HRP20200376T1 - Receptori t-stanica protiv ljudskog papiloma virusa 16e7 - Google Patents
Receptori t-stanica protiv ljudskog papiloma virusa 16e7 Download PDFInfo
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- HRP20200376T1 HRP20200376T1 HRP20200376TT HRP20200376T HRP20200376T1 HR P20200376 T1 HRP20200376 T1 HR P20200376T1 HR P20200376T T HRP20200376T T HR P20200376TT HR P20200376 T HRP20200376 T HR P20200376T HR P20200376 T1 HRP20200376 T1 HR P20200376T1
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- 108091008874 T cell receptors Proteins 0.000 title claims 25
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title claims 25
- 241001631646 Papillomaviridae Species 0.000 title 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 40
- 229920001184 polypeptide Polymers 0.000 claims 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims 14
- 102000004196 processed proteins & peptides Human genes 0.000 claims 14
- 210000004027 cell Anatomy 0.000 claims 12
- 241000701806 Human papillomavirus Species 0.000 claims 11
- 102000004169 proteins and genes Human genes 0.000 claims 10
- 108090000623 proteins and genes Proteins 0.000 claims 10
- 102000039446 nucleic acids Human genes 0.000 claims 7
- 108020004707 nucleic acids Proteins 0.000 claims 7
- 150000007523 nucleic acids Chemical class 0.000 claims 7
- 239000002773 nucleotide Substances 0.000 claims 6
- 125000003729 nucleotide group Chemical group 0.000 claims 6
- 239000013604 expression vector Substances 0.000 claims 5
- 238000003259 recombinant expression Methods 0.000 claims 5
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims 4
- 241000124008 Mammalia Species 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 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 2
- 230000000890 antigenic effect Effects 0.000 claims 2
- 208000015181 infectious disease Diseases 0.000 claims 2
- 241001529936 Murinae Species 0.000 claims 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
- 210000002255 anal canal Anatomy 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 108091007433 antigens Proteins 0.000 claims 1
- 102000036639 antigens Human genes 0.000 claims 1
- 210000000436 anus Anatomy 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 108020001507 fusion proteins Proteins 0.000 claims 1
- 102000037865 fusion proteins Human genes 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 210000004962 mammalian cell Anatomy 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 210000003300 oropharynx Anatomy 0.000 claims 1
- 210000003899 penis Anatomy 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 210000001215 vagina Anatomy 0.000 claims 1
- 210000003905 vulva Anatomy 0.000 claims 1
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Claims (15)
1. Receptor T-stanice (TCR) koji sadrži ljudsko varijabilno područje i mišje konstantno područje, ili funkcionalna varijanta TCR, naznačen time što TCR i funkcionalna varijanta sadrže područje 1 koje određuje komplementarnost na lanac α (CDR) aminokiselinski slijed SEQ ID NO: 3, CDR2 za lanac α s aminokiselinskim slijedom SEQ ID NO: 4, CDR3 za lanac α s aminokiselinskim slijedom SEQ ID NO: 5, CDR1 za lanac β s aminokiselinskim slijedom SEQ ID NO: 6, CDR2 za lanac β s aminokiselinskim slijedom SEQ ID NO: 7, te CDR3 za lanac β s aminokiselinskim slijedom SEQ ID NO: 8 i ima antigensku specifičnost za ljudski papilomavirus (HPV) 16 E711-19 SEQ ID NO: 2, gdje TCR može sadržavati aminokiselinske sljedove: (a) SEQ ID NO: 9 i (b) SEQ ID NO: 10, gdje je X na položaju 2 Ala ili Gly.
