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1.发明授权BIOLOGICAL SYSTEMS FOR MANUFACTURE OF POLYHYDROXYALKANOATE POLYMERS CONTAINING 4-HYDROXYACIDS 有权生物SYSTEMS FOR聚合物聚羟基烷酸酯的制备4-羟基酸
公开(公告)号：EP1015565B1
公开(公告)日：2006-04-12
申请号：EP98948384.7
申请日：1998-09-18
申请人： METABOLIX, INC.
CPC分类号： C12N9/0008 , C08G63/06 , C12N9/1029 , C12N9/1096 , C12N15/8243 , C12P7/625
摘要： The gene encoding a 4-hydroxybutyryl-Co A transferase has been isolated from bacteria and integrated into the genome of bacteria also expressing a polyhydroxyalkanoate synthase, to yield an improved production process for 4HB-containing polyhydroxyalkanoates using transgenic organisms, including both bacteria and plants. The new pathways provide means for producing 4HB containing PHAs from cheap carbon sources such as sugars and fatty acids, in high yields, which are stable. Useful strains are obtained by screening strains having integrated into their genomes a gene encoding a 4HB-CoA transferase and/or PHA synthase, for polymer production. Processes for polymer production use recombinant systems that can utilize cheap substrates. Systems are provided which can utilize amino acid degradation pathways, α-ketoglutarate, or succinate as substrate.
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公开(公告)号：EP0981381A2
公开(公告)日：2000-03-01
申请号：EP98922281.5
申请日：1998-05-12
申请人： METABOLIX, INC.
IPC分类号： A61L15/26
CPC分类号： C12P7/625 , A61B17/06166 , A61B42/00 , A61K47/593 , A61K47/6957 , A61L15/26 , A61L17/10 , A61L27/18 , A61L27/34 , A61L29/06 , A61L31/06 , C08G63/06 , C08G63/6852 , C08G63/6882 , C08G63/912 , C12N5/0068 , C12N2533/30 , Y10S977/775 , Y10T428/139 , C08L67/04
摘要： Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided for use in numerous biomedical applications. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelia system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. PHAs are provided which are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone and other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses. Properties which are selected for include degradability, elasticity, inclusion of functional groups or derivatized groups, which can in turn be used to attach targeting agents, and bioadhesion.
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公开(公告)号：EP1654373B1
公开(公告)日：2012-08-15
申请号：EP03808364.8
申请日：2003-05-07
申请人： METABOLIX, INC. , Tepha, Inc.
IPC分类号： C12P7/62
CPC分类号： C12P7/625 , Y10T428/31507
摘要： Genetically engineered organisms for production of PHA copolymers containing 2-hydroxyacid monomers and the methods of making and using thereof have been developed. The copolymers containing 2-hydroxyacid monomers can be synthesized via biosynthesis by the action of a PHA polymerase in a living cell. By changing the genetic background of the cells, one can control specific metabolic pathways allowing control of the level of glycolic acid co-monomer in the PHA polymer.
摘要翻译： 已经开发了用于生产含有2-羟基酸单体的PHA共聚物的基因工程生物体及其制备和使用方法。 含有2-羟基酸单体的共聚物可以通过在活细胞中通过PHA聚合酶的作用进行生物合成来合成。 通过改变细胞的遗传背景，可以控制特定的代谢途径，从而控制PHA聚合物中乙醇酸共聚单体的水平。
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公开(公告)号：EP1042388B1
公开(公告)日：2006-11-15
申请号：EP98964258.2
申请日：1998-12-22
申请人： METABOLIX, INC.
IPC分类号： C08G63/06 , C08G63/91 , C08K3/00 , C08K5/00 , C08J9/26 , C08J9/28 , C08L67/04 , C12P7/62 , A61K47/34 , A61L17/00 , A61L27/00 , A61L31/00
CPC分类号： A61L31/06 , A61K9/1647 , A61K9/204 , A61K47/34 , A61K47/593 , A61L15/26 , A61L17/12 , A61L24/0042 , A61L26/0019 , A61L26/009 , A61L27/18 , A61L27/34 , A61L27/58 , A61L29/06 , A61L31/148 , C08G63/06 , C08G63/60 , C08G63/64 , C08G63/664 , C08G63/6852 , C08G63/6882 , C08J9/26 , C08J2201/044 , C08J2201/0482 , C08J2367/04 , C08K5/0033 , C08L67/04 , C08L101/00 , C12P7/625 , C08L2666/02
摘要： Biocompatible polyhydroxyalkanoate compositions, particularly based on biotechnologically produced homo- and copolymers of 4- hydroxybutyric acid, with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives like, for example, pore forming agents to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant groups or modifications in their backbones to alter their degradation rates. In still another embodiment, the polyhydroxyalkanoates are chemically modified. Methods for manufacturing the devices which increase porosity or exposed surface area can be used to alter degradability. As demonstrated by the examples, these polyhydroxyalkanoate compositions have extremely favorable mechanical properties, as well as are biocompatible and degrade within desirable time frames under physioogical conditions. These polyhydroxyalkanoate materials provide a wider range of polyhydroxyalkanoate degradation rates than are currently available. Methods for processing these materials, particularly for therapeutic, prophylactic or diagnostic applications, or into devices which can be implanted or injected, are also described.
