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21. 发明授权

US06331422B1 Enzyme-mediated modification of fibrin for tissue engineering 失效
标题翻译：酶介导的组织工程纤维蛋白修饰
公开(公告)号：US06331422B1
公开(公告)日：2001-12-18
申请号：US09057052
申请日：1998-04-08
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。

22. 发明授权

US6149931A Methods and pharmaceutical compositions for the closure of retinal breaks 有权
公开(公告)号：US6149931A
公开(公告)日：2000-11-21
申请号：US181041
申请日：1998-10-27
申请人： Daniel M. Schwartz , Jeffrey A. Hubbell , Alexander R. Irvine
发明人： Daniel M. Schwartz , Jeffrey A. Hubbell , Alexander R. Irvine
IPC分类号： A61K31/74 , A61K31/77 , A61K41/00 , A61K45/06 , A61L24/04 , A61L24/06 , A61L24/10 , A61P27/02 , C08F299/02 , A61F2/14 , A61K47/30 , A61K13/02
CPC分类号： A61L24/10 , A61K31/74 , A61K31/77 , A61K41/0061 , A61K45/06 , A61L24/046 , A61L24/06 , A61L2430/16
摘要： Described are compositions, methods, and articles of manufacture for the closure of retinal breaks with a non-toxic polymer. Transformation to a gel-like coat is achieved by photochemical reactivity, chemical reactivity, and by physicochemical response.

23. 发明授权

US6129761A Injectable hydrogel compositions 失效
标题翻译：可注射的水凝胶组合物
公开(公告)号：US6129761A
公开(公告)日：2000-10-10
申请号：US478690
申请日：1995-06-07
申请人： Jeffrey A. Hubbell
发明人： Jeffrey A. Hubbell
IPC分类号： C12N5/06 , A61L27/00 , A61L27/38 , C12N5/00 , C12N5/08 , A61F2/02
CPC分类号： A61L27/3804 , A61L27/3839 , C12N5/0068 , C12N2533/70
摘要： Slowly polymerizing hydrogels are provided which are useful as a means of delivering large numbers of isolated cells via injection. The gels promote engraftment and provide three dimensional templates for new cell growth. The resulting tissue is similar in composition and histology to naturally occurring tissue. This method can be used for a variety of reconstructive procedures, including custom molding of cell implants to reconstruct three dimensional tissue defects, as well as implantation of tissues generally. The polymers permit construction of muscle and cartilage tissues which are useful to repair defects such as reflux and incontinence.
摘要翻译：提供缓慢聚合的水凝胶，其可用作通过注射递送大量分离的细胞的手段。凝胶促进植入，并为新细胞生长提供三维模板。所得到的组织在组成和组织学上与天然存在的组织相似。该方法可用于各种重建程序，包括定型成型细胞植入物以重建三维组织缺陷，以及一般植入组织。聚合物允许构建肌肉和软骨组织，其可用于修复诸如回流和失禁的缺陷。

24. 发明授权

US5844016A Redox and photoinitiator priming for improved adherence of gels to substrates 失效
标题翻译：氧化还原和光引发剂引发，以提高凝胶对底物的粘附性
公开(公告)号：US5844016A
公开(公告)日：1998-12-01
申请号：US478104
申请日：1995-06-07
申请人： Amarpreet S. Sawhney , David A. Melanson , Chandrashekar P. Pathak , Jeffrey A. Hubbell , Luis Z. Avila , Mark T. Kieras , Stephen D. Goodrich , Shikha P. Barman , Arthur J. Coury , Ronald S. Rudowsky , Douglas J. K. Weaver
发明人： Amarpreet S. Sawhney , David A. Melanson , Chandrashekar P. Pathak , Jeffrey A. Hubbell , Luis Z. Avila , Mark T. Kieras , Stephen D. Goodrich , Shikha P. Barman , Arthur J. Coury , Ronald S. Rudowsky , Douglas J. K. Weaver
IPC分类号： A61B17/00 , A61B17/08 , A61L24/00 , A61L24/04 , A61L24/06 , A61L29/00 , A61L31/00 , C08F2/48 , C08F2/50 , C08F4/00 , C08F4/40 , C08F265/04 , C08F271/00 , C08F283/00 , C08F289/00 , C08F290/06 , C08F290/14 , C08F291/00 , C09D4/00 , C09D7/00 , C09D171/00 , C09J151/00 , C08F4/42
CPC分类号： A61L24/0031 , A61L24/0015 , A61L24/0042 , A61L24/046 , A61L24/06 , C08F2/48 , C08F265/04 , C08F271/00 , C08F283/00 , C08F289/00 , C08F290/06 , C08F290/062 , C08F290/14 , C08F291/00 , C09D4/00 , C09J151/00 , A61B17/00491 , A61B17/085 , A61B2017/00495 , A61L2300/00 , Y10S602/90 , Y10S602/904
摘要： An improved barrier or drug delivery system which is highly adherent to the surface to which it is applied is disclosed, along with methods for making the barrier. The barrier can be prepared by staining tissue with a photoinitiator, applying a solution containing a polymerizable barrier material solution and a photoinitiator to the tissue, and polymerizing the polymer solution on exposure to light. The resulting polymer adheres strongly to the tissue surface, and also forms a gel in the rest of the applied volume. The polymerizable barrier materials are highly useful for sealing tissue surfaces and junctions against leaks of fluids. The method can be used to adhere preformed barriers to tissue or other surfaces, or to adhere tissue surfaces to each other. Tissue surfaces can be adhered to each other to repair wounds. In addition to photochemical initiators, non-photochemical initiators and combinations of chemical initiators and photochemical initiators can be used.
摘要翻译：公开了与施加的表面高度附着的改进的屏障或药物递送系统，以及用于制造屏障的方法。屏障可以通过用光引发剂染色组织，将含有可聚合阻挡材料溶液和光引发剂的溶液施加到组织上，以及在暴露于光下聚合聚合物溶液来制备。所得聚合物强烈地粘附到组织表面，并且在其余施用体积中形成凝胶。可聚合的阻挡材料对于密封组织表面和防止流体泄漏的接头非常有用。该方法可用于将预先形成的障碍物粘附到组织或其它表面，或将组织表面彼此粘附。组织表面可以彼此粘附以修复伤口。除了光化学引发剂之外，还可以使用非光化学引发剂以及化学引发剂和光化学引发剂的组合。

