CN101171027A - 组蛋白用于治疗目的的用途 - Google Patents

组蛋白用于治疗目的的用途 Download PDF

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CN101171027A
CN101171027A CNA2006800157213A CN200680015721A CN101171027A CN 101171027 A CN101171027 A CN 101171027A CN A2006800157213 A CNA2006800157213 A CN A2006800157213A CN 200680015721 A CN200680015721 A CN 200680015721A CN 101171027 A CN101171027 A CN 101171027A
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treatment
histone
segment
disease
thrombocytopenia
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迈克尔·泽皮祖尔
克拉斯·雷恩尔
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Symbiotec GmbH Gesellschaft zur Forschung und Entwicklung der Biotechnologie
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    • 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
    • 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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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—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
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    • A61K38/00—Medicinal preparations containing peptides
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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Abstract

本发明涉及至少一种人重组组蛋白，特别是至少一种H1亚型组蛋白和/或治疗性组蛋白片断作为主要成分用于治疗血小板减少的用途。

Description

组蛋白用于治疗目的的用途
本发明涉及至少一种人重组H1亚型组蛋白和/或其有效治疗片断，特别是组蛋白H1.3，用于治疗目的的用途。
基于人重组组蛋白H1亚型的治疗活性物质用于治疗癌症(例如白血病)的用途公开于文章Reiner Class et al.in Am.J.Clin.Oncol.(CCT)vol.19No.51996及欧洲专利申请98919254.7中。
牛胸腺组蛋白H1和H2A/H2B片断对正常和辐射过的大鼠血液干细胞(CTU-S)的作用如俄语文章Semina O.V.et al.in RadiatsionnaiaBiologiia，Radioccologiia 34(4-5)，1994，Jul.Oct.所述。
在复杂的病理学条件(如急性骨髓白血病)下，常常观察到血小板减少，所述血小板减少可被白血病的化疗进一步增强。然而，血小板减少也可由其他疾病引起。由于血小板减少可导致危及生命的内出血，治疗各种可能引起血小板减少的病理症状常常特别难以做到。
因此，本发明的一个目的是发现一种活性物质，该物质可用于治疗血小板减少，以从根本上有助于成功治疗诱导血小板减少的基本症状。
根据本发明已可能达到该目的，尤其是通过使用基于至少一种人重组组蛋白(特别是至少一种H1亚型的组蛋白)和/或其有效治疗片断的活性物质，用于治疗干细胞分化错误或巨核细胞增殖减弱引起的血小板减少。
这特别适用于与血液病并发的血小板减少。
此外，还可能将本发明的治疗方法用于治疗在治疗血液疾病(特别是急性骨髓白血病)的化疗期间或之后的血小板减少。
令人惊讶地是，已可能表明本发明的活性物质一方面在血液疾病如白血病的治疗中显示阳性结果，另一方面也在与血液疾病相关的血小板减少的治疗中也显示阳性结果。
因此，可能以一种相同的活性物质来消退白血病和增加血小板。
使用人重组组蛋白H1.3也可能达到对患者的治疗试验结果，其可能显著减少AML患者病理肿瘤细胞的数量，并且同时，从根本上增加血小板的产量，因此可能从根本上改善治疗患者的前景。
试验结果将在下文更详细地展开，此时使用的基于人重组H1.3的活性物质，浓度为37.5mg/qm2体表面积，静脉施用其0.9％的NaCl溶液，每周3次，每次约4小时。
以37.5mg/qm2体表面积的本发明活性物质(0.9％NaCl溶液中)对患者的血小板减少的作用如附图所示。
纵坐标上外周血中的血小板数量为0至40×109。将本发明活性物质治疗3周显示于横坐标上，第一次治疗前测定的患者血小板计数被显著降低为约8×109。然后在各个实例中，每周进行3次点滴注射，各个实例中每次注射4小时，在第一周的第1、3、5天进行第1至3次注射，第二周的第8、10和12天进行第4至6次注射，最后在第三周的第15、17和19天进行第7至9次注射。在第一次注射后的第29天，进行血小板数量的对照计数，不再进一步注射本发明的活性物质。在后来的时间FU1，从患者取出约34×109的几乎正常的血小板数量，本发明的活性物质甚至未用一次。该值排除了提供储备血的需要。要求患者参加回访检查，如果血小板计数自身没有进一步改善或甚至恶化，则可能恢复治疗。此处未显示回访检查结果。
附图显示从第二周的起点一直到第三周治疗结束，治疗5天后血小板计数突升，然后从治疗的第8天至随后的第19天血小板数量持续增加，在第29天第一次对照试验时以及在后来不进一步施加本发明活性物质的从患者取血的FU1天，血小板数量进一步更缓慢地增加，最后测定的血小板数量如上所述约为32.5×109。
本发明不限于人重组H1.3的用途。由于H1各亚型之间的紧密关系，对于技术人员而言，将作为本发明活性物质基础的其它人重组H1亚型用作活性物质是显然的。
继使用人重组组蛋白H1.3成功治疗患者的血小板减少(此处为AML白血病的并发症)之后，对于技术人员而言特别显然的是也根据本发明将其它重组H1亚型单独地或组合地用作备选的活性物质。
本发明活性物质优选地由完整的未被缩短的组蛋白亚型组成。然而，对于技术人员而言，在该情况下他能以其专业知识和经验作为基础直接寻找有效治疗片断，而不必具有突出的创新贡献也是显然的。因此，这些有疗效的组蛋白片断处于此处公开的本发明教导的等价物的范围内。
本发明进一步公开了当存在危险的或早期的原发疾病(经验表明，该原发疾病可导致血小板减少)时，使用本发明的活性物质预防性地针对危险的血小板减少的治疗性教导，即使本发明活性物质对原发疾病不像对白血病那样有效。

