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1. 发明授权

US08986759B2 Method to increase the growth velocity of human infants 有权
标题翻译：增加人类婴幼儿生长速度的方法
公开(公告)号：US08986759B2
公开(公告)日：2015-03-24
申请号：US13278662
申请日：2011-10-21
申请人： Olle Hernell , Birgitta Olsson , Patrik Strömberg , Lennart Svensson , Kristina Timdahl , M{hacek over (a)}rten Vågerö , Maria Öhman
发明人： Olle Hernell , Birgitta Olsson , Patrik Strömberg , Lennart Svensson , Kristina Timdahl , M{hacek over (a)}rten Vågerö , Maria Öhman
IPC分类号： A61K38/46 , C12N9/20 , A23L1/00
CPC分类号： A61K38/465 , A23L5/00 , A23L33/17 , A23L33/40 , A23V2002/00 , C12Y301/01003 , C12Y301/01013
摘要： The present invention relates to a method to increase the growth velocity of a human infant, said method comprising the enteral administration to said infant of recombinant human bile-salt-stimulated lipase (rhBSSL). Such method has particular utility for underweight or preterm human infants, particular those in medical need of increasing their growth velocity. The invention also relates to compositions, including infant feeds, kits, packaged-pharmaceutical-products and pharmaceutical compositions, and also to methods to prepare infant feeds. In another aspect, the present invention relates to methods to: (X) protect the small bowel mucosa of a human infant from damage; to (Y) protect an immature intestinal epithelium of a human infant from the deleterious effects of incompletely digested and/or excess fat and/or lipid; and/or to (Z) limit accumulation of incompletely digested and/or excess fat and/or lipid in the ileum of a human infant; said methods in each case comprising the step of enteral administration of rhBSSL.
摘要翻译：本发明涉及一种增加人类婴儿生长速度的方法，所述方法包括向所述婴儿重组人胆汁盐刺激的脂肪酶（rhBSSL）进行肠内给药。这种方法对于体重不足或早产儿的婴儿特别有用，特别是医疗需要增加其生长速度的方法。本发明还涉及组合物，包括婴儿饲料，试剂盒，包装的药物产品和药物组合物，以及制备婴儿饲料的方法。另一方面，本发明涉及以下方法：（X）保护人类婴儿的小肠粘膜免受损伤; 至（Y）保护人类婴幼儿的未成熟肠上皮细胞不完全消化和/或过量脂肪和/或脂质的有害作用; 和/或（Z）限制人类婴儿回肠中不完全消化和/或多余的脂肪和/或脂质的积累; 所述方法在每种情况下包括rhBSSL的肠内给药步骤。

2. 发明授权

US08986682B2 Method to increase the absorption of unsaturated fatty acids by human infants 有权
标题翻译：增加人类不饱和脂肪酸吸收的方法
公开(公告)号：US08986682B2
公开(公告)日：2015-03-24
申请号：US13278682
申请日：2011-10-21
申请人： Olle Hernell , Birgitta Olsson , Patrik Strömberg , Lennart Svensson , Kristina Timdahl , Mårten Vågerö , Maria Öhman
发明人： Olle Hernell , Birgitta Olsson , Patrik Strömberg , Lennart Svensson , Kristina Timdahl , Mårten Vågerö , Maria Öhman
IPC分类号： A61P27/02 , C12N9/20 , A23C9/20 , A23L1/03 , A23L1/29 , A61K38/46 , A23C9/12
CPC分类号： A61K38/465 , A23C9/1216 , A23C9/206 , A23L29/06 , A23L33/12 , A23L33/40 , A23V2002/00 , C12Y301/01003 , A23V2200/08 , A23V2250/54 , A23V2300/50
摘要： The present invention relates to a method to increase the absorption by a human infant of at least one unsaturated fatty acid, said method comprising the enteral administration to said infant of recombinant human bile-salt-stimulated lipase (rhBSSL). In another aspect the invention also relates to a method to improve the visual and/or cognitive development of a human infant, said method comprising the enteral administration to said infant of rhBSSL. Such methods have particular utility for preterm human infants, particular those in medical need of increasing their absorption of or availability to such unsaturated fatty acids. In further aspects, the invention relates to kits, packaged-pharmaceutical-products, recombinant human bile-salt-stimulated lipase and pharmaceutical compositions, in each case useful for increasing the absorption by a human infant of at least one unsaturated fatty acid, or for increasing the visual and/or cognitive development of a human infant.
摘要翻译：本发明涉及一种增加人类婴幼儿至少一种不饱和脂肪酸吸收的方法，所述方法包括向所述婴儿重组人胆汁盐刺激的脂肪酶（rhBSSL）进行肠内施用。在另一方面，本发明还涉及一种改善人类婴儿的视觉和/或认知发育的方法，所述方法包括对所述婴儿的rhBSSL的肠内施用。这些方法对于早产儿的婴儿具有特别的用途，特别是在医学上需要增加其对这种不饱和脂肪酸的吸收或可用性的这些方法。在另外的方面，本发明涉及试剂盒，包装的药物产品，重组人胆汁盐刺激的脂肪酶和药物组合物，在每种情况下都可用于增加人类婴幼儿至少一种不饱和脂肪酸的吸收，或用于增加人类婴儿的视觉和/或认知发育。

