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1. 发明授权

US07767415B2 Compositions and methods for modifying blood cell carbohydrates 有权
标题翻译：使用具有独特的底物特异性和动力学性质的α-正乙酰半乳糖胺酶和α-半乳糖苷酶对血型a，b和ab血细胞进行酶转化
公开(公告)号：US07767415B2
公开(公告)日：2010-08-03
申请号：US10251271
申请日：2002-09-20
申请人： Henrik Clausen , Humberto de la Vega , Cheryl Hill , Qiyong Peter Liu
发明人： Henrik Clausen , Humberto de la Vega , Cheryl Hill , Qiyong Peter Liu
IPC分类号： C12P21/06
CPC分类号： C12N5/0641 , C12N9/2402 , C12N9/2465 , C12Q1/34 , C12R1/465 , C12Y302/01022 , C12Y302/01049
摘要： This invention relates to enzymatic removal of type A and B antigens from blood group A, B, and AB reactive cells in blood products, and thereby converting these to non-A and non-B reactive cells. The invention further relates to using unique αN-acetylgalactosaminidases and α-galactosidases with superior kinetic properties for removing the immunodominant monosaccharides of the blood group A and B antigens and improved performance in enzymatic conversion of red blood cells. The preferred unique α-N-acetylgalactosaminidases and α-galactosidases exhibit the following characteristics: (i) exclusive, preferred or no less than 10% substrate specificity for the type A and B branched polysaccharide structures relative to measurable activity with simple mono- and disaccharide structures and aglycon derivatives hereof; (ii) optimal performance at neutral pH with blood group oligosaccharides and in enzymatic conversion of cells; and (iii) a favorable kinetic constant Km with mono- and oligosaccharide substrates. The conversion methods of the invention use significantly lower amounts of recombinant glycosidase enzymes than previous and result in complete sero-conversion of all blood group A and B red cells.
摘要翻译：本发明涉及从血型A，B，AB型反应性细胞中分离A型和B型抗原，从而将其转化为非A型和非B型细胞。本发明还涉及使用独特的αN-乙酰半乳糖胺酶和具有优异动力学性质的α-半乳糖苷酶来除去血型A和B抗原的免疫优势单糖，并提高红细胞酶促转化的表现。优选的独特的α-N-乙酰半乳糖胺酶和α-半乳糖苷酶具有以下特征：（i）相对于简单的单糖和二糖的可测量的活性，对于A型和B型支链多糖结构，独特的，优选的或不低于10％的底物特异性结构和糖苷配基衍生物; （ii）在中性pH下用血型寡糖和细胞酶促转化的最佳性能; 和（iii）具有单糖和寡糖底物的有利的动力学常数Km。本发明的转化方法比以前使用显着更低量的重组糖苷酶，并导致所有血型A和B红细胞的完全血清转化。

2. 发明申请

US20120321722A1 Platelet Storage and Reduced Bacterial Proliferation In Platelet Products Using A Sialidase Inhibitor 审中-公开
标题翻译：使用唾液酸酶抑制剂的血小板储存和减少血小板产物中的细菌增殖
公开(公告)号：US20120321722A1
公开(公告)日：2012-12-20
申请号：US13474627
申请日：2012-05-17
申请人： Qiyong Peter Liu , Karin Hoffmeister
发明人： Qiyong Peter Liu , Karin Hoffmeister
IPC分类号： C12N5/078 , A61P31/04 , A61P7/04 , A61K35/14
CPC分类号： A01N1/0226 , A01N1/0215 , A61K35/19 , C12N5/0644 , C12N9/2402 , C12Y302/01018
摘要： The present invention relates to methods and compositions for reducing sialidase activity and inhibiting bacterial proliferation of one or more bacteria in a platelet product preparation from one or more donors. In general, the method includes contacting the platelet product preparation with an amount of a sialidase inhibitor, to thereby obtain a sialidase inhibitor-treated platelet product preparation. Sialidase activity is reduced and the proliferation of one or more bacteria is inhibited, as compared to a platelet product preparation not subjected to the sialidase inhibitor treatment.
摘要翻译：本发明涉及用于降低唾液酸酶活性并抑制来自一种或多种供体的血小板产品制剂中的一种或多种细菌的细菌增殖的方法和组合物。通常，该方法包括使血小板产物制剂与一定量的唾液酸酶抑制剂接触，从而获得唾液酸酶抑制剂处理的血小板产品制剂。与未进行唾液酸酶抑制剂处理的血小板产品制剂相比，唾液酸酶活性降低并且抑制一种或多种细菌的增殖。

