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1. 发明授权

US06511958B1 Compositions for regeneration and repair of cartilage lesions 有权
标题翻译：用于软骨损伤再生和修复的组合物
公开(公告)号：US06511958B1
公开(公告)日：2003-01-28
申请号：US09505209
申请日：2000-02-16
申请人： Brent Atkinson , James J. Benedict
发明人： Brent Atkinson , James J. Benedict
IPC分类号： A01N3718
CPC分类号： B82Y5/00 , A61B17/06166 , A61F2/30756 , A61F2002/2817 , A61F2002/30062 , A61F2002/30677 , A61F2210/0004 , A61F2310/00365 , A61L27/227 , A61L27/24 , A61L27/26 , A61L27/54 , A61L2300/252 , A61L2300/414 , A61L2300/45 , A61L2430/06 , Y10S530/84 , Y10S977/907 , Y10S977/908 , Y10S977/91 , Y10S977/912 , Y10S977/914 , Y10S977/915 , C08L89/06
摘要： Disclosed is a cartilage repair product that induces both cell ingrowth into a bioresorbable material and cell differentiation into cartilage tissue. Such a product is useful for regenerating and/or repairing both vascular and avascular cartilage lesions, particularly articular cartilage lesions, and even more particularly mensical tissue lesions, including tears as well as segmental defects. Also disclosed is a method of regenerating and repairing cartilage lesions using such a product.
摘要翻译：公开了一种软骨修复产品，其诱导细胞向生长可再生材料向内生长并将细胞分化为软骨组织。这种产品可用于再生和/或修复血管和非血管软骨损伤，特别是关节软骨病变，甚至更特别是包括眼泪以及节段性缺损的神经组织病变。还公开了使用这种产品再生和修复软骨损伤的方法。

2. 发明申请

US20060216325A1 Composition and device for in vivo cartilagerepair 审中-公开
标题翻译：用于体内软骨修复的组合物和装置
公开(公告)号：US20060216325A1
公开(公告)日：2006-09-28
申请号：US11433968
申请日：2006-05-15
申请人： Brent Atkinson , Pedro Bittman , James Benedict , John Ranieri , Marsha Whitney , Donald Chickering
发明人： Brent Atkinson , Pedro Bittman , James Benedict , John Ranieri , Marsha Whitney , Donald Chickering
IPC分类号： A61F2/28
CPC分类号： A61K9/5153 , A61B17/06166 , A61F2/30756 , A61F2002/2817 , A61F2002/30036 , A61F2002/30062 , A61F2002/30677 , A61F2210/0004 , A61F2250/0035 , A61F2310/00365 , A61L27/227 , A61L27/24 , A61L27/26 , A61L27/48 , A61L27/50 , A61L27/54 , A61L2300/252 , A61L2300/30 , A61L2300/624 , A61L2400/12 , A61L2430/06 , B82Y5/00 , Y10S977/91 , Y10S977/914 , C08L89/06 , C08L5/08
摘要： The composition as described serves for in vivo cartilage repair. It basically consists of a naturally derived osteoinductive and/or chondroinductive mixture of factors (e.g. derived from bone) or of a synthetic mimic of such a mixture combined with a nanosphere delivery system. A preferred mixture of factors is the combination of factors isolated from bone, known as BP and described by Poser and Benedict (WO 95/13767). The nanosphere delivery system consists of nanospheres defined as polymer particles of less than 1000 nm in diameter (whereby the majority of particles preferably ranges between 200-400 nm) in which nanospheres the combination of factors is encapsulated. The nanospheres are loaded with the mixture of factors in a weight ratio of 0.001 to 17% (w/w), preferably of 1 to 4% (w/w) and have a release profile with an initial burst of 10 to 20% of the total load over the first 24 hours and a long time release of at least 0.1 per day during at least seven following days. The nanospheres are composed of e.g. ((D,L)-lactic acid/glycolic acid)-copolymer (PLGA). The loaded nanospheres are e.g. made by phase inversion. The composition is advantageously utilized as a device comprising any biodegradable matrix in which the nanospheres loaded with the factor combination is contained.
摘要翻译：所述的组合物用于体内软骨修复。其基本上由天然衍生的成骨诱导和/或软骨诱导的因子（例如衍生自骨）的混合物或与纳米球递送系统组合的这种混合物的合成模拟物组成。因素的优选混合物是从骨分离的因子（称为BP）并由Poser和Benedict（WO 95/13767）描述的组合。纳米球传递系统由纳米球定义为直径小于1000nm的聚合物颗粒（其中大多数颗粒的范围优选在200-400nm之间），其中纳米球包封因子的组合。纳米球以重量比为0.001至17％（w / w），优选1至4％（w / w）的因子混合物加载，并具有释放曲线，初始爆发为10至20％至少在接下来的七天内，前24小时的总负荷和每天至少0.1次的长时间释放。纳米球由例如，（（D，L） - 乳酸/乙醇酸） - 共聚物（PLGA）。负载的纳米球是例如。通过相位反演。组合物有利地用作包含其中包含加载因子组合的纳米球的任何可生物降解的基质的装置。

