WO2002080958A1 - Interferon supercompose de recombinaison utilise comme inhibiteur de l'antigene de surface et de l'antigene e de l'hepatite b - Google Patents
Interferon supercompose de recombinaison utilise comme inhibiteur de l'antigene de surface et de l'antigene e de l'hepatite b Download PDFInfo
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- WO2002080958A1 WO2002080958A1 PCT/CN2002/000128 CN0200128W WO02080958A1 WO 2002080958 A1 WO2002080958 A1 WO 2002080958A1 CN 0200128 W CN0200128 W CN 0200128W WO 02080958 A1 WO02080958 A1 WO 02080958A1
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- interferon
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- hepatitis
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- highly efficient
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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
- C07K14/555—Interferons [IFN]
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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
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- Recombinant high-efficiency complex interferon is used as hepatitis B surface antigen and e-antigen inhibitor
- the present invention relates to the application of a recombinant and highly efficient interferon by changing the spatial structure of a protein, and is characterized in that as a preparation, it not only inhibits hepatitis B virus DNA, but also inhibits HBsAg and HBeAg. Background technique
- Recombinant high-efficiency compound interferon is a new type of interferon molecule constructed by genetic engineering from the most common conserved amino acid structure in several natural human ⁇ -interferon subtypes. This type of interferon is described in US Patent Nos. 4,756,623 and 4897471. Interferon has been described, rSIFN-co has been proven to have a broad spectrum of interferon activity, and has strong antiviral and antitumor and natural killer cell activities. US Patent No. 5,372,808 discloses the use of recombinant and highly effective interferon to treat diseases. Methods: Chinese patent 97193506.8 discloses a method for treating hepatitis C again by using a recombinant high-efficiency compound interferon.
- Chinese patent 98114663.5 publicly discloses a method for preparing the recombinant high-efficiency compound interferon and the use for treating hepatitis B and hepatitis C.
- the US Food and Drug Administration (FDA) has approved rSIFN-co produced by E. coli in the United States for the treatment of clinical hepatitis C patients at the end of 1997.
- hepatitis B patients For the diagnosis of hepatitis B patients, when the surface antigen (HBsAg) positive and e antigen (HBeAg) positive are detected, they can be judged as hepatitis B patients.
- various types of ⁇ -interferon are used in chronic hepatitis B clinically.
- the treatment mechanism for hepatitis patients is: Interferon binds to special membrane receptors on the cell surface to exert its anti-DNA and RNA effects. This includes the induction of certain enzymes to prevent virus replication in virus-infected cells. However, all interferons can only inhibit viral DNA and RNA, not e-antigen and s-antigen. Summary of the Invention
- the present invention surprisingly found that a recombinant highly efficient interferon that changes the spatial structure of a protein, as a preparation, not only inhibits hepatitis B virus DNA, but also inhibits HBsAg and HBeAg, thereby proving that the recombinant highly efficient interferon can By inhibiting hepatitis B virus DNA and inhibiting The hepatitis B HBsAg antigen and HBeAg antigen achieve the purpose of treating hepatitis B.
- the purpose of the present invention is to provide a recombinant and highly effective interferon drug for treating hepatitis B.
- this drug not only the viral DNA is inhibited, but also the hepatitis B surface antigen and the hepatitis B e antigen are reduced to normal levels. To achieve the purpose of treatment.
- the invention is achieved by:
- a recombinant highly efficient interferon having a sequence as shown in FIG. 1 is first prepared by gene recombination technology.
- the recombination technology of the present invention uses E. coli to preferentially express codons, and to ensure that the amino acid sequence is unchanged, the DNA coding sequence is performed. After redesigning, the full-length cDNA of rSIFN-co was artificially synthesized.
- the present invention uses recombinant DNA technology to clone the full-length rSIFN-co cDNA sequence into a highly efficient expression vector of E. coli, and then uses the L-arabinose induction / activation expression regulation mechanism to activate the strong P BAD promoter in the vector to mediate downstream rSIFN-co gene is highly expressed.
- This arabinose induction / activation expression control system has obvious advantages over the temperature control, pH control, and IPTG induction systems commonly used in genetic engineering production: (1) Several control systems commonly used are “de-repressed” The "form releases the inhibitory effect on the functional promoter, so that the promoter can mediate the expression of downstream genes.
