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1. 发明授权

US09102753B2 Anti-inflammatory pharmaceutical products 有权
标题翻译：抗炎药品
公开(公告)号：US09102753B2
公开(公告)日：2015-08-11
申请号：US13524381
申请日：2012-06-15
申请人： Angelo P. Consalvo , Nozer M. Mehta , Mauro Perretti , Jesmond Dalli
发明人： Angelo P. Consalvo , Nozer M. Mehta , Mauro Perretti , Jesmond Dalli
IPC分类号： C07K14/47 , A61K38/17 , A61K38/00
CPC分类号： C07K14/4703 , A61K38/00 , A61K38/1709 , C07K14/4721
摘要： Polypeptides having homology to regions of the N-terminal 50 residues of human Annexin 1 are provided for medical use as anti-inflammatory agents. Some of the polypeptides have homology to the N-terminal 48 residues of human Annexin 1, especially to residues 2-48 and 11-48 thereof. In some embodiments, properties of these compounds are improved by at least one modification at residues corresponding to residues 11, 22, 25 and/or 36 of human Annexin 1, and/or by C-terminal amidation of the polypeptide. Analogs of amino acids 2-26 of human Annexin 1, especially acetylated at the N-terminus and/or amidated at the C-terminus and having modifications at 11 and/or 22 are also disclosed for medical use as anti-inflammatory agents.
摘要翻译：与人膜联蛋白1的N-末端50个残基的区域具有同源性的多肽被提供作为抗炎剂用于医学用途。一些多肽与人膜联蛋白1的N-末端48个残基具有同源性，特别是其与其残基2-48和11-48的同源性。在一些实施方案中，这些化合物的性质通过对应于人膜联蛋白1的残基11,22,25和/或36的残基的至少一个修饰和/或通过多肽的C-末端酰胺化来改善。人膜联蛋白1的氨基酸2-26的类似物，特别是在N-末端乙酰化和/或在C-末端酰胺化并在11和/或22上具有修饰的类似物也公开用于医学用作抗炎剂。

2. 发明授权

US08664178B2 Peptide pharmaceutical for oral delivery 有权
标题翻译：用于口服递送的肽药
公开(公告)号：US08664178B2
公开(公告)日：2014-03-04
申请号：US13487784
申请日：2012-06-04
申请人： William Stern , Angelo P. Consalvo
发明人： William Stern , Angelo P. Consalvo
IPC分类号： A61K38/23
CPC分类号： A61K38/2235 , A61K9/14 , A61K9/20 , A61K9/2013 , A61K9/2027 , A61K9/2846 , A61K9/48 , A61K9/4858 , A61K9/4866 , A61K9/50 , A61K38/23 , A61K38/29
摘要： Acid-containing oral pharmaceutical compositions are provided wherein the pharmaceutical active agents are peptide compounds (i.e., those that include a plurality of amino acids and at least one peptide bond in their molecular structures). Certain barrier layers and/or particulate coated acid are used to reduce any adverse interactions that might otherwise occur between the acid of the compositions and other components of the composition. Use of these barrier layers and/or use of particulate coated acid is believed to promote a more simultaneous release of the components of the composition than is achieved by prior art acid-protection techniques, thus enhancing, and making more consistent, the bioavailability of the active peptide compounds.
摘要翻译：提供含酸的口服药物组合物，其中药物活性剂是肽化合物（即，包括多个氨基酸和在其分子结构中至少一个肽键的那些）。使用某些阻隔层和/或颗粒涂覆的酸来减少组合物的酸和组合物的其它组分之间可能发生的任何不利相互作用。认为使用这些阻挡层和/或使用颗粒涂覆的酸可以促进组合物的组分比通过现有技术的酸保护技术实现的更多的同时释放，从而增强和更一致的生物利用度活性肽化合物。

3. 发明授权

US08592366B2 Peptide pharmaceutical for oral delivery 有权
公开(公告)号：US08592366B2
公开(公告)日：2013-11-26
申请号：US13487856
申请日：2012-06-04
申请人： William Stern , Angelo P. Consalvo
发明人： William Stern , Angelo P. Consalvo
IPC分类号： A61K38/00
CPC分类号： A61K38/2235 , A61K9/14 , A61K9/20 , A61K9/2013 , A61K9/2027 , A61K9/2846 , A61K9/48 , A61K9/4858 , A61K9/4866 , A61K9/50 , A61K38/23 , A61K38/29
摘要： Acid-containing oral pharmaceutical compositions are provided wherein the pharmaceutical active agents are peptide compounds (i.e., those that include a plurality of amino acids and at least one peptide bond in their molecular structures). Certain barrier layers and/or particulate coated acid are used to reduce any adverse interactions that might otherwise occur between the acid of the compositions and other components of the composition. Use of these barrier layers and/or use of particulate coated acid is believed to promote a more simultaneous release of the components of the composition than is achieved by prior art acid-protection techniques, thus enhancing, and making more consistent, the bioavailability of the active peptide compounds.

