Patents Assigned to President & Fellows of Harvard College
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Publication number: 20230305006Abstract: Provided herein are methods, compositions, kits, and systems for the detection of neutralization targets such as neutralizing antibodies.Type: ApplicationFiled: April 4, 2023Publication date: September 28, 2023Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng XUAN, Yu Wang, Peng Yin, Tsz Wing Fan
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Publication number: 20230302420Abstract: Parallel uses of microfluidic methods and devices for focusing and/or forming discontinuous sections of similar or dissimilar size in a fluid are described. In some aspects, the present invention relates generally to flow-focusing-type technology, and also to microfluidics, and more particularly parallel use of microfluidic systems arranged to control a dispersed phase within a dispersant, and the size, and size distribution, of a dispersed phase in a multi-phase fluid system, and systems for delivery of fluid components to multiple such devices.Type: ApplicationFiled: November 1, 2022Publication date: September 28, 2023Applicant: President and Fellows of Harvard CollegeInventors: David A. Weitz, Mark Romanowsky, Adam R. Abate
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Patent number: 11768174Abstract: To sense the translocation of a molecule through a nanopore, there is directed to an inlet of the nanopore, having a nanopore fluidic resistance, RP, a molecule disposed in a cis fluidic ionic solution having a cis fluidic access resistance, RC. The molecule is caused to translocate through the nanopore from the inlet of the nanopore to an outlet of the nanopore and to a trans fluidic ionic solution having a trans fluidic access resistance, RT. The trans fluidic access resistance, RT, is of the same order of magnitude as the nanopore fluidic resistance, RP, and both RT and RP are at least an order of magnitude greater than the cis fluidic access resistance, RC. An indication of local electrical potential is produced at a site within the nanopore sensor that is on the trans fluidic ionic solution-side of the nanopore, to sense translocation of the molecule through the nanopore.Type: GrantFiled: April 29, 2022Date of Patent: September 26, 2023Assignee: President and Fellows of Harvard CollegeInventors: Ping Xie, Charles M. Lieber
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Patent number: 11767341Abstract: Provided are lincosamide compounds for the treatment of infectious diseases. The lincosamides described herein are modified at the amino acid (southern) region. The lincosamides may have further modification at the C-1 and C-7 positions of the aminooctose (northern) region, thus distinguishing them from lincomycin and clindamycin. Also provided are methods for preparing the lincosamide compounds, pharmaceutical compositions comprising the lincosamide compounds, and methods of treating infectious diseases using the disclosed lincosamide compounds.Type: GrantFiled: September 8, 2021Date of Patent: September 26, 2023Assignee: President and Fellows of Harvard CollegeInventors: Andrew G. Myers, Matthew James Mitcheltree, Katherine J. Silvestre
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Patent number: 11768196Abstract: Methods and systems for stimulating and monitoring electrogenic cells are described. Some systems for stimulating electrogenic cells are based on the injection of electric currents into the cells via electrodes connected to the cells. Such stimulators may comprise an impedance element having an input terminal and an output terminal coupled to an electrode, and a voltage follower coupled between the input terminal and the output terminal of the impedance element, the voltage follower being configured to maintain a substantially constant voltage between the input terminal and the output terminal of the impedance element. The impedance element may comprise one or more switched capacitors at least in some embodiments. In some embodiments, the voltage follower may be implemented using a source follower.Type: GrantFiled: July 6, 2018Date of Patent: September 26, 2023Assignee: President and Fellows of Harvard CollegeInventors: Donhee Ham, Jeffrey T. Abbott, Hongkun Park, Wenxuan Wu
