August 2020 patents
Innovations in anti-inflammatory agents, microbiotic treatments, tools for assessing gestational diabetes, optically active structures, vaccine nanotechnology, and more
Harvard faculty Bruce Bean, George Whitesides, Don Ingber, Alan Michelson, Mikhail Lukin, Uli von Andrian, David Weitz, George Church, Eric Mazur, Cynthia Friend, David Liu, Eric Lander, Peng Yin, Stuart Schreiber, Arlene Sharpe, Kit Parker, and Lee Rubin are among the inventors issued U.S. patents in August 2020.
The innovations recognized are as follows:
Permanently charged sodium and calcium channel blockers as anti-inflammatory agents
U.S. Patent 10,729,664 (August 4, 2020)
Clifford J. Woolf and Bruce P. Bean
Abstract: The invention provides compounds, compositions, methods, and kits for the treatment of neurogenic inflammation.
Compositions of microbiota and methods related thereto
U.S. Patent 10,729,732 (August 4, 2020)
Lee M. Kaplan, Alice P. Liou, Peter J. Turnbaugh, and Jason L. Harris
Abstract: Methods and compositions are provided for treating weight related conditions and metabolic disorders by altering microbiota in a subject. One aspect provides methods and compositions to alter microbiota in a subject by administering to the subject a composition that includes a substantially purified microbiota from phyla such as Bacteroidetes, Proteobacteria, Firmicutes and Verrucomicrobia or orders such as Bacteroidales, Verrucomicrobiales, Clostridiales and Enterobacteriales or genera such as Alistipes, Clostridium, Escherichia, and Akkermansia. Another aspect includes a pharmaceutical composition for altering microbiota that includes a therapeutically effective amount of substantially purified microbiota and a pharmaceutically acceptable carrier. Yet another aspect includes methods for treating a disorder, such as obesity, in a subject in need of such treatment by changing relative abundance of microbiota in a gastrointestinal tract of the subject without or in addition to a surgical procedure.
Anti-clogging microfluidic multichannel device
U.S. Patent 10,731,012 (August 4, 2020)
Juan Perez-Mercader and Yuandu Hu
Abstract: An anti-clogging microfluidic multichannel device comprising a first mixing chamber comprising a first and a second end, wherein the first end comprises at least one inlet connected in fluid communication with the first mixing chamber, and at least one first capillary element comprising a first and a second end, wherein the first end of the at least one first capillary element is connected in fluid communication with the second end of the first mixing chamber, at least one septum located within the at least one first capillary element, which divides the cross section of the at least one first capillary element in a plurality of channels, wherein the at least one first capillary element comprises a reduction of section along its longitudinal axis between a section of the at least one first capillary element and the second end of the at least one first capillary element. It is also described a microfluidics system and a method of production of emulsions using said microfluidics system.
Multiphase systems and uses thereof
U.S. Patent 10,732,167 (August 4, 2020)
Charles R. Mace, Ozge Akbulut Halatci, Ashok A. Kumar, Nathan D. Shapiro, and George M. Whitesides
Abstract: A multi-phase system includes a phase-separated solution comprising at least two phases, each phase having a phase component selected from the group consisting of a polymer, a surfactant and combinations thereof, wherein at least one phase comprises a polymer, wherein the phases, taken together, represent a density gradient. Novel two-phase, three-phase, four-phase, five-phase, or six-phase systems are disclosed. Using the disclosed multi-phase polymer systems, particles, or other analyte of interest can be separated based on their different densities or affinities.
Methods, systems, and compositions for determining blood clot formation, and uses thereof
U.S. Patent 10,732,172 (August 4, 2020)
Donald E. Ingber, Abhishek Jain, Andries D. van der Meer, Alan David Michelson, Andrew L. Frelinger, III, and Riccardo Barrile
Abstract: A method is directed to determining a thrombosis function and includes flowing a fluid sample over a surface having a fixed endothelial cell monolayer. The method further includes stimulating the fixed endothelial cell monolayer to induce formation of a clot, the clot being formed via interaction between the fixed endothelial cell monolayer and the fluid sample. In response to the clot formation, the method further includes determining a thrombosis function associated with the fluid sample and the fixed endothelial cell monolayer.
