September 2017 patents
Innovations in fluid injection, sequencing polynucleotides, isolation of white blood cells, DNA origami devices, film deposition, and more
Harvard faculty David Scadden, George Church, David Weitz, Kevin Eggan, Clifford Woolf, David Mooney, Leonard Zon, Amy Wagers, David Liu, and Marko Loncar are among the inventors issued U.S. patents during September 2017.
The innovations recognized are as follows:
IL-18 inhibition for promotion of early hematopoietic progenitor expansion
U.S. Patent 9,750,767 (September 5, 2017)
David T. Scadden, Lev Silberstein, and Peter Kharchenko
Abstract: Disclosed herein are methods for enhancing hematopoietic reconstitution of a subject. One method involves administering a therapeutically effective amount of an inhibitor of IL-18 to a recipient subject and also administering hematopoietic stem/progenitor cells to the subject. Another method involves administering an inhibitor of IL-18 to a donor prior to harvest of hematopoietic stem/progenitor cells. Pharmaceutical compositions relating to the methods are also described.
Methods for sequencing nucleic acid molecules
U.S. Patent 9,752,178 (September 5, 2017)
Chao-ting Wu and George M. Church
Abstract: Methods and compositions for determining the nucleic acid sequence of polynucleotides that are at least 1500 nucleotides in length are provided.
U.S. Patent 9,757,698 (September 12, 2017)
David A. Weitz, Adam R. Abate, Tony Hung, and Pascaline Mary
Abstract: The present invention generally relates to systems and methods for the control of fluids and, in some cases, to systems and methods for flowing a fluid into and/or out of other fluids. As examples, fluid may be injected into a droplet contained within a fluidic channel, or a fluid may be injected into a fluidic channel to create a droplet. In some embodiments, electrodes may be used to apply an electric field to one or more fluidic channels, e.g., proximate an intersection of at least two fluidic channels. For instance, a first fluid may be urged into and/or out of a second fluid, facilitated by the electric field. The electric field, in some cases, may disrupt an interface between a first fluid and at least one other fluid. Properties such as the volume, flow rate, etc. of a first fluid being urged into and/or out of a second fluid can be controlled by controlling various properties of the fluid and/or a fluidic droplet, for example curvature of the fluidic droplet, and/or controlling the applied electric field.
Methods and apparatus for isolation of white blood cells using a multiposition valve
U.S. Patent 9,764,079 (September 19, 2017)
Amin I. Kassis
Abstract: Kits and methods provide for the isolation of white blood cells from bodily fluids. In one exemplary aspect, a method for isolating white blood cells from blood includes the act of adding a blood sample to a separation tube having a distal end, a proximal end, and a valve located proximate said proximal end, said valve being configured to transition between at least first, second, and third positions. The method also includes the act of removably attaching a cap to the distal end, centrifuging the separation tube with the valve in the first position, removing the cap at the distal end of the separation tube and removably attaching a first syringe to the proximal end, switching the valve to the second position and withdrawing, via the first syringe, a red blood cell sediment. The method also includes the act of switching the valve to the first position and removing the first syringe, adding a small volume of buffer to the separation tube, removably attaching a cap to the distal end and centrifuging the separation tube and removing the cap at the distal end of the separation tube and removably attaching a second syringe to the proximal end. Additional acts include switching the valve to the second position, withdrawing the remaining red blood cell sediment via the second syringe and switching the valve to the first position and removing the second syringe.
DNA origami devices
U.S. Patent 9,765,341 (September 19, 2017)
Ido Bachelet, Shawn Douglas, and George Church
Abstract: Provided herein are DNA origami devices useful in the targeted delivery of biologically active entities to specific cell populations.
Frizzled 2 as a target for therapeutic antibodies in the treatment of cancer
U.S. Patent 9,765,401 (September 19, 2017)
Taranjit S. Gujral and Gavin Macbeath
Abstract: Disclosed herein are methods of treating cancer in a subject, and methods for inhibiting growth, migration and/or invasion of a cancer cell in the subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that downmodulates Fzd2. The antibody may specifically bind Fzd2, and may promote internalization of the Fzd2 receptor by the cancer cells and/or prevent ligand binding to Fzd2. Specific antibodies, and also specific portions of the Fzd2 molecule for antibody binding are disclosed. In one embodiment the antibody specifically binds to the epitope HGAEQICVGQNHSEDGAPAL (SEQ ID NO: 1). Specific cancers (e.g. late stage hepatocellular carcinoma), intended for treatment are provided, and include cancers that exhibit overexpression of Fzd2, and/or Wnt5a.
