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1. 发明申请

WO2022094051A2 TRUNCATED MODIFIED RECOMBINANT ADAMTS13 AND USES THEREOF 审中-公开
公开(公告)号：WO2022094051A2
公开(公告)日：2022-05-05
申请号：PCT/US2021/057013
申请日：2021-10-28
申请人： CHILDREN'S MEDICAL CENTER CORPORATION , THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
发明人： KOHANE, Daniel S. , IBLA, Juan C. , KATNENI, Upendra , KIMCHI-SARFATY, Chava
IPC分类号： C12N9/64 , C07K2319/21 , C07K2319/40 , C12N9/6489 , C12Y304/24087
摘要： Provided herein are polypeptides that are truncated modified recombinant forms of ADAMTS13, nucleic acid molecules encoding the polypeptides, drug delivery compositions and pharmaceutical compositions comprising the polypeptides, and methods of using the polypeptides and compositions (e.g., in the treatment of thrombotic thrombocytopenic purpura (TTP)).

2. 发明申请

WO2014145580A1 NEOSAXITOXIN COMBINATION FORMULATIONS FOR PROLONGED LOCAL ANESTHESIA 审中-公开
标题翻译：用于局部麻醉的NEOSAXITOXIN组合制剂
公开(公告)号：WO2014145580A1
公开(公告)日：2014-09-18
申请号：PCT/US2014/030372
申请日：2014-03-17
申请人： THE CHILDREN'S MEDICAL CENTER CORPORATION
发明人： BERDE, Charles , KOHANE, Daniel S.
IPC分类号： A61K31/137 , A61K31/445 , A61K31/52 , A61P43/00
CPC分类号： A61K31/445 , A61K9/0019 , A61K31/137 , A61K31/245 , A61K31/519 , A61K31/52 , A61K2300/00
摘要： Since each of the site I sodium channel blockers have a unique activity and cannot be used to extrapolate the same effective dosage for another site I sodium channel blocker, studies were conducted to identify dosages of neosaxitoxin ("NeoSTX") and bupivacaine, alone or in combination with epinephrine, to provide two to three days of pain relief in humans. Bupivacaine-NeoSTX combinations produce more reliable blockade and longer duration blockade compared to NeoSTX alone. The three-way combination of NeoSTX-bupivacaine-epinephrine produces more prolonged local anesthesia than the two-way combination of NeoSTX- bupivacaine. Addition of epinephrine to this NeoSTX-bupivacaine combination dramatically prolongs the duration of complete blockade to a mechanical stimulus. These results led to development of specific combination dosage formulations.
摘要翻译：由于每个位点I钠通道阻断剂具有独特的活性，不能用于外推另一个位点I钠通道阻滞剂的相同有效剂量，进行研究以确定单用或单独使用新西沙星毒素（“NeoSTX”）和布比卡因结合肾上腺素，在人体内提供2〜3天的疼痛缓解。与NeoSTX相比，布比卡因-NeoSTX组合产生更可靠的阻断和更长时间的阻断。 NeoSTX-布比卡因 - 肾上腺素的三重组合比NeoSTX-布比卡因的双向组合产生更长时间的局部麻醉。向这种NeoSTX布比卡因组合中添加肾上腺素显着地延长了完全阻断到机械刺激的持续时间。这些结果导致特定组合剂量制剂的开发。

3. 发明申请

WO2012116001A2 PARTICLES AND OTHER SUBSTRATES USEFUL IN PROTEIN PURIFICATION AND OTHER APPLICATIONS 审中-公开
标题翻译：用于蛋白质纯化和其他应用的颗粒和其他基质
公开(公告)号：WO2012116001A2
公开(公告)日：2012-08-30
申请号：PCT/US2012/026008
申请日：2012-02-22
申请人： CHILDREN'S MEDICAL CENTER CORPORATION , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , MIZRAHI, Boaz , KOHANE, Daniel S.
发明人： MIZRAHI, Boaz , KOHANE, Daniel S.
IPC分类号： C08L33/18 , C08L33/26 , C08L33/08 , C08K3/08 , G01N33/545
CPC分类号： C07K1/22 , B01J20/3265 , C07K14/435 , C08F220/06 , C08F220/56 , C08F220/60 , C08F222/385 , C08K5/175 , G01N33/545 , Y10T428/2982
摘要： The present invention generally relates to particles, including microgel particles, for purifying proteins and other species. In one aspect, the particles comprise a metal-chelating moiety, which may be distributed substantially evenly throughout the particle in certain embodiments. In some cases, the particles may be porous, and in some embodiments, the particles may be made sufficiently small, for example, in order to form a microgel containing the particles. Such particles may be useful, for example, in binding metal ions (for example, nickel ions) using the metal-chelating moieties. In some embodiments, such particles may also be used to bind certain analytes (for example, proteins) containing tags which attract metal ions, for example, histidine tags. Accordingly, in certain embodiments, the particles may be used for binding or trapping proteins. In some cases, this process is reversible; for example, upon exposure of the particles to a histidine competitor, proteins or other analytes containing the histidine tags may be released form the particles. Other aspects of the invention are generally directed to methods of using such particles, methods of forming such particles, kits including such particles, or the like.
摘要翻译：本发明一般涉及用于纯化蛋白质和其他物种的颗粒，包括微凝胶颗粒。在一个方面，颗粒包含金属螯合部分，在某些实施方案中，其可以基本均匀地分布在整个颗粒中。在一些情况下，颗粒可以是多孔的，并且在一些实施方案中，例如，为了形成含有颗粒的微凝胶，可以使颗粒足够小。这种颗粒可用于例如使用金属螯合部分结合金属离子（例如镍离子）。在一些实施方案中，这些颗粒也可用于结合含有吸引金属离子的标签的某些分析物（例如蛋白质），例如组氨酸标签。因此，在某些实施方案中，这些颗粒可以用于结合或捕获蛋白质。在某些情况下，这个过程是可逆的; 例如，当颗粒暴露于组氨酸竞争剂时，含有组氨酸标签的蛋白质或其他分析物可从颗粒释放。本发明的其它方面通常涉及使用这样的颗粒的方法，形成这样的颗粒的方法，包括这样的颗粒的试剂盒等。