4. 发明授权

US08163871B2 Enzymatic reactions in the presence of keto acids 有权
标题翻译：在酮酸存在下的酶反应
公开(公告)号：US08163871B2
公开(公告)日：2012-04-24
申请号：US12284552
申请日：2008-09-22
申请人： Angelo P. Consalvo , Nozer M. Mehta , William Stern , James P. Gilligan
发明人： Angelo P. Consalvo , Nozer M. Mehta , William Stern , James P. Gilligan
IPC分类号： C07K7/00 , C12P13/00 , C12P21/06
CPC分类号： C12Y114/17003 , C12P13/02 , C12P21/02 , C12Y403/02005
摘要： Conversion in vitro of X-Gly to X-alpha-hydroxy-Gly or X-NH2 (X being a peptide or any other compound having a carbonyl group capable of forming a covalent bond with glycine) is accomplished enzymatically in the presence of keto acids, or salts or esters thereof, to provide a good yield without the necessity of catalase or similar enzymatic reaction enhancers. Peptidylglycine α-amidating monooxygenase (PAM) is a preferred enzyme for catalyzing the conversion. Alternatively, peptidylglycine α-hydroxylating monooxygenase (PHM) is utilized to convert X-Gly to X-alpha-hydroxy-Gly which may be recovered, or optionally may be simultaneously or sequentially converted to an amide by either a Lewis base or action of the enzyme peptidyl α-hydroxyglycine α-amidating lyase (PAL). Both PHM and PAL are functional domains of PAM.
摘要翻译：将X-Gly体外转化为X-α-羟基-Gly或X-NH2（X为肽或具有能与甘氨酸形成共价键的羰基的任何其它化合物）在酮酸存在下酶促完成，或其盐或酯，以提供良好的产率而不需要过氧化氢酶或类似的酶促反应增强剂。肽基甘氨酸α-酰胺化单加氧酶（PAM）是催化转化的优选酶。或者，使用肽基甘氨酸α-羟化化单加氧酶（PHM）将X-Gly转化成可被回收的X-α-羟基-Gly，或任选地可以通过路易斯碱同时或依次转化为酰胺，或通过酶肽β-羟基甘氨酸α-酰胺化裂解酶（PAL）。 PHM和PAL都是PAM的功能域。

5. 发明授权

US07968311B2 Direct expression of peptides into culture media 有权
标题翻译：将肽直接表达到培养基中
公开(公告)号：US07968311B2
公开(公告)日：2011-06-28
申请号：US10818966
申请日：2004-04-05
申请人： Nozer M Mehta , Angelo P Consalvo , Martha V Ray , Christopher P Meenan
发明人： Nozer M Mehta , Angelo P Consalvo , Martha V Ray , Christopher P Meenan
IPC分类号： C12P21/06 , C12N15/63 , C12N1/20 , C07K1/00
CPC分类号： A61K38/23 , C07K14/461 , C07K14/585 , C07K14/635 , C07K2319/02 , C12N15/70 , C12N15/71 , C12N15/72 , C12P21/02
摘要： Expression systems are disclosed for the direct expression of peptide products into the culture media where genetically engineered host cells are grown. High yield was achieved with novel vectors, a special selection of hosts, and/or fermentation processes which include careful control of cell growth rate, and use of an inducer during growth phase. Special vectors are provided which include control regions having multiple promoters linked operably with coding regions encoding a signal peptide upstream from a coding region encoding the peptide of interest. Multiple transcription cassettes are also used to increase yield. The production of amidated peptides using the expression systems is also disclosed.
摘要翻译：公开了表达系统用于将肽产物直接表达到其中生长基因工程的宿主细胞的培养基中。通过新型载体，特异选择的宿主和/或发酵过程实现了高产量，其包括细胞生长速率的仔细控制，以及在生长阶段期间使用诱导物。提供了特殊载体，其包括具有多个启动子的控制区，所述启动子与编码感兴趣的肽的编码区上游的编码区编码区可操作地连接。多个转录片段也用于提高产量。还公开了使用表达系统产生酰胺化肽。

