KR20180030180A - Il22 면역컨쥬게이트 - Google Patents

Il22 면역컨쥬게이트 Download PDF

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Publication number
KR20180030180A
KR20180030180A KR1020187004633A KR20187004633A KR20180030180A KR 20180030180 A KR20180030180 A KR 20180030180A KR 1020187004633 A KR1020187004633 A KR 1020187004633A KR 20187004633 A KR20187004633 A KR 20187004633A KR 20180030180 A KR20180030180 A KR 20180030180A
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South Korea
Prior art keywords
ser
conjugate
gly
leu
thr
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KR1020187004633A
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English (en)
Korean (ko)
Inventor
프란치스카 소피 부츠
다리오 네리
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필로겐 에스.피.에이.
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Priority claimed from GBGB1512486.0A external-priority patent/GB201512486D0/en
Priority claimed from GBGB1517649.8A external-priority patent/GB201517649D0/en
Priority claimed from GBGB1521470.3A external-priority patent/GB201521470D0/en
Application filed by 필로겐 에스.피.에이. filed Critical 필로겐 에스.피.에이.
Publication of KR20180030180A publication Critical patent/KR20180030180A/ko
Withdrawn legal-status Critical Current

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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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • 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
    • A61K47/6813—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin the drug being a peptidic cytokine, e.g. an interleukin or interferon
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • 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
    • A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • 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
    • A61P1/04—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/626—Diabody or triabody
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Cell Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Dermatology (AREA)
KR1020187004633A 2015-07-16 2016-07-15 Il22 면역컨쥬게이트 Withdrawn KR20180030180A (ko)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
GBGB1512486.0A GB201512486D0 (en) 2015-07-16 2015-07-16 IL22 immunoconjugates
GB1512486.0 2015-07-16
GB1517649.8 2015-10-06
GBGB1517649.8A GB201517649D0 (en) 2015-10-06 2015-10-06 IL22 Immunoconjugates
GBGB1521470.3A GB201521470D0 (en) 2015-12-04 2015-12-04 IL22 immunoconjugates
GB1521470.3 2015-12-04
PCT/EP2016/066979 WO2017009469A1 (en) 2015-07-16 2016-07-15 Il22 immunoconjugates

Publications (1)

Publication Number Publication Date
KR20180030180A true KR20180030180A (ko) 2018-03-21

Family

ID=56413683

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020187004633A Withdrawn KR20180030180A (ko) 2015-07-16 2016-07-15 Il22 면역컨쥬게이트

Country Status (21)

Country Link
US (2) US10246502B2 (cg-RX-API-DMAC10.html)
EP (1) EP3322719B1 (cg-RX-API-DMAC10.html)
JP (1) JP6735822B2 (cg-RX-API-DMAC10.html)
KR (1) KR20180030180A (cg-RX-API-DMAC10.html)
CN (1) CN108137667A (cg-RX-API-DMAC10.html)
AU (1) AU2016293114A1 (cg-RX-API-DMAC10.html)
BR (1) BR112018000909A2 (cg-RX-API-DMAC10.html)
CA (1) CA2992366A1 (cg-RX-API-DMAC10.html)
CL (1) CL2018000131A1 (cg-RX-API-DMAC10.html)
CO (1) CO2018000414A2 (cg-RX-API-DMAC10.html)
CR (1) CR20180087A (cg-RX-API-DMAC10.html)
DO (1) DOP2018000019A (cg-RX-API-DMAC10.html)
EC (1) ECSP18010616A (cg-RX-API-DMAC10.html)
ES (1) ES2778430T3 (cg-RX-API-DMAC10.html)
HK (1) HK1250237A1 (cg-RX-API-DMAC10.html)
IL (1) IL256849A (cg-RX-API-DMAC10.html)
MX (1) MX2018000687A (cg-RX-API-DMAC10.html)
PE (1) PE20180797A1 (cg-RX-API-DMAC10.html)
PH (1) PH12018500131A1 (cg-RX-API-DMAC10.html)
RU (1) RU2018105687A (cg-RX-API-DMAC10.html)
WO (1) WO2017009469A1 (cg-RX-API-DMAC10.html)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3091139A1 (en) * 2018-02-21 2019-08-29 Genentech, Inc. Dosing for treatment with il-22 fc fusion proteins
WO2020249757A1 (en) 2019-06-14 2020-12-17 Philogen S.P.A Immunoconjugates comprising a single chain diabody and interleukin-15 or interleukin-15 and a sushi domain of interleukin-15 receptor alpha
EP4185615A1 (en) 2020-07-22 2023-05-31 Philogen S.p.A. Treatment of pulmonary hypertension
US12240879B2 (en) 2020-07-30 2025-03-04 Anwita Biosciences, Inc. Interleukin-22 fusion proteins, and their pharmaceutical compositions
WO2022073038A1 (en) * 2020-10-02 2022-04-07 Abbvie Inc. Interleukin-22 (il-22) fusion proteins and uses thereof
CN115703841A (zh) * 2021-08-10 2023-02-17 复旦大学 白介素17a抗体与白介素22细胞因子融合蛋白及其制备方法与用途
US20250197485A1 (en) 2022-03-17 2025-06-19 Universitätsklinikum Jena Anti-ED-A Antibodies for the Treatment of Pulmonary Hypertension
WO2025101842A1 (en) * 2023-11-09 2025-05-15 Flagship Pioneering Innovations Vii, Llc Compositions and methods for targeted delivery of therapeutic agents
WO2026003203A1 (en) 2024-06-27 2026-01-02 Philogen S.P.A. Combination of an immunocytokine comprising targeted il2 and a jak inhibitor

