公开(公告)号：WO2020205565A1

公开(公告)日：2020-10-08

申请号：PCT/US2020/025343

申请日：2020-03-27

Applicant: ARKEMA FRANCE ,  LIU, David, Shen-Ren

Inventor： LIU, David, Shen-Ren ,  CALVIN, Mary, K. ,  BARSOTTI, Robert, J. ,  WANG, Jing-Han (Helen)

IPC: B22F3/105 ,  B29C67/00

Abstract: The invention relates to an acrylic copolymer composition useful for 3-D printing, that can be formed into a uniform filament and 3-D printed using material extrusion additive manufacturing, into an article having low warpage, low shrinkage, good internal optical properties, and good mechanical properties. The acrylic copolymer has a low Tg, providing the proper stiffness for good 3-D printing. The invention also relates to the printing and processing of the acrylic composition where internally transparent 3-D printed thermoplastic parts can be produced at a reasonable rate (>0.05mm per layer) with good/great layer adhesion, and near isotropic properties.

公开(公告)号：WO2020051360A8

公开(公告)日：2020-03-12

申请号：PCT/US2019/049793

申请日：2019-09-05

Applicant: THE BROAD INSTITUTE, INC. ,  PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  VANDERBILT UNIVERSITY ,  BAYLOR COLLEGE OF MEDICINE ,  LIU, David, R. ,  KOBLAN, Luke W. ,  BROWN, Jonathan D. ,  LIN, Charles Yang

Inventor： LIU, David, R. ,  KOBLAN, Luke W. ,  BROWN, Jonathan D. ,  LIN, Charles Yang

IPC: C12N15/11 ,  C12N15/113 ,  C12N9/00

Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA to treat Hutchinson-Gilford progeria syndrome (HOPS). The disclosure also provides fusion proteins, guide RNAs and compositions comprising a Cas9 ( e.g ., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA, for example in a LMNA gene. In some embodiments, adenosine deaminases provided herein are used to correct a C1824T mutation in LMNA . In some embodiments, the methods and compositions provided herein are used to treat Hutchinson-Gilford progeria syndrome (HGPS).

公开(公告)号：WO2017210286A1

公开(公告)日：2017-12-07

申请号：PCT/US2017/035200

申请日：2017-05-31

Applicant: ARKEMA FRANCE ,  LIU, David Shin-Ren ,  REILLY, Jack J. ,  AUBART, Mark A.

Inventor： LIU, David Shin-Ren ,  REILLY, Jack J. ,  AUBART, Mark A.

IPC: B33Y10/00 ,  B33Y70/00

CPC classification number: C08F20/00 ,  B29C64/118 ,  B29C64/314 ,  B33Y70/00 ,  C08L33/10 ,  C08L101/16

Abstract: The invention relates to an acrylic alloy composition that can be 3-D printed by a material extrusion additive manufacturing process, to an acrylic filament that has a very uniform diameter useful in the extrusion additive manufacturing process, to acrylic articles made from the acrylic alloy composition by a material extrusion additive process, and to a material extrusion additive manufacturing process for producing the acrylic articles. The acrylic alloy composition is an alloy of an acrylic polymer, and a low melt viscosity polymer, such as polylactic acid. The alloy may optionally be impact modified, preferably with hard core core-shell impact modifiers.

Abstract translation: 本发明涉及一种丙烯酸类合金组合物，其可以通过材料挤出添加剂制造工艺进行3-D印刷，在挤出添加剂制造工艺中可用于具有非常均匀直径的丙烯酸长丝， 通过材料挤出添加法由丙烯酸类合金组合物制成的丙烯酸类制品，以及用于制造丙烯酸类制品的材料挤出添加剂制造方法。 丙烯酸类合金组合物是丙烯酸类聚合物与低熔点粘度聚合物如聚乳酸的合金。 该合金可以任选地进行冲击改性，优选使用硬核芯 - 壳抗冲改性剂。

公开(公告)号：WO2013133873A3

公开(公告)日：2014-02-20

申请号：PCT/US2012067802

申请日：2012-12-04

Applicant: LIU DAVID L

Inventor： LIU DAVID L

IPC: A61K33/00 ,  A61K33/06 ,  A61P35/00

CPC classification number: A61K33/14 ,  A61K33/00 ,  A61K2300/00

Abstract: The invention relates to a unique formulated pharmaceutical composition and a novel treatment method of intratumoral injection. The pharmaceutical composition of the invention is the saturated ionic solution of sodium ions and calcium ions (the "medicinal ion bomb"). The invention of intratumoral injection with the "medicinal ion bomb" can be used as the first-line treatment in treating cancer and tumor in nine human organs (carcinoma and tumor of the skin and subcutaneous tissue, breast, prostate, thyroid, lung, liver, genital organ, brain and pancreas) and certain other benign diseases (skin and subcutaneous neoplasm, breast fibrocystic change, benign prostatic hyperplasia and thyroid nodules).

