HRP20240603T1 - Optimizirane fuzije binukleaze i postupci njihove upotrebe - Google Patents
Optimizirane fuzije binukleaze i postupci njihove upotrebe Download PDFInfo
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- HRP20240603T1 HRP20240603T1 HRP20240603TT HRP20240603T HRP20240603T1 HR P20240603 T1 HRP20240603 T1 HR P20240603T1 HR P20240603T T HRP20240603T T HR P20240603TT HR P20240603 T HRP20240603 T HR P20240603T HR P20240603 T1 HRP20240603 T1 HR P20240603T1
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- 238000000034 method Methods 0.000 title claims 3
- 230000004927 fusion Effects 0.000 title 1
- 239000000833 heterodimer Substances 0.000 claims 15
- 230000035772 mutation Effects 0.000 claims 10
- 102000016911 Deoxyribonucleases Human genes 0.000 claims 9
- 108010053770 Deoxyribonucleases Proteins 0.000 claims 9
- 229920001184 polypeptide Polymers 0.000 claims 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims 6
- 101710123428 Ribonuclease pancreatic Proteins 0.000 claims 5
- 102100039832 Ribonuclease pancreatic Human genes 0.000 claims 5
- 101710163270 Nuclease Proteins 0.000 claims 4
- 208000023275 Autoimmune disease Diseases 0.000 claims 3
- 101000667595 Homo sapiens Ribonuclease pancreatic Proteins 0.000 claims 3
- 108010083644 Ribonucleases Proteins 0.000 claims 3
- 102000006382 Ribonucleases Human genes 0.000 claims 3
- 102000039446 nucleic acids Human genes 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 150000007523 nucleic acids Chemical class 0.000 claims 3
- 238000002360 preparation method Methods 0.000 claims 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 3
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 0.000 claims 2
- 238000003259 recombinant expression Methods 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 208000026872 Addison Disease Diseases 0.000 claims 1
- 208000004300 Atrophic Gastritis Diseases 0.000 claims 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 claims 1
- 206010071155 Autoimmune arthritis Diseases 0.000 claims 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 206010063075 Cryptogenic cirrhosis Diseases 0.000 claims 1
- 102220518153 DNA-directed RNA polymerases I and III subunit RPAC1_E13R_mutation Human genes 0.000 claims 1
- 208000036495 Gastritis atrophic Diseases 0.000 claims 1
- 208000024869 Goodpasture syndrome Diseases 0.000 claims 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims 1
- 206010020850 Hyperthyroidism Diseases 0.000 claims 1
- 208000007466 Male Infertility Diseases 0.000 claims 1
- 206010028665 Myxoedema Diseases 0.000 claims 1
- 206010034277 Pemphigoid Diseases 0.000 claims 1
- 201000011152 Pemphigus Diseases 0.000 claims 1
- 208000031845 Pernicious anaemia Diseases 0.000 claims 1
- 102220644742 Plakophilin-2_N76S_mutation Human genes 0.000 claims 1
- 208000002500 Primary Ovarian Insufficiency Diseases 0.000 claims 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims 1
- 206010039710 Scleroderma Diseases 0.000 claims 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 1
- 206010042742 Sympathetic ophthalmia Diseases 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 206010046851 Uveitis Diseases 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 230000001363 autoimmune Effects 0.000 claims 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims 1
- 208000018631 connective tissue disease Diseases 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 201000001981 dermatomyositis Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 claims 1
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- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- 208000006454 hepatitis Diseases 0.000 claims 1
- 231100000283 hepatitis Toxicity 0.000 claims 1
- 230000028993 immune response Effects 0.000 claims 1
- 201000002364 leukopenia Diseases 0.000 claims 1
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- 206010028417 myasthenia gravis Diseases 0.000 claims 1
- 208000003786 myxedema Diseases 0.000 claims 1