- an arabinose induction / activation system is used to establish an efficient and stable rSIFN-co expressing E. coli engineering strain.
- the application method of the present invention is to use a recombinant high-efficiency complex interferon to achieve therapeutic purposes for patients.
- the recombinant high-efficiency complex interferon used by patients can be made into various dosage forms such as tablets, capsules, oral solutions, patches, injections, sprays, Suppositories, solution preparations, the recommended formulation is injection, which can be administered subcutaneously or intravenously.
- the carrier in the pharmaceutical composition can use any suitable acceptable pharmaceutical carrier. These carriers can be sugars, cellulose products, adhesives Mixtures, disintegrants, lubricants, fillers, solubilizers, buffers, preservatives, thickeners, complexing agents and other adjuvants.
- Figure 1 DNA coding sequence and deduced amino acid sequence for rSIFN-co
- the present invention verifies the inhibitory effect of recombinant high-efficiency complex interferon that changes the spatial conformation on hepatitis B virus DNA, surface antigen and e antigen through the following experiments.
- the experimental method is as follows:
- Solvent and preparation method When preparing the test drug, add 1 ml of physiological saline to each raw material bottle, and after dissolving, dissolve it in MEM culture solution according to the concentration difference of the different dose groups set. Active use.
- Control drug The interference energy of IFN-ot2b produced by Schering is a lyophilized preparation. Each 3 ⁇ 10 6 U experiment was prepared with a culture solution into a 3 ⁇ 10 6 IU / ml solution. Ganjin produced by Amgen is an injection. Each 9 ⁇ ⁇ , 0.3ml, equivalent to 9 X 10 6 IU / branch, the culture solution was used to prepare a 9X 10 0 IU / ml solution in the experiment, stored in a refrigerator at 4 ° C, 2.2.15 cells: Hepatitis B virus (HBV ) DNA clone was transfected into 2.2.15 cell line of human hepatoma cell line (Hep G2) and constructed by Mount Sinai Medical Center.
- HBV Hepatitis B virus
- HBeAg solid-phase radioimmunoassay kit purchased from Northern Institute of Immunology, China Isotope Company; Kanamycin, a product from North China Pharmaceutical Factory; Lipofectin, a product from Gibco, USA. ,
- 2.2.15 Cell Culture Add 0.25% trypsin to the culture flask with 2.2.15 cells. 37. C digestion for 3 minutes, pipetted with culture medium, passaged at 1: 3, and grown for 10 days.
- Drug-to-cytotoxicity test The experiment was divided into a drug-free cell control group and a different drug concentration administration group. Cells were digested and formulated into 100,000 cells per milliliter, inoculated into culture plates, 200 ⁇ l per well in a 96-well plate, and cultured at 37 ° C and 5% CO 2 for 24 hours. The cells were grown into a monolayer for experiments.
- High-efficiency recombination and high-efficiency complex interferon was prepared into a L8x10 7 IU / ml solution with a culture solution, diluted twice and added to a 96-well cell culture plate, 3 holes per concentration, and the same concentration of drug solution was changed every 4 days, with the observation of cell lesions as indicators, 8 Observe the cytopathic effect under the microscope, the complete destruction is 4; 75% is 3; 50% is 2; 25% is 1; no lesion is 0. Calculate the average degree of cytopathy and% inhibition of each concentration of drug solution. The Reed Muench method was used to calculate the half toxic concentration (TC50) and the maximum non-toxic concentration (TC0).
- TC50 Antilog (B + —— xC)
- A log> 50% drug concentration
- B log ⁇ 50% drug concentration
- C log dilution factor on HBeAg, HBsAg inhibition test: The test consists of HBeAg, HBsAg positive control group, negative control group, cell control group and different drug concentrations group. 700,000 2.2.15 cells per ml were inoculated into a 6-well cell culture plate, 3 ml per well, and cultured at 37 ° C and 5% CO 2 for 24 hours, and the test solution was diluted 3 times below the non-toxic concentration, and the five dilutions were 4.5 X 10 6 IU / ml, 1.5 X 10 6 IU / ml, 0.5 X 10 6 IU / ml, 0.17
- HBsAg and HBeAg were determined by the Northern Immune Reagent Research Institute of China Isotope Company, and the solid-phase radioimmunoassay box was used for the determination.
