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公开(公告)号：US20090280182A1
公开(公告)日：2009-11-12
申请号：US12387318
申请日：2009-04-29
申请人： Stayce Beck , David Myung , Curtis W. Frank , Jennifer R. Cochran , Michael T. Longaker , George P. Yang , Daphne P. Ly , Shira G. Mandel
发明人： Stayce Beck , David Myung , Curtis W. Frank , Jennifer R. Cochran , Michael T. Longaker , George P. Yang , Daphne P. Ly , Shira G. Mandel
CPC分类号： A61L15/60 , A61L15/225 , C08L71/02
摘要： Interpenetrating network hydrogels are described that may be incorporated into wound dressings and/or in implants. The properties of the interpenetrating network hydrogel may be tuned to control an amount of moisture in a wound environment. The devices, methods, and kits described herein may be adapted to treat a variety of wound types at a variety of healing stages over a range of time scales. Some hydrogels may be configured to deliver one or more vulnerary agents to a wound. The interpenetrating network hydrogels may also be adapted to control a rate and/or amount of moisture uptake so that the hydrogels may be used as expandable implants to expand tissue.
摘要翻译： 描述了可以并入伤口敷料和/或植入物中的互穿网络水凝胶。 可以调节互穿网络水凝胶的性质以控制伤口环境中的水分量。 本文描述的装置，方法和试剂盒可适用于在多个时间范围内的各种愈合阶段处理各种伤口类型。 一些水凝胶可以被配置成将一种或多种弱毒剂递送到伤口。 互穿网络水凝胶还可以适于控制吸湿的速率和/或量，使得水凝胶可以用作可膨胀植入物以膨胀组织。
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公开(公告)号：US20090117166A1
公开(公告)日：2009-05-07
申请号：US12228884
申请日：2008-08-15
申请人： David Myung , Stayce Beck , Jaan Noolandi , Christopher N. Ta , Jennifer R. Cochran , Curtis W. Frank
发明人： David Myung , Stayce Beck , Jaan Noolandi , Christopher N. Ta , Jennifer R. Cochran , Curtis W. Frank
摘要： A bio-mimetic or bio-implantable material based on a sequential process of coupling biomolecule layers to a polymer layer is provided. In general, the material could be based on two or more biomolecule layers starting with one of the layers covalently linked to the polymer layer via cross-linkers and the other layers sequentially and covalently linked using cross-linkers to the previously added layer. The polymer layer could be a hydrogel or an interpenetrating polymer network hydrogel. The first layer of biomolecules could be a collagen type, fibronectin, laminin, extracellular matrix protein, or any combinations thereof. The second layer of biomolecules typically is a growth factor, protein or stimulant. The cross-linkers are either water soluble or insoluble bifunctional cross-linkers or azide-active-ester crosslinkers. The material and process as taught in this invention are useful in the field of tissue engineering and wound healing.
摘要翻译： 提供了基于将生物分子层耦合到聚合物层的顺序方法的生物模拟或生物可植入材料。 通常，该材料可以基于两个或更多个生物分子层，其起始于通过交联剂共价连接到聚合物层的层之一，并且其它层使用交联剂顺序并共价连接到先前添加的层。 聚合物层可以是水凝胶或互穿聚合物网络水凝胶。 第一层生物分子可以是胶原型，纤连蛋白，层粘连蛋白，细胞外基质蛋白或其任何组合。 第二层生物分子通常是生长因子，蛋白质或兴奋剂。 交联剂是水溶性或不溶性双功能交联剂或叠氮化物 - 活性酯交联剂。 本发明教导的材料和方法可用于组织工程和伤口愈合领域。
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公开(公告)号：US20100113708A1
公开(公告)日：2010-05-06
申请号：US12590288
申请日：2009-11-05
CPC分类号： C08J3/246 , C08G85/004 , C08J2300/14
摘要： Surface modification methods for an interpenetrating polymer network (IPN) hydrogel to provide a basis for cell or tissue attachment are provided. The method involves the activation of functional groups on the surface of the IPN hydrogel. The activated functional groups are then reacted with amine-containing molecules or hydroxyl-containing molecules. The methods (i) can be performed in an aqueous environment and do not require the use of any organic solvent, (ii) do not require UV treatment, thereby avoiding denaturation of the IPN hydrogel or proteins, and/or (iii) can be performed as a one pot reaction.