3. 发明申请

US20140099323A1 METHODS FOR TREATMENT OF INFLAMMATORY DISEASES 有权
标题翻译：治疗炎症性疾病的方法
公开(公告)号：US20140099323A1
公开(公告)日：2014-04-10
申请号：US14067495
申请日：2013-10-30
申请人： OLLE HERNELL , SUSANNE LINDQUIST , LENNART GUSTAV LUNDBERG
发明人： OLLE HERNELL , SUSANNE LINDQUIST , LENNART GUSTAV LUNDBERG
IPC分类号： A61K39/395 , A61K31/7105
CPC分类号： C07K16/40 , A61K31/7105 , A61K39/3955 , A61K2039/505 , C07K2317/76 , C12N9/20
摘要： It provides methods and pharmaceutical compositions comprising antagonists to the protein Bile Salt-Stimulated Lipase (BSSL) for the prevention, prophylaxis and treatment of inflammatory diseases, such as rheumatoid arthritis. It further relates to pharmaceutical compositions comprising BSSL antagonists and their use in methods for the prevention, prophylaxis and treatment of inflammatory diseases, such as rheumatoid arthritis. Suitable BSSL antagonists to be used according to the invention are BSSL antibodies.
摘要翻译：它提供了包含用于预防，预防和治疗炎性疾病如类风湿性关节炎的胆汁盐刺激脂肪酶（BSSL）的拮抗剂的方法和药物组合物。它还涉及包含BSSL拮抗剂的药物组合物及其在预防，预防和治疗炎性疾病如类风湿性关节炎的方法中的用途。根据本发明使用的合适的BSSL拮抗剂是BSSL抗体。