- Southern blot @ 2.2.15 intracellular 13 ⁇ 4 ⁇ ⁇ 0 ⁇ Extraction: 2.2.15 cells were cultured for 8 days after dosing, the cells were aspirated to collect cells, cell lysate was added, cells were lysed, and equal volume of phenol: chloroform: iso The amyl alcohol was extracted twice, centrifuged at 10,000 g at high speed, the supernatant was taken out, the nucleic acid was precipitated by adding absolute ethanol, vacuum-dried, and redissolved in 20 ⁇ 1 TE buffer. 2 Electrophoresis: Add 6X DNA sample buffer, and add the sample to 1.5% agarose gel for electrophoresis, IV / cm, constant pressure, 14-18 hours.
- Denaturation and hybridization Immerse the glue in HC1, denaturing solution and neutralizing solution. 4 Transfer the membrane: Transfer the DNA to Hybond-N membrane according to the procedure. Blotting, blotting, and exposure with spot blotting. The scanner scans the light sheet and analyzes the relative density with gel-pro analysis software to calculate the inhibition rate and IC50.
- Compound interferon has obvious activity of inhibiting hepatitis B surface antigen and e antigen, while the control group interfering energy and Ganfujin do not have the above activities.
- Clinical cases have also confirmed that patients with chronic active hepatitis B can reduce or return to normal levels of hepatitis B surface antigen and e antigen by taking recombinant high-efficiency compound interferon.
- the recombinant high-efficiency compound interferon preparation applied by the present invention can be prepared by the following examples:
- Preparation process Weigh according to the prescription, dissolve with sterile pyrogen-free injection water, sterilize and filter with a 0.22 ⁇ pore size filter membrane, and store at 8 ⁇ 2 ° C. Take a sample for sterility and pyrogen inspection after passing the test. Packed in vials, single-dose 1.0ml bottles. After packaging, place them in a lyophilizer and freeze-dry.
- Preparation process Weigh according to the prescription, dissolve with sterile pyrogen-free injection water, sterilize and filter with a 0.22 ⁇ m pore size filter membrane, and store at 8 ⁇ 2 ° C. After sampling for sterility and pyrogen inspection, Dispensed in a closed container. Divide into a vial, and store a single dose of 1.0 mL of each bottle in a dark place at 2-10 ° C. Table 1: Test results of rSIFN-co on hepatitis B surface antigen and e-antigen inhibition rate The first batch of experiments
- E antigen IC50 mean 450.2434 standard deviation 132.315479
- Surface antigen IC50 mean 649.1894 standard deviation 42.29580
Description
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Priority Applications (17)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002578997A JP4617058B2 (ja) | 2001-02-28 | 2002-02-28 | コンセンサスインターフェロンのB型肝炎表面抗原とe抗原の抑制剤としての応用 |
DE60234085T DE60234085D1 (de) | 2001-02-28 | 2002-02-28 | Rekombinantes super-verbindungs-interferon zur verwendung als hepatitis b oberflächenatigen und e-antigen-inhibitor |
EP02702211A EP1371373B1 (en) | 2001-02-28 | 2002-02-28 | Recombination super compound interferon used as hepatitis b surface antigen and e antigen inhibitor |
AT02702211T ATE446104T1 (de) | 2001-02-28 | 2002-02-28 | Rekombinantes super-verbindungs-interferon zur verwendung als hepatitis b oberflächenatigen und e-antigen-inhibitor |
CA002439503A CA2439503A1 (en) | 2001-02-28 | 2002-02-28 | Recombination super compound interferon used as hepatitis b surface antigen and e antigen inhibitor |
US10/650,365 US7364724B2 (en) | 2001-02-28 | 2003-08-28 | Recombinant super-compound interferon |
AU2003248419A AU2003248419B2 (en) | 2001-02-28 | 2003-09-26 | Recombinant super-compound interferon |
HK04104296.9A HK1061201A1 (en) | 2001-02-28 | 2004-06-15 | Recombination super compound interferon used as hepatitis b surface antigen and e antigen inhibitor |
US10/927,975 US20050079579A1 (en) | 2001-02-28 | 2004-08-26 | Uses of spatial configuration to modulate protein function |
US11/077,813 US20060035327A1 (en) | 2001-02-28 | 2005-03-10 | Recombinant super-compound interferon and uses thereof |
US12/105,455 US8114395B2 (en) | 2001-02-28 | 2008-04-18 | Treatment of viral diseases with recombinant interferon α |
US12/246,153 US8551469B2 (en) | 2001-02-28 | 2008-10-06 | Treatment of tumors and viral diseases with recombinant interferon alpha |
US12/889,521 US20110070195A1 (en) | 2001-02-28 | 2010-09-24 | Uses of spatial configuration to modulate protein function |
US13/019,044 US8425896B2 (en) | 2001-02-28 | 2011-02-01 | Treatment of tumors with recombinant interferon alpha |
US13/923,378 US20130281667A1 (en) | 2001-02-28 | 2013-06-21 | Uses of spatial configuration to modulate protein function |
US14/019,519 US9944686B2 (en) | 2001-02-28 | 2013-09-05 | Treatment of tumors with recombinant interferon alpha |
US15/910,165 US20180258151A1 (en) | 2001-02-28 | 2018-03-02 | Recombinant super-compound interferon and uses thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB011043679A CN1245215C (zh) | 2001-02-28 | 2001-02-28 | 重组高效复合干扰素用作乙型肝炎表面抗原和e抗原抑制剂 |
CN01104367.9 | 2001-02-28 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/650,365 Continuation-In-Part US7364724B2 (en) | 2001-02-28 | 2003-08-28 | Recombinant super-compound interferon |
Publications (1)
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WO2002080958A1 true WO2002080958A1 (fr) | 2002-10-17 |
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PCT/CN2002/000128 WO2002080958A1 (fr) | 2001-02-28 | 2002-02-28 | Interferon supercompose de recombinaison utilise comme inhibiteur de l'antigene de surface et de l'antigene e de l'hepatite b |
Country Status (10)
Country | Link |
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US (3) | US7364724B2 (zh) |
EP (1) | EP1371373B1 (zh) |
JP (1) | JP4617058B2 (zh) |
CN (1) | CN1245215C (zh) |
AT (1) | ATE446104T1 (zh) |
AU (1) | AU2003248419B2 (zh) |
CA (1) | CA2439503A1 (zh) |
DE (1) | DE60234085D1 (zh) |
HK (1) | HK1061201A1 (zh) |
WO (1) | WO2002080958A1 (zh) |
Cited By (8)
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WO2005034853A3 (en) * | 2003-08-28 | 2006-04-27 | Huiyangtech Usa Inc | Uses of interferons with altered spatial structure |
JP2008532995A (ja) * | 2005-03-09 | 2008-08-21 | ウェイ グアンウェン | 組換え高効率複合インターフェロンの使用方法 |
US7585647B2 (en) | 2003-08-28 | 2009-09-08 | Guangwen Wei | Nucleic acid encoding recombinant interferon |
JP2011103899A (ja) * | 2003-06-05 | 2011-06-02 | Ajinomoto Co Inc | 目的物質の製造法 |
US8114395B2 (en) | 2001-02-28 | 2012-02-14 | Sichuan Biotechnology Research Center | Treatment of viral diseases with recombinant interferon α |
US8551469B2 (en) | 2001-02-28 | 2013-10-08 | Superlab Far East Limited | Treatment of tumors and viral diseases with recombinant interferon alpha |
KR101431172B1 (ko) * | 2003-08-28 | 2014-08-19 | 수퍼랩 파 이스트 리미티드 | 변경된 공간 구조를 갖는 인터페론의 용도 |
US10874716B2 (en) | 2013-01-07 | 2020-12-29 | Superlab Far East Limited | Methods and compositions for treatment of bone, skin, subcutaneous, mucosal and/or submucosal cancer by percutaneous and/or transmucosal administration of interferon |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050079579A1 (en) * | 2001-02-28 | 2005-04-14 | Guangwen Wei | Uses of spatial configuration to modulate protein function |
US20060035327A1 (en) * | 2001-02-28 | 2006-02-16 | Guangwen Wei | Recombinant super-compound interferon and uses thereof |
AU2011202683B2 (en) * | 2003-08-28 | 2012-08-09 | Superlab Far East Limited | Uses of interferons with altered spatial structure |
CN1740197B (zh) * | 2004-08-26 | 2010-05-12 | 辉阳科技美国公司 | 具有全新空间构象且功效增强的重组干扰素、其制备方法及应用 |
CN101525381B (zh) * | 2008-03-04 | 2012-04-18 | 北京百川飞虹生物科技有限公司 | 一种重组复合干扰素及其表达载体的构建和表达 |
CN102101886A (zh) * | 2009-12-18 | 2011-06-22 | 四川辉阳生命工程股份有限公司 | 构象改变的重组干扰素晶体、其三维结构及应用 |
WO2013055811A1 (en) * | 2011-10-12 | 2013-04-18 | Hitachi Chemical Co., Ltd. | Ex vivo methods of predicting responsiveness of a subject to interferon therapy |
US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
UY34401A (es) | 2011-10-21 | 2013-05-31 | Abbvie Inc | Métodos para el tratamiento de hcv |
DE202012012956U1 (de) | 2011-10-21 | 2014-10-16 | Abbvie Inc. | Kombination aus mindestens zwei direkt wirkenden antiviralen Wirkstoffen für die Verwendung zur Behandlung von HCV, umfassend Ribavirin aber nicht Interferon |
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WO2017189978A1 (en) | 2016-04-28 | 2017-11-02 | Emory University | Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1983004053A1 (en) * | 1982-05-06 | 1983-11-24 | Applied Molecular Genetics, Inc. | The manufacture and expression of large structural genes |
WO1993021229A1 (en) * | 1992-04-15 | 1993-10-28 | Amgen Inc. | Methods and compositions for the treatment of diseases with interferon while reducing side effects |
Family Cites Families (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
ZA828917B (en) | 1981-12-07 | 1983-09-28 | Hoffmann La Roche | Crystalline human leukocyte interferon |
US4672108A (en) | 1981-12-07 | 1987-06-09 | Hoffmann-La Roche Inc. | Crystalline human leukocyte interferon |
US4462940A (en) * | 1982-09-23 | 1984-07-31 | Cetus Corporation | Process for the recovery of human β-interferon-like polypeptides |
US4681930A (en) | 1983-09-20 | 1987-07-21 | Hoffmann-La Roche Inc. | Immune interferon and a method for its extraction and purification |
US5441734A (en) | 1993-02-25 | 1995-08-15 | Schering Corporation | Metal-interferon-alpha crystals |
EP0626448A3 (de) * | 1993-05-26 | 1998-01-14 | BOEHRINGER INGELHEIM INTERNATIONAL GmbH | Verfahren zur Herstellung und Reinigung von alpha-Interferon |
DE4329756A1 (de) | 1993-09-03 | 1995-03-09 | Boehringer Ingelheim Int | Verfahren zur Herstellung und Reinigung von alpha-Interferon |
US5766582A (en) | 1994-10-11 | 1998-06-16 | Schering Corporation | Stable, aqueous alfa interferon solution formulations |
TW426523B (en) | 1995-04-06 | 2001-03-21 | Hoffmann La Roche | Interferon solution |
CA2232230C (en) | 1995-10-13 | 2005-06-28 | Ralph H. Lambalot | Phosphopantetheinyl transferases and uses thereof |
US5972331A (en) | 1995-12-22 | 1999-10-26 | Schering Corporation | Crystalline interferon alpha for pulmonary delivery and method for producing the same |
US5874304A (en) | 1996-01-18 | 1999-02-23 | University Of Florida Research Foundation, Inc. | Humanized green fluorescent protein genes and methods |
US5980884A (en) | 1996-02-05 | 1999-11-09 | Amgen, Inc. | Methods for retreatment of patients afflicted with Hepatitis C using consensus interferon |
US6532437B1 (en) | 1996-10-23 | 2003-03-11 | Cornell Research Foundation, Inc. | Crystalline frap complex |
CN1186120A (zh) | 1996-12-24 | 1998-07-01 | 深圳科兴生物制品有限公司 | 在大肠杆菌中表达作为分泌的重组人干扰素α1b蛋白 |
US6114145A (en) * | 1997-12-05 | 2000-09-05 | Human Genome Sciences, Inc. | Synferon, a synthetic interferon |
US6087478A (en) | 1998-01-23 | 2000-07-11 | The Rockefeller University | Crystal of the N-terminal domain of a STAT protein and methods of use thereof |
JP2004510681A (ja) | 1998-02-06 | 2004-04-08 | イレクサス・ピーティーワイ・リミテッド | Fc受容体の三次元構造およびモデル並びにその使用 |
CN1062565C (zh) | 1998-06-29 | 2001-02-28 | 深圳九先生物工程有限公司 | 重组人α型复合干扰素及其制备方法和用途 |
KR100399156B1 (ko) | 1999-11-19 | 2003-09-26 | 주식회사 엘지생명과학 | α-인터페론의 용액제형 |
CN1175901C (zh) | 1999-12-06 | 2004-11-17 | 天津华立达生物工程有限公司 | 一种稳定的干扰素水溶液 |
US20020043262A1 (en) * | 2000-08-22 | 2002-04-18 | Alan Langford | Spray device |
US7544354B2 (en) * | 2000-10-27 | 2009-06-09 | Novartis Vaccines And Diagnostics | Methods of protein purification and recovery |
EP1355939A2 (en) | 2000-11-03 | 2003-10-29 | Pestka Biomedical Laboratories, Inc. | Interferons, uses and compositions related thereto |
CN1245215C (zh) | 2001-02-28 | 2006-03-15 | 四川省生物工程研究中心 | 重组高效复合干扰素用作乙型肝炎表面抗原和e抗原抑制剂 |
US6546074B1 (en) | 2001-03-27 | 2003-04-08 | Astex Technology Limited | Protein crystal structure and method for identifying protein modulators |
CN1375502A (zh) | 2001-10-25 | 2002-10-23 | 南京药科大学 | 聚乙二醇修饰重组人干扰素 |
US6807478B2 (en) * | 2001-12-27 | 2004-10-19 | Koninklijke Philips Electronics N.V. | In-building navigation system |
CN1176946C (zh) | 2002-05-16 | 2004-11-24 | 中国人民解放军第二军医大学 | 一种新型α干扰素 |
CN1202861C (zh) | 2003-07-18 | 2005-05-25 | 中国科学院微生物研究所 | 复合干扰素在治疗sars疾病中的用途 |
PL2325202T3 (pl) | 2003-08-28 | 2015-03-31 | Superlab Far East Ltd | Zastosowania interferonów o zmienionej strukturze przestrzennej |
WO2005067963A1 (en) | 2003-12-23 | 2005-07-28 | Intermune, Inc. | Use of polyethylene glycol-modified interferon-alpha in therapeutic dosing regimens |
MY167668A (en) | 2005-03-09 | 2018-09-21 | Superlab Far East Ltd | Uses of recombinant super-compound interferons |
-
2001
- 2001-02-28 CN CNB011043679A patent/CN1245215C/zh not_active Expired - Lifetime
-
2002
- 2002-02-28 AT AT02702211T patent/ATE446104T1/de not_active IP Right Cessation
- 2002-02-28 EP EP02702211A patent/EP1371373B1/en not_active Expired - Lifetime
- 2002-02-28 WO PCT/CN2002/000128 patent/WO2002080958A1/zh active Application Filing
- 2002-02-28 JP JP2002578997A patent/JP4617058B2/ja not_active Expired - Lifetime
- 2002-02-28 DE DE60234085T patent/DE60234085D1/de not_active Expired - Lifetime
- 2002-02-28 CA CA002439503A patent/CA2439503A1/en not_active Abandoned
-
2003
- 2003-08-28 US US10/650,365 patent/US7364724B2/en not_active Expired - Lifetime
- 2003-09-26 AU AU2003248419A patent/AU2003248419B2/en not_active Expired
-
2004
- 2004-06-15 HK HK04104296.9A patent/HK1061201A1/xx not_active IP Right Cessation
-
2008
- 2008-04-18 US US12/105,455 patent/US8114395B2/en not_active Expired - Fee Related
-
2011
- 2011-02-01 US US13/019,044 patent/US8425896B2/en not_active Expired - Lifetime
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1983004053A1 (en) * | 1982-05-06 | 1983-11-24 | Applied Molecular Genetics, Inc. | The manufacture and expression of large structural genes |
WO1993021229A1 (en) * | 1992-04-15 | 1993-10-28 | Amgen Inc. | Methods and compositions for the treatment of diseases with interferon while reducing side effects |
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US8551469B2 (en) | 2001-02-28 | 2013-10-08 | Superlab Far East Limited | Treatment of tumors and viral diseases with recombinant interferon alpha |
US8425896B2 (en) | 2001-02-28 | 2013-04-23 | Sichuan Biotechnology Research Center | Treatment of tumors with recombinant interferon alpha |
US8114395B2 (en) | 2001-02-28 | 2012-02-14 | Sichuan Biotechnology Research Center | Treatment of viral diseases with recombinant interferon α |
JP2011103899A (ja) * | 2003-06-05 | 2011-06-02 | Ajinomoto Co Inc | 目的物質の製造法 |
JP2011083292A (ja) * | 2003-08-28 | 2011-04-28 | Huiyangtech (Usa) Inc | 空間構造によるタンパク質の機能の調節 |
JP2007516214A (ja) * | 2003-08-28 | 2007-06-21 | ヒュイヤンテック(ユーエスエー),インク. | 空間構造が変えられるインターフェロン及びその応用 |
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AU2004279350B2 (en) * | 2003-08-28 | 2011-03-10 | Superlab Far East Limited | Uses of interferons with altered spatial structure |
WO2005034853A3 (en) * | 2003-08-28 | 2006-04-27 | Huiyangtech Usa Inc | Uses of interferons with altered spatial structure |
EP2325202A1 (en) * | 2003-08-28 | 2011-05-25 | Huiyangtech (USA), Inc. | Uses of interferons with altered spatial structure |
EP1670817A4 (en) * | 2003-08-28 | 2008-07-16 | Huiyangtech Usa Inc | USE OF A SPATIAL CONFIGURATION FOR MODULATING A PROTEIN FUNCTION |
KR101431172B1 (ko) * | 2003-08-28 | 2014-08-19 | 수퍼랩 파 이스트 리미티드 | 변경된 공간 구조를 갖는 인터페론의 용도 |
EP1670817A2 (en) * | 2003-08-28 | 2006-06-21 | Huiyangtech (USA), Inc. | Uses of spatial configuration to modulate protein function |
JP2012162567A (ja) * | 2003-08-28 | 2012-08-30 | Huiyangtech (Usa) Inc | 変えられた空間構造を備えるインターフェロン及びその応用 |
US8287852B2 (en) | 2003-08-28 | 2012-10-16 | Superlab Far East Limited | Treatment of viral diseases with recombinant interferon α |
JP2007503812A (ja) * | 2003-08-28 | 2007-03-01 | ヒュイヤンテック(ユーエスエー),インク. | 空間構造によるタンパク質の機能の調節 |
AU2006257286B2 (en) * | 2005-03-09 | 2012-08-16 | Superlab Far East Limited | Uses of recombinant super-compound interferons |
JP2008532995A (ja) * | 2005-03-09 | 2008-08-21 | ウェイ グアンウェン | 組換え高効率複合インターフェロンの使用方法 |
US10874716B2 (en) | 2013-01-07 | 2020-12-29 | Superlab Far East Limited | Methods and compositions for treatment of bone, skin, subcutaneous, mucosal and/or submucosal cancer by percutaneous and/or transmucosal administration of interferon |
Also Published As
Publication number | Publication date |
---|---|
US20040202641A1 (en) | 2004-10-14 |
EP1371373A4 (en) | 2005-05-04 |
EP1371373A1 (en) | 2003-12-17 |
US7364724B2 (en) | 2008-04-29 |
US20080305080A1 (en) | 2008-12-11 |
AU2003248419B2 (en) | 2007-01-04 |
JP4617058B2 (ja) | 2011-01-19 |
CN1245215C (zh) | 2006-03-15 |
AU2003248419A1 (en) | 2003-11-06 |
ATE446104T1 (de) | 2009-11-15 |
CA2439503A1 (en) | 2002-10-17 |
HK1061201A1 (en) | 2004-09-10 |
DE60234085D1 (de) | 2009-12-03 |
US8114395B2 (en) | 2012-02-14 |
US8425896B2 (en) | 2013-04-23 |
CN1311035A (zh) | 2001-09-05 |
US20110189128A1 (en) | 2011-08-04 |
EP1371373B1 (en) | 2009-10-21 |
JP2005508848A (ja) | 2005-04-07 |
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