Harvard faculty David Liu, Marc Kirschner, Stuart Schreiber, Stephen Haggarty, Bruce Bean, George Church, Conor Walsh, Uli von Andrian, Doug Melton, Min Dong, Peng Yin, Gary King, and Eric Mazur are among the inventors issued U.S. patents in January 2019.

The innovations recognized are as follows:

Nucleobase editors and uses thereof
U.S. Patent 10,167,457 (January 1, 2019)

David R. Liu, Alexis Christine Komor, Holly A. Rees, and Yongjoo Kim

Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing proteins or protein domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing proteins or domains, are provided.

Cancer treatment and immune system regulation through FAT10 pathway inhibition
U.S. Patent 10,167,469 (January 1, 2019)

Yifat Merbl and Marc W. Kirschner

Abstract: Described herein are methods of inhibiting mitosis, treating cancer and/or treating immune disorders through the use of agents that inhibit FAT10 and/or the FAT10 pathway.

Histone deacetylase inhibitors
U.S. Patent 10,172,821 (January 8, 2019)

James Elliot Bradner and Ralph Mazitschek

Abstract: In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.

Treatment of protein degradation disorders
U.S. Patent 10,172,905 (January 8, 2019)

Kenneth C. Anderson, James E. Bradner, Edward Franklin Greenberg, Teru Hideshima, Nicholas Paul Kwiatkowski, Ralph Mazitschek, Stuart L. Schreiber, Jared Shaw, and Stephen J. Haggarty

Abstract: The invention relates to methods of treating protein degradation disorders, such cellular proliferative disorders (e.g., cancer) and protein deposition disorders (e.g., neurodegenerative disorders). The invention provides methods and pharmaceutical compositions for treating these diseases using aggresome inhibitors or combinations of aggresome inhibitors and proteasome inhibitors. The invention further relates to methods and pharmaceutical compositions for treating multiple myeloma. New HDAC/TDAC inhibitors and aggresome inhibitors are also provided as well as synthetic methodologies for preparing these compounds.

Methods, compositions, and kits for treating pain and pruritis
U.S. Patent 10,179,116 (January 15, 2019)

Bruce P. Bean and Clifford J. Woolf

Abstract: The invention features a method for inhibiting one or more voltage-gated ion channels in a cell by contacting the cell with (i) a first compound that activates a channel-forming receptor that is present on nociceptors and/or pruriceptors; and (ii) a second compound that inhibits one or more voltage-gated ion channels when applied to the internal face of the channels but does not substantially inhibit said channels when applied to the external face of the channels, wherein the second compound is capable of entering nociceptors or pruriceptors through the channel-forming receptor when the receptor is activated. The invention also features a quarternary amine derivative or other permanently or transiently charged derivative of a compound that inhibits one or more voltage-gated ion channels when applied to the internal face of the channels but does not substantially inhibit said channels when applied to the external face of the channels.

Negative selection and stringency modulation in continuous evolution systems
U.S. Patent 10,179,911 (January 15, 2019)

David R. Liu, Jacob Charles Carlson, Ahmed Hussein Badran, and Kevin Michael Esvelt

Abstract: Strategies, systems, methods, reagents, and kits for phage-assisted continuous evolution are provided herein. These include strategies, systems, methods, reagents, and kits allowing for stringency modulation to evolve weakly active or inactive biomolecule variants, negative selection of undesired properties, and/or positive selection of desired properties.

Methods for high-throughput labelling and detection of biological features in situ using microscopy
U.S. Patent 10,179,932 (January 15, 2019)

George M. Church, Je-Hyuk Lee, and Evan R. Daugharthy

Abstract: Methods of labelling one or more subcellular components (e.g., an organelle and/or subcellular region) in vivo are provided. Methods of labelling a protein in vivo are provided. Methods of determining a nucleic acid sequence in situ are also provided.

