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April 5th, 2020

March 2020 patents

Innovations in soft robotics, modulating immune responses, CRISPR-Cas systems, single-cell sequencing, surgical catheter technology, and more

Harvard faculty George Whitesides, Arlene Sharpe, Uli von Andrian, Conor Walsh, Jennifer Lewis, David Weitz, Kit Parker, Joost Vlassak, Allon Klein, Marc Kirschner, David Liu, Pamela Silver, Daniel Nocera, Katia Bertoldi, Peng Yin, and William Shih are among the inventors issued U.S. patents in March 2020.

The innovations recognized are as follows:

Sensors for soft robots and soft actuators
U.S. Patent 10,576,643 (March 3, 2020)

Joshua Aaron Lessing, George M. Whitesides, Ramses V. Martinez, Dian Yang, Bobak Mosadegh, Kevin C. Galloway, Firat Guder, and Alok Suryavamsee Tayi

Abstract: A soft robotic device with one or more sensors is described. The sensor may be embedded in the soft body of the soft robotic device, attached to the soft body of the soft robotic device, or otherwise linked to the soft body of the soft robotic device.

Compositions and methods for modulating an immune response
U.S. Patent 10,577,586 (March 3, 2020)

Arlene H. Sharpe, Peter T. Sage, and Loise M. Francisco

Abstract: The invention provides methods of modulating follicular regulatory T (TFR) cell-mediated immune responses, follicular helper T (TFH) cell-mediated immune responses or both, and the use of those methods in the treatment of diseases or conditions mediated by TFR or TFH cells. The invention also provides novel methods for identifying TFR and TFH cells in a population of cells. The invention also provides compositions comprising TFR cells that have enhanced suppressive activity as compared wild type TFR cells. The invention also provides compositions comprising T follicular regulatory (TFR) cells isolated from the peripheral blood of a subject wherein the composition is enriched for TFR cells. Methods of making and using the compositions of the invention to modulate an immune response are also provided.

Delivery and use of the CRISPR-Cas systems, vectors and compositions for hepatic targeting and therapy
U.S. Patent 10,577,630 (March 3, 2020)

Feng Zhang, Le Cong, and Fei Ran

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Amphiphile-polymer particles
U.S. Patent 10,583,091 (March 10, 2020)

Jinjun Shi, Xi Zhu, Omid C. Farokhzad, Xiaoding Xu, Yanlan Liu, Aude Thiriot, and Ulrich Von Andrian

Abstract: This invention relates to amphiphile-polymer particles comprising obtaining a first solution comprising a water-insoluble polymer, a payload and a first amphiphile in a water-miscible solvent; mixing the first solution with an aqueous second solution to form an aqueous composition comprising a particle comprising a water-insoluble polymeric core comprising the water-insoluble polymer; the payload; and the first amphiphile.

Single cell nucleic acid detection and analysis
U.S. Patent 10,584,382 (March 10, 2020)

Xiaoliang Sunney Xie, Katsuyuki Shiroguchi, Peter A. Sims, and Tony Z. Jia

Abstract: Methods and compositions for digital profiling of nucleic acid sequences present in a sample are provided.

Soft buckling actuators
U.S. Patent 10,584,724 (March 10, 2020)

Dian Yang and George M. Whitesides

Abstract: A soft actuator is described, including: a rotation center having a center of mass; a plurality of bucklable, elastic structural components each comprising a wall defining an axis along its longest dimension, the wall connected to the rotation center in a way that the axis is offset from the center of mass in a predetermined direction; and a plurality of cells each disposed between two adjacent bucklable, elastic structural components and configured for connection with a fluid inflation or deflation source; wherein upon the deflation of the cell, the bucklable, elastic structural components are configured to buckle in the predetermined direction. A soft actuating device including a plurality of the soft actuators and methods of actuation using the soft actuator or soft actuating device disclosed herein are also described.