25. 发明授权

US5834274A Gels for encapsulation of biological materials 失效
公开(公告)号：US5834274A
公开(公告)日：1998-11-10
申请号：US467693
申请日：1995-06-06
申请人： Jeffrey A. Hubbell , Chandrashekhar P. Pathak , Amarpreet S. Sawhney , Neil P. Desai , Jennifer L. Hill , Syed F. A. Hossainy
发明人： Jeffrey A. Hubbell , Chandrashekhar P. Pathak , Amarpreet S. Sawhney , Neil P. Desai , Jennifer L. Hill , Syed F. A. Hossainy
IPC分类号： A61K9/16 , A61K9/50 , A61K35/12 , A61K38/42 , A61K38/44 , A61L24/00 , A61L24/04 , A61L26/00 , A61L27/34 , A61L27/38 , A61L27/52 , A61L29/08 , A61L31/10 , A61L31/14 , C08B37/08 , C08F290/00 , C08F290/02 , C08F290/06 , C08F290/08 , C08F290/10 , C08F291/00 , C09D153/00 , C12N5/00 , C12N5/071 , C12N5/077 , C12N11/04 , C12N11/02 , C08J7/16 , A61K47/32
CPC分类号： C12N11/04 , A61K38/42 , A61K38/44 , A61K47/48315 , A61K47/48784 , A61K47/48876 , A61K9/1635 , A61K9/1647 , A61K9/5026 , A61K9/5031 , A61K9/5073 , A61L24/0031 , A61L24/0042 , A61L24/046 , A61L26/0019 , A61L27/34 , A61L27/3683 , A61L27/38 , A61L27/52 , A61L29/085 , A61L31/10 , A61L31/145 , A61L31/148 , B82Y5/00 , C08B37/003 , C08B37/0072 , C08B37/0084 , C08F290/00 , C08F290/02 , C08F290/06 , C08F290/062 , C08F290/08 , C08F290/10 , C08F291/00 , C09D153/00 , C12N5/0012 , C12N5/0677 , A61K2035/128 , C12N2533/30 , C12N2533/32 , C12N2533/40 , C12N2533/74 , Y10S514/801 , Y10S530/812 , Y10S530/813 , Y10S530/815 , Y10S530/817 , Y10T428/2987 , Y10T428/2989
摘要： Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.

