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81. 发明授权

US07413739B2 Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds 有权
标题翻译：药物活性化合物受控输送的共轭加成反应
公开(公告)号：US07413739B2
公开(公告)日：2008-08-19
申请号：US11257818
申请日：2005-10-25
申请人： Jeffrey A. Hubbell , Donald Elbert , Ronald Schoenmakers
发明人： Jeffrey A. Hubbell , Donald Elbert , Ronald Schoenmakers
IPC分类号： A61K38/54 , A61K39/40 , A61K39/00 , C12Q1/68 , C07H21/00 , C12N9/96
CPC分类号： A61L27/52 , A61K47/60 , A61K47/6903 , C07H21/04 , C08G65/329 , C08G65/3322 , C12N5/0068 , C12N2501/585 , C12N2533/30
摘要： The invention features polymeric biomaterials formed by nucleophilic addition reactions to conjugated unsaturated groups. These biomaterials may be used for medical treatments.
摘要翻译：本发明的特征在于通过对共轭不饱和基团的亲核加成反应形成的聚合物生物材料。这些生物材料可用于医疗治疗。

82. 发明申请

US20080118523A1 Polypeptide ligands for targeting cartilage and methods of use thereof 有权
标题翻译：用于靶向软骨的多肽配体及其使用方法
公开(公告)号：US20080118523A1
公开(公告)日：2008-05-22
申请号：US11545819
申请日：2006-10-10
申请人： Jeffrey A. Hubbell , Dominique A. Rothenfluh
发明人： Jeffrey A. Hubbell , Dominique A. Rothenfluh
IPC分类号： A61K39/00 , C07H21/04 , C12P21/06 , C07K7/08 , C07K7/06 , C07K14/705
CPC分类号： C07K7/06
摘要： Ligands that specifically bind to articular cartilage tissues are disclosed, including uses for targeting therapeutics towards articular cartilage tissue and new materials for articular cartilage. The ligands are effective in vivo to target therapeutic materials to articular cartilage.
摘要翻译：公开了特异性结合关节软骨组织的配体，包括用于将治疗剂靶向关节软骨组织的用途和用于关节软骨的新材料。配体在体内是有效的，以将治疗材料靶向关节软骨。

83. 发明授权

US07316845B2 Multifunctional polymeric tissue coatings 有权
标题翻译：多功能聚合物组织涂层
公开(公告)号：US07316845B2
公开(公告)日：2008-01-08
申请号：US10804787
申请日：2004-03-19
申请人： Jeffrey A. Hubbell , Donald L. Elbert , Curtis B. Herbert
发明人： Jeffrey A. Hubbell , Donald L. Elbert , Curtis B. Herbert
IPC分类号： B32B15/04 , B32B17/06
CPC分类号： C08G81/00 , A61K9/10 , A61K9/5031 , A61K9/5073 , A61K31/00 , A61K47/34 , A61L27/34 , A61L31/10 , B33Y80/00 , Y10T428/31504 , Y10T428/31678 , Y10T428/31725 , Y10T428/31855 , Y10T428/31971
摘要： Compositions for coating biological and non-biological surfaces, which minimize or prevent cell-cell contact and tissue adhesion, and methods of preparation and use thereof, are disclosed. Embodiments include polyethylene glycol/polylysine (PEG/PLL) block or comb-type copolymers with high molecular weight PLL (greater than 1000, more preferably greater than 100,000); PEG/PLL copolymers in which the PLL is a dendrimer which is attached to one end of the PEG; and multilayer compositions including alternating layers of polycationic and polyanionic materials. The multi-layer polymeric material is formed by the ionic interactions of a polycation and a polyanion. The molecular weights of the individual materials are selected such that the PEG portion of the copolymer inhibits cellular interactions, and the PLL portion adheres well to tissues. The compositions and methods are useful, for example, in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells. The compositions and methods are also useful for coating non-biological surfaces such as metallic surfaces.
摘要翻译：公开了用于涂覆生物和非生物表面的组合物，其最小化或防止细胞 - 细胞接触和组织粘附，以及其制备和使用方法。实施方案包括具有高分子量PLL（大于1000，更优选大于100,000）的聚乙二醇/聚赖氨酸（PEG / PLL）嵌段或梳型共聚物; PEG / PLL共聚物，其中PLL是连接到PEG的一端的树枝状大分子; 以及包括聚阳离子和聚阴离子材料的交替层的多层组合物。多层聚合物材料通过聚阳离子和聚阴离子的离子相互作用形成。选择各种材料的分子量使得共聚物的PEG部分抑制细胞相互作用，并且PLL部分粘附到组织上。组合物和方法可用于例如抑制手术后粘连的形成，保护受损的血管免受血栓形成和再狭窄，以及降低附着依赖性肿瘤细胞的转移程度。组合物和方法也可用于涂覆非生物表面如金属表面。

