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NZ751995B2 - Modified factor h binding protein - Google Patents
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NZ751995B2 - Modified factor h binding protein - Google Patents

Modified factor h binding protein Download PDF

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Publication number
NZ751995B2
NZ751995B2 NZ751995A NZ75199517A NZ751995B2 NZ 751995 B2 NZ751995 B2 NZ 751995B2 NZ 751995 A NZ751995 A NZ 751995A NZ 75199517 A NZ75199517 A NZ 75199517A NZ 751995 B2 NZ751995 B2 NZ 751995B2
Authority
NZ
New Zealand
Prior art keywords
modified
fhbp
binding protein
nucleic acid
composition
Prior art date
Application number
NZ751995A
Other versions
NZ751995A (en
Inventor
Christoph M Tang
Original Assignee
Oxford University Innovation Limited
Filing date
Publication date
Priority claimed from GBGB1614687.0A external-priority patent/GB201614687D0/en
Application filed by Oxford University Innovation Limited filed Critical Oxford University Innovation Limited
Publication of NZ751995A publication Critical patent/NZ751995A/en
Publication of NZ751995B2 publication Critical patent/NZ751995B2/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505Inorganic adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/57Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/575Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/60Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031Proteins
    • A61K2039/6068Other bacterial proteins, e.g. OMP
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/095Neisseria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/22Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Neisseriaceae (F)

Abstract

The invention relates to a modified factor H binding protein (fHbp), comprising fHbp, or a variant thereof, modified with the addition of at least one exogenous peptide loop; and associated nucleic acid, compositions, and uses. The invention further relates to treatment or prevention of a pathogenic infection or colonisation of a subject using the modified factor H binding protein (fHbp).

Claims (19)

1. A modified factor H binding protein (fHbp), sing wild-type fHbp or the ype ccal homologue of fHbp (Ghfp), or a t thereof 5 having at least 75% ty with any of the sequences of SEQ ID NOs: 1-13, which is further modified with the addition of any one of PorA loops comprising a sequence according to any one of SEQ ID NOs: 45 to 79, or variant thereof having no more than 1, 2, 3, 4 or 5 amino acid additions, deletions or substitutions, 10 n the PorA loop is between 8 and 20 amino acids in length and wherein the PorA loop is inserted at an amino acid position that is corresponding to any one of the amino acid residue numbers 49-54, 83-88, 114- 124, 199-206, 227-233, and 240-246 of SEQ ID NO: 1, or equivalent residues in any one of SEQ ID NOs: 2 to 13.
2. T he ed factor H binding protein ing to claim 1, wherein the PorA loop(s) are about 16 amino acids in length.
3. The modified factor H binding protein according to any preceding claim, 20 wherein the modified fHbp comprises two or more PorA loops.
4. T he modified factor H binding protein according to any preceding claim, wherein the modified fHbp comprises between 1 and 7 PorA loops. 25
5. T he modified factor H binding protein according to any preceding claim, wherein the modified fHbp, or variant thereof, is modified with a PorA loop in at least two positions.
6. T he modified factor H binding protein according to any preceding claim, 30 wherein the modified fHbp is a fusion protein.
7. An isolated nucleic acid encoding the modified fHbp according to any one of claims 1 to 6.
8. The nucleic acid ing to claim 7, wherein the nucleic acid is a vector.
9. The nucleic acid according to claim 8, wherein the vector is a viral vector.
10. A composition sing the modified fHbp according to any one of claims 1 to 6, or the nucleic acid according to any one of claims 7 to 9.
11. The composition according to claim 10, wherein the ition comprises two or more different modified fHbp molecules.
12. The composition accor ding to claim 10 or claim 11, wherein the 15 composition comprises a pharmaceutically able carrier.
13. The composition according to any one of claims 10 to 12, wherein the composition further comprises an adjuvant. 20
14. The composition according to any one of claims 10 to 13, wherein the composition r comprises at least one other prophylactically or therapeutically active molecule.
15. The composition according to claim 14, 25 wherein the at least one other prophylactically or therapeutically active molecule comprises: a protein:capsule polysaccharide e; or a conjugate vaccine, wherein antigen(s) comprising the ed fHbp is incorporated as the protein carrier molecule in the conjugate vaccine.
16. Use of a modified fHbp according to any one of claims 1 to 6, a nucleic acid according to any one of claims 7 to 9, or a composition according to any one of claims 10 to 15, in the manufacture of a ment for treatment or prevention of a Neisseria meningitidis or Neisseria gonorrhoeae infection or colonisation of a subject. 5
17. Use of a modified fHbp according to any one of claims 1 to 6, a nucleic acid ing to any one of claims 7 to 9, or a composition according to any one of claims 10 to 15, in the manufacture of a ment for vaccination of a subject. 10
18. A c ombination of a therapeutically effective amount of the modified fHbp according to any one of claims 1 to 6, a nucleic acid according to any one of claims 7 to 9, or a composition according to any one of claims 10 to 15, and a eutically amount of a protein:capsule polysaccharide vaccine. 15
19. Use of the modified factor H binding protein (fHbp) according to any one of claims 1 to 6 as an epitope display scaffold. 3 mam SEE m@588 $ng 3E \i EEBAV ..... :x .. HT . Tantm?ummomzoogs . mmcm?ummzom @338 L330 mcEgEmE zmg?ma gEmmao?u acmEEmE SUBSTITUTE SHEET (RULE 26) E Em 0 2 LOMUML @ m mEmEoQ E“ m\\\\\\\\
NZ751995A 2017-08-31 Modified factor h binding protein NZ751995B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB1614687.0A GB201614687D0 (en) 2016-08-31 2016-08-31 fHbp scaffold
PCT/GB2017/052535 WO2018042178A1 (en) 2016-08-31 2017-08-31 Modified factor h binding protein

Publications (2)

Publication Number Publication Date
NZ751995A NZ751995A (en) 2024-03-22
NZ751995B2 true NZ751995B2 (en) 2024-06-25

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