- 201000001976 pemphigus vulgaris Diseases 0.000 claims 1
- 208000005987 polymyositis Diseases 0.000 claims 1
- 206010036601 premature menopause Diseases 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 102200062706 rs121908046 Human genes 0.000 claims 1
- 102200139516 rs35960830 Human genes 0.000 claims 1
- 102220041142 rs587778635 Human genes 0.000 claims 1
- 102220092172 rs753180642 Human genes 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 206010043778 thyroiditis Diseases 0.000 claims 1
- 208000005057 thyrotoxicosis Diseases 0.000 claims 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases RNAses, DNAses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/21—Endodeoxyribonucleases producing 5'-phosphomonoesters (3.1.21)
- C12Y301/21001—Deoxyribonuclease I (3.1.21.1)
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
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- C12Y301/27—Endoribonucleases producing 3'-phosphomonoesters (3.1.27)
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/72—Increased effector function due to an Fc-modification
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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Claims (15)
1. Heterodimer, naznačen time što sadrži prvi polipeptidni slijed i drugi polipeptidni slijed, gdje prvi polipeptidni slijed sadrži prvu nukleaznu domenu, drugu nukleaznu domenu i prvu Fc domena, te gdje se drugi polipeptidni slijed sastoji od druge Fc domene, gdje je prva nukleazna domena DNaza 1, a druga nukleazna domena je RNaza 1, te gdje prva i druga Fc domena sadrže jednu ili više CH3 mutacija kako bi po mogućnosti tvorile heterodimere, te gdje je DNaza 1 operabilno povezana uz pomoć ili bez spojnice s N-krajem prve Fc domene, a RNaza 1 je operabilno povezana uz pomoć ili bez spojnice s C-krajem prve Fc domene.
2. Heterodimer u skladu s patentnim zahtjevom 1, naznačen time što:
(i) DNaza 1 je operabilno povezana bez spojnice s N-krajem prve Fc domene, a RNaza 1 je operabilno povezana uz pomoć spojnice s C-krajem prve Fc domene; ili
(ii) DNaza 1 je operabilno povezana uz pomoć spojnice s N-krajem prve Fc domene, a RNaza 1 je operabilno povezana uz pomoć spojnice s C-krajem prve Fc domene.
3. Heterodimer u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je RNaza ljudska RNaza 1 divljeg tipa, ili mutant RNaza, poput aglikozilirane, hipoglikozilirane ili deglikozilirane RNaze 1, poput ljudske RNaze 1 N34S/N76S/N88S, gdje obrojčavanje mutacija odgovara onom u SEQ ID NO: 27; po mogućnosti gdje je RNaza ljudska RNaza 1 divljeg tipa.
4. Heterodimer u skladu s bilo kojim od patentnih zahtjeva 1-3, naznačen time što je DNaza ljudska DNaza divljeg tipa 1, ili mutantna ljudska DNaza 1 A114F, ili aglikozilirana, hipoglikozilirana ili deglikozilirana mutantna ljudska DNaza 1 N18S/N106S/A114F, ili mutantna ljudska DNaza 1 E13R/N74K/A114F/T205K; gdje obrojčavanje mutacija odgovara onom u SEQ ID NO: 20.
5. Heterodimer u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što prva i druga Fc domena sadrže zglobnu domenu, domenu CH2 i domenu CH3, gdje izborno prva i druga Fc domena sadrže zamjenu jednog ili više od tri cisteinska ostatka u području zgloba serinom, gdje dodatno izborno prva i druga Fc domena sadrže mutaciju koju se bira iz skupine koju čine SCC, SSS (ostaci 220, 226, te 229), G236R, L328R, L234A, te L235A, čije je obrojčavanje u skladu s EU indeksom; po mogućnosti gdje prva i druga Fc domena sadrže mutaciju SCC (ostaci 220, 226, te 229); gdje obrojčavanje mutacija odgovara onom u SEQ ID NO: 45, čije je obrojčavanje u skladu s EU indeksom.
6. Heterodimer u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što (i) prva i druga Fc domena sadrže mutacije P238S i P331, čije je obrojčavanje u skladu s EU indeksom; (ii) gdje izborno prva Fc domena sadrži CH3 mutacije T350V, L351Y, F405A, te Y407V, a druga Fc domena sadrži CH3 mutacije T350V, T366L, K392L, T394W; gdje obrojčavanje mutacija odgovara onom u SEQ ID NO: 45, čije je obrojčavanje u skladu s EU indeksom.