84. 发明授权

US07132475B2 Block copolymers for multifunctional self-assembled systems 有权
公开(公告)号：US07132475B2
公开(公告)日：2006-11-07
申请号：US10047404
申请日：2001-10-19
申请人： Jeffrey A. Hubbell , Alessandro Napoli , Nicola Tirelli
发明人： Jeffrey A. Hubbell , Alessandro Napoli , Nicola Tirelli
IPC分类号： C08K5/372 , C08F28/02
CPC分类号： C08L71/02 , A61K9/1075 , A61K9/1273 , C08G65/3344 , C08G75/08 , C08G2650/34 , C08L81/02 , C08L2205/05 , C08L81/00 , C08L83/00 , C08L2666/22 , C08L71/00
摘要： The invention provides methods for the preparation of multiblock copolymers, dispersions of multiblock copolymers, vesicles and micelles containing multiblock copolymers, and oxidative degradation products of multiblock copolymers.

85. 发明授权

US07091127B2 Methods and apparatus for patterning a surface 有权
公开(公告)号：US07091127B2
公开(公告)日：2006-08-15
申请号：US10246500
申请日：2002-09-18
申请人： Jeffrey A. Hubbell , Jane P. Bearinger , Marcus Textor
发明人： Jeffrey A. Hubbell , Jane P. Bearinger , Marcus Textor
IPC分类号： H01L21/302
CPC分类号： B29C43/003 , B29C2043/025 , B41M3/006 , C23F1/02 , G01Q80/00 , G03F7/0002 , H01L51/0015 , H01L51/0021
摘要： The present invention provides methods and apparatus for locally patterning surfaces. In one such method, an oxidizable thioether is adsorbed onto a conductive surface. The surface is then contacted with a fluid medium. A conducting stamp is then brought into contact with the fluid medium above the thioether-coated surface. Next, a potential is applied between the stamp and the surface. It is expected that the charge will be transferred through the medium to the coated surface along a shortest distance path, thereby locally oxidizing the thioether and effectively creating a negative patterned image of the conducting stamp on the surface. Remaining adsorbed thioether may then be used as a mask for standard etching or material addition procedures.

86. 发明授权

US06958212B1 Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds 有权
标题翻译：药物活性化合物受控输送的共轭加成反应
公开(公告)号：US06958212B1
公开(公告)日：2005-10-25
申请号：US09586937
申请日：2000-06-02
申请人： Jeffrey A. Hubbell , Donald Elbert , Ronald Schoenmakers
发明人： Jeffrey A. Hubbell , Donald Elbert , Ronald Schoenmakers
IPC分类号： A61K38/54 , A61K39/40 , A61K47/48 , C07H21/04 , C12N9/96 , C12Q1/68
CPC分类号： A61L27/52 , A61K47/60 , A61K47/6903 , C07H21/04 , C08G65/329 , C08G65/3322 , C12N5/0068 , C12N2501/585 , C12N2533/30
摘要： The invention features polymeric biomaterials formed by nucleophilic addition reactions to conjugated unsaturated groups. These biomaterials may be used for medical treatments.
摘要翻译：本发明的特征在于通过对共轭不饱和基团的亲核加成反应形成的聚合物生物材料。这些生物材料可用于医疗治疗。

