HRP20220091T1 - Inzulin-fc fuzijski proteini ultradugog djelovanja i postupci uporabe - Google Patents
Inzulin-fc fuzijski proteini ultradugog djelovanja i postupci uporabe Download PDFInfo
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- HRP20220091T1 HRP20220091T1 HRP20220091TT HRP20220091T HRP20220091T1 HR P20220091 T1 HRP20220091 T1 HR P20220091T1 HR P20220091T T HRP20220091T T HR P20220091TT HR P20220091 T HRP20220091 T HR P20220091T HR P20220091 T1 HRP20220091 T1 HR P20220091T1
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- 108020001507 fusion proteins Proteins 0.000 title claims 39
- 102000037865 fusion proteins Human genes 0.000 title claims 39
- 241001465754 Metazoa Species 0.000 claims 8
- 210000004027 cell Anatomy 0.000 claims 7
- 102000004877 Insulin Human genes 0.000 claims 5
- 108090001061 Insulin Proteins 0.000 claims 5
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims 4
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims 4
- 239000002299 complementary DNA Substances 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 238000010254 subcutaneous injection Methods 0.000 claims 3
- 239000007929 subcutaneous injection Substances 0.000 claims 3
- 210000004369 blood Anatomy 0.000 claims 2
- 239000008280 blood Substances 0.000 claims 2
- 239000000710 homodimer Substances 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 210000002966 serum Anatomy 0.000 claims 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- 102000003746 Insulin Receptor Human genes 0.000 claims 1
- 108010001127 Insulin Receptor Proteins 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 239000011324 bead Substances 0.000 claims 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 230000003442 weekly effect Effects 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/22—Affinity chromatography or related techniques based upon selective absorption processes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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
- C07K16/2869—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
-
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
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- General Engineering & Computer Science (AREA)
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Claims (27)
1. Fuzijski protein koji se sastoji od polipeptida inzulina i Fc fragmenta, pri čemu su polipeptid inzulina i Fc fragment povezani veznikom, kao što je peptidni veznik, pri čemu Fc fragment sadrži sljedeću sekvencu:
[image]
i polipeptid inzulina sadrži sljedeću sekvencu:
FVNQHLCGSX1LVEALALVCGERGFHYGGGGGGSGGGGGIVEQCCX2STCSLDQLENYC (SEQ ID NO: 10).
gdje X1 nije D, a X2 nije H.
2. Fuzijski protein prema zahtjevu 1, naznačen time što polipeptid inzulina sadrži sljedeću sekvencu:
FVNQHLCGSX1LVEALALVCGERGFHYGGGGGGSGGGGGIVEQCCX2STCSLDQLENYC (SEQ ID NO: 10).
gdje je X1 H, a X2 je T.
3. Fuzijski protein prema zahtjevima 1 ili 2, naznačen time što su polipeptid inzulina i Fc fragment povezani veznikom, kao što je peptidni veznik, koji sadrži sljedeću sekvencu:
GGGGGQGGGGQGGGGQGGGGG (SEQ ID NO: 14).
4. Fuzijski protein prema zahtjevu 1, naznačen time što fuzijski protein sadrži sljedeću sekvencu:
[image]
5. Fuzijski protein prema bilo kojem od zahtjeva 1-5 sadrži domene u sljedećoj orijentaciji od N- do C-terminusa: (N-terminus) – polipeptid inzulina-veznik--Fc fragment--(C-terminus).
6. Fuzijski protein prema bilo kojem od zahtjeva 1-5 sadrži domene u sljedećoj orijentaciji od (N-terminus)--B-lanca-C-lanca-A-lanca-veznik-Fc fragment-(C- terminus).
7. Fuzijski protein prema bilo kojem od prethodnih zahtjeva, naznačen time što je fuzijski protein homodimer.
8. Fuzijski protein prema zahtjevu 7 naznačen time što je postotak homodimera fuzijskog proteina veći od 90%.
9. Fuzijski protein prema bilo kojem od prethodnih zahtjeva, naznačen time što je fuzijski protein napravljen korištenjem HEK293 stanica, i rezultirajući titar homodimera nakon pročišćavanja korištenjem zrnca proteina A ili stupca proteina A veći je od 50 mg/L.
10. Fuzijski protein prema bilo kojem od prethodnih zahtjeva, naznačen time da je IC50 receptora inzulina za fuzijski protein manji ili jednak 5000 nM.
11. Fuzijski protein prema bilo kojem od prethodnih zahtjeva, naznačen time što je poluživot fuzijskog proteina u serumu u krvi ili serumu ciljne životinje nakon davanja dulje od oko 3 dana.
