CN1230892A - 作为抗自身免疫疾病试剂的蛋白的用途 - Google Patents

作为抗自身免疫疾病试剂的蛋白的用途 Download PDF

Info

Publication number
CN1230892A
CN1230892A CN97198012A CN97198012A CN1230892A CN 1230892 A CN1230892 A CN 1230892A CN 97198012 A CN97198012 A CN 97198012A CN 97198012 A CN97198012 A CN 97198012A CN 1230892 A CN1230892 A CN 1230892A
Authority
CN
China
Prior art keywords
ala
val
gly
leu
glu
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.)
Granted
Application number
CN97198012A
Other languages
English (en)
Other versions
CN1151838C (zh
Inventor
A·E·帕尼雷
A·巴托莱利
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.)
Zetesis SpA
Original Assignee
Zetesis SpA
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
Priority claimed from ITMI961919 external-priority patent/IT1284553B1/it
Priority claimed from ITMI961921 external-priority patent/IT1284555B1/it
Priority claimed from ITMI961920 external-priority patent/IT1284554B1/it
Priority claimed from ITMI961922 external-priority patent/IT1284556B1/it
Application filed by Zetesis SpA filed Critical Zetesis SpA
Publication of CN1230892A publication Critical patent/CN1230892A/zh
Application granted granted Critical
Publication of CN1151838C publication Critical patent/CN1151838C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C07K14/4703—Inhibitors; Suppressors
    • 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
    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/827—Proteins from mammals or birds
    • Y10S530/843—Digestive system
    • Y10S530/846—Liver

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Transplantation (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

