Compositions of phosphorylated tau peptides and uses thereof
Inventors
Ramsburg, Elizabeth Anne • De Marco, Donata • Sadaka, Charlotte • Goudsmit, Jaap • Muhs, Andreas • Pihlgren Bosch, Maria • Vukicevic Verhille, Marija • Piot, Nicolas • Ghimire, Saroj Raj
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11124552-B2
Publication Date
2021-09-21
Expiration Date
Abstract
Liposomes containing tau peptides, preferably phosphorylated tau peptides, and conjugates containing tau peptides, preferably phosphorylated tau peptides, conjugated to an immunogenic carrier are described. Pharmaceutical compositions and uses of the liposomes and/or conjugates for treating or preventing a neurodegenerative disease or disorder, such as Alzheimer's Disease, are also described.
Core Innovation
The invention provides a liposome comprising a tau peptide having an amino acid sequence selected from SEQ ID NOs: 2, 5, 9, and 12, together with a helper T cell epitope comprising at least one amino acid sequence selected from SEQ ID NOs:23, 24, 25, and 26. The liposome further includes a lipidated CpG oligonucleotide having the nucleotide sequence of SEQ ID NO:18 that is covalently linked to at least one cholesterol via a linker, and monophosphoryl lipid A (MPLA). The tau peptide is presented on the surface of the liposome.
A further embodiment provides a liposome in which the tau peptide comprises the amino acid sequence of SEQ ID NO:2 and the helper T cell epitope has an amino acid sequence selected from SEQ ID NOs:39, 40, 41, 42, and 43. In this embodiment, the lipidated CpG oligonucleotide having the nucleotide sequence of SEQ ID NO:18 is covalently linked to at least one cholesterol via a linker, and monophosphoryl lipid A (MPLA) is included. The tau peptide is again presented on the surface of the liposome.
The invention addresses tauopathy and neurodegenerative diseases, including Alzheimer’s disease, by providing immunogenic compositions intended to induce an immune response against phosphorylated tau, including ePHF and anti-phosphorylated tau antibodies. The documented composition formats include liposomes presenting phosphorylated tau peptides on the liposome surface together with helper T-cell epitopes, and immunogenic carrier conjugates for tau phosphopeptides, including conjugates using CRM197 or KLH linked via specified linkers.
Claims Coverage
The partial content includes two independent claims. Each independent claim defines a liposome with surface-presented tau peptide and specifies a helper T cell epitope, a lipidated CpG oligonucleotide linked to cholesterol via a linker, and monophosphoryl lipid A (MPLA).
Surface-presented tau peptide liposome with helper T cell epitope and lipidated CpG linked to cholesterol via linker
A liposome comprising a tau peptide having an amino acid sequence selected from SEQ ID NOs: 2, 5, 9, and 12; a helper T cell epitope comprising at least one amino acid sequence selected from SEQ ID NOs:23, 24, 25, and 26; a lipidated CpG oligonucleotide having the nucleotide sequence of SEQ ID NO:18, wherein the CpG oligonucleotide comprises one or more phosphorothioate internucleotide linkages, and wherein the CpG oligonucleotide is covalently linked to at least one cholesterol via a linker; and monophosphoryl lipid A (MPLA), wherein the tau peptide is presented on the surface of the liposome.
Surface-presented tau peptide liposome with fixed tau SEQ ID and lipidated CpG linked to cholesterol via linker
A liposome comprising a tau peptide comprising the amino acid sequence of SEQ ID NO: 2; a helper T cell epitope having an amino acid sequence selected from SEQ ID NOs:39, 40, 41, 42, and 43; a lipidated CpG oligonucleotide having the nucleotide sequence of SEQ ID NO:18, wherein the CpG oligonucleotide is covalently linked to at least one cholesterol via a linker; and monophosphoryl lipid A (MPLA), wherein the tau peptide is presented on the surface of the liposome.
Both independent claims center on a liposome that presents a tau peptide on the surface and includes a helper T cell epitope, a lipidated CpG oligonucleotide covalently linked to cholesterol via a linker, and monophosphoryl lipid A (MPLA). One independent claim further requires phosphorothioate internucleotide linkages in the CpG oligonucleotide.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?