Claims for Patent: 9,821,043

Summary for Patent: 9,821,043

Title:	Anti-HER2 vaccine based upon AAV derived multimeric structures
Abstract:	The present invention relates to parvovirus mutated structural proteins comprising insertions of mimotopes of a HER2, compositions, multimeric structures, medicaments and vaccines comprising the same, nucleic acids, expression cassettes, constructs, vectors and cells comprising the nucleic acids, methods of preparing the structural proteins and methods of inducing a B-cell response or of treating a HER2-related disease.
Inventor(s):	Michaelis; Uwe (Weilheim, DE), Jensen-Jarolim; Erika (Vienna, AT), Rehfuess; Christoph (Munchen, DE), Weghofer; Margit (Vienna, AT)
Assignee:	Medigene AG (Planegg-Martinsried, DE)
Application Number:	14/344,783
Patent Claims:	1. Parvovirus mutated structural protein for inducing a B-cell response against human epidermal growth factor receptor (HER2), which comprises one or more mimotopes of HER2 capable of specifically binding to an antibody directed against HER2, wherein at least one of the mimotopes comprises an amino acid sequence of SEQ ID NO: 66, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 97, SEQ ID NO: 98 or SEQ ID NO: 99. 2. Parvovirus mutated structural protein according to claim 1, wherein the antibody is Trastuzumab or Pertuzumab. 3. Parvovirus mutated structural protein according to claim 1, wherein a plurality of structural proteins is capable of forming a capsomeric structure, capsid or virus-like particle. 4. Parvovirus mutated structural protein according to claim 3, wherein the one or more mimotopes of HER2 are arranged in the parvovirus mutated structural protein to be located on the surface of the capsomeric structure, capsid or virus-like particle. 5. Parvovirus mutated structural protein according to claim 1, wherein the parvovirus is selected from the group consisting of adeno-associated virus (AAV), bovine AAV (b-AAV), canine AAV (CAAV), canine parvovirus (CPV), mouse parvovirus, minute virus of mice (MVM), B19, H1, avian AAV (AAAV), feline panleukopenia virus (FPV), and goose parvovirus (GPV). 6. Parvovirus mutated structural protein according to claim 5, wherein the AAV is AAV-1, AAV-2, AAV-3b, AAV-4, AAV-5, AAV-6, AAV-7, AAV-8, AAV-9, AAV-10, AAV-11, or AAV-12. 7. Parvovirus mutated structural protein according to claim 1, wherein the parvovirus mutated structural protein is a fusion protein further comprising a second protein or peptide domain. 8. Parvovirus mutated structural protein according to claim 1, wherein at least one of the mimotopes is not present in a wild type parvoviral structural protein, or wherein the wild type parvoviral structural protein is not capable of specifically binding to Trastuzumab. 9. A multimeric structure comprising parvovirus mutated structural proteins according to claim 1, wherein the structure is an aggregate of at least 5, at least 10, at least 30, or at least 60 mutated structural proteins. 10. The multimeric structure according to claim 9, wherein the multimeric structure is a capsomeric structure, capsomer, a capsid, a virus-like particle, or a virus. 11. The multimeric structure according to claim 9, wherein the one or more HER2 mimotopes are located on the surface of the multimeric structure. 12. The multimeric structure according to claim 9, wherein the spacing of at least two HER2 mimotopes on the surface of one multimeric structure is 10-500 angstroms, 50-300 angstroms, or 80 to 120 angstroms. 13. A medicament for treating or preventing a HER2-related disease, the medicament comprising at least one parvovirus mutated structural protein according to claim 1, and at least one suitable excipient, carrier, and/or stabilizer. 14. A vaccine comprising at least one parvovirus mutated structural protein according to claim 1, and at least one suitable adjuvant, excipient, carrier, and/or stabilizer. 15. The vaccine according to claim 14, wherein the adjuvant is selected from the group consisting of mineral oil-based adjuvants, oil in water emulsion adjuvants, syntax adjuvant formulation containing muramyl dipeptide, and aluminum salt adjuvants. 16. The vaccine according to claim 15, wherein the adjuvant is selected from the group consisting of Freund's complete or incomplete adjuvant, CpG, imidazoquinoline, MPL, MDP, MALP, flagellin, LPS, LTA, cholera toxin, a cholera toxin derivative, HSP60, HSP70, HSP90, saponins, QS21, ISCOMs, CFA, SAF, MF59, admamantane, aluminum hydroxide, aluminum phosphate, and a cytokine. 17. The vaccine according to claim 14, wherein the vaccine comprises a combination of more than one, adjuvants. 18. A medicament comprising at least one parvovirus mutated structural protein according to claim 1, and at least one suitable excipient, carrier, and/or stabilizer. 19. A method of inducing a B-cell response against HER2, the method comprising administering the Parvovirus mutated structural protein according to claim 1, in an effective dose to a mammal. 20. The method of inducing a B-cell response according to claim 19, wherein the parvovirus mutated structural protein is administered parenterally. 21. The method according to claim 19, wherein the Parvovirus mutated structural protein is administered multiple times. 22. A method of treating a HER2-related disease, the method comprising administering the Parvovirus mutated structural protein according to claim 1, in an effective dose to a mammal. 23. The method according to claim 22, wherein the HER2-related disease is cancer. 24. A nucleic acid coding for a parvovirus mutated structural protein according to claim 1. 25. An expression cassette, construct, or vector comprising the nucleic acid according to claim 24. 26. A cell comprising the expression cassette, construct, or vector according to claim 24. 27. The cell according to claim 26, wherein the cell is a bacterium, a yeast cell, an insect cell, or a mammalian cell. 28. A method of preparing a structural protein, the method comprising: a) expressing a nucleic acid coding for a parvovirus mutated structural protein by cultivating a the cell according to claim 26 under suitable conditions, and b) isolating the expressed parvovirus mutated structural protein of step a). 29. A composition for inducing a B-cell response comprising: a) a support capable of presenting peptides in a repetitive array; and b) at least three peptides, identical and/or different, each having an amino acid sequence independently selected from SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 97, SEQ ID NO: 98, or SEQ ID NO: 99, the peptides being joined to the support so as to form a HER2 mimotope-presenting support. 30. The composition according to claim 29, wherein the support is selected from the group consisting of a bead, a lipid membrane, a protein, or an inorganic carrier. 31. The composition according to claim 30, wherein the bead is selected from a polyacrylamide bead, an agarose bead, a polystyrene bead, a magnetic bead, a latex particle, a carbohydrate assembly. 32. The composition according to claim 30, wherein the lipid membrane is selected from a lipid assembly and a liposome. 33. The composition according to claim 30, wherein the protein is a protein assembly comprising a structural protein of a virus or phage, a virus-like particle or a virus; a polymer; KLH (Keyhole limpet hemocyanin); or LPH (Hemocyanin from Limulus polyphemus hemolymph). 34. The composition according to claim 30, wherein the inorganic carrier is selected from silica material and wherein the one or more HER2 mimotopes are covalently linked through a hydroxy, carboxy, or amino group and with a reactive group on the carrier. 35. Parvovirus mutated structural protein for inducing a B-cell response against human epidermal growth factor receptor (HER2) which comprises one or more mimotopes of HER2 capable of specifically binding to an antibody directed against HER2, wherein at least one of the mimotopes comprises an amino acid sequence of any one of SEQ ID NO: 100-166 or a sequence thereof having one or two amino acid substitutions.

Details for Patent 9,821,043

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2031-09-15
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2031-09-15
Genentech, Inc.	PERJETA	pertuzumab	Injection	125409	06/08/2012		2031-09-15