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1. 发明授权

US08309518B2 Drug delivery matrices to enhance wound healing 有权
标题翻译：药物递送基质以增强伤口愈合
公开(公告)号：US08309518B2
公开(公告)日：2012-11-13
申请号：US12845354
申请日：2010-07-28
申请人： Jason C. Schense , Hugo Schmoekel , Jeffrey A. Hubbell , Franz Weber
发明人： Jason C. Schense , Hugo Schmoekel , Jeffrey A. Hubbell , Franz Weber
IPC分类号： A61K38/18 , A61K38/36 , C07K14/495 , C07K14/51
CPC分类号： A61L31/046 , A61L24/0015 , A61L24/106 , A61L27/225 , A61L27/227 , A61L27/54 , A61L2300/236 , A61L2300/252 , A61L2300/412 , A61L2300/414 , A61L2300/45
摘要： Bioactive molecules are entrapped within a matrix for the controlled delivery of these compounds for therapeutic healing applications. The matrix may be formed of natural or synthetic compounds. The primary method of entrapment of the bioactive molecule is through precipitation of the bioactive molecule during gelation of the matrix, either in vitro or in vivo. The bioactive molecule may be modified to reduce its effective solubility in the matrix to retain it more effectively within the matrix, such as through the deglycosylation of members within the cystine knot growth factor superfamily and particularly within the TGFβ superfamily. The matrix may be modified to include sites with binding affinity for different bioactive molecules, for example, for heparin binding.
摘要翻译：生物活性分子被包埋在基质内，用于受控递送这些化合物用于治疗性愈合应用。基质可以由天然或合成的化合物形成。捕获生物活性分子的主要方法是通过体外或体内在基质凝胶化过程中沉淀生物活性分子。生物活性分子可以被修饰以降低其在基质中的有效溶解度，以便在基质内更有效地保留生物活性分子，例如通过胱氨酸结生长因子超家族内，特别是在TGF-bgr内的成员的去糖基化; 超家族可以修饰基质以包括对不同生物活性分子具有结合亲和力的位点，例如用于肝素结合的位点。

2. 发明授权

US07601685B2 Growth factor modified protein matrices for tissue engineering 有权
标题翻译：用于组织工程的生长因子修饰蛋白质基质
公开(公告)号：US07601685B2
公开(公告)日：2009-10-13
申请号：US10323046
申请日：2002-12-17
申请人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama-Elbert
发明人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama-Elbert
IPC分类号： A61K38/00
CPC分类号： C07K14/475
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.
摘要翻译：将蛋白质掺入用于组织修复，再生和/或重塑和/或药物递送的蛋白质或多糖基质中。可以掺入蛋白质，使其通过降解基质，通过酶作用和/或扩散来释放。如实施例所示，一种方法是通过共价或非共价方法将肝素与基质结合，形成肝素基质。然后肝素将肝素结合生长因子非共价结合到蛋白质基质上。或者，可以构建融合蛋白，其包含交联区域，例如因子XIIIa底物和天然蛋白质序列。当需要长期药物递送时，例如在神经再生的情况下，在基质和生物活性因子之间引入可降解的键可能是特别有用的，其中期望在空间上改变作为再生的功能的药物释放速率，例如快速靠近生物组织界面，并进一步向进入损伤区更慢。额外的益处包括递送系统内的总药物剂量越少，释放的空间调节，允许在最大的细胞活动时释放更多百分比的药物。

3. 发明授权

US06960452B2 Enzyme-mediated modification of fibrin for tissue engineering: incorporation of proteins 有权
标题翻译：酶介导的纤维蛋白修饰组织工程：掺入蛋白质
公开(公告)号：US06960452B2
公开(公告)日：2005-11-01
申请号：US09798338
申请日：2001-03-02
申请人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama
发明人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama
IPC分类号： C07K14/475 , C12P21/00 , A01N1/00 , A61K9/14
CPC分类号： C07K14/475
摘要： Disclosed are materials that may be used in the design of improved devices and wound treatment platforms though covalent and/or non-covalent attachment of bioactive proteins. The proteins comprise any variety of cell growth and/or healing promoting proteins, such as growth factor. The incorporation of these whole proteins may be designed to provide controlled release thereof in a biological system through further use of enzyme degradation sites. Heparin-binding protein or fusion proteins synthesized to contain a heparin-binding domain are two mechanisms that may be used in providing these properties to a matrix, such as a fibrinogen matrix. The proteins will be used to provide enhanced healing in various tissues including vasculature, skin, nerve, and liver. The materials disclosed will be used to enhance would?? Healing and other generative processes by engineering the fibrin gel to contain appropriate proteins with specifically designed release and/or degradation characteristics.
摘要翻译：公开了可以用于设计改进的装置和伤口治疗平台的材料，尽管共价和/或非共价连接生物活性蛋白质。蛋白质包括任何多种细胞生长和/或愈合促进蛋白质，例如生长因子。可以将这些全蛋白的掺入设计成通过进一步使用酶降解位点来提供其在生物系统中的受控释放。合成含有肝素结合结构域的肝素结合蛋白或融合蛋白是可用于向基质例如纤维蛋白原基质提供这些性质的两种机制。蛋白质将用于在各种组织中提供增强的愈合，包括脉管系统，皮肤，神经和肝脏。所披露的材料将被用来增强通过设计纤维蛋白凝胶来包含具有专门设计的释放和/或降解特性的合适蛋白质来治疗和其他生成过程。

