US20110262385A1 - Use of interleukin-22 in the treatment of fatty liver disease - Google Patents

Use of interleukin-22 in the treatment of fatty liver disease Download PDF

Info

Publication number
US20110262385A1
US20110262385A1 US12/672,274 US67227408A US2011262385A1 US 20110262385 A1 US20110262385 A1 US 20110262385A1 US 67227408 A US67227408 A US 67227408A US 2011262385 A1 US2011262385 A1 US 2011262385A1
Authority
US
United States
Prior art keywords
fatty liver
cells
liver
use according
human
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US12/672,274
Other languages
English (en)
Inventor
Yu Liang HUANG
Zhi Hua Huang
Qi Sun
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Generon Shanghai Corp Ltd
Original Assignee
Generon Shanghai Corp Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Generon Shanghai Corp Ltd filed Critical Generon Shanghai Corp Ltd
Assigned to GENERON (SHANGHAI) CORPORATION reassignment GENERON (SHANGHAI) CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HUANG, YU LIANG, HUANG, ZHI HUA, SUN, QI
Publication of US20110262385A1 publication Critical patent/US20110262385A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • Fatty liver is a disease in which excessive amounts of lipids accumulate in the liver cells. Normally lipids account for 3%-4% of the total weight of the liver. If the amount of lipid goes beyond 5%, a fatty liver forms. Lipids may comprise up to 40%-50% of the liver weight in severe fatty liver diseases. Fatty liver mainly comes from the disorder of lipid metabolism of the liver. The main form of lipid in the liver is triglyceride, which is characterized by macrovesicular steatosis. Fatty liver can lead to fibrosis of liver, cirrhosis and hepatocellular carcinoma. In US, around 31% of the adults are indicated to have fatty liver by NMR.
  • available clinical therapeutic strategies include, antioxidant, e.g., vitamin C, vitamin E; compounds in methione metabolism, e.g., betaine; metformin, which can sensitize insulin, other similar medications include: thiazolidinediones (TZD), inhibitors of angiotension II receptor; urodeoxycholic acid, which has the effect of cell protection, anti-apoptosis and regulation of immunity; pentoxifylline, which can act by inhibiting inflammatory factors such as tumor necrosis factor (TNF)- ⁇ ; other medicaments such as troglitazone, rosiglitazone and pioglitazone. All the therapeutic methods are not satisfactory.
  • TNF tumor necrosis factor
  • IL-22 functions by binding to its receptor IL-22R1 and IL-22R2.
  • IL-22R1 is specific receptor for IL-22, which is mainly expressed in skin, kidney, digestive system (pancreas, intestine, liver, large intestine, and colon) and respiratory system (lung, bronchus).
  • IL-22R1 is specific receptor for IL-22, which is mainly expressed in skin, kidney, digestive system (pancreas, intestine, liver, large intestine, and colon) and respiratory system (lung, bronchus).
  • A Oil Red O stained liver section of ob/ob mice (control);
  • FIG. 8A shows that treatment of high fat diet-induced FLD rats reduced body weight
  • FIG. 12 shows electron microscopy imaging of liver sections showing the size of fat droplets in hepatocytes.
  • IL-22 refers to a protein, which has essentially the same amino acid sequence as the human/murine IL-22 as described by Dumoutier in U.S. Pat. No. 6,359,117 and the same biological activity as natural IL-22.
  • IL-22 of the present invention includes but is not limited to human IL-22, recombinant human IL-22, murine IL-22 and recombinant murine IL-22.
  • subject refers to mice, human or other mammal animals.
  • therapeutically effective amount refers to an amount of IL-22 which can achieve the goal of therapy. It is to be understood by one of ordinary skill in the art that, therapeutically effective dose may change, depending on the routes of administration, the types of other ingredients used and the combination with other medicaments.
  • IL-22 of the present invention is expressed by recombinant gene clone technique.
  • the expression system includes prokaryotic cells, yeast or higher eukaryotic cells.
  • Suitable prokaryotic cell includes, but is not limited to G + or G ⁇ bacteria, such as E. coli .
  • Available strains of E. coli includes K12MM294 (ATCC 31,446), X1776 (ATCC 31,537), W3110 (ATCC 27,325) and K5772 (ATCC 53,635) etc.
  • Other suitable prokaryotic expression system includes, but is not limited to Erwinia, Klebsiella, Proteus, Salmonella , such as Salmonella typhimurium, Serratia such as Serratia marcescans, Shigella, B. subtilis, B. licheniformis, Pseudomonas such as P. aeruginosa and Streptomyces.
  • E. coli W3110 is preferred since it is often used as the host cell for
  • Host cells used to express glycosylated IL-22 of the present invention are mainly derived from multicellular organism.
