Peptide conjugated particles
Inventors
Shea, Lonnie D. • Miller, Stephen D. • Yap, Jonathan Woon Teck • GETTS, Daniel R. • McCarthy, Derrick
Assignees
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Publication Number
US-12533403-B2
Publication Date
2026-01-27
Expiration Date
Abstract
The present invention provides compositions comprising peptide-coupled biodegradable poly(lactide-co-glycolide) (PLG) particles. In particular, PLG particles are surface-functionalized to allow for coupling of peptide molecules to the surface of the particles (e.g., for use in eliciting induction of immunological tolerance).
Core Innovation
The invention concerns peptide-coupled biodegradable poly(lactide-co-glycolide) particles and a composition comprising a negatively charged liposome comprising encapsulated antigens or one or more antigenic epitopes. The particle is characterized by a negative zeta potential between −30 mV and −100 mV and a diameter between 0.3 μm and 10 μm.
The invention addresses antigen-specific immunological tolerance in autoimmune diseases, allergy, and transplantation. It states that negatively charged particle properties, including zeta potential ranges and particle diameters, are associated with reduced relapsing autoimmune disease activity, modulation of Th1/Th17/Th2 responses, and improved tolerance when antigens are provided via encapsulation.
The invention further describes immune uptake and tolerance mechanisms, including MARCO scavenger receptor-dependent uptake and roles of anergy and regulatory T cells, including Tregs/CD25 and iTregs. It also states that tolerance can be reversed or abrogated in the presence of anti-PD-1, agonistic anti-CD40, anti-IL-12, or anti-CD25.
Claims Coverage
The independent claims identify two inventive feature sets: a negatively charged liposome composition with defined zeta potential and size, and a method of inducing antigen-specific tolerance by administering that composition. The claim coverage centers on the combination of negatively charged liposomes with encapsulated antigens or antigenic epitopes and defined physicochemical parameters.
Negatively charged liposome with encapsulated antigens or epitopes defined by zeta potential and diameter
A composition comprising a negatively charged liposome comprising encapsulated antigens or one or more antigenic epitopes, wherein the particle has a negative zeta potential of between −30 mV and −100 mV and a diameter of between 0.3 μm to 10 μm.
Inducing antigen-specific tolerance by administering a negatively charged liposome with encapsulated antigens or epitopes
A method of inducing antigen specific tolerance in a subject by administering a composition of a negatively charged liposome comprising encapsulated antigens or one or more antigenic epitopes, wherein the particle has a negative zeta potential of between −30 mV and −100 mV and a diameter of between 0.3 μm to 10 μm.
The claim coverage is anchored in using negatively charged liposomes with defined negative zeta potential and particle diameter, loaded with encapsulated antigens or antigenic epitopes, as a composition and as the basis for inducing antigen-specific tolerance in a subject.
Stated Advantages
Prevents or treats relapsing autoimmune disease.
Induces long-lasting antigen-specific tolerance.
Inhibits Th1/Th17 and Th2 responses.
Reduces immune cell infiltration and blood-brain barrier disruption.
Reduced anaphylaxis risk versus surface-coupled antigen.
Improved antigen-specific immunological tolerance when antigens are provided via encapsulation.
Modulation of Th1/Th17/Th2 responses.
Involvement of regulatory T cells (Tregs/CD25).
Documented Applications
Prevention or treatment of relapsing autoimmune disease in models including experimental autoimmune encephalitis (EAE) and relapsing EAE (R-EAE) associated with PLP139-151 and related epitopes.
Application to allergic airway inflammation (AAI) associated with antigen or epitope use and Th2-related readouts.
Application to type 1 diabetes in the context of insulin or p31 peptide and NOD mice.
Application relating to autoimmune diseases and conditions listed in the document, including inflammatory bowel disease, autoimmune hepatitis, graft-versus-host disease (GvHD), and transplantation-related contexts.
Prevention and treatment in relapsing experimental autoimmune encephalitis (R-EAE)/EAE models using PLP139-151-PLG.
Allergy-related outcomes using encapsulation of ovalbumin (OVA).
Type 1 diabetes models using insulin/proinsulin peptides and related insulin tolerance contexts.
Transplantation tolerance studies described via chimerism.
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