4. 发明申请

WO2019109065A1 COVALENT ANESTHETIC-POLYMER CONJUGATES FOR PROLONGED LOCAL ANESTHESIA 审中-公开
公开(公告)号：WO2019109065A1
公开(公告)日：2019-06-06
申请号：PCT/US2018/063573
申请日：2018-12-03
申请人： THE CHILDREN'S MEDICAL CENTER CORPORATION
发明人： KOHANE, Daniel S. , ZHAO, Chao
IPC分类号： A61K47/60 , A61K47/10 , A61P29/02
CPC分类号： A61K47/60 , A61K9/0019 , A61K47/10
摘要： Anesthetics covalently conjugated onto biodegradable and biocompatible hydrophilic polymers via hydrolysable linkages provide controlled release of local anesthetics in vivo in an effective amount for nerve blockade with reduced toxicity relative to the unconjugated anesthetic agent. The rate of anesthetic release can be tuned by changing the hydrophilicity of the polymer. Exemplary formulations of Poly (glycerol sebacate) (PGS), optionally including Poly ethylene glycol (PEG) polymers conjugated to Tetrodotoxin (TTX) (PGS-PEG-TTX and PGS-TTX), and methods of use thereof are provided Nerve blockade from PGS-PEG-TTX and PGS-TTX was associated with minimal systemic and local toxicity to the muscle and the peripheral nerves. TDP-TTX conjugates homogeneously dispersed into PEG200 are also described. PEG200 not only worked as a medium, but also worked as a chemical permeation enhancer (CPE) to enhance the effectiveness of TTX.

5. 发明申请

WO2017062875A1 COMPOSITIONS AND METHODS FOR ON-DEMAND HIGH-EFFICIENCY TRIGGERABLE ANESTHESIA 审中-公开
标题翻译：高剂量可触发麻醉剂的组合物和方法
公开(公告)号：WO2017062875A1
公开(公告)日：2017-04-13
申请号：PCT/US2016/056139
申请日：2016-10-07
申请人： THE CHILDREN'S MEDICAL CENTER CORPORATION
发明人： RWEI, Alina Y. , ZHAN, Changyou , CULLION, Kathleen, J. , KOHANE, Daniel S.
IPC分类号： A61K9/127 , A61K31/436 , A61K31/4174 , A61K41/00 , A61P25/04
CPC分类号： A61K9/1278 , A61K31/4174 , A61K31/445 , A61K31/519 , A61K41/0028 , A61K45/06 , A61K2300/00
摘要： Compositions and methods for administration of local anesthetics that are delivered by a single injection and enable repeated on-demand or high influx analgesia over extended periods have been developed. Pharmaceutical compositions including an effective amount of one or more sodium channel blockers including site 1 sodium channel blockers, optionally one or more alpha-2-adrenergic agonists, which are optionally encapsulated in liposomes, particles or microbubbles, and one or more triggerable elements are provided. The triggerable elements allow delivery of the encapsulated anesthetic drugs when an appropriate triggering stimuli are applied. Exemplary triggering agents or stimuli include near-infrared irradiation, UV- and visible light, ultrasound and magnetic field. In one embodiment, ultrasound is used to trigger a burst of microbubbles to enhance penetration of local anesthetic.
摘要翻译：已经开发了通过单次注射输送的局部麻醉药的施用组合物和方法，并且能够在长时间内重复按需或高流量镇痛。提供包括有效量的一种或多种钠通道阻滞剂的药物组合物，其包括任选地包被在脂质体中的位点1钠通道阻断剂，任选的一种或多种α-2-肾上腺素能激动剂，颗粒或微泡，以及一种或多种可触发元件。当施加适当的触发刺激时，可触发元件允许包封的麻醉药物的递送。示例性的触发剂或刺激物包括近红外辐射，紫外线和可见光，超声波和磁场。在一个实施例中，使用超声波来触发爆发的微泡以增强局部麻醉剂的渗透。