3. 发明授权

US06482594B2 Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands 失效
标题翻译：配体通过指数富集的系统演化：核酸配体的选择
公开(公告)号：US06482594B2
公开(公告)日：2002-11-19
申请号：US09882246
申请日：2001-06-14
申请人： Larry Gold , Michael Willis , Tad Koch , Steven Ringquist , Kirk Jensen , Brent Atkinson
发明人： Larry Gold , Michael Willis , Tad Koch , Steven Ringquist , Kirk Jensen , Brent Atkinson
IPC分类号： C12Q168
CPC分类号： G01N33/76 , A61K47/547 , A61K47/549 , B82Y5/00 , C07H19/06 , C07H19/10 , C07H21/00 , C07K14/001 , C12N9/1276 , C12N15/1048 , C12N15/115 , C12N2310/13 , C12N2310/322 , C12N2310/53 , C12Q1/37 , C12Q1/6811 , C12Q1/703 , C40B40/00 , F02B2075/027 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/56988 , G01N33/68 , G01N2333/163 , G01N2333/575 , G01N2333/62 , G01N2333/8125 , G01N2333/96433 , G01N2333/96455 , G01N2333/966 , G01N2333/9726 , G01N2333/974 , G01N2333/976 , C12Q2541/101 , C12Q2523/313
摘要： Methods to obtain nucleic acid ligands that photocrosslink to target molecules associated with a disease state are provided. The methods presented are variations on the photoSELEX methods for obtaining nucleic acid ligands. In one method, a candidate mixture of photocrosslinkable nucleic acids is contacted with a biological substance obtained from a source associated with a disease state suspected of containing a target molecule to form nucleic acid-target molecule complexes, the complexes are irradiated to form crosslinked complexes, the photocrosslinked complexes are partitioned from the remainder of the candidate mixture; and the nucleic acid ligands that photocrosslink to molecule are retained. These nucleic acids are then contacted with a second biological substance of the same type as the first, but obtained from a source not associated with a disease state. This removes nucleic acids with affinity to molecules that are not associated with the disease state. In another method, photocrosslinkable nucleic acids are not incorporated in the initial candidate mixture, but rather are incorporated in an enriched candidate mixture obtained by contacting a biological substance associated with a disease state containing a target molecule to form nucleic acid-target molecule complexes, partitioning the complexes away from the candidate mixture.
摘要翻译：提供了获得与疾病状态相关的靶分子光交联的核酸配体的方法。所提出的方法是用于获得核酸配体的photoSELEX方法的变化。在一种方法中，光可交联核酸的候选混合物与从怀疑含有靶分子的疾病状态的来源获得的生物物质接触以形成核酸 - 靶分子复合物，照射复合物以形成交联的复合物，将光致交联复合物与候选混合物的其余部分分隔开; 并保留与分子光交联的核酸配体。然后将这些核酸与与第一种相同类型的第二生物物质接触，但从不与疾病状态相关的来源获得。这样就可以去除与疾病状态无关的分子的亲和力的核酸。在另一种方法中，光可交联核酸不并入初始候选混合物中，而是掺入通过使与含有靶分子的疾病状态相关的生物物质接触形成核酸 - 靶分子复合物，分配远离候选混合物的复合物。

