HRP20201458T1 - Trimer koji stabilizira mutacije proteina omotača hiv - Google Patents
Trimer koji stabilizira mutacije proteina omotača hiv Download PDFInfo
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- HRP20201458T1 HRP20201458T1 HRP20201458TT HRP20201458T HRP20201458T1 HR P20201458 T1 HRP20201458 T1 HR P20201458T1 HR P20201458T T HRP20201458T T HR P20201458TT HR P20201458 T HRP20201458 T HR P20201458T HR P20201458 T1 HRP20201458 T1 HR P20201458T1
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- hiv env
- ile
- env protein
- amino acid
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- 230000035772 mutation Effects 0.000 title claims 9
- 101710091045 Envelope protein Proteins 0.000 title claims 2
- 101710188315 Protein X Proteins 0.000 title claims 2
- 239000013638 trimer Substances 0.000 title claims 2
- 102100021696 Syncytin-1 Human genes 0.000 title 1
- 230000000087 stabilizing effect Effects 0.000 title 1
- 241000725303 Human immunodeficiency virus Species 0.000 claims 34
- 102100034353 Integrase Human genes 0.000 claims 29
- 108010078428 env Gene Products Proteins 0.000 claims 29
- 125000000539 amino acid group Chemical group 0.000 claims 12
- 125000003275 alpha amino acid group Chemical group 0.000 claims 6
- 150000001413 amino acids Chemical group 0.000 claims 5
- 238000006467 substitution reaction Methods 0.000 claims 5
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims 4
- 108020004707 nucleic acids Proteins 0.000 claims 4
- 102000039446 nucleic acids Human genes 0.000 claims 4
- 150000007523 nucleic acids Chemical class 0.000 claims 4
- 238000000034 method Methods 0.000 claims 3
- 102000004961 Furin Human genes 0.000 claims 2
- 108090001126 Furin Proteins 0.000 claims 2
- 238000003776 cleavage reaction Methods 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000002245 particle Substances 0.000 claims 2
- 230000007017 scission Effects 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 108091035707 Consensus sequence Proteins 0.000 claims 1
- 102100034349 Integrase Human genes 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000002502 liposome Substances 0.000 claims 1
- 239000002105 nanoparticle Substances 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
- C07K14/08—RNA viruses
- C07K14/15—Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus human T-cell leukaemia-lymphoma virus
- C07K14/155—Lentiviridae, e.g. visna-maedi virus, equine infectious virus, FIV, SIV
- C07K14/16—HIV-1 ; HIV-2
- C07K14/162—HIV-1 ; HIV-2 env, e.g. gp160, gp110/120, gp41, V3, peptid T, CD4-Binding site
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/21—Retroviridae, e.g. equine infectious anemia virus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
- C12N7/02—Recovery or purification
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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Claims (24)
1. Rekombinantni protein omotača (Env) virusa humane imunodeficijencije (HIV), koji sadrži dva ili više od sljedećih aminokiselinskih ostataka:
(i) Phe, Leu, Met, ili Trp, poželjno Phe, na položaju 651;
(ii) Phe, Ile, Met, ili Trp, poželjno Ile, na položaju 655;
(iii) Asn ili Gln, poželjno Asn, na položaju 535;
(iv) Val, Ile ili Ala, poželjno Val, na položaju 589;
(v) Phe ili Trp, poželjno Phe, na položaju 573;
(vi) Ile na položaju 204; i/ili
(vii) Phe, Met, ili Ile, poželjno Phe, na položaju 647,
pri čemu je numeriranje položaja prema numeriranju u gp160 izolata HIV-1 HXB2.