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2552590A1 (en) 2004-01-05 2005-07-21 Emd Lexigen Research Center Corp. Interleukin-12 targeted to oncofoetal fibronectin
EP1831254B1 (en) 2004-12-23 2012-06-06 Molmed SpA Conjugation product
US20060263368A1 (en) * 2005-01-10 2006-11-23 Research Development Foundation Targeted chimeric molecules for cancer therapy
MX2007013875A (es) 2005-05-11 2008-01-28 Philogen Spa Proteinas de fusion del anticuerpo l19 contra fibronectina ed-b e interlucina 12.
CA2682851C (en) 2007-04-02 2017-01-17 Philogen S.P.A. A novel antigen associated with the neovasculature of tumour metastases
EA017995B1 (ru) 2007-07-25 2013-04-30 Филоджен С.П.А. Антиген, связанный с вариантами рака легкого и лимфомами
EP2209805B1 (en) 2007-10-30 2017-09-06 Philogen S.p.A. An antigen associated with rheumatoid arthritis
US20130121959A1 (en) 2010-01-13 2013-05-16 Joseph R. Maxwell Il-22-fc and hepcidin activity
TWI500427B (zh) * 2010-05-14 2015-09-21 Abbvie Inc Ｉｌ－１結合蛋白
PL2970422T3 (pl) * 2013-03-15 2018-09-28 F.Hoffmann-La Roche Ag Polipeptydy IL-22 i białka fuzyjne IL-22 Fc i sposoby zastosowania
JP2016519111A (ja) * 2013-04-26 2016-06-30 フィロゲン エスピーエー 細胞外マトリックス成分に対する抗体にコンジュゲートしたｉｌ４
CN104623639A (zh) * 2013-11-07 2015-05-20 健能隆医药技术（上海）有限公司 白介素22二聚体在制备治疗胰腺炎药物中的应用

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CA2992366A1 (en) 2017-01-19
CO2018000414A2 (es) 2018-04-10
BR112018000909A2 (pt) 2018-09-11
US10246502B2 (en) 2019-04-02
CR20180087A (es) 2018-05-14
US10858411B2 (en) 2020-12-08
JP2018525032A (ja) 2018-09-06
AU2016293114A1 (en) 2018-02-01
DOP2018000019A (es) 2018-10-15
RU2018105687A (ru) 2019-08-16
EP3322719B1 (en) 2019-12-18
PH12018500131A1 (en) 2018-07-23
EP3322719A1 (en) 2018-05-23
US20170305989A1 (en) 2017-10-26
CL2018000131A1 (es) 2018-06-01
PE20180797A1 (es) 2018-05-09
HK1250237A1 (zh) 2018-12-07
US20190169250A1 (en) 2019-06-06
JP6735822B2 (ja) 2020-08-05
ES2778430T3 (es) 2020-08-10
ECSP18010616A (es) 2018-04-30
IL256849A (en) 2018-03-29
WO2017009469A1 (en) 2017-01-19
CN108137667A (zh) 2018-06-08
MX2018000687A (es) 2018-08-01

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