Targeted drug delivery through affinity based linkers
The current invention discloses targeted drug delivery conjugates comprising a targeting moiety linked to a drug via a molecule having an affinity for the targeting moiety. Typically, the conjugate comprises a targeting ligand and a molecule of interest, e.g., a therapeutic agent. The targeting ligand and the molecule of interest are linked to each other via an affinity ligand. The affinity ligand is further covalently or non-covalently linked to a drug or therapeutic agent. The drug can be modified to make it more soluble and so that it cleaves from the linking molecule at the target site.
1. A targeted drug delivery conjugate comprising:
a targeting ligand;
(ii) an affinity ligand linked to said targeting ligand; and
(iii) a therapeutic agent linked to said affinity ligand via a linker;
wherein said affinity ligand is covalently connected to said therapeutic agent; said affinity ligand is non-covalently connected to said targeting ligand, wherein the targeting ligand is an antibody and the affinity ligand is a ligand that binds non-covalently and specifically to an antibody; and wherein the affinity ligand is 4-mercaptoethyl pyridine (4-MEP).
2. The targeted drug delivery conjugate of claim 1 wherein the targeting ligand binds a protein, receptor, or marker expressed on the surface of a cancer cell.
3. The conjugate of claim 1 , wherein the therapeutic agent is an anticancer agent or a cytotoxic drug.
4. The targeted drug delivery conjugate of claim 1 , wherein the therapeutic agent is linked to the linker via a cleavable linking group.
5. The targeted drug delivery conjugate of claim 1 , wherein the affinity ligand is linked to the linker via a cleavable linking group.
6. The targeted drug delivery conjugate of claim 1 , wherein the linker is a branched linker.
7. The targeted drug delivery conjugate of claim 6 , wherein the conjugate comprises at least two therapeutic agents linked to the affinity molecule via the branched linker.
8. The targeted drug delivery conjugate of claim 6 , wherein the conjugate comprises two or more affinity ligands linked to the therapeutic agent.
9. A pharmaceutical composition comprising a conjugate of claim 1 and a pharmaceutically acceptable carrier.