6. 发明申请

US20130034600A1 PEPTIDE PHARMACEUTICAL OF ORAL DELIVERY 有权
标题翻译：口服药物的药物制剂
公开(公告)号：US20130034600A1
公开(公告)日：2013-02-07
申请号：US13487856
申请日：2012-06-04
申请人： William Stern , Angelo P. Consalvo
发明人： William Stern , Angelo P. Consalvo
IPC分类号： A61K9/00 , A61K9/20 , A61K9/48 , A61K38/02 , A61K38/23
CPC分类号： A61K38/2235 , A61K9/14 , A61K9/20 , A61K9/2013 , A61K9/2027 , A61K9/2846 , A61K9/48 , A61K9/4858 , A61K9/4866 , A61K9/50 , A61K38/23 , A61K38/29
摘要： Acid-containing oral pharmaceutical compositions are provided wherein the pharmaceutical active agents are peptide compounds (i.e., those that include a plurality of amino acids and at least one peptide bond in their molecular structures). Certain barrier layers and/or particulate coated acid are used to reduce any adverse interactions that might otherwise occur between the acid of the compositions and other components of the composition. Use of these barrier layers and/or use of particulate coated acid is believed to promote a more simultaneous release of the components of the composition than is achieved by prior art acid-protection techniques, thus enhancing, and making more consistent, the bioavailability of the active peptide compounds.
摘要翻译：提供含酸的口服药物组合物，其中药物活性剂是肽化合物（即，包括多个氨基酸和在其分子结构中至少一个肽键的那些）。使用某些阻隔层和/或颗粒涂覆的酸来减少组合物的酸和组合物的其它组分之间可能发生的任何不利相互作用。认为使用这些阻挡层和/或使用颗粒涂覆的酸可以促进组合物的组分比通过现有技术的酸保护技术实现的更多的同时释放，从而增强和更一致的生物利用度活性肽化合物。

7. 发明授权

US08252580B2 Bacterial host cell for the direct expression of peptides 有权
公开(公告)号：US08252580B2
公开(公告)日：2012-08-28
申请号：US11928994
申请日：2007-10-30
申请人： Nozer M. Mehta , Angelo P. Consalvo , Martha V. L. Ray , Christopher P. Meenan
发明人： Nozer M. Mehta , Angelo P. Consalvo , Martha V. L. Ray , Christopher P. Meenan
IPC分类号： C12N1/20 , C12N1/12
CPC分类号： C12N15/70 , C07K14/605 , C07K14/62 , C07K14/635 , C12N9/52 , C12P21/02
摘要： Expression systems are disclosed for the direct expression of peptide products into the culture media where genetically engineered host cells are grown. High yield was achieved with a special selection of hosts, and/or fermentation processes which include careful control of cell growth rate, and use of an inducer during growth phase. Special universal cloning vectors are provided for the preparation of expression vectors which include control regions having multiple promoters linked operably with coding regions encoding a signal peptide upstream from a coding region encoding the peptide of interest. Multiple transcription cassettes are also used to increase yield. The production of amidated peptides using the expression systems is also disclosed.

8. 发明授权

US08216822B2 Bacterial host cell for the direct expression of peptides 有权
标题翻译：用于直接表达肽的细菌宿主细胞
公开(公告)号：US08216822B2
公开(公告)日：2012-07-10
申请号：US11928936
申请日：2007-10-30
申请人： Nozer M. Mehta , Angelo P. Consalvo , Martha V. L. Ray , Christopher P. Meenan
发明人： Nozer M. Mehta , Angelo P. Consalvo , Martha V. L. Ray , Christopher P. Meenan
IPC分类号： C12N1/20 , C12N1/12
CPC分类号： C12N15/70 , C07K14/605 , C07K14/62 , C07K14/635 , C12N9/52 , C12P21/02
摘要： Expression systems are disclosed for the direct expression of peptide products into the culture media where genetically engineered host cells are grown. High yield was achieved with a special selection of hosts, and/or fermentation processes which include careful control of cell growth rate, and use of an inducer during growth phase. Special universal cloning vectors are provided for the preparation of expression vectors which include control regions having multiple promoters linked operably with coding regions encoding a signal peptide upstream from a coding region encoding the peptide of interest. Multiple transcription cassettes are also used to increase yield. The production of amidated peptides using the expression systems is also disclosed.
摘要翻译：公开了表达系统用于将肽产物直接表达到其中生长基因工程的宿主细胞的培养基中。通过特殊选择的宿主和/或包括仔细控制细胞生长速率的发酵过程以及在生长阶段期间使用诱导剂来实现高产量。提供特异的通用克隆载体用于制备表达载体，所述表达载体包括具有多个启动子的对照区，所述启动子与编码感兴趣的肽的编码区上游的编码区编码信号肽可操作地连接。多个转录片段也用于提高产量。还公开了使用表达系统产生酰胺化肽。

