December 2019 patents
Innovations in targeting genome editors, synthesizing cortistatin analogues, systems to modulate cardiac rhythm using light, microfluidic devices, and more
Harvard faculty Don Ingber, Chao-ting Wu, Junying Yuan, Matthew Shair, Brian Liau, David Weitz, George Church, David R. Liu, and Kit Parker are among the inventors issued U.S. patents in December 2019.
The innovations recognized are as follows:
Engineered heme-binding compositions and uses thereof
U.S. Patent 10,501,729 (December 10, 2019)
Michael Super, Alexander L. Watters, Philip T. Snell, and Donald E. Ingber
Abstract: Described herein are heme-binding compositions and methods relating to their use, for example methods of treatment of sepsis and rhabdomyolysis.
U.S. Patent 10,501,779 (December 10, 2019)
Chao-ting Wu and Brian Beliveau
Abstract: Novel methods and compositions for identifying one or more factors associated with a nucleic acid sequence (e.g., DNA and/or RNA) of interest are provided.
Inhibitors of cellular necrosis and related methods
U.S. Patent 10,508,102 (December 17, 2019)
Junying Yuan, Yijun Zhou, Shan Qian, and Dawei Ma
Abstract: A compound having the following structure (I):
or a pharmaceutically acceptable salt, prodrug, stereoisomer or tautomer thereof, is provided. Related compounds, methods for preparation of the same and uses of the compounds for treatment of various indications, including treatment of necrotic cell diseases and/or inflammation, are also provided.
Cortistatin analogues and syntheses and uses thereof
U.S. Patent 10,508,121 (December 17, 2019)
Matthew D. Shair, Juergen Ramharter, Henry Efrem Pelish, Brian Bor-Jen Liau, and Jae Young Ahn
Abstract: Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof.
Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the ?-catenin pathway, methods of modulating STAT 1 activity, methods of modulating the TGFβ/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.
Assays and other reactions involving droplets
U.S. Patent 10,508,294 (December 17, 2019)
David A. Weitz, Jeremy Agresti, Liang-Yin Chu, Jin-Woong Kim, Amy Rowat, Morten Sommer, Gautam Dantas, and George 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.
Methods for identifying a target site of a CAS9 nuclease
U.S. Patent 10,508,298 (December 17, 2019)
David R. Liu and Vikram Pattanayak
Abstract: Some aspects of this disclosure provide strategies, methods, and reagents for determining nuclease target site preferences and specificity of site-specific endonucleases. Some methods provided herein utilize a novel "one-cut" strategy for screening a library of concatemers comprising repeat units of candidate nuclease target sites and constant insert regions to identify library members that can been cut by a nuclease of interest via sequencing of an intact target site adjacent and identical to a cut target site.
CRP capture/detection of gram positive bacteria
U.S. Patent 10,513,546 (December 24, 2019)
Alexander L. Watters, Donald E. Ingber, Mark J. Cartwright, Michael Super, Martin Rottman, Evangelia Murray, and Brendon Dusel
Abstract: Described herein are engineered microbe-targeting molecules, microbe-targeting articles, kits comprising the same, and uses thereof. Such microbe-targeting molecules, microbe-targeting articles, or the kits comprising the same can bind or capture of a microbe or microbial matter thereof, and can thus be used in various applications, such as diagnosis or treatment of an infection caused by microbes in a subject or any environmental surface.
Photosensitive cardiac rhythm modulation systems
U.S. Patent 10,518,107 (December 31, 2019)
Kevin Kit Parker
Abstract: Photosensitive cardiac rhythm modulation structures and systems are described. A genetically-engineered tissue comprising a population of pacing cells expressing a photosensitive membrane transport mechanism that is responsive to light of a particular wavelength(s) combined with one or more of a light source, a power generator, and a sensor provides pacemaker and/or defibrillator function to a subject. The systems further provide in vitro model systems for electrophysiological studies.
Scale-up of microfluidic devices
U.S. Patent 10,518,230 (December 31, 2019)
David A. Weitz, Mark Romanowsky, and Adam R. Abate
Abstract: 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.
Immersed rotary jet spinning devices (IRJS) and uses thereof
U.S. Patent 10,519,569 (December 31, 2019)
Kevin Kit Parker, Grant Michael Gonzalez, Holly M. Golecki, Kwanwoo Shin, and Josue Adrian Goss
Abstract: Exemplary embodiments provide systems, devices and methods for the fabrication of three-dimensional polymeric fibers having micron, submicron and nanometer dimensions, as well as methods of use of the polymeric fibers.