用高氯酸从动物器官中提取的蛋白的用途,用于具有抗自身免疫疾病活性,特别是具有抗动脉粥样硬化、关节炎、多发性硬化和糖尿病活性的药物的制备。

Description

作为抗自身免疫疾病试剂的蛋白的用途
本发明涉及从动物器官，特别是从哺乳动物肝脏中提取的蛋白的用途，用于具有抗自身免疫疾病活性，尤其具有抗动脉粥样硬化、关节炎、多发性硬化、糖尿病活性的药物的制备。
已证明施用氟氏完全佐剂能在大鼠体中诱导与类风湿性关节炎非常相似的实验性关节炎。另一方面，对兔子施用佐剂不诱导关节炎病变，而诱导动脉粥样硬化。已进行的研究表明，在这两种损伤中存在对内源因子的免疫反应性，该内源因子已被鉴定为热击蛋白60(HSP60)。随后的研究证明可用HSP60的施用代替氟氏完全佐剂的施用，并产生相同的病理学变化，这证实了上述观察结果。后来，又证明用佐剂、HSP60或其片段预处理大鼠能预防关节炎的发作，其抗理仍不清楚，而继佐剂之后给药使疾病进程恶化。
最近发现用佐剂预处理也可预防其它一些一般说来定义为自身免疫疾病的实验性病变如糖尿病或实验性变应性脑脊髓炎(EAE)。最后，发现HSP60与很多自身抗原的结构相似，因此推测它与比迄今观察到的更广泛的各种病理学变化有关。
WO92/10197公开了可用高氯酸从哺乳动物器官提取的蛋白组分和它们作为抗原剂的用途。在这些蛋白组分中可鉴定出三种在凝胶电泳上分子量为50，14和10KDa的主要组分。以下将含有这种组分的纯化提取物称为UK101。在下面表格和WO96/02567中报告了14KDa蛋白组分的序列，该蛋白组分是具有上述活性的主要组分但不是唯一的组分，并发现它与其它作者[Levy-Favatier,Eur.Biochem.1903,212(3)665-73]所述的蛋白有关，推测新鉴定的序列属于已知为分子伴侣(chaperonin)的蛋白家族，HSP本身也属于这一家族。
WO92/10197和96/02567中所述的蛋白(以下称为UK114)表现出未在分子伴侣蛋白或其类似物中观察到的某些性质。更特别地，已发现该蛋白可以用于预防和治疗自身免疫疾病，特别是动脉粥样硬化疾病如由器官移植诱导的动脉粥样硬化、关节炎、多发性硬化和糖尿病。
优选地，本发明涉及纯化的蛋白UK101和UK114的用途，用于预防和治疗自身免疫疾病如器官移植后的动脉粥样硬化、关节炎、多发性硬化和糖尿病的药物的制备。
而且本发明包括表现与UK114有至少80％，优选地至少90％高度同源性的蛋白的用途。抗动脉粥样硬化活性
如今发现，器官移植很快失败的更常见原因不再是排斥，而是在移植器官血管和宿主血管的接触点形成的动脉粥样硬化斑块。常用的免疫抑制剂如环胞霉素使此病理学变化恶化，而使用叠氮胸苷(AZT)，虽毒性很大，似乎有好处。
可以用常规动脉粥样硬化模型和移植动脉粥样硬化模型来证明蛋白UK101和UK114的活性，常规粥样硬化模型是用氟氏完全佐剂预处理的兔子作为模型。在第一种情况下，用佐剂进行皮下处理，在21天之内在髂动脉分枝和主动脉弓处诱导动脉粥样硬化斑块的形成。用UK101或UK114(提前7天)进行预处理，与仅用佐剂的处理(在所有受试动物体内导致疾病的发展)相比，可以在高比例的病例中明显防止病理学变化的发展。
另一方面，移植动脉粥样硬化的实验模型存在于大鼠动脉水平的静脉分流术中。短时间后，如人体病理学变化中所发生的那样，在宿主血管水平上观察到动脉粥样硬化的形成。用UK101和UK114(提前7天)进行预处理，与器官移植之前不进行预处理的动物中所观察到的相比，可在高比例的病例中防止病理学变化的发展。抗关节炎活性
用常规关节炎模型，即佐剂诱导的关节炎来证明抗关节炎活性。在此模型中，在路易士(Lewis)鼠的尾基部注射氟氏完全佐剂，在7天之内于其后肢出现以肿胀和关节变形为特征的病理学变化。从第14天到第21天病理学变化达到高峰，然后逐渐下降，直到后肢恢复正常。用UK101或UK114(提前7天)预处理，与仅用佐剂处理(在100％的动物体内导致病理学变化的发展)相比，可在高比例的病例中明显防止病理学变化的发展。在施用佐剂之后再用UK101或UK114处理，会使病理学变化的进程恶化。
因此，认为UK101和UK114能够改善诸如关节炎和类风湿性关节炎的病理学病征的进展或防止其发生。抗多发性硬化病活性
该活性用常规多发性硬化病模型：试验性应变性脑脊髓炎(EAE)加以证明。用豚鼠脊髓匀浆与氟氏佐剂一起皮下注射路易士(Lewis)鼠以诱导病理学变化。大约第12天从后肢开始出现渐进的麻庳症状，在大约第21天达到最大值，大约在给予免疫原后第30天得到缓解。用UK101或UK114(7天前)预处理，与仅用髓匀浆和佐剂的处理(在100％受试动物中导致病理学变化发展)相比，可在高比例的病例中明显防止病理学变化的发展，并且出现更不严重的病征。
因而相信UK101和UK114能够改善诸如多发性硬化病的病理学病征的进展或防止其发生。抗糖尿病活性
此活性用以BB鼠可为代表的常规糖尿病模型加以证明，BB鼠在其生长第45天左右自发产生糖尿病，在该动物生长第30天时用UK101或UK114进行处理并观察其病理学变化的发展，与未处理的对照动物比较。已发现预处理降低实验模型中的发病率和病理学变化的严重程度。一些在身体不同部位受肿瘤侵袭并同时患有糖尿病的病人，曾经在进行安慰治疗的过程中用UK101治疗。所有受治疗的病人都表现出糖尿病症征的缓解，以至可以放弃胰岛素治疗，这些与对肿瘤病理学的影响无关。
因此相信，UK101和UK114能够改变糖尿病的进程或预防它的发生。
事实上抗糖尿病活性已在糖尿病患者体内得到证实，虽然至今只在有限的病例中得到证实。
本发明的蛋白可采用合适的配方，主要是注射配方给药。
给药方式(如给药剂量、频率等)根据情况依赖于诸如病人情况、疾病阶段等因素而定，但通常每日合适的剂量范围为1-100mg。
表Met Ser Glu Asn Ser Glu Glu Pro Val Gly Glu Ala Lys  Ala1               5                   10Pro Ala Ala IlE Gly Pro Tyr Ser Gln Ala Val Leu Val  Asp15                  20                  25Arg Thr Ile Tyr Ile Ser Gly Gln Leu Gly Met Asp Pro  Ala
30                  35                  40Ser Gly Gln Leu Val Pro Gly Gly Val Val Glu Glu Ala  Lys
    45                  50                  55Gln Ala Leu Thr Asn Ile Gly Glu Ile Leu Lys Ala Ala  Gly
        60                  65                   70Cys Asp Phe Thr Asn Val Val Lys Ala Thr Val Leu Leu  Ala
            75                  80Asp Ile Asn Asp Phe Ser Ala Val Asn Asp Val Tyr Lys  Gln85                  90                  95Tyr Phe Gln Ser Ser Phe Pro Ala Arg Ala Ala Tyr Gln Val
l00                 105                 110Ala Ala Leu Pro Lys Gly Gly Arg Val Glu Ile Glu Ala Ile
    115                 120                 125Ala Val Gln Gly Pro Leu Thr Thr Ala Ser Val
        130                 135
                   序列表(1)基本信息：
(ⅰ)申请人
    (A)名称：zetesis s.p.a.
    (B)街名：Galleria del Corso 2
    (C)城市：Milano
    (E)国家：意大利
    (F)邮政编码(ZIP):20122
(ⅱ)发明名称：作为抗自身免疫病试剂的蛋白的用途
(ⅲ)序列数目：1
(ⅳ)计算机可读形式：
    (A)介质类型：软盘
    (B)计算机：IBM PC兼容机
    (C)操作系统：PC-DOS/MS-DOS
    (D)软件：PatentIn Release#1.0，版本#1.30(EPO)(2)关于SEQ ID NO:1的信息：
(ⅰ)序列特征：
    (A)长度：137个氨基酸
    (B)类型：氨基酸
    (C)链型：
    (D)拓扑结构：线型
(ⅱ)分子类型：蛋白质
(ⅲ)假设：无
(ⅳ)反义：无
(ⅹⅰ)序列描述：SEQ ID NO:1:Met Ser Glu Asn Ser Glu Glu Pro Val Gly Glu Ala Lys  Ala1               5                   10Pro Ala Ala Ile Gly Pro Tyr Ser Gln Ala Val Leu Val  Asp15                  20                  25Arg Thr Ile Tyr Ile Ser Gly Gln Leu Gly Met Asp Pro  Ala
30                  35                  40Ser Gly Gln Leu Val Pro Gly Gly Val Val Glu Glu Ala  Lys
    45                  50                  55Gln Ala Leu Thr Asn Ile Gly Glu Ile Leu Lys Ala Ala  Gly
        60                  65                   70Cys Asp Phe Thr Asn Val Val Lys Ala Thr Val Leu Leu  Ala
            75                  80Asp Ile Asn Asp Phe Ser Ala Val Asn Asp Val Tyr Lys  Gln85                  90                  95Tyr Phe Gln Ser Ser Phe Pro Ala Arg Ala Ala Tyr Gln Val
100                 105                 110Ala Ala Leu Pro Lys Gly Gly Arg Val Glu Ile Glu Ala  Ile
    115                 120                 125Ala Val Gln Gly Pro Leu Thr Thr Ala Ser Val
        130                 135

