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1. 发明授权

US5674710A Recombinant techniques for production of human brain natriuretic peptide 失效
标题翻译：用于生产人脑利钠肽的重组技术
公开(公告)号：US5674710A
公开(公告)日：1997-10-07
申请号：US477226
申请日：1990-02-08
申请人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
发明人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61P9/08 , A61P9/12 , C07K7/08 , C07K14/00 , C07K14/575 , C07K14/58 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/12 , C12N15/16 , C12P21/02 , C12R1/19 , C12N15/85
CPC分类号： C12P21/02 , C07K14/58 , C07K14/582 , C07K16/241 , C07K16/2803 , G01N33/74 , A61K38/00 , C07K2317/622
摘要： The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically.
摘要翻译：公开了编码猪脑利钠肽的cDNA序列和编码具有利尿钠活性的犬和人肽的相关基因。该基因显示可使得其他脊椎动物物种中编码类似利尿钠肽的DNA可见。编码这些NP的基因可用于影响序列的修饰以产生NP的替代形式并提供实际量的这些蛋白质。本发明的NP也可以化学合成。

2. 发明授权

US5948761A Recombinant canine brain natriuretic peptide 失效
标题翻译：重组犬脑利钠肽
公开(公告)号：US5948761A
公开(公告)日：1999-09-07
申请号：US850910
申请日：1997-05-05
申请人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
发明人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61P9/08 , A61P9/12 , C07K7/08 , C07K14/00 , C07K14/575 , C07K14/58 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/12 , C12N15/16 , C12P21/02 , C12R1/19 , C12N15/85
CPC分类号： C12P21/02 , C07K14/58 , C07K14/582 , C07K16/241 , C07K16/2803 , G01N33/74 , A61K38/00 , C07K2317/622
摘要： Peptides of the formula R.sup.1 -Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R.sup.2wherein R.sup.1 is selected from the group consisting of:(H);Gly-;Ser-Gly-;Lys-Ser-Gly-;His-Lys-Ser-Gly-;Met-His-Lys-Ser-Gly-;Thr-Met-His-Lys-Ser-Gly-;Lys-Thr-Met-His-Lys-Ser-Gly-;Pro-Lys-Thr-Met-His-Lys-Ser-Gly-;Ser-Pro-Lys-Thr-Met-His-Lys-Ser-Gly-;or is the amino acid sequence of the dog prepro sequence upstream of position 100 shown in FIG. 8 herein or a C-terminal portion thereof;R.sup.2 is (OH), NH.sub.2, or NR.sub.2 wherein each R is independently H or lower alkyl (1-4C) or isAsn;Asn-Val;Asn-Val-Leu;Asn-Val-Leu-Arg;Asn-Val-Leu-Arg-Lys;Asn-Val-Leu-Arg-Lys-Tyr;or the amides thereof are useful in treating conditions characterized by high levels of extracellular fluid.
摘要翻译：式R1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R2的肽，其中R1选自：（H）; 甘氨酸 Ser-Gly-; Lys-Ser-Gly-; His-Lys-Ser-Gly-; Met-His-Lys-Ser-Gly-; Thr-Met-His-Lys-Ser-Gly-; Lys-Thr-Met-His-Lys-Ser-Gly-; Pro-Lys-Thr-Met-His-Lys-Ser-Gly-; Ser-Pro-Lys-Thr-Met-His-Lys-Ser-Gly-; 或者是图1所示位置100上游的狗前原序列的氨基酸序列。 8或其C末端部分; R2是（OH），NH2或NR2，其中每个R独立地是H或低级烷基（1-4C）或是Asn; 阿斯瓦尔 Asn-Val-Leu; Asn-Val-Leu-Arg; Asn-Val-Leu-Arg-Lys; Asn-Val-Leu-Arg-Lys-Tyr; 或其酰胺可用于治疗以高水平的细胞外液为特征的病症。