4. 发明授权

US06291184B1 Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex 失效
标题翻译：配体通过指数富集的系统演化：核酸配体的照片选择和溶液溶解
公开(公告)号：US06291184B1
公开(公告)日：2001-09-18
申请号：US09459553
申请日：1999-12-13
申请人： Larry Gold , Michael Willis , Tad Koch , Steven Ringquist , Kirk Jensen , Brent Atkinson
发明人： Larry Gold , Michael Willis , Tad Koch , Steven Ringquist , Kirk Jensen , Brent Atkinson
IPC分类号： C12Q168
CPC分类号： G01N33/76 , A61K47/547 , A61K47/549 , B82Y5/00 , C07H19/06 , C07H19/10 , C07H21/00 , C07K14/001 , C12N9/1276 , C12N15/1048 , C12N15/115 , C12N2310/13 , C12N2310/322 , C12N2310/53 , C12Q1/37 , C12Q1/6811 , C12Q1/703 , C40B40/00 , F02B2075/027 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/56988 , G01N33/68 , G01N2333/163 , G01N2333/575 , G01N2333/62 , G01N2333/8125 , G01N2333/96433 , G01N2333/96455 , G01N2333/966 , G01N2333/9726 , G01N2333/974 , G01N2333/976 , C12Q2541/101 , C12Q2523/313
摘要： A method for identifying nucleic acid ligands to target molecules using the SELEX procedure wherein the candidate nucleic acids contain photoreactive groups and nucleic acid ligands identified thereby are claimed. The complexes of increased affinity nucleic acids and target molecules formed in the procedure are crosslinked by irradiation to facilitate separation from unbound nucleic acids. In other methods partitioning of high and low affinity nucleic acids is facilitated by primer extension steps as shown in the figure in which chain termination nucleotides, digestion resistant nucleotides or nucleotides that allow retention of the cDNA product on an affinity matrix are differentially incorporated into the cDNA products of either the high or low affinity nucleic acids and the cDNA products are treated accordingly to amplification, enzymatic or chemical digestion or by contact with an affinity matrix.
摘要翻译：使用SELEX方法鉴定靶分子的核酸配体的方法，其中候选核酸含有由其鉴定的光反应性基团和核酸配体。本方法中形成的增加的亲和核酸和靶分子的复合物通过照射进行交联，以促进与未结合核酸的分离。在其他方法中，通过如图所示的引物延伸步骤促进了高亲和性核酸的分配，其中使得能够将亲和基质上的cDNA产物保留的链终止核苷酸，消化抗性核苷酸或核苷酸差异并入cDNA 相应地对高亲和性核酸和cDNA产物的产物进行扩增，酶促或化学消化或通过与亲和基质接触。