Abstract translation: 本发明涉及独特的配制药物组合物和肿瘤内注射的新型治疗方法。 本发明的药物组合物是钠离子和钙离子的饱和离子溶液（“药用离子炸弹”）。 肿瘤内注射“药用离子炸弹”的发明可用作九种人体器官（癌和皮肤和皮下组织，乳腺，前列腺，甲状腺，肺，肝脏的肿瘤）治疗癌症和肿瘤的一线治疗 ，生殖器，脑和胰腺）和某些其他良性疾病（皮肤和皮下肿瘤，乳腺纤维囊性变化，良性前列腺增生和甲状腺结节）。

公开(公告)号：WO2013133873A2

公开(公告)日：2013-09-12

申请号：PCT/US2012/067802

申请日：2012-12-04

Applicant: LIU, David, L.

Inventor： LIU, David, L.

CPC classification number: A61K33/14 ,  A61K33/00 ,  A61K2300/00

Abstract: The invention relates to a unique formulated pharmaceutical composition and a novel treatment method of intratumoral injection. The pharmaceutical composition of the invention is the saturated ionic solution of sodium ions and calcium ions (the "medicinal ion bomb"). The invention of intratumoral injection with the "medicinal ion bomb" can be used as the first-line treatment in treating cancer and tumor in nine human organs (carcinoma and tumor of the skin and subcutaneous tissue, breast, prostate, thyroid, lung, liver, genital organ, brain and pancreas) and certain other benign diseases (skin and subcutaneous neoplasm, breast fibrocystic change, benign prostatic hyperplasia and thyroid nodules).

Abstract translation: 本发明涉及独特的配制药物组合物和肿瘤内注射的新型治疗方法。 本发明的药物组合物是钠离子和钙离子的饱和离子溶液（“药用离子炸弹”）。 肿瘤内注射“药用离子炸弹”的发明可用作九种人体器官（癌和皮肤和皮下组织，乳腺，前列腺，甲状腺，肺，肝脏的肿瘤）治疗癌症和肿瘤的一线治疗 ，生殖器，脑和胰腺）和某些其他良性疾病（皮肤和皮下肿瘤，乳腺纤维囊性变化，良性前列腺增生和甲状腺结节）。

公开(公告)号：WO2013066438A2

公开(公告)日：2013-05-10

申请号：PCT/US2012/047778

申请日：2012-07-22

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE ,  LIU, David, R. ,  GUILINGER, John, Paul ,  PATTANAYAK, Vikram

Inventor： LIU, David, R. ,  GUILINGER, John, Paul ,  PATTANAYAK, Vikram

CPC classification number: C12N9/22 ,  C12Q1/44 ,  C12Q1/68 ,  C12Q1/6874 ,  C12Q1/6802 ,  C12Q2521/30

Abstract: Engineered nucleases (e.g., zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and others) are promising tools for genome manipulation and determining off-target cleavage sites of these enzymes is of great interest. We developed an in vitro selection method that interrogates 10 11 DNA sequences for their ability to be cleaved by active, dimeric nulceases, e.g., ZFNs and TALENs. The method revealed hundreds of thousands of DNA sequences, some present in the human genome, that can be cleaved in vitro by two ZFNs, CCR5-224 and VF2468, which target the endogenous human CCR5 and VEGF-A genes, respectively. Analysis of the identified sites in cultured human cells revealed CCR5-224-induced mutagenesis at nine off-target loci. Similarly, we observed 31 off-target sites cleaved by VF2468 in cultured human cells. Our findings establish an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage and suggest strategies for the improvement of future nuclease design. It was also observed that TALENs can achieve cleavage specificity similar to or higher than that observed in ZFNs.