4. 发明授权

US06894022B1 Growth factor modified protein matrices for tissue engineering 有权
标题翻译：用于组织工程的生长因子修饰蛋白质基质
公开(公告)号：US06894022B1
公开(公告)日：2005-05-17
申请号：US09563760
申请日：2000-05-01
申请人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama-Elbert
发明人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama-Elbert
IPC分类号： C07K14/475 , A61K31/727
CPC分类号： C07K14/475
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling, and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, enzymatic action, and/or diffusion. In one embodiment, a fusion protein, which contains a crosslinking region, such as a factor XIIIa substrate, and a native protein sequence, such as a bioactive factor, is constructed. Degradable linkages may be included between the crosslinking region and the bioactive factor.
摘要翻译：将蛋白质掺入用于组织修复，再生和/或重塑和/或药物递送的蛋白质或多糖基质中。可以掺入蛋白质，使其通过降解基质，酶作用和/或扩散而释放。在一个实施方案中，构建了含有交联区域（例如因子XIIIa底物）和天然蛋白质序列（例如生物活性因子）的融合蛋白质。交联区域和生物活性因子之间可以包括可降解的连接。

5. 发明授权

US06468731B1 Enzyme-mediated modification of fibrin for tissue engineering: incorporation of proteins 有权
标题翻译：酶介导的纤维蛋白修饰组织工程：掺入蛋白质
公开(公告)号：US06468731B1
公开(公告)日：2002-10-22
申请号：US09675922
申请日：2000-09-29
申请人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama
发明人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama
IPC分类号： A01N102
CPC分类号： C07K14/475
摘要： Disclosed are materials that may be used in the design of improved devices and wound treatment platforms though covalent and/or non-covalent attachment of bioactive proteins. The proteins comprise any variety of cell growth and/or healing promoting proteins, such as growth factor. The incorporation of these whole proteins may be designed to provide controlled release thereof in a biological system through further use of enzyme degradation sites. Heparin-binding protein or fusion proteins synthesized to contain a heparin binding domain are two mechanisms that may be used in providing these properties to a matrix, such as a fibrinogen matrix. The proteins will be used to provide enhanced healing in various tissues including vasculature, skin, nerve, and liver. The materials disclosed will be used to enhance would healing and other generative processes by engineering the fibrin gel to contain appropriate proteins with specifically designed release and/or degradation characteristics.
摘要翻译：公开了可以用于设计改进的装置和伤口治疗平台的材料，尽管共价和/或非共价连接生物活性蛋白质。蛋白质包括任何多种细胞生长和/或愈合促进蛋白质，例如生长因子。可以将这些全蛋白的掺入设计成通过进一步使用酶降解位点来提供其在生物系统中的受控释放。合成含有肝素结合结构域的肝素结合蛋白或融合蛋白是可用于向基质例如纤维蛋白原基质提供这些性质的两种机制。蛋白质将用于在各种组织中提供增强的愈合，包括脉管系统，皮肤，神经和肝脏。所公开的材料将用于通过将纤维蛋白凝胶工程化以含有具有专门设计的释放和/或降解特征的合适蛋白质来增强愈合和其它生成过程。