2. Izolirani ili pročišćeni receptor T-stanice (TCR), naznačen time što sadrži CDR1 za lanac α s aminokiselinskim slijedom SEQ ID NO: 3, CDR2 za lanac α s aminokiselinskim slijedom SEQ ID NO: 4, CDR3 za lanac α s aminokiselinskim slijedom SEQ ID NO: 5, CDR1 za lanac β s aminokiselinskim slijedom SEQ ID NO: 6, CDR2 za lanac β s aminokiselinskim slijedom SEQ ID NO: 7, te CDR3 za lanac β s aminokiselinskim slijedom SEQ ID NO: 8 i ima antigensku specifičnost za ljudski papilomavirus (HPV) 16 E711-19 SEQ ID NO: 2, gdje TCR:
(i) može sadržavati ljudsko konstantno područje; i/ili
(ii) može sadržavati aminokiselinske sljedove: (a) SEQ ID NO: 9 i (b) SEQ ID NO: 10, gdje X na položaju 2 je Ala ili Gly.
3. TCR ili funkcionalna varijanta u skladu s patentnim zahtjevom 1 ili izolirani ili pročišćeni TCR u skladu s patentnim zahtjevom 2, naznačen time što ima aminokiselinske sljedove:
(a) SEQ ID NO: 16, gdje
(i) X na položaju 48 je Thr ili Cys;
(ii) X na položaju 112 je Ser, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met ili Trp;
(iii) X na položaju 114 je Met, Gly, Ala, Val, Leu, Ile, Pro, Phe, Met ili Trp; i
(iv) X na položaju 115 je Gly, Ala, Val, Leu, Ile, Pro, Phe, Met ili Trp; i
(b) SEQ ID NO: 18, gdje je X na položaju 56 Ser ili Cys.
4. TCR ili funkcionalna varijanta u skladu s patentnim zahtjevom 1 ili 3 ili izolirani ili pročišćeni TCR u skladu s patentnim zahtjevom 2 ili 3, naznačen time što ima aminokiselinske sljedove:
(I)
(a) bilo koji od SEQ ID NO: 14, 17, 21, 24, i 25; i
(b) bilo koji od SEQ ID NO: 15, 19, i 23
(II)
(a) (i) SEQ ID NO: 12, (ii) SEQ ID NO: 22, (iii) SEQ ID NO: 26, (iv) SEQ ID NO: 9 i 24, (v) SEQ ID NO: 9 i 16, ili (vi) SEQ ID NO: 9 i 17; i
(b) (i) SEQ ID NO: 10 i 18 ili (ii) bilo koji od SEQ ID NO: 13, 20, i 27; ili
(III) SEQ ID NO: 29 ili 30.
5. Izolirani ili pročišćeni polipeptid, naznačen time što sadrži funkcionalni dio iz (i) TCR ili funkcionalne varijante u skladu s bilo kojim od patentnih zahtjeva 1 i 3-4 ili (ii) izoliranog ili pročišćenog TCR u skladu s bilo kojim od patentnih zahtjeva 2-4, gdje se funkcionalni dio specifično veže na HPV 16 E711-19 i sadrži CDR1 za lanac α s aminokiselinskim slijedom SEQ ID NO: 3, CDR2 za lanac α s aminokiselinskim slijedom SEQ ID NO: 4, CDR3 za lanac α s aminokiselinskim slijedom SEQ ID NO: 5, CDR1 za lanac β s aminokiselinskim slijedom SEQ ID NO: 6, CDR2 za lanac β s aminokiselinskim slijedom SEQ ID NO: 7, te CDR3 za lanac β s aminokiselinskim slijedom SEQ ID NO: 8, gdje funkcionalni dio može sadržavati jedan ili više aminokiselinskih sljedova:
(I) (a) SEQ ID NO: 9, (b) SEQ ID NO: 10, ili (c) SEQ ID NO: 9 i 10, gdje je X na položaju 2 u SEQ ID NO: 10 Ala ili Gly, te kada je X na položaju 2 u SEQ ID NO: 10 Gly, polipeptid je izoliran ili pročišćen; ili
(II)
(a) (i) SEQ ID NO: 9 i 24; (ii) SEQ ID NO: 9 i 17; (iii) SEQ ID NO: 9 i 16; (iv) SEQ ID NO: 10 i 18; ili (v) bilo koji od SEQ ID NO: 12, 13, 20, 22, 26, 27, 29 i 30;
(b) SEQ ID NO: 12 i 13;
(c) SEQ ID NO: 20 i 22;
(d) SEQ ID NO: 26 i 27;
(e) SEQ ID NO: 9, 24, i 27;
(f) SEQ ID NO: 9, 17, i 20; ili
(g) SEQ ID NO: 9, 10, 16, i 18,
gdje je polipeptid koji sadrži aminokiselinski slijed s jednim od ili i SEQ ID NO: 12 i 13 izoliran ili pročišćen.
