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    TG-APROTININ FUSION PROTEINS AND MATRICES THEREOF
    1.
    发明申请
    TG-APROTININ FUSION PROTEINS AND MATRICES THEREOF 审中-公开
    TG-APROTININ融合蛋白及其基质

    公开(公告)号：WO2011025957A2

    公开(公告)日：2011-03-03

    申请号：PCT/US2010/046991

    申请日：2010-08-27

    Applicant: ECOLE POLYTECHNIQUE FEDERAL DE LAUSANNE ,  HUBBELL, Jeffrey, A. ,  FREY, Peter ,  LORENTZ, Kristen

    Inventor： HUBBELL, Jeffrey, A. ,  FREY, Peter ,  LORENTZ, Kristen

    IPC: A61L24/10

    CPC classification number: A61L24/106 ,  A61L24/108 ,  A61L31/046 ,  A61L31/047

    Abstract: Fusion proteins containing a first domain and a second domain, where the first domain contains a crosslinkable substrate domain and the second domain contains a fibrinolysis inhibitor, are provided. In a preferred embodiment, the fibrinolysis inhibitor is a protease inhibitor, preferably, aprotinin. The fusion protein optionally contains a degradable site between the fist domain and the second domain. In a preferred embodiment, the crosslinkable substrate domain is a transglutaminase substrate domain, more preferably a Factor XIIIa substrate domain. Also provided is a method for decreasing the degradation of a fibrin matrix, and supplemented fibrin matrices with reduced degradation rates. The method includes covalently crossHnking a fusion protein containing a fibrinolysis inhibitor to the matrix. The supplemented fibrin matrices contain lower concentrations of a fibrinolysis inhibitor covalently bound to the matrix, compared to the concentration of unbound fibrinolysis inhibitor required to achieve the same reduction in degradation of the fibrin matrix.

    Abstract translation: 提供了含有第一结构域和第二结构域的融合蛋白，其中第一结构域含有可交联底物结构域并且第二结构域含有纤维蛋白溶解抑制剂。 在一个优选的实施方案中，纤维蛋白溶解抑制剂是蛋白酶抑制剂，优选抑肽酶。 融合蛋白任选地在第一结构域和第二结构域之间含有可降解位点。 在优选的实施方案中，可交联底物结构域是转谷氨酰胺酶底物结构域，更优选是因子XIIIa底物结构域。 还提供了一种降低纤维蛋白基质降解的方法，以及降低降解速率的补充纤维蛋白基质。 该方法包括将含有纤维蛋白溶解抑制剂的融合蛋白共价交联到基质上。 与实现纤维蛋白基质降解相同降低所需的未结合的纤维蛋白溶解抑制剂的浓度相比，补充的纤维蛋白基质含有较低浓度的与基质共价结合的纤维蛋白溶解抑制剂。

    TRIBLOCK COPOLYMERS FOR CYTOPLASMIC DELIVERY OF GENE-BASED DRUGS
    3.
    发明申请
    TRIBLOCK COPOLYMERS FOR CYTOPLASMIC DELIVERY OF GENE-BASED DRUGS 审中-公开
    三嵌段共聚物用于基因组药物的细胞内输送

    公开(公告)号：WO2007008300A2

    公开(公告)日：2007-01-18

    申请号：PCT/US2006/020760

    申请日：2006-05-31

    Applicant: ECOLE POLYTECHNIQUE FÉDÉRALE DE LAUSANNE ,  SEGURA, Tatiana ,  HUBBELL, Jeffrey, A.

    Inventor： SEGURA, Tatiana ,  HUBBELL, Jeffrey, A.

    IPC: C08G73/02

    CPC classification number: C08F297/02 ,  A61L31/048 ,  C08L53/00 ,  C08L53/005

    Abstract: The invention features a triblock copolymer including a hydrophilic block; a hydrophobic block; and a positively charged block capable of reversibly complexing a negatively charged molecule, e.g., a nucleic acid, wherein the hydrophobic block is disposed between the hydrophilic block and the positively charged block. Desirably, the triblock copolymer is capable of self-assembling into a supramolecular structure, such as a micelle or vesicle. The invention further features methods of delivering negatively charged molecules and methods of treating a disease or condition using the polymers of the invention.