Claims (8)

1．可用高氯酸从哺乳动物肝脏中提取的蛋白的用途，用于制备具有抗自身免疫疾病活性的药物。
2．根据权利要求1所述的用途，其中蛋白具有以下序列：Met Ser Glu Asn Ser Glu Glu Pro Val Gly Glu Ala Lys  Ala1               5                   10Pro Ala Ala Ile Gly Pro Tyr Ser Gln Ala Val Leu Val  AsP15                  20                  25Arg Thr Ile Tyr Ile Ser Gly Gln Leu Gly Met Asp Pro  Ala30                  35                  40Ser Gly Gln Leu Val Pro Gly Gly Val Val Glu Glu Ala  Lys45                  50                  55Gln Ala Leu Thr Asn Ile Gly Glu Ile Leu Lys Ala Ala  Gly60                  65                     70Cys Asp Phe Thr Asn Val Val Lys Ala Thr Val Leu Leu  Ala75                  80Asp Ile Asn Asp Phe Ser Ala Val Asn Asp Val Tyr Lys  Gln85                  90                  95Tyr Phe Gln Ser Ser Phe Pro Ala Arg Ala Ala Tyr Gln Val100                 105                 110Ala Ala Leu Pro Lys Gly Gly Arg Val Glu Ile Glu Ala  Ile115                 120                 125Ala Val Gln Gly Pro Leu Thr Thr Ala Ser Val130                 135
3．根据权利要求1所述的用途，其中所用的蛋白与权利要求2的蛋白有至少80％的同源性。
4．含有与适当赋形剂混合的权利要求1-3的蛋白作为活性成分的药物组合物。
5．根据权利要求1所述的用途，用于预防和治疗移植后动脉粥样硬化的药物的制备。
6．根据权利要求1所述的用途，用于预防和治疗关节炎的药物的制备。
7．根据权利要求1所述的用途，用于预防和治疗多发性硬化的药物的制备。
8．根据权利要求1所述的用途，用于预防和治疗糖尿病的药物的制备。
CNB971980128A 1996-09-18 1997-09-17 作为抗自身免疫疾病试剂的蛋白的用途 Expired - Fee Related CN1151838C (zh)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
ITMI961919 IT1284553B1 (it) 1996-09-18 1996-09-18 Uso di proteine come agenti antiartritici
ITMI961921 IT1284555B1 (it) 1996-09-18 1996-09-18 Uso di proteine come agenti antidiabetici
ITMI961920 IT1284554B1 (it) 1996-09-18 1996-09-18 Uso di proteine come agenti antiaterosclerotici
ITMI96A001921 1996-09-18
ITMI961922 IT1284556B1 (it) 1996-09-18 1996-09-18 Uso di proteine come agenti contro la sclerosi multipla
ITMI96A001922 1996-09-18
ITMI96A001919 1996-09-18
ITMI96A001920 1996-09-18