5. 再颁专利

USRE41286E1 Compositions for regeneration and repair of cartilage lesions 有权
标题翻译：用于软骨损伤再生和修复的组合物
公开(公告)号：USRE41286E1
公开(公告)日：2010-04-27
申请号：US11046674
申请日：2005-01-28
申请人： Brent Atkinson , James J. Benedict
发明人： Brent Atkinson , James J. Benedict
IPC分类号： A01N37/18 , A61K38/00 , A61K9/14 , A61K35/32 , A61F13/00 , A61F2/00 , C07K1/00 , C07K14/00 , C07K17/00
CPC分类号： A61K9/5153 , A61B17/06166 , A61F2/30756 , A61F2002/2817 , A61F2002/30036 , A61F2002/30062 , A61F2002/30677 , A61F2210/0004 , A61F2250/0035 , A61F2310/00365 , A61L27/227 , A61L27/24 , A61L27/26 , A61L27/48 , A61L27/50 , A61L27/54 , A61L2300/252 , A61L2300/30 , A61L2300/624 , A61L2400/12 , A61L2430/06 , B82Y5/00 , Y10S977/91 , Y10S977/914 , C08L89/06 , C08L5/08
摘要： Disclosed is a cartilage repair product that induces both cell ingrowth into a bioresorbable material and cell differentiation into cartilage tissue. Such a product is useful for regenerating and/or repairing both vascular and avascular cartilage lesions, particularly articular cartilage lesions, and even more particularly mensical tissue lesions, including tears as well as segmental defects. Also disclosed is a method of regenerating and repairing cartilage lesions using such a product.
摘要翻译：公开了一种软骨修复产品，其诱导细胞向生长可再生材料向内生长并将细胞分化为软骨组织。这种产品可用于再生和/或修复血管和非血管软骨损伤，特别是关节软骨病变，甚至更特别是包括眼泪以及节段性缺损的神经组织病变。还公开了使用这种产品再生和修复软骨损伤的方法。

6. 发明授权

US06514514B1 Device and method for regeneration and repair of cartilage lesions 失效
标题翻译：软骨损伤再生和修复的装置和方法
公开(公告)号：US06514514B1
公开(公告)日：2003-02-04
申请号：US09250370
申请日：1999-02-16
申请人： Brent Atkinson , James J. Benedict
发明人： Brent Atkinson , James J. Benedict
IPC分类号： A61E1300
CPC分类号： A61K9/5153 , A61B17/06166 , A61F2/30756 , A61F2002/2817 , A61F2002/30036 , A61F2002/30062 , A61F2002/30677 , A61F2210/0004 , A61F2250/0035 , A61F2310/00365 , A61L27/227 , A61L27/24 , A61L27/26 , A61L27/48 , A61L27/50 , A61L27/54 , A61L2300/252 , A61L2300/30 , A61L2300/624 , A61L2400/12 , A61L2430/06 , B82Y5/00 , Y10S977/91 , Y10S977/914 , C08L89/06 , C08L5/08
摘要： Disclosed is a cartilage repair product that induces both cell ingrowth into a bioresorbable material and cell differentiation into cartilage tissue. Such a product is useful for regenerating and/or repairing both vascular and avascular cartilage lesions, particularly articular cartilage lesions, and even more particularly mensical tissue lesions, including tears as well as segmental defects. Also disclosed is a method of regenerating and repairing cartilage lesions using such a product.
摘要翻译：公开了一种软骨修复产品，其诱导细胞向生长可再生材料向内生长并将细胞分化为软骨组织。这种产品可用于再生和/或修复血管和非血管软骨损伤，特别是关节软骨病变，甚至更特别是包括眼泪以及节段性缺损的神经组织病变。还公开了使用这种产品再生和修复软骨损伤的方法。

