公开(公告)号：US20100105870A1

公开(公告)日：2010-04-29

申请号：US12606445

申请日：2009-10-27

申请人： Sathyamangalam V. Balasubramanian ,  Robert M. Straubinger ,  Karthik Ramani ,  Marc Besman ,  Ramesh Kashi

发明人： Sathyamangalam V. Balasubramanian ,  Robert M. Straubinger ,  Karthik Ramani ,  Marc Besman ,  Ramesh Kashi

IPC分类号： C07K14/555 ,  C07K1/00 ,  C07K14/755

CPC分类号： C12P21/02 ,  A61K9/127 ,  A61K9/1271 ,  A61K38/37 ,  A61K38/47 ,  A61K47/10 ,  A61K47/18 ,  C07K1/1077 ,  C07K14/755 ,  C12N9/2462 ,  C12Y302/01017

摘要： The present invention relates to methods for complexing a protein in a dispersed medium. Also disclosed are associated proteins produced by the methods of complexing of the present invention. Pharmaceutically effective stabilized protein dosages are also disclosed. The present invention also relates to a method for associating AHF protein in a dispersed medium.

摘要翻译： 本发明涉及在分散介质中络合蛋白质的方法。 还公开了通过本发明的络合方法产生的相关蛋白质。 还公开了药学上有效的稳定蛋白质剂量。 本发明还涉及在分散介质中使AHF蛋白质结合的方法。

公开(公告)号：US07625584B2

公开(公告)日：2009-12-01

申请号：US10872638

申请日：2004-06-21

申请人： Sathyamangalam V. Balasubramanian ,  Robert M. Straubinger ,  Karthik Ramani ,  Marc Besman ,  Ramesh Kashi

发明人： Sathyamangalam V. Balasubramanian ,  Robert M. Straubinger ,  Karthik Ramani ,  Marc Besman ,  Ramesh Kashi

IPC分类号： A61K9/127

CPC分类号： C12P21/02 ,  A61K9/127 ,  A61K9/1271 ,  A61K38/37 ,  A61K38/47 ,  A61K47/10 ,  A61K47/18 ,  C07K1/1077 ,  C07K14/755 ,  C12N9/2462 ,  C12Y302/01017

摘要： The present invention relates to methods for complexing a protein in a dispersed medium. Also disclosed are associated proteins produced by the methods of complexing of the present invention. Pharmaceutically effective stabilized protein dosages are also disclosed. The present invention also relates to a method for associating AHF protein in a dispersed medium.

摘要翻译： 本发明涉及在分散介质中络合蛋白质的方法。 还公开了通过本发明的络合方法产生的相关蛋白质。 还公开了药学上有效的稳定蛋白质剂量。 本发明还涉及在分散介质中使AHF蛋白质结合的方法。

公开(公告)号：US20080176791A1

公开(公告)日：2008-07-24

申请号：US11764770

申请日：2007-06-18

申请人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

发明人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

IPC分类号： A61K38/37

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/02 ,  A61K47/10 ,  A61K47/18 ,  A61K47/183 ,  A61K47/26 ,  A61K47/38 ,  Y10S514/834 ,  Y10S530/829

摘要： A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

摘要翻译： 不含白蛋白的因子VIII组合物，除了因子VIII外还包含以下制剂赋形剂：4％至10％的选自甘露醇，甘氨酸和丙氨酸的填充剂; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。或者，制剂可以包含2％至6％的羟乙基淀粉; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。在另一个实施方案中，制剂可以包含：300mM至500mM NaCl; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 和缓冲剂。

公开(公告)号：US07247707B2

公开(公告)日：2007-07-24

申请号：US11434634

申请日：2006-05-15

申请人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

发明人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

IPC分类号： A61K35/14 ,  A61K38/16

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/02 ,  A61K47/10 ,  A61K47/18 ,  A61K47/183 ,  A61K47/26 ,  A61K47/38 ,  Y10S514/834 ,  Y10S530/829

摘要： A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

摘要翻译： 不含白蛋白的因子VIII组合物，除了因子VIII外还包含以下制剂赋形剂：4％至10％的选自甘露醇，甘氨酸和丙氨酸的填充剂; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。或者，制剂可以包含2％至6％的羟乙基淀粉; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。在另一个实施方案中，制剂可以包含：300mM至500mM NaCl; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 和缓冲剂。

公开(公告)号：US07087723B2

公开(公告)日：2006-08-08

申请号：US10610723

申请日：2003-07-01

申请人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

发明人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

IPC分类号： A61K35/14 ,  A61K38/16

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/02 ,  A61K47/10 ,  A61K47/18 ,  A61K47/183 ,  A61K47/26 ,  A61K47/38 ,  Y10S514/834 ,  Y10S530/829

摘要： A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

摘要翻译： 不含白蛋白的因子VIII组合物，除了因子VIII外还包含以下制剂赋形剂：4％至10％的选自甘露醇，甘氨酸和丙氨酸的填充剂; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。或者，制剂可以包含2％至6％的羟乙基淀粉; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。在另一个实施方案中，制剂可以包含：300mM至500mM NaCl; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 和缓冲剂。