Claims (7)

1.至少一种人重组组蛋白，特别是至少一种H1亚型组蛋白和/或其有效治疗片断作为主要成分用于治疗血小板减少的用途。
2.权利要求1中所述的一种组蛋白和/或其有效治疗片断，其用于治疗性治疗与血液疾病并发的血小板减少。
3.权利要求1中所述的一种组蛋白和/或其有效治疗片断，其用于治疗性治疗在治疗血液疾病的治疗期间或之后的血小板减少，特别是在化疗之后。
4.权利要求1中所述的一种组蛋白和/或其有效治疗片断，其用于治疗性治疗白血病，特别是急性骨髓白血病，同时治疗性治疗血小板减少。
5.权利要求1中所述的一种组蛋白和/或其有效治疗片断，其用于治疗任何病因的疾病引起的血小板减少的情况。
6.权利要求5中所述的一种组蛋白和/或其有效治疗片断，其用于预防性治疗任何病因的疾病引起的危险的血小板减少的情况。
7.权利要求1中所述的一种组蛋白和/或其有疗效的片断，特征在于其为重组的人组蛋白H1.3。
CNA2006800157213A 2005-05-10 2006-05-04 组蛋白用于治疗目的的用途 Pending CN101171027A (zh)

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DE102005022319A DE102005022319A1 (de) 2005-05-10 2005-05-10 Verwendung von Histonen zu therapeutischen Zwecken
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AU3834589A (en) 1988-05-31 1990-01-05 Schering Biotech Corporation Method of treating myeloid leukemias
DE4000154A1 (de) * 1990-01-04 1991-07-11 Symbiotec Gmbh Chemotherapeutisches mittel, insbesondere zur behandlung von krebserkrankungen
US5571686A (en) * 1994-04-14 1996-11-05 Massachusetts Institute Of Technology Method of using megapoietin for prolonging the survival & viability of platlets
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DE19715149A1 (de) * 1997-04-11 1998-10-15 Symbiotec Gmbh Krebstherapeutikum und Diagnose zur Charakterisierung von Krebszellen mit individueller Eigenschaft
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WO2000064466A1 (en) * 1999-04-28 2000-11-02 Northwestern University Localization of major peptide autoepitopes for nucleosome specific t cells of systemic lupus erythematosus
DE10001113A1 (de) * 2000-01-13 2001-07-26 Strathmann Ag & Co Rekombinante Herstellung von humanen Histon 1-Subtypen sowie deren Verwendung für therapeutische Zwecke
US7931897B2 (en) 2001-02-07 2011-04-26 Chugai Seiyaku Kabushiki Kaisha Therapeutic agent for hematopoietic tumors
JP2004519476A (ja) 2001-02-22 2004-07-02 シンビオテック・ゲゼルシャフト・ミット・ベシュレンクター・ハフツンク 血小板凝集防止用組成物及び方法
JP2002355048A (ja) * 2001-05-31 2002-12-10 Communication Research Laboratory リボヌクレオチド還元酵素ｒ１とその阻害ペプチド
DE10230223A1 (de) * 2002-07-04 2004-01-22 Tegenero Ag Mikropartikel mit CD28-spezifischen monoklonalen Antikörpern
US20040146585A1 (en) * 2002-10-31 2004-07-29 Oregon Health & Science University Use of thiol-based compositions in treating chemotherapeutic agent-induced thrombocytopenia
DE102005022319A1 (de) * 2005-05-10 2006-11-23 Symbiotec Gesellschaft Zur Forschung Und Entwicklung Auf Dem Gebiet Der Biotechnologie Mbh Verwendung von Histonen zu therapeutischen Zwecken

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US20090305966A1 (en) 2009-12-10
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JP5667238B2 (ja) 2015-02-12
US20150119331A1 (en) 2015-04-30
JP2008540473A (ja) 2008-11-20
US8962562B2 (en) 2015-02-24
DE102005022319A1 (de) 2006-11-23
CA2608019A1 (en) 2006-11-16
CA2608019C (en) 2013-07-02
PT1879609E (pt) 2014-06-09
WO2006119912A2 (de) 2006-11-16
CA2811995A1 (en) 2006-11-16
HUE027070T2 (en) 2016-08-29
EP1879609A2 (de) 2008-01-23
KR20130099207A (ko) 2013-09-05
US20140148391A1 (en) 2014-05-29
KR20080007351A (ko) 2008-01-18
EP1879609B1 (de) 2014-03-12
PL1879609T3 (pl) 2014-08-29
WO2006119912A3 (de) 2007-04-12

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