7. 发明授权

US5763177A Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex 失效
标题翻译：配体通过指数富集的系统演化：核酸配体的照片选择和溶液溶解
公开(公告)号：US5763177A
公开(公告)日：1998-06-09
申请号：US612895
申请日：1996-03-08
申请人： Larry Gold , Michael Willis , Tad Koch , Steven Ringquist , Kirk Jensen , Brent Atkinson
发明人： Larry Gold , Michael Willis , Tad Koch , Steven Ringquist , Kirk Jensen , Brent Atkinson
IPC分类号： C07B61/00 , C07H19/06 , C07H19/10 , C07H21/00 , C07K14/00 , C12N9/12 , C12N15/10 , C12Q1/37 , C12Q1/68 , C12Q1/70 , F02B75/02 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/569 , G01N33/68 , G01N33/76 , C07H21/02 , C07H21/04 , C12P19/34
CPC分类号： G01N33/76 , C07H19/06 , C07H19/10 , C07H21/00 , C07K14/001 , C12N15/1048 , C12N9/1276 , C12Q1/37 , C12Q1/6811 , G01N33/531 , G01N33/532 , G01N33/535 , G01N33/56988 , G01N33/68 , C12N2310/13 , C12N2310/322 , C12N2310/53 , C40B40/00 , F02B2075/027 , G01N2333/163 , G01N2333/8125 , G01N2333/96433 , G01N2333/96436 , G01N2333/96486 , G01N2333/966 , G01N2333/974
摘要： A method for identifying nucleic acid ligands to target molecules using the SELEX pocedure wherein the candidate nucleic acids contain photoreactive groups and nucleic acid ligands identified thereby are claimed. The complexes of increased affinity nucleic acids and target molecules formed in the procedure are crosslinked by irradiation to facilitate separation from unbound nucleic acids. In other methods partioning of high and low affinity nucleic acids is facilitated by primer extension steps as shown in the figure in which chain termination nucleotides, digestion resistant nucleotides or nucleotides that allow retention of the cDNA product on an affinity matrix are differentially incorporated into the cDNA products of either the high or low affinity nucleic acids and the cDNA products are treated accordingly to amplification, enzymatic or chemical digestion or by contact with an affinity matrix.
摘要翻译： PCT No.PCT / US94 / 10562 Sec。 371日期：1996年3月8日 102（e）1996年3月8日PCT PCT 1994年9月16日PCT公布。公开号WO95 / 08003 日期1995年3月23日使用SELEX沉积物鉴定靶分子的核酸配体的方法，其中候选核酸含有由其识别的光反应性基团和核酸配体。本方法中形成的增加的亲和核酸和靶分子的复合物通过照射进行交联，以促进与未结合核酸的分离。在其他方法中，通过如图所示的引物延伸步骤促进了高亲和性核酸的分离，其中将亲和基质上的cDNA产物保留的链终止核苷酸，消化抗性核苷酸或核苷酸差异并入cDNA 相应地对高亲和性核酸和cDNA产物的产物进行扩增，酶促或化学消化或通过与亲和基质接触。

8. 发明申请

US20140024115A1 METHODS OF COMBINING MESENCHYMAL STEM CELLS AND CARTILAGE CONTAINING ALLOGRAFTS, AND PRODUCTS OF COMBINED MESENCHYMAL STEM CELLS AND CARTILAGE CONTAINING ALLOGRAFTS 审中-公开
标题翻译：组合骨髓间充质干细胞的方法和含有合成纤维素的组合物，以及组合的骨髓间充质干细胞和包含合成纤维的产品
公开(公告)号：US20140024115A1
公开(公告)日：2014-01-23
申请号：US12965335
申请日：2010-12-10
申请人： Simon Bogdansky , Yaling Shi , Brent Atkinson
发明人： Simon Bogdansky , Yaling Shi , Brent Atkinson
IPC分类号： C12N5/0775
CPC分类号： A61L27/3608 , A61K35/12 , A61L27/3834 , A61L27/3847 , A61L27/54 , A61L2430/02 , C12N5/0667 , C12N2533/90
摘要： There is disclosed a method of combining mesenchymal stem cells (MSCs) with an osteochondral allograft. In an embodiment, the method includes obtaining adipose tissue having MSCs with unwanted cells. The tissue is digested to form a cell suspension having MSCs and unwanted cells. The suspension is added to seed the allograft. The MSCs are allowed to attach to the allograft. There is disclosed an allograft product including MSCs with an osteochondral allograft. There is disclosed a method of combining MSCs with decellularized, morselized cartilage. In an embodiment, the method includes obtaining adipose tissue having MSCs with unwanted cells. The tissue is digested to form a cell suspension having MSCs and unwanted cells. The suspension is added to seed the cartilage. The MSCs are allowed to attach to the cartilage to. There is disclosed an allograft product including MSCs with morselized cartilage. Other embodiments are also disclosed.
摘要翻译：公开了将间充质干细胞（MSC）与骨软骨同种异体移植物组合的方法。在一个实施方案中，该方法包括获得具有不想要的细胞的MSC的脂肪组织。将组织消化以形成具有MSC和不想要的细胞的细胞悬浮液。加入悬浮液以种植同种异体移植物。允许MSC附着于同种异体移植物。公开了包括具有骨软骨同种异体移植物的MSC的同种异体移植物产品。公开了将MSC与脱细胞的，随机化的软骨组合的方法。在一个实施方案中，该方法包括获得具有不想要的细胞的MSC的脂肪组织。将组织消化以形成具有MSC和不想要的细胞的细胞悬浮液。加入悬浮液以使软骨种子。允许MSCs附着在软骨上。公开了一种同种异体移植物产品，其中包括具有小块软骨的MSC。还公开了其他实施例。