摘要翻译： 已经开发了具有可控降解速率的生物相容性聚羟基链烷酸酯组合物，特别是基于生物技术生产的4-羟基丁酸均聚物和共聚物的组合物。 在一个实施方案中，聚羟基链烷酸酯含有添加剂，例如成孔剂以改变降解速率。 在另一个实施方案中，聚羟基链烷酸酯由单体混合物形成或在其骨架中包含侧基或修饰以改变其降解速率。 在又一个实施方案中，聚羟基链烷酸酯是化学改性的。 制造增加孔隙率或暴露表面积的装置的方法可用于改变可降解性。 如实施例所证实的，这些聚羟基链烷酸酯组合物具有非常有利的机械性能，并且在理疗条件下在所需的时间范围内具有生物相容性和降解性。 这些聚羟基链烷酸酯材料提供比目前可获得的更宽范围的聚羟基链烷酸酯降解速率。 还描述了用于处理这些材料的方法，特别是用于治疗，预防或诊断应用，或者可以植入或注射的装置。
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公开(公告)号：EP1163019A1
公开(公告)日：2001-12-19
申请号：EP00919621.3
申请日：2000-03-24
申请人： METABOLIX, INC.
CPC分类号： A61L27/58 , A61F2/07 , A61F2210/0004 , A61K31/715 , A61L17/12 , A61L27/18 , A61L31/06 , A61L31/148 , A61L31/16 , A61L2300/00 , C08G63/06 , C08J9/26 , C08J2201/0444 , C08J2201/0482 , C08J2367/04 , C08K5/0033 , C08L67/04 , C12P7/625 , Y10S606/911
摘要： Devices formed of or including biocompatible polyhydroxylkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating system, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.
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6.发明公开BIOLOGICAL SYSTEMS FOR MANUFACTURE OF POLYHYDROXYLALKANOATE POLYMERS CONTAINING 4-HYDROXYACIDS 有权生物SYSTEMS FOR聚合物聚羟基烷酸酯的制备4-羟基酸
公开(公告)号：EP1015565A2
公开(公告)日：2000-07-05
申请号：EP98948384.7
申请日：1998-09-18
申请人： METABOLIX, INC.
CPC分类号： C12N9/0008 , C08G63/06 , C12N9/1029 , C12N9/1096 , C12N15/8243 , C12P7/625
摘要： The gene encoding a 4-hydroxybutyryl-Co A transferase has been isolated from bacteria and integrated into the genome of bacteria also expressing a polyhydroxyalkanoate synthase, to yield an improved production process for 4HB-containing polyhydroxyalkanoates using transgenic organisms, including both bacteria and plants. The new pathways provide means for producing 4HB containing PHAs from cheap carbon sources such as sugars and fatty acids, in high yields, which are stable. Useful strains are obtained by screening strains having integrated into their genomes a gene encoding a 4HB-CoA transferase and/or PHA synthase, for polymer production. Processes for polymer production use recombinant systems that can utilize cheap substrates. Systems are provided which can utilize amino acid degradation pathways, α-ketoglutarate, or succinate as substrate.
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公开(公告)号：EP1654373A2
公开(公告)日：2006-05-10
申请号：EP03808364.8
申请日：2003-05-07
申请人： METABOLIX, INC. , Tepha, Inc.
IPC分类号： C12P1/00
CPC分类号： C12P7/625 , Y10T428/31507
摘要： Genetically engineered organisms for production of PHA copolymers containing 2-hydroxyacid monomers and the methods of making and using thereof have been developed. The copolymers containing 2-hydroxyacid monomers can be synthesized via biosynthesis by the action of a PHA polymerase in a living cell. By changing the genetic background of the cells, one can control specific metabolic pathways allowing control of the level of glycolic acid co-monomer in the PHA polymer.
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公开(公告)号：EP1098655B1
公开(公告)日：2004-11-24
申请号：EP99935846.8
申请日：1999-07-22
申请人： Metabolix, Inc.
