SI2797950T1 - Fuzijski protein proti raku - Google Patents

Fuzijski protein proti raku Download PDF

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SI2797950T1
SI2797950T1 SI201231178T SI201231178T SI2797950T1 SI 2797950 T1 SI2797950 T1 SI 2797950T1 SI 201231178 T SI201231178 T SI 201231178T SI 201231178 T SI201231178 T SI 201231178T SI 2797950 T1 SI2797950 T1 SI 2797950T1
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gly gly
seq
sequence
domain
fusion protein
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Jerzy Szczepan Pieczykolan
Sebastian Dominik Pawlak
Bartlomiej Maciej Zerek
Piotr Kamil Rozga
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Adamed Sp. Z.O.O.
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Publication of SI2797950T1 publication Critical patent/SI2797950T1/sl

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Claims (18)

  1. Fuzijski protein proti raku Patentni zahtevki
    1. Fuzij ski protein, ki vsebuj e: domeno (a), ki vsebuje funkcionalni delec topnega zaporedja proteina hTRAIL, kjer je omenjeni protein hTRAIL predstavljen kot SEQ ID No. 90, kjer se delec prične z amino kislino na položaju iz območja hTRAIL95 do vključno hTRAIL121 in se konča z amino kislino na položaju hTRAIL121, ali homolog omenjenega funkcionalnega delca, ki ima vsaj 70% enakost zaporedja, prednostno 85% enakosti, kjer sta omenjeni funkcionalni delec ali njegov homolog zmožna sprožiti apoptopski signal v celicah sesalca po vezavi na njihove receptorje na površini celic, in - domeno (b), kije zaporedje citolitičnega efektorskega peptida z amfipatično konformacijo alfa-vijačnica, ki tvori pore v membrani celice; kjer je zaporedje domene (b) pripeto na C-terminus ali N-terminus domene (a).
  2. 2. Fuzijski protein po zahtevku 1, kjer je domena (a) izbrana iz skupine, ki vsebuje hTRAIL95-281, hTRAIL 114-281, hTRAIL 115-281, hTRAIL 116-281, hTRAIL 119-281 in hTRAIL 121-281
  3. 3. Fuzijski protein po zahtevku 1 ali 2, v katerem je domena (b) izbrana iz skupine, ki vsebuje: - pilosulin-1 zaporedja SEQ. No. 36, - pilosulin-5 zaporedja SEQ. No. 37, 14-amino kislin dolg sintetični litični peptid zaporedja SEQ. No. 41, - 27- amino kislin dolg peptid FFhCAP18 zaporedja SEQ. No. 43, - BAMP-28 peptid zaporedja SEQ. No. 44, - analog izo-oblike C litičnega peptida iz Entamoeba histolytica zaporedja SEQ. No. 45, - analoge izo-oblike A litičnega peptida iz Entamoeba histolytica zaporedja SEQ. No. 46, - analog izo-oblike B litičnega peptida iz Entamoeba histolytica zaporedja SEQ. No. 47, - delec domene HA2 hemaglutinina virusa influenza zaporedja SEQ. No. 48, - aktivni delec humanega perforina zaporedja SEQ. No. 54, - parasporin-2 z Bacillus zaporedja SEQ. No. 55, - fuzijski protein, ki vsebuje sintetični litični peptid z motivom KLLK in peptid, kije antagonist receptorja PDGF zaporedja SEQ. No. 125, - analog pleurocidina zaporedja SEQ. No. 126, - analog pleurocidina zaporedja SEQ. No. 127, in - sintetični litični peptid zaporedja SEQ. No. 128.
  4. 4. Fuzijski protein po kateremkoli zahtevku od 1 do 3, ki med domeno (a) in domeno (b) ali med domenama (b) vsebuje domeno (c), ki vsebuje cepitveno mesto za proteazo, izbrano izmed zaporedja, ki ga prepozna metaloproteaza MMP, zaporedja, ki ga prepozna urokinaza uPA in in zaporedja, ki ga prepozna furin in zaporedja, ki ga prepozna naravni furin.
  5. 5. Fuzijski protein po zahtevku 4, kjer je zaporedje, ki ga prepozna metaloproteaza MMP zaporedje Pro Leu Gly Leu Ala Gly, zaporedje, ki ga prepozna urokinaza uPA je Arg Val Val Arg, zaporedje, ki ga prepozna furin je Arg Lys Lys Arg, in zaporedje, ki ga prepozna naravni furin je Arg His Arg Gin Pro Arg Gly Trp Glu Gin Leu ali His Arg Gin Pro Arg Gly Trp Glu Gin.