  • invertebrate include insect, such as Drosophila S2 and Spodoptera Sf9, plant cells.
  • Suitable mammalian cells include Chinese Hamster Ovary (CHO), COS cells, in particular, SV40-transformed CV1 cell line (COS-7, ATCC CRL 1651); human embryo kidney cell line 293 (Graham et al., J. Gen Virol., 36:59 (1997)); CHO/-DHFR (Urlaub and Chasin, Proc. Natl. Acad. Sci. USA, 77:4216 (1980)); murine Sertoli cell (TM4, Mather, Biol.
  • nucleic acid micro-injection electroporation
  • bacterial protoplast fusion with intact cells or polycations
  • polycations such as polybrene, polyornithine
  • Keown et al. Methods in Enzymology, 185:527-537 (1990) and Mansour et al., Nature, 336:348-352 (1988).
  • Some other inducible yeast promoter can regulate transcription according to different growing conditions, including promoters for alcohol dehydrogenase 2, isocytochrome c, acid phosphatase, degrading enzymes related to degradation of nitrogen, Metallothionein, Glyceraldehyde-3-Phosphate, degrading enzymes of maltose and galactose.
  • promoters for alcohol dehydrogenase 2, isocytochrome c, acid phosphatase, degrading enzymes related to degradation of nitrogen, Metallothionein, Glyceraldehyde-3-Phosphate, degrading enzymes of maltose and galactose Detailed description of vectors and promoters suitable for yeast expression system can be seen in EP 73,657.
  • Enhancer is a kind of cis-acting element of DNA molecules, usually 10-300 bp, which can enhance the transcription of DNA molecules by acting on the promoters. Numbers of enhancers known enhancers are from mammalian gene, e.g. haptoglobin, elastase, albumin, ⁇ -fetoprotein and insulin.
  • the IL-22 encoding DNA sequence of the present invention can be used in gene therapy.
  • Gene therapy includes traditional therapy, which has long term effects after one time therapy and administration of gene therapy drugs, in which effective DNA or mRNA are administered one or several times.
  • Antisense RNA or DNA may also be used as gene therapy drugs to block the expression of some genes. It has been demonstrated that antisense oligonucleotide can act as inhibitors in cells, although they are only adsorbed by cell membrane to a limited extent and have a low concentration in cells (Zamecnik et al., Proc. Natl. Acad. Sci. USA 83:4143-4146 [1986]).
  • the absorbance of oligonucleotides may be improved by modification, such as substituent of the negative charged phosphodiester by balance charged groups.
  • micro-capsule containing IL-22 of the present invention can be used as sustained release system.
  • Sustained release micro-capsule system of recombinant protein has been successfully applied to rhGH, rhIFN, IL-2 and MNrgp 120 (Johnson et al., Nat. Med., 2:795-799 (1996); Yasuda, Biomed. Ther 27:1221-1223 (1993); WO 97/03692, WO 96/40072, WO 96/07399; U.S. Pat. No. 5,654,010).
  • IL-22 has the effect of treating fatty liver diseases. 2. IL-22 has the effect of decreasing levels of transaminases (especially, aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT).
  • transaminases especially, aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT).
  • Both human IL-22 and murine IL-22 were verified by DNA sequencing, as shown in FIG. 1 and FIG. 2 .
  • E. coli strain BL21(+) was used to express the recombinant protein.
  • the E. coli cells were homogenized under high pressure.
  • IL-22 inclusion bodies were obtained by centrifugation and washed with buffers (Tris-HCl 50 mM, NaCl 100 mM, EDTA 1 mM, DTT 1 mM, and sodium deoxycholate 0.5%) completely.
  • Inclusion bodies were solubilized in 8M urea, 50 mM Mes, 10 mM EDTA, and 0.1 mM DTT, pH 6.5.
  • Inclusion bodies was refolded 4 times for 20 hours in 100 mM Tris-HCl, 2 mM EDTA, 0.5 M L-arginine, 1 mM reduced glutathion, and 0.1 mM oxidized glutathion, pH 8. The mixture was then concentrated and purified using a Superdex75 (Amersham) column chromatography. The protein was eluted with 20 mM Tris-HCl, 50 mM NaCl, pH 7. The purity of IL-22 was determined by SDS-PAGE (>95%) as shown in FIG. 3 and FIG. 4 . IL-22 protein aliquot was stored at ⁇ 80° C.
  • the recombinant murine IL-22 obtained in example 2 was injected to obese ob/ob mice (8-12 weeks, 35-50 g) at a dose of 300 ⁇ g/kg/d for 14 days. Same amount of vehicle solution (0.1% BSA, PBS) was injected to the mice in control groups. The animals were sacrificed at day 15 and the serum was collected. Levels of serum ALT and AST were determined. The results are shown in FIG. 5 .
  • the recombinant murine IL-22 obtained in example 2 was injected to obese ob/ob mice (8-12 weeks, 35-50 g) at a dose of 300 ⁇ g/kg/d for 14 days. Same amount of vehicle solution (0.1% BSA, PBS) was injected to the mice in control groups. The animals were sacrificed at day 15. The liver was collected and fixed in 10% formalin. Tissue section was stained with Hematoxylin-Eosin. The results were shown in FIG. 6 .

