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1. 发明申请

WO1995013767A1 OSTEOGENIC PRODUCT AND PROCESS 审中-公开
标题翻译：生物产品和方法
公开(公告)号：WO1995013767A1
公开(公告)日：1995-05-26
申请号：PCT/US1994013351
申请日：1994-11-15
申请人： INTERMEDICS ORTHOPEDICS/DENVER, INC.
发明人： INTERMEDICS ORTHOPEDICS/DENVER, INC. , POSER, James, William , BENEDICT, James, John
IPC分类号： A61F02/28
CPC分类号： A61L27/227 , A61F2/28 , A61F2/32 , A61F2/38 , A61F2/4455 , A61F2002/30011 , A61F2002/30062 , A61F2210/0004 , A61F2250/0023 , A61K38/1875 , A61L27/025 , C07K14/51 , A61K2300/00
摘要： Disclosed is a product which includes calcium carbonate and bone growth factor useful for the promotion of bone formation when implanted in the body. The calcium carbonate is preferably in the form of aragonite which can be recovered from naturally occurring coral. A preferred bone growth factor of the present invention is a protein mixture purified from bone. Also disclosed is a process for the induction of bone formation which includes implanting the product in a body. The product and process of the present invention are particularly useful in hip replacement operations, knee replacement operations, spinal fusion operations, repair of periodontal defects, treatment of osteoporosis, repair of bone tumor defects and repair of bone fractures.
摘要翻译：公开了一种产品，其包括碳酸钙和骨生长因子，其用于在植入体内促进骨形成。碳酸钙优选为可从天然存在的珊瑚回收的文石形式。本发明优选的骨生长因子是从骨中纯化的蛋白质混合物。还公开了一种用于诱导骨形成的方法，其包括将产品植入体内。本发明的产品和方法在髋关节置换手术，膝关节置换手术，脊柱融合手术，牙周缺损修复，骨质疏松症治疗，骨肿瘤缺损修复和骨折修复中特别有用。

2. 发明申请

WO1992018142A1 OSTEOINDUCTIVE PROTEIN MIXTURES AND PURIFICATION PROCESSES 审中-公开
标题翻译： OSTEOINDUCTIVE蛋白质混合物和纯化方法
公开(公告)号：WO1992018142A1
公开(公告)日：1992-10-29
申请号：PCT/US1992003295
申请日：1992-04-21
申请人： INTERMEDICS ORTHOPEDICS/DENVER, INC.
发明人： INTERMEDICS ORTHOPEDICS/DENVER, INC. , POSER, James, William , BENEDICT, James, John
IPC分类号： A61K37/00
CPC分类号： C07K14/51 , A61F2/28 , A61F2/32 , A61F2/38 , A61F2/4455 , A61F2002/30011 , A61F2002/30062 , A61F2210/0004 , A61F2250/0023 , A61K38/1875 , A61L27/025 , A61L27/227 , Y10S530/84 , A61K2300/00
摘要： A method for purifying bone-derived osteoinductive factors including an ultrafiltration process, an anion exchange process, a cation exchange process, and a reverse phase HPLC process. The ultrafiltration process preferably includes a first ultrafiltration step using a membrane having a nominal molecular weight cutoff of approximately 100 kilodaltons (kD) and a second ultrafiltration step employing a membrane having a nominal molecular weight cutoff of approximately 10 kD. For the anion exchange process, a strongly cationic resin is used, preferably having quaternary amine functional groups. Typically, the eluant for the anion exchange process has a conductivity from about 10,260 micromhos (νmhos) (1.026 x 10-2 siemens (S)) to about 11,200 νmhos (1.120 x 10-2 S). For the cation exchange process, a strongly anionic resin is used, preferably having sulfonic acid functional groups. The eluant for the cation exchange process typically has a conductivity from about 39,100 νmhos (3.91 x 10-2 S) to about 82,700 νmhos (8.27 x 10-2 S) or more. The HPLC process typically utilizes a column containing hydrocarbon-modified silica packing material. The osteoinductive proteins can be eluted from the HPLC column with an acetonitrile solution in combination with aqueous trifluoracetic acid. The purification processes yield osteoinductively active protein mixtures.