6. 发明授权

US08034618B2 PTH containing cell growth matrix 有权
标题翻译：含PTH的细胞生长基质
公开(公告)号：US08034618B2
公开(公告)日：2011-10-11
申请号：US11679807
申请日：2007-02-27
申请人： Matthias Lutolf , Jason C. Schense , Jeffrey A. Hubbell , Anna Jen
发明人： Matthias Lutolf , Jason C. Schense , Jeffrey A. Hubbell , Anna Jen
IPC分类号： C12N5/00
CPC分类号： A61L27/225 , A61K38/00 , A61L27/227 , C07K14/635 , C07K2319/00
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.
摘要翻译：将蛋白质掺入用于组织修复，再生和/或重塑和/或药物递送的蛋白质或多糖基质中。可以掺入蛋白质，使其通过降解基质，通过酶作用和/或扩散来释放。如实施例所示，一种方法是通过共价或非共价方法将肝素与基质结合，形成肝素基质。然后肝素将肝素结合生长因子非共价结合到蛋白质基质上。或者，可以构建融合蛋白，其包含交联区域，例如因子XIIIa底物和天然蛋白质序列。当需要长期药物递送时，例如在神经再生的情况下，在基质和生物活性因子之间引入可降解的键可能是特别有用的，其中期望在空间上改变作为再生的功能的药物释放速率，例如快速靠近生物组织界面，并进一步向进入损伤区更慢。额外的益处包括递送系统内的总药物剂量越少，释放的空间调节，允许在最大的细胞活动时释放更多百分比的药物。

7. 发明授权

US07241730B2 Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides 失效
标题翻译：用于组织工程的酶介导的纤维蛋白修饰：具有肽的纤维蛋白制剂
公开(公告)号：US07241730B2
公开(公告)日：2007-07-10
申请号：US10106804
申请日：2002-03-25
申请人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama
发明人： Jeffrey A. Hubbell , Jason C. Schense , Shelly E. Sakiyama
IPC分类号： A01N37/18
CPC分类号： C07K14/75 , A61L26/0042 , C12N5/0068 , C12N5/0619 , C12N2501/91 , C12N2533/56
摘要： Heparin-binding regions of several proteins, such as neural cell adhesion molecule, fibronectin, laminin, midkine, and anti-thrombin III have been shown to promote neurite extension on two-dimensional surfaces. The effect of heparin-binding peptides on neurite extension through three-dimensional matrices was investigated by culturing embryonic chick dorsal root ganglia (DRG) within fibrin gels containing chemically attached heparin-binding peptide (HBP). The length of neurites within fibrin gels containing cross-linked HBP was increased by more than 70% over extension through fibrin gels containing no peptide. The HBP sequence of antithrombin III was incorporated into the fibrin gel as the C-terminal domain of a bidomian, chimeric peptide; the N-terminal second domain of this peptide contained the ∀2-plasmin inhibitor substrate for Factor XIIIa. Factor XIIIa, a transglutaminase, was used to chemically attach the HBP-containing chimeric peptide to the fibrin gels during polymerization. The amount of HBP cross-linked into the fibrin gels was determined, after degradation by plasmin using gel permeation chromatography, to be approximately 8 moles of peptide per mole fibrinogen. A peptide (HBP), where the cross-linking glutamine was replaced with glycine, showed no increase in extension in comparison with fibrin gels. The additional of heparin to the gel percursors resulted in no increase in neurite extension in comparison with fibrin gels. HBPs promote neurite extension by binding to cell surface proteoglycans on the DRG.
摘要翻译：几种蛋白质的肝素结合区域，例如神经细胞粘附分子，纤连蛋白，层粘连蛋白，中期因子和抗凝血酶III已被证明可促进二维表面的神经突延伸。通过在包含化学连接的肝素结合肽（HBP）的纤维蛋白凝胶内培养胚胎小鸡背根神经节（DRG），研究肝素结合肽对通过三维基质的神经突延伸的作用。含有交联HBP的纤维蛋白凝胶中的神经突的长度比通过不含肽的纤维蛋白凝胶延长超过70％。抗凝血酶III的HBP序列被掺入纤维蛋白凝胶中，作为bid族嵌合肽的C-末端结构域; 该肽的N末端第二结构域含有因子XIIIa的∀2-纤溶酶抑制剂底物。在聚合期间，使用因子XIIIa，转谷氨酰胺酶将含HBP的嵌合肽化学连接到纤维蛋白凝胶上。在使用凝胶渗透色谱法的纤溶酶降解之后，测定交联到纤维蛋白凝胶中的HBP的量为每摩尔纤维蛋白原约8摩尔肽。交联谷氨酰胺被甘氨酸取代的肽（HBP）与纤维蛋白凝胶相比显示延长不增加。与纤维蛋白凝胶相比，附加的凝胶过程中的肝素导致神经突延伸不增加。 HBP通过与DRG上的细胞表面蛋白聚糖结合来促进神经突延伸。