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Patent number: 11761832Abstract: A strain sensor comprising a conductive member having a plurality of elements arranged adjacent to one another, and a non-conductive and elastically deformable material encapsulating the conductive member, wherein, in an equilibrium state, compressive forces cause at least one of the plurality of elements to contact at least a portion of an adjacent element, and wherein, when a strain is applied, a resulting elastic deformation causes at least one of the plurality of elements to space apart from an adjacent element such that the contacted portion decreases or is eliminated. A multi-axis force sensor comprising a sensing array comprising at least two planar sensors arranged radially on a planar substrate in antagonistic pairs, and a compressible member positioned between the substrate and a central portion of the sensing array, the compressible member acting to displace the central portion of the sensing array away from the substrate.Type: GrantFiled: July 8, 2022Date of Patent: September 19, 2023Assignee: President and Fellows of Harvard CollegeInventors: Oluwaseun A. Araromi, Conor J. Walsh, Robert J. Wood
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Patent number: 11760986Abstract: Some aspects of this disclosure provide methods for phage-assisted continuous evolution (PACE) of proteases. Some aspects of this invention provide methods for evaluating and selecting protease inhibitors based on the likelihood of the emergence of resistant proteases as determined by the protease PACE methods provided herein. Some aspects of this disclosure provide strategies, methods, and reagents for protease PACE, including fusion proteins for translating a desired protease activity into a selective advantage for phage particles encoding a protease exhibiting such an activity and improved mutagenesis-promoting expression constructs. Evolved proteases that recognize target cleavage sites which differ from their canonical cleavage site are also provided herein.Type: GrantFiled: December 16, 2020Date of Patent: September 19, 2023Assignee: President and Fellows of Harvard CollegeInventors: David R. Liu, Bryan Dickinson, Michael S. Packer, Ahmed Hussein Badran
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Publication number: 20230287373Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRJSPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CR.ISPR-Cas enzyme systems. In particular the present invention comprehends engineered new guide architectures and enzymes to be used in optimized Staphylococcus aureus CRISPR-Cas enzyme systems.Type: ApplicationFiled: January 26, 2023Publication date: September 14, 2023Applicants: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard College, University of TokyoInventors: Feng ZHANG, Winston YAN, Osamu NUREKI, Kaijie ZHENG, Le CONG, Hiroshi NISHIMASU, Fei RAN, Yinqing LI
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Publication number: 20230288716Abstract: An optical component comprises a metasurface comprising nanoscale elements. The metasurface is configured to receive incident light and to generate optical outputs. The geometries and/or orientations of the nanoscale elements provide a first optical output upon receiving a polarized incident light with a first polarization, and provide a second optical output upon receiving a polarized incident light with a second polarization that is different from the first polarization.Type: ApplicationFiled: March 13, 2023Publication date: September 14, 2023Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Noah A. RUBIN, Jan Philipp Balthasar MUELLER, Federico CAPASSO
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Publication number: 20230287142Abstract: Described herein are polypeptides, compositions, kits, and analyte detection systems for the detection of the presence or absence of small molecules (e.g. histamine and/or histidine) in a test sample.Type: ApplicationFiled: July 6, 2021Publication date: September 14, 2023Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Alexander WATTERS, Pawan JOLLY, Donald E. INGBER, Thomas CUNNINGHAM
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Publication number: 20230287357Abstract: Described herein are methods of generating a programmable multicellular organoid and/or a 3D organ-specific tissue. Also, described are the programmable multicellular organoid and/or a 3D organ-specific tissue produced by the described methods. Also, described herein are in vitro methods of generating functional human tissue construct.Type: ApplicationFiled: July 6, 2021Publication date: September 14, 2023Applicant: President and Fellows of Harvard CollegeInventors: Mark Andrew SKYLAR-SCOTT, Jennifer A. LEWIS, Jeremy Yuenchen HUANG, Jingcheng LU, Tomoya DUENKI
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Publication number: 20230287510Abstract: As described below, the present invention features compositions, panels of biomarkers, and methods for characterizing chronic lymphocytic leukemia (CLL) for prognosis and selection of a subject for a treatment and/or inclusion in a clinical trial.Type: ApplicationFiled: August 9, 2021Publication date: September 14, 2023Applicants: The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., The General Hospital Corporation, President and Fellows of Harvard CollegeInventors: Catherine J. WU, Gad GETZ, Binyamin A. KNISBACHER, Ziao LIN, Cynthia K. HAHN