7. Heterodimer u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je spojnička domena polipeptidna spojnica, poput spojnice Gly-Ser ili spojnice NLG (vdgasspvnvsspsvqdi).
8. Heterodimer u skladu s patentnim zahtjevom 1, naznačen time što sadrži prvi i drugi polipeptidni slijed, gdje prvi polipeptidni slijed sadrži aminokiselinski slijed iznijet u SEQ ID NO:5 ili aminokiselinski slijed koji je najmanje 90% istovjetan aminokiselinskom slijedu iznijetom u SEQ ID NO:5; a drugi polipeptidni slijed sadrži aminokiselinski slijed iznijet u SEQ ID NO:6 ili aminokiselinski slijed koji je najmanje 90% istovjetan aminokiselinskom slijedu iznijetom u SEQ ID NO:6.
9. Pripravak, naznačen time što sadrži heterodimer u skladu s bilo kojim od prethodnih patentnih zahtjeva i farmaceutski prihvatljivi nosač.
10. Molekula nukleinske kiseline, naznačena time što sadrži nukleotidni slijed koji kodira heterodimer u skladu s bilo kojim od patentnih zahtjeva 1 to 8.
11. Rekombinantni ekspresijski vektor, naznačen time što sadrži molekulu nukleinske kiseline u skladu s patentnim zahtjevom 10.
12. Stanica domaćin, naznačena time što je transformirana rekombinantnim ekspresijskim vektorom u skladu s patentnim zahtjevom 11.
13. Postupak dobivanja heterodimera u skladu s bilo kojim od patentnih zahtjeva 1-8, naznačen time što se sastoji u: osiguravanju stanice domaćina koja sadrži molekulu nukleinske kiseline koja sadrži nukleotidni slijed koji kodira heterodimer; i održavanju stanice domaćina u uvjetima u kojima se eksprimira heterodimer.
14. Heterodimer u skladu s bilo kojim od patentnih zahtjeva 1-8 ili pripravak u skladu s patentnim zahtjevom 9, namijenjeni upotrebi u postupku liječenja ili sprječavanja stanja povezanog s abnormalnim imunosnim odgovorom, naznačeni time što ih se na subjektu primijenjuje u djelotvornoj količini.
15. Heterodimer ili pripravak namijenjeni upotrebi u skladu s patentnim zahtjevom 14, naznačeni time što je stanje autoimuna bolest; gdje se autoimunu bolest može birati iz skupine koju čine dijabetes melitus ovisan o inzulinu, multipla skleroza, eksperimentalni autoimuni encefalomijelitis, reumatoid artritis, eksperimentalni autoimuni artritis, miastenija gravis, tiroiditis, eksperimentalni oblik uveoretinitisa, Hashimotov tiroiditis, primarni miksedem, tirotoksikoza, perniciozna anemija, autoimuni atrofični gastritis, Addisonova bolest, prerana menopauza, muška neplodnost, mladenački dijabetes, Goodpastureov sindrom, pemfigus vulgaris, pemfigoid, simpatička oftalmija, fakogeni uveitis, autoimuna hemolitička anemija, idiopatska leukopenija, primarna bilijarna ciroza, aktivni kronični hepatitis Hbs-ve, kriptogena ciroza, ulcerozni kolitis, Sjögrenov sindrom, skleroderma, Wegenerova granulomatoza, polimiozitis, dermatomiozitis, diskoidni LE, sistemni eritematozni lupus (SLE), te bolest vezivnog tkiva;
i gdje je po mogućnosti autoimuna bolest SLE ili Sjögrenov sindrom.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662357756P | 2016-07-01 | 2016-07-01 | |
| EP17743419.8A EP3478830B1 (en) | 2016-07-01 | 2017-06-30 | Optimized binuclease fusions and methods |
| PCT/US2017/040267 WO2018005954A2 (en) | 2016-07-01 | 2017-06-30 | Optimized binuclease fusions and methods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20240603T1 true HRP20240603T1 (hr) | 2024-07-19 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20240603TT HRP20240603T1 (hr) | 2016-07-01 | 2017-06-30 | Optimizirane fuzije binukleaze i postupci njihove upotrebe |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US20190241878A1 (hr) |
| EP (2) | EP4410378A3 (hr) |
| JP (3) | JP7308034B2 (hr) |
| CN (1) | CN109790526A (hr) |
| AU (2) | AU2017290389B2 (hr) |
| CA (1) | CA3029627A1 (hr) |
| DK (1) | DK3478830T3 (hr) |
| HR (1) | HRP20240603T1 (hr) |
| MA (1) | MA45554A (hr) |
| WO (1) | WO2018005954A2 (hr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2496691T3 (en) | 2009-11-02 | 2017-06-06 | Univ Washington | THERAPEUTIC NUCLEASE COMPOSITIONS AND PROCEDURES |
| HRP20240603T1 (hr) | 2016-07-01 | 2024-07-19 | Resolve Therapeutics, Llc | Optimizirane fuzije binukleaze i postupci njihove upotrebe |
| CN111315767A (zh) | 2017-08-22 | 2020-06-19 | 萨纳生物有限责任公司 | 可溶性干扰素受体及其用途 |
| SG11202106686PA (en) * | 2019-01-04 | 2021-07-29 | Resolve Therapeutics Llc | Treatment of sjogren's disease with nuclease fusion proteins |
| EP4090736A4 (en) * | 2020-01-11 | 2024-02-21 | Yale University | COMPOSITIONS AND METHODS FOR THE TREATMENT, RELIEF AND/OR PREVENTION OF ILLNESSES OR DISORDERS ASSOCIATED WITH DNASE1 AND/OR DNASE1L3 DEFICIENCY |
| AU2021288567A1 (en) * | 2020-06-08 | 2023-02-09 | Yale University | Compositions and methods for treating and/or preventing coagulopathy and/or sepsis in patients suffering from bacterial and/or viral infections |
| CN112322607B (zh) * | 2020-11-20 | 2023-03-28 | 江南大学 | 一种融合型腈水合酶及其应用 |
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-
2017
- 2017-06-30 HR HRP20240603TT patent/HRP20240603T1/hr unknown
- 2017-06-30 WO PCT/US2017/040267 patent/WO2018005954A2/en unknown
- 2017-06-30 JP JP2018569138A patent/JP7308034B2/ja active Active
- 2017-06-30 US US16/313,656 patent/US20190241878A1/en not_active Abandoned
- 2017-06-30 DK DK17743419.8T patent/DK3478830T3/da active
- 2017-06-30 MA MA045554A patent/MA45554A/fr unknown
- 2017-06-30 AU AU2017290389A patent/AU2017290389B2/en active Active
- 2017-06-30 EP EP24162480.8A patent/EP4410378A3/en active Pending
- 2017-06-30 CA CA3029627A patent/CA3029627A1/en active Pending
- 2017-06-30 EP EP17743419.8A patent/EP3478830B1/en active Active
- 2017-06-30 CN CN201780053637.9A patent/CN109790526A/zh active Pending
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2021
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2022
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| EP4410378A3 (en) | 2024-10-09 |
| WO2018005954A2 (en) | 2018-01-04 |
| JP2024026334A (ja) | 2024-02-28 |
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| US20190241878A1 (en) | 2019-08-08 |
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| AU2024219520A1 (en) | 2024-10-03 |
| AU2017290389A1 (en) | 2019-02-14 |
| EP3478830B1 (en) | 2024-04-10 |
| MA45554A (fr) | 2019-05-08 |
| DK3478830T3 (da) | 2024-05-21 |
| CN109790526A (zh) | 2019-05-21 |
| JP2022153588A (ja) | 2022-10-12 |
| CA3029627A1 (en) | 2018-01-04 |
| WO2018005954A3 (en) | 2018-03-29 |
| EP3478830A2 (en) | 2019-05-08 |
| EP4410378A2 (en) | 2024-08-07 |
| JP7308034B2 (ja) | 2023-07-13 |
| US12077790B2 (en) | 2024-09-03 |
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