3. 发明公开

EP0729325A1 OSTEOGENIC PRODUCT AND PROCESS 失效
标题翻译：成骨产品并使用
公开(公告)号：EP0729325A1
公开(公告)日：1996-09-04
申请号：EP95902616.0
申请日：1994-11-15
申请人： INTERMEDICS ORTHOPEDICS/DENVER, INC.
发明人： POSER, James, William , BENEDICT, James, John , DAMIEN, Christopher J.
IPC分类号： A61K38 , A61F2 , A61K31 , A61K33 , A61K35 , A61L27 , A61P1 , A61P19 , A61P43 , C07K14 , C12N15
CPC分类号： A61L27/227 , A61F2/28 , A61F2/32 , A61F2/38 , A61F2/4455 , A61F2002/30011 , A61F2002/30062 , A61F2210/0004 , A61F2250/0023 , A61K38/1875 , A61L27/025 , C07K14/51 , A61K2300/00
摘要： Disclosed is a product which includes calcium carbonate and bone growth factor useful for the promotion of bone formation when implanted in the body. The calcium carbonate is preferably in the form of aragonite which can be recovered from naturally occurring coral. A preferred bone growth factor of the present invention is a protein mixture purified from bone. Also disclosed is a process for the induction of bone formation which includes implanting the product in a body. The product and process of the present invention are particularly useful in hip replacement operations, knee replacement operations, spinal fusion operations, repair of periodontal defects, treatment of osteoporosis, repair of bone tumor defects and repair of bone fractures.

4. 发明授权

EP0584283B1 OSTEOINDUCTIVE PROTEIN MIXTURES AND PURIFICATION PROCESSES 失效转让
标题翻译：骨诱导蛋白混合物清洗等
公开(公告)号：EP0584283B1
公开(公告)日：1999-12-15
申请号：EP92915177.7
申请日：1992-04-21
申请人： INTERMEDICS ORTHOPEDICS/DENVER, INC.
发明人： POSER, James, William , BENEDICT, James, John
IPC分类号： C07K14/51 , C07K1/34 , C07K1/18 , A61K38/02
CPC分类号： C07K14/51 , A61F2/28 , A61F2/32 , A61F2/38 , A61F2/4455 , A61F2002/30011 , A61F2002/30062 , A61F2210/0004 , A61F2250/0023 , A61K38/1875 , A61L27/025 , A61L27/227 , Y10S530/84 , A61K2300/00
摘要： A method for purifying bone-derived osteoinductive factors including an ultrafiltration process, an anion exchange process, a cation exchange process, and a reverse phase HPLC process. The ultrafiltration process preferably includes a first ultrafiltration step using a membrane having a nominal molecular weight cutoff of approximately 100 kilodaltons (kD) and a second ultrafiltration step employing a membrane having a nominal molecular weight cutoff of approximately 10 kD. For the anion exchange process, a strongly cationic resin is used, preferably having quaternary amine functional groups. Typically, the eluant for the anion exchange process has a conductivity from about 10,260 micromhos (νmhos) (1.026 x 10-2 siemens (S)) to about 11,200 νmhos (1.120 x 10-2 S). For the cation exchange process, a strongly anionic resin is used, preferably having sulfonic acid functional groups. The eluant for the cation exchange process typically has a conductivity from about 39,100 νmhos (3.91 x 10-2 S) to about 82,700 νmhos (8.27 x 10-2 S) or more. The HPLC process typically utilizes a column containing hydrocarbon-modified silica packing material. The osteoinductive proteins can be eluted from the HPLC column with an acetonitrile solution in combination with aqueous trifluoracetic acid. The purification processes yield osteoinductively active protein mixtures.