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US12/672,274 2007-08-06 2008-08-01 Use of interleukin-22 in the treatment of fatty liver disease Abandoned US20110262385A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CNCN200710044592.7 2007-08-06
CN2007100445927A CN101361968B (zh) 2007-08-06 2007-08-06 白介素-22在治疗脂肪肝中的应用
PCT/US2008/071859 WO2009020844A1 (en) 2007-08-06 2008-08-01 Use of interleukin-22 in the treatment of fatty liver disease

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/071859 A-371-Of-International WO2009020844A1 (en) 2007-08-06 2008-08-01 Use of interleukin-22 in the treatment of fatty liver disease

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US14/483,175 Division US20140377222A1 (en) 2007-08-06 2014-09-11 Use of interleukin-22 in the treatment of fatty liver disease

Publications (1)

Publication Number Publication Date
US20110262385A1 true US20110262385A1 (en) 2011-10-27

Family

ID=40341656

Family Applications (3)

Application Number Title Priority Date Filing Date
US12/672,274 Abandoned US20110262385A1 (en) 2007-08-06 2008-08-01 Use of interleukin-22 in the treatment of fatty liver disease
US14/483,175 Abandoned US20140377222A1 (en) 2007-08-06 2014-09-11 Use of interleukin-22 in the treatment of fatty liver disease
US15/694,670 Active US10786551B2 (en) 2007-08-06 2017-09-01 Use of interleukin-22 in the treatment of fatty liver disease

Family Applications After (2)

Application Number Title Priority Date Filing Date
US14/483,175 Abandoned US20140377222A1 (en) 2007-08-06 2014-09-11 Use of interleukin-22 in the treatment of fatty liver disease
US15/694,670 Active US10786551B2 (en) 2007-08-06 2017-09-01 Use of interleukin-22 in the treatment of fatty liver disease

Country Status (7)

Country Link
US (3) US20110262385A1 (th)
EP (1) EP2185202B1 (th)
JP (1) JP5546453B2 (th)
CN (1) CN101361968B (th)
AU (1) AU2008284116B2 (th)
CA (1) CA2695734C (th)
WO (1) WO2009020844A1 (th)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9273108B2 (en) 2010-05-25 2016-03-01 Generon (Shanghai) Corporation Ltd. Recombinant human G-CSF dimer and use thereof for the treatment of neurological diseases
US9352024B2 (en) 2011-12-27 2016-05-31 Generon (Shanghai) Corporation Ltd. Uses of interleukin-22(IL-22) in treating and preventing nerve damage diseases or neurodegenerative diseases
US9629898B2 (en) 2010-08-31 2017-04-25 Generon (Shanghai) Corporation, Ltd. Use of interleukin-22 in treating viral hepatitis
US9642917B2 (en) 2011-07-25 2017-05-09 Generon (Shanghai) Corporation, Ltd. Use of G-CSF dimer in preparation of medicament for treatment of neurodegenerative diseases
US10543169B2 (en) 2013-11-07 2020-01-28 Generon (Shanghai) Corporation Ltd. Use of IL-22 dimer in manufacture of a medicament for intravenous administration
US10695406B2 (en) 2014-05-27 2020-06-30 The University Of Queensland Modulation of cellular stress using a B-cell oxidative and/or endoplasmic reticulum stress inhibitor and a targeting agent
US10786551B2 (en) 2007-08-06 2020-09-29 Generon (Shanghai) Corporation Ltd. Use of interleukin-22 in the treatment of fatty liver disease
US11510966B2 (en) 2016-04-15 2022-11-29 Evive Biotechnology (Shanghai) Ltd Use of IL-22 in treating necrotizing enterocolitis