9. 发明授权

US07445911B2 Enzymatic reactions in the presence of keto acids 有权
标题翻译：在酮酸存在下的酶反应
公开(公告)号：US07445911B2
公开(公告)日：2008-11-04
申请号：US11285136
申请日：2005-11-22
申请人： Angelo P. Consalvo , Nozer M. Mehta , William Stern , James P. Gilligan
发明人： Angelo P. Consalvo , Nozer M. Mehta , William Stern , James P. Gilligan
IPC分类号： C12P21/06
CPC分类号： C12Y114/17003 , C12P13/02 , C12P21/02 , C12Y403/02005
摘要： Conversion in vitro of X-Gly to X-alpha-hydroxy-Gly or X—NH2 (X being a peptide or any other compound having a carbonyl group capable of forming a covalent bond with glycine) is accomplished enzymatically in the presence of keto acids, or salts or esters thereof, to provide a good yield without the necessity of catalase or similar enzymatic reaction enhancers. Peptidylglycine α-amidating monooxygenase (PAM) is a preferred enzyme for catalyzing the conversion. Alternatively, peptidylglycine α-hydroxylating monooxygenase (PHM) is utilized to convert X-Gly to X-alpha-hydroxy-Gly which may be recovered, or optionally may be simultaneously or sequentially converted to an amide by either a Lewis base or action of the enzyme peptidyl α-hydroxyglycine α-amidating lyase (PAL). Both PHM and PAL are functional domains of PAM.
摘要翻译： X-Gly转化为X-α-羟基-Gly或X-NH 2（X为肽或具有能够与甘氨酸形成共价键的羰基的任何其它化合物）为在酮酸或其盐或酯的存在下酶促完成，以提供良好的产率而不需要过氧化氢酶或类似的酶促反应增强剂。肽基甘氨酸α-酰胺化单加氧酶（PAM）是催化转化的优选酶。或者，使用肽基甘氨酸α-羟化化单加氧酶（PHM）将X-Gly转化为可被回收的X-α-羟基-Gly，或任选地可以通过路易斯碱同时或顺序地转化为酰胺，或通过酶肽肽α-羟基甘氨酸α-酰胺化裂解酶（PAL）。 PHM和PAL都是PAM的功能域。

10. 发明授权

US08835161B2 Bacterial host cell for the direct expression of peptides 有权
标题翻译：用于直接表达肽的细菌宿主细胞
公开(公告)号：US08835161B2
公开(公告)日：2014-09-16
申请号：US13544228
申请日：2012-07-09
申请人： Nozer M. Mehta , Angelo P. Consalvo , Martha V. L. Ray , Christopher P. Meenan
发明人： Nozer M. Mehta , Angelo P. Consalvo , Martha V. L. Ray , Christopher P. Meenan
IPC分类号： C12N15/00 , C12N1/20 , C12N15/70 , C12P21/02 , C12N9/52 , C07K14/62 , C07K14/635 , C07K14/605
CPC分类号： C12N15/70 , C07K14/605 , C07K14/62 , C07K14/635 , C12N9/52 , C12P21/02
摘要： Expression systems are disclosed for the direct expression of peptide products into the culture media where genetically engineered host cells are grown. High yield was achieved with a special selection of hosts, and/or fermentation processes which include careful control of cell growth rate, and use of an inducer during growth phase. Special universal cloning vectors are provided for the preparation of expression vectors which include control regions having multiple promoters linked operably with coding regions encoding a signal peptide upstream from a coding region encoding the peptide of interest. Multiple transcription cassettes are also used to increase yield. The production of amidated peptides using the expression systems is also disclosed.
摘要翻译：公开了表达系统用于将肽产物直接表达到其中生长基因工程的宿主细胞的培养基中。通过特殊选择的宿主和/或包括仔细控制细胞生长速率的发酵过程以及在生长阶段期间使用诱导剂来实现高产量。提供特异的通用克隆载体用于制备表达载体，所述表达载体包括具有多个启动子的对照区，所述多个启动子与编码感兴趣的肽的编码区上游的编码区编码信号肽可操作地连接。多个转录片段也用于提高产量。还公开了使用表达系统产生酰胺化肽。

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