Publications (2)

Publication Number Publication Date
CN1230892A true CN1230892A (zh) 1999-10-06
CN1151838C CN1151838C (zh) 2004-06-02

Family

ID=27453037

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB971980128A Expired - Fee Related CN1151838C (zh) 1996-09-18 1997-09-17 作为抗自身免疫疾病试剂的蛋白的用途

Country Status (22)

Country Link
US (2) US6468536B1 (zh)
EP (1) EP0928197B1 (zh)
JP (1) JP2001501925A (zh)
KR (1) KR20000036207A (zh)
CN (1) CN1151838C (zh)
AR (1) AR009952A1 (zh)
AT (1) ATE233569T1 (zh)
AU (1) AU723669B2 (zh)
BR (1) BR9711499A (zh)
CA (1) CA2266346A1 (zh)
CZ (1) CZ293926B6 (zh)
DE (1) DE69719525T2 (zh)
DK (1) DK0928197T3 (zh)
ES (1) ES2192669T3 (zh)
IL (1) IL129024A0 (zh)
NO (1) NO991175D0 (zh)
NZ (1) NZ334714A (zh)
PL (1) PL188746B1 (zh)
PT (1) PT928197E (zh)
RU (1) RU2196606C2 (zh)
TR (1) TR199900596T2 (zh)
WO (1) WO1998011909A1 (zh)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3521382B2 (ja) 1997-02-27 2004-04-19 日本たばこ産業株式会社 細胞間接着及びシグナル伝達を媒介する細胞表面分子
US7112655B1 (en) 1997-02-27 2006-09-26 Japan Tobacco, Inc. JTT-1 protein and methods of inhibiting lymphocyte activation
IT1290828B1 (it) * 1997-03-25 1998-12-11 Zetesis Spa Uso di proteine estraibili da organi animali per la preparazione di medicamenti per il trattamento di condizioni patologiche
JP4210454B2 (ja) 2001-03-27 2009-01-21 日本たばこ産業株式会社 炎症性腸疾患治療剤
JP3871503B2 (ja) 1999-08-30 2007-01-24 日本たばこ産業株式会社 免疫性疾患治療剤
JP3597140B2 (ja) 2000-05-18 2004-12-02 日本たばこ産業株式会社 副刺激伝達分子ａｉｌｉｍに対するヒトモノクローナル抗体及びその医薬用途
WO2001093888A2 (en) * 2000-06-08 2001-12-13 Rakepoll Holding B.V. A method of treatment of amyotrophic lateral sclerosis with a protein extractable from mammalian organs
JP4212278B2 (ja) 2001-03-01 2009-01-21 日本たばこ産業株式会社 移植片拒絶反応抑制剤
ITMI20010762A1 (it) * 2001-04-10 2002-10-10 Zetesis Spa Uso della proteina uk114 o di suoi frammenti per il trattamento e la prevenzione dello shock endotossico
ITMI20010761A1 (it) * 2001-04-10 2002-10-10 Zetesis Spa Uso della proteina uk114 per il trattamento e la prevenzione dell'epatite cronica attiva
US20070275890A1 (en) * 2004-01-16 2007-11-29 Johnson Barbara J Chaperonin 10 Modulation Of Toll-Like Receptor-Inducible Cytokine And Chemokine Secretion

