LONG LASTING ANTI-ANGIOGENIC PEPTIDES
Modified anti-angiogenic peptides are disclosed. The modified peptides are capable of forming a peptidase stabilized anti-angiogenic peptide. The modified anti-angiogenic peptides, particularly modified kringle 5 peptides are capable of forming a conjugate with a blood protein. Conjugates are prepared from anti-angiogenic peptides, particularly kringle 5 peptides, by combining the peptide with a reactive functional group with a blood protein. The conjugates may be formed in vivo or ex vivo. The conjugates are administered to patients to provide an anti-angiogenic effect.
1 .- 21 . (canceled)
22 . A method for providing an anti-angiogenic effect to a patient, comprising administering to the patient a conjugate formed by a method comprising covalently coupling a modified kringle 5 peptide with human serum albumin, wherein the modified kringle 5 peptide comprises a kringle 5 peptide and a maleimido group coupled to the kringle 5 peptide, optionally via a linking group;
wherein the kringle 5 peptide is a peptide fragment of amino acid residues 443 to 546 of SEQ ID NO:1, of between 4 and 104 amino acids and having anti-angiogenic activity, and optionally having an amino acid substitution at Cys 523 ;
wherein the maleimido group and optional linking group is optionally coupled to the kringle 5 peptide by one or more additional amino acids;
wherein the kringle 5 peptide is optionally coupled to an N-terminal protecting group;
wherein the kringle 5 peptide has an α-C-terminal carboxy, an α-C-terminal carboxamide, or an α-C-terminal alkylcarboxamide;
wherein said maleimido group reacts with a thiol group of Cys 34 of said human serum albumin to form a conjugate that has a 1:1 loading of said kringle 5 peptide to said human serum albumin.
23 . A method for providing an anti-angiogenic effect to a patient, comprising administering to the patient a conjugate formed by a method comprising covalently coupling a modified kringle 5 peptide with human serum albumin, wherein the modified kringle 5 peptide comprises a kringle 5 peptide and a reactive group coupled to the kringle 5 peptide, optionally via a linking group, wherein the reactive group is selected from the group consisting of succinimidyl and maleimido groups.
24 . A conjugate formed by a method comprising covalently coupling a modified kringle 5 peptide with human serum albumin, wherein the modified kringle 5 peptide comprises a kringle 5 peptide and a reactive group coupled to the kringle 5 peptide, optionally via a linking group, wherein the reactive group is selected from the group consisting of succinimidyl and maleimido groups.