Fibrin/fibrinogen-binding conjugate
AssigneesBaxter Aktiengesellschaft, Baxter International Inc.
InventorsHeinz Redl, Walter Fuerst, Rudolf Kneidinger, Sam L. Helgerson, Douglas Looker, Elisabeth M. Inman, Jane P. Richards, Catalina Wong
Life of this patent
Estimating the term…
Abstract
A fibrin/fibrinogen binding conjugate for forming a depot for the sustained release of a pharmaceutically active substance from a fibrin clot. The conjugate comprises a fibrin/fibrinogen binding moiety bound to a pharmaceutically active substance either directly or via an intervening substance capturing moiety such as an antibody. The conjugate can also be a recombinant fusion protein comprising a fibrin/fibrinogen binding moiety such as VEGF165 C-terminal domain fused to a wound-healing substance such as leptin.
Claims45
Fibrin/fibrinogen-binding conjugate comprising
- a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165,
- a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance, and
- a pharmaceutically active substance,
- wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety.
Fibrin/fibrinogen-binding conjugate comprising
- a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, and
- a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance,
- wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety.
Fibrin/fibrinogen-binding conjugate comprising
- a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, and
- a pharmaceutically active substance,
- wherein said fibrin/fibrinogen-binding moiety is bound to said pharmaceutically active substance.
Kit for forming a depot for a pharmaceutically active substance comprising
- a tissue adhesive based on fibrinogen and
- a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, and a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety.
Method for producing a depot of pharmaceutically active substance comprising
- providing a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance and a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety,
- administering said conjugate at a depot site together with a fibrinogen preparation,
- allowing processing of said fibrinogen to fibrin whereby a fibrin clot is formed, and
- allowing binding of said conjugate to said fibrinogen within said fibrin clot.
Method for producing a depot of a pharmaceutically active substance comprising
- providing a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance and a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety,
- administering said conjugate at a depot site together with a fibrinogen preparation,
- allowing processing of said fibrinogen to fibrin whereby a fibrin clot is formed, and
- allowing binding of said conjugate to said fibrin clot.
Depot for a pharmaceutically active substance comprising fibrin and a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance and a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety.
Depot for a pharmaceutically active substance, said depot obtainable by the steps comprising:
- providing a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance and a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety,
- administering said conjugate at a depot site together with a fibrinogen preparation,
- allowing processing of said fibrinogen to fibrin whereby a fibrin clot is formed, and
- allowing binding of said conjugate to said fibrinogen or said fibrin clot.
Method for treating a patient suffering from a pathological state, said pathological state being treatable with a pharmaceutically active substance, comprising administering to said patient an effective amount of a tissue adhesive based on fibrinogen and a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, a substance capturing moiety capable of reversibly binding to a pharmaceutically active substance and said pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said substance capturing moiety.
Kit for forming a depot for a pharmaceutically active substance comprising
- a tissue adhesive based on fibrinogen and
- a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165.
Method for producing a depot of pharmaceutically active substance comprising
- providing a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, and a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said pharmaceutically active substance,
- administering said conjugate at a depot site together with a fibrinogen preparation,
- allowing processing of said fibrinogen to fibrin whereby a fibrin clot is formed, and
- allowing binding of said conjugate to said fibrinogen within said fibrin clot.
Method for producing a depot of a pharmaceutically active substance comprising
- providing a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, and a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said pharmaceutically active substance,
- administering said conjugate at a depot site together with a fibrinogen preparation,
- allowing processing of said fibrinogen to fibrin whereby a fibrin clot is formed, and
- allowing binding of said conjugate to said fibrin clot.
Depot for a pharmaceutically active substance comprising fibrin and a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, and a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said pharmaceutically active substance.
Depot for a pharmaceutically active substance, said depot obtainable by the steps comprising:
- providing a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, and a pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said pharmaceutically active substance,
- administering said conjugate at a depot site together with a fibrinogen preparation,
- allowing processing of said fibrinogen to fibrin whereby a fibrin clot is formed, and
- allowing binding of said conjugate to said fibrinogen or said fibrin clot.
Method for treating a patient suffering from a pathological state, said pathological state being treatable with a pharmaceutically active substance, comprising administering to said patient an effective amount of a tissue adhesive based on fibrinogen and a fibrin/fibrinogen-binding conjugate comprising a fibrin/fibrinogen-binding moiety, wherein said fibrin/fibrinogen-binding moiety is a VEGF165 fragment comprising a fibrin-binding C-terminal domain of VEGF165, and said pharmaceutically active substance, wherein said fibrin/fibrinogen-binding moiety is bound to said pharmaceutically active substance.
Dependencies are inferred from the claim text.