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
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11684576-B2
Publication Date
2023-06-27
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 relates to a method of inducing anti-phosphorylated Tau (pTau) antibodies in a human subject without inducing a severe adverse event. The method administers an effective amount of liposomes that comprise a toll-like receptor 4 agonist and a Tau phosphopeptide. The Tau phosphopeptide is presented on the surface of the liposome and comprises an amino acid sequence selected from specified SEQ ID NO ranges.
The disclosed approach addresses a specific safety concern by aiming to avoid severe adverse events, including encephalitis/meningoencephalitis, while inducing anti-phosphorylated Tau antibodies. The formulation supports the intended immunogenic response by combining the surface-presented Tau phosphopeptide with a TLR4 agonist.
In further embodiments, the liposomes include additional immunostimulatory components, including a helper T-cell epitope and a lipidated CpG oligonucleotide with a defined nucleotide sequence. The independent-claim example specifies monophosphoryl hexa-acyl Lipid A, 3-deacyl as the TLR4 agonist and at least one lipid selected from DMPC, DMPG, and cholesterol, with quantitative per-dose ranges for the liposome components.
Claims Coverage
The document includes two independent claims, each directed to inducing anti-phosphorylated Tau antibodies in a human subject without inducing a severe adverse event. The inventive features center on liposomes that present selected Tau phosphopeptides on the surface together with a TLR4 agonist, and, in one independent claim, additional defined immunostimulatory components plus specified lipids and per-dose quantitative ranges.
Surface-presented Tau phosphopeptide with TLR4 agonist liposomes to induce anti-pTau antibodies without severe adverse events
Administering to the human subject 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 NO:1 to SEQ ID NO:3 and SEQ ID NO:5 to SEQ ID NO:12, wherein the Tau phosphopeptide is administered at about 25 nmoles to about 750 nmoles per dose and is presented on the surface of the liposome, thereby inducing anti-phosphorylated Tau antibodies without inducing a severe adverse event.
Defined pTau liposome composition with TLR4 agonist, helper T-cell epitope, lipidated CpG, and specified lipids
Administering an effective amount of liposomes comprising a Tau phosphopeptide having the amino acid sequence of SEQ ID NO:28, a toll-like receptor 4 agonist comprising monophosphoryl hexa-acyl Lipid A, 3-deacyl, a helper T-cell epitope comprising the amino acid sequence of SEQ ID NO:39, a lipidated CpG oligonucleotide comprising the nucleotide sequence of SEQ ID NO:18, and at least one lipid selected from DMPC, DMPG, and cholesterol, with specified per-dose component ranges, thereby inducing anti-phosphorylated Tau antibodies without inducing a severe adverse event.
Across both independent claims, coverage is directed to administering liposomes that present an anti-phosphorylated Tau immunogen on the liposome surface together with a TLR4 agonist to induce anti-phosphorylated Tau antibodies while avoiding severe adverse events. One independent claim further narrows to a fully defined liposome composition including a specific Tau phosphopeptide, monophosphoryl hexa-acyl Lipid A, 3-deacyl, helper T-cell epitope, lipidated CpG, and selected lipids, with specified per-dose ranges.
Stated Advantages
Inducing anti-phosphorylated Tau antibodies in a human subject without inducing a severe adverse event.
Documented Applications
A method of inducing anti-phosphorylated Tau antibodies without inducing a severe adverse event in a human subject in need thereof.
The method is applied to a subject who needs treatment for Alzheimer's Disease.
Interested in licensing this patent?