Growing films via sequential liquid/vapor phases
U.S. Patent 9,765,429 (September 19, 2017)
Philippe P. Derouffignac
Abstract: A method for depositing a film on a polymer substrate is disclosed. The method includes exposing a polymer substrate to a liquid comprising a first reactant to provide a plurality of reactive sites over the polymer substrate, wherein the first reactant comprises aluminum or boron; and introducing a second reactant comprising silicon in a vapor form to said plurality of reactive sites that provide a catalytic growth of the film, wherein the growth of the film is self-limited. In certain embodiments, the film can include silica, aluminum silicate, or borosilicate.
Biosensors engineered from conditionally stable ligand-binding domains
U.S. Patent 9,766,255 (September 19, 2017)
George M. Church, Justin Feng, Daniel J. Mandell, David Baker, Stanley Fields, Benjamin Ward Jester, and Christine Elaine Tinberg
Abstract: Disclosed is a biosensor engineered to conditionally respond to the presence of specific small molecules, the biosensors including conditionally stable ligand-binding domains (LBDs) which respond to the presence of specific small molecules, wherein readout of binding is provided by reporter genes or transcription factors (TFs) fused to the LBDs.
Conversion of somatic cells into functional spinal motor neurons, and methods and uses thereof
U.S. Patent 9,770,471 (September 26, 2017)
Kevin Carl Eggan, Clifford J. Woolf, Brian J. Wainger, Justin K. Ichida, and Esther Yesde Son
Abstract: The present invention provides methods of transdifferentiation of somatic cells, for example, directly converting a somatic cell of a first cell type, e.g., a fibroblast into a somatic cell of a second cell type, are described herein. In particular, the present invention generally relates to methods for converting a somatic cell, e.g., a fibroblast into a motor neuron, e.g., an induced motor neuron (iMN) with characteristics of a typical motor neuron. The present invention also relates to an isolated population comprising induced motor neurons (iMNs), compositions and their use in the treatment of motor neuron diseases such as ALS and SMA. In particular, the present invention relates to direct conversion of a somatic cell to an induced motor neuron (iMN) having motor neuron characteristics by increasing the protein expression of at least three motor-neuron inducing (MN-inducing) factors selected from Lhx3, Ascl1, Brn2, Myt1l, Isl1, Hb9, Ngn2 or NeuroD1 in a somatic cell, e.g., a fibroblast to convert the fibroblast to an induced motor neuron (iMN) which exhibits at least two characteristics of an endogenous motor neuron.
Scaffolds for cell collection or elimination
U.S. Patent 9,770,535 (September 26, 2017)
David J. Mooney and Omar Abdel-Rahman Ali
Abstract: A device that includes a scaffold composition and a bioactive composition with the bioactive composition being incorporated therein or thereon, or diffusing from the scaffold composition such that the scaffold composition and/or a bioactive composition captures and eliminates undesirable cells from the body a mammalian subject. The devices mediate active recruitment, sequestration, and removal or elimination of undesirable cells from their host.
High-throughput image-based chemical screening in zebrafish blastomere cell culture
U.S. Patent 9,771,560 (September 26, 2017)
Leonard I. Zon, Cong Xu, Amy J. Wagers, and C. Ronald Kahn
Abstract: Disclosed are methods of inducing differentiation of stem into myogenic cells without gene manipulation and for inducing proliferation of satellite cells. The cells can be used as a source of cells for transplantation in a subject in need thereof. Also disclosed is a screening assay for screening test compounds using blastomere cultures.
Apparatus for continuous directed evolution of proteins and nucleic acids
U.S. Patent 9,771,574 (September 26, 2017)
David R. Liu and Kevin Michael Esvelt
Abstract: Aspects of the disclosure relate to an apparatus for continuous directed evolution of a gene of interest. In some embodiments, the apparatus comprises a cellstat and a turbidostat. In some embodiments, the apparatus is useful in methods of passing a nucleic acid from cell to cell in a desired function-dependent manner.
Biomedical and chemical sensing with nanobeam photonic crystal cavities using optical bistability
U.S. Patent 9,772,284 (September 26, 2017)
Qimin Quan, Marko Loncar, and Frank Vollmer
Abstract: A miniature optical biosensor and biosensor array where high sensitivity for detection of biomolecular interaction does not require a fluorescent label. Non-linear frequency-shifts of optical resonators ('nanobeams') provide a digital all-or-nothing response to equilibrium binding of a biomarker to surface-immobilized bio-recognition elements, a signal suitable to identify active components in genetic and proteomic circuits, as well as toxic substances. The threshold level for the digital response is adjustable to accommodate for varying receptor affinities. A bistable cavity sensing (BCS) method can be used to track the shift of the resonance induced by the analyte more precisely than the conventional cavity sensing method, where the resolution is limited by the cavity linewidth. BCS method can be used to quantitate the concentration of the analyte, and their binding kinetics, affinities and etc.