Catheter device for transmitting and reflecting light
U.S. Patent 10,588,695 (March 17, 2020)

Conor J. Walsh, Ellen T. Roche, Panagiotis Polygerinos, Lucia R. Schuster, Jeffrey Michael Karp, Yuhan Lee, Pedro J. del Nido, Assunta Fabozzo, Ingeborg Friehs, and Steven Charles Wasserman

Abstract: An insertable light-dispensing catheter device, comprising a shaft including a proximal and distal end, a light guide extending through the shaft, and a mirror displaceably extendable from the catheter into a position where the mirror receives and reflects light emitted from the light guide. The mirror can be in the form of a coating on an inflatable balloon; and the balloon, when inflated, can press a patch against a defect (e.g., a ventricular septical defect), while the light cures an adhesive that binds the patch to the structure with the defect, thereby remedying the defect.

Methods for preparation of concentrated graphene ink compositions and related composite materials
U.S. Patent 10,590,294 (March 17, 2020)

Mark C. Hersam, Yu Teng Liang, Ethan B. Secor, Pradyumna L. Prabhumirashi, Kanan P. Puntambekar, Michael L. Geier, Bok Y. Ahn, and Jennifer A. Lewis

Abstract: A rapid, scalable methodology for graphene dispersion and concentration with a polymer-organic solvent medium, as can be utilized without centrifugation, to enhance graphene concentration.

Systems and methods for biomimetic fluid processing
U.S. Patent 10,590,373 (March 17, 2020)

Jonathan N. Thon, Joseph E. Italiano, Linas Mazutis, and David A. Weitz

Abstract: Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.

Anisotropic muscular tissue devices with integrated electrical force readouts
U.S. Patent 10,591,458 (March 17, 2020)

Kevin Kit Parker, Johan Ulrik Lind, Jennifer Ann Lewis, Joost Johan Vlassak, Hongyan Yuan, Travis Alexander Busbee, Ian Perkins, and Christophe Chantre

Abstract: Embodiments described herein are directed to devices for supporting growth of anisotropic muscle tissue layers and in vitro readout and quantification of force generated by the tissue layers using one or more strain-sensing elements integrated into the device. Embodiments also include multiplexed apparatuses of multiple independent devices, methods of fabricating the devices and apparatuses, and methods of using the devices and apparatuses.

Systems and methods for barcoding nucleic acids
U.S. Patent 10,596,541 (March 24, 2020)

David A. Weitz, Allon Moshe Klein, Ilke Akartuna, Linas Mazutis, and Marc W. Kirschner

Abstract: The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets. In one set of embodiments, the nucleic acids may include "barcodes" or unique sequences that can be used to distinguish nucleic acids in a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together. In some cases, the unique sequences may be incorporated into individual droplets using particles and attached to nucleic acids contained within the droplets (for example, released from lysed cells). In some cases, the barcodes may be used to distinguish tens, hundreds, or even thousands of nucleic acids, e.g., arising from different cells or other sources.

Foam ink composition and 3D printed hierarchical porous structure
U.S. Patent 10,597,545 (March 24, 2020)

Jennifer A. Lewis and Joseph T. Muth

Abstract: A foam ink composition for printing porous structures comprises stabilizing particles and gas bubbles dispersed in a solvent. The stabilizing particles comprise a predetermined interfacial energy so as to exhibit a contact angle with the solvent of from about 15° to about 90°. At least a portion of the stabilizing particles are positioned at interfacial regions between the solvent and the gas bubbles, thereby stabilizing the gas bubbles in the foam ink composition. A 3D printed hierarchical porous structure comprises one or more continuous filaments arranged in a predetermined pattern on a substrate, the one or more continuous filaments comprising a sintered material and including a porosity of at least about 40 vol. %.

