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1. 发明授权

US06555116B1 Alleviation of the allergenic potential of airborne and contact allergens by thioredoxin 失效
标题翻译：通过硫氧还蛋白降低机载和接触过敏原的过敏潜能
公开(公告)号：US06555116B1
公开(公告)日：2003-04-29
申请号：US09238379
申请日：1999-01-27
申请人： Bob B. Buchanan , Gregorio del Val , Rosa M. Lozano , Joshua H. Wong , Boihon C. Yee , Oscar L. Frick
发明人： Bob B. Buchanan , Gregorio del Val , Rosa M. Lozano , Joshua H. Wong , Boihon C. Yee , Oscar L. Frick
IPC分类号： A61K3936
CPC分类号： A21D2/26 , A21D2/264 , A21D2/265 , A21D2/266 , A21D2/36 , A21D8/04 , A21D13/064 , A23C9/1209 , A23C9/1213 , A23C9/152 , A23J1/12 , A23J1/14 , A23J3/08 , A23J3/18 , A23K20/147 , A23L5/27 , A23L7/109 , A23L11/34 , A23L13/48 , A23L33/17 , A61K39/35 , A61K2035/122 , C07K1/1133 , C07K14/415 , C07K14/43504 , C07K14/46 , C07K14/76 , C07K14/811 , C12N9/0036 , C12N9/20 , C12P21/02 , C12Q1/26 , C12Q1/34 , C12Y108/01008 , C12Y108/01009 , Y10S436/904 , Y10T436/182
摘要： Thioredoxin, a small dithiol protein, is a specific reductant for allergenic proteins and particularly allergenic proteins present in pollen and animal and plant sources. All targeted proteins contain disulfide (S—S) bonds that are reduced to the sulfhydryl (SH) level by thioredoxin. The proteins are allergenically active and less digestible in the oxidized (S—S) state. When reduced (SH state), they lose their allergenicity and/or become more digestible. Thioredoxin achieved this reduction when activated (reduced) either by NADPH via NADP-thioredoxin reductase (physiological conditions) or by lipoic acid chemical reductant. Skin tests carried out with sensitized dogs showed that treatment of the pollens with reduced thioredoxin prior to injection eliminated or decreased the allergenicity of the pollen. Studies showed increased digestion of the pollen proteins by pepsin following reduction by thioredoxin. Pollen proteins that have been reduced by thioredoxin are effective and safe immunotherapeutic agents for decreasing or eliminating an animal's allergic reaction that would otherwise occur upon exposure to the non-reduced pollen protein.
摘要翻译：硫氧还蛋白，一种小二硫醇蛋白，是一种特异性的还原剂，适用于过敏原蛋白，特别是花粉和动植物来源的变应原蛋白。所有靶向蛋白含有通过硫氧还蛋白还原成巯基（SH）水平的二硫键（S-S）键。蛋白质是过敏性活性的，在氧化（S-S）状态下消化不良。当减少（SH状态）时，它们失去过敏原性和/或变得更易消化。当NADPH通过NADP-硫氧还蛋白还原酶（生理条件）或硫辛酸化学还原剂被活化（还原）时，硫氧还蛋白实现了这一还原。用致敏狗进行的皮肤试验表明，在注射前用降低的硫氧还蛋白处理花粉消除或降低了花粉的致敏性。研究显示硫氧还蛋白还原后，通过胃蛋白酶消化花粉蛋白。通过硫氧还蛋白还原的花粉蛋白是有效和安全的免疫治疗剂，用于减少或消除否则在暴露于未还原花粉蛋白时会发生的动物过敏反应。