26. 发明授权

US5612050A Apparatus and method for local application of polymeric material to tissue 失效
标题翻译：将聚合物材料局部应用于组织的装置和方法
公开(公告)号：US5612050A
公开(公告)日：1997-03-18
申请号：US476124
申请日：1995-06-07
申请人： Stephen C. Rowe , Jeffrey A. Hubbell , Stephen J. Herman , Vae Sun , Michael F. Lang , George E. Selecman , Frederick F. Ahari
发明人： Stephen C. Rowe , Jeffrey A. Hubbell , Stephen J. Herman , Vae Sun , Michael F. Lang , George E. Selecman , Frederick F. Ahari
IPC分类号： A61B17/04 , A61B1/00 , A61B17/00 , A61C13/15 , A61F2/02 , A61M37/00 , B05C17/01 , A61K31/74 , A61M1/30
CPC分类号： B05C17/01 , A61B1/00165 , A61C19/004 , A61M37/00 , A61B17/00491
摘要： An apparatus is provided for applying to a surface of mammalian tissue including soft, living tissue an initially fluent material and then activating the material by exposure to an energy source. The material may be a liquid capable of polymerization to a non-fluent state by exposure to actinic light. The device, and methods that may be practiced in association with the device, enable a wide range of medical conditions to be treated including, for example, the application of a barrier to, soft tissue to prevent post-surgical adhesions.
摘要翻译：提供了一种装置，用于向哺乳动物组织的表面施加包括软的活体组织的初始流畅的材料，然后通过暴露于能量源来激活材料。该材料可以是能够通过暴露于光化光聚合成非流动状态的液体。可以与装置相关联地实施的装置和方法使得能够治疗的宽范围的医疗条件包括例如对软组织的屏障的应用以防止手术后粘连。

27. 发明授权

US5330911A Surfaces having desirable cell adhesive effects 失效
标题翻译：表面具有理想的细胞粘合效果
公开(公告)号：US5330911A
公开(公告)日：1994-07-19
申请号：US527198
申请日：1990-05-21
申请人： Jeffrey A. Hubbell , Stephen P. Massia , Neil P. Desai
发明人： Jeffrey A. Hubbell , Stephen P. Massia , Neil P. Desai
IPC分类号： A61L27/00 , A61L17/14 , A61L27/22 , A61L27/34 , A61L29/04 , A61L29/08 , A61L31/04 , A61L31/10 , C07K17/08 , C07K17/14 , C12M3/00 , C12N5/00 , C12N5/06 , C12N11/08 , C07K5/10 , C07K7/06
CPC分类号： C12N5/0068 , A61L17/145 , A61L27/227 , A61L27/34 , A61L29/048 , A61L29/085 , A61L31/047 , A61L31/10 , C07K17/08 , C12N2533/50
摘要： An absorbed protein-independent cell-adhesive surface is disclosed. The treated surface comprises a chemically derivatized material to which small peptides, having less than 12 amino acid residues and including YIGSR, RGD or REDV amino acid sequence are covalently linked to. The peptides of the present invention include a terminal glycine amino acid. Tresyl chloride activation of surface hydroxyl moieties provides the active surface sites by which a terminal glycine arm of a selected peptide attaches to form covalent bonds between the substrate and peptide. Peptides high with cell adhesive properties are bound in high efficiency.By way of example, surfaces which may be used in conjunction with the present invention include polymer, metal, and ceramic surfaces. The most preferred polymer surfaces include PHEMA and PET polymer surfaces, with the most preferred glass surfaces being glycophase glass.The present methods also include a pretreatment method which provides hydroxyl moieties to surfaces devoid of readily available hydroxyl moieties. The pretreatment, by way of example, comprises immersion of the surface in a mixture of formaldehyde and acetic acid.Methods of preparing the treated surfaces are also included in the present invention.Also included are surface-treated biomedical implant devices and cell culturing devices. The treated surface promotes an enhanced rate and an enhanced amount of cell adhesion to the surface, independent of media serum concentrations or other absorbed proteins. The treated surfaces of the present invention are thermally stable, reusable, peptide efficient (attached to surface only) and resistant to cell proteolysis.The invention further concerns polymeric substrates with a surface having physically interpenetrating water-soluble polymer chains, and methods for production thereof.
摘要翻译：公开了一种吸收的与蛋白质无关的细胞粘合剂表面。经处理的表面包括化学衍生的材料，具有小于12个氨基酸残基并且包括YIGSR，RGD或REDV氨基酸序列的小肽共价连接到该材料上。本发明的肽包括末端甘氨酸氨基酸。表面羟基部分的甲苯氯化物活化提供活性表面位点，通过该活性表面位点所选肽的末端甘氨酸臂附着形成底物和肽之间的共价键。具有细胞粘附性能的高肽结合效率高。作为示例，可以与本发明结合使用的表面包括聚合物，金属和陶瓷表面。最优选的聚合物表面包括PHEMA和PET聚合物表面，最优选的玻璃表面是糖相玻璃。本方法还包括将羟基部分提供到没有容易得到的羟基部分的表面的预处理方法。例如，预处理包括将表面浸入甲醛和乙酸的混合物中。制备处理过的表面的方法也包括在本发明中。还包括表面处理的生物医学植入装置和细胞培养装置。经处理的表面促进了与培养基血清浓度或其他吸收的蛋白质无关的增强的速率和增加的表面附着量。本发明的处理表面是热稳定的，可重复使用的，肽效率的（仅附着于表面）并且抗细胞蛋白水解。本发明还涉及具有物理上互穿的水溶性聚合物链的表面的聚合物基材及其生产方法。