3. 发明申请

US20120202273A1 Enzymatic Conversion Of Blood Group A, B, And AB Red Blood Cells Using Alpha-N-Acetylgalactosaminidases and Alpha-Galactosidases With Unique Substrate Specificities And Kinetic Properties 有权
标题翻译：使用具有独特底物特异性和动力学性质的α-N-乙酰半乳糖胺酶和α-半乳糖苷酶对A组，B组和AB组血液细胞进行酶转化
公开(公告)号：US20120202273A1
公开(公告)日：2012-08-09
申请号：US13205588
申请日：2011-08-08
申请人： Henrik Clausen , Humberto de la Vega , Chery Hill , Qiyong Peter Liu
发明人： Henrik Clausen , Humberto de la Vega , Chery Hill , Qiyong Peter Liu
IPC分类号： C12N1/20
CPC分类号： C12N5/0641 , C12N9/2402 , C12N9/2465 , C12Q1/34 , C12R1/465 , C12Y302/01022 , C12Y302/01049
摘要： This invention relates to enzymatic removal of type A and B antigens from blood group A, B, and AB reactive cells in blood products, and thereby converting these to non-A and non-B reactive cells. The invention further relates to using unique α-N-acetylgalactosaminidases and α-galactosidases with superior kinetic properties for removing the immunodominant monosaccharides of the blood group A and B antigens and improved performance in enzymatic conversion of red blood cells. The preferred unique α-N-acetylgalactosaminidases and α-galactosidases exhibit the following characteristics: (i) exclusive, preferred or no less than 10% substrate specificity for the type A and B branched polysaccharide structures relative to measurable activity with simple mono- and disaccharide structures and aglycon derivatives hereof; (ii) optimal performance at neutral pH with blood group oligosaccharides and in enzymatic conversion of cells; and (iii) a favorable kinetic constant Km with mono- and oligosaccharide substrates. The conversion methods of the invention use significantly lower amounts of recombinant glycosidase enzymes than previous and result in complete sero-conversion of all blood group A and B red cells.
摘要翻译：本发明涉及从血型A，B，AB型反应性细胞中分离A型和B型抗原，从而将其转化为非A型和非B型细胞。本发明还涉及使用独特的α-N-乙酰半乳糖胺酶和具有优异动力学性质的α-半乳糖苷酶，用于去除血型A和B抗原的免疫优势单糖，并提高了红细胞酶促转化的表现。优选的独特的α-N-乙酰半乳糖胺酶和α-半乳糖苷酶具有以下特征：（i）相对于简单的单糖和二糖的可测量的活性，对A型和B型支链多糖结构的排列，优选或不低于10％的底物特异性结构和糖苷配基衍生物; （ii）在中性pH下用血型寡糖和细胞酶促转化的最佳性能; 和（iii）具有单糖和寡糖底物的有利的动力学常数Km。本发明的转化方法比以前使用显着更低量的重组糖苷酶，并导致所有血型A和B红细胞的完全血清转化。

4. 发明申请

US20110014170A1 NOVEL ALPHA-GALACTOSIDASES 有权
标题翻译：新的阿尔法胶质糖
公开(公告)号：US20110014170A1
公开(公告)日：2011-01-20
申请号：US12709070
申请日：2010-02-19
申请人： Qiyong Peter LIU , Henrik Clausen
发明人： Qiyong Peter LIU , Henrik Clausen
IPC分类号： A61K35/18 , A61P7/00 , C12N5/078 , C12N9/24
CPC分类号： C12N5/0654 , A61K35/32 , A61K35/35 , A61L27/3687 , A61L27/3695 , C12N5/0652 , C12N9/2465 , C12N2501/73 , C12N2506/09 , C12N2506/13 , C12N2506/1315 , C12N2506/14 , C12N2506/25 , C12Y302/01022
摘要： This invention relates to novel α-galactosidases for the enzymatic removal of the immunodominant monosaccharides on blood products and tissues. Specifically this invention provides a novel family of α3 glycosidases, used for the enzymatic removal of type B antigens from blood group B and AB reactive blood products, and the Galili antigen from non-human animal tissues, thereby converting these to non-immunogenic cells and tissues suitable for transplantation.
摘要翻译：本发明涉及用于在血液制品和组织上酶促去除免疫优势单糖的新型α-半乳糖苷酶。具体地说，本发明提供了一种新型的α3糖苷酶家族，用于从血型B和AB反应性血液制品中酶切除B型抗原，从非人动物组织中提取Galectin抗原，从而将其转化为非免疫原性细胞，适合移植的组织。

5. 发明申请

US20120294842A1 Platelet Additive Solution Having a Sialidase Inhibitor 审中-公开
标题翻译：具有唾液酸酶抑制剂的血小板添加剂溶液
公开(公告)号：US20120294842A1
公开(公告)日：2012-11-22
申请号：US13474679
申请日：2012-05-17
申请人： Qiyong Peter Liu , Karin Hoffmeister
发明人： Qiyong Peter Liu , Karin Hoffmeister
IPC分类号： A61K35/16 , C12N5/078 , A61P7/04
CPC分类号： A61K35/19 , A01N1/0215
摘要： The present invention relates to a platelet additive solution (PAS) having an amount of one or more sialidase inhibitors and optionally one or more glycan-modifying agents; and one or more of PAS components that includes a salt, a citrate source, a carbon source, and any combination thereof.
摘要翻译：本发明涉及具有一种或多种唾液酸酶抑制剂和任选的一种或多种聚糖改性剂量的血小板添加剂溶液（PAS）; 以及一种或多种包含盐，柠檬酸盐源，碳源及其任何组合的PAS组分。

6. 发明授权

US08883478B2 Methods of preparing tissues for xenotransplantation using α-galactosidases 有权
标题翻译：使用α-半乳糖苷酶制备异种移植组织的方法
公开(公告)号：US08883478B2
公开(公告)日：2014-11-11
申请号：US12709070
申请日：2010-02-19
申请人： Qiyong Peter Liu , Henrik Clausen
发明人： Qiyong Peter Liu , Henrik Clausen
IPC分类号： C12Q1/34 , C12N9/40 , C12P21/00 , C07K14/00
CPC分类号： C12N5/0654 , A61K35/32 , A61K35/35 , A61L27/3687 , A61L27/3695 , C12N5/0652 , C12N9/2465 , C12N2501/73 , C12N2506/09 , C12N2506/13 , C12N2506/1315 , C12N2506/14 , C12N2506/25 , C12Y302/01022
摘要： This invention relates to novel α-galactosidases for the enzymatic removal of the immunodominant monosaccharides on blood products and tissues. Specifically this invention provides a novel family of α3 glycosidases, used for the enzymatic removal of type B antigens from blood group B and AB reactive blood products, and the Galili antigen from non-human animal tissues, thereby converting these to non-immunogenic cells and tissues suitable for transplantation.
摘要翻译：本发明涉及用于在血液制品和组织上酶促去除免疫优势单糖的新型α-半乳糖苷酶。具体地说，本发明提供了一种新型的α3糖苷酶家族，用于从血型B和AB反应性血液制品中酶切除B型抗原，从非人动物组织中提取Galectin抗原，从而将其转化为非免疫原性细胞，适合移植的组织。