  6. 6. Fuzijski protein po zahtevku 4 ali 5, kjer je domena (c) kombinacija zaporedja, ki ga prepozna metaloproteaza MMP in zaporedja, ki ga prepozna urokinaza uPA, ki se nahajata drugo poleg drugega.
  7. 7. Fuzijski protein po kateremkoli zahtevku, v katerem je efektorski peptid domene (b) dodatno povezan s transportno domeno (d), izbrano iz skupine, ki vsebuje: (dl) zaporedje polihistidina, ki transportira skozi celično membrano, ki vsebuje 6,7,8, 9,10 ali 11 ostankov His, in (d2) zaporedje poliarginin, ki transportira skozi celično membrano, ki sestoji iz 6, 7, 8, 9, 10 ali 11 ostankov Arg, (d3) transportno zaporedje PD4 (protein transdukcijska domena 4) Tyr Ala Arg Ala Ala Ala Arg Gin Ala Arg Ala, (d4) transportno zaporedje, ki sestoji iz zaporedja, ki veže receptor transferina Thr His Arg Pro Pro Met Trp Ser Pro Val Trp Pro, in (d5) transportno zaporedje PD5 (protein transdukcijska domena 5, TAT protein) Tyr Gly Arg Lys Lys Arg Arg Gin Arg Arg Arg, in njihove kombinacije.
  8. 8. Fuzijski protein po zahtevku 7, kjer se zaporedje (d) nahaja na položaju C-terminus ali N-terminus domene efektorskega peptida (b).
  9. 9. Fuzijski protein po zahtevku 7, kjer se transportna domena (d) nahaja med domeno (b) in domeno (c) ali med domeno (a) in domeno (c) ali med dvema domenama (c).
  10. 10. Fuzijski protein po zahtevku 7, kjer se zaporedje (d) nahaja na položaju C-terminus fuzijskega proteina.
  11. 11. Fuzijski protein po kateremkoli zahtevku od 4 do 10, ki med dvema domenama (c) vsebuje domeno (e), kije linker za pripetje molekule PEG, izbrano izmed Ala Ser Gly Cys Gly Pro Glu Gly in Ala Ser Gly Cys Gly Pro Glu.
  12. 12. Fuzijski protein po kateremkoli zahtevku od 4 do 11, ki med domenami (a), (b) in/ali (c) dodatno vsebuje gibljiv sterični linker.
  13. 13. Fuzijski protein po zahtevku 12, kjer je sterični linker izbran izmed Gly Gly, Gly Gly Gly, Gly Ser Gly, Gly Gly Gly Gly Ser, Gly Gly Gly Gly Gly Ser, Gly Gly Ser Gly Gly, Gly Gly Gly Ser Gly Gly Gly, Gly Gly Gly Gly Ser Gly, Gly Gly Gly Ser Gly Gly Gly Gly Gly Ser, Gly Gly Gly Gly Ser Gly Gly Gly Gly, Gly Ser Gly Gly Gly Ser Gly Gly Gly, Cys Ala Ala Cys Ala Ala Ala Cys, Cys Ala Ala Ala Cys Ala Ala Cys, Ser Gly Gly, enojnega ostanka glicina Gly in enojnega ostanka cisteina Cys in njihovih kombinacij.
  14. 14. Fuzijski protein po zahtevku 1, ki ima zaporedje amino kislin izbrano iz skupine, ki vsebuje zaporedja SEQ. No. 4; SEQ. No. 5; SEQ. No. 6; SEQ. No. 11; SEQ. No. 12; SEQ. No. 13; SEQ. No. 14; SEQ. No. 15; SEQ. No. 16; SEQ. No. 18; SEQ. No. 19; SEQ. No. 20; SEQ. No. 21; SEQ. No. 22; SEQ. No. 23; SEQ. No. 30; SEQ. No. 31; SEQ. No. 32; SEQ. No. 91; SEQ. No. 92; SEQ. No. 93; SEQ. No. 94; SEQ. No. 95; SEQ. No. 96; SEQ. No. 97, SEQ. No. 98 in SEQ. No. 102.
  15. 15. Fuzijski protein po kateremkoli predhodnem zahtevku, kije rekombinantni protein.
  16. 16. Farmacevtski sestavek, ki kot aktivno učinkovino vsebuje fuzijski protein po kateremkoli zahtevku od 1 do 15 v kombinaciji s farmacevtsko sprejemljivim nosilcem.
  17. 17. Farmacevtski sestavek po zahtevku 16 v obliki za paranteralno administracijo.
  18. 18. Fuzijski protein po kateremkoli zahtevku od 1 do 15 za uporabo v zdravljenju neoplastičnih bolezni v sesalcih, vključno z ljudmi.
SI201231178T 2011-12-28 2012-12-22 Fuzijski protein proti raku SI2797950T1 (sl)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
PL397595A PL223487B1 (pl) 2011-12-28 2011-12-28 Przeciwnowotworowe białko fuzyjne
PCT/IB2012/057657 WO2013098755A2 (en) 2011-12-28 2012-12-22 Anticancer fusion protein
EP12824731.9A EP2797950B1 (en) 2011-12-28 2012-12-22 Anticancer fusion protein

