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1. 发明申请

WO1996012731A1 PEPTIDE SPECIFICITY OF ANTI-MYELIN BASIC PROTEIN AND THE ADMINISTRATION OF MYELIN BASIC PROTEIN PEPTIDES TO MULTIPLE SCLEROSIS PATIENTS 审中-公开
标题翻译：抗谷氨酸蛋白酶基因蛋白的肽特异性和髓鞘基础蛋白质肽对多发性硬化症患者的治疗
公开(公告)号：WO1996012731A1
公开(公告)日：1996-05-02
申请号：PCT/CA1995000583
申请日：1995-10-20
申请人： THE GOVERNORS OF THE UNIVERSITY OF ALBERTA
发明人： THE GOVERNORS OF THE UNIVERSITY OF ALBERTA , WARREN, Kenneth, G. , CATZ, Ingrid
IPC分类号： C07K07/06
CPC分类号： C07K14/4713 , A61K38/00
摘要： Human myelin basic protein (h-MBP) has a molecular weight of 18.5 KD and contains 170 amino acid residues. Synthetic peptides ranging in length from about 8 to 25 residues and covering the entire length of the protein have been produced. Antibodies to h-MBP (anti-MBP) were found to be neutralized by the synthetic peptides, in vitro, which span the h-MBP from about amino acid residue 61 to about amino acid residue 106. The peptides, which cover both the amino (about residues 1 to 63) and carboxy (about residues 117 to 162) terminals of h-MBP did not neutralize purified anti-MBP. Intrathecal administration of peptide MBP75-95, either as a single dose, or as repeated injections for periods up to 10 weeks, produced complete binding-neutralization of free (F) anti-MBP with no change in bound (B) levels. A control peptide MBP35-58 had no effect on F or B anti-MBP levels. Intravenous administration of MBP75-95 resulted in significant decline of F and B CSF anti-MBP levels over a period of one month. Administration of MBP synthetic peptides to MS patients either intrathecally or intravenously did not have any adverse neurological effects and systemic complications did not occur. The MBP epitope for MS anti-MBP has been localized to an area between Pro85 and Pro96.
摘要翻译：人髓磷脂碱性蛋白（h-MBP）的分子量为18.5KD，含有170个氨基酸残基。已经生产了长度为约8至25个残基并覆盖蛋白质整个长度的合成肽。发现h-MBP（抗MBP）的抗体在体外被合成肽中和，其跨越从约氨基酸残基61至约氨基酸残基106的h-MBP。涵盖氨基酸（约1至63个残基）和羧基（约117至162个）末端未中和纯化的抗MBP。鞘内给药MBP75-95作为单一剂量，或重复注射至多达10周，产生游离（F）抗MBP的完全结合中和，结合（B）水平无变化。对照肽MBP35-58对F或B抗MBP水平没有影响。 MBP75-95的静脉内给药导致F和B CSF抗MBP水平在一个月内显着下降。对鞘内或静脉内的MS患者施用MBP合成肽没有任何不良的神经系统影响，并没有发生全身并发症。用于MS抗MBP的MBP表位已被定位到Pro85和Pro96之间的区域。

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