6. Izolirani ili pročišćeni protein, naznačen time što se specifično veže na HPV 16 E711-19 i koji sadrži prvi polipeptidni lanac koji sadrži CDR1 za lanac α s aminokiselinskim slijedom SEQ ID NO: 3, CDR2 za lanac α s aminokiselinskim slijedom SEQ ID NO: 4, i CDR3 za lanac α s aminokiselinskim slijedom SEQ ID NO: 5, i drugi polipeptidni lanac koji sadrži CDR1 za lanac β s aminokiselinskim slijedom SEQ ID NO: 6, CDR2 za lanac β s aminokiselinskim slijedom SEQ ID NO: 7, te CDR3 za lanac β s aminokiselinskim slijedom SEQ ID NO: 8, gdje protein:
(i) može biti fuzijski protein ili rekombinantno protutijelo;
(ii) može sadržavati prvi polipeptidni lanac koji ima aminokiselinski slijed SEQ ID NO: 9 i drugi polipeptidni lanac koji ima aminokiselinski slijed SEQ ID NO: 10, gdje (A) X na položaju 2 u SEQ ID NO: 10 je Ala ili Gly, i (B) protein koji ima SEQ ID NO: 9 i 10, gdje je X na položaju 2 u SEQ ID NO: 10 Gly, je izoliran ili pročišćen; ili
(iii) može sadržavati prvi polipeptidni lanac koji ima aminokiselinski slijed: (i) SEQ ID NO: 12, (ii) SEQ ID NO: 22, (iii) SEQ ID NO: 26, (iv) SEQ ID NO: 9 i 16, (v) SEQ ID NO: 9 i 17, ili (vi) SEQ ID NO: 9 i 24 i drugi polipeptidni lanac koji ima aminokiselinski slijed: (i) SEQ ID NO: 10 i 18, ili (ii) bilo koji od SEQ ID NO: 13, 20, i 27,
gdje je protein koji ima SEQ ID NO: 12 i 13 izoliran ili pročišćen.
7. Protein, naznačen time što ima SEQ ID NO: 29 ili 30.
8. (a) Nukleinska kiselina koja ima nukleotidni slijed koji kodira TCR ili funkcionalnu varijantu u skladu s bilo kojim od patentnih zahtjeva 1 i 3-4, polipeptid u skladu s patentnim zahtjevom 5, ili protein u skladu s patentnim zahtjevom 6 ili 7, ili
(b) izolirana ili pročišćena nukleinska kiselina koja ima nukleotidni slijed koji kodira TCR u skladu s bilo kojim od patentnih zahtjeva 2-4, polipeptid u skladu s patentnim zahtjevom 5, ili protein u skladu s patentnim zahtjevom 6 ili 7, naznačena time što:
(i) nukleinska kiselina može sadržavati nukleotidni slijed SEQ ID NO: 31, SEQ ID NO: 32, ili i SEQ ID NO: 31 i 32; ili
(ii) nukleinska kiselina može sadržavati nukleotidni slijed: (1) bilo koji od 33-36, (2) i SEQ ID NO: 33 i 34, ili (3) i SEQ ID NO: 35 i 36.
9. Rekombinantni ekspresijski vektor, naznačen time što sadrži nukleinsku kiselinu u skladu s patentnim zahtjevom 8, gdje:
(i) nukleotidni slijed koji kodira lanac β se može nalaziti 5’ od nukleotidnog slijeda koji kodira lanac α; ili
(ii) rekombinantni ekspresijski vektor može sadržavati SEQ ID NO: 37, 38, 39 ili 40.
10. Stanica domaćin, naznačena time što sadrži rekombinantni ekspresijski vektor u skladu s patentnim zahtjevom 9, gdje stanica može biti ljudska.