12. Fuzijski protein prema bilo kojem od prethodnih zahtjeva, naznačen time što je vrijeme tijekom kojeg postoji statistički značajno smanjenje razine glukoze u krvi kod subjekta u odnosu na razinu pred-doze duže od jednog od 2 sata, 6 sati, 9 sati, 12 sati, 18 sati, 1 dan, 1.5 dana, 2 dana, 2.5 dana, 3 dana, 4 dana, 5 dana, 6 dana, 7 dana, ili duže.
13. Fuzijski protein prema bilo kojem od prethodnih zahtjeva naznačen time što je NAOC nakon prve supkutane injekcije u ciljnoj životinji veći od 150 %FBGL·dani·kg/mg.
14. Fuzijski protein prema bilo kojem od prethodnih zahtjeva naznačen time što je omjer NAOC nakon treće tjedne potkožne injekcije fuzijskog proteina u ciljnu životinju prema NAOC-u nakon prve supkutane injekcije fuzijskog proteina u ciljnoj životinji veći od 0.50.
15. Fuzijski protein prema bilo kojem od zahtjeva 1-14, naznačen time što je fuzijski protein formuliran kao farmaceutski pripravak.
16. Fuzijski protein prema zahtjevu 15 naznačen time što je fuzijski protein prisutan u farmaceutskom pripravku u koncentraciji od oko 3 mg/mL ili većoj.
17. Fuzijski protein prema zahtjevima 15 ili 16 naznačen time što je pripravak prikladan za supkutanu primjenu.
18. Fuzijski protein prema bilo kojem od zahtjeva 1-6 ili njegov farmaceutski pripravak za uporabu u liječenju dijabetesa u ciljne životinje.
19. Fuzijski protein za uporabu prema zahtjevu 18, naznačen time što je ciljna životinja pas.
20. Fuzijski protein za uporabu prema zahtjevima 18 ili 19, naznačen time što se fuzijski protein primjenjuje supkutano.
21. Fuzijski protein za uporabu prema zahtjevu 20, naznačen time što se fuzijski protein daje dnevno, dva puta tjedno, ili jednom tjedno ciljnoj životinji.
22. Fuzijski protein za uporabu prema zahtjevu 21, naznačen time što se fuzijski protein daje jednom tjedno ciljnoj životinji u dozi između 0.025 i 0.5 mg/kg/tjedno.
23. Stanica projektirana za ekspresiju fuzijskog proteina prema bilo kojem od zahtjeva 1-6.
24. Stanica prema zahtjevu 23 naznačena time što je stanica transficirana nukleinskom kiselinom koja kodira fuzijski protein.
25. Stanica prema zahtjevu 24 naznačena time što je stanica HEK293 stanica ili CHO stanica.
26. cDNA koja kodira fuzijski protein prema bilo kojem od zahtjeva 1-6.
27. cDNA prema zahtjevu 26 naznačena time što cDNA sadrži sljedeću sekvencu nukleinske kiseline:
[image]
Applications Claiming Priority (17)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862692498P | 2018-06-29 | 2018-06-29 | |
| US201862692507P | 2018-06-29 | 2018-06-29 | |
| US201862693814P | 2018-07-03 | 2018-07-03 | |
| US201862696645P | 2018-07-11 | 2018-07-11 | |
| US201862698648P | 2018-07-16 | 2018-07-16 | |
| US201862702167P | 2018-07-23 | 2018-07-23 | |
| US201862719347P | 2018-08-17 | 2018-08-17 | |
| US201862740735P | 2018-10-03 | 2018-10-03 | |
| US201862743358P | 2018-10-09 | 2018-10-09 | |
| US201862774682P | 2018-12-03 | 2018-12-03 | |
| US201862781378P | 2018-12-18 | 2018-12-18 | |
| US201862781368P | 2018-12-18 | 2018-12-18 | |
| US201962824176P | 2019-03-26 | 2019-03-26 | |
| US201962827809P | 2019-04-01 | 2019-04-01 | |
| US201962837188P | 2019-04-22 | 2019-04-22 | |
| EP19826154.7A EP3655006B1 (en) | 2018-06-29 | 2019-06-28 | Ultra-long acting insulin-fc fusion proteins and methods of use |
| PCT/US2019/040010 WO2020006529A1 (en) | 2018-06-29 | 2019-06-28 | Ultra-long acting insulin-fc fusion proteins and methods of use |
Publications (1)
| Publication Number | Publication Date |
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| HRP20220091T1 true HRP20220091T1 (hr) | 2022-04-15 |
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Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
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| HRP20220091TT HRP20220091T1 (hr) | 2018-06-29 | 2019-06-28 | Inzulin-fc fuzijski proteini ultradugog djelovanja i postupci uporabe |