2. Rekombinantni HIV Env protein, koji sadrži jedan ili više od sljedećih aminokiselinskih ostataka:
(i)Phe, Leu, Met, ili Trp, poželjno Phe, na položaju 651;
(ii) Phe, Ile, Met, ili Trp, poželjno Ile, na položaju 655;
(iii) Asn ili Gln, poželjno Asn, na položaju 535;
(iv) Val, Ile ili Ala, poželjno Val, na položaju 589;
(v) Phe ili Trp, poželjno Phe, na položaju 573;
(vi) Ile na položaju 204; i/ili
(vii) Phe, Met, ili Ile, poželjno Phe, na položaju 647,
pri čemu je HIV Env protein odabran iz skupine koju čine:
(1) konsenzusna sekvenca HIV Env, na primjer iz klade C na primjer koja sadrži aminokiselinsku sekvencu SEQ ID NO: 2 ili 3 ili na primjer iz klade B na primjer koja sadrži aminokiselinsku sekvencu SEQ ID NO: 4 ili 5;
(2) sintetski HIV Env protein, na primjer koji sadrži aminokiselinsku sekvencu (a): SEQ ID NO: 6; ili (b): SEQ ID NO: 6 s mutacijom Glu u Arg na položaju 166; ili (c): (a) ili (b) s mutacijom aminokiselina na položajima 501 i 605 u Cys ostatke i mutacijom aminokiseline na položaju 559 u Pro ostatak; ili (d): (a), (b) ili (c) koji imaju daljnju mutaciju furinskog mjesta cijepanja, npr. zamjenu aminokiselina na položajima 508-511 sa RRRRRR (SEQ ID NO: 10); ili (e) SEQ ID NO: 7; ili (f) SEQ ID NO: 8 ili SEQ ID NO: 9; i
(3) roditeljski HIV Env protein koji je poželjno divlji tip HIV Env proteina, poželjno iz klade C, koji sadrži najmanje jednu popravnu mutaciju aminokiselinskog ostatka koji je prisutan na odgovarajućem položaju s učestalošću manjom od 7.5%, poželjno manjom od 2%, HIV Env sekvenci u kolekciji od najmanje 1000, poželjno najmanje 10000, divljih vrsta HIV Env sekvenci, pri čemu popravna mutacija je supstitucija aminokiselinskim ostatkom koji je prisutan na odgovarajućem položaju s učestalošću najmanje 10% HIV Env sekvenci u navedenoj kolekciji i poželjno popravna mutacija je supstitucija aminokiselinskim ostatkom koji je na odgovarajućem položaju najčešće prisutan u navedenoj kolekciji;
i
pri čemu je numeriranje položaja prema numeriranju u gp160 izolata HIV-1 HXB2.
3. Rekombinantni HIV Env protein, koji sadrži jedan ili više od sljedećih aminokiselinskih ostataka:
(i) Phe, Leu, Met, ili Trp, poželjno Phe, na položaju 651;
(ii) Phe, Ile, Met, ili Trp, poželjno Ile, na položaju 655;
(iii) Asn ili Gln, poželjno Asn, na položaju 535;
(iv) Val, Ile ili Ala, poželjno Val, na položaju 589;
(v) Phe ili Trp, poželjno Phe, na položaju 573;
(vi) Ile na položaju 204; i/ili
(vii) Phe, Met, ili Ile, poželjno Phe, na položaju 647,
pri čemu HIV Env protein je HIV Env protein koji sadrži najmanje jedno od slijedećeg:
(a) Cys na položajima 501 i 605;
(b) Pro na položaju 559;
(c) Cys na položajima 501 i 605 i Pro na položaju 559; i
numeriranje položaja je prema numeriranju u gp160 izolata HIV-1 HXB2.
4. Rekombinantni HIV Env protein prema zahtjevu 2 ili 3, naznačen time što sadrži dva ili više aminokiselinskih ostataka naznačenih u (i) do (vii).
5. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1, 2, i 4, naznačen time što sadrži Cys na položajima 501 i 605 ili Pro na položaju 559, poželjno Cys na položajima 501 i 605 i Pro na položaju 559.
6. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time što sadrži tri ili više aminokiselinskih ostataka naznačenih u (i) do (vii).
7. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time što sadrži četiri ili više aminokiselinskih ostataka naznačenih u (i) do (vii).
8. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 7, naznačen time što sadrži Phe na položaju 651, Ile na položaju 655, Asn na položaju 535, i Val na položaju 589.
9. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 8, naznačen time što sadrži pet ili više aminokiselinskih ostataka naznačenih u (i) do (vii).
10. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 9, naznačen time što nadalje sadrži jedno ili više od slijedećih:
(viii) Gln, Glu, Ile, Met, Val, Trp, ili Phe, poželjno Gln ili Glu, na položaju 588;
(ix) Lys na položaju 64 ili Arg na položaju 66 ili Lys na položaju 64 i Arg na položaju 66;
(x) Trp na položaju 316;
(xi) Cys na oba položaja 201 i 433;
(xii) Pro na položaju 556 ili 558 ili na oba položaja 556 i 558;
(xiii) zamjena petlje na aminokiselinskim položajima 548-568 (HR1-petlja) petljom koja ima 7-10 aminokiselina, poželjno petljom od 8 aminokiselina, na primjer koja ima sekvencu odabranu iz bilo koje od (SEQ ID NOs: 12-17);
(xiv) Gly na položaju 568, ili Gly na položaju 569, ili Gly na položaju 636, ili Gly na oba položaja 568 i 636, ili Gly na oba položaja 569 i 636; i/ili
(xv) Tyr na položaju 302, ili Arg na položaju 519, ili Arg na položaju 520, ili Tyr na položaju 302 i Arg na položaju 519, ili Tyr na položaju 302 i Arg na položaju 520, ili Tyr na položaju 302 i Arg na oba položaja 519 i 520.
11. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 10, naznačen time što nadalje sadrži mutaciju u furinskoj sekvenci cijepanja HIV Env proteina, poželjno zamjenu na položajima 508-511 sa RRRRRR (SEQ ID NO: 10).
12. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 11, naznačen time što sadrži aminokiselinsku sekvencu koja je najmanje 95% identična bilo kojoj od SEQ ID NOs: 3, 5, 20, 22, 24, 26, 27, 28, 29, 30, 31, ili 32.
13. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 12, naznačen time što nadalje sadrži: (xvi) aminokiselinski ostatak odabran između Val, Ile, Phe, Met, Ala, ili Leu, poželjno Val ili Ile, najpoželjnije Val, na položaju 658.
14. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 13, naznačen time što je gpl40 ili gpl60 protein.
15. Rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 14, naznačen time što je iz klade C ili klade A, poželjno iz klade C.
16. Trimerni kompleks naznačen time što sadrži nekovalentni oligomer od tri rekombinantna HIV Env proteina prema bilo kojem od patentnih zahtjeva 1 do 15.
17. Čestica, poželjno liposom ili nanočestica, naznačena time što prikazuje na svojoj površini rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 15 ili trimerni kompleks prema zahtjevu 16.
18. Izolirana molekula nukleinske kiseline naznačena time što kodira rekombinantni HIV Env protein prema bilo kojem od patentnih zahtjeva 1 do 15.
19. Vektor naznačen time što sadrži izoliranu molekulu nukleinske kiseline prema patentnom zahtjevu 18 operativno povezan s promotorom.
20. Vektor prema patentnom zahtjevu 19, naznačen time što je adenovirusni vektor.
21. Stanica domaćina naznačena time što sadrži izoliranu molekulu nukleinske kiseline prema zahtjevu 18 ili vektor prema zahtjevu 19 ili 20.
22. Postupak za proizvodnju rekombinantnog HIV Env proteina, naznačen time što obuhvaća uzgoj stanice domaćina prema zahtjevu 21 pod uvjetima pogodnim za proizvodnju rekombinantnog HIV Env proteina.
23. Pripravak naznačen time što sadrži rekombinantni IV Env protein prema bilo kojem od patentnih zahtjeva 1 do 15, trimerni kompleks prema zahtjevu 16, česticu prema zahtjevu 17, izoliranu molekulu nukleinske kiseline prema zahtjevu 18, ili vektor prema zahtjevu 19 ili 20, te farmaceutski prihvatljiv nosač.