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SI2797950T1 true SI2797950T1 (sl) 2018-02-28

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KR (1) KR20140110017A (sl)
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WO2014141094A1 (en) 2013-03-14 2014-09-18 Adamed Sp. Z O.O. Anticancer conjugate
GB201406705D0 (en) 2014-04-15 2014-05-28 Univ Liverpool Fusion proteins,polynucleotides,expression vectors, and their uses
WO2016127346A1 (zh) * 2015-02-11 2016-08-18 四川大学华西医院 一种肿瘤坏死因子相关凋亡诱导配体变异体及其制备方法和用途
CN107216385A (zh) * 2017-05-19 2017-09-29 何向锋 肿瘤特异性重组水蛭素及其制备方法和用途
WO2018219301A1 (zh) * 2017-05-31 2018-12-06 四川大学华西医院 一种PDGFRβ靶向性肿瘤坏死因子相关凋亡诱导配体变异体及其制备方法和用途
WO2019067740A1 (en) * 2017-09-27 2019-04-04 Emory University FUSION PROTEINS COMPRISING CANCER TOXIN AND MARKER, NANOPARTICLES AND USES THEREOF
CN111909275A (zh) * 2019-05-08 2020-11-10 上海大学 延长多肽药物循环半衰期的靶向载药体系及其构建方法
CN110669146B (zh) * 2019-10-24 2023-05-23 常州大学 一种可特异性阻断衔接蛋白Nck的结合位点用于预防肠道EPEC感染的活性肽
KR102659285B1 (ko) * 2020-08-11 2024-04-22 경북대학교 산학협력단 암세포 유래 엑소좀에 선택적으로 결합하는 펩타이드 및 이의 용도
CN114031673B (zh) * 2021-12-22 2023-09-22 杭州长龄生物科技有限公司 一种多肽及其制备方法
CN114605517B (zh) * 2022-05-12 2022-09-27 广东海洋大学 一种具有广谱抗癌作用的多肽lxp-7及其应用
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WO2013098755A2 (en) 2013-07-04
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UA115436C2 (uk) 2017-11-10
PT2797950T (pt) 2018-01-24
HUE035794T2 (en) 2018-05-28
KR20140110017A (ko) 2014-09-16
AU2012360086B2 (en) 2016-12-22
AU2012360086A1 (en) 2014-08-07
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NO2797950T3 (sl) 2018-03-17
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