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Patent number: 11752238Abstract: Disclosed are compositions and related methods of recapitulating bone marrow stroma using scaffold materials (e.g., a porous alginate hydrogel scaffold) containing one or more cellular differentiation factors, and one or more growth factors. Such methods and compositions promote the formation of an ectopic nodule or site that can improve transplanted cell engraftment and selectively drive the development of lymphocytes and the reconstitution of the adaptive immunity after hematopoietic stem cell transplant.Type: GrantFiled: February 6, 2017Date of Patent: September 12, 2023Assignees: President and Fellows of Harvard College, The General Hospital CorporationInventors: Nisarg J. Shah, Ting-Yu Shih, Angelo Mao, David J. Mooney, David T. Scadden
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Patent number: 11753633Abstract: Embodied herein are engineered fusion proteins that bind and target nociceptor neurons, compositions comprising these engineered fusion proteins, and methods for treatment of pain using these engineered fusion proteins or compositions containing the engineered fusion proteins. The engineered fusion proteins contain domains derived from protein toxins such as the anthrax toxin, clostridial botulinum family of toxins, disulphide-containing toxins, and AB component type toxins.Type: GrantFiled: August 26, 2016Date of Patent: September 12, 2023Assignees: President and Fellows of Harvard College, Massachusetts Institute of Technology, IPSEN PHARMA S.A.S.Inventors: R. John Collier, Isaac Chiu, Bradley L. Pentelute, Keith Alan Foster, Shilpa Palan, Sai Man Liu
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Publication number: 20230279387Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.Type: ApplicationFiled: April 7, 2023Publication date: September 7, 2023Applicant: President and Fellows of Harvard CollegeInventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
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Publication number: 20230279018Abstract: The invention provides agents that inhibit L-Phe in cytoplasmic phenylalanine tRNA-synthetase (cFRS), methods for identifying them, compositions comprising such agents, and therapeutic methods of using such agents.Type: ApplicationFiled: March 22, 2023Publication date: September 7, 2023Applicants: The Broad Institute, Inc., President and Fellows of Harvard College, Eisai R&D Management Co., LTD.Inventors: Eamon COMER, Bruno MELILLO, Francis G. FANG, Branko MITASEV
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Publication number: 20230279443Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.Type: ApplicationFiled: December 21, 2022Publication date: September 7, 2023Applicant: President and Fellows of Harvard CollegeInventors: David R. Liu, Kevin Davis
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Publication number: 20230277685Abstract: Provided herein are methods and compositions related to the treatment of a neurodegenerative disease or an ocular disease.Type: ApplicationFiled: April 8, 2021Publication date: September 7, 2023Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Sean K. WANG, Constance L. CEPKO
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Publication number: 20230279383Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.Type: ApplicationFiled: October 13, 2022Publication date: September 7, 2023Applicant: President and Fellows of Harvard CollegeInventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
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Patent number: 11745420Abstract: A method of forming a three-dimensional structure includes forming a layer of resin comprising liquid crystal oligomers and a photoinitiator, applying a magnetic field to the formed layer in a predefined alignment direction for substantially aligning the liquid crystal oligomers in a first orientation; and exposing the formed layer to radiation for curing a first portion of the layer during application of the magnetic field thereby resulting in the first portion having liquid crystal elastomers substantially aligned in the first orientation. The method includes applying a second magnetic field to the formed layer in a predefined second alignment direction for substantially aligning uncured liquid crystal oligomers in a second orientation, and exposing the layer to radiation for curing a second portion of the layer during application of the second magnetic field thereby resulting in the second portion having liquid crystal elastomers substantially aligned in the second orientation.Type: GrantFiled: June 23, 2022Date of Patent: September 5, 2023Assignees: Lawrence Livermore National Security, LLC, President and Fellows of Harvard CollegeInventors: Rodrigo Telles Arriaga, Caitlyn Christian Krikorian, Elaine Lee, Jennifer Lewis