| HRP20240408TT HRP20240408T1 (hr) | 2018-06-29 | 2019-06-28 | Inzulin-fc fuzijski proteini ultradugog djelovanja i metode uporabe |
| HRP20221418TT HRP20221418T1 (hr) | 2018-06-29 | 2019-06-28 | Inzulin-fc fuzijski proteini ultra-dugog djelovanja i postupci uporabe |
| HRP20230991TT HRP20230991T1 (hr) | 2018-06-29 | 2019-06-28 | Inzulin-fc fuzijski proteini ultradugog djelovanja i metode uporabe |
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| HRP20240408TT HRP20240408T1 (hr) | 2018-06-29 | 2019-06-28 | Inzulin-fc fuzijski proteini ultradugog djelovanja i metode uporabe |
| HRP20221418TT HRP20221418T1 (hr) | 2018-06-29 | 2019-06-28 | Inzulin-fc fuzijski proteini ultra-dugog djelovanja i postupci uporabe |
| HRP20230991TT HRP20230991T1 (hr) | 2018-06-29 | 2019-06-28 | Inzulin-fc fuzijski proteini ultradugog djelovanja i metode uporabe |
Country Status (15)
| Country | Link |
|---|---|
| US (8) | US10947292B2 (hr) |
| EP (5) | EP4011908B1 (hr) |
| JP (2) | JP7417277B2 (hr) |
| KR (1) | KR20210029210A (hr) |
| CN (1) | CN113038964A (hr) |
| AU (1) | AU2019291945A1 (hr) |
| BR (1) | BR112020026777A2 (hr) |
| CA (1) | CA3104144A1 (hr) |
| DK (4) | DK3655006T3 (hr) |
| FI (2) | FI4186920T3 (hr) |
| HR (4) | HRP20220091T1 (hr) |
| HU (4) | HUE065725T2 (hr) |
| LT (4) | LT3892628T (hr) |
| SI (4) | SI3892628T1 (hr) |
| WO (1) | WO2020006529A1 (hr) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3551209T3 (da) | 2016-12-09 | 2021-08-23 | Akston Biosciences Corp | Insulin-fc-fusioner og fremgangsmåder til anvendelse |
| US11267862B2 (en) | 2018-06-29 | 2022-03-08 | Akston Biosciences Corporation | Ultra-long acting insulin-Fc fusion proteins and methods of use |
| LT3892628T (lt) | 2018-06-29 | 2022-12-12 | Akston Biosciences Corporation | Itin ilgai veikiantys insulino-fc sulieti baltymai ir naudojimo būdai |
| WO2021011827A1 (en) * | 2019-07-16 | 2021-01-21 | Akston Biosciences Corporation | Ultra-long acting insulin-fc fusion proteins and methods of use |
| US11352407B2 (en) | 2019-12-19 | 2022-06-07 | Akston Biosciences Corporation | Ultra-long acting insulin-Fc fusion proteins |
| US11186623B2 (en) | 2019-12-24 | 2021-11-30 | Akston Bioscience Corporation | Ultra-long acting insulin-Fc fusion proteins and methods of use |
| EP4248983A3 (en) | 2020-04-10 | 2024-01-24 | Akston Biosciences Corporation | Antigen specific immunotherapy for covid-19 fusion proteins and methods of use |
| US11192930B2 (en) | 2020-04-10 | 2021-12-07 | Askton Bioscences Corporation | Ultra-long acting insulin-Fc fusion protein and methods of use |
| US11198719B2 (en) | 2020-04-29 | 2021-12-14 | Akston Biosciences Corporation | Ultra-long acting insulin-Fc fusion protein and methods of use |
| EP4230216A1 (en) * | 2020-07-24 | 2023-08-23 | Jiangsu Gensciences Inc. | Insulin-fc fusion protein and application thereof |
| TW202237175A (zh) * | 2020-12-14 | 2022-10-01 | 美商美國禮來大藥廠 | 治療糖尿病之方法 |
| WO2023004406A2 (en) | 2021-07-23 | 2023-01-26 | Akston Biosciences Corporation | Insulin-fc fusion proteins and methods of use to treat cancer |
| WO2023064711A2 (en) * | 2021-10-14 | 2023-04-20 | Akston Biosciences Corporation | Ultra-long acting insulin-fc fusion proteins and methods of use |
| AR127619A1 (es) | 2021-11-15 | 2024-02-14 | Lilly Co Eli | FORMULACIONES CONSERVADAS DE FUSIONES DE INSULINA-Fc |
| TW202342552A (zh) * | 2022-03-16 | 2023-11-01 | 大陸商北京拓界生物醫藥科技有限公司 | 人胰島素類似物、其融合蛋白及醫藥用途 |
| WO2023247640A1 (en) * | 2022-06-23 | 2023-12-28 | Sanofi | Single chain insulins and fc conjugates thereof |
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| US20030040601A1 (en) | 2001-06-08 | 2003-02-27 | Ivan Diers | Method for making insulin precursors and insulin analog precursors |
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