    Abstract translation: 本发明的特征在于包含亲水嵌段的三嵌段共聚物; 疏水性嵌段; 和能够可逆地络合带负电荷的分子（例如核酸）的带正电的嵌段，其中疏水嵌段位于亲水嵌段和带正电的嵌段之间。 理想地，三嵌段共聚物能够自组装成超分子结构，例如胶束或囊泡。 本发明进一步特征在于递送带负电的分子的方法和使用本发明的聚合物治疗疾病或病症的方法。

    METHODS AND APPARATUS FOR PATTERNING A SURFACE
    4.
    发明申请
    METHODS AND APPARATUS FOR PATTERNING A SURFACE 审中-公开
    用于绘制表面的方法和装置

    公开(公告)号：WO03024186A3

    公开(公告)日：2003-05-22

    申请号：PCT/US0229562

    申请日：2002-09-18

    Applicant: EIDGENOESS TECH HOCHSCHULE ,  UNIV ZUERICH ,  HUBBELL JEFFREY A ,  BEARINGER JANE P ,  TEXTOR MARCUS

    Inventor： HUBBELL JEFFREY A ,  BEARINGER JANE P ,  TEXTOR MARCUS

    IPC: B41M3/00 ,  G03F7/00 ,  H01L21/302 ,  H01L21/461 ,  H01L51/00 ,  H01L51/40 ,  B44C1/22

    CPC classification number: B29C43/003 ,  B29C2043/025 ,  B41M3/006 ,  C23F1/02 ,  G01Q80/00 ,  G03F7/0002 ,  H01L51/0015 ,  H01L51/0021

    Abstract: The present invention provides methods and apparatus for locally patterning surfaces. In one such method, an oxidizable thioether is adsorbed onto a conductive surface 10. The surface is then contacted with a fluid medium M. A conducting stamp 12 is then brought into contact with the fluid medium above the thioether-coated surface. Next, a potential V 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.

    Abstract translation: 本发明提供了用于局部图案化表面的方法和装置。 在一种这样的方法中，可氧化的硫醚被吸附到导电表面10上。然后使该表面与流体介质M接触。然后使导电印模12与硫醚涂覆表面上方的流体介质接触。 接下来，在印模和表面之间施加电位V。 预期电荷将沿着最短的距离路径通过介质转移到涂覆表面，从而局部氧化硫醚，并有效地在表面上产生导电印模的负图案图像。 然后可以将剩余的吸附硫醚用作标准蚀刻或材料添加程序的掩模。

    METHODS AND APPARATUS FOR COATING SURFACES TO REDUCE PROTEIN ADSORPTION AND CELL ADHESION AND PRESENT LIGANDS
    5.
    发明申请
    METHODS AND APPARATUS FOR COATING SURFACES TO REDUCE PROTEIN ADSORPTION AND CELL ADHESION AND PRESENT LIGANDS 审中-公开
    用于涂覆表面以减少蛋白质吸附和细胞粘附和本发明配体的方法和装置

    公开(公告)号：WO03024897A2

    公开(公告)日：2003-03-27

    申请号：PCT/US0229569

    申请日：2002-09-18

    Applicant: EIDGENOESS TECH HOCHSCHULE ,  UNIV ZUERICH ,  HUBBELL JEFFREY A ,  BEARINGER JANE P ,  NAPOLI ALESSANDRO ,  TEXTOR MARCUS ,  TIRELLI NICOLA

