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November 1st, 2018

October 2018 patents

Innovations in robotics, rejuvenation of muscle stem cells, new Cas9 proteins, DNA base editors, ways to detect overstriding in runners, and more

Harvard faculty Radhika Nagpal, Don Ingber, Kit Parker, Amy Wagers, Rich Lee, Gerhard Wagner, Peng Yin, George Church, Conor Walsh, Rob Wood, Wendy Garrett, Dan Kahne, Suzanne Walker, David Liu, and Daniel Lieberman are among the inventors issued U.S. patents in October 2018.

The innovations recognized are as follows:

Membrane-based fluid-flow control devices
U.S. Patent 10,086,372 (October 2, 2018)

Guy Thompson, Daniel Levner, and Christopher David Hinojosa

Abstract: Described herein are fluid-flow control devices for transferring a fluid from a place to another and/or controlling a fluid flow. In some embodiments, fluid-flow control devices described herein can be used as pumping devices to transfer a fluid by peristaltic motion and/or as valve devices to control fluid flow for various applications, e.g., in a microfluidic platform.

Color- or grayscale-sensing, magnetic, mobile, marking robot
U.S. Patent 10,086,516 (October 2, 2018)

Zivthan A. Dubrovsky, Raphael G. Cherney, Michael Mogenson, Justin Werfel, Kathleen O'Donnell, Radhika Nagpal, Nils Napp, Hani M. Sallum, and Julian U. da Silva Gillig

Abstract: In a method for interactive marking by a mobile robot on a vertical surface, a mobile robot that includes a sensor and an actuated marker is displaced across a vertical surface. Features on, in or behind the vertical surface are detected with the sensor. Displacement of the mobile robot and actuation of the actuated marker is controlled in response to the detection of these features.

Organ chips and uses thereof
U.S. Patent 10,087,422 (October 2, 2018)

Donald E. Ingber, Kevin Kit Parker, Geraldine A. Hamilton, and Anthony Bahinski

Abstract: Disclosed herein are organ chips that can be individually used or integrated together to form different microphysiological systems, e.g., for use in cell culturing, drug screening, toxicity assays, personalized therapeutic treatment, scaffolding in tissue repair and/or replacement, and/or pharmacokinetic or pharmacodynamics studies.

Methods and compositions for rejuvenating skeletal muscle stem cells
U.S. Patent 10,092,627 (October 9, 2018)

Amy J. Wagers and Richard T. Lee

Abstract: Methods and compositions for rejuvenating skeletal muscle stem cells are disclosed.

Methods and apparatus for sample temperature control in NMR spectrometers
U.S. Patent 10,094,892 (October 9, 2018)

Sebastian Hiller and Gerhard Wagner

Abstract: Described are methods and apparatus, referred to as "temperature-lock," which can control and stabilize the sample temperature in an NMR spectrometer, in some instances with a precision and an accuracy of below about 0.1 K. In conventional setups, sample heating caused by experiments with high-power radio frequency pulses is not readily detected and is corrected by a cumbersome manual procedure. In contrast, the temperature-lock disclosed herein automatically maintains the sample at the same reference temperature over the course of different NMR experiments. The temperature-lock can work by continuous or non-continuous measurement of the resonance frequency of a suitable temperature-lock nucleus and simultaneous adaptation of a temperature control signal to stabilize the sample at a reference temperature value. Inter-scan periods with variable length can be used to maintain the sample at thermal equilibrium over the full length of an experiment.

Scalable nucleic acid-based nanofabrication
U.S. Patent 10,099,920 (October 16, 2018)

Jie Shen, Wei Sun, and Peng Yin

Abstract: The present disclosure relates to the alignment of moieties (e.g., nanoparticles and/or nanowires) into prescribed architectures on two- and/or three-dimensional substrates (e.g., nucleic acid nanostructures/crystals). The present disclosure also relates to a nucleic acid (e.g., DNA) lithography method that includes, in some embodiments, adsorbing a bare nucleic acid nanostructure onto a surface of a substrate, and etching the surface of the substrate containing the bare nucleic acid nanostructure, thereby producing a patterned substrate.

Mutant Cas9 proteins
U.S. Patent 10,100,291 (October 16, 2018)

Alejandro Chavez, Frank Poelwijk, and George M. Church

Abstract: Methods of making deletion mutants of Cas9 proteins and making chimeric Cas9 proteins are described. The Cas9 N- and C-terminal domains may play critical roles in crRNAitracrRNA binding and/or PAM selectivity. To analyze activity, a series of domain exchange mutants between NM and STI (Streptococcus thermophilus Cas9) were made, replacing the N and/or C terminus of NM (Neisseria meningitides Cas9) with the homologous region from STI. The chimeric proteins were then tested using the transcriptional reporter assay described herein altering the guideRNA and/or Cas9 specific PAM within the reporter to determine the influence of the domain exchanges on protein specificity. None of the N-terminal domain swaps between NM and STI endowed NM with novel properties. The C-terminal exchange generated a NM-STI hybrid that was capable of interacting with the STI crRNAitracrRNA complex and was further able to suppress a reporter with a STI specific PAM.