7. 发明申请

US20110045569A1 ENZYMATIC CONVERSION OF BLOOD GROUP A, B, AND AB RED BLOOD CELLS USING ALPHA-N- ACETYLGALACTOSAMINIDASES AND ALPHA-GALACTOSIDASES WITH UNIQUE SUBSTRATE SPECIFICITIES AND KINETIC PROPERTIES 失效
标题翻译：使用ALPHA-N-乙酰胆碱酯酶和ALPHA-GALACTOSIDASES具有独特的底物特异性和动力学特性的组A，B和AB红血细胞的酶转化
公开(公告)号：US20110045569A1
公开(公告)日：2011-02-24
申请号：US12789946
申请日：2010-05-28
申请人： Henrik Clausen , Humberto De La Vega , Cheryl Hill , Qiyong Peter Liu
发明人： Henrik Clausen , Humberto De La Vega , Cheryl Hill , Qiyong Peter Liu
IPC分类号： C12N9/40 , C12N1/20
CPC分类号： C12N5/0641 , C12N9/2402 , C12N9/2465 , C12Q1/34 , C12R1/465 , C12Y302/01022 , C12Y302/01049
摘要： This invention relates to enzymatic removal of type A and B antigens from blood group A, B, and AB reactive cells in blood products, and thereby converting these to non-A and non-B reactive cells. The invention further relates to using unique α-N-acetylgalactosaminidases and α-galactosidases with superior kinetic properties for removing the immunodominant monosaccharides of the blood group A and B antigens and improved performance in enzymatic conversion of red blood cells. The preferred unique α-N-acetylgalactosaminidases and α-galactosidases exhibit the following characteristics: (i) exclusive, preferred or no less than 10% substrate specificity for the type A and B branched polysaccharide structures relative to measurable activity with simple mono- and disaccharide structures and aglycon derivatives hereof; (ii) optimal performance at neutral pH with blood group oligosaccharides and in enzymatic conversion of cells; and (iii) a favorable kinetic constant Km with mono- and oligosaccharide substrates. The conversion methods of the invention use significantly lower amounts of recombinant glycosidase enzymes than previous and result in complete sero-conversion of all blood group A and B red cells.
摘要翻译：本发明涉及从血型A，B，AB型反应性细胞中分离A型和B型抗原，从而将其转化为非A型和非B型细胞。本发明还涉及使用独特的α-N-乙酰半乳糖胺酶和具有优异动力学性质的α-半乳糖苷酶，用于去除血型A和B抗原的免疫优势单糖，并提高了红细胞酶促转化的表现。优选的独特的α-N-乙酰半乳糖胺酶和α-半乳糖苷酶具有以下特征：（i）相对于简单的单糖和二糖的可测量的活性，对于A型和B型支链多糖结构，独特的，优选的或不低于10％的底物特异性结构和糖苷配基衍生物; （ii）在中性pH下用血型寡糖和细胞酶促转化的最佳性能; 和（iii）具有单糖和寡糖底物的有利的动力学常数Km。本发明的转化方法比以前使用显着更低量的重组糖苷酶，并导致所有血型A和B红细胞的完全血清转化。

8. 发明授权

US08697411B2 Streptomyces griseoplanus comprising an α-galactosidase for removing immunodominant α-galactose monosaccharides from blood group B or AB reactive cells 有权
标题翻译：包含α-半乳糖苷酶的灰色链霉菌，用于从血型B或AB反应性细胞中除去免疫优势的α-半乳糖单糖
公开(公告)号：US08697411B2
公开(公告)日：2014-04-15
申请号：US13205588
申请日：2011-08-08
申请人： Henrik Clausen , Humberto de la Vega , Cheryl Hill , Qiyong Peter Liu
发明人： Henrik Clausen , Humberto de la Vega , Cheryl Hill , Qiyong Peter Liu
IPC分类号： C12N9/24
CPC分类号： C12N5/0641 , C12N9/2402 , C12N9/2465 , C12Q1/34 , C12R1/465 , C12Y302/01022 , C12Y302/01049
摘要： This invention relates to enzymatic removal of type A and B antigens from blood group A, B, and AB reactive cells in blood products, and thereby converting these to non-A and non-B reactive cells. The invention further relates to using unique α-N-acetylgalactosaminidases and α-galactosidases with superior kinetic properties for removing the immunodominant monosaccharides of the blood group A and B antigens and improved performance in enzymatic conversion of red blood cells. The preferred unique α-N-acetylgalactosaminidases and α-galactosidases exhibit the following characteristics: (i) exclusive, preferred or no less than 10% substrate specificity for the type A and B branched polysaccharide structures relative to measurable activity with simple mono- and disaccharide structures and aglycon derivatives hereof; (ii) optimal performance at neutral pH with blood group oligosaccharides and in enzymatic conversion of cells; and (iii) a favorable kinetic constant Km with mono- and oligosaccharide substrates. The conversion methods of the invention use significantly lower amounts of recombinant glycosidase enzymes than previous and result in complete sero-conversion of all blood group A and B red cells.
摘要翻译：本发明涉及从血型A，B，AB型反应性细胞中分离A型和B型抗原，从而将其转化为非A型和非B型细胞。本发明还涉及使用独特的α-N-乙酰半乳糖胺酶和具有优异动力学性质的α-半乳糖苷酶，用于去除血型A和B抗原的免疫优势单糖，并提高了红细胞酶促转化的表现。优选的独特的α-N-乙酰半乳糖胺酶和α-半乳糖苷酶具有以下特征：（i）相对于简单的单糖和二糖的可测量的活性，对于A型和B型支链多糖结构，独特的，优选的或不低于10％的底物特异性结构和糖苷配基衍生物; （ii）在中性pH下用血型寡糖和细胞酶促转化的最佳性能; 和（iii）具有单糖和寡糖底物的有利的动力学常数Km。本发明的转化方法比以前使用显着更低量的重组糖苷酶，并导致所有血型A和B红细胞的完全血清转化。