2. 发明授权

US07074900B2 Alleviation of the allergenic potential of airborne and contact allergens by thioredoxin 失效
公开(公告)号：US07074900B2
公开(公告)日：2006-07-11
申请号：US10422422
申请日：2003-04-23
申请人： Bob B. Buchanan , Gregorio del Val , Rosa M. Lozano , Joshua H. Wong , Boihan C. Yee , Oscar L. Frick
发明人： Bob B. Buchanan , Gregorio del Val , Rosa M. Lozano , Joshua H. Wong , Boihan C. Yee , Oscar L. Frick
IPC分类号： C07K14/00 , C07K14/415 , A61K39/35 , A61K39/36
CPC分类号： A21D2/26 , A21D2/264 , A21D2/265 , A21D2/266 , A21D2/36 , A21D8/04 , A21D13/064 , A23C9/1209 , A23C9/1213 , A23C9/152 , A23J1/12 , A23J1/14 , A23J3/08 , A23J3/18 , A23K20/147 , A23L5/27 , A23L7/109 , A23L11/34 , A23L13/48 , A23L33/17 , A61K39/35 , A61K2035/122 , C07K1/1133 , C07K14/415 , C07K14/43504 , C07K14/46 , C07K14/76 , C07K14/811 , C12N9/0036 , C12N9/20 , C12P21/02 , C12Q1/26 , C12Q1/34 , C12Y108/01008 , C12Y108/01009 , Y10S436/904 , Y10T436/182
摘要： Thioredoxin, a small dithiol protein, is a specific reductant for allergenic proteins and particularly allergenic proteins present in pollen and animal and plant sources. All targeted proteins contain disulfide (S—S) bonds that are reduced to the sulfhydryl (SH) level by thioredoxin. The proteins are allergenically active and less digestible in the oxidized (S—S) state. When reduced (SH state), they lose their allergenicity and/or become more digestible. Thioredoxin achieved this reduction when activated (reduced) either by NADPH via NADP-thioredoxin reductase (physiological conditions) or by lipoic acid chemical reductant. Skin tests carried out with sensitized dogs showed that treatment of the pollens with reduced thioredoxin prior to injection eliminated or decreased the allergenicity of the pollen. Studies showed increased digestion of the pollen proteins by pepsin following reduction by thioredoxin. Pollen proteins that have been reduced by thioredoxin are effective and safe immunotherapeutic agents for decreasing or eliminating an animal's allergic reaction that would otherwise occur upon exposure to the non-reduced pollen protein.

3. 发明授权

US06677433B2 Stabilization of hypoallergenic, hyperdigestible previously reduced proteins 失效
标题翻译：稳定低变应原，超可消化的先前减少的蛋白质
公开(公告)号：US06677433B2
公开(公告)日：2004-01-13
申请号：US09779375
申请日：2001-02-07
申请人： Bob B. Buchanan , Susumu Morigasaki , Gregorio del Val , Oscar L. Frick
发明人： Bob B. Buchanan , Susumu Morigasaki , Gregorio del Val , Oscar L. Frick
IPC分类号： C07K1400
CPC分类号： A21D2/26 , A21D2/264 , A21D2/265 , A21D2/266 , A21D2/36 , A21D8/04 , A21D13/064 , A23C9/1209 , A23C9/1213 , A23C9/152 , A23J1/12 , A23J1/14 , A23J3/08 , A23J3/18 , A23K20/147 , A23L5/27 , A23L7/109 , A23L11/34 , A23L13/48 , A23L33/17 , A61K38/00 , A61K39/35 , A61K2035/122 , C07K1/1133 , C07K14/415 , C07K14/43504 , C07K14/46 , C07K14/76 , C07K14/811 , C12N9/0036 , C12N9/20 , C12P21/02 , C12Q1/26 , C12Q1/34 , C12Y108/01008 , C12Y108/01009
摘要： Disulfide proteins showed mitigated allergenicity and increased digestibility by pepsin following reduction by thioredoxin. The sulfhydryl groups newly formed on reduction by thioredoxin (at 4° C.) or dithiothreitol (DTT) (at 55° C.) were blocked with a physiological disulfide, such as cystamine or oxidized glutathione (GSSG) to obtain stable forms of the disarmed allergen. When derivatized with cystamine, BLG was separated from its oxidized and reduced forms on non-reducing SDS-PAGE and appeared to lack sulfhydryl groups. Although less effective GSSG, gave similar results. Allergenicity of the two derivatives was compared with that of the oxidized, reduced and reoxidized forms of BLG by skin testing dogs from a colony sensitized to cow's milk. Both the cystamine and GSSG derivatized BLG showed decreased allergenicity and increased sensitivity to pepsin as compared to controls. The reoxidized form resembled the derivatives in having lower allergenicity. The thioredoxin- and DTT-reduced forms showed hypoallergenic, hyperdigestible properties, most effectively when the reduced proteins were heated at 55° C. Whole milk subjected to these procedures showed results similar to those obtained with pure BLG. Other proteins are similarly stabilized. Stable forms of such disarmed, hypoallergenic and hyperdigestible disulfide protein allergens or just hypoallergenic or just hyperdigestible protein allergens are useful in foods as well as clinical preparations.
摘要翻译：二硫化物蛋白质在硫氧还蛋白还原后显示减轻的过敏原性和胃蛋白酶的消化率增加。通过硫氧还蛋白（4℃）还原二硫苏糖醇（DTT）（在55℃）下新形成的巯基用生理二硫化物如胱氨酸或氧化型谷胱甘肽（GSSG）封闭，得到稳定形式的解除武装的过敏原当用胱胺衍生化时，BLG在非还原性SDS-PAGE上从其氧化和还原形式分离出来，并且似乎缺少巯基。虽然GSSG效果较差，但得到了类似的结果。将两种衍生物的过敏原与来自对牛奶敏感的菌落进行皮肤测试的狗的氧化，还原和再氧化形式的BLG进行比较。与对照相比，胱氨酸和GSSG衍生的BLG都显示出降低的过敏原性和对胃蛋白酶的敏感性增加。再氧化形式类似于具有较低过敏原性的衍生物。当减少的蛋白质在55℃下加热时，硫氧还蛋白和DTT减少的形式显示出低变应原性，超消化性质，最有效的是，经过这些程序的全脂乳显示出与用纯BLG获得的结果相似的结果。其他蛋白质同样稳定。这种解除武装，低变应原和超可消化的二硫化物蛋白质过敏原或刚刚低变应原或仅仅是超可消化的蛋白质过敏原的稳定形式可用于食物以及临床制剂。