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4024247A (en) * 1971-12-27 1977-05-17 Palolab Pharmaceuticals Corporation Composition and method of using a protein mixture derived from liver
IT1244879B (it) 1990-12-11 1994-09-12 Alberto Bartorelli Estratti da tessuti animali, utili in terapia e in diagnostica.
FR2688227A1 (fr) * 1992-03-04 1993-09-10 Inst Nat Sante Rech Med Proteines formant des complexes avec des chaperones et leurs ligands, leurs fragments, leur obtention et leurs applications biologiques.
IT1270618B (it) * 1994-07-14 1997-05-07 Zetesis Spa Proteine ad attivita' antitumorale

Also Published As

Publication number Publication date
BR9711499A (pt) 1999-08-24
DE69719525D1 (de) 2003-04-10
CZ293926B6 (cs) 2004-08-18
CA2266346A1 (en) 1998-03-26
AU723669B2 (en) 2000-08-31
EP0928197B1 (en) 2003-03-05
US20030108558A1 (en) 2003-06-12
IL129024A0 (en) 2000-02-17
NO991175L (no) 1999-03-10
ES2192669T3 (es) 2003-10-16
PL332282A1 (en) 1999-08-30
JP2001501925A (ja) 2001-02-13
AR009952A1 (es) 2000-05-17
PT928197E (pt) 2003-06-30
RU2196606C2 (ru) 2003-01-20
WO1998011909A1 (en) 1998-03-26
EP0928197A1 (en) 1999-07-14
CZ91599A3 (cs) 1999-08-11
NZ334714A (en) 2000-08-25
DE69719525T2 (de) 2003-10-02
US6468536B1 (en) 2002-10-22
KR20000036207A (ko) 2000-06-26
AU4774797A (en) 1998-04-14
PL188746B1 (pl) 2005-04-29
TR199900596T2 (xx) 1999-06-21
ATE233569T1 (de) 2003-03-15
NO991175D0 (no) 1999-03-10
CN1151838C (zh) 2004-06-02
DK0928197T3 (da) 2003-06-23

Similar Documents

Publication Publication Date Title
CN1230892A (zh) 作为抗自身免疫疾病试剂的蛋白的用途
EP0115157B1 (en) Hypocholesterolemically active protein
CN1146576C (zh) 得自哺乳动物肝脏的蛋白质及其在肿瘤学中的应用
KR970701724A (ko) 스타니어스 단백질인 스타니오칼신의 소체(Corpuscles of stannius protein, stanniocalcin)
US5284664A (en) Method of treating the symptoms of Alzheimer's disease
Gipson et al. Comparison of 10 nm filaments from three bovine tissues
Levine et al. Exacerbation and transformation of allergic encephalomyelitis by pertussis vaccine.
EP0403458B1 (en) Novel polypeptides and their use
US8034777B2 (en) Modified anticholinergic neurotoxins as modulators of the autoimmune reaction
AU770076B2 (en) Alpha-conotoxin peptides
CN1251043A (zh) 可从动物器官中提取的蛋白质在制备可用于治疗疾病的药物中的用途
US4024247A (en) Composition and method of using a protein mixture derived from liver
Low et al. Thymosins: Isolation, structural studies, and biological activities
CN1041170C (zh) 菠萝蛋白酶脱痂制剂及其制备方法
Gaddum et al. An antistrychnine extract from horse intestine
WO1992004368A1 (en) Pharmacologically active substance bpc, the process for its preparation and its use in the therapy
Lenzi et al. Acid Mucopolysaccharides in the Skin of Lathyritic Rats.
CN1231674A (zh) 作为抗逆转录病毒试剂的蛋白的用途
Camp Polypeptide neutrophil chemoattractants in the skin
MXPA99002571A (en) Use of proteins as agents against autoimmune diseases
JP2795346B2 (ja) 血管収縮ペプチド
ZA200307901B (en) Use of the protein UK114 or of fragments thereof for the treatment and prevention of the endotoxic shock.
CN1388131A (zh) 系列新型药物载体、新型载体－酪氨酸羟化酶融合蛋白及其制备
Vartanyan et al. Induction of postural asymmetry in an intact recipient by brain extract from a donor with the same syndrome
AU2002338299A1 (en) Use of the protein UK114 or of fragments thereof for the treatment and prevention of the endotoxic shock

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee