even monthly.

First claim

1 .- 115 . (canceled)

116 . A method of preventing bleeding in a subject, comprising prophylactically administering to the subject a fusion protein comprising
a) Factor IX (FIX) and b) human albumin, wherein the FIX is connected to the N-terminus of human albumin via a peptide linker cleavable by proteases involved in coagulation or activated by coagulation enzymes, and wherein the fusion protein is administered intravenously at a dose of about 25-50 IU/kg and a dosing interval of once about every 6 to 8 days.

117 . The method according to claim 116 , wherein the dose is about 35-50 IU/kg.

118 . The method according to claim 116 , wherein the dose is about 25-40 IU/kg.

119 . The method according to claim 116 , wherein the dose is about 40, 45 or 50 IU/kg.

120 . The method according to claim 116 , wherein the dosing interval is once about every 7 days.

121 . The method according to claim 116 , wherein a FIX plasma level trough of at least about 1%, at least about 2%, or between 5 and 15%, above baseline is maintained for the entire dosing interval.

122 . The method according to claim 116 , wherein the FIX is a human FIX.

123 . The method according to claim 116 , wherein the peptide linker is cleavable by FIXa and/or by FVIIa/Tissue Factor (TF).

124 . The method according to claim 123 , wherein the peptide linker comprises an amino acid sequence selected from SEQ ID NO: 2 and SEQ ID NO: 3.

125 . The method according to claim 116 , wherein the fusion protein has an amino acid sequence at least 70% identical to the amino acid sequence set forth in SEQ ID NO: 1.

126 . The method according to claim 116 , wherein the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1.

127 . The method according to claim 116 , wherein the subject is a human.

128 . The method according to claim 127 , wherein the human suffers from hemophilia B.

129 . (canceled)

130 . The method according to claim 116 , wherein the fusion protein is administered at a concentration of about 100 to 400 IU/ml.

131 . A method of preventing bleeding in a subject, comprising prophylactically administering to the subject a fusion protein comprising
a) Factor IX (FIX) and b) human albumin, wherein the FIX is connected to the N-terminus of human albumin via a peptide linker cleavable by proteases involved in coagulation or activated by coagulation enzymes, and wherein the fusion protein is administered intravenously at a dose of about 50-75 IU/kg and a dosing interval of once about every 10 to 14 days.

132 . The method according to claim 131 , wherein the dosing interval is once about every 14 days.

133 . The method according to claim 131 , wherein the dose is about 75 IU/kg and the dosing interval is once about every 14 days.

134 . The method according to claim 131 , wherein the FIX is a human FIX.

135 . The method according to claim 131 , wherein the peptide linker is cleavable by FIXa and/or by FVIIa/Tissue Factor (TF).

136 . The method according to claim 135 , wherein the peptide linker comprises an amino acid sequence selected from SEQ ID NO: 2 and SEQ ID NO: 3.

137 . The method according to claim 131 , wherein the fusion protein has an amino acid sequence at least 70% identical to the amino acid sequence set forth in SEQ ID NO: 1.

138 . The method according to claim 131 , wherein the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1.

139 . The method according to claim 131 , wherein the subject is a human.

140 . The method according to claim 139 , wherein the human suffers from hemophilia B.

141 . (canceled)

142 . The method according to claim 131 , wherein the fusion protein is administered at a concentration of about 100 to 400 IU/ml.

143 . A method of preventing bleeding in a subject, comprising prophylactically administering to the subject a fusion protein comprising
a) Factor IX (FIX) and b) human albumin, wherein the FIX is connected to the N-terminus of human albumin via a peptide linker cleavable by proteases involved in coagulation or activated by coagulation enzymes, and wherein the fusion protein is administered intravenously at a dose of about 90-250 IU/kg and a dosing interval of once about every 3 weeks or longer.

144 . The method according to claim 143 , wherein the dose is about 100 IU/kg.

145 . The method according to claim 143 , wherein a FIX plasma level trough of at least about 2-4% above baseline is maintained for the entire dosing interval.

146 . The method according to claim 143 , wherein the dosing interval is once about every 21 days.

147 . The method according to claim 143 , wherein the FIX is a human FIX.

148 . The method according to claim 143 , wherein the peptide linker is cleavable by FIXa and/or by FVIIa/Tissue Factor (TF).

149 . The method according to claim 148 , wherein the peptide linker comprises an amino acid sequence selected from SEQ ID NO: 2 and SEQ ID NO: 3.

150 . The method according to claim 143 , wherein the fusion protein has an amino acid sequence at least 70% identical to the amino acid sequence set forth in SEQ ID NO: 1.

151 . The method according to claim 143 , wherein the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 1.

152 . The method according to claim 143 , wherein the subject is a human.

153 . The method according to claim 152 , wherein the human suffers from hemophilia B.

154 . (canceled)

155 . The method according to claim 143 , wherein the fusion protein is administered at a concentration of about 100 to 400 IU/ml.

Assignees

• Csl Ltd

Inventors

• Jacobs Iris
• Bensen-Kennedy Debra
• Voigt Christine

Classifications

• C07K2319/31

  fusions, other than Fc, for prolonged plasma life, e.g. albumin · CPC title

• C12N9/644

  Coagulation factor IXa (3.4.21.22) · CPC title

• C12Y304/21022

  Coagulation factor IXa (3.4.21.22) · CPC title

• C07K14/745

  Blood coagulation or fibrinolysis factors · CPC title

• A61K38/4846 Primary

  Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38) · CPC title