6. 发明申请

WO2017004310A1 TRIPLET-TRIPLET ANNIHILATION-BASED UPCONVERSION 审中-公开
标题翻译：基于TRIPLET-TRIPLET ANNIHILATION的UPCONVERSION
公开(公告)号：WO2017004310A1
公开(公告)日：2017-01-05
申请号：PCT/US2016/040271
申请日：2016-06-30
申请人： CHILDREN'S MEDICAL CENTER CORPORATION
发明人： KOHANE, Daniel S. , WANG, Weiping , LIU, Qian
IPC分类号： A61K41/00 , A61K47/48 , A61K47/30 , A61K9/00 , A61K31/573 , A61K31/704
CPC分类号： A61K31/704 , A61K31/409 , A61K31/4745 , A61K31/573 , A61K31/661 , A61K41/0038 , A61K47/64 , A61K47/6937 , A61K2300/00
摘要： The present invention generally relates to various photoreactions, including reactions generally based on triplet-triplet annihilation upconversion. One aspect of the present invention is directed to systems and methods for absorbing energy (e.g., from a photon) in a photosensitizer, transferring that energy by triplet-triplet energy transfer to an annihilator to produce a higher energy state via upconversion, then transferring that energy to cleave a cleavable or other active moiety, for instance, in order to cause the release of a releasable moiety. The energy may be transferred to the moiety via Forster resonance energy transfer. In some cases, these may be contained within a suitable carrier material, for example, a particle or a micelle. Such systems and methods may be used in a variety of applications, including various biological or physical applications. For example, such systems and methods may be useful for delivering drugs or other releasable moieties to regions of the body which may be affected by too much light, such as the eye. Other aspects of the present invention are generally directed to methods for making or using such systems, kits including such systems, or the like.
摘要翻译：本发明通常涉及各种光反应，包括通常基于三重态三重态湮灭向上转换的反应。本发明的一个方面涉及用于吸收光敏剂中的能量（例如，从光子）的系统和方法，通过三重态三重态能量传递将能量传递到湮灭器，以通过上变频产生更高的能量状态，然后将该以切割可切割或其它活性部分的能量，例如为了引起可释放部分的释放。能量可以通过福斯特共振能量转移转移到该部分。在一些情况下，这些可以包含在合适的载体材料，例如颗粒或胶束中。这样的系统和方法可以用于各种应用中，包括各种生物或物理应用。例如，这样的系统和方法可用于将药物或其它可释放部分递送到可能受太多光如眼睛影响的身体的区域。本发明的其它方面一般涉及用于制造或使用这种系统的方法，包括这种系统的套件等。

7. 发明申请

WO2016064882A1 SUSTAINED AND REVERSIBLE ORAL DRUG DELIVERY SYSTEMS 审中-公开
标题翻译：持续和可逆的口服药物输送系统
公开(公告)号：WO2016064882A1
公开(公告)日：2016-04-28
申请号：PCT/US2015/056469
申请日：2015-10-20
申请人： THE CHILDREN'S MEDICAL CENTER CORPORATION
发明人： KOHANE, Daniel S. , WYLIE, Ryan
IPC分类号： A61K9/127 , A61K47/48 , A61K9/14 , A61K9/51 , A61K31/00 , A61K31/185
CPC分类号： A61K9/006 , A61K8/55 , A61K8/86 , A61K9/107 , A61K9/127 , A61K9/14 , A61K9/51 , A61K9/5115 , A61K9/5123 , A61K31/663 , A61K47/34 , A61K47/60 , A61Q11/00
摘要： A composition that achieves sustained oral drug release is provided. The composition includes liposomes, micelles, or polymeric particles, for example, having a hydrophobic core and an amphipathic corona, wherein the core contains a therapeutic, diagnostic, nutraceutical, cosmeceutical or prophylactic agent to be released, and the corona has targeting ligands immobilized to it. In a preferred embodiment the targeting ligands are bisphosphonate molecules, which enable binding to hydroxyapatite present on teeth. The incorporation of short polyethylene glycol (PEG) chains prevents chain entanglement and ionic interactions, minimizes mucus adhesion, increases particle diffusion rates in mucus, and increases the overall stability of particles in saliva. In a preferred embodiment the agent incorporated is a dental bleaching agent and the ligands selectively bind hydroxyapatite.
摘要翻译：提供了实现持续口服药物释放的组合物。组合物包括脂质体，胶束或聚合物颗粒，例如具有疏水核心和两亲性电晕，其中核心包含待释放的治疗，诊断，营养保健，药妆或预防剂，并且电晕具有固定在它。在优选的实施方案中，靶向配体是双膦酸盐分子，其能够结合存在于牙齿上的羟基磷灰石。短聚乙二醇（PEG）链的引入防止链缠结和离子相互作用，最小化粘液粘附，增加粘液中的颗粒扩散速率，并增加唾液中颗粒的总体稳定性。在优选的实施方案中，所引入的试剂是牙齿漂白剂，并且配体选择性地结合羟基磷灰石。

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