HRP20211627T1 - Farmaceutski pripravak koji se sastoji od agonista receptora čimbenika rasta i proteina inhibitora adhezije za pretvaranje neoplastične stanice u neneoplastičnu stanicu i njegova upotreba - Google Patents
Farmaceutski pripravak koji se sastoji od agonista receptora čimbenika rasta i proteina inhibitora adhezije za pretvaranje neoplastične stanice u neneoplastičnu stanicu i njegova upotreba Download PDFInfo
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- HRP20211627T1 HRP20211627T1 HRP20211627TT HRP20211627T HRP20211627T1 HR P20211627 T1 HRP20211627 T1 HR P20211627T1 HR P20211627T T HRP20211627T T HR P20211627TT HR P20211627 T HRP20211627 T HR P20211627T HR P20211627 T1 HRP20211627 T1 HR P20211627T1
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- 210000005170 neoplastic cell Anatomy 0.000 title claims 7
- 229940124108 Growth factor receptor agonist Drugs 0.000 title 1
- 239000012268 protein inhibitor Substances 0.000 title 1
- 229940121649 protein inhibitor Drugs 0.000 title 1
- 102000009465 Growth Factor Receptors Human genes 0.000 claims 20
- 108010009202 Growth Factor Receptors Proteins 0.000 claims 20
- 150000001875 compounds Chemical group 0.000 claims 12
- 239000000825 pharmaceutical preparation Substances 0.000 claims 12
- 239000000816 peptidomimetic Substances 0.000 claims 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims 6
- 150000001413 amino acids Chemical class 0.000 claims 5
- 239000003112 inhibitor Substances 0.000 claims 4
- 102000001189 Cyclic Peptides Human genes 0.000 claims 3
- 108010069514 Cyclic Peptides Proteins 0.000 claims 3
- 125000004122 cyclic group Chemical group 0.000 claims 3
- 238000003745 diagnosis Methods 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 230000001613 neoplastic effect Effects 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- 102000007623 Dystroglycans Human genes 0.000 claims 2
- 108010071885 Dystroglycans Proteins 0.000 claims 2
- 108010088535 Pep-1 peptide Proteins 0.000 claims 2
- 102000003800 Selectins Human genes 0.000 claims 2
- 108090000184 Selectins Proteins 0.000 claims 2
- 102000019361 Syndecan Human genes 0.000 claims 2
- 108050006774 Syndecan Proteins 0.000 claims 2
- 150000001923 cyclic compounds Chemical class 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N n-butylhexane Natural products CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims 2
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 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
- 108010043648 Discoidin Domain Receptors Proteins 0.000 claims 1
- 102000002706 Discoidin Domain Receptors Human genes 0.000 claims 1
- 102000001301 EGF receptor Human genes 0.000 claims 1
- 108060006698 EGF receptor Proteins 0.000 claims 1
- 108091008815 Eph receptors Proteins 0.000 claims 1
- 108091008794 FGF receptors Proteins 0.000 claims 1
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 claims 1
- 101001004623 Homo sapiens Lactase-like protein Proteins 0.000 claims 1
- 108010001127 Insulin Receptor Proteins 0.000 claims 1
- 102000003746 Insulin Receptor Human genes 0.000 claims 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims 1
- 108091008555 LTK receptors Proteins 0.000 claims 1
- 102100025640 Lactase-like protein Human genes 0.000 claims 1
- 108091008553 MuSK receptors Proteins 0.000 claims 1
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 claims 1
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 claims 1
- 108091008606 PDGF receptors Proteins 0.000 claims 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 claims 1
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 claims 1
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 claims 1
- 108091008551 RET receptors Proteins 0.000 claims 1
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- 101100517381 Rattus norvegicus Ntrk1 gene Proteins 0.000 claims 1
- 241000711981 Sais Species 0.000 claims 1
- 102000004584 Somatomedin Receptors Human genes 0.000 claims 1
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- 102000013275 Somatomedins Human genes 0.000 claims 1
- 102000005450 TIE receptors Human genes 0.000 claims 1
- 108010006830 TIE receptors Proteins 0.000 claims 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims 1
- 102000009618 Transforming Growth Factors Human genes 0.000 claims 1
- 102100037236 Tyrosine-protein kinase receptor UFO Human genes 0.000 claims 1
- 108091008605 VEGF receptors Proteins 0.000 claims 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims 1
- 230000021164 cell adhesion Effects 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 108091006086 inhibitor proteins Proteins 0.000 claims 1
- 229940125798 integrin inhibitor Drugs 0.000 claims 1
- 108010044426 integrins Proteins 0.000 claims 1
- 102000006495 integrins Human genes 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 102000035160 transmembrane proteins Human genes 0.000 claims 1
- 108091005703 transmembrane proteins Proteins 0.000 claims 1
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 claims 1
Classifications
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- C07K16/2842—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta1-subunit-containing molecules, e.g. CD29, CD49
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- C07K16/2851—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
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Claims (17)
1. Farmaceutski pripravak koji sadrži barem jedan spoj za vezivanje na receptor čimbenika rasta, koji aktivira barem jedan receptor čimbenika rasta neoplastične stanice i barem jedan protein inhibitor adhezije koji inhibira barem jedan transmembranski protein za staničnu adheziju navedene neoplastične stanice,
pri čemu navedeni spoj za vezivanje na receptor čimbenika rasta sadrži peptid s četiri aminokiseline, PEP1, i
pri čemu se PEP1 označava kao SAIS.
