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US 2006/0222588 A1Published application
Antilymphoma targeting agents with effector and affinity functions linked by a trifunctional reagent
OwnerBengt Sandberg, Rune Nilssoninventors
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Abstract
A medical agent comprising a reagent conjugated to an anti-lymphoma antibody is disclosed, as well as a kit containing said medical agent, use of said medical agent, and a method for treatment of lymphoma. The reagent may comprise an effector, e.g. an antitumor agent or a diagnostic marker, and an affinity ligand enabling extracorporeal clearance of the agent. The three components are bound by a trifunctional linker.
Claims27
A medical agent comprising an anti-CD20 anti-body or variants thereof conjugated to 1.5 to 3.5 reagents, wherein each reagent comprises
- a) a trifunctional cross-linking moiety selected from the group consisting of triaminobenzene, tricarboxybenzene, dicarboxyaniline and diaminobenzoic acid, coupled to
- b) a biotin molecule selected from the group consisting of biotin and biotin derivatives having essentially the same binding function to avidin or streptavidin as biotin, via a linker 1, wherein the linker 1 contains hydrogen bonding atoms, preferably ethers or thioethers, or ionisable groups, preferably carboxylate, sulphonates and ammonium to aid in water solubilisation of the biotin moiety, and stability against enzymatic cleavage has been provided by introducing substituents to the biotinamide amine or to an atom adjacent to that amine, to
- c) an effector agent covalently linked to the trifunctional cross-linking moiety, optionally via a linker 2, wherein the linker 2 provides a spacer length of 1-25 atoms and the linker contains hydrogen bonding atoms, preferably ethers or thioethers, or ionisable groups to aid in water solubility, and to
- d) a linker 3, which covalently links the anti-CD20 antibody to the reagent, wherein the linker 3 provides a spacer length of 1-25 atoms and contains hydrogen bonding atoms, preferably ethers or thioethers, or ionisable groups to aid in water solubility, wherein the anti-CD20 antibody is selected from a group of antibodies or variants thereof having a specific binding to CD20 antigens and having an affinity binding constant of at least 5×106 M−1.
1 more element
Dependencies are inferred from the claim text.