Abstract translation: 工程核酸酶（例如锌指核酸酶（ZFN），转录激活物样效应物核酸酶（TALEN）等）是用于基因组操作的有希望的工具并且确定这些酶的脱靶切割位点是 非常感兴趣。 我们开发了一种体外选择方法，用于询问10 11 DNA序列被活性二聚体蛋白酶（例如ZFN和TALEN）切割的能力。 该方法揭示了成千上万的DNA序列，一些存在于人类基因组中，可以被两个靶向内源性人CCR5和VEGF-A的ZFNs，CCR5-224和VF2468在体外切割 基因，分别。 在培养的人类细胞中鉴定的位点的分析揭示了在9个脱靶位点处的CCR5-224诱导的诱变。 同样，我们在培养的人类细胞中观察到了VF2468切割的31个脱靶位点。 我们的研究结果建立了ZFN特异性的能量补偿模型，其中过量结合能量有助于脱靶ZFN切割并提出改进未来核酸酶设计的策略。 还观察到TALEN可以实现与在ZFN中观察到的相似或更高的切割特异性。

公开(公告)号：WO2013032425A1

公开(公告)日：2013-03-07

申请号：PCT/US2011/049374

申请日：2011-08-26

Applicant: TOSHIBA INTERNATIONAL CORPORATION ,  BIHLER, Kurt Allen ,  LIU, David ,  RAYNER, Mark Douglas

Inventor： BIHLER, Kurt Allen ,  LIU, David ,  RAYNER, Mark Douglas

IPC: F04B49/00

CPC classification number: F04D27/004 ,  F04D15/00 ,  F04D15/0066 ,  F04D17/10

Abstract: A demand-based load balancing function may be provided by one or more drive controllers that takes advantage of the affinity laws to linearize the control of the variable of interest (e.g., flow, pressure, etc.). Each drive controller may be set up by the user simply inputting a few values into the drive controller. Based on the inputs, the drive controllers may interpolate control points using an assumed linear relationship between the variable to be controlled (e.g., pressure) and the current driven to the pump. Feedback data from the system may be used to continually update the drive controllers so as to potentially allow them to better balance power usage to each pump.

Abstract translation: 可以由一个或多个驱动控制器提供基于需求的负载平衡功能，所述驱动器控制器利用亲和度定律来线性化感兴趣变量的控制（例如，流量，压力等）。 每个驱动器控制器可以由用户简单地将几个值输入到驱动控制器中来设置。 基于输入，驱动控制器可以使用待控制的变量（例如，压力）与被驱动到泵的电流之间的假设线性关系来内插控制点。 来自系统的反馈数据可用于不断更新驱动控制器，以便潜在地允许它们更好地平衡每个泵的功率使用。

公开(公告)号：WO2012154973A1

公开(公告)日：2012-11-15

申请号：PCT/US2012/037349

申请日：2012-05-10

Applicant: JONKER, LLC ,  LIU, David

Inventor： LIU, David

IPC: H01L27/115

CPC classification number: H01L29/7885 ,  H01L27/11521 ,  H01L27/11541 ,  H01L27/11558 ,  H01L29/1095 ,  H01L29/42324 ,  H01L29/66825 ,  H01L29/7816 ,  H01L29/7883

Abstract: A non-volatile memory cell and array structure is disclosed situated within a high voltage region of an integrated circuit. The cell utilizes capacitive coupling based on an overlap between a gate and a drift region to impart a programming voltage. Programming is effectuated using a drain extension which can act to inject hot electrons. The cell can be operated as a one-time programmable (OTP) or multiple-time programmable (MTP) device. The fabrication of the cell relies on processing steps associated with high voltage devices, thus avoiding the need for additional masks, manufacturing steps, etc.

Abstract translation: 公开了一种位于集成电路的高电压区域内的非易失性存储单元和阵列结构。 电池利用基于栅极和漂移区域之间的重叠的电容耦合来施加编程电压。 使用可以用于注入热电子的漏极延伸来实现编程。 电池可以作为一次性可编程（OTP）或多时间可编程（MTP）器件运行。 电池的制造依赖于与高电压装置相关的处理步骤，因此避免了对附加掩模，制造步骤等的需要。

公开(公告)号：WO2012094653A2

公开(公告)日：2012-07-12

申请号：PCT/US2012/020567

申请日：2012-01-07

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  PIRIE, Christopher, Michael ,  LIU, David, Victor ,  YANG, Nicole ,  WITTRUP, Karl, Dane

Inventor： PIRIE, Christopher, Michael ,  LIU, David, Victor ,  YANG, Nicole ,  WITTRUP, Karl, Dane

