HRP20231297T1 - Fasl-konstruirani biomaterijali s imunomodulacijskom funkcijom - Google Patents
Fasl-konstruirani biomaterijali s imunomodulacijskom funkcijom Download PDFInfo
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- HRP20231297T1 HRP20231297T1 HRP20231297TT HRP20231297T HRP20231297T1 HR P20231297 T1 HRP20231297 T1 HR P20231297T1 HR P20231297T T HRP20231297T T HR P20231297TT HR P20231297 T HRP20231297 T HR P20231297T HR P20231297 T1 HRP20231297 T1 HR P20231297T1
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- 239000012620 biological material Substances 0.000 title claims 31
- 230000008975 immunomodulatory function Effects 0.000 title 1
- 210000004027 cell Anatomy 0.000 claims 21
- 102000015212 Fas Ligand Protein Human genes 0.000 claims 8
- 108010039471 Fas Ligand Protein Proteins 0.000 claims 8
- 239000000017 hydrogel Substances 0.000 claims 6
- 210000004443 dendritic cell Anatomy 0.000 claims 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims 4
- 239000003018 immunosuppressive agent Substances 0.000 claims 4
- 229940124589 immunosuppressive drug Drugs 0.000 claims 4
- 230000002265 prevention Effects 0.000 claims 4
- 230000006058 immune tolerance Effects 0.000 claims 3
- 108090001008 Avidin Proteins 0.000 claims 2
- 241000283690 Bos taurus Species 0.000 claims 2
- 241000283073 Equus caballus Species 0.000 claims 2
- 241000282326 Felis catus Species 0.000 claims 2
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 claims 2
- 241000699666 Mus <mouse, genus> Species 0.000 claims 2
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 2
- 241001494479 Pecora Species 0.000 claims 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 2
- 241000700159 Rattus Species 0.000 claims 2
- 108010090804 Streptavidin Proteins 0.000 claims 2
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims 2
- 229960002685 biotin Drugs 0.000 claims 2
- 235000020958 biotin Nutrition 0.000 claims 2
- 239000011616 biotin Substances 0.000 claims 2
- 210000004271 bone marrow stromal cell Anatomy 0.000 claims 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims 2
- 102000055647 human CSF2RB Human genes 0.000 claims 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims 2
- 229920001223 polyethylene glycol Polymers 0.000 claims 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims 2
- 229960002930 sirolimus Drugs 0.000 claims 2
- 210000004988 splenocyte Anatomy 0.000 claims 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 230000005784 autoimmunity Effects 0.000 claims 1
- 210000001185 bone marrow Anatomy 0.000 claims 1
- 210000002798 bone marrow cell Anatomy 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 210000004153 islets of langerhan Anatomy 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/37—Digestive system
- A61K35/39—Pancreas; Islets of Langerhans
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/178—Lectin superfamily, e.g. selectins
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6903—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus
- C12M3/02—Tissue, human, animal or plant cell, or virus culture apparatus with means providing suspensions
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
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- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Cell Biology (AREA)
- Immunology (AREA)
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- Genetics & Genomics (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
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- General Chemical & Material Sciences (AREA)
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Claims (21)
1. Biomaterijal konstruiran za prikazivanje FasL proteina, naznačen time što je biomaterijal hidrogel, pri čemu hidrogel sadrži kimerni FasL protein koji sadrži FasL dio i streptavidinski ili avidinski dio konjugiran preko biotina na hidrogel.
2. Biomaterijal prema zahtjevu 1, naznačen time što je hidrogel mikrogel.
3. Biomaterijal prema zahtjevima 1 ili 2, naznačen time što je hidrogel mikrogel polietilen glikola (PEG) konstruiran za prikazivanje biotinskog dijela.
4. Biomaterijal prema bilo kojem od zahtjeva 1 do 3, naznačen time što je FasL dio FasL proteina otporan na matričnu metaloproteinazu.
5. Biomaterijal prema zahtjevu 1, naznačen time što biomaterijal nadalje sadrži imunosupresivni lijek.
6. Biomaterijal prema zahtjevu 5, naznačen time što je imunosupresivni lijek rapamicin.
7. Biomaterijal prema zahtjevu 1, naznačen time što biomaterijal nadalje sadrži stanicu transplantata.
8. Biomaterijal prema zahtjevu 7, naznačen time što je stanica transplantata inkapsulirana biomaterijalom.
9. Biomaterijal prema zahtjevu 7, naznačen time što stanica transplantata nije inkapsulirana biomaterijalom.
10. Biomaterijal konstruiran za prikazivanje FasL proteina prema bilo kojem od zahtjeva 1-9 naznačen time što je za upotrebu u induciranju imunološke tolerancije kod subjekta kojem je to potrebno.
11. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što se hidrogel transplantira u subjekta.
12. Biomaterijal za upotrebu prema zahtjevu 10 u kombinaciji s imunosupresivnim lijekom, po izboru pri čemu je imunosupresivni lijek rapamicin.
13. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što je subjekt čovjek, primat koji nije čovjek, svinja, pas, mačka, krava, ovca, konj, zec, miš ili štakor.
14. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što je subjektu potrebna imunološka tolerancija na transplatiranu stanicu, po izboru pri čemu se subjektu daje stanica transplantata, po izboru pri čemu biomaterijal dalje sadrži stanicu transplantata, po izboru pri čemu je stanica transplantata inkapsulirana biomaterijalom, izborno pri čemu je stanica transplantata odabrana između PBMC-a, stanica koštane srži, hematopoetskih matičnih stanica, matičnih stanica, mezenhimalnih matičnih stanica, dendritičnih stanica, dendritičnih stanica pulsiranih autoantigenima, produkata ljudskih beta stanica i splenocita.
15. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što je subjektu potrebna imunološka tolerancija na transplatiranu stanicu, izborno pri čemu se subjektu daje stanica transplantata pri čemu stanica transplantata nije inkapsulirana biomaterijalom, izborno pri čemu je stanica transplantata odabrana između PBMC-a, stanica koštane srži, hematopoetskih matičnih stanica, matičnih stanica, mezenhimalnih matičnih stanica, dendritičnih stanica, dendritičnih stanica pulsiranih autoantigenima, produkata ljudskih beta stanica i splenocita.
16. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što je subjektu potrebno liječenje dijabetesa tipa 1, izborno pri čemu se subjektu daju stanice otočića gušterače.
17. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što je subjektu potrebno liječenje ili prevencija odbacivanja alografta, izborno pri čemu se subjektu daju stanice iz donora alografta.
18. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što je subjektu potrebno liječenje ili prevencija odbacivanja ksenografta, izborno pri čemu se subjektu daju stanice donora ksenografta, izborno pri čemu se je donator ksenografta čovjek, primat koji nije čovjek, svinja, pas, mačka, krava, ovca, konj, zec, miš ili štakor.
19. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što je subjektu potrebno liječenje ili prevencija odbacivanja autotransplantata, izborno pri čemu se subjektu daju autologne transplantirane stanice, izborno pri čemu su autologne transplantirane stanice dobivene induciranom pluripotencijom.
20. Biomaterijal za upotrebu prema zahtjevu 10, naznačen time što je subjektu potrebno liječenje ili prevencija autoimunosti, po izboru, pri čemu se subjektu daje autoantigen predstavljen na stanici odabranoj između (i) stanice koja eksprimira autoantigen (ii) stanice koja je ukrašena autoantigenom i (iii) dendritične stanice pulsirane autoantigenom.
21. Postupak za izradu biomaterijala prema bilo kojem od zahtjeva 1-9, naznačen time što obuhvaća dovođenje u kontakt biotiniliranog biomaterijala s kimernim FasL proteinom koji sadrži FasL dio i streptavidinski ili avidinski dio.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762469802P | 2017-03-10 | 2017-03-10 | |
| PCT/US2018/021742 WO2018165547A1 (en) | 2017-03-10 | 2018-03-09 | Fasl-engineered biomaterials with immunomodulatory function |
| EP18764623.7A EP3592392B1 (en) | 2017-03-10 | 2018-03-09 | Fasl-engineered biomaterials with immunomodulatory function |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20231297T1 true HRP20231297T1 (hr) | 2024-02-02 |
Family
ID=63448048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20231297TT HRP20231297T1 (hr) | 2017-03-10 | 2018-03-09 | Fasl-konstruirani biomaterijali s imunomodulacijskom funkcijom |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US11602547B2 (hr) |
| EP (2) | EP4299749A3 (hr) |
| JP (1) | JP7335821B2 (hr) |
| CN (1) | CN110582560B (hr) |
| AU (1) | AU2018230474B2 (hr) |
| CA (1) | CA3055908A1 (hr) |
| DK (1) | DK3592392T3 (hr) |
| ES (1) | ES2963331T3 (hr) |
| FI (1) | FI3592392T3 (hr) |
| HR (1) | HRP20231297T1 (hr) |
| HU (1) | HUE064306T2 (hr) |
| LT (1) | LT3592392T (hr) |
| PL (1) | PL3592392T3 (hr) |
| PT (1) | PT3592392T (hr) |
| RS (1) | RS64754B1 (hr) |
| SI (1) | SI3592392T1 (hr) |
| WO (1) | WO2018165547A1 (hr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11202104337PA (en) * | 2018-11-26 | 2021-05-28 | Massachusetts Inst Technology | Compositions and methods for immune tolerance |