3. 发明授权

US06586396B1 Subcutaneous administration of natriuretic peptide 失效
标题翻译：皮下给药利尿钠肽
公开(公告)号：US06586396B1
公开(公告)日：2003-07-01
申请号：US09287892
申请日：1999-04-07
申请人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
发明人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
IPC分类号： A61K3822
CPC分类号： C12P21/02 , A61K38/00 , C07K14/58 , C07K14/582 , C07K16/241 , C07K16/2803 , C07K2317/622 , G01N33/74
摘要： The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically. The invention peptides have the formula: R1-Cys-Phe-Gly-Arg-Arg-/-Leu/-Asp-Arg- (1) Lys Met Ile-Gly/-Ser-Leu/-Ser-Gly-Leu-Gly-Cys-R2 Ser Ser wherein R1 is selected from the group consisting of: (H); Gly-; Ser-Gly-; Asp/ Lys/ -Ser-Gly-; Gly Arg/ Asp/ His/ - Lys/ -Ser-Gly-; Gln Gly Arg/ Asp/ Met/ - His/ - Lys/ -Ser-Gly-; Val Gln Gly Arg/ Asp/ Thr/ -Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Lys- Thr/ -Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Pro-Lys- Thr/ -Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Ser-Pro-Lys- Thr/ -Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly or a 10- to 109-amino acid sequence shown as the native upstream sequence for porcine, canine or human BNP in FIG. 8, or a composite thereof; R2 is (OH), NH2, or NR′R″ wherein R′ and R″ are independently lower alkyl (1-4C) or is Asn/ Lys Asn/ -Val Lys Asn/ -Val-Leu Lys Asn/ -Val-Leu-Arg Lys Asn/ -Val-Leu-Arg- Arg/ Lys Lys Asn/ -Val-Leu-Arg- Arg/ - Tyr/ Lys Lys His or the amides (NH2 or NR′R″) thereof, with the proviso that if formula (1) is R1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg- Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R2 and R1 is Asp-Ser-Gly-, R2 cannot be Asn-Val-Leu-Arg-Arg-Tyr. The peptides of the invention can be formulated into pharmaceutical compositions and used to treat conditions associated with high extracellular fluid levels, especially congestive heart failure.
摘要翻译：公开了编码猪脑利钠肽的cDNA序列和编码具有利尿钠活性的犬和人肽的相关基因。该基因显示可使得其他脊椎动物物种中编码类似利尿钠肽的DNA可见。编码这些NP的基因可用于影响序列的修饰以产生NP的替代形式并提供实际量的这些蛋白质。本发明的NP也可以化学合成。本发明的肽具有下式：其中R 1选自由图中的猪，犬或人BNP的天然上游序列显示的10-或109-氨基酸序列。 8或其复合物; R 2为（OH），NH 2或NR'R“，其中R'和R”独立地为低级烷基（1-4C）或R 1为Asp-Ser-Gly-，R 2不能是Asn-Val-Leu-Arg-Arg-Tyr。本发明的肽可以配制成药物组合物并用于治疗与高细胞外液体水平，特别是充血性心力衰竭相关的病症。

4. 发明授权

US06974861B2 Pharmaceutical compositions and methods using natriuretic peptides 失效
公开(公告)号：US06974861B2
公开(公告)日：2005-12-13
申请号：US10402021
申请日：2003-03-27
申请人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
发明人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61P9/08 , A61P9/12 , C07K7/08 , C07K14/00 , C07K14/575 , C07K14/58 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/12 , C12N15/16 , C12P21/02 , C12R1/19 , C07K17/00
CPC分类号： C12P21/02 , A61K38/00 , C07K14/58 , C07K14/582 , C07K16/241 , C07K16/2803 , C07K2317/622 , G01N33/74
摘要： The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically. The invention peptides have the formula: R1-Cys-Phe-Gly-Arg- Arg/ - Leu/ -Asp-Arg- Lys Met (1) Ile- Gly/ -Ser- Leu/ -Ser-Gly-Leu-Gly-Cys-R-2 Ser Ser wherein R1 is selected from the group consisting of: (H); Gly-; Ser-Gly-; Asp/ Lys/ -Ser-Gly-; Gly Arg/ Asp/ His/ - Lys/ -Ser-Gly-; Gln Gly Arg/ Asp/ Met/ - His/ - Lys/ -Ser-Gly-; Val Gln Gly Arg/ Asp/ Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Pro-Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Ser-Pro-Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly or a 10- to 109-amino acid sequence shown as the native upstream sequence for porcine, canine or human BNP in FIG. 8, or a composite thereof; R2 is (OH), NH2, or NR′R″ wherein R′ and R″ are independently lower alkyl (1-4C) or is Asn/ Lys Asn/ -Val Lys Asn/ -Val-Leu Lys Asn/ -Val-Leu-Arg Lys Asn/ -Val-Leu-Arg- Arg/ Lys Lys Asn/ -Val-Leu-Arg- Arg/ - Tyr/ Lys Lys His or the amides (NH2 or NR′R″) thereof, with the proviso that if formula (1) is R1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg- Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R2 and R1 is Asp-Ser-Gly-, R2 cannot be Asn-Val-Leu-Arg-Arg-Tyr. The peptides of the invention can be formulated into pharmaceutical compositions and used to treat conditions associated with high extracellular fluid levels, especially congestive heart failure.