9. 发明申请

US20120321601A1 Increased In Vivo Circulation Time of Platelets After Storage With A Sialidase Inhibitor 审中-公开
标题翻译：用唾液酸酶抑制剂储存后血小板体内循环时间增加
公开(公告)号：US20120321601A1
公开(公告)日：2012-12-20
申请号：US13474473
申请日：2012-05-17
申请人： Qiyong Peter Liu , Karin Hoffmeister , Robert Sackstein
发明人： Qiyong Peter Liu , Karin Hoffmeister , Robert Sackstein
IPC分类号： C12N5/078 , A61J1/10 , A61J1/05 , A61K35/14 , A61P7/04
CPC分类号： A01N1/0226 , A01N1/0215 , A61K35/19 , C12N5/0644 , C12N9/2402 , C12Y302/01018
摘要： The present invention relates to methods, compositions and kits for increasing the in vivo circulation time of isolated platelets by storing the platelets with one or more sialidase inhibitors.
摘要翻译：本发明涉及通过将血小板与一种或多种唾液酸酶抑制剂一起储存来增加分离血小板的体内循环时间的方法，组合物和试剂盒。

10. 发明授权

US07993896B2 Streptomyces griseoplanus α-galactosidases for removing immunodominant α-galactose monosaccharides from blood group B or AB reactive cells 失效
标题翻译：用于从血型B或AB反应性细胞中去除免疫显性α-半乳糖单糖的灰色链霉菌α-半乳糖苷酶
公开(公告)号：US07993896B2
公开(公告)日：2011-08-09
申请号：US12789946
申请日：2010-05-28
申请人： Henrik Clausen , Humberto de la Vega , Cheryl Hill , Qiyong Peter Liu
发明人： Henrik Clausen , Humberto de la Vega , Cheryl Hill , Qiyong Peter Liu
IPC分类号： C12N9/24
CPC分类号： C12N5/0641 , C12N9/2402 , C12N9/2465 , C12Q1/34 , C12R1/465 , C12Y302/01022 , C12Y302/01049
摘要： This invention relates to enzymatic removal of type A and B antigens from blood group A, B, and AB reactive cells in blood products, and thereby converting these to non-A and non-B reactive cells. The invention further relates to using unique α-N-acetylgalactosaminidases and α-galactosidases with superior kinetic properties for removing the immunodominant monosaccharides of the blood group A and B antigens and improved performance in enzymatic conversion of red blood cells. The preferred unique α-N-acetylgalactosaminidases and α-galactosidases exhibit the following characteristics: (i) exclusive, preferred or no less than 10% substrate specificity for the type A and B branched polysaccharide structures relative to measurable activity with simple mono- and disaccharide structures and aglycon derivatives hereof; (ii) optimal performance at neutral pH with blood group oligosaccharides and in enzymatic conversion of cells; and (iii) a favorable kinetic constant Km with mono- and oligosaccharide substrates. The conversion methods of the invention use significantly lower amounts of recombinant glycosidase enzymes than previous and result in complete sero-conversion of all blood group A and B red cells.
摘要翻译：本发明涉及从血型A，B，AB型反应性细胞中分离A型和B型抗原，从而将其转化为非A型和非B型细胞。本发明还涉及使用独特的α-N-乙酰半乳糖胺酶和具有优异动力学性质的α-半乳糖苷酶，用于去除血型A和B抗原的免疫优势单糖，并提高了红细胞酶促转化的表现。优选的独特的α-N-乙酰半乳糖胺酶和α-半乳糖苷酶具有以下特征：（i）相对于简单的单糖和二糖的可测量的活性，对于A型和B型支链多糖结构，独特的，优选的或不低于10％的底物特异性结构和糖苷配基衍生物; （ii）在中性pH下用血型寡糖和细胞酶促转化的最佳性能; 和（iii）具有单糖和寡糖底物的有利的动力学常数Km。本发明的转化方法比以前使用显着更低量的重组糖苷酶，并导致所有血型A和B红细胞的完全血清转化。

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