    Inventor： HUBBELL JEFFREY A ,  BEARINGER JANE P ,  NAPOLI ALESSANDRO ,  TEXTOR MARCUS ,  TIRELLI NICOLA

    IPC: A61L27/34 ,  C07B

    CPC classification number: A61L27/34 ,  C08L81/02

    Abstract: The present invention provides methods and apparatus for coating surfaces with specially designed thioethers and amphiphilic thioethers that reduce protein adsorption and/or cell adhesion. This reduction may be achieved, for example, by controlling the spacing or length of pendant chains or hydrophilic blocks in an amphiphilic thioether. Techniques for determining spacing include adsorbing the thioether from a solution or a colloidal suspension, or controlling the degree of polymerization of the thioether. Techniques for controlling the length of the pendant chains include controlling the degree of polymerization of the pendant chains. Multiblock copolymers of poly(propylene sulfide) and poly(ethylene glycol) ("PPS-PEG") represent an exemplary family of amphiphilic thioethers. Methods for coating surfaces with amphiphilic thioethers are also provided.

    Abstract translation: 本发明提供了用特别设计的硫醚和两亲硫醚涂覆表面的方法和装置，其减少蛋白质吸附和/或细胞粘附。 该还原可以通过例如通过控制两亲性硫醚中的侧链或亲水嵌段的间隔或长度来实现。 用于确定间隔的技术包括从溶液或胶体悬浮液中吸附硫醚，或控制硫醚的聚合度。 用于控制侧链长度的技术包括控制侧链的聚合度。 聚（丙烯硫醚）和聚（乙二醇）（“PPS-PEG”）的多嵌段共聚物代表两亲性硫醚的典型族。 还提供了用两亲硫醚涂覆表面的方法。

    GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING
    7.
    发明申请
    GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING 审中-公开
    生长因子改良组织工程蛋白质矩阵

    公开(公告)号：WO0183522A2

    公开(公告)日：2001-11-08

    申请号：PCT/US0011947

    申请日：2000-05-01

    Applicant: ETH ZUERICH ,  HUBBELL JEFFREY A

    Inventor： HUBBELL JEFFREY A ,  SCHENSE JASON C ,  SAKIYAMA-ELBERT SHELLY E

    IPC: A61K31/727 ,  A61K31/737 ,  A61K38/17 ,  A61K47/48 ,  A61L27/00 ,  A61L27/20 ,  A61L27/22 ,  A61L27/54 ,  A61L33/00 ,  A61P41/00 ,  A61P43/00 ,  C07K1/04 ,  C07K14/495 ,  C07K14/52 ,  C07K14/745 ,  C07K19/00 ,  C07K14/00

    CPC classification number: A61L27/20 ,  A61K47/61 ,  A61K47/62 ,  A61L27/227 ,  A61L27/54 ,  A61L2300/236 ,  A61L2300/252 ,  A61L2300/414 ,  A61L2300/604

    Abstract: 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.

    Abstract translation: 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。

    TG-APROTININ FUSION PROTEINS AND MATRICES THEREOF
    8.
    发明申请
    TG-APROTININ FUSION PROTEINS AND MATRICES THEREOF 审中-公开
    TG-APROTININ融合蛋白及其基因

    公开(公告)号：WO2011025957A3

    公开(公告)日：2011-07-07

    申请号：PCT/US2010046991

    申请日：2010-08-27

    Applicant: ECOLE POLYTECH ,  HUBBELL JEFFREY A ,  FREY PETER ,  LORENTZ KRISTEN

    Inventor： HUBBELL JEFFREY A ,  FREY PETER ,  LORENTZ KRISTEN

    IPC: A61L24/10

    CPC classification number: A61L24/106 ,  A61L24/108 ,  A61L31/046 ,  A61L31/047

    Abstract: Fusion proteins containing a first domain and a second domain, where the first domain contains a crosslinkable substrate domain and the second domain contains a fibrinolysis inhibitor, are provided. In a preferred embodiment, the fibrinolysis inhibitor is a protease inhibitor, preferably, aprotinin. The fusion protein optionally contains a degradable site between the fist domain and the second domain. In a preferred embodiment, the crosslinkable substrate domain is a transglutaminase substrate domain, more preferably a Factor XIIIa substrate domain. Also provided is a method for decreasing the degradation of a fibrin matrix, and supplemented fibrin matrices with reduced degradation rates. The method includes covalently crossHnking a fusion protein containing a fibrinolysis inhibitor to the matrix. The supplemented fibrin matrices contain lower concentrations of a fibrinolysis inhibitor covalently bound to the matrix, compared to the concentration of unbound fibrinolysis inhibitor required to achieve the same reduction in degradation of the fibrin matrix.