5. 发明授权

US06897030B2 Immunoassays for human brain natriuretic peptide 失效
标题翻译：人脑利钠肽的免疫测定
公开(公告)号：US06897030B2
公开(公告)日：2005-05-24
申请号：US09902517
申请日：2001-07-09
申请人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
发明人： J. Jeffrey Seilhamer , John Lewicki , Robert M. Scarborough , J. Gordon Porter
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61P9/08 , A61P9/12 , C07K7/08 , C07K14/00 , C07K14/575 , C07K14/58 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/12 , C12N15/16 , C12P21/02 , C12R1/19 , G01N33/53 , C07K16/00 , C12N5/06
CPC分类号： C12P21/02 , A61K38/00 , C07K14/58 , C07K14/582 , C07K16/241 , C07K16/2803 , C07K2317/622 , G01N33/74
摘要： Immunoassays and antibodies useful in conducting them for human and canine brain natriuretic peptide are described.
摘要翻译：描述了可用于进行人和犬脑利钠肽的免疫测定和抗体。

6. 发明授权

US07179790B2 Brain natriuretic peptide 有权
标题翻译：脑利钠肽
公开(公告)号：US07179790B2
公开(公告)日：2007-02-20
申请号：US11234424
申请日：2005-09-23
申请人： J. Jeffrey Seilhamer , John A. Lewicki , Robert M. Scarborough , J. Gordon Porter
发明人： J. Jeffrey Seilhamer , John A. Lewicki , Robert M. Scarborough , J. Gordon Porter
IPC分类号： A61K38/00
CPC分类号： C12P21/02 , A61K38/00 , C07K14/58 , C07K14/582 , C07K16/241 , C07K16/2803 , C07K2317/622 , G01N33/74
摘要： Peptides comprising the effective portion of human brain natriuretic peptide are provided in pharmaceutical compositions and methods to effect vasodilation and/or natriuresis.
摘要翻译：包含人脑钠肽的有效部分的肽在药物组合物和方法中提供以实现血管舒张和/或利尿。

7. 发明授权

US5114923A Recombinant techniques for production of novel natriuretic and vasodilator peptides 失效
标题翻译：用于生产新型利尿钠和血管舒张肽的重组技术
公开(公告)号：US5114923A
公开(公告)日：1992-05-19
申请号：US460855
申请日：1990-02-02
申请人： Jeffrey J. Seilhamer , John A. Lewicki , Robert M. Scarborough , J. Gordon Porter
发明人： Jeffrey J. Seilhamer , John A. Lewicki , Robert M. Scarborough , J. Gordon Porter
IPC分类号： A61K38/00 , C07K14/58
CPC分类号： C07K14/582 , C07K14/58 , A61K38/00
摘要： The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically. The invention peptides have the formula: ##STR1## wherein R.sup.1 is selected from the group consisting of: ##STR2## or a 10- to 109-amino acid sequence shown as the native upstream sequence for porcine, canine or human NP in FIG. 6, or a composite thereof;R.sup.2 is (OH), NH.sub.2, or NR'R" wherein R' and R" are independently lower alkyl (1-4C) or is ##STR3## or the amides (NH.sub.2 or NR'R") thereof, with the proviso that if formula (1) isR.sup.1 -Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg- Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R.sup.2and R.sup.1 is Asp-Ser-Gly-, R.sup.2 cannot be Asn-Val-Leu-Arg-Arg-Tyr.The peptides of the invention can be formulated into pharmaceutical compositions and used to treat conditions associated with high extracellular fluid levels, especially congestive heart failure.
摘要翻译： PCT No.PCT / US89 / 02373。 371日期1990年2月2日 102（e）1990年2月2日PCT PCT日期为1989年5月31日。公开了编码猪脑利钠肽的cDNA序列和编码具有利尿钠活性的犬和人肽的相关基因。该基因显示可使得其他脊椎动物物种中编码类似利尿钠肽的DNA可见。编码这些NP的基因可用于影响序列的修饰以产生NP的替代形式并提供实际量的这些蛋白质。本发明的NP也可以化学合成。本发明的肽具有下式：其中R 1选自：（H）;（C）甘氨酸 Ser-Gly-; 或者图像中显示为猪，犬或人NP的天然上游序列的10至109个氨基酸序列的图像。 6，或其复合物; R2是（OH），NH2或NR'R“，其中R'和R”独立地是低级烷基（1-4C），或者是或其酰胺（NH 2或NR'R“），条件是如果式（1）为R1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-Ile-Gly-Ser-Leu- Ser-Gly-Leu-Gly-Cys-R2和R1是Asp-Ser-Gly-，R2不能是Asn-Val-Leu-Arg-Arg-Tyr。本发明的肽可以配制成药物组合物并用于治疗与高细胞外液体水平相关的病症，特别是充血性心力衰竭。

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