HRP20200973T1 - Rekombinatne probiotične bakterije - Google Patents
Rekombinatne probiotične bakterije Download PDFInfo
- Publication number
- HRP20200973T1 HRP20200973T1 HRP20200973TT HRP20200973T HRP20200973T1 HR P20200973 T1 HRP20200973 T1 HR P20200973T1 HR P20200973T T HRP20200973T T HR P20200973TT HR P20200973 T HRP20200973 T HR P20200973T HR P20200973 T1 HRP20200973 T1 HR P20200973T1
- Authority
- HR
- Croatia
- Prior art keywords
- interleukin
- growth factor
- factor
- probiotic bacteria
- indicated
- Prior art date
Links
- 241000894006 Bacteria Species 0.000 title claims 32
- 239000006041 probiotic Substances 0.000 title claims 31
- 230000000529 probiotic effect Effects 0.000 title claims 31
- 235000018291 probiotics Nutrition 0.000 title claims 31
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims 20
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims 20
- 102100033499 Interleukin-34 Human genes 0.000 claims 17
- 101710181549 Interleukin-34 Proteins 0.000 claims 17
- 102000004388 Interleukin-4 Human genes 0.000 claims 15
- 108090000978 Interleukin-4 Proteins 0.000 claims 15
- 229940028885 interleukin-4 Drugs 0.000 claims 15
- 108090000174 Interleukin-10 Proteins 0.000 claims 12
- 102000003814 Interleukin-10 Human genes 0.000 claims 12
- 102000003816 Interleukin-13 Human genes 0.000 claims 12
- 108090000176 Interleukin-13 Proteins 0.000 claims 12
- 229940076144 interleukin-10 Drugs 0.000 claims 12
- 239000003102 growth factor Substances 0.000 claims 11
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 claims 10
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 10
- 108090000623 proteins and genes Proteins 0.000 claims 9
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 claims 8
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims 8
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims 8
- 101800004564 Transforming growth factor alpha Proteins 0.000 claims 8
- 230000001684 chronic effect Effects 0.000 claims 8
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims 8
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 claims 7
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Classifications
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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- C07K—PEPTIDES
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- C07K14/50—Fibroblast growth factor [FGF]
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/503—Fibroblast growth factor [FGF] basic FGF [bFGF]
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Claims (20)
1. Rekombinantne probiotične bakterije, koje sadrže
slijed(ove) nukleinskih kiselina koji kodira(ju) za prvi heterologni faktor, slijed(ove) nukleinskih kiselina koji kodira(ju) za drugi heterologni faktor i prvenstveno slijed(ove) nukleinskih kiselina koji kodira(ju) za treći heterologni faktor, pod uvjetom da su navedeni prvi faktor, navedeni drugi faktor i navedeni treći faktor funkcionalno različiti jedan od drugoga,
naznačene time,
da navedeni prvi faktor jest faktor rasta, kod čega je navedeni drugi faktor odabran iz skupine koja se sastoji od M2 polarizirajućih faktora, i u čemu je prvenstveno navedeni treći faktor odabran iz skupine koja se sastoji iz M2-polarizirajućih faktora i faktora rasta,
da navedeni M2-polarizirajući faktor jest odabran iz skupine koja se sastoji od interleukina 4 (IL-4), interleukina 10 (IL-10), interleukina 13 (IL-13), faktora-1 stimulacije kolonije (CSF-1), interleukina 34 (IL-34) i njihovih smjesa, a navedeni faktor rasta je odabran iz skupine koja se sastoji od fibroblastnih faktora rasta (FGF), vaskularnih endotelnih faktora rasta (VEGF), epidermalnog faktora rasta (EGF), heparin-vezujućeg, nalik EGF-u faktora rasta (HB-EGF), transformirajućeg faktora rasta α (TGF-α), inzulinu sličnih faktora rasta (IGF), trombocitnih faktora rasta (PDGF), transformirajućeg faktora rasta-ß (TGF-ß) i njihovih smjesa.
2. Rekombinantne probiotične bakterije prema patentnom zahtjevu 1,
naznačene time, da
naveden(i) slijed(ovi) nukleinskih kiselina je (su) lociran(i) na barem jednom od kromozoma i plazmida navedenih rekombinantnih probiotičnih bakterija.
3. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 ili 2,
naznačene time, da
ekspresija navedenog(ih) slijeda(ova) nukleinskih kiselina je kontrolirana konstitutivnim promotorom ili inducibilnim promotorom.
4. Rekombinantne probiotične bakterije prema patentnom zahtjevu 3,
naznačene time, da
ekspresija navedenog(ih) slijeda(ova) nukleinskih kiselina je kontrolirana inducibilnim promotorom, a naveden slijed(ovi) nukleinskih kiselina se može(gu) eksprimirati u prisutnosti barem jednog induktora.
5. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 3 ili 4,
naznačene time, da
navedeni inducibilni promotor koji se može inducirati induktorom, je promotor gena mikroba koji kodira za lantibiotički peptid ili njegov funkcionalni analog, gdje navedeni inducibilni promotor jest prvenstveno PnisA, PnisZ, PnisQ, PnisF, PnisU, ili njihove kombinacije od Lactococcus lactis.
6. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 4 ili 5,
naznačene time, da
je induktor barem jedan lantibiotični peptid ili njegov funkcionalni analog, prvenstveno odabran iz skupine koja se sastoji od nizina A, nizina Z, nizina Q, nizina F, nizina U, njihovih funkcionalnih analoga i njihovih smjesa.
7. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 6,
naznačene time, da
navedene probiotične bakterije nadalje sadrže barem jedan inaktivirani gen koji kodira za esencijalni protein, neophodan za preživljavanje navedenih probiotičnih bakterija.
8. Rekombinantne probiotične bakterije prema patentnom zahtjevu 7,
naznačene time, da
je barem jedan inaktivirani gen neophodan za preživljavanje navedenih probiotičnih bakterija odabran iz skupine koja se sastoji od alanin racemaze (alaR), timidilat sintaze (thyA), asparagin sintaze (asnH), CTP sintaze (pyrG), triptofan sintaze (trpBA) i njihovih kombinacija.
9. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 7 ili 8,
naznačene time, da
je navedeni gen inaktiviran delecijom navedenog gena, mutacijom navedenog gena, epigenetskom modifikacijom navedenog gena, interferirajućom RNA (RNAi) posredovanim stišavanjem navedenog gena, inhibicijom translacije navedenog gena ili njihovim kombinacijama.
10. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 9,
naznačene time, da
se barem jedan od navedenog prvog faktora, navedenog drugog faktora i navedenog trećeg faktora može otpustiti iz navedenih rekombinantnih probiotičnih bakterija.
11. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 10,
naznačene time, da
su navedeni fibroblastni faktori rasta (FGF) odabrani iz skupine koja se sastoji od fibroblastnog faktora rasta 1, fibroblastnog faktora rasta 2, fibroblastnog faktora rasta 7 (keratinocitnog faktora rasta), fibroblastnog faktora rasta 10 (keratinocitnog faktora rasta 2) i njihovih smjesa.
12. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 11,
naznačene time, da
su prvi, drugi i treći heterologni faktor kombinacija od:
• fibroblastnog faktora rasta 2, faktora stimulacije kolonije 1 i interleukina 4,
• fibroblastnog faktora rasta 2, interleukina 34 i interleukina 4,
• fibroblastnog faktora rasta 2, faktora stimulacije kolonije 1 i interleukina 13,
• fibroblastnog faktora rasta 2, interleukina 34 i interleukina 13,
• fibroblastnog faktora rasta 2, faktora stimulacije kolonije 1 i interleukina 10,
• fibroblastnog faktora rasta 2, interleukina 34 i interleukina 10,
• fibroblastnog faktora rasta 7, faktora stimulacije kolonije 1 i interleukina 4,
• fibroblastnog faktora rasta 7, interleukina 34 i interleukina 4,
• fibroblastnog faktora rasta 7, faktora stimulacije kolonije 1 i interleukina 13,
• fibroblastnog faktora rasta 7, interleukina 34 i interleukina 13,
• fibroblastnog faktora rasta 7, faktora stimulacije kolonije 1 i interleukina 10,
• fibroblastnog faktora rasta 7, interleukina 34 i interleukina 10,
• transformirajućeg faktora rasta beta, faktora stimulacije kolonije 1 i interleukina 4,
• transformirajućeg faktora rasta beta, interleukina 34 i interleukina 4,
• transformirajućeg faktora rasta beta, faktora stimulacije kolonije 1 i interleukina 13,
• transformirajućeg faktora rasta beta, interleukina 34 i interleukina 13,
• transformirajućeg faktora rasta beta, faktora stimulacije kolonije 1 i interleukina 10,
• transformirajućeg faktora rasta beta, interleukina 34 i interleukina 10,
• transformirajućeg faktora rasta alfa, faktora stimulacije kolonije 1 i interleukina 4,
• transformirajućeg faktora rasta alfa, interleukina 34 i interleukina 4,
• transformirajućeg faktora rasta alfa, faktora stimulacije kolonije 1 i interleukina 13,
• transformirajućeg faktora rasta alfa, interleukina 34 i interleukina 13,
• transformirajućeg faktora rasta alfa, faktora stimulacije kolonije 1 i interleukina 10,
• transformirajućeg faktora rasta alfa, interleukina 34 i interleukina 10,
• trombocitnog faktora rasta BB, faktora stimulacije kolonije 1 i interleukina 4,
• trombocitnog faktora rasta BB, interleukina 34 i interleukina 4,
• trombocitnog faktora rasta BB, faktora stimulacije kolonije 1 i interleukina 13,
• trombocitnog faktora rasta BB, interleukina 34 i interleukina 13,
• trombocitnog faktora rasta BB, faktora stimulacije kolonije 1 i interleukina 10, ili
• trombocitnog faktora rasta BB, interleukina 34 i interleukina 10,
13. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 12,
naznačene time, da
su navedeni prvi, drugi i treći heterologni faktor kombinacija fibroblastnog faktora rasta 2, faktora stimulacije kolonije 1 i interleukina 4, njihovih funkcionalnih analoga i njihovih biosimilara.
14. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 13,
naznačene time, da
navedene rekombinantne probiotične bakterije jesu bakterije laktičke kiseline, prvenstveno vrste Lactobacillus ili Lactococcus.
15. Rekombinantne probiotične bakterije prema patentnom zahtjevu 14,
naznačene time, da
navedena vrsta Lactococcus jest Lactococcus lactis, prvenstveno podvrsta Lactococcus cremoris.
16. Rekombinante probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 15,
naznačene time, da
navedene rekombinantne probiotične bakterije jesu u otopini, smrznute ili sušene, prvenstveno liofilizirane ili sušene sprejem.
17. Rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 16,
naznačene time, da
se navedene rekombinantne probiotične bakterije daju na kožu i/ili supkutanom injekcijom.
18. Rekombinantne probiotične bakterije za primjenu u liječenju kronične rane,
naznačene time, da
navedene rekombinantne probiotične bakterije, jesu rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 16, u čemu su navedeni prvi, drugi i treći heterologni faktor kombinacija fibroblastnog faktora rasta 2, faktora stimulacije kolonije 1 i interleukina 4.
19. Rekombinantne probiotične bakterije za primjenu prema patentnom zahtjevu 18,
naznačene time, da
navedena kronična rana jest barem jedno od kroničnog venskog ulkusa, kroničnog arterijskog ulkusa, kroničnog dijabetskog ulkusa, kroničnog ulkusa izazvanog mehaničkim pritiskom ili uklještenjem i njihovog kroničnog predulkusnog stadija.
20. Farmaceutski sastav za primjenu u liječenju kronične rane,
naznačen time, da
sadrži rekombinantne probiotične bakterije prema bilo kojem od patentnih zahtjeva 1 do 16, u čemu su navedeni prvi, drugi i treći heterologni faktor kombinacija fibroblastnog faktora rasta 2, faktora stimulacije kolonije 1 i interleukina 4.
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| PCT/EP2015/052345 WO2016124239A1 (en) | 2015-02-04 | 2015-02-04 | Recombinant probiotic bacteria for use in the treatment of a skin dysfunction |
| EP15821025.2A EP3253402B1 (en) | 2015-02-04 | 2015-11-02 | Recombinant probiotic bacteria |
| PCT/EP2015/075484 WO2016124266A1 (en) | 2015-02-04 | 2015-11-02 | Recombinant probiotic bacteria |
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| US11850270B2 (en) | 2017-12-04 | 2023-12-26 | The BioCollective, LLC | Probiotics and methods of use |
| WO2019162935A1 (en) * | 2018-02-24 | 2019-08-29 | Clearskin Ltd | Compositions, devices, systems, kits and methods for the treatment of a skin condition |
| EP3837993A4 (en) * | 2018-06-19 | 2022-04-20 | Coenbio Co., Ltd. | COMPOSITION FOR IMPROVING INTESTINAL FUNCTION WITH LEUCONOSTOC SP. STRAIN |
| WO2019245223A1 (ko) * | 2018-06-19 | 2019-12-26 | (주)코엔바이오 | 류코노스톡속 균주를 포함하는 간 기능 개선용 조성물 |
| KR102173168B1 (ko) * | 2018-06-19 | 2020-11-03 | 주식회사 엠디헬스케어 | 류코노스톡속 균주를 포함하는 장 기능 개선용 조성물 |
| KR102283127B1 (ko) * | 2018-06-19 | 2021-07-29 | 주식회사 엠디헬스케어 | 류코노스톡속 균주를 포함하는 간 기능 개선용 조성물 |
| US20220177533A1 (en) * | 2018-08-08 | 2022-06-09 | Sree Chitra Tirunal Institute For Medical Sciences And Technology | Recombinant TGF a for wound healing purposes, and the process thereof |
| CN109078171A (zh) * | 2018-09-10 | 2018-12-25 | 因之彩生物科技（武汉）有限公司 | 一种外用组合物及其应用以及外用治疗剂 |
| PL3921422T3 (pl) * | 2019-03-04 | 2024-04-02 | Aurealis Therapeutics AG | Indukowalny chlorkiem prokariotyczny układ ekspresji |
| IT201900003115A1 (it) * | 2019-03-04 | 2020-09-04 | Univ Degli Studi Roma La Sapienza | Lattococco ingegnerizzato |
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