Method of safe administration of tau phosphopeptide conjugate
AssigneesJanssen Pharmaceuticals, Inc., AC Immunce SA
InventorsAndrea Pfeifer, Elizabeth Anne Ramsburg
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Abstract
Methods for inducing anti-phosphorylated Tau antibodies without inducing a serious adverse event in humans are described. The methods include administering to the subject an effective amount of a composition containing a Tau phosphopeptide conjugated to an immunogenic carrier.
Claims48
A method of inducing antibodies against Tau, preferably at least one of phosphorylated Tau and enriched paired helical filaments (ePHFs), in a human subject in need thereof, the method comprising administering to the human subject a composition comprising a pharmaceutically acceptable carrier and 5 μg to 200 μg per dose of a conjugate having the structure of formula (I):
- or having the structure of formula (II):
- wherein
- x is an integer of 0 to 10, preferably 2 to 6, most preferably 3;
- n is an integer of 3 to 15, preferably 3 to 12;
- Carrier represents an immunogenic carrier selected from the group consisting of keyhole limpet hemocyanin (KLH), tetanus toxoid, CRM197 and an outer membrane protein mixture from N. meningitidis (OMP), or a derivative thereof;
- and
- Tau peptide represents a Tau phosphopeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:
- 1 to SEQ ID NO:
- 3 and SEQ ID NO:
- 5 to SEQ ID NO:
- 12.
A method of inducing antibodies against at least one of phosphorylated Tau and enriched paired helical filaments (ePHFs) in a human subject in need thereof, the method comprising administering to the subject a composition comprising a pharmaceutically acceptable carrier, a CpG oligonucleotide having the nucleotide sequence of SEQ ID NO:
- 14, and 5 μg to 200 μg per dose of a conjugate having the structure of:
- wherein n is an integer of 3 to 7 and VYKS(p)PVVSGDTS(p)PRHL-CONH2 comprises the phospho-tau peptide of SEQ ID NO:2.
A method of inducing a sustained immune response against a phosphorylated Tau protein (pTau) in a human subject in need thereof, comprising:
- i. intramuscularly administering to the subject a primer vaccine comprising an effective amount of a conjugate;
- and
- ii. intramuscularly administering to the subject a first booster vaccine comprising the effective amount of the conjugate 6-10 weeks after the administration of the primer vaccine,
- wherein:
- the sustained immune response lasts at least about 20 weeks after the administration of the primer vaccine;
- the conjugate has the structure of formula (I):
- or has the structure of formula (II):
- wherein
- x is an integer of 0 to 10, preferably 2 to 6, most preferably 3;
- n is an integer of 3 to 15, preferably 3 to 12;
- Carrier represents an immunogenic carrier selected from the group consisting of keyhole limpet hemocyanin (KLH), tetanus toxoid, CRM197 and an outer membrane protein mixture from N. meningitidis (OMP), or a derivative thereof;
- and
- Tau peptide represents a Tau phosphopeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:
- 1 to SEQ ID NO:
- 3 and SEQ ID NO:
- 5 to SEQ ID NO:
- 12;
- the effective amount of the conjugate comprises 5 μg to 200 μg per dose of the conjugate.
Dependencies are inferred from the claim text.