8. 发明授权

US08323696B2 Nanoparticles for immunotherapy 有权
标题翻译：用于免疫治疗的纳米颗粒
公开(公告)号：US08323696B2
公开(公告)日：2012-12-04
申请号：US12231310
申请日：2008-08-29
申请人： Jeffrey A. Hubbell , Conlin P. O'Neil , Sai T. Reddy , Melody A. Swartz , Diana Velluto , André van der Vlies , Eleonora Simeoni
发明人： Jeffrey A. Hubbell , Conlin P. O'Neil , Sai T. Reddy , Melody A. Swartz , Diana Velluto , André van der Vlies , Eleonora Simeoni
IPC分类号： A61K9/14
CPC分类号： A61K9/5146 , A61K9/0034 , A61K9/006 , A61K38/19 , A61K39/0011 , A61K47/6907 , A61K47/6935 , A61K2039/6093 , B82Y5/00
摘要： Nanoparticles that activate complement in the absence of biological molecules are described. The nanoparticles are shown to specifically target antigen presenting cells in specifically in lymph nodes, without the use of a biological molecule for targeting. These particles are useful vehicles for delivering immunotherapeutics. Surface chemistries and chemical formulations for the nanoparticles are described.
摘要翻译：描述了在不存在生物分子的情况下激活补体的纳米颗粒。显示了纳米颗粒特异性靶向抗原呈递细胞，特别是在淋巴结中，而不用生物分子进行靶向。这些颗粒是用于递送免疫治疗剂的有用载体。描述了纳米颗粒的表面化学和化学配方。

9. 发明申请

US20110223217A1 BLOCK COPOLYMERS AND USES THEREOF 有权
标题翻译：嵌段共聚物及其用途
公开(公告)号：US20110223217A1
公开(公告)日：2011-09-15
申请号：US13130892
申请日：2009-11-24
申请人： James Brandon Dixon , Jeffrey A. Hubbell , Conlin P. O'Neil , Melody Swartz , Diana Velluto
发明人： James Brandon Dixon , Jeffrey A. Hubbell , Conlin P. O'Neil , Melody Swartz , Diana Velluto
IPC分类号： A61K47/34 , C08G75/14 , A61K31/56 , A61K31/337 , A61K38/13 , A61K31/436 , A61K31/7048 , A61K31/704 , A61K38/00 , A61K31/7052 , A61K39/395 , A61K9/00 , C12N15/00
CPC分类号： A61K48/0041 , A61K9/1075 , A61K9/1273 , A61K9/5146 , A61K31/337 , A61K31/573 , A61K31/713 , A61K47/10 , A61K47/22 , A61K47/34 , C07K16/00 , C08G65/329 , C08G65/3344 , C08G75/08 , C08G83/008 , C08L71/02 , C08L81/02 , C08L2203/02 , C08L2205/05 , C12N15/113 , C12N15/115 , C12N2310/11 , C12N2310/14 , C12N2310/141 , C12N2310/16 , C12N2320/32 , Y02A50/387 , Y10S977/773 , Y10S977/906 , Y10S977/916 , C08L81/00
摘要： An encoding/decoding apparatus and method using a low-density parity-check code (LDPC code) is disclosed. Basic column group information, serving as a set of information regarding positions of rows with weight 1, is extracted from a reference column in each column group of a predetermined parity-check matrix. Column group information transforms the positions of rows with weight 1 into positions whose lengths are within a required parity length. A parity-check matrix is generated according to the generated column group information. Data is encoded or decoded based on the generated parity-check matrix.
摘要翻译：公开了一种使用低密度奇偶校验码（LDPC码）的编码/解码装置和方法。从预定奇偶校验矩阵的每列组中的参考列中提取用作关于具有权重1的行的位置的信息集合的基本列组信息。列组信息将具有权重1的行的位置变换为长度在所需奇偶校验长度内的位置。根据生成的列组信息生成奇偶校验矩阵。基于生成的奇偶校验矩阵对数据进行编码或解码。

10. 发明申请

US20100080850A1 POLYPEPTIDE LIGANDS FOR TARGETING CARTILAGE AND METHODS OF USE THEREOF 审中-公开
标题翻译：用于靶向治疗的多肽配体及其使用方法
公开(公告)号：US20100080850A1
公开(公告)日：2010-04-01
申请号：US12563201
申请日：2009-09-21
申请人： Jeffrey A. Hubbell , Dominique A. Rothenfluh
发明人： Jeffrey A. Hubbell , Dominique A. Rothenfluh
IPC分类号： A61K9/14 , C07K7/06 , C07K7/08 , C07K14/00 , C07H21/00 , C12N15/74 , A61K38/08 , A61K38/10 , A61K38/16 , A61P19/02
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。

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