4. 发明授权

US06190723B1 Neutralization of food allergens by thioredoxin 失效
标题翻译：通过硫氧还蛋白中和食物过敏原
公开(公告)号：US06190723B1
公开(公告)日：2001-02-20
申请号：US09046780
申请日：1998-03-23
申请人： Bob B. Buchanan , Karoly Kobrehel , Boihon C. Yee , Rosa Lozano , Oscar L. Frick , Richard W. Ermel
发明人： Bob B. Buchanan , Karoly Kobrehel , Boihon C. Yee , Rosa Lozano , Oscar L. Frick , Richard W. Ermel
IPC分类号： C07K100
CPC分类号： A21D13/064 , A21D2/26 , A21D2/264 , A21D2/265 , A21D2/266 , A21D2/36 , A21D8/04 , A23C9/1209 , A23C9/1213 , A23C9/152 , A23J1/12 , A23J1/14 , A23J3/08 , A23J3/18 , A23K20/147 , A23L5/27 , A23L7/109 , A23L7/196 , A23L11/34 , A23L13/48 , A23L33/17 , A61K39/35 , C07K1/1133 , C07K14/415 , C07K14/43504 , C07K14/46 , C07K14/76 , C07K14/811 , C12N9/0036 , C12N9/20 , C12P21/02 , C12Q1/26 , C12Q1/34 , C12Y108/01008 , C12Y108/01009
摘要： Thioredoxin, a small dithiol protein, is a specific reductant for major allergenic proteins present in widely used foods from animal and plant sources. All targeted allergenic proteins contain disulfide (S—S) bonds that are reduced to the sulfhydryl (SH) level by thioredoxin. The proteins are allergenically active in the oxidized (S—S) state. When reduced (SH state), they lose their allergenicity. Thioredoxin achieved this reduction when activated (reduced) either by NADPH via NADP-thioredoxin reductase (physiological conditions) or by dithiothreitol, a chemical reductant. Skin tests and feeding experiments carried out with sensitized dogs showed that treatment of the food with reduced thioredoxin prior to ingestion eliminated or decreased the allergenicity of the food.
摘要翻译：硫氧还蛋白，小二硫醇蛋白，是来自动物和植物来源的广泛使用的食品中存在的主要变应原蛋白的特异性还原剂。所有靶向过敏原蛋白都含有通过硫氧还蛋白还原成巯基（SH）水平的二硫键（S-S）键。蛋白质在氧化（S-S）状态下具有过敏性活性。当减少（SH状态）时，它们失去其过敏原性。当NADPH通过NADP-硫氧还蛋白还原酶（生理条件）或二硫苏糖醇（化学还原剂）活化（还原）时，硫氧还蛋白实现了这种还原。用敏化狗进行的皮肤试验和喂养实验表明，在摄取之前用硫氧还蛋白降低的食物处理消除或降低了食物的变应原性。

