Method of safe administration of phosphorylated Tau peptide vaccine
Inventors
Pfeifer, Andrea • Muhs, Andreas • Pihlgren Bosch, Maria • Vukicevic Verhille, Marija • Piot, Nicolas • Ghimire, Saroj Raj • Ramsburg, Elizabeth Anne • De Marco, Donata • Sadaka, Charlotte
Assignees
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Publication Number
US-12324855-B2
Publication Date
2025-06-10
Expiration Date
Abstract
Methods for inducing anti-phosphorylated Tau antibodies without inducing a severe adverse event in humans are described. The methods include administering to the subject an effective amount of liposomes including a toll-like receptor 4 agonist and a Tau phosphopeptide presented on the surface of the liposome.
Core Innovation
The invention concerns inducing anti-phosphorylated Tau antibodies in a human subject while avoiding a severe adverse event. The approach administers liposomes comprising a toll-like receptor 4 agonist and a Tau phosphopeptide, where the Tau phosphopeptide is presented on the surface of the liposome. The method is directed to a subject in need thereof and uses an effective amount of the liposomes to induce the anti-phosphorylated Tau antibodies.
A key element is the use of a Tau phosphopeptide whose amino acid sequence is selected from specified SEQ ID NOs. The Tau phosphopeptide is administered at an amount of about 25 nmoles to about 750 nmoles per dose. By surface presentation on the liposome together with a TLR4 agonist, the invention aims to generate an antibody response targeting phosphorylated Tau.
Safety is emphasized as avoiding encephalitis and other severe adverse events while demonstrating immunogenicity. The provided summary describes immunogenicity and safety outcomes across animal and human studies, including Phase Ib/IIa results indicating safety/tolerability and induction of anti-pTau antibodies without evidence of CNS inflammation. Additional described formulations include optional components such as helper T-cell epitopes and lipidated CpG oligonucleotides, which are presented as part of the liposome contents.
Claims Coverage
The independent claim is directed to a method of inducing anti-phosphorylated Tau antibodies without inducing a severe adverse event in a human subject, using surface-displayed Tau phosphopeptide on liposomes together with a TLR4 agonist. The dependent claims further specify Tau phosphopeptide sequence options, dosing amounts, possible TLR4 agonist/liposome contents, routes of administration, and optional immunostimulatory components such as helper T-cell epitopes and lipidated CpG oligonucleotides.
Inducing anti-phosphorylated Tau antibodies without severe adverse event using surface-displayed Tau phosphopeptide liposomes plus TLR4 agonist
Administering an effective amount of liposomes comprising a toll-like receptor 4 agonist and a Tau phosphopeptide comprising an amino acid sequence selected from SEQ ID NOs: 2, 5, 9 and 12, wherein the Tau phosphopeptide is presented on the surface of the liposome, and wherein inducing is performed without inducing a severe adverse event in a human subject in need thereof.
Tau phosphopeptide dose amount for liposome surface presentation
Administering the Tau phosphopeptide at an amount of about 25 nmoles to about 750 nmoles per dose in the liposomes presenting the Tau phosphopeptide on the surface.
TLR4 agonist-containing liposomes
Providing liposomes comprising a toll-like receptor 4 agonist as part of the administering step for inducing anti-phosphorylated Tau antibodies.
Optional helper T-cell epitope and lipidated CpG oligonucleotide in liposomes
Including, in the liposomes, a helper T-cell epitope and a lipidated CpG oligonucleotide.
Subcutaneous administration route for the liposome method
Administering the liposomes subcutaneously.
Claim coverage centers on surface-presented Tau phosphopeptide on liposomes combined with a toll-like receptor 4 agonist to induce anti-phosphorylated Tau antibodies in humans while avoiding a severe adverse event. Dependent claim elements further constrain Tau phosphopeptide sequences and dose amounts, and add optional helper T-cell epitope and lipidated CpG components, including a narrowed administration route (subcutaneous).
Stated Advantages
Induces anti-phosphorylated Tau antibodies in a human subject.
Does not induce a severe adverse event in the human subject.
Safety is emphasized as avoiding encephalitis while maintaining immunogenicity.
Phase Ib/IIa results indicate safety/tolerability and induction of anti-pTau antibodies without evidence of CNS inflammation.
Documented Applications
Use of the method for a human subject in need thereof for inducing anti-phosphorylated Tau antibodies.
Immunogenicity and safety evaluation in humans in Phase Ib/IIa clinical studies, including induction of anti-pTau antibodies without evidence of CNS inflammation.
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