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April 1st, 2019

March 2019 patents

Innovations in reprogramming cells, compounds for activating killer T cells, polypeptides to modulate insulin receptors, analyte detection kits, slippery surfaces, and more

Harvard faculty Doug Melton, David Weitz, George Church, Jon Clardy, Greg Verdine, David Liu, Daniel Branton, Joanna Aizenberg, George Whitesides, Clifford Woolf, Bob Datta, Xiaowei Zhuang, and Jeffrey Moffitt are among the inventors issued U.S. patents in March 2019.

The innovations recognized are as follows:

Methods of reprogramming cells
U.S. Patent 10,221,393 (March 5, 2019)

Douglas A. Melton and Qiao Zhou

Abstract: The present invention provides methods of reprogramming cells, for example, directly reprogramming a somatic cell of a first cell type into a somatic cell of a second cell type, are described herein. In particular, the present invention generally relates to methods for reprogramming a cell of an endoderm origin to a cell having pancreatic β-cell characteristics. The present invention also relates to an isolated population comprising reprogrammed cells, compositions and their use in the treatment of diabetes mellitus. In particular, the present invention relates to reprogramming a cell of an endoderm origin to a cell having pancreatic β-cell characteristics by increasing the protein expression of at least one transcription factor selected from Pdx1, Ngn3 or MafA in the cell of endoderm origin to reprogram the cell of an endoderm cell to a cell which exhibits at least one or at least two characteristics of an endogenous pancreatic β-cell.

Assays and other reactions involving droplets
U.S. Patent 10,221,437 (March 5, 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.

Glycosphingolipids for use in modulating immune responses
U.S. Patent 10,227,290 (March 12, 2019)

Michael A. Fischbach, Jeffrey A. Bluestone, Cristina Penaranda, Laura Brown, and Jon Clardy

Abstract: Provided herein are sphingolipid compounds that are useful for activating natural killer T cells. Also provided are methods for treating or preventing a disease or disorder that is treatable by activating the immune system by stimulating natural killer T cells. The compounds are therefore useful for treating or reducing the likelihood of occurrence of an immune diseases and disorders, such as autoimmune diseases or disorders. The compounds may also be used for treating or reducing the likelihood of occurrence of a microbial infection or for treating or reducing the likelihood of occurrence of a cancer in a subject by administering the sphingolipid compounds described herein.

Stabilized polypeptide insulin receptor modulators
U.S. Patent 10,227,390 (March 12, 2019)

Gregory L. Verdine, Gerard Hilinski, Rebecca Yue Liang, Yvonne Alice Nagel, and Minyun Zhou

Abstract: Provided herein are stabilized α-CT polypeptides comprising an alpha-helical segment, and wherein the polypeptide is of Formula (I-1) or Formula (I-2):

Rf—[XAA]s—XA1—XA2—XA3—XA4—XA5—XA6—XA7—XA8—XA9—XA10—XA11—XA12—XA13—XA14—[XAA]t—Re (I-1)

Rf—[XAA]s—XC1—XC2—XC3—XC4—XC5—XC6—XC7—XC8—XC9—XC10—XC11—XC12—XC13—XC14—XC15—XC16—XC17—XC18—XC19—XC20—[XAA]t—Re (I-2)

wherein the α-CT polypeptide binds to the insulin receptor, and wherein the α-CT polypeptide includes at least one staple (i.e. two cross-linked amino acids) and/or at least one stitch (i.e. three cross-linked amino acids). Further provided are insulin analogs including the stapled or stitched α-CT polypeptides, pharmaceutical compositions thereof, methods of use, e.g., methods of treating a diabetic condition or complications thereof.

Engineered transcription activator-like effector (TALE) domains and uses thereof
U.S. Patent 10,227,581 (March 12, 2019)

David R. Liu, John Paul Guilinger, and Vikram Pattanayak

Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides engineered TALE domains and TALEs comprising such engineered domains, e.g., TALE nucleases (TALENs), TALE transcriptional activators, TALE transcriptional repressors, and TALE epigenetic modification enzymes, with improved specificity and methods for generating and using such TALEs.

Compositions and methods for analyte detection
U.S. Patent 10,227,639 (March 12, 2019)

Daniel Levner, Je-Hyuk Lee, George M. Church, and Michael Super

Abstract: The inventions provided herein relate to detection reagents, compositions, methods, and kits comprising the detection reagents for use in detection, identification, and/or quantification of analytes in a sample. Such detection reagents and methods described herein allow multiplexing of many more labeled species in the same procedure than conventional methods, in which multiplexing is limited by the number of available and practically usable colors.

Molecular characterization device
U.S. Patent 10,228,348 (March 12, 2019)

Daniel Branton and Jene A. Golovchenko

Abstract: Provided is a solid state support structure including an aperture having a molecular entrance and a molecular exit. A first reservoir is in fluidic communication with the molecular entrance of the aperture and contains a molecule-bearing liquid solution. A second reservoir is in fluidic communication with the molecular exit of the aperture for containing a molecule-bearing liquid solution. A first liquid channel is connected to the first reservoir within less than about 300 microns of the aperture in the support structure and includes molecule-bearing liquid solution for delivery to the first reservoir. A second liquid channel is connected to the second reservoir for accepting molecule-bearing liquid solution from the second reservoir. An electrical connection between the first reservoir and the second reservoir imposes an electrical bias between the first reservoir and the second reservoir for driving the molecule-bearing liquid solution through the aperture in the solid state support structure.

Containers, bottles, drums, vats, and tanks having a slippery surface
U.S. Patent 10,233,334 (March 19, 2019)

Joanna Aizenberg, Michael Aizenberg, Sung Hoon Kang, Philseok Kim, and Tak Sing Wong

Abstract: The present disclosure describes a strategy to create self-healing, slippery liquid-infused porous surfaces. Roughened (e.g., porous) surfaces can be utilized to lock in place a lubricating fluid, referred to herein as Liquid B to repel a wide range of materials, referred to herein as Object A (Solid A or Liquid A). Slippery liquid-infused porous surfaces outperforms other conventional surfaces in its capability to repel various simple and complex liquids (water, hydrocarbons, crude oil and blood), maintain low-contact-angle hysteresis (<2.5°), quickly restore liquid-repellency after physical damage (within 0.1-1 s), resist ice, microorganisms and insects adhesion, and function at high pressures (up to at least 690 atm). Some exemplary application where slippery liquid-infused porous surfaces will be useful include energy-efficient fluid handling and transportation, optical sensing, medicine, and as self-cleaning, and anti-fouling materials operating in extreme environments.

Flexible thin robotic actuators
U.S. Patent 10,233,910 (March 19, 2019)

Aaron D. Mazzeo, Stephen A. Morin, Robert F. Shepherd, George M. Whitesides, and William B. Kalb

Abstract: Some embodiments of the disclosed subject matter includes a laminated robotic actuator. The laminated robotic actuator includes a strain-limiting layer comprising a flexible, non-extensible material in the form of a sheet or thin film, a flexible inflatable layer in the form of a thin film or sheet in facing relationship with the strain-limiting layer, wherein the inflatable layer is selectively adhered to the strain-limiting layer, and wherein a portion of an un-adhered region between the strain-limiting layer and the inflatable layer defines a pressurizable channel, and at least one fluid inlet in fluid communication with the pressurizable channel. The first flexible non-extensible material has a stiffness that is greater than the stiffness of the second flexible elastomeric material and the flexible elastomer is non-extensible under actuation conditions.

Devices and methods for analyzing rodent behavior
U.S. Patent 10,238,085 (March 26, 2019)

Clifford J. Woolf, David P. Roberson, Alexander B. Wiltschko, and Sandeep Robert Datta

Abstract: A device for detecting and recording animal behavior is provided. The device includes at least one corral that defines contained field, the base surface of the at least one corral being sensitive to the animal's footprint. The device also includes an image capturing device that cooperates with the base surface to capture both a profile of the animal's full footprint and a profile of the animal's toe print when the animal is standing on its toes. In some embodiments, the device is capable of providing a stimulus to the animal and observing the resulting behavior of the animal via the image capturing device.

Probe library construction
U.S. Patent 10,240,146 (March 26, 2019)

Xiaowei Zhuang, Jeffrey R. Moffitt, and Alistair Boettiger

Abstract: The present invention generally relates to systems and methods for producing nucleic acids. In some aspects, relatively large quantities of oligonucleotides can be produced, and in some cases, the oligonucleotides may have a variety of different sequences and/or lengths. For instance, a relatively small quantity of oligonucleotides may be amplified to produce a large amount of nucleotides. In one set of embodiments, oligonucleotides may be amplified using PCR, then transcribed to produce RNA. The RNA may then be reverse transcribed to produce DNA, and optionally, the RNA may be selectively degraded or removed, relative to the DNA. In one set of embodiments, the oligonucleotides may be chemically modified. These modifications may include, but are not limited, to the adding of fluorescent dyes or other signaling entities.

Tags: Issued Patents

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