87. 发明授权

US06939557B2 Slow release protein polymers 失效
标题翻译：缓释蛋白聚合物
公开(公告)号：US06939557B2
公开(公告)日：2005-09-06
申请号：US10650115
申请日：2003-08-26
申请人： Stephen C. Rowe , Kalvin Yim , Beadle P. Retnarajan , Jeffrey A. Hubbell , Durga Annavajula
发明人： Stephen C. Rowe , Kalvin Yim , Beadle P. Retnarajan , Jeffrey A. Hubbell , Durga Annavajula
IPC分类号： A61K47/18 , A01N37/18 , A01N43/04 , A01N61/00 , A61K9/14 , A61K9/16 , A61K38/27 , A61K45/08 , A61K47/20 , A61K47/26 , A61K47/32 , A61K47/34 , A61K47/36 , A61K47/42 , C12N11/02 , A61F2/02
CPC分类号： A61K9/0019 , A61K9/0043 , A61K9/0053 , A61K9/0073 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K9/5138 , A61K9/5146 , A61K38/09 , A61K38/1816 , A61K38/193 , A61K38/21 , A61K38/27 , A61K38/28
摘要： The invention features articles for delivery of a biologically active substance, methods for making such articles, and methods for treating an animal using the articles.
摘要翻译：本发明的特征在于用于递送生物活性物质的制品，用于制备这些制品的方法，以及使用制品治疗动物的方法。

88. 发明授权

US06723344B2 Controlled release of non heparin-binding growth factors from heparin-containing matrices 失效
标题翻译：从含肝素的基质中控制非肝素结合生长因子的释放
公开(公告)号：US06723344B2
公开(公告)日：2004-04-20
申请号：US09848664
申请日：2001-05-03
申请人： Shelly E. Sakiyama-Elbert , Jeffrey A. Hubbell
发明人： Shelly E. Sakiyama-Elbert , Jeffrey A. Hubbell
IPC分类号： A61K914
CPC分类号： A61L27/20 , A61K47/62 , A61K47/6903 , A61L27/227 , A61L27/54 , A61L2300/25 , A61L2300/252 , A61L2300/414 , A61L2300/602
摘要： Matrices that support cell adhesion and growth are disclosed that deliver low heparin-binding affinity growth factor protein peptides in a controlled manner. These matrices comprise covalently or non-covalently bound heparin or heparin-like polymers, which serve to sequester the low heparin-binding affinity growth factor protein peptides within the matrix. The controlled release of some low heparin-binding affinity growth factor or peptides thereof occurs by degradation of some matrix component or dissociation of the low heparin-binding affinity growth factor protein peptides from the bound heparin. This differs from many controlled delivery devices in that release is not controlled solely by diffusion, and the rate of release may therefore be regulated by altering the rate of degradation of the matrix component or the amount of heparin bound within the matrix. The controlled release of such low heparin-binding affinity growth factor proteins such as NGF-&bgr;, NT-3 and BDNF, is demonstrated. The invention also identifies basic domains that can be utilized to identify other low heparin-binding affinity growth factor protein peptides useful in delivery as part of the matrices described herein.
摘要翻译：公开了以受控方式递送低肝素结合亲和力生长因子蛋白质肽的支持细胞粘附和生长的基质。这些基质包括共价或非共价结合的肝素或肝素样聚合物，其用于螯合基质内的低肝素结合亲和力生长因子蛋白质肽。一些低肝素结合亲和力生长因子或其肽的受控释放通过某些基质成分的降解或从结合肝素解离低肝素结合亲和力生长因子蛋白质肽而发生。这与许多控制递送装置不同，因为释放不仅仅通过扩散控制，因此可以通过改变基质组分的降解速率或在基质内结合的肝素的量来调节释放速率。证明了这种低肝素结合亲和力生长因子蛋白如NGF-β，NT-3和BDNF的受控释放。本发明还鉴定了可用于鉴定作为本文所述的基质的一部分用于递送的其它低水平肝素结合亲和力生长因子蛋白质肽的基本结构域。