4. 发明授权

US5739407A Human .beta.-casein, process for producing it and use thereof 失效
标题翻译：人β-酪蛋白，其生产方法及其用途
公开(公告)号：US5739407A
公开(公告)日：1998-04-14
申请号：US78090
申请日：1993-06-18
申请人： Sven Bergstrom , Olle Hernell , Bo Lonnerdal , Karin Hjalmarsson , Lennart Hanson , Jan Tornell , Mats Stromqvigt
发明人： Sven Bergstrom , Olle Hernell , Bo Lonnerdal , Karin Hjalmarsson , Lennart Hanson , Jan Tornell , Mats Stromqvigt
IPC分类号： A01K67/027 , A23C9/152 , C07K14/47 , C07K14/81 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/00 , C12N15/09 , C12N15/12 , C12N15/85 , C12P21/02 , C12R1/19 , C12R1/865 , C12R1/91 , C12N5/00
CPC分类号： C12N15/8509 , A01K67/0275 , A01K67/0278 , C07K14/4732 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/10 , A01K2227/101 , A01K2227/105 , A01K2267/01 , Y10S426/801
摘要： The present invention relates to a DNA sequence encoding the human milk protein .beta.-casein or an analogue or variant thereof which has either the calcium binding activity of human .beta.-casein, or opioid activity, or angiotensin converting enzyme (ACE) inhibitory activity, or a combination of any two or three of these activities. The DNA sequence may optionally contain one or more intron sequences and permissive RNA splice signals. The DNA sequence is used in the production of recombinant human .beta.-casein, advantageously by means of production in transgenic non-human mammals such as bovine species. In one embodiment, the DNA sequence is inserted into a milk protein gene of a mammal such as a whey acidic protein (WAP) gene. The main use of the recombinant human .beta.-casein is as a constituent of infant formulae. It is contemplated that the recombinant human .beta.-casein provides a substantial improvement of the nutritional and biological value of the formulae in that a closer similarity to human milk is obtained.
摘要翻译：本发明涉及编码人乳蛋白β-酪蛋白或其类似物或变体的DNA序列，其具有人β-酪蛋白的钙结合活性或阿片样物质活性或血管紧张素转换酶（ACE）抑制活性，或任何两个或三个这些活动的组合。 DNA序列可以任选地含有一个或多个内含子序列和允许的RNA剪接信号。 DNA序列用于生产重组人β-酪蛋白，有利地通过在转基因非人哺乳动物如牛物种中的生产。在一个实施方案中，将DNA序列插入哺乳动物如乳清酸性蛋白（WAP）基因的乳蛋白基因中。重组人β-酪蛋白的主要用途是作为婴儿配方奶粉的成分。预期重组人β-酪蛋白提供了配方的营养和生物学价值的显着改善，因为获得了更接近于人乳的相似性。

5. 发明授权

US08597650B2 Methods for treating rheumatoid arthritis with anti-bile salt-stimulated lipase (BSSL) antibodies 有权
标题翻译：用抗胆汁盐刺激的脂肪酶（BSSL）抗体治疗类风湿性关节炎的方法
公开(公告)号：US08597650B2
公开(公告)日：2013-12-03
申请号：US13262805
申请日：2010-04-06
申请人： Olle Hernell , Susanne Lindquist , Lennart Gustav Lundberg
发明人： Olle Hernell , Susanne Lindquist , Lennart Gustav Lundberg
IPC分类号： A61K39/395 , C07K16/00 , C07K16/40
CPC分类号： C07K16/40 , A61K31/7105 , A61K39/3955 , A61K2039/505 , C07K2317/76 , C12N9/20
摘要： It provides methods and pharmaceutical compositions comprising antagonists to the protein Bile Salt-Stimulated Lipase (BSSL) for the prevention, prophylaxis and treatment of inflammatory diseases, such as rheumatoid arthritis. It further relates to pharmaceutical compositions comprising BSSL antagonists and their use in methods for the prevention, prophylaxis and treatment of inflammatory diseases, such as rheumatoid arthritis. Suitable BSSL antagonists to be used according to the invention are BSSL antibodies.
摘要翻译：它提供了包含用于预防，预防和治疗炎性疾病如类风湿性关节炎的胆汁盐刺激脂肪酶（BSSL）的拮抗剂的方法和药物组合物。它还涉及包含BSSL拮抗剂的药物组合物及其在预防，预防和治疗炎性疾病如类风湿性关节炎的方法中的用途。根据本发明使用的合适的BSSL拮抗剂是BSSL抗体。

6. 发明申请

US20120093829A1 NEW METHODS FOR TREATMENT OF INFLAMMATORY DISEASES 有权
标题翻译：治疗炎症性疾病的新方法
公开(公告)号：US20120093829A1
公开(公告)日：2012-04-19
申请号：US13262805
申请日：2010-04-06
申请人： Olle Hernell , Susanne Lindquist , Lennart Gustav Lundberg
发明人： Olle Hernell , Susanne Lindquist , Lennart Gustav Lundberg
IPC分类号： A61K39/395 , A61P29/00 , A61P19/02 , A61P37/08 , A61P27/02 , A61P1/00 , A61P9/00 , A61P17/00 , A61P25/00 , A61K31/7088 , A61P11/00
CPC分类号： C07K16/40 , A61K31/7105 , A61K39/3955 , A61K2039/505 , C07K2317/76 , C12N9/20
摘要： It provides methods and pharmaceutical compositions comprising antagonists to the protein Bile Salt-Stimulated Lipase (BSSL) for the prevention, prophylaxis and treatment of inflammatory diseases, such as rheumatoid arthritis. It further relates to pharmaceutical compositions comprising BSSL antagonists and their use in methods for the prevention, prophylaxis and treatment of inflammatory diseases, such as rheumatoid arthritis. Suitable BSSL antagonists to be used according to the invention are BSSL antibodies.
摘要翻译：它提供了包含用于预防，预防和治疗炎性疾病如类风湿性关节炎的胆汁盐刺激脂肪酶（BSSL）的拮抗剂的方法和药物组合物。它还涉及包含BSSL拮抗剂的药物组合物及其在预防，预防和治疗炎症性疾病如类风湿性关节炎的方法中的用途。根据本发明使用的合适的BSSL拮抗剂是BSSL抗体。