5. 发明授权

US5792506A Neutralization of food allergens by thioredoxin 失效
标题翻译：通过硫氧还蛋白中和食物过敏原
公开(公告)号：US5792506A
公开(公告)日：1998-08-11
申请号：US326976
申请日：1994-10-21
申请人： Bob B. Buchanan , Karoly Kobrehel , Boihon C. Yee , Rosa Lozano , Oscar L. Frick , Richard W. Ermel
发明人： Bob B. Buchanan , Karoly Kobrehel , Boihon C. Yee , Rosa Lozano , Oscar L. Frick , Richard W. Ermel
IPC分类号： A23K1/18 , A21D2/26 , A21D2/36 , A21D8/04 , A21D13/06 , A23C9/00 , A23C9/12 , A23C9/152 , A23J1/12 , A23J1/14 , A23J3/08 , A23J3/18 , A23K1/16 , A23L1/015 , A23L1/10 , A23L1/16 , A23L1/182 , A23L1/20 , A23L1/211 , A23L1/305 , A23L1/31 , A23L1/314 , A61K35/20 , A61K35/34 , A61K35/54 , A61K36/899 , A61K38/44 , A61K38/46 , A61K39/35 , A61P37/08 , C07K1/00 , C07K1/113 , C07K14/415 , C07K14/435 , C07K14/46 , C07K14/76 , C07K14/81 , C12N9/02 , C12N9/20 , C12P21/02 , C12Q1/26 , C12Q1/34 , A23L1/03
CPC分类号： A21D13/064 , A21D2/26 , A21D2/264 , A21D2/265 , A21D2/266 , A21D2/36 , A21D8/04 , A23C9/1209 , A23C9/1213 , A23C9/152 , A23J1/12 , A23J1/14 , A23J3/08 , A23J3/18 , A23K20/147 , A23L11/34 , A23L13/48 , A23L33/17 , A23L5/27 , A23L7/109 , A23L7/196 , A61K39/35 , C07K1/1133 , C07K14/415 , C07K14/43504 , C07K14/46 , C07K14/76 , C07K14/811 , C12N9/0036 , C12N9/20 , C12P21/02 , C12Q1/26 , C12Q1/34 , C12Y108/01008 , C12Y108/01009
摘要： Thioredoxin, a small dithiol protein, is a specific reductant for major allergenic proteins present in widely used foods from animal and plant sources. All targeted allergenic proteins contain disulfide (S--S) bonds that are reduced to the sulfhydryl (SH) level by thioredoxin. The proteins are allergenically active in the oxidized (S--S) state. When reduced (SH state), they lose their allergenicity. Thioredoxin achieved this reduction when activated (reduced) either by NADPH via NADP-thioredoxin reductase (physiological conditions) or by dithiothreitol, a chemical reductant. Skin tests and feeding experiments carried out with sensitized dogs showed that treatment of the food with reduced thioredoxin prior to ingestion eliminated or decreased the allergenicity of the food.
摘要翻译：硫氧还蛋白，小二硫醇蛋白，是来自动物和植物来源的广泛使用的食品中存在的主要变应原蛋白的特异性还原剂。所有靶向过敏原蛋白都含有通过硫氧还蛋白还原成巯基（SH）水平的二硫键（S-S）键。蛋白质在氧化（S-S）状态下具有过敏性活性。当减少（SH状态）时，它们失去其过敏原性。当NADPH通过NADP-硫氧还蛋白还原酶（生理条件）或二硫苏糖醇（化学还原剂）活化（还原）时，硫氧还蛋白实现了这种还原。用敏化狗进行的皮肤试验和喂养实验表明，在摄取之前用硫氧还蛋白降低的食物处理消除或降低了食物的过敏原性。

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