Methods of determining polymorphisms
U.S. Patent 10,100,349 (October 16, 2018)

Iain J. Macleod, Christopher F. Rowley, and Max Essex

Abstract: Methods and compositions for determining the presence of a polymorphism at a target nucleotide position in a plurality of target nucleic acid sequences is provided.

Creation of nearly-equivalent nuclear spin singlet states using spin-lock induced crossing
U.S. Patent 10,101,423 (October 16, 2018)

Stephen J. Devience, Ronald L. Walsworth, and Matthew S. Rosen

Abstract: Methods and systems for Nuclear Magnetic Resonance (NMR) spectra of samples having unresolved peaks are described. The methods and systems allow for the creation nuclear spin singlet states in nearly-equivalent spin pairs, for example, using continuous spin-locking with a nutation frequency matched to the coupling strength between spins. The invention relates generally to the field Nuclear Magnetic Resonance (NMR). Nuclear magnetic resonance (NMR) spectroscopy can be used as a tool for determining the chemical structure and/or geometry of a molecule in a sample. In many samples, however, resonance frequencies of different nuclei fully or partially overlap, which makes chemical identification of molecule(s) in a sample difficult or impossible.

Modular, millimeter-scale, light-intensity-based force sensing system
U.S. Patent 10,105,035 (October 23, 2018)

Joshua Gafford, Conor J. Walsh, and Robert J. Wood

Abstract: A light-intensity-based forced sensor comprises a Sarrus linkage, a biasing mechanism, a light emitter, and a light detector includes a first plate, a second plate, and at least one collapsible linkage pivotably coupled to both the first and the second plates. The biasing mechanism biases the collapsible linkage toward an extended configuration. The light emitter is coupled with and displaceable with the first plate; and the light detector is coupled with and displaceable with the second plate and configured to receive light emitted from the light emitter and generate an electrical signal in response to light received from the light emitter, wherein the generated electrical signal provides an indication of the distance between the first plate and the second plate. The sensor can be distally mounted on, e.g., an endoscope to provide haptic feedback at the distal end of the endoscope.

Modulation of regulatory T cells via G-coupled protein receptor 43
U.S. Patent 10,105,329 (October 23, 2018)

Wendy S. Garrett and Patrick M. Smith

Abstract: Disclosed herein are compositions and methods that are useful for inducing the development of regulatory T cells (Treg). Such compositions and methods are useful for treating inflammatory conditions and in particular inflammatory conditions affecting the gastrointestinal tract of a subject. In certain embodiments, the present inventions generally relate to short chain fatty acids and the discovery that such short chain fatty acids may be used to treat and/or prevent inflammatory conditions by enhancing the size and immune function of a subject's endogenous Treg population.

Methods and compounds for identifying glycosyltransferase inhibitors
U.S. Patent 10,106,833 (October 23, 2018)

Daniel Evan Kahne, Suzanne Walker Kahne, Christian M. Gampe, and Hirokazu Tsukamoto

Abstract: The present invention provides moenomycin-based probe compounds of Formula (I) for use in screening inhibitors of bacterial glycosyltransferases. The present invention also provides bacterial glycosyltransferase screening assays using compounds of Formula (I).

Adenosine nucleobase editors and uses thereof
U.S. Patent 10,113,163 (October 30, 2018)

David R. Liu and Nicole Gaudelli

Abstract: The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins further comprise a nuclear localization sequence (NLS), and/or an inhibitor of base repair, such as, a nuclease dead inosine specific nuclease (dISN).

Methods and assays for factor VIII activity
U.S. Patent 10,114,017 (October 30, 2018)

Gary Eugene Gilbert, Jialan Shi, and Valerie A. Novakovic

Abstract: The methods and compositions described herein relate to the measurement of factor VIII (fVIII) levels and/or activity.

Systems and methods for detecting overstriding in runners
U.S. Patent 10,115,319 (October 30, 2018)

Conor J. Walsh, Stephanie Hsiang-Ting Liu, Panagiotis Polygerinos, and Daniel E. Lieberman

Abstract: Methods and systems for detecting overstride in runners include measuring, using an inertial measurement unit affixed to a shank of a person, an acceleration and an angle of the shank during a stride, monitoring, using a microprocessor, the shank acceleration measurements to detect an acceleration profile indicative of the corresponding foot making initial contact with the ground during the stride, determining, using the microprocessor, the corresponding shank angle at initial contact from the shank angle measurements, comparing, using the microprocessor, the shank angle at initial contact to a threshold shank angle, and identifying, using the microprocessor, an overstride of the corresponding leg if the shank angle at initial contact exceeds the threshold shank angle.

Tags: Issued Patents

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