Methods and reagents for the assessment of gestational diabetes
U.S. Patent 10,732,186 (August 4, 2020)
Michael Chorev and Jose Alberto Halperin
Abstract: The invention involves assays, diagnostics, kits, and assay components for determining levels of glycated CD59 in the assessment of gestational diabetes mellitus and/or related disorders and/or conditions.
Implanted vacancy centers with coherent optical properties
U.S. Patent 10,734,781 (August 4, 2020)
Ruffin E. Evans, Alp Sipahigil, and Mikhail D. Lukin
Abstract: In an exemplary embodiment, a structure comprises a plurality of deterministically positioned optically active defects, wherein each of the plurality of deterministically positioned optically active defects has a linewidth within a factor of one hundred of a lifetime limited linewidth of optical transitions of the plurality of deterministically positioned optically active defects, and wherein the plurality of deterministically positioned optically active defects has an inhomogeneous distribution of wavelengths, wherein at least half of the plurality of deterministically positioned optically active defects have transition wavelengths within a less than 8 nm range. In a further exemplary embodiment, method of producing at least one optically active defect comprises deterministically implanting at least one ion in a structure using a focused ion beam; heating the structure in a vacuum at a first temperature to create at least one optically active defect; and heating the structure in the vacuum at a second temperature to remove a plurality of other defects in the structure, wherein the second temperature is higher than the first temperature.
U.S. Patent 10,736,848 (August 11, 2020)
Ulrich H. Von Andrian, Omid C. Farokhzad, Robert S. Langer, Tobias Junt, Elliott Ashley Moseman, Liangfang Zhang, Pamela Basto, Matteo Iannacone, and Frank Alexis
Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.
Enhanced immunogenicity of mRNA with co-encoded adjuvant sequences
U.S. Patent 10,736,957 (August 11, 2020)
Ying Kai Chan and Jessica Jing-Shiuan Chiang
Abstract: Described herein are in vitro-transcribed (IVT) RNA molecules comprising, a 5' cap structure, a coding region encoding an antigen polypeptide, an immunostimulatory RNA sequence, and a poly(A) tail.
Assays and other reactions involving droplets
U.S. Patent 10,738,337 (August 11, 2020)
David A. Weitz, Jeremy Agresti, Liang-Yin Chu, Jin-Woong Kim, Amy Rowat, Morten Sommer, Gautam Dantas, and George M. Church
Abstract: The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer. After the PCR reaction, unbound DNA may be removed from the gel, e.g., via diffusion or washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention.
Femtosecond laser-induced formation of submicrometer spikes on a semiconductor substrate
U.S. Patent 10,741,399 (August 11, 2020)
Eric Mazur and Mengyan Shen
Abstract: The present invention generally provides semiconductor substrates having submicron-sized surface features generated by irradiating the surface with ultra short laser pulses. In one aspect a method of processing a semiconductor substrate is disclosed that includes placing at least a portion of a surface of the substrate in contact with a fluid, and exposing that surface portion to one or more femtosecond pulses so as to modify the topography of that portion. The modification can include, e.g., generating a plurality of submicron-sized spikes in an upper layer of the surface.
Ozone-activated nanoporous gold and methods of its use
U.S. Patent 10,744,488 (August 18, 2020)
Cynthia M. Friend, Robert J. Madix, Branko Zugic, Lucun Wang, Michelle L. Personick, Juergen Biener, and Monika Margarete Biener
Abstract: The invention relates to nanoporous gold nanoparticle catalysts formed by exposure of nanoporous gold to ozone at elevated temperatures, as well as methods for production of esters and other compounds.
Editing of CCR5 receptor gene to protect against HIV infection
U.S. Patent 10,745,677 (August 18, 2020)
Juan Pablo Maianti and David R. Liu
Abstract: Provided herein are systems, compositions, and methods of introducing protective and/or loss-of-function variants of CCR5 and CCR2. Variants may be introduced using a CRISPR/Cas9-based nucleobase editor or other guide nucleotide sequence-programmable DNA binding protein domain-based fusion protein described herein. Further provided herein are compositions and methods of preventing and treating conditions related to HIV infection and progression as well as to AIDS.
HiC: method of identifying interactions between genomic loci
U.S. Patent 10,745,744 (August 18, 2020)
Job Dekker, Erez Lieberman Aiden, Nynke Van Berkum, Andreas Gnirke, Eric Lander, Chad Nusbaum, Louise Williams, Alexandre Melnikov, Georgia Giannoukos
Abstract: The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.