28. 发明授权

US5278063A Chemical modification of promote animal cell adhesion on surfaces 失效
标题翻译：化学改性以促进表面上的动物细胞粘附
公开(公告)号：US5278063A
公开(公告)日：1994-01-11
申请号：US414144
申请日：1989-09-28
申请人： Jeffrey A. Hubbell , Stephen P. Massia
发明人： Jeffrey A. Hubbell , Stephen P. Massia
IPC分类号： A61L17/14 , A61L27/22 , A61L27/34 , A61L29/04 , A61L29/08 , A61L31/04 , A61L31/10 , C07K17/08 , C12N5/00 , C07K5/10 , C07K7/06
CPC分类号： C12N5/0068 , A61L17/145 , A61L27/227 , A61L27/34 , A61L29/048 , A61L29/085 , A61L31/047 , A61L31/10 , C07K17/08 , C12N2533/50
摘要： A cell culture substrate which promotes cell adhesion and the formation of focal contacts is disclosed. Polymer, ceramic and glass surfaces may be used. The surfaces are derivatized with peptides having less than 12 amino acid residues and containing one of the following sequences of amino acids: GRGD, GYIGSR, GREDV. The peptides are covalently attached to the surface throuThe U.S. Government may have rights in the present invention as relevant developmental work was supported by National Science Foundation Grant CBT-881020268, and National Institutes of Health Grant HL-39714.
摘要翻译：公开了促进细胞粘附和焦点接触形成的细胞培养基质。可以使用聚合物，陶瓷和玻璃表面。表面用具有少于12个氨基酸残基的肽衍生并含有以下氨基酸序列之一：GRGD，GYIGSR，GREDV。肽通过N-末端甘氨酸残基的末端氨基共价连接在表面上，并且以每平方厘米表面积约50皮摩尔或更少的浓度有效。公开了制备表面的方法。

29. 发明授权

US09518087B2 Erythrocyte-binding therapeutics 有权
标题翻译：红细胞结合治疗
公开(公告)号：US09518087B2
公开(公告)日：2016-12-13
申请号：US13206034
申请日：2011-08-09
申请人： Jeffrey A. Hubbell , Stéphane Kontos , Karen Y. Dane
发明人： Jeffrey A. Hubbell , Stéphane Kontos , Karen Y. Dane
IPC分类号： A61K39/00 , A61K35/18 , C07K7/08 , B82Y5/00 , C07K16/18 , C07K16/28 , C07K16/30 , C07K14/47 , A61K38/00
CPC分类号： C07K16/28 , A61K38/00 , A61K39/0008 , A61K39/001 , A61K47/6849 , A61K2039/505 , A61K2039/6031 , A61K2039/6056 , B82Y5/00 , C07K7/08 , C07K14/4701 , C07K14/77 , C07K16/18 , C07K16/30 , C07K2317/34 , C07K2317/622 , C07K2319/00 , C07K2319/21 , C07K2319/22 , C07K2319/23 , C07K2319/33 , C07K2319/41 , C07K2319/43 , C07K2319/74 , A61K2039/57 , A61K2039/577
摘要： Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired. Fusions with targeting peptides direct the fusions to the target, for instance a tumor, where the erythrocyte-binding ligands reduce or entirely eliminate blood flow to the tumor by recruiting erythrocytes to the target.
摘要翻译：描述了特异性结合红细胞的肽。这些作为肽配体提供，其具有与红细胞特异性结合的序列，或作为提供特异性结合的抗体或其片段。肽可以制备成具有治疗剂，耐受抗原或靶向肽的分子融合物。可以通过使用融合物和在需要耐受性的物质上选择抗原来产生免疫耐受性。与靶向肽的融合将融合物引导到靶，例如肿瘤，其中红细胞结合配体通过向目标募集红细胞而减少或完全消除血液流向肿瘤的血液。

30. 发明授权

US09505867B2 Triblock copolymers for cytoplasmic delivery of gene-based drugs 有权
标题翻译：用于基因型药物细胞质传递的三嵌段共聚物
公开(公告)号：US09505867B2
公开(公告)日：2016-11-29
申请号：US11916252
申请日：2006-05-31
申请人： Tatiana Segura , Jeffrey A. Hubbell
发明人： Tatiana Segura , Jeffrey A. Hubbell
IPC分类号： A61L31/04 , C08F297/02 , C08L53/00
CPC分类号： C08F297/02 , A61L31/048 , C08L53/00 , C08L53/005
摘要： 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.
摘要翻译：本发明具有包含亲水嵌段的三嵌段共聚物; 疏水块以及能够使带负电荷的分子（例如核酸）可逆地络合的带正电荷的嵌段，其中疏水性嵌段位于亲水性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。本发明还涉及使用本发明的聚合物递送带负电荷的分子的方法和治疗疾病或病症的方法。

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