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11246915B2 (en) 2010-09-15 2022-02-15 Applied Molecular Transport Inc. Cholix toxin-derived fusion molecules for oral delivery of biologically active cargo
CN105541978B (zh) 2010-09-15 2019-12-13 兰德尔·J·米斯尼 使用细菌毒素衍生的转运序列递送生物活性剂的系统和方法
DK2970422T3 (en) 2013-03-15 2018-07-16 Hoffmann La Roche IL-22 POLYPEPTIDES AND IL-22 FC-FUSION PROTEINS AND METHODS OF USE
CA2948346C (en) 2014-05-07 2023-06-27 Applied Molecular Transport Llc Cholix toxin-derived fusion molecules for oral delivery of biologically active cargo
AU2016229982B2 (en) 2015-03-09 2020-06-18 Intekrin Therapeutics, Inc. Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy
EP3606527A1 (en) 2017-04-03 2020-02-12 Coherus Biosciences, Inc. Ppar-gamma agonist for treatment of progressive supranuclear palsy
WO2020097394A1 (en) 2018-11-07 2020-05-14 Applied Molecular Transport Inc. Delivery constructs for transcytosis and related methods
BR112021009001A8 (pt) 2018-11-07 2021-10-26 Applied Molecular Transport Inc Veículos derivados de cholix para administração oral de carga útil heteróloga
CA3150859A1 (en) 2019-08-16 2021-02-25 Applied Molecular Transport Inc. Compositions, formulations, and interleukin production and purification
WO2022050230A1 (ja) * 2020-09-03 2022-03-10 学校法人埼玉医科大学 アデノシン受容体の活性化を抑制する組成物

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006073508A1 (en) * 2005-01-04 2006-07-13 Generon Corporation Use of il-22 for the treatment of conditions of metabolic disorders