    Abstract translation: 提供了含有第一结构域和第二结构域的融合蛋白，其中第一结构域含有可交联的底物结构域，第二结构域含有纤维蛋白溶解抑制剂。 在优选的实施方案中，纤维蛋白溶解抑制剂是蛋白酶抑制剂，优选抑肽酶。 融合蛋白任选地包含第一结构域和第二结构域之间的可降解位点。 在优选的实施方案中，可交联底物结构域是转谷氨酰胺酶底物结构域，更优选因子XIIIa底物结构域。 还提供了降低纤维蛋白基质降解的方法，以及降低降解速率的补充的纤维蛋白基质。 该方法包括将含有纤维蛋白溶解抑制剂的融合蛋白共价交叉到基质上。 与实现纤维蛋白基质降解相同的降低所需的未结合的纤维蛋白溶解抑制剂的浓度相比，补充的纤维蛋白基质含有较低浓度的与基质共价结合的纤维蛋白溶解抑制剂。

    MICELLES FOR DELIVERY OF NITRIC OXIDE
    9.
    发明申请
    MICELLES FOR DELIVERY OF NITRIC OXIDE 审中-公开
    用于递送一氧化氮的胶束

    公开(公告)号：WO2010002450A2

    公开(公告)日：2010-01-07

    申请号：PCT/US2009/003885

    申请日：2009-06-30

    Applicant: ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE ,  HUBBELL, Jeffrey, A. ,  JO, Yun, Suk ,  VAN DER VLIES, Andre

    Inventor： HUBBELL, Jeffrey, A. ,  JO, Yun, Suk ,  VAN DER VLIES, Andre

    IPC: A61K9/127 ,  A61K33/00 ,  A61K47/34 ,  A61P9/10

    CPC classification number: A61K31/77 ,  A61K9/1075 ,  A61K9/1273 ,  A61K31/787 ,  A61K31/80 ,  A61K47/48176 ,  A61K47/488 ,  A61K47/58 ,  A61K47/6907 ,  Y10S977/906

    Abstract: Embodiments include a vehicle for delivery of nitric oxide comprising: a collection of micelles having an internal micelle core that comprises a polymer with N-diazeniumdiolate comprising NO complexed with secondary amines of the polymer. Embodiments include a method of making a nitric oxide vehicle comprising dissolving a polymer that comprises secondary amines in an aqueous solution and combining the polymer with nitric oxide in the solution to form a N-diazeniumdiolate comprising the nitric oxide complexed with the secondary amines, with the formation of the N-diazeniumdiolate causing the polymer to be at least partially insoluble in the solution and to form a collection of micelles that have an internal core that comprises N-diazeniumdiolate.

    Abstract translation: 实施方案包括用于递送一氧化氮的媒介物，其包含：具有内部胶束核心的胶束集合体，所述内部胶束核心包含具有包含与聚合物的仲胺络合的NO的N-二醇二氮烯鎓的聚合物。 实施方案包括制备一氧化氮载体的方法，所述方法包括将包含仲胺的聚合物溶解在水溶液中并且将聚合物与一氧化氮在溶液中结合以形成包含与仲胺络合的一氧化氮的N-二醇二氮烯鎓， N-二醇二氮烯鎓的形成导致聚合物至少部分不溶于溶液中并形成具有包含N-二氮烯鎓二醇化物的内核的胶束集合。

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