89. 发明授权

US06699504B2 Slow release protein polymers 失效
公开(公告)号：US06699504B2
公开(公告)日：2004-03-02
申请号：US09772174
申请日：2001-01-29
申请人： Stephen C. Rowe , Kalvin Yim , Beadle P. Retnarajan , Jeffrey A. Hubbell , Durga Annavajula
发明人： Stephen C. Rowe , Kalvin Yim , Beadle P. Retnarajan , Jeffrey A. Hubbell , Durga Annavajula
IPC分类号： A61K914
CPC分类号： A61K9/0019 , A61K9/0043 , A61K9/0053 , A61K9/0073 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K9/5138 , A61K9/5146 , A61K38/09 , A61K38/1816 , A61K38/193 , A61K38/21 , A61K38/27 , A61K38/28
摘要： The invention features articles for delivery of a biologically active substance, methods for making such articles, and methods for treating an animal using the articles.

90. 发明授权

US06607740B1 Enzyme-mediated modification of fivrin for tissue engineering 有权
标题翻译：酶介导的组织工程纤维蛋白修饰
公开(公告)号：US06607740B1
公开(公告)日：2003-08-19
申请号：US09695466
申请日：2000-10-24
申请人： Jeffrey A. Hubbell , Jason Schense
发明人： Jeffrey A. Hubbell , Jason Schense
IPC分类号： C12N910
CPC分类号： A61L31/046 , A61F2310/00377 , A61L24/106 , A61L27/225 , A61L27/227 , C07K2319/00 , C12N5/0068 , C12N2533/56
摘要： The invention provides fibrin-based, biocompatible materials useful in promoting cell growth, wound healing, and tissue regeneration. These materials are provided as part of several cell and tissue scaffolding structures that provide particular application for use in wound-healing and tissue regenerating. Methods for preparing these compositions and using them are also disclosed as part of the invention. A variety of peptides may be used in conjunction with the practice of the invention, in particular, the peptide IKVAV, and variants thereof. Generally, the compositions may be described as comprising a protein network (e.g., fibrin) and a peptide having an amino acid sequence that comprises a transglutaminase substrate domain (e.g., a factor XIIIa substrate domain) and a bioactive factor (e.g., a peptide or protein, such as a polypeptide growth factor), the peptide being covalently bound to the protein network. Other applications of the technology include their use on implantable devices (e.g., vascular graphs), tissue and cell scaffolding. Other applications include use in surgical adhesive or sealant, as well as in peripheral nerve regeneration and angiogenesis.
摘要翻译：本发明提供了用于促进细胞生长，伤口愈合和组织再生的基于纤维蛋白的生物相容性材料。提供这些材料作为几种细胞和组织脚手架结构的一部分，其提供用于伤口愈合和组织再生的特定应用。制备这些组合物并使用它们的方法也作为本发明的一部分公开。多种肽可以与本发明的实践结合使用，特别是肽IKVAV及其变体。通常，组合物可以被描述为包括蛋白质网络（例如，纤维蛋白）和具有包含转谷氨酰胺酶底物结构域（例如，因子XIIIa底物结构域）和生物活性因子（例如肽或其衍生物）的氨基酸序列的肽蛋白质，例如多肽生长因子），肽共价结合蛋白质网络。该技术的其他应用包括它们在可植入装置（例如血管图），组织和细胞支架上的使用。其他应用包括用于手术粘合剂或密封剂，以及在周围神经再生和血管生成中。

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