摘要翻译： 提供了互穿聚合物网络（IPN）水凝胶的表面改性方法，以提供细胞或组织附着的基础。 该方法涉及IPN水凝胶表面上的官能团的活化。 然后将活化的官能团与含胺分子或含羟基的分子反应。 方法（i）可以在水性环境中进行，不需要使用任何有机溶剂，（ii）不需要UV处理，从而避免IPN水凝胶或蛋白质变性，和/或（iii）可以 作为一锅反应进行。
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4.发明申请HEPATOCYTE GROWTH FACTOR FRAGMENTS THAT FUNCTION AS POTENT MET RECEPTOR AGONISTS AND ANTAGONISTS 有权HEPATOCYTE生长因子片段功能作为MET受体激动剂和拮抗剂公开(公告)号：US20130171068A1
公开(公告)日：2013-07-04
申请号：US13636053
申请日：2011-03-21
IPC分类号： C07K14/475
CPC分类号： C07K14/4753 , A61K38/00
摘要： The NK1 fragment of hepatocyte growth factor (HGF) binds to and activates the Met receptor, a transmembrane receptor tyrosine kinase that plays a critical role in embryonic development and organ formation. The instant application discloses NK1 variant polypeptides which act as agonists or antagonists of HGF. Further disclosed are covalently linked NK1 variant polypeptides. Many of the disclosed variant polypeptides possess improved stability characteristics.
摘要翻译： 肝细胞生长因子（HGF）的NK1片段结合并激活Met受体，一种跨膜受体酪氨酸激酶，在胚胎发育和器官形成中起关键作用。 本申请公开了作为HGF的激动剂或拮抗剂的NK1变体多肽。 进一步公开的是共价连接的NK1变体多肽。 所公开的变体多肽中的许多具有改善的稳定性特征。
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公开(公告)号：US09074192B2
公开(公告)日：2015-07-07
申请号：US13595936
申请日：2012-08-27
申请人： Amato J. Giaccia , Erinn Bruno Rankin , Jennifer R. Cochran , Douglas Jones , Mihalis Kariolis , Katherine Fuh , Yu Miao
发明人： Amato J. Giaccia , Erinn Bruno Rankin , Jennifer R. Cochran , Douglas Jones , Mihalis Kariolis , Katherine Fuh , Yu Miao
CPC分类号： C12N9/12 , A61K38/45 , A61K45/06 , C07K14/71 , C07K16/22 , C07K2319/30 , C12Q1/485 , C12Y207/10001 , G01N2333/912 , G01N2800/52 , G01N2800/7028
摘要： Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL and its ligand GAS6.
摘要翻译： 提供了通过施用治疗剂量的抑制AXL蛋白活性的药物组合物来减轻哺乳动物癌症的组合物和方法，例如通过竞争性或非竞争性地抑制AXL与其配体GAS6之间的结合相互作用。
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6.发明授权Cystine knot peptides binding to alpha IIb beta 3 integrins and methods of use 有权结合αIIbβ3整联蛋白的胱氨酸结结合肽和使用方法公开(公告)号：US08778888B2
公开(公告)日：2014-07-15
申请号：US12938216
申请日：2010-11-02
摘要： Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against αIIbβ3 integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to αIIbβ3 integrin or to both αIIbβ3 and αVβ3 integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for αIIbβ3 integrin.
摘要翻译： 公开了具有胱氨酸结结构基序的肽，并且包含在血小板上发现的针对αIIb和bgr3整联蛋白的特异性工程的序列，以及在抗血栓形成治疗中使用该序列的方法。 本发明的肽利用衍生自修饰的agouti相关蛋白或恶性毒素的胱氨酸结支架。使用替代文库筛选策略来分离选择性结合αIIb和bgr3整合素或αIIb和bgr 3和αV和bgr 3整合素的肽的变体。 在鉴定的肽中鉴定出独特的共有序列，表明替代的分子识别事件决定了不同的整联蛋白结合特异性。 此外，工程化肽可防止基于血浆的测定中的人血小板聚集，并显示出对αIIb和bgr3整合素的高结合亲和力。
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公开(公告)号：US20130108644A1
公开(公告)日：2013-05-02
申请号：US13595936
申请日：2012-08-27
申请人： Amato J. Giaccia , Erinn Bruno Rankin , Jennifer R. Cochran , Douglas Jones , Mihalis Kariolis , Katherine Fuh , Yu Miao
发明人： Amato J. Giaccia , Erinn Bruno Rankin , Jennifer R. Cochran , Douglas Jones , Mihalis Kariolis , Katherine Fuh , Yu Miao
CPC分类号： C12N9/12 , A61K38/45 , A61K45/06 , C07K14/71 , C07K16/22 , C07K2319/30 , C12Q1/485 , C12Y207/10001 , G01N2333/912 , G01N2800/52 , G01N2800/7028
摘要： Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL and its ligand GAS6.