公开(公告)号：US08058226B2

公开(公告)日：2011-11-15

申请号：US11764770

申请日：2007-06-18

申请人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

发明人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

IPC分类号： A61K35/14 ,  A61K38/16 ,  A61K39/00 ,  A61K51/00

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/02 ,  A61K47/10 ,  A61K47/18 ,  A61K47/183 ,  A61K47/26 ,  A61K47/38 ,  Y10S514/834 ,  Y10S530/829

摘要： A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

摘要翻译： 不含白蛋白的因子VIII组合物，除了因子VIII外还包含以下制剂赋形剂：4％至10％的选自甘露醇，甘氨酸和丙氨酸的填充剂; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。或者，制剂可以包含2％至6％的羟乙基淀粉; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。在另一个实施方案中，制剂可以包含：300mM至500mM NaCl; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 和缓冲剂。

公开(公告)号：US20060205661A1

公开(公告)日：2006-09-14

申请号：US11434634

申请日：2006-05-15

申请人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

发明人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

IPC分类号： A61K38/36 ,  A61K38/37

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/02 ,  A61K47/10 ,  A61K47/18 ,  A61K47/183 ,  A61K47/26 ,  A61K47/38 ,  Y10S514/834 ,  Y10S530/829

摘要： A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

摘要翻译： 不含白蛋白的因子VIII组合物，除了因子VIII外还包含以下制剂赋形剂：4％至10％的选自甘露醇，甘氨酸和丙氨酸的填充剂; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。或者，制剂可以包含2％至6％的羟乙基淀粉; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。在另一个实施方案中，制剂可以包含：300mM至500mM NaCl; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 和缓冲剂。

公开(公告)号：US08372800B2

公开(公告)日：2013-02-12

申请号：US13250789

申请日：2011-09-30

申请人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

发明人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

IPC分类号： A61K38/00 ,  A61K38/16 ,  A61K35/14 ,  A61K47/00 ,  A61K31/715 ,  A61K51/00 ,  A01N43/04 ,  C07K1/00 ,  C07K14/00 ,  C07K16/00 ,  C07K17/00

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/02 ,  A61K47/10 ,  A61K47/18 ,  A61K47/183 ,  A61K47/26 ,  A61K47/38 ,  Y10S514/834 ,  Y10S530/829

摘要： An albumin-free Factor VIII formulation comprising: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

摘要翻译： 不含白蛋白的因子VIII制剂，其包含：4％至10％的选自甘露醇，甘氨酸和丙氨酸的填充剂; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 和缓冲剂。 或者，制剂可以包含2％至6％的羟乙基淀粉; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 和缓冲剂。 在另一个实施方案中，制剂可包含：300mM至500mM NaCl; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 和缓冲剂。

公开(公告)号：US20120083446A1

公开(公告)日：2012-04-05

申请号：US13250789

申请日：2011-09-30

申请人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

发明人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

IPC分类号： A61K38/37 ,  A61P7/04

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/02 ,  A61K47/10 ,  A61K47/18 ,  A61K47/183 ,  A61K47/26 ,  A61K47/38 ,  Y10S514/834 ,  Y10S530/829

摘要： An albumin-free Factor VIII formulation comprising, 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

摘要翻译： 不含白蛋白的因子VIII制剂，其包含4％至10％的选自甘露醇，甘氨酸和丙氨酸的填充剂; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 和缓冲剂。或者，制剂可以包含2％至6％的羟乙基淀粉; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 和缓冲剂。 在另一个实施方案中，制剂可包含：300mM至500mM NaCl; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 和缓冲剂。

公开(公告)号：US06586573B1

公开(公告)日：2003-07-01

申请号：US09507011

申请日：2000-02-22

申请人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

发明人： Marc Besman ,  Erik Bjornson ,  Feroz Jameel ,  Ramesh Kashi ,  Michael Pikal ,  Serguei Tchessalov ,  John Carpenter

IPC分类号： A61K3514

CPC分类号： A61K38/37 ,  A61K9/0019 ,  A61K9/19 ,  A61K47/02 ,  A61K47/10 ,  A61K47/18 ,  A61K47/183 ,  A61K47/26 ,  A61K47/38 ,  Y10S514/834 ,  Y10S530/829

摘要： A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

摘要翻译： 不含白蛋白的因子VIII组合物，除了因子VIII外还包含以下制剂赋形剂：4％至10％的选自甘露醇，甘氨酸和丙氨酸的填充剂; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。或者，制剂可以包含2％至6％的羟乙基淀粉; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 100mM至300mM NaCl; 以及用于保持约6至8的pH的缓冲剂。在另一个实施方案中，制剂可以包含：300mM至500mM NaCl; 1％至4％的选自蔗糖，海藻糖，棉子糖和精氨酸的稳定剂; 1mM至5mM钙盐; 和缓冲剂。