2. Farmaceutski pripravak prema zahtjevu 1., pri čemu je navedeni spoj za vezivanje na receptor čimbenika rasta neciklički spoj za vezivanje na receptor čimbenika rasta čija je molekularna masa manja od 4000 daltona ili ciklički spoj za vezivanje na receptor čimbenika rasta čija je molekularna masa manja od 7000 daltona.
3. Farmaceutski pripravak prema zahtjevu 1. ili 2., pri čemu se navedeni receptor čimbenika rasta odabire iz skupine koja se sastoji od receptora epidermalnog čimbenika rasta, receptora čimbenika rasta fibroblasta, receptora vaskularnog endotelnog čimbenika rasta, receptora čimbenika rasta živaca, obitelji inzulinskih receptora, obitelji Trk receptora, obitelji Eph receptora, obitelji AXL receptora, obitelji LTK receptora, obitelji TIE receptora, obitelji ROR receptora, obitelji DDR receptora, obitelji RET receptora, obitelji KLG receptora, obitelji RYK receptora, obitelji MuSK receptora, receptora čimbenika rasta hepatocita, receptora čimbenika rasta somatomedina ili inzulinu sličnih čimbenika rasta, receptora čimbenika rasta iz trombocita te proteina transformirajućeg čimbenika rasta iz beta superobitelji.
4. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 3., pri čemu se navedeni inhibitor adhezije odabire iz skupine koja se sastoji od inhibitora integrina koji inhibira barem jedan integrin, inhibitora sindekana koji inhibira barem jedan sindekan, inhibitora selektina koji inhibira barem jedan selektin, inhibitora distroglikana koji inhibira barem jedan distroglikan i svih njihovih kombinacija.
5. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 4., pri čemu je navedeni spoj za vezivanje na receptor čimbenika rasta peptid ili peptidomimetik.
6. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 5., pri čemu je navedeni spoj za vezivanje na receptor čimbenika rasta neciklički peptid koji sadrži između 8 i 30 aminokiselina s mogućnošću vezivanja na receptor čimbenika rasta ili neciklički peptidomimetik s mogućnošću vezivanja na receptor čimbenika rasta, pri čemu molekularna masa navedenog peptidomimetika iznosi između 600 i 4000 daltona.
7. Farmaceutski pripravak prema zahtjevu 6., pri čemu navedeni peptidomimetik sadrži između 8 i 30 aminokiselina.
8. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 7., pri čemu vrijednost RMSD koordinata strukture navedenog peptida ili peptidomimetika u odnosu na PEPREF iznosi 2,45 Å (angstrema) ili manje, a pri čemu je PEPREF
[image]
[image]
[image]
9. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 5., pri čemu je navedeni spoj za vezivanje na receptor čimbenika rasta ciklički peptid koji sadrži između 10 i 60 aminokiselina s mogućnošću vezivanja na receptor čimbenika rasta ili ciklički peptidomimetik koji sadrži između 10 i 60 aminokiselina s mogućnošću vezivanja na receptor čimbenika rasta.
10. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 5. te prema zahtjevu 9., pri čemu je navedeni spoj za vezivanje na receptor čimbenika rasta ciklički peptid ili ciklički peptidomimetik čija molekularna masa iznosi između 1000 i 7000 daltona.
11. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 10., pri čemu se navedeni spoj za vezivanje na receptor čimbenika rasta odabire iz skupine koja se sastoji od bilo kojih peptida s identifikacijskim brojevima SEQ ID NO: 2 do 10, SEQ ID NO: 36, SEQ ID NO: 48 do 50, SEQ ID NO: 56, SEQ ID NO: 127 do 146, SEQ ID NO: 516, SEQ ID NO: 517, SEQ ID NO: 1043, SEQ ID NO: 1045, SEQ ID NO: 1396, SEQ ID NO: 1401, SEQ ID NO: 1403, SEQ ID NO: 1404, SEQ ID NO: 1413, SEQ ID NO: 1417, SEQ ID NO: 1418, SEQ ID NO: 1420, SEQ ID NO: 1421, SEQ ID NO: 1423, SEQ ID NO: 1426, SEQ ID NO: 1428 do 1430, SEQ ID NO: 1445 do 1447, SEQ ID NO: 1451, SEQ ID NO: 1452, SEQ ID NO: 1455, SEQ ID NO: 1460, SEQ ID NO: 1461, SEQ ID NO: 1466, SEQ ID NO: 1470, SEQ ID NO: 1474, SEQ ID NO: 1480, SEQ ID NO: 1482, SEQ ID NO: 1486, SEQ ID NO: 1490, SEQ ID NO: 1493, SEQ ID NO: 1503, SEQ ID NO: 1506, SEQ ID NO: 1509, SEQ ID NO: 1510, SEQ ID NO: 1512 do 1514, SEQ ID NO: 1517, SEQ ID NO: 1519, SEQ ID NO: 1521, SEQ ID NO: 1525, SEQ ID NO: 1527 do 1530, SEQ ID NO: 1535, SEQ ID NO: 1536, SEQ ID NO: 1538, SEQ ID NO: 1539, SEQ ID NO: 1552, SEQ ID NO: 1564, SEQ ID NO: 1566, SEQ ID NO: 1567, SEQ ID NO: 1572, SEQ ID NO: 1577 do 1579, SEQ ID NO: 1582, SEQ ID NO: 1588 do 1591, SEQ ID NO: 1594, SEQ ID NO: 1596, SEQ ID NO: 1598, SEQ ID NO: 1603, SEQ ID NO: 1604, SEQ ID NO: 1611, SEQ ID NO: 1612, SEQ ID NO: 1618, SEQ ID NO: 1620, SEQ ID NO: 1621, SEQ ID NO: 1623, SEQ ID NO: 1648, SEQ ID NO: 1650, SEQ ID NO: 1652, SEQ ID NO: 1668, SEQ ID NO: 1672, SEQ ID NO: 1674, SEQ ID NO: 1676, SEQ ID NO: 1698, SEQ ID NO: 1702, SEQ ID NO: 1708, SEQ ID NO: 1712, SEQ ID NO: 1959, SEQ ID NO: 1976, SEQ ID NO: 1983, SEQ ID NO: 1997, SEQ ID NO: 2074, SEQ ID NO: 2096, SEQ ID NO: 2105, SEQ ID NO: 2123, SEQ ID NO: 2142, SEQ ID NO: 2154, SEQ ID NO: 2179, SEQ ID NO: 4659, SEQ ID NO: 4716, SEQ ID NO: 4718, SEQ ID NO: 4725, SEQ ID NO: 4726, SEQ ID NO: 4743, SEQ ID NO: 4744, SEQ ID NO: 4745, SEQ ID NO: 4748, SEQ ID NO: 4751, SEQ ID NO: 4752, SEQ ID NO: 4754, SEQ ID NO: 4758, SEQ ID NO: 4760, SEQ ID NO: 4761, SEQ ID NO: 4762, SEQ ID NO: 4764, SEQ ID NO: 4782, SEQ ID NO: 4784, SEQ ID NO: 4787, SEQ ID NO: 4788, SEQ ID NO: 4789, SEQ ID NO: 4839, SEQ ID NO: 4856, SEQ ID NO: 5142, SEQ ID NO: 5143, SEQ ID NO: 5172, SEQ ID NO: 5187, SEQ ID NO: 5188, SEQ ID NO: 5217, SEQ ID NO: 5232, SEQ ID NO: 5233, SEQ ID NO: 5262, SEQ ID NO: 5275, SEQ ID NO: 5292, SEQ ID NO: 7003, SEQ ID NO: 7007, SEQ ID NO: 7008, SEQ ID NO: 7015, SEQ ID NO: 7018, SEQ ID NO: 7021, SEQ ID NO: 7022, SEQ ID NO: 7023, SEQ ID NO: 7033, SEQ ID NO: 7034, SEQ ID NO: 7035, SEQ ID NO: 7036, SEQ ID NO: 7040, SEQ ID NO: 7041, SEQ ID NO: 7044, SEQ ID NO: 7045, SEQ ID NO: 7046, SEQ ID NO: 7048, SEQ ID NO: 7051, SEQ ID NO: 7052, SEQ ID NO: 7054, SEQ ID NO: 7055, SEQ ID NO: 7057, SEQ ID NO: 7060, SEQ ID NO: 7068, SEQ ID NO: 7069, SEQ ID NO: 7072, SEQ ID NO: 7074, SEQ ID NO: 7078, SEQ ID NO: 7079, SEQ ID NO: 7086, SEQ ID NO: 7088, SEQ ID NO: 7089, SEQ ID NO: 7094, SEQ ID NO: 7103, SEQ ID NO: 7104, SEQ ID NO: 7106, SEQ ID NO: 7109, SEQ ID NO: 7113, SEQ ID NO: 7115, SEQ ID NO: 7121, SEQ ID NO: 7125, SEQ ID NO: 7136, SEQ ID NO: 7137, SEQ ID NO: 7139, SEQ ID NO: 7140, SEQ ID NO: 7142, SEQ ID NO: 7143, SEQ ID NO: 7144, SEQ ID NO: 7147, SEQ ID NO: 7149, SEQ ID NO: 7150, SEQ ID NO: 7151, SEQ ID NO: 7154, SEQ ID NO: 7157, SEQ ID NO: 7158, SEQ ID NO: 7160, SEQ ID NO: 7163, SEQ ID NO: 7166, SEQ ID NO: 7173, SEQ ID NO: 7178, SEQ ID NO: 7186, SEQ ID NO: 7188, SEQ ID NO: 7196, SEQ ID NO: 7203, SEQ ID NO: 7204, SEQ ID NO: 7205, SEQ ID NO: 7206, SEQ ID NO: 7208, SEQ ID NO: 7214, SEQ ID NO: 7215, SEQ ID NO: 7216, SEQ ID NO: 7218, SEQ ID NO: 7223, SEQ ID NO: 7224, SEQ ID NO: 7229, SEQ ID NO: 7230, SEQ ID NO: 7232, SEQ ID NO: 7237, SEQ ID NO: 7242, SEQ ID NO: 7244, SEQ ID NO: 7250, SEQ ID NO: 7255, SEQ ID NO: 7257, SEQ ID NO: 7259, SEQ ID NO: 7261, SEQ ID NO: 7272, SEQ ID NO: 7284, SEQ ID NO: 7287, SEQ ID NO: 7301, SEQ ID NO: 7305, SEQ ID NO: 7307, SEQ ID NO: 7314, SEQ ID NO: 7317, SEQ ID NO: 7319, SEQ ID NO: 7321, SEQ ID NO: 7328, SEQ ID NO: 7335, SEQ ID NO: 7341, SEQ ID NO: 7343, SEQ ID NO: 7344, SEQ ID NO: 7359, SEQ ID NO: 7363, SEQ ID NO: 7365, SEQ ID NO: 7377, SEQ ID NO: 7380, SEQ ID NO: 7381, SEQ ID NO: 7383, SEQ ID NO: 7384, SEQ ID NO: 7394, SEQ ID NO: 7395, SEQ ID NO: 7396, SEQ ID NO: 7397, SEQ ID NO: 7405, SEQ ID NO: 7407, SEQ ID NO: 7408, SEQ ID NO: 7414, SEQ ID NO: 7419, SEQ ID NO: 7420, SEQ ID NO: 7424, SEQ ID NO: 7426, SEQ ID NO: 7433, SEQ ID NO: 7437, SEQ ID NO: 7439, SEQ ID NO: 7442, SEQ ID NO: 7443, SEQ ID NO: 7454, SEQ ID NO: 7461, SEQ ID NO: 7465, SEQ ID NO: 7479, SEQ ID NO: 7488, SEQ ID NO: 7501, SEQ ID NO: 7506, SEQ ID NO: 7511, SEQ ID NO: 7514, SEQ ID NO: 7515, SEQ ID NO: 7520, SEQ ID NO: 7524, SEQ ID NO: 7527, SEQ ID NO: 7529, SEQ ID NO: 7533, SEQ ID NO: 7550, SEQ ID NO: 7553, SEQ ID NO: 7555, SEQ ID NO: 7558, SEQ ID NO: 7559, SEQ ID NO: 7561, SEQ ID NO: 7564, SEQ ID NO: 7566, SEQ ID NO: 7567, SEQ ID NO: 7570, SEQ ID NO: 7571, SEQ ID NO: 7578, SEQ ID NO: 7579, SEQ ID NO: 7581, SEQ ID NO: 7586, SEQ ID NO: 7587, SEQ ID NO: 7591, SEQ ID NO: 7592, SEQ ID NO: 7600, SEQ ID NO: 7602, SEQ ID NO: 7621, SEQ ID NO: 7622, SEQ ID NO: 7631, SEQ ID NO: 7635, SEQ ID NO: 7653, SEQ ID NO: 7659, SEQ ID NO: 7674, SEQ ID NO: 7678, SEQ ID NO: 8141, SEQ ID NO: 8153, SEQ ID NO: 8161, SEQ ID NO: 8193, SEQ ID NO: 8227, SEQ ID NO: 8240, SEQ ID NO: 8288, SEQ ID NO: 8308, SEQ ID NO: 8311, SEQ ID NO: 8314, SEQ ID NO: 8346, SEQ ID NO: 8356, SEQ ID NO: 8367, SEQ ID NO: 8385, SEQ ID NO: 8476, SEQ ID NO: 8502, SEQ ID NO: 8512, SEQ ID NO: 8520, SEQ ID NO: 8531, SEQ ID NO: 8556, SEQ ID NO: 13391, SEQ ID NO: 13498.