7. 发明授权

US06232094B1 DNA encoding human &kgr; casein and process for obtaining the protein 失效
标题翻译：编码人类kappa酪蛋白的DNA和获得蛋白质的方法
公开(公告)号：US06232094B1
公开(公告)日：2001-05-15
申请号：US08462437
申请日：1995-06-05
申请人： Lennart Hansson , Mats Strömqvist , Sven Bergström , Olle Hernell , Jan Törnell
发明人： Lennart Hansson , Mats Strömqvist , Sven Bergström , Olle Hernell , Jan Törnell
IPC分类号： C12N2106
CPC分类号： C12N15/8509 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2227/10 , A01K2227/101 , A01K2227/105 , A01K2267/01 , A23C9/20 , C07K14/4732 , C12N15/85 , C12N2830/002 , C12N2830/85 , C12N2840/44
摘要： The present invention relates to an expression system comprising a DNA sequence encoding a polypeptide which has a biological activity of human &kgr;-casein, the system comprising a 5′-flanking sequence capable of mediating expression of said DNA sequence. In preferred embodiments the 5′-flanking sequence is from a milk protein gene of a mammal such as a casein gene or whey acidic protein (WAP) gene and the DNA sequence contains at least one intron sequence selected from the intron sequences presented in SEQ ID NO:30. The invention also relates to DNA sequences, replicable expression vectors and cells harboring said vectors, recombinant polypeptide e.g. in glycosylated form, and milk, infant formula or nutrient supplement comprising recombinant polypeptide. The invention further relates to a transgenic non-human mammal such as a mouse, rat, rabbit, goat, sheep, pig, lama, camel or bovine species whose germ cells and somatic cells contain a DNA sequence as defined above as a result of chromosomal incorporation into the non-human mammalian genome, or into the genome of an ancestor of said non-human mammal.
摘要翻译：本发明涉及包含编码具有人κ-酪蛋白生物活性的多肽的DNA序列的表达系统，所述系统包含能够介导所述DNA序列表达的5'-侧翼序列。在优选的实施方案中，5'-侧翼序列来自哺乳动物的乳蛋白基因，例如酪蛋白基因或乳清酸性蛋白（WAP）基因，并且DNA序列含有至少一个选自SEQ ID NO：本发明还涉及DNA序列，可复制表达载体和携带所述载体的细胞，例如重组多肽包含重组多肽的牛奶，婴儿配方食品或营养补充剂。本发明还涉及一种转基因非人哺乳动物如小鼠，大鼠，兔，山羊，绵羊，猪，喇嘛，骆驼或牛种，其胚芽细胞和体细胞含有如上所定义的DNA序列，作为染色体掺入非人哺乳动物基因组或所述非人哺乳动物祖先的基因组的结果。