Switchable Cas9 nucleases and uses thereof
U.S. Patent 10,597,679 (March 24, 2020)

David R. Liu and Johnny Hao Hu

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an "on" or "off state, which control the binding and hence cleavage activity of RNA-programmable endo-nucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endo-nucleases based on the presence or absence of a target mRNA. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Carbon fixation systems and methods
U.S. Patent 10,597,681 (March 24, 2020)

Brendan Cruz Colon, Chong Liu, Marika Ziesack, Pamela Ann Silver, and Daniel G. Nocera

Abstract: Systems and methods for fixing carbon using bacteria are described. In one embodiment, a system includes a reactor chamber with a solution contained therein. The solution may include hydrogen (H2), carbon dioxide (CO2), bioavailable nitrogen, and a chemolithoautotrophic bacteria. The system may also include a pair of electrodes that split water contained within the solution to form the hydrogen. Additionally, the system may be operated so that a concentration of the bioavailable nitrogen in the solution is below a threshold nitrogen concentration to cause the chemolithoautotrophic bacteria to produce a product.

Dopant-driven phase transitions in correlated metal oxides
U.S. Patent 10,600,959 (March 24, 2020)

Jian Shi, You Zhou, and Shriram Ramanathan

Abstract: Reversible phase transitions of exceptional magnitude may be induced in correlated metal oxides by altering their chemical compositions through reversible introduction of dopant ions and electronic carriers into the correlated metal oxides. One or more catalyst electrodes may be deposited onto a surface of a film of a correlated metal oxide such as a perovskite or a transition metal oxide. Dopant ions and electronic carriers may be electrochemically introduced into the catalyst-deposited correlated metal oxide, for example by annealing the catalyst-deposited film of correlated metal oxide in a chamber containing the dopant molecules. In this way, a reversible phase transition of about five to eight orders of magnitude may be induced.

Hybrid dimple-and-void auxetic structures with engineered patterns for customized NPR behavior
U.S. Patent 10,603,866 (March 31, 2020)

Katia Bertoldi, Fabian Enrique Sanchez Guerrero, Farhad Javid, Francois Jette, Minh Quan Pham, Megan Schaenzer, and Ali Shanian

Abstract: Auxetic structures, low porosity auxetic sheets, systems and devices with auxetic structures, and methods of using and methods of making auxetic structures are disclosed. An auxetic structure is disclosed which includes an elastically rigid body with a plurality of apertures extending through the elastically rigid body and a plurality of protrusions projecting from the elastically rigid body. The apertures and protrusions are arranged in an engineered pattern, such as an array of rows and columns. The apertures are cooperatively configured with the protrusions to provide a predefined porosity while exhibiting stress reduction through negative Poisson's Ratio (NPR) behavior under macroscopic planar loading conditions. In some embodiments, the protrusions, which are elliptical or semispherical dimples, are interposed in square or hexagonal patterns with the apertures, which are S-shaped through slots or circular boreholes.

Lipids that increase insulin sensitivity and methods of using the same
U.S. Patent 10,604,473 (March 31, 2020)

Barbara B. Kahn, Mark A. Herman, Alan Saghatelian, and Edwin Homan

Abstract: The invention provides, inter alia, fatty acyl hydroxy fatty acid (FAHFA; a novel class of estolide-related molecules) and diagnostic and treatment methods for a variety of disorders--including diabetes-related disorders, Metabolic Syndrome, polycystic ovarian syndrome, cancer, and inflammatory disorders--using them; as well as methods of screening for additional compounds that are useful in treating these disorders and/or that modulate FAHFA levels, FAHFA-mediated signaling, and FAHFA-mediated biological effects.

Self-assembly of nucleic acid nanostructures
U.S. Patent 10,604,543 (March 31, 2020)

Peng Yin, William M. Shih, Yonggang Ke, and Luvena L. Ong

Abstract: The invention involves the synthesis of nucleic acid structures of controlled size and shape and comprised of a plurality of oligonucleotides. The structures are formed, at least in part, by the self-assembly of single-stranded oligonucleotides. The location of each oligonucleotide in the resultant structure is known. Accordingly, the structures may be modified with specificity.

Press Contact: Kirsten Mabry | (617) 495-4157