5. 发明公开

EP0584283A1 OSTEOINDUCTIVE PROTEIN MIXTURES AND PURIFICATION PROCESSES 失效转让
标题翻译： OSTEOINDUCTIVE蛋白质混合物和净化过程
公开(公告)号：EP0584283A1
公开(公告)日：1994-03-02
申请号：EP92915177.0
申请日：1992-04-21
申请人： INTERMEDICS ORTHOPEDICS/DENVER, INC.
发明人： POSER, James, William , BENEDICT, James, John
IPC分类号： A61K38 , A61F2 , A61L27 , A61P43 , C07K14
CPC分类号： C07K14/51 , A61F2/28 , A61F2/32 , A61F2/38 , A61F2/4455 , A61F2002/30011 , A61F2002/30062 , A61F2210/0004 , A61F2250/0023 , A61K38/1875 , A61L27/025 , A61L27/227 , Y10S530/84 , A61K2300/00
摘要： Technique de purification de facteur ostéoinductif dérivé d'os comprenant un procédé d'ultra-filtration, un procédé d'échange d'anions, un procédé d'échange de cations ainsi qu'un procédé HPLC (chromatographie liquide à haute performance) à phase inverse. Le procédé d'ultra-filtration consiste de préférence en une première étape d'ultra-filtration utilisant une membrane ayant un niveau de rupture de masse moléculaire nominale d'approximativement 100 kilodaltons (kD), ainsi qu'une seconde étape d'ultra-filtration utilisant une membrane ayant un niveau de rupture de masse moléculaire nominale d'approximativement 10 kD. Dans le procédé d'échange d'anions, on utilise une résine fortement cationique, de préférence ayant des groupes fonctionnels aminés quaternaires. Typiquement, l'éluant pour le procédé d'échange anionique présente une conductivité comprise entre environ 10260 micromhos (mumhos) (1,026 x 10-2 siemens (S)) et environ 11200 mumhos (1,120 x 10-2 S). Pour le procédé d'échange cationique, on utilise une résine fortement anionique, comportant de préférence des groupes fonctionnels d'acide sulfonique. L'éluant utilisé dans le procédé d'échange cationique présente typiquement une conductivité comprise entre environ 39100 mumhos (3,91 x 10-2 S) et environ 82700 mumhos (8,27 x 10 -2 S) ou plus. Le procédé HPLC utilise typiquement une colonne contenant une matière de remplissage de dioxyde de silicium modifié par hydrocarbure. Les protéines ostéoinductives peuvent être éluées à partir de la colonne HPLC au moyen d'une solution d'acétonitrile en combinaison avec de l'acide trifluoroacétique aqueux. Les procédés de purification produisent des mélanges de protéines ostéoinductivement actives.
摘要翻译：骨衍生骨诱导因子纯化技术包括超滤法，阴离子交换法，阳离子交换法和相HPLC（高效液相色谱）法反转。超滤的方法，优选地由超过滤的第一步骤中使用具有大约100千道尔顿（kD）的分子量的公称断裂的膜，和超的第二步骤的使用具有约10kD标称分子量分解的膜进行过滤。在阴离子交换过程中，使用强阳离子树脂，优选具有季氨基官能团。典型地，对于阴离子交换过程中的洗脱剂具有从约10,260微姆欧（mumhos）至约11200 mumhos（1.120×10 -2 S）的电导率（1.026×10-2西门子（S））。对于阳离子交换过程，使用强阴离子树脂，优选具有功能性磺酸基团。在阳离子交换方法中使用的洗脱剂通常具有介于约39100 mumhos（3.91×10 -2 S）的约82700 mumhos（8.27×10 -2 S）或更高的导电性。 HPLC方法通常使用含有烃改性的二氧化硅填料的柱。借助于与三氟乙酸水溶液组合的乙腈溶液，可将骨诱导蛋白从HPLC柱洗脱。纯化过程产生骨诱导活性蛋白质的混合物。

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