Targeted drug delivery through affinity based linkers
Inventors
Sengupta, Shiladitya • Roy, Monideepa • GUPTA, Nimish • Hossain, Seikh Samad
Assignees
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Publication Number
US-11701429-B2
Publication Date
2023-07-18
Expiration Date
Abstract
The current invention describes a conjugate of a targeting moiety linked to a drug via a molecule having high affinity for the targeting moiety at physiological pH such that the drug releases at low pH from the targeting moiety.
Core Innovation
The invention relates to targeted drug delivery conjugates in which a targeting ligand, such as an antibody or antibody fragment, binds an affinity ligand non-covalently at physiological pH. The affinity ligand is connected to the targeting ligand to form an affinity binding arrangement that enables delivery of a therapeutically active agent to an antigen expressing cell via affinity binding to the affinity ligand.
In the conjugates, the affinity ligand is a triazine having affinity to the targeting ligand, and the therapeutic agent is linked to the affinity ligand via a linker. This arrangement combines antibody-mediated delivery with triazine-mediated affinity binding to position the therapeutic agent on antigen expressing cells.
The non-covalent connection involving the affinity ligand provides reduced binding at low pH, which is associated with release of the therapeutically active agent, followed by cleavage and drug translocation to the target site. The disclosure further includes linkers and spacers, including branched linkers and cleavable linking groups responsive to intracellular conditions such as pH/redox/enzyme-labile groups.
Claims Coverage
The claims cover three inventive features defining the conjugate architecture: an antibody targeting ligand non-covalently connected to a triazine affinity ligand, and a therapeutic agent linked to the affinity ligand via a linker for delivery to antigen expressing cells.
Antibody targeting ligand with non-covalent affinity ligand connection
A targeted drug delivery conjugate comprising a targeting ligand that is an antibody and an affinity ligand linked to the targeting ligand, wherein the affinity ligand is non-covalently connected to the targeting ligand.
Triazine affinity ligand having affinity to the antibody
The affinity ligand is a triazine having affinity to the targeting ligand.
Therapeutic agent linked via a linker for delivery to antigen expressing cells
A therapeutic agent is linked to the affinity ligand via a linker, wherein the therapeutic agent is an anticancer agent or a cytotoxic drug, and the targeting ligand delivers the therapeutic agent to an antigen expressing cell through affinity binding to the triazine.
Monoclonal antibody targeting ligand
The antibody targeting ligand is a monoclonal antibody.
Branched linker
The linker is a branched linker.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition including the conjugate and a pharmaceutically acceptable carrier.
Overall, the claims cover antibody-based conjugates using a non-covalently connected triazine affinity ligand and a linker-attached anticancer or cytotoxic therapeutic agent, with delivery to antigen expressing cells through triazine affinity binding. Dependent features further specify a monoclonal antibody, a branched linker, and a pharmaceutical composition including a pharmaceutically acceptable carrier.
Stated Advantages
Reduced binding at low pH.
Release of the therapeutically active agent, followed by cleavage and drug translocation to the target site.
Documented Applications
No documented applications found
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