Specific nucleic acid amplification with compounded selectivity
U.S. Patent 10,745,746 (August 18, 2020)
Xi Chen, David Yu Zhang, and Peng Yin
Abstract: The present disclosure provides, in various aspects and embodiments, methods and compositions for selectively amplifying a rare target nucleic acid and/or suppressing amplification of non-target nucleic acids with sequences similar to the rare target nucleic acid. The methods and composition are useful, for example, for detecting rare alleles among a population of wild-type alleles.
Enzymatic nucleic acid synthesis
U.S. Patent 10,745,814 (August 18, 2020)
Reza Kalhor, Henry Hung-yi Lee, and George M. Church
Abstract: The present disclosure provides methods of activating an enzyme, such as error prone or template independent polymerase, using electricity to alter pH of a reaction zone and reaction site from an inactivating pH at which the enzyme is inactive to an activating pH at which the enzyme is active to add a nucleotide to an initiator or growing polymer chain. The activating pH can then be changed back to an inactivating pH and the process repeated as many times as desired to produce a target nucleic acid sequence.
Compounds and methods for treating synovial sarcomas
U.S. Patent 10,752,628 (August 25, 2020)
Cigall Kadoch, Enrique Garcia-Rivera, Micah Maetani, and Stuart L. Schreiber
Abstract: The present invention includes compound and methods that are useful in treating certain cancers, such as synovial sarcomas.
Antibody molecules to PD-1 and uses thereof
U.S. Patent 10,752,687 (August 25, 2020)
Gordon James Freeman, Arlene Helen Sharpe, Walter A. Blattler, Jennifer Marie Mataraza, Catherine Anne Sabatos-Peyton, Hwai Wen Chang, and Gerhard Johann Frey
Abstract: Antibody molecules that specifically bind to PD-1 are disclosed. The anti-PD-1 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious conditions and disorders.
High-throughput single cell barcoding
U.S. Patent 10,752,895 (August 25, 2020)
George M. Church and Francois Vigneault
Abstract: Methods and compositions for high-throughput, single cell analyses are provided. The methods and compositions can be used for analysis of genomes and transcriptomes, as well as antibody discovery, HLA typing, haplotyping and drug discovery.
Precise microbiota engineering at the cellular level
U.S. Patent 10,752,906 (August 25, 2020)
Kevin M. Esvelt and Stephanie Yaung
Abstract: Stably immunized cells and methods of making stably immunized cells are provided. Methods of altering the microbiota of an ecological environment are provided. Methods of modifying target chromosomes are provided. Methods of delivering genetic material to target cells are provided.
Devices comprising muscle thin films and uses thereof in high throughput assays for determining contractile function
U.S. Patent 10,753,925 (August 25, 2020)
Kevin Kit Parker, Adam W. Feinberg, Patrick W. Alford, Anna Grosberg, Mark Daniel Brigham, and Josue A. Goss
Abstract: The present invention provides high throughput assays for identifying compounds that modulate a contractile function, as well as devices suitable for use in these assays.
Enhanced electrochemical detection using nanoparticles and precipitation
U.S. Patent 10,753,940 (August 25, 2020)
Donald E. Ingber, Olivier Y. F. Henry, and Michael Super
Abstract: The invention described herein relates generally to methods, sensors, devices and kits for electrochemical detection of a target analyte in a sample. In certain aspects, the methods, sensors, devices and kits described herein can be used to detect low concentrations of at least one target analyte using small sample volumes. In some embodiments, methods, sensors and kits for detecting a microbe, microbe fragment or released endotoxin in a test sample, including bodily fluids such as blood and tissues of a subject, food, water, and environmental surfaces, are also provided herein.
Methods and devices for live cell imaging analysis
U.S. Patent 10,755,078 (August 25, 2020)
Lee L. Rubin, Yasujiro Kiyota, Chieko Nakada, Keiichi Niikura, and Kathleen L. Pfaff
Abstract: Provided herein are methods for analysis of target cells on a population or individual basis, including before and after contact with a stimulus in order to determine the effect of such stimulus on the target cells. Also provided are devices for performing such methods. The analysis methods involve identifying and measuring or tracking morphological changes that occur in target cells over a period of time. Tracking is accomplished using imaging systems capable of imaging target cells individually over a period of time either continuously or at discrete intervals of time.