8. 发明申请

US20120100127A1 Method to Increase the Absorption of Unsaturated Fatty Acids by Human Infants 有权
标题翻译：增加人类婴幼儿不饱和脂肪酸吸收的方法
公开(公告)号：US20120100127A1
公开(公告)日：2012-04-26
申请号：US13278682
申请日：2011-10-21
申请人： Olle Hernell , Birgitta Olsson , Patrik Strömberg , Lennart Svensson , Kristina Timdahl , Mårten Vågerö , Maria Öhman
发明人： Olle Hernell , Birgitta Olsson , Patrik Strömberg , Lennart Svensson , Kristina Timdahl , Mårten Vågerö , Maria Öhman
IPC分类号： A61K38/46 , A61P3/00 , A61P25/00 , A23C9/152 , A61P27/02
CPC分类号： A61K38/465 , A23C9/1216 , A23C9/206 , A23L29/06 , A23L33/12 , A23L33/40 , A23V2002/00 , C12Y301/01003 , A23V2200/08 , A23V2250/54 , A23V2300/50
摘要： The present invention relates to a method to increase the absorption by a human infant of at least one unsaturated fatty acid, said method comprising the enteral administration to said infant of recombinant human bile-salt-stimulated lipase (rhBSSL). In another aspect the invention also relates to a method to improve the visual and/or cognitive development of a human infant, said method comprising the enteral administration to said infant of rhBSSL. Such methods have particular utility for preterm human infants, particular those in medical need of increasing their absorption of or availability to such unsaturated fatty acids. In further aspects, the invention relates to kits, packaged-pharmaceutical-products, recombinant human bile-salt-stimulated lipase and pharmaceutical compositions, in each case useful for increasing the absorption by a human infant of at least one unsaturated fatty acid, or for increasing the visual and/or cognitive development of a human infant.
摘要翻译：本发明涉及一种增加人类婴幼儿至少一种不饱和脂肪酸吸收的方法，所述方法包括向所述婴儿重组人胆汁盐刺激的脂肪酶（rhBSSL）进行肠内施用。在另一方面，本发明还涉及一种改善人类婴儿的视觉和/或认知发育的方法，所述方法包括对所述婴儿的rhBSSL的肠内施用。这些方法对于早产儿的婴儿具有特别的用途，特别是在医学上需要增加其对这种不饱和脂肪酸的吸收或可用性的这些方法。在另外的方面，本发明涉及试剂盒，包装的药物产品，重组人胆汁盐刺激的脂肪酶和药物组合物，在每种情况下都可用于增加人类婴幼儿至少一种不饱和脂肪酸的吸收，或用于增加人类婴儿的视觉和/或认知发育。

9. 发明申请

US20120100126A1 Method to Increase the Growth Velocity of Human Infants 有权
标题翻译：增加人类生长速度的方法
公开(公告)号：US20120100126A1
公开(公告)日：2012-04-26
申请号：US13278662
申请日：2011-10-21
申请人： Olle Hernell , Birgitta Olsson , Patrik Strömberg , Lennart Svensson , Kristina Timdahl , Mårten Vågerö , Maria Öhman
发明人： Olle Hernell , Birgitta Olsson , Patrik Strömberg , Lennart Svensson , Kristina Timdahl , Mårten Vågerö , Maria Öhman
IPC分类号： A61K38/46 , A61P43/00 , A61P1/00
CPC分类号： A61K38/465 , A23L5/00 , A23L33/17 , A23L33/40 , A23V2002/00 , C12Y301/01003 , C12Y301/01013
摘要： The present invention relates to a method to increase the growth velocity of a human infant, said method comprising the enteral administration to said infant of recombinant human bile-salt-stimulated lipase (rhBSSL). Such method has particular utility for underweight or preterm human infants, particular those in medical need of increasing their growth velocity. The invention also relates to compositions, including infant feeds, kits, packaged-pharmaceutical-products and pharmaceutical compositions, and also to methods to prepare infant feeds. In another aspect, the present invention relates to methods to: (X) protect the small bowel mucosa of a human infant from damage; to (Y) protect an immature intestinal epithelium of a human infant from the deleterious effects of incompletely digested and/or excess fat and/or lipid; and/or to (Z) limit accumulation of incompletely digested and/or excess fat and/or lipid in the ileum of a human infant; said methods in each case comprising the step of enteral administration of rhBSSL.
摘要翻译：本发明涉及一种增加人类婴儿生长速度的方法，所述方法包括向所述婴儿重组人胆汁盐刺激的脂肪酶（rhBSSL）进行肠内给药。这种方法对于体重不足或早产儿的婴儿特别有用，特别是医疗需要增加其生长速度的方法。本发明还涉及组合物，包括婴儿饲料，试剂盒，包装的药物产品和药物组合物，以及制备婴儿饲料的方法。另一方面，本发明涉及以下方法：（X）保护人类婴儿的小肠粘膜免受损伤; 至（Y）保护人类婴幼儿的未成熟肠上皮细胞不完全消化和/或过量脂肪和/或脂质的有害作用; 和/或（Z）限制人类婴儿回肠中不完全消化和/或多余的脂肪和/或脂质的积累; 所述方法在每种情况下包括rhBSSL的肠内给药步骤。