| AU2021306315A1 (en) * | 2020-07-08 | 2023-03-02 | Georgia Tech Research Corporation | Crosslinked hydrogel for immune checkpoint blockade delivery |
| WO2023220690A1 (en) * | 2022-05-12 | 2023-11-16 | Itolerance, Inc. | Transient sirolimus with fasl microgels |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6022951A (en) | 1995-04-11 | 2000-02-08 | Univ Boston | Streptavidin mutants |
| AU724856B2 (en) * | 1995-06-30 | 2000-10-05 | Mochida Pharmaceutical Co., Ltd. | Anti-Fas ligand antibody and assay method using the anti-Fas ligand antibody |
| GB9523469D0 (en) * | 1995-11-16 | 1996-01-17 | Sandoz Ltd | Organic compounds |
| US7927602B2 (en) * | 2002-07-23 | 2011-04-19 | University Of Louisville Research Foundation, Inc. | Fas ligand-avidin/streptavidin fusion proteins |
| US7238360B2 (en) | 2000-06-30 | 2007-07-03 | Unversity Of Louisville Research Foundation, Inc. | Alteration of cell membrane with B7 |
| AU2003297573A1 (en) * | 2002-11-27 | 2004-06-23 | Cedric Francois | Compositions and methods for treating transplants |
| AU2006279541A1 (en) * | 2005-08-15 | 2007-02-22 | The Regents Of The University Of California | VEGF-activated FAS ligands |
| WO2011041240A1 (en) * | 2009-09-30 | 2011-04-07 | The Brigham And Women's Hospital, Inc. | Tissue transplant compositions and methods for use |
| PL2459220T3 (pl) | 2009-07-31 | 2021-03-08 | Ascendis Pharma A/S | Biodegradowalne nierozpuszczalne w wodzie hydrożele na bazie poli(glikolu etylenowego) |
| CN102781436B (zh) * | 2009-11-06 | 2014-01-08 | 爱思开生物制药株式会社 | 纤维肌痛综合征的治疗方法 |
| MY178680A (en) | 2012-10-11 | 2020-10-20 | Ascendis Pharma As | Hydrogel prodrugs |
| WO2015034928A1 (en) * | 2013-09-03 | 2015-03-12 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
| US9381217B2 (en) | 2013-09-09 | 2016-07-05 | Georgia Tech Research Corporation | Microgels for encapsulation of cells and other biologic agents |
| WO2016205714A1 (en) | 2015-06-19 | 2016-12-22 | University Of Louisville Research Foundation, Inc. | Immunomodulation for the long term prevention and treatment of autoimmune diseases and foreign tissue rejection |
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2018
- 2018-03-09 FI FIEP18764623.7T patent/FI3592392T3/fi active
- 2018-03-09 US US16/492,441 patent/US11602547B2/en active Active
- 2018-03-09 EP EP23196606.0A patent/EP4299749A3/en active Pending
- 2018-03-09 DK DK18764623.7T patent/DK3592392T3/da active
- 2018-03-09 PT PT187646237T patent/PT3592392T/pt unknown
- 2018-03-09 EP EP18764623.7A patent/EP3592392B1/en active Active
- 2018-03-09 HU HUE18764623A patent/HUE064306T2/hu unknown
- 2018-03-09 RS RS20230876A patent/RS64754B1/sr unknown
- 2018-03-09 SI SI201831008T patent/SI3592392T1/sl unknown
- 2018-03-09 CA CA3055908A patent/CA3055908A1/en active Pending
- 2018-03-09 ES ES18764623T patent/ES2963331T3/es active Active
- 2018-03-09 PL PL18764623.7T patent/PL3592392T3/pl unknown
- 2018-03-09 JP JP2019570350A patent/JP7335821B2/ja active Active
- 2018-03-09 CN CN201880029433.6A patent/CN110582560B/zh active Active
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- 2018-03-09 HR HRP20231297TT patent/HRP20231297T1/hr unknown
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- 2018-03-09 LT LTEPPCT/US2018/021742T patent/LT3592392T/lt unknown
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| Publication number | Publication date |
|---|---|
| AU2018230474B2 (en) | 2023-08-03 |
| DK3592392T3 (da) | 2023-10-23 |
| US11602547B2 (en) | 2023-03-14 |
| HUE064306T2 (hu) | 2024-02-28 |
| US20230310510A1 (en) | 2023-10-05 |
| EP3592392A4 (en) | 2020-12-16 |
| AU2018230474A1 (en) | 2019-10-31 |
| EP4299749A2 (en) | 2024-01-03 |
| ES2963331T3 (es) | 2024-03-26 |
| JP7335821B2 (ja) | 2023-08-30 |
| CN110582560B (zh) | 2024-06-14 |
| LT3592392T (lt) | 2024-01-25 |
| US20200046780A1 (en) | 2020-02-13 |
| PL3592392T3 (pl) | 2024-03-18 |
| SI3592392T1 (sl) | 2024-02-29 |
| CN110582560A (zh) | 2019-12-17 |
| EP3592392B1 (en) | 2023-09-13 |
| EP4299749A3 (en) | 2024-03-27 |
| RS64754B1 (sr) | 2023-11-30 |
| PT3592392T (pt) | 2023-11-23 |
| EP3592392A1 (en) | 2020-01-15 |
| FI3592392T3 (fi) | 2023-11-09 |
| JP2020511531A (ja) | 2020-04-16 |
| WO2018165547A1 (en) | 2018-09-13 |
| CA3055908A1 (en) | 2018-09-13 |
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