Multi-segment reinforced actuators and applications
U.S. Patent 10,184,500 (January 22, 2019)

Kevin Galloway, Conor Walsh, Donal Holland, Panagiotis Polygerinos, Tyler Clites, Paxton Maeder-York, Ryan Neff, Emily Marie Boggs, and Zivthan Dubrovsky

Abstract: A multi-segment reinforced actuator includes (a) a soft actuator body that defines a chamber and (b) a plurality of distinct reinforcement structures on or in respective segments of the soft actuator body. First and second reinforcement structures are respectively configured to produce a first and second actuation motions, respectively, in first and second segments of the soft actuator or body when fluid flows into or out of the chamber. The actuation motions are selected bending, extending, expansion, contraction, twisting, and combinations thereof; and the first actuation motion differs from the second actuation motion. The actuator can be used, e.g., to facilitate bending of the thumb with corresponding bending, extending, expansion, contraction, and twisting actuation motions.

Vaccines comprising bisphosphonate and methods of use thereof
U.S. Patent 10,188,733 (January 29, 2019)

Ulrich H. von Andrian, Matteo Iannacone, Elena Tonti, and Elliott Ashley Moseman

Abstract: The present invention demonstrates that bisphosphonates have an intrinsic adjuvant activity and directly stimulate B cell antibody secretion. Accordingly, the present invention provides vaccines comprising a bisphosphonate, methods for stimulating an immune response, enhancing the immunogenicicty of an immunogen, and methods of treating an infection, an autoimmune disease, an allergy, and/or a cancer using the same.

Actuators with conforming sleeves
U.S. Patent 10,189,165 (January 29, 2019)

Kevin Galloway

Abstract: An actuator includes at least one actuator body and a sleeve covering a portion of the actuator body. The actuator body comprises a first material, and the sleeve comprises a second material that is more rigid than the first material. The sleeve constrains bending of the actuator body where the sleeve covers the actuator body.

Thioamide-modified peptides and uses thereof
U.S. Patent 10,189,884 (January 29, 2019)

E. James Petersson and Alan Saghatelian

Abstract: The invention includes a thioamide-modified peptide, wherein the thioamide modification increases the in vivo half-life of the peptide. The invention further includes methods of treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a thioamide-modified peptide of the invention.

Methods for generating stem cell-derived β cells and uses thereof
U.S. Patent 10,190,096 (January 29, 2019)

Douglas A. Melton and Jeffrey R. Millman

Abstract: Disclosed herein are methods for generating SC-β cells, and isolated populations of SC-β cells for use in various applications, such as cell therapy.

Engineered botulinum neurotoxin
U.S. Patent 10,190,110 (January 29, 2019)

Min Dong, Lisheng Peng, Pal Erik Gustav Stenmark, Ronnie Per Arne Berntsson

Abstract: Disclosed herein are botulinum neurotoxin (BoNT) polypeptides with a modified receptor binding domain of Clostridial botulinum serotype B (B-H_c), comprising one or more substitution mutations corresponding to substitution mutations in serotype B, strain 1, V1118M; Y1183M; E1191M; E1191I; E1191Q; E1191T; S1199Y; S1199F; S1199L; S1201V; or combinations thereof. Specific combination mutations include E1191M and S1199L, E1191M and S1199Y, E1191M and S1199F, E1191Q and S1199L, E1191Q and S1199Y, or E1191Q and S1199F. Other substitution mutations are also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical compositions, and methods of using the same are also disclosed.

High-throughput and highly multiplexed imaging with programmable nucleic acid probes
U.S. Patent 10,190,151 (January 29, 2019)

Peng Yin, Sarit Agasti, Xi Chen, and Ralf Jungmann

Abstract: The present invention provides, inter alia, methods and compositions for imaging, at high spatial resolution, targets of interest.

Stimulating online discussion in interactive learning environments
U.S. Patent 10,192,456 (January 29, 2019)

Gary King, Eric Mazur, Kelly Miller, and Brian Lukoff

Abstract: In various embodiments, online discussions in connection with an educational resource are improved by analyzing annotations made by students assigned to a discussion group to identify high-quality annotations likely to generate responses and stimulate discussion threads and by making the identified annotations visible to students not assigned to the discussion group.