12. Medicinski pripravak koji sadrži barem jedan farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 11. te barem jednu medicinski prihvatljivu pomoćnu tvar, nositelja ili prijenosnika.
13. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 11. ili medicinski pripravak prema zahtjevu 12. za upotrebu pri liječenju, sprječavanju i/ili dijagnosticiranju neoplastične bolesti.
14. Postupak pretvorbe neoplastične stanice u neneoplastičnu stanicu, in vitro ili ex vivo, pri čemu se navedeni postupak sastoji od primjene učinkovite količine farmaceutskog pripravka ili spoja na neoplastičnu stanicu kako je definirano u bilo kojem od zahtjeva od 1. do 12.
15. Protein inhibitor adhezije koji se koristi za sprječavanje, dijagnosticiranje i/ili liječenje neoplastične bolesti zajedno s barem jednim spojem za vezivanje na receptor čimbenika rasta kako je definirano u bilo kojem zahtjevu od 1. do 11.
16. Spoj za vezivanje na receptor čimbenika rasta kako je definirano u bilo kojem zahtjevu od 1. do 11. koji se koristi za sprječavanje, dijagnosticiranje i/ili liječenje neoplastične bolesti zajedno s barem jednim proteinom inhibitorom adhezije kako je definirano u bilo kojem zahtjevu od 1. do 11.
17. Farmaceutski pripravak prema bilo kojem od zahtjeva od 1. do 10., pri čemu navedeni spoj za vezivanje na receptor čimbenika rasta sadrži peptid koji se odabire iz skupine koja se sastoji od peptida s identifikacijskim brojevima SEQ ID NO kako je definirano u zahtjevu 11.
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| PCT/EP2016/071795 WO2017046228A2 (en) | 2015-09-17 | 2016-09-15 | Pharmaceutical association for converting a neoplastic cell into a non-neoplastic cell and uses thereof |
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| CN110331124B (zh) * | 2019-06-14 | 2022-03-22 | 浙江大学 | 一种导电聚吡咯/细胞外基质复合薄膜及其制备方法 |
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| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
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| US20030185792A1 (en) * | 1996-01-22 | 2003-10-02 | Curis, Inc. | Morphogen analogs of bone morphogenic proteins |
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| DE19748688C2 (de) * | 1997-04-22 | 2001-09-06 | Hans Georg Graeber | Membransystem zur gesteuerten Geweberegeneration bei Erkrankungen des Zahnhalteapparates |
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| WO2017046228A3 (en) | 2017-06-29 |
| AU2016323408A1 (en) | 2018-04-19 |
| IL258132A (en) | 2018-05-31 |
| EP3998076A1 (en) | 2022-05-18 |
| SG10201913380WA (en) | 2020-03-30 |
| JP7145503B2 (ja) | 2022-10-03 |
| ES2900480T3 (es) | 2022-03-17 |
| IL299624A (en) | 2023-03-01 |
| WO2017046228A2 (en) | 2017-03-23 |
| US20190330290A1 (en) | 2019-10-31 |
| PL3349778T3 (pl) | 2021-12-27 |
| KR20180052726A (ko) | 2018-05-18 |
| LT3349778T (lt) | 2021-11-10 |
| EP3349778B1 (en) | 2021-09-01 |
| EP3949975A1 (en) | 2022-02-09 |
| CA2998455A1 (en) | 2017-03-23 |
| SI3349778T1 (sl) | 2021-12-31 |
| JP2018537404A (ja) | 2018-12-20 |
| CN109715191A (zh) | 2019-05-03 |
| EP3349778A2 (en) | 2018-07-25 |
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| IL258132B2 (en) | 2023-06-01 |
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