9. 发明申请

US20080063622A1 Composition and Method for Delivery of BMP-2 Amplifier/Co-Activator for Enhancement of Osteogenesis 有权
标题翻译：用于增强骨形成的BMP-2放大器/辅助活化剂的组合物和方法
公开(公告)号：US20080063622A1
公开(公告)日：2008-03-13
申请号：US11767391
申请日：2007-06-22
申请人： Paul Zamora , Brent Atkinson
发明人： Paul Zamora , Brent Atkinson
IPC分类号： A61K35/32 , A61K31/765 , A61P19/00
CPC分类号： C07K14/4705 , A61K38/1875 , A61L27/12 , A61L27/227 , A61L27/24 , A61L2430/02
摘要： A composition comprising a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor and an osteoconductive material where the synthetic growth factor analogue is attached to and can be released from the osteoconductive material and is an amplifier/co-activator of osteoinduction.
摘要翻译：包含合成生长因子类似物的组合物，其包含非生长因子肝素结合区，接头和与细胞表面受体特异性结合的序列和骨传导性材料，其中所述合成生长因子类似物与所述合成生长因子类似物连接并可从骨传导材料是骨诱导的放大器/辅助激活物。

10. 发明申请

US20070269518A1 Light-curable bone growth material for treating dental bone defects 审中-公开
标题翻译：用于治疗牙齿缺陷的可光固化骨生长材料
公开(公告)号：US20070269518A1
公开(公告)日：2007-11-22
申请号：US11644587
申请日：2006-12-22
申请人： Katherine Walline , Brent Atkinson
发明人： Katherine Walline , Brent Atkinson
IPC分类号： A61K9/14 , A61K35/12 , C12N5/06
CPC分类号： A61K6/087 , A61K6/0052 , A61K6/097 , A61L27/3608 , A61L27/365 , A61L27/44 , A61L27/50 , A61L27/52 , A61L2430/02 , C08L5/08 , C08L1/284
摘要： Improved compositions comprising a mixture of particulate bone growth material and polymeric carrier are provided. The particulate is preferably porous, resorbable, anorganic bone material. The polymeric carrier can be light-cured to form a cross-linked, biodegradable hydrogel. In one version, the bone growth material is a synthetic peptide bound to anorganic bone matrix particles and the carrier is methacrylated sodium hyaluronate (MHy) or methacrylated hydroxyethylcellulose (MHEC). The composition is particularly suitable for repairing defective dental and orthopedic bone tissue. The particulate and hydrogel carrier are biodegradable so the composition can be replaced by new bone formation over time.
摘要翻译：提供包含颗粒骨生长材料和聚合物载体的混合物的改进的组合物。颗粒优选是多孔的，可再吸收的，无机骨材料。聚合物载体可以光固化形成交联的可生物降解的水凝胶。在一个版本中，骨生长材料是与无机骨基质颗粒结合的合成肽，载体是甲基丙烯酸化的透明质酸钠（MHy）或甲基丙烯酸羟乙基纤维素（MHEC）。该组合物特别适用于修复有缺陷的牙科和矫形骨组织。颗粒和水凝胶载体是可生物降解的，因此随着时间的推移，组合物可以被新的骨形成代替。

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