10. 发明授权

US06222094B1 Transgenic non-human mammal expressing the DNA sequence encoding kappa casein mammary gland and milk 失效
标题翻译：表达编码k酪蛋白乳腺和牛奶的DNA序列的转基因非人哺乳动物
公开(公告)号：US06222094B1
公开(公告)日：2001-04-24
申请号：US08256799
申请日：1994-12-06
申请人： Lennart Hansson , Mats Strömqvist , Sven Bergström , Olle Hernell , Jan Törnell
发明人： Lennart Hansson , Mats Strömqvist , Sven Bergström , Olle Hernell , Jan Törnell
IPC分类号： A01K67027
CPC分类号： C12N15/8509 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2227/10 , A01K2227/101 , A01K2227/105 , A01K2267/01 , A23C9/20 , C07K14/4732 , C12N15/85 , C12N2830/002 , C12N2830/85 , C12N2840/44
摘要： The present invention relates to an expression system comprising a DNA sequence encoding a polypeptide which ha a biological activity of human &kgr;-casein, the system comprising a 5′-flanking sequence capable of mediating expression of said DNA sequence. In preferred embodiments the 5′-flanking sequence is from a milk protein gene of a mammal such as a casein gene or whey acidic protein (WAP) gene and the DNA sequence contains at least one intron sequence. The invention further relates to DNA sequences, replicable expression vectors and cells harboring said vectors, recombinant polypeptide e.g. in glycosylated form, and milk, infant formula or nutrient supplement comprising recombinant polypeptide. The invention also relates to a method for producing a transgenic non-human mammal comprising injecting an expression system as defined above and optionally a further DNA encoding &bgr;-casein or an analog, variant or subsequence thereof into a fertilized egg or a cell of an embryo of a mammal so as to incorporate the expression system into the germline of the mammal and developing the resulting injected fertilized egg or embryo into an adult female mammal. In one embodiment, the endogenous polypeptide expressing capability of the mammal is destroyed and/or replaced with the expression system defined above. The invention further relates to a transgenic non-human mammal such as a mouse, rat, rabbit, goat, sheep, pig, lama, camel or bovine species whose germ cells a somatic cells contain a DNA sequence as defined above as a result of chromosomal incorporation into the non-human mammalian genome, or into the genome of an ancestor of said non-human mammal.
摘要翻译：本发明涉及包含编码具有人κ-酪蛋白的生物活性的多肽的DNA序列的表达系统，该系统包含能够介导所述DNA序列表达的5'-侧翼序列。在优选的实施方案中，5'-侧翼序列来自哺乳动物的乳蛋白基因，例如酪蛋白基因或乳清酸性蛋白（WAP）基因，并且DNA序列含有至少一个内含子序列。本发明还涉及DNA序列，可复制表达载体和携带所述载体的细胞，重组多肽例如糖基化形式，以及包含重组多肽的乳，婴儿配方食品或营养补充剂。本发明还涉及一种用于产生转基因非人哺乳动物的方法，包括将如上定义的表达系统和任选的编码β-酪蛋白或其类似物，变体或亚序列的另外的DNA注射入受精卵或胚胎细胞以将表达系统并入哺乳动物的种系，并将所得的注射的受精卵或胚胎发育成成年雌性哺乳动物。在一个实施方案中，表达哺乳动物的内源多肽被破坏和/或用上述定义的表达系统代替。本发明还涉及一种转基因非人哺乳动物，例如小鼠，大鼠，兔，山羊，绵羊，猪，羔羊，骆驼或牛，其生殖细胞体细胞含有如上文所定义的DNA序列作为染色体掺入非人哺乳动物基因组中，或并入所述非人哺乳动物的祖先的基因组中。

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