IPC: A61K47/48 ,  A61K47/30 ,  A61K38/43 ,  A61K9/127 ,  A61P35/00

CPC classification number: A61K47/48246 ,  A61K31/713 ,  A61K47/62 ,  A61K47/6825 ,  A61K47/6849 ,  A61K47/6853

Abstract: The present invention features compositions and methods for delivering a therapeutic agent to the cytoplasm of a cell. We have developed, inter alia, a system in which two or more distinct moieties - at least one therapeutic moiety and at least one potentiating moiety - selectively target and specifically bind cell surface molecules that are then internalized to an intracellular, membrane-bound compartment, such as an endosome. In some embodiments, as discussed further below, a third moiety that induces clustering of the targeted cell surface molecule can also be employed. Regardless of whether the compositions and methods include two or three moieties, the therapeutic agent can be any agent one wishes to deliver to the cytoplasm of a cell, and the potentiating agent can be any agent that destabilizes the intracellular, sub-cellular compartment in which the therapeutic agent is sequestered. The potentiating moiety can include, for example, a lytic agent (i.e., an agent that lyses or otherwise increases the permeability of the membrane of the intracellular compartment containing the therapeutic agent). To direct the various moieties of the system, including the therapeutic, potentiating, and clustering moieties, to a selected cellular target, any of the moieties can include a binding agent that selectively targets and specifically binds a molecule present on the surface of the targeted cell.

Abstract translation: 本发明的特征在于将治疗剂递送至细胞的细胞质的组合物和方法。 我们特别开发了一种系统，其中两个或多个不同部分 - 至少一个治疗部分和至少一个增强部分 - 选择性地靶向和特异性结合细胞表面分子，然后细胞表面分子被内化到胞内膜结合的隔室， 如内体。 在一些实施方案中，如下文进一步讨论的，也可以使用诱导靶细胞表面分子聚集的第三部分。 不管组合物和方法是否包括两个或三个部分，治疗剂可以是希望递送至细胞的细胞质的任何试剂，并且增效剂可以是使细胞内，亚细胞隔室不稳定的任何试剂，其中 治疗剂被隔离。 增强部分可以包括例如溶解剂（即，裂解或以其它方式增加含有治疗剂的细胞内隔室的膜的渗透性的试剂）。 为了将系统的各种部分（包括治疗性，增强和聚集部分）引导至所选择的细胞靶，任何部分可以包括选择性靶向和特异性结合存在于靶细胞表面上的分子的结合剂 。

公开(公告)号：WO2011056185A3

公开(公告)日：2011-06-30

申请号：PCT/US2010002732

申请日：2010-10-13

Applicant: HARVARD COLLEGE ,  LIU DAVID R ,  GORIN DAVID ,  KAMLET ADAM ,  MCGREGOR LYNN M ,  DUMELIN CHRISTOPH E

Inventor： LIU DAVID R ,  GORIN DAVID ,  KAMLET ADAM ,  MCGREGOR LYNN M ,  DUMELIN CHRISTOPH E

IPC: C12P19/34

CPC classification number: C12Q1/686 ,  C12N15/1075 ,  C12Q1/6853 ,  C12Q2563/179 ,  C12Q2563/131 ,  C12Q2525/301

Abstract: Methods, reagents, compositions, and kits for reactivity-dependent polymerase chain reaction (RD-PCR) and interaction-dependent polymerase chain reaction (ID-PCR) are provided herein. RD-PCR is a technique useful for determining whether a reactive moiety can form a covalent bond to a target reactive moiety, for example, in screening a library of candidate reactive moieties for reactivity with a target reactive moiety, and in identifying an enzyme substrate, for example, in protease substrate profiling. ID-PCR is a technique useful for determining whether a ligand can non-covalently bind to a target molecule, for example, in screening a library of candidate ligands for non-covalent interaction with a target molecule. RD-PCR and ID-PCR are also useful in detecting the presence of an analyte or an environmental condition.

Abstract translation: 本文提供了用于反应性依赖性聚合酶链式反应（RD-PCR）和相互作用依赖性聚合酶链式反应（ID-PCR）的方法，试剂，组合物和试剂盒。 RD-PCR是用于确定反应性部分是否可以与靶反应性部分形成共价键的技术，例如筛选与靶反应性部分反应的候选反应性部分的文库以及鉴定酶底物， 例如在蛋白酶底物分析中。 ID-PCR是用于确定配体是否可以非共价结合靶分子的技术，例如筛选用于与靶分子非共价相互作用的候选配体文库。 RD-PCR和ID-PCR也可用于检测分析物或环境条件的存在。