Molecular guide system peptides and uses thereof
Inventors
Brown, Kathlynn C. • Collins, Nathan • Li, Shunzi “Susan” • Allred, Curtis • Chung, Keen • McGuire, Michael
Assignees
Publication Number
US-11965004-B2
Publication Date
2024-04-23
Expiration Date
2038-07-10
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Disclosed are compositions comprising an antibody conjugated to one or more molecular guidance system (MGS) peptides. Disclosed are methods of treating a subject in need thereof comprising administering to the subject in need thereof an effective amount of an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target involved in the disease process. Disclosed are methods of targeting an intracellular target comprising administering an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target.
Core Innovation
Disclosed are compositions comprising an antibody conjugated to one or more molecular guidance system (MGS) peptides. These compositions enable the targeting of antibodies to intracellular targets by facilitating their internalization into specific cell types and subcellular compartments. The MGS peptides can be selected from specific sequences, such as SEQ ID NOs: 2, 3, 20-22, and 38-41, and may be conjugated to antibodies directly or via a linker (for example, PEG-based linkers).
The invention addresses the problem that monoclonal antibodies (MAbs) are not cell permeable, limiting their clinical use to extracellular or cell surface targets. As many therapeutically relevant targets, particularly those involving protein-protein interactions, are located within the cell, there is a significant unmet need for systematic methods to deliver therapeutic antibodies to intracellular sites, especially for the treatment of serious diseases such as cancer, infectious diseases, and genetically-inherited conditions.
The disclosed MGS-antibody conjugates localize antibodies to discrete subcellular compartments—including lysosome, Golgi apparatus, endoplasmic reticulum, cytoplasm, and nucleus—enabling targeted engagement of intracellular targets involved in disease processes. Furthermore, methods for preparing these conjugates, as well as pharmaceutical compositions and methods of treatment using such compositions for a range of diseases, are described. The platform is exemplified by peptides optimized for specific cellular uptake and subcellular localization, and by antibody conjugates effective in cellular and animal models.
Claims Coverage
The patent presents three main inventive features through its independent claims, addressing novel compositions, peptides, and methods for targeting and treating intracellular targets.
Antibody conjugate with specific MGS peptides
A composition comprising an antibody conjugated to one or more molecular guidance system (MGS) peptides, either directly or via a linker, with the MGS peptides selected from SEQ ID NOs: 2, 3, 20-22, and 38-41. Key aspects: - The antibody can be any antibody, including monoclonal or anti-Ras monoclonal antibodies. - The composition may use various linker types, such as polyethylene glycol (PEG). - The MGS peptide component enables intracellular localization to subcellular compartments such as the lysosome, Golgi apparatus, endoplasmic reticulum, cytoplasm, or nucleus.
Defined MGS peptide sequences
A molecular guidance system (MGS) peptide selected from the group consisting of SEQ ID NOs: 2, 3, 20-22, and 38-41. Key elements: - The independent claim covers the defined peptide sequences as compounds themselves, which can be used as components for targeted delivery.
Methods for targeting and treating intracellular targets using MGS-antibody conjugates
A method of targeting an intracellular target in a cell in vitro or in a subject by contacting the cell or administering to the subject a composition comprising an antibody conjugated to one or more defined MGS peptides, where the antibody targets an intracellular target. Additionally, a method of treating a subject having a disease by administering an effective amount of such a composition, where the antibody targets an intracellular target involved in the disease process.
Collectively, these inventive features cover compositions of antibody-MGS peptide conjugates, the MGS peptides themselves, and methods for their use in targeting and treating intracellular disease targets.
Stated Advantages
Enables delivery of therapeutic antibodies to specific intracellular targets and subcellular compartments, overcoming the cell impermeability limitation of conventional antibodies.
Creates a new class of intracellular-acting drugs capable of targeting heretofore 'undruggable' targets within cells, expanding therapeutic options for various diseases.
Allows precise delivery of antibodies and other payloads to desired cell types and subcellular locations, improving therapeutic specificity and efficacy.
Reduces non-specific tissue uptake and increases retention of therapeutics in target tissues, as demonstrated with tumor-targeting conjugates.
Enables rapid generation of targeted therapeutics for new and emerging disease threats, including pathogens and bioterrorism agents.
Facilitates delivery of a wide variety of payloads beyond antibodies, including small molecules, imaging agents, nucleic acids, and nanoparticles.
Documented Applications
Treatment of infectious diseases, cancer, diabetes, neurological and neurodegenerative diseases, and genetically-inherited diseases by targeting intracellular disease-related targets.
Therapeutic applications in subjects exposed to bioterrorism agents.
Use in early disease detection and as companion diagnostics to monitor response to treatment.
Delivery of cell-impermeable therapeutics, such as protein toxins or DNA alkylators, to intracellular or subcellular locations in cancer cells.
Intracellular delivery of antibodies, as well as other payloads (e.g. small molecule drugs, imaging agents, nanoparticles, DNA, proteins), for targeted therapies or in vitro/in vivo diagnostics.
Personalized therapies for cancer and intracellular nanoparticle delivery.
Interested in licensing this patent?