IPC分类号： A61K31/765 , A61K31/19 , A23L1/30 , A61P3/00
CPC分类号： A61K31/765 , A23K20/105 , A23K50/10 , A23L33/10 , A23V2002/00 , A61K31/00 , A61K31/19 , A23V2250/206 , A23V2250/21 , A23V2250/30
摘要： Nutritional or therapeutic compositions are provided for increasing ketone body levels in the blood of mammals by providing a source of ketone bodies in the form of linear or cyclic oligomers and/or derivatives of 3-hydroxyacids. The 3-hydroxyacid can be in the form of a linear oligomer of 3-hydroxyacids other than linear homo-oligomers of 3-hydroxybutyric acid if administered in combination with acetoacetate, cyclic oligomers of 3-hydroxyacids, esters of the linear or cyclic oligomers, esters of 3-hydroxyacids other than 3-hydroxybutyric acid, and combinations thereof. An oligomer generally refers to a polymer of three or more hydroxyacids. Preferred 3-hydroxyacids include 3-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxyhexanoate, and 3-hydroxyheptanoate. Oligomers of odd-carbon number 3-hydroxyacids such as 3-hydroxyvalerate have advantages since they have a higher energy content than oligomers of 3-hydroxyacids having an even-number of carbons. The cyclic oligomers have advantageous properties since they result in a sustained, and/or controlled, ketone blood level over a period of hours. The compositions can be administered orally, for example, as a nutritional or dietary supplement, or intravenously. Increasing blood ketone levels is useful for seizure control, metabolic disease control, reduction of protein catabolism, appetite suppression, parenteral nutrition, increasing cardiac efficiency, treatment of diabetes and insulin resistant states, and treatment of effects of neurodegenerative disorders and epilepsy.
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9.发明公开
公开(公告)号：EP1212052A2
公开(公告)日：2002-06-12
申请号：EP00963475.9
申请日：2000-09-14
申请人： Tepha Inc. , METABOLIX, INC.
IPC分类号： A61K31/19 , A61K31/765 , A61P25/00 , A61P25/18
CPC分类号： A61K31/19 , A61K31/765
摘要： Oligomers and polymer compositions are provided which comprise GHB and produce GHB after administration in vivo. Devices for the storage and delivery of these polymers and oligomers are also provided. These oligomers and polymer compositions are useful in a variety of applications. The compositions can be used therapeutically, for example, in the treatment of patients with narcolepsy, chronic schizophrenia, catatonic schizophrenia, atypical psychoses, chronic brain syndrome, neurosis, alcoholism, drug addiction and withdrawal, Parkinson's disease and other neuropharmacological illnesses, hypertension, ischemia, circulatory collapse, radiation exposure, cancer, and myocardial infarction. Other uses for the compositions include anesthesia induction, sedation, growth hormone production, heightened sexual desire, anorectic effects, euphoria, smooth muscle relaxation, muscle mass production, and sleep, including rapid eye movement sleep. In a still further embodiment, the oligomers and polymers may be used to produce absence seizures.
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公开(公告)号：EP1098655A2
公开(公告)日：2001-05-16
申请号：EP99935846.8
申请日：1999-07-22
申请人： METABOLIX, INC.
IPC分类号： A61K31/765 , A61K31/19 , A23L1/30
CPC分类号： A61K31/765 , A23K20/105 , A23K50/10 , A23L33/10 , A23V2002/00 , A61K31/00 , A61K31/19 , A23V2250/206 , A23V2250/21 , A23V2250/30
摘要： Nutritional or therapeutic compositions are provided for increasing ketone body levels in the blood of mammals by providing a source of ketone bodies in the form of linear or cyclic oligomers and/or derivatives of 3-hydroxyacids. The 3-hydroxyacid can be in the form of a linear oligomer of 3-hydroxyacids other than linear homo-oligomers of 3-hydroxybutyric acid if administered in combination with acetoacetate, cyclic oligomers of 3-hydroxyacids, esters of the linear or cyclic oligomers, esters of 3-hydroxyacids other than 3-hydroxybutyric acid, and combinations thereof. An oligomer generally refers to a polymer of three or more hydroxyacids. Preferred 3-hydroxyacids include 3-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxyhexanoate, and 3-hydroxyheptanoate. Oligomers of odd-carbon number 3-hydroxyacids such as 3-hydroxyvalerate have advantages since they have a higher energy content than oligomers of 3-hydroxyacids having an even-number of carbons. The cyclic oligomers have advantageous properties since they result in a sustained, and/or controlled, ketone blood level over a period of hours. The compositions can be administered orally, for example, as a nutritional or dietary supplement, or intravenously. Increasing blood ketone levels is useful for seizure control, metabolic disease control, reduction of protein catabolism, appetite suppression, parenteral nutrition, increasing cardiac efficiency, treatment of diabetes and insulin resistant states, and treatment of effects of neurodegenerative disorders and epilepsy.
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