11. Populacija stanica, naznačena time što sadrži najmanje jednu stanicu domaćina u skladu s patentnim zahtjevom 10.
12. Protutijelo, ili njegov antigenski vežući dio, naznačeno time što se specifično veže na epitop u TCR, gdje je epitop formiran iz područja 1 koje određuje komplementarnost na lanac α (CDR) s aminokiselinskim slijedom SEQ ID NO: 3, CDR2 za lanac α s aminokiselinskim slijedom SEQ ID NO: 4, CDR3 za lanac α s aminokiselinskim slijedom SEQ ID NO: 5, CDR1 za lanac β s aminokiselinskim slijedom SEQ ID NO: 6, CDR2 za lanac β s aminokiselinskim slijedom SEQ ID NO: 7, te CDR3 za lanac β s aminokiselinskim slijedom SEQ ID NO: 8.
13. Farmaceutski pripravak, naznačen time što sadrži TCR ili funkcionalnu varijantu u skladu s bilo kojim od patentnih zahtjeva 1 i 3-4, izolirani ili pročišćeni TCR u skladu s bilo kojim od patentnih zahtjeva 2-4, polipeptid u skladu s patentnim zahtjevom 5, protein u skladu s patentnim zahtjevom 6 ili 7, nukleinsku kiselinu u skladu s patentnim zahtjevom 8, rekombinantni ekspresijski vektor u skladu s patentnim zahtjevom 9, stanicu domaćina u skladu s patentnim zahtjevom 10, ili populaciju stanica u skladu s patentnim zahtjevom 11, kao i farmaceutski prihvatljivi nosač.
14. Postupak in vitro detektiranja prisutnosti stanja kod sisavca, naznačen time što se sastoji u:
(a) stavljanju u kontakt uzorka koji sadrži jednu ili više stanica iz sisavca s TCR ili funkcionalnom varijantom u skladu s bilo kojim od patentnih zahtjeva 1 i 3-4, izoliranim ili pročišćenim TCR u skladu s bilo kojim od patentnih zahtjeva 2-4, polipeptidom u skladu s patentnim zahtjevom 5, proteinom u skladu s patentnim zahtjevom 6 ili 7, stanicom domaćinom u skladu s patentnim zahtjevom 10, ili populacijom stanica u skladu s patentnim zahtjevom 11, gdje stanica domaćin i populacija stanica eksprimira TCR ili funkcionalnu varijantu, pri čemu nastaje kompleks, i
(b) detektiranju kompleksa, gdje detektiranje kompleksa ukazuje na prisutnost stanja kod sisavca, gdje je stanje rak, infekcija s HPV 16 ili premalignitet pozitivan na HPV.
15. TCR ili funkcionalna varijanta u skladu s bilo kojim od patentnih zahtjeva 1 i 3-4, izolirani ili pročišćeni TCR u skladu s bilo kojim od patentnih zahtjeva 2-4, polipeptid u skladu s patentnim zahtjevom 5, protein u skladu s patentnim zahtjevom 6 ili 7, nukleinska kiselina u skladu s patentnim zahtjevom 8, rekombinantni ekspresijski vektor u skladu s patentnim zahtjevom 9, stanica domaćin u skladu s patentnim zahtjevom 10, populacija stanica u skladu s patentnim zahtjevom 11, ili farmaceutski pripravak u skladu s patentnim zahtjevom 13, naznačeni time što su namijenjeni upotrebi u liječenju ili sprječavanju stanja kod sisavca, gdje je stanje rak, infekcija s HPV 16 ili premalignitet pozitivan na HPV, gdje stanje može biti:
(i) rak vrata maternice, orofarinksa, anusa, analnog kanala, anorektuma, vagine, vulve ili penisa; ili
(ii) rak pozitivan na HPV 16.
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| US201462004335P | 2014-05-29 | 2014-05-29 | |
| PCT/US2015/033129 WO2015184228A1 (en) | 2014-05-29 | 2015-05-29 | Anti-human papillomavirus 16 e7 t cell receptors |
| EP15729004.0A EP3149031B1 (en) | 2014-05-29 | 2015-05-29 | Anti-human papillomavirus 16 e7 t cell receptors |
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