Family Cites Families (78)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
US4657760A (en) 1979-03-20 1987-04-14 Ortho Pharmaceutical Corporation Methods and compositions using monoclonal antibody to human T cells
JPS6023084B2 (ja) 1979-07-11 1985-06-05 味の素株式会社 代用血液
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
ZA811368B (en) 1980-03-24 1982-04-28 Genentech Inc Bacterial polypedtide expression employing tryptophan promoter-operator
NZ201705A (en) 1981-08-31 1986-03-14 Genentech Inc Recombinant dna method for production of hepatitis b surface antigen in yeast
US4640835A (en) 1981-10-30 1987-02-03 Nippon Chemiphar Company, Ltd. Plasminogen activator derivatives
US4943529A (en) 1982-05-19 1990-07-24 Gist-Brocades Nv Kluyveromyces as a host strain
US4713339A (en) 1983-01-19 1987-12-15 Genentech, Inc. Polycistronic expression vector construction
AU2353384A (en) 1983-01-19 1984-07-26 Genentech Inc. Amplification in eukaryotic host cells
AU3145184A (en) 1983-08-16 1985-02-21 Zymogenetics Inc. High expression of foreign genes in schizosaccharomyces pombe
US4496689A (en) 1983-12-27 1985-01-29 Miles Laboratories, Inc. Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer
US4879231A (en) 1984-10-30 1989-11-07 Phillips Petroleum Company Transformation of yeasts of the genus pichia
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4965188A (en) 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
EP0206448B1 (en) 1985-06-19 1990-11-14 Ajinomoto Co., Inc. Hemoglobin combined with a poly(alkylene oxide)
US5206344A (en) 1985-06-26 1993-04-27 Cetus Oncology Corporation Interleukin-2 muteins and polymer conjugation thereof
WO1987005330A1 (en) 1986-03-07 1987-09-11 Michel Louis Eugene Bergh Method for enhancing glycoprotein stability
US4849227A (en) 1986-03-21 1989-07-18 Eurasiam Laboratories, Inc. Pharmaceutical compositions
GB8610600D0 (en) 1986-04-30 1986-06-04 Novo Industri As Transformation of trichoderma
US4791192A (en) 1986-06-26 1988-12-13 Takeda Chemical Industries, Ltd. Chemically modified protein with polyethyleneglycol
US5010182A (en) 1987-07-28 1991-04-23 Chiron Corporation DNA constructs containing a Kluyveromyces alpha factor leader sequence for directing secretion of heterologous polypeptides
DE3889546T2 (de) 1987-12-21 1994-09-08 Univ Toledo Transformation von keimenden pflanzensamen mit hilfe von agrobacterium.
AU4005289A (en) 1988-08-25 1990-03-01 Smithkline Beecham Corporation Recombinant saccharomyces
US5225538A (en) 1989-02-23 1993-07-06 Genentech, Inc. Lymphocyte homing receptor/immunoglobulin fusion proteins
ATE144281T1 (de) 1989-04-28 1996-11-15 Rhein Biotech Proz & Prod Gmbh Hefezellen der gattung-schwanniomyces
EP0402226A1 (en) 1989-06-06 1990-12-12 Institut National De La Recherche Agronomique Transformation vectors for yeast yarrowia
FR2649120B1 (fr) 1989-06-30 1994-01-28 Cayla Nouvelle souche et ses mutants de champignons filamenteux, procede de production de proteines recombinantes a l'aide de ladite souche et souches et proteines obtenues selon ce procede
US5225212A (en) 1989-10-20 1993-07-06 Liposome Technology, Inc. Microreservoir liposome composition and method
EP1013270A3 (en) 1992-12-02 2001-03-28 Alkermes Controlled Therapeutics, Inc. Controlled release growth hormone containing microspheres
US5951974A (en) 1993-11-10 1999-09-14 Enzon, Inc. Interferon polymer conjugates
US5446090A (en) 1993-11-12 1995-08-29 Shearwater Polymers, Inc. Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules
AU1684195A (en) 1994-02-22 1995-09-04 Georgia Tech Research Corporation Reduction of friction during wire drawing
EP0779806B2 (en) 1994-09-09 2008-04-16 Takeda Pharmaceutical Company Limited Sustained release preparation containing metal salt of a peptide
DK0831787T3 (da) 1995-06-07 2001-12-17 Alkermes Inc Sammensætning til vedvarende frigivelse af humant væksthormon
ZA965368B (en) 1995-07-14 1997-01-14 Novo Nordisk As A pharmaceutical formulation
US6551799B2 (en) * 1999-12-07 2003-04-22 Genentech, Inc. Interleukin-22 polypeptides, nucleic acids encoding the same and methods for the treatment of pancreatic disorders
US20010023070A1 (en) 1998-05-29 2001-09-20 Reinhard Ebner Interleukins-21 and 22
US20030003545A1 (en) 1998-05-29 2003-01-02 Reinhard Ebner Interleukins-21 and 22
CN1238367C (zh) 1998-10-26 2006-01-25 路德维格癌症研究院 分离的编码t细胞诱导因子(tif)的核酸分子,其编码蛋白及其应用
US6274710B1 (en) 1998-10-26 2001-08-14 Ludwig Institute For Cancer Research Antibodies which specifically bind T Cell inducible factors (TIFs)
US7307161B1 (en) 1999-04-28 2007-12-11 Genetics Institute, Llc Human Gil-19/AE289 polynucleotides
US7226591B2 (en) 2000-05-22 2007-06-05 Genentech, Inc. Interleukin-22 polypeptides, nucleic acids encoding the same and methods for the treatment of pancreatic disorders
CN1163263C (zh) 2000-01-07 2004-08-25 华中理工大学 一种多肽类药物口腔喷雾剂
GB0024442D0 (en) 2000-10-05 2000-11-22 Isis Innovation Genetic factors affecting the outcome of viral infections
CN1335182A (zh) 2001-08-08 2002-02-13 华中科技大学 胰岛素口腔喷剂及其制备工艺
US6797493B2 (en) 2001-10-01 2004-09-28 Lee-Hwei K. Sun Fc fusion proteins of human granulocyte colony-stimulating factor with increased biological activities
MXPA04004266A (es) 2001-11-06 2004-07-08 Lilly Co Eli Uso de il-19, il-22 e il-24 para tratar trastornos hematopoyeticos.
EP1463752A4 (en) 2001-12-21 2005-07-13 Human Genome Sciences Inc ALBUMIN FUSION PROTEINS
CN1176137C (zh) 2002-01-15 2004-11-17 泛亚生物技术有限公司 多臂树杈型功能化聚乙二醇制备方法及它在药物中的应用
US7597876B2 (en) 2007-01-11 2009-10-06 Immunomedics, Inc. Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules
US20030235561A1 (en) 2002-06-25 2003-12-25 Cell Based Delivery Inc. Vascularized organized tissues and uses thereof
US20050148029A1 (en) 2003-09-29 2005-07-07 Biosite, Inc. Methods and compositions for determining treatment regimens in systemic inflammatory response syndromes
BRPI0416240A (pt) 2003-11-05 2007-01-09 Inst Rech Developpement Ird usos de um ou vários agonistas de famìlia de receptores de receptores de formil peptìdeo e semelhante a receptores de formil peptìdeo, composições farmecêuticas para evitar ou tratar infecções virais ou retro-virais, e, método para favorecer a resistência inata de hospedeiros a infecções virais
BRPI0507680A (pt) 2004-02-13 2007-07-17 Nod Pharmaceuticals Inc partìculas de fosfato de cálcio terapêuticas e métodos de fabricação e uso das mesmas
US7670595B2 (en) 2004-06-28 2010-03-02 Merck Patent Gmbh Fc-interferon-beta fusion proteins
EP2322553A3 (en) 2005-02-14 2011-11-16 Wyeth LLC Interleukin-17F antibodies and other IL-17F signaling antagonists and uses therefor
AU2006304605A1 (en) * 2005-10-17 2007-04-26 Institute For Systems Biology Tissue-and serum-derived glycoproteins and methods of their use
UA95613C2 (ru) * 2005-11-09 2011-08-25 Уеллстат Терепьютикс Корпорейшн Соединения для лечения расстройсв метаболизма
WO2007115230A2 (en) 2006-03-30 2007-10-11 University Of Medicine And Dentistry Of New Jersey A strategy for homo- or hetero-dimerization of various proteins in solutions and in cells
WO2007123765A2 (en) 2006-03-31 2007-11-01 Human Genome Sciences Inc. Neutrokine-alpha and neutrokine-alpha splice variant
CN101472611A (zh) 2006-06-19 2009-07-01 惠氏公司 调节il-22和il-17的方法
WO2008085229A2 (en) 2006-11-15 2008-07-17 Arteriocyte Inc. Cell-based therapies for treating liver disease
CN101361968B (zh) 2007-08-06 2011-08-03 健能隆医药技术(上海)有限公司 白介素-22在治疗脂肪肝中的应用
WO2009041734A1 (ja) 2007-09-26 2009-04-02 Kyowa Hakko Kirin Co., Ltd. ヒトトロンボポエチン受容体に対するアゴニスト抗体
CN101225110B (zh) 2007-10-23 2010-10-20 中国人民解放军军事医学科学院基础医学研究所 人白细胞介素-22突变体及其构建方法和应用
CN101168049A (zh) * 2007-10-23 2008-04-30 中国人民解放军军事医学科学院基础医学研究所 白介素-22在制备治疗肝病药物中的应用及其制备方法
AU2008323770B2 (en) 2007-11-07 2014-08-07 Genentech, Inc. Compositions and methods for treatment of microbial disorders
US8956605B2 (en) 2009-01-12 2015-02-17 Generon (Shanghai) Corporation Prevention and/or treatment of multiple organ dysfunction syndrome with interleukin-22
US20130121959A1 (en) 2010-01-13 2013-05-16 Joseph R. Maxwell Il-22-fc and hepcidin activity
CN102380091A (zh) 2010-08-31 2012-03-21 健能隆医药技术(上海)有限公司 白介素-22在治疗病毒性肝炎中的应用
CN103182072B (zh) 2011-12-27 2017-05-03 健能隆医药技术(上海)有限公司 白介素‑22在治疗和预防神经损伤疾病或神经退行性疾病中的用途
DK2970422T3 (en) 2013-03-15 2018-07-16 Hoffmann La Roche IL-22 POLYPEPTIDES AND IL-22 FC-FUSION PROTEINS AND METHODS OF USE
CN106029100A (zh) 2013-11-07 2016-10-12 纪念斯隆–凯特林癌病中心 在胃肠道移植物抗宿主病的治疗中使用il-22的方法
CN104623637A (zh) 2013-11-07 2015-05-20 健能隆医药技术(上海)有限公司 Il-22二聚体在制备静脉注射药物中的应用
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
WO2017181143A1 (en) 2016-04-15 2017-10-19 Generon (Shanghai) Corporation, Ltd. Use of il-22 in treating necrotizing enterocolitis