24. Postupak za poboljšanje formiranja trimera HIV Env proteina, te postupak obuhvaća supstituciju jednog ili više aminokiselinskih ostataka u roditeljskom HIV Env proteinu, pri čemu jedna ili više supstitucija rezultira s jednom ili više od sljedećih aminokiselina:
(i) Phe, Leu, Met, ili Trp, poželjno Phe, na položaju 651;
(ii) Phe, Ile, Met, ili Trp, poželjno Ile, na položaju 655;
(iii) Asn ili Gln, poželjno Asn, na položaju 535;
(iv) Val, Ile ili Ala, poželjno Val, na položaju 589;
(v) Phe ili Trp, poželjno Phe, na položaju 573;
(vi) Ile na položaju 204; i/ili
(vii) Phe, Met, ili Ile, poželjno Phe, na položaju 647,
pri čemu je numeriranje položaja prema numeriranju u gp160 izolata HIV-1 HXB2.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16188866 | 2016-09-15 | ||
| EP17769027.8A EP3512543B1 (en) | 2016-09-15 | 2017-09-14 | Trimer stabilizing hiv envelope protein mutations |
| PCT/EP2017/073141 WO2018050747A1 (en) | 2016-09-15 | 2017-09-14 | Trimer stabilizing hiv envelope protein mutations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20201458T1 true HRP20201458T1 (hr) | 2020-12-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20201458TT HRP20201458T1 (hr) | 2016-09-15 | 2020-09-14 | Trimer koji stabilizira mutacije proteina omotača hiv |
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| Country | Link |
|---|---|
| US (3) | US10793607B2 (hr) |
| EP (2) | EP3512543B1 (hr) |
| JP (2) | JP7178344B2 (hr) |
| KR (1) | KR102513146B1 (hr) |
| CN (1) | CN109689091A (hr) |
| AR (1) | AR109528A1 (hr) |
| AU (2) | AU2017327672B2 (hr) |
| BR (1) | BR112019004593A2 (hr) |
| CA (1) | CA3036959A1 (hr) |
| CY (1) | CY1124518T1 (hr) |
| DK (1) | DK3512543T3 (hr) |
| EA (1) | EA201990715A1 (hr) |
| ES (1) | ES2824525T3 (hr) |
| HR (1) | HRP20201458T1 (hr) |
| HU (1) | HUE052008T2 (hr) |
| IL (2) | IL294832A (hr) |
| LT (1) | LT3512543T (hr) |
| MA (1) | MA46230B1 (hr) |
| MD (1) | MD3512543T2 (hr) |
| MX (1) | MX2019002938A (hr) |
| MY (1) | MY190534A (hr) |
| PH (1) | PH12019500280A1 (hr) |
| PL (1) | PL3512543T3 (hr) |
| PT (1) | PT3512543T (hr) |
| RS (1) | RS60919B1 (hr) |
| SG (2) | SG10202001956UA (hr) |
| SI (1) | SI3512543T1 (hr) |
| TW (1) | TWI742158B (hr) |
| WO (1) | WO2018050747A1 (hr) |
| ZA (1) | ZA201901597B (hr) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2016369326B2 (en) | 2015-12-15 | 2019-02-21 | Janssen Vaccines & Prevention B.V. | Human immunodeficiency virus antigens, vectors, compositions, and methods of use thereof |
| US11318197B2 (en) | 2016-03-03 | 2022-05-03 | Duke University | Compositions and methods for inducing HIV-1 antibodies |
| CA3016352A1 (en) | 2016-03-03 | 2017-09-08 | Duke University | Compositions and methods for inducing hiv-1 antibodies |
| AU2017259275C1 (en) * | 2016-05-02 | 2022-01-27 | The Scripps Research Institute | Compositions and methods related to HIV-1 immunogens |
| US10273268B2 (en) | 2016-06-16 | 2019-04-30 | Janssen Vaccines & Prevention B.V. | HIV vaccine formulation |
| AU2017318689A1 (en) | 2016-09-02 | 2019-04-11 | Beth Israel Deaconess Medical Center, Inc. | Methods for inducing an immune response against human immunodeficiency virus infection in subjects undergoing antiretroviral treatment |
| HUE052008T2 (hu) | 2016-09-15 | 2021-04-28 | Janssen Vaccines & Prevention Bv | Trimert stabilizáló HIV-burokfehérje-mutációk |
| EP3519428A4 (en) | 2016-10-03 | 2020-07-08 | Duke University | METHOD FOR IDENTIFYING IMMUNOGENIC BY TARGETING UNLIKIBLE MUTATIONS |
| MA49397A (fr) | 2017-06-15 | 2020-04-22 | Bavarian Nordic As | Vecteurs à poxvirus codant pour des antigènes du vih, et leurs procédés d'utilisation |
| BR112020000867A2 (pt) * | 2017-07-19 | 2020-07-21 | Janssen Vaccines & Prevention B.V. | mutações da proteína do envelope do hiv estabilizando o trímero |
| CA3103460A1 (en) | 2018-06-13 | 2019-12-19 | The Scripps Research Institute | Nanoparticle vaccines with novel structural components |
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