摘要翻译： 提供了通过施用治疗剂量的抑制AXL蛋白活性的药物组合物来减轻哺乳动物癌症的组合物和方法，例如通过竞争性或非竞争性地抑制AXL与其配体GAS6之间的结合相互作用。
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8.发明申请CYSTINE KNOT PEPTIDES BINDING TO ALPHA IIb BETA 3 INTEGRINS AND METHODS OF USE 有权CYSTINE KNOT PEPDDES与ALPHA结合IIb BETA 3 INTEGRINS AND METHODS OF USE公开(公告)号：US20110136740A1
公开(公告)日：2011-06-09
申请号：US12938216
申请日：2010-11-02
摘要： Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against αIIbβ3 integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to αIIbβ3 integrin or to both αIIbβ3 and αVβ3 integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for αIIbβ3 integrin.
摘要翻译： 公开了具有胱氨酸结结构基序的肽，并且包含在血小板上发现的针对αIIb和bgr3整联蛋白的特异性工程的序列，以及在抗血栓形成治疗中使用该序列的方法。 本发明的肽利用衍生自修饰的agouti相关蛋白或恶性毒素的胱氨酸结支架。使用替代文库筛选策略来分离选择性结合αIIb和bgr3整合素或αIIb和bgr 3和αV和bgr 3整合素的肽的变体。 在鉴定的肽中鉴定出独特的共有序列，表明替代的分子识别事件决定了不同的整联蛋白结合特异性。 此外，工程化肽可防止基于血浆的测定中的人血小板聚集，并显示出对αIIb和bgr3整合素的高结合亲和力。
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9.发明授权Hepatocyte growth factor fragments that function as potent met receptor agonists and antagonists 有权作为有效的受体激动剂和拮抗剂起作用的肝细胞生长因子片段公开(公告)号：US09556248B2
公开(公告)日：2017-01-31
申请号：US13636053
申请日：2011-03-21
IPC分类号： A61K38/18 , C07K14/475 , A61K38/00
CPC分类号： C07K14/4753 , A61K38/00
摘要： The NK1 fragment of hepatocyte growth factor (HGF) binds to and activates the Met receptor, a transmembrane receptor tyrosine kinase that plays a critical role in embryonic development and organ formation. The instant application discloses NK1 variant polypeptides which act as agonists or antagonists of HGF. Further disclosed are covalently linked NK1 variant polypeptides. Many of the disclosed variant polypeptides possess improved stability characteristics.
摘要翻译： 肝细胞生长因子（HGF）的NK1片段结合并激活Met受体，一种跨膜受体酪氨酸激酶，在胚胎发育和器官形成中起关键作用。 本申请公开了作为HGF的激动剂或拮抗剂的NK1变体多肽。 进一步公开的是共价连接的NK1变体多肽。 所公开的变体多肽中的许多具有改善的稳定性特征。
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10.发明申请公开(公告)号：US20140073518A1
公开(公告)日：2014-03-13
申请号：US13883216
申请日：2011-11-07
IPC分类号： C07K14/705 , C07K14/47 , C07K14/475 , C07K14/81
CPC分类号： C07K14/705 , C07K14/43518 , C07K14/47 , C07K14/4702 , C07K14/475 , C07K14/71 , C07K14/81 , C07K14/8121 , C07K2319/00
摘要： The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform for increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.
摘要翻译： 本公开提出了通过域添加和进化来设计现有蛋白质 - 蛋白质相互作用的一般方法。 该公开内容教导了包括knottin肽的新型融合蛋白的产生，其中一部分knottin肽被用于结合特定靶标的序列替代。 这样的融合蛋白也可以是双特异性或多特异性的，因为它们可以结合和/或抑制两种或多种受体或受体配体。 Knottins可以与现有配体（或受体）融合，作为增加配体 - 受体相互作用或产生多特异性蛋白质的亲和力的通用平台。 此外，融合蛋白可以包含与另一种蛋白质融合的knottin肽，其中另一种蛋白促进knottin的正确表达和折叠。
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