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006073508A1 (en) * 2005-01-04 2006-07-13 Generon Corporation Use of il-22 for the treatment of conditions of metabolic disorders

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Pan et al. (2004), Cellular and Molecular Immunology, Vol. 1(1), pp43-49. *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10786551B2 (en) 2007-08-06 2020-09-29 Generon (Shanghai) Corporation Ltd. Use of interleukin-22 in the treatment of fatty liver disease
US9273108B2 (en) 2010-05-25 2016-03-01 Generon (Shanghai) Corporation Ltd. Recombinant human G-CSF dimer and use thereof for the treatment of neurological diseases
US9629898B2 (en) 2010-08-31 2017-04-25 Generon (Shanghai) Corporation, Ltd. Use of interleukin-22 in treating viral hepatitis
US9642917B2 (en) 2011-07-25 2017-05-09 Generon (Shanghai) Corporation, Ltd. Use of G-CSF dimer in preparation of medicament for treatment of neurodegenerative diseases
US9352024B2 (en) 2011-12-27 2016-05-31 Generon (Shanghai) Corporation Ltd. Uses of interleukin-22(IL-22) in treating and preventing nerve damage diseases or neurodegenerative diseases
US10543169B2 (en) 2013-11-07 2020-01-28 Generon (Shanghai) Corporation Ltd. Use of IL-22 dimer in manufacture of a medicament for intravenous administration
US11654104B2 (en) 2013-11-07 2023-05-23 Evive Biotechnology (Shanghai) Ltd Use of IL-22 dimer in manufacture of a medicament for intravenous administration
US10695406B2 (en) 2014-05-27 2020-06-30 The University Of Queensland Modulation of cellular stress using a B-cell oxidative and/or endoplasmic reticulum stress inhibitor and a targeting agent
US11510966B2 (en) 2016-04-15 2022-11-29 Evive Biotechnology (Shanghai) Ltd Use of IL-22 in treating necrotizing enterocolitis

Also Published As

Publication number Publication date
EP2185202A1 (en) 2010-05-19
AU2008284116A1 (en) 2009-02-12
EP2185202B1 (en) 2015-05-06
EP2185202A4 (en) 2013-11-06
CA2695734A1 (en) 2009-02-12
CN101361968B (zh) 2011-08-03
US20140377222A1 (en) 2014-12-25
AU2008284116B2 (en) 2014-01-09
JP5546453B2 (ja) 2014-07-09
WO2009020844A1 (en) 2009-02-12
JP2010535786A (ja) 2010-11-25
US10786551B2 (en) 2020-09-29
US20180028614A1 (en) 2018-02-01
CN101361968A (zh) 2009-02-11
CA2695734C (en) 2017-02-14

Similar Documents

Publication Publication Date Title
US10786551B2 (en) Use of interleukin-22 in the treatment of fatty liver disease
US7718604B2 (en) Use of IL-22 for the treatment of conditions of metabolic disorders
US20230301901A1 (en) Use of il-22 dimer in manufacture of a medicament for intravenous administration
JP6325585B2 (ja) インターロイキン−22のウイルス性肝炎の治療における応用
CN101219208B (zh) 白介素-22的医药用途
JPH0680584A (ja) グリセンチンを有効成分とする医薬
JPH03127741A (ja) 悪性腫瘍治療剤

Legal Events

Date Code Title Description
AS Assignment

Owner name: GENERON (SHANGHAI) CORPORATION, CHINA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:HUANG, YU LIANG;HUANG, ZHI HUA;SUN, QI;REEL/FRAME:025770/0862

Effective date: 20100205

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION