DE69616803T2 - Pharmazeutische zusammensetzung enthaltend interferon-gamma inhibitoren - Google Patents
Pharmazeutische zusammensetzung enthaltend interferon-gamma inhibitorenInfo
- Publication number
- DE69616803T2 DE69616803T2 DE69616803T DE69616803T DE69616803T2 DE 69616803 T2 DE69616803 T2 DE 69616803T2 DE 69616803 T DE69616803 T DE 69616803T DE 69616803 T DE69616803 T DE 69616803T DE 69616803 T2 DE69616803 T2 DE 69616803T2
- Authority
- DE
- Germany
- Prior art keywords
- ifn
- inhibitor
- wounds
- healing
- injury
- 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.)
- Expired - Lifetime
Links
- 108010074328 Interferon-gamma Proteins 0.000 title claims description 51
- 239000003112 inhibitor Substances 0.000 title claims description 22
- 102000008070 Interferon-gamma Human genes 0.000 title description 3
- 229960003130 interferon gamma Drugs 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 208000027418 Wounds and injury Diseases 0.000 claims abstract description 60
- 206010052428 Wound Diseases 0.000 claims abstract description 40
- 230000035876 healing Effects 0.000 claims abstract description 24
- 239000000203 mixture Substances 0.000 claims abstract description 10
- 230000001737 promoting effect Effects 0.000 claims abstract description 10
- 230000001684 chronic effect Effects 0.000 claims abstract description 8
- 102100037850 Interferon gamma Human genes 0.000 claims description 48
- 208000014674 injury Diseases 0.000 claims description 20
- 230000006378 damage Effects 0.000 claims description 19
- 230000037390 scarring Effects 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 230000003176 fibrotic effect Effects 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 10
- 206010016654 Fibrosis Diseases 0.000 claims description 6
- 230000004761 fibrosis Effects 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 230000003472 neutralizing effect Effects 0.000 claims description 2
- 238000011830 transgenic mouse model Methods 0.000 claims description 2
- 239000003981 vehicle Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 102000008186 Collagen Human genes 0.000 description 12
- 108010035532 Collagen Proteins 0.000 description 12
- 229920001436 collagen Polymers 0.000 description 12
- 231100000241 scar Toxicity 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000000835 fiber Substances 0.000 description 5
- 230000004913 activation Effects 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000029663 wound healing Effects 0.000 description 4
- 208000032544 Cicatrix Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 230000037387 scars Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 230000001969 hypertrophic effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 210000002435 tendon Anatomy 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 208000025962 Crush injury Diseases 0.000 description 1
- 206010056340 Diabetic ulcer Diseases 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101001044384 Mus musculus Interferon gamma Proteins 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000000558 Varicose Ulcer Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000002278 reconstructive surgery Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Classifications
-
- 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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/249—Interferons
-
- 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
- A61K38/21—Interferons [IFN]
- A61K38/217—IFN-gamma
-
- 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
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9516967A GB2304342A (en) | 1995-08-18 | 1995-08-18 | Pharmaceutical comprising either an inhibitor or a stimulator of interferon gamma |
| PCT/GB1996/001949 WO1997007136A2 (en) | 1995-08-18 | 1996-08-09 | Pharmaceutical composition containing inhibitors of interferon-gamma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69616803D1 DE69616803D1 (de) | 2001-12-13 |
| DE69616803T2 true DE69616803T2 (de) | 2002-06-20 |
Family
ID=10779448
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69616803T Expired - Lifetime DE69616803T2 (de) | 1995-08-18 | 1996-08-09 | Pharmazeutische zusammensetzung enthaltend interferon-gamma inhibitoren |
| DE69626050T Expired - Lifetime DE69626050T2 (de) | 1995-08-18 | 1996-08-09 | Pharmazeutische zusammensetzung enthaltend interferon-gamma stimulatoren |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69626050T Expired - Lifetime DE69626050T2 (de) | 1995-08-18 | 1996-08-09 | Pharmazeutische zusammensetzung enthaltend interferon-gamma stimulatoren |
Country Status (12)
| Country | Link |
|---|---|
| EP (2) | EP0845007B1 (enExample) |
| JP (2) | JP4070809B2 (enExample) |
| AT (2) | ATE231728T1 (enExample) |
| AU (1) | AU713809B2 (enExample) |
| CA (1) | CA2229590C (enExample) |
| DE (2) | DE69616803T2 (enExample) |
| DK (2) | DK0845007T3 (enExample) |
| ES (2) | ES2164911T3 (enExample) |
| GB (1) | GB2304342A (enExample) |
| PT (2) | PT972521E (enExample) |
| WO (1) | WO1997007136A2 (enExample) |
| ZA (1) | ZA966953B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| DE69927520T2 (de) | 1998-12-09 | 2006-06-22 | Protein Design Labs, Inc., Fremont | Verwendung von il-12 antikörpern zur behandlung von psoriasis |
| EP1180037A2 (en) * | 1999-05-26 | 2002-02-20 | The Brigham and Women's Hospital | Therapeutic uses of agents that modulate the activity of alpha-smooth muscle actin |
| US6710025B1 (en) | 1999-05-26 | 2004-03-23 | The Brigham And Women's Hospital, Inc. | Treatment of damaged tissue using agents that modulate the activity of alpha-smooth muscle actin |
| US10080779B2 (en) | 2004-12-15 | 2018-09-25 | Universite D'angers | Method for increasing the expression of anti-microbial peptides by keratinocytes comprising administering a composition comprising IL-17, TNF-alpha and OSM |
| JP5530635B2 (ja) * | 2007-02-14 | 2014-06-25 | 独立行政法人科学技術振興機構 | 腸管癒着抑制剤 |
| GB0724231D0 (en) * | 2007-12-12 | 2008-01-30 | Renono Ltd | Methods for inhibiting scarring |
| RU2539383C1 (ru) * | 2013-11-29 | 2015-01-20 | Закрытое акционерное общество "ФИРН М" (ЗАО "ФИРН М") | Фармацевтическая композиция для лечения трофических язв и длительно незаживающих ран различной этиологии в виде мази |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL78444A (en) * | 1986-04-08 | 1992-05-25 | Yeda Res & Dev | Human gamma interferon-specific receptor protein,antibody against said protein,and compositions containing said protein and antibody |
| JPH01502980A (ja) * | 1986-06-17 | 1989-10-12 | レイチ，スティーブン デー | ガンマインターフェロンと抗炎症剤または抗発熱剤との組合せ並びに疾患処置方法 |
| NL8700927A (nl) * | 1987-04-16 | 1988-11-16 | Stichting Rega V Z W | Anti-interferon-gamma-antilichamen; en hun therapeutische toepassing. |
| CA1335792C (en) * | 1987-08-18 | 1995-06-06 | Chaim O. Jacob | Method and dosage form using an antagonist to gamma interferon to control mhc-associated autoimmune disease |
| AU2855189A (en) * | 1988-01-25 | 1989-07-27 | Baker Cummins Dermatologicals, Inc. | Method of treating fibrotic disorders |
| IL88378A (en) * | 1988-11-14 | 2000-11-21 | Yeda Res & Dev | Human interferon-gamma binding proteins their manufacture and pharmaceutical compositions comprising them |
| SG43205A1 (en) * | 1988-12-19 | 1997-10-17 | American Cyanamid Co | A method for the treatment of endotoxic shock in a mammal |
| GB8905400D0 (en) * | 1989-03-09 | 1989-04-19 | Jonker Margreet | Medicaments |
| ATE132191T1 (de) * | 1989-04-19 | 1996-01-15 | Hoffmann La Roche | Auflösbare interferon-gamma-rezeptoren sowie verfahren zu deren herstellung |
| IT1231727B (it) * | 1989-08-11 | 1991-12-21 | Enrico Savoldi | Peptidi utili per la determinazione e la purificazione di anticorpi anti gamma interferone. |
| IL91562A0 (en) * | 1989-09-07 | 1990-04-29 | Yeda Res & Dev | Interferon-gamma receptor fragment and its production |
| JPH05506247A (ja) * | 1990-09-27 | 1993-09-16 | シェリング・コーポレーション | ヒトγインターフェロンのアンタゴニスト |
| WO1992014480A1 (en) * | 1991-02-22 | 1992-09-03 | Amgen Inc. | Use of gm-csf and g-csf to promote accelerated wound healing |
| NL9101290A (nl) * | 1991-07-23 | 1993-02-16 | Stichting Rega V Z W | Recombinant dna-molecuul voor de expressie van een fv-fragment van een antilichaam. |
| DE4234380A1 (de) * | 1992-10-06 | 1994-04-07 | Schering Ag | Verwendung von Dopaminagonisten zur Aktivierung des gamma-Interferon-Produktion |
| AU5669694A (en) * | 1992-11-20 | 1994-06-22 | Schering Corporation | Antagonists of human gamma interferon |
| EP0695189B1 (en) * | 1992-12-29 | 1998-11-25 | Genentech, Inc. | Treatment of inflammatory bowel disease with ifn-gamma inhibitors |
| JPH09506263A (ja) * | 1993-12-09 | 1997-06-24 | アゲット，ミヒェル | ＩＦＮ−γレセプターβ−鎖およびその誘導体 |
-
1995
- 1995-08-18 GB GB9516967A patent/GB2304342A/en not_active Withdrawn
-
1996
- 1996-08-09 PT PT99202497T patent/PT972521E/pt unknown
- 1996-08-09 EP EP96927141A patent/EP0845007B1/en not_active Expired - Lifetime
- 1996-08-09 ES ES96927141T patent/ES2164911T3/es not_active Expired - Lifetime
- 1996-08-09 DE DE69616803T patent/DE69616803T2/de not_active Expired - Lifetime
- 1996-08-09 AT AT99202497T patent/ATE231728T1/de not_active IP Right Cessation
- 1996-08-09 CA CA2229590A patent/CA2229590C/en not_active Expired - Fee Related
- 1996-08-09 DK DK96927141T patent/DK0845007T3/da active
- 1996-08-09 EP EP99202497A patent/EP0972521B1/en not_active Expired - Lifetime
- 1996-08-09 WO PCT/GB1996/001949 patent/WO1997007136A2/en not_active Ceased
- 1996-08-09 DK DK99202497T patent/DK0972521T3/da active
- 1996-08-09 AU AU67071/96A patent/AU713809B2/en not_active Ceased
- 1996-08-09 AT AT96927141T patent/ATE208402T1/de not_active IP Right Cessation
- 1996-08-09 DE DE69626050T patent/DE69626050T2/de not_active Expired - Lifetime
- 1996-08-09 JP JP50902597A patent/JP4070809B2/ja not_active Expired - Fee Related
- 1996-08-09 PT PT96927141T patent/PT845007E/pt unknown
- 1996-08-09 ES ES99202497T patent/ES2192018T3/es not_active Expired - Lifetime
- 1996-08-16 ZA ZA9606953A patent/ZA966953B/xx unknown
-
2007
- 2007-02-13 JP JP2007031760A patent/JP4616291B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE208402T1 (de) | 2001-11-15 |
| WO1997007136A2 (en) | 1997-02-27 |
| DK0972521T3 (da) | 2003-05-05 |
| HK1023516A1 (en) | 2000-09-15 |
| GB2304342A (en) | 1997-03-19 |
| ES2164911T3 (es) | 2002-03-01 |
| EP0972521B1 (en) | 2003-01-29 |
| ATE231728T1 (de) | 2003-02-15 |
| EP0845007B1 (en) | 2001-11-07 |
| DE69626050D1 (de) | 2003-03-06 |
| JP2007119497A (ja) | 2007-05-17 |
| JP4070809B2 (ja) | 2008-04-02 |
| PT845007E (pt) | 2002-03-28 |
| DK0845007T3 (da) | 2001-12-17 |
| AU713809B2 (en) | 1999-12-09 |
| ZA966953B (en) | 1998-02-16 |
| AU6707196A (en) | 1997-03-12 |
| EP0845007A2 (en) | 1998-06-03 |
| GB9516967D0 (en) | 1995-10-18 |
| DE69626050T2 (de) | 2004-01-22 |
| EP0972521A1 (en) | 2000-01-19 |
| CA2229590A1 (en) | 1997-02-27 |
| JPH11511160A (ja) | 1999-09-28 |
| DE69616803D1 (de) | 2001-12-13 |
| JP4616291B2 (ja) | 2011-01-19 |
| PT972521E (pt) | 2003-06-30 |
| WO1997007136A3 (en) | 1997-08-21 |
| CA2229590C (en) | 2010-10-12 |
| ES2192018T3 (es) | 2003-09-16 |
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