Harvard faculty Andrew Myers, Lee Rubin, David Weitz, David Mooney, David Liu, George Church, Steven McCarroll, Rob Wood, George Whitesides, Gary King, Eric Mazur, Don Ingber, and Peng Yin are among the inventors issued U.S. patents in June 2020.

The innovations recognized are as follows:

Synthesis of tetracyclines and analogues thereof
U.S. Patent 10,669,244 (June 2, 2020)

Andrew G. Myers, Mark G. Charest, Christian D. Lerner, Jason D. Brubaker, and Dionicio R. Siegel

Abstract: The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The modular synthesis of tetracyclines and tetracycline analogs described provides an efficient and enantioselective route to a variety of tetracycline analogs and polycyclines previously inaccessible via earlier tetracycline syntheses and semi-synthetic methods. These analogs may be used as anti-microbial agents or anti-proliferative agents in the treatment of diseases of humans or other animals.

Methods and compositions relating to hematopoietic stem cell expansion, enrichment, and maintenance
U.S. Patent 10,669,528 (June 2, 2020)

Derrick J. Rossi, Wataru Ebina, Morag Stewart, Paula Gutierrez-Martinez, Lee L. Rubin, and Lance Davidow

Abstract: The methods and compositions described herein relate to producing, expanding, enriching, and/or maintaining hematopoietic stem cells ex vivo by treating the cells with an agent(s) that exhibits two or more activities selected from modulation of histone methylation; inhibition of TGFβ signaling; inhibition of p38 signaling; activation of canonical Wnt signaling; and modulation of histone acetylation. In some embodiments, the technology described herein relates to transplantation of hematopoietic stem cells.

CRISPR enzymes and systems
U.S. Patent 10,669,540 (June 2, 2020)

Feng Zhang, Bernd Zetsche, Ian Slaymaker, Jonathan Gootenberg, and Omar O. Abudayyeh

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Manipulation of fluids, fluid components and reactions in microfluidic systems
U.S. Patent 10,675,626 (June 9, 2020)

Seth Fraden, Hakim Boukellal, Yanwei Jia, Seila Selimovic, Amy Rowat, Jeremy Agresti, and David A. Weitz

Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.

Combination vaccine devices and methods of killing cancer cells
U.S. Patent 10,682,400 (June 16, 2020)

Omar Abdel-Rahman Ali, David J. Mooney, and Glenn Dranoff

Abstract: The present invention comprises compositions, methods, and devices for enhancing an endogenous immune response against a cancer. Devices and methods provide therapeutic immunity to subjects against cancer.

Delivery system for functional nucleases
U.S. Patent 10,682,410 (June 16, 2020)

David R. Liu, John Anthony Zuris, and David B. Thompson

Abstract: Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases. Compositions, methods, strategies, and systems for the delivery of functional effector proteins into cells is useful for therapeutic and research purposes, including, but not limited to, the targeted manipulation of a gene associated with disease, the modulation of the expression level of a gene associated with disease, and the programming of cell fate.

Mutant Cas9 proteins
U.S. Patent 10,683,490 (June 16, 2020)

Alejandro Chavez, Frank J. Poelwijk, and George M. Church

Abstract: Methods of making mutant Cas9 proteins are described.

Assays and other reactions involving droplets
U.S. Patent 10,683,524 (June 16, 2020)

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.

Clonal haematopoiesis
U.S. Patent 10,683,552 (June 16, 2020)

Steven Andrew McCarroll and Giulio Genovese

Abstract: The present invention relates to clonal expansion of somatic cells in subjects, and acquired selective advantage of cell clones during the lifetime of a subject. In particular, the invention relates to methods for predicting the development of cancer based on the observation of specific genetic mutations in somatic cell clones, as well as to methods for treating or preventing cancer in a subject, in which clonal expansion of cells comprising specific modifications is observed.

Enhancing diagnosis of disorder through artificial intelligence and mobile health technologies without compromising accuracy
U.S. Patent 10,687,751 (June 23, 2020)

Dennis Wall

Abstract: A computer system for generating a diagnostic tool by applying artificial intelligence to an instrument for diagnosis of a disorder, such as autism. For autism, the instrument can be a caregiver-directed set of questions designed for an autism classification tool or an observation of the subject in a video, video conference, or in person and associated set of questions about behavior that are designed for use in a separate autism classification tool. The computer system can have one or more processors and memory to store one or more computer programs having instructions for generating a highly statistically accurate set of diagnostic items selected from the instrument, which are tested against a first test using a technique using artificial intelligence and a second test against an independent source. Also, a computer implemented method and a non-transitory computer-readable storage medium are disclosed.

Resilient, untethered soft robot
U.S. Patent 10,689,044 (June 23, 2020)

Michael T. Tolley, Robert F. Shepherd, Bobak Mosadegh, Robert J. Wood, and George M. Whitesides

Abstract: A pneumatically powered, fully untethered mobile soft robot is described. Composites consisting of silicone elastomer, polyaramid fabric, and hollow glass microspheres were used to fabricate a sufficiently large soft robot to carry the miniature air compressors, battery, valves, and controller needed for autonomous operation. Fabrication techniques were developed to mold a 0.65 meter long soft body with modified Pneumatic network actuators capable of operating at the elevated pressures (up to 138 kPa) required to actuate the legs of the robot and hold payloads of up to 8 kg. The soft robot is safe to handle, and its silicone body is innately resilient to a variety of adverse environmental conditions including snow, puddles of water, direct (albeit limited) exposure to flames, and the crushing force of being run over by an automobile.

Instructional support platform for interactive learning environments
U.S. Patent 10,692,391 (June 23, 2020)

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

Abstract: In various embodiments, subject matter for improving discussions in connection with an educational resource is identified and summarized by analyzing annotations made by students assigned to a discussion group to identify high-quality annotations likely to generate responses and stimulate discussion threads, identifying clusters of high-quality annotations relating to the same portion or related portions of the educational resource, extracting and summarizing text from the annotations, and combining, in an electronically represented document, the extracted and summarized text and (i) at least some of the annotations and the portion or portions of the educational resource or (ii) clickable links thereto.

Scaffolds for cell collection or elimination
U.S. Patent 10,695,468 (June 30, 2020)

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.

Microbe-binding molecules and uses thereof
U.S. Patent 10,696,733 (June 30, 2020)

Alexander Watters, Brendon Dusel, Michael Super, Mark Cartwright, and Donald E. Ingber

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 not only bind or capture of a microbe or microbial matter thereof, but they also have improved capability (e.g., enhanced sensitivity or signal intensity) of detecting a microbe or microbial matter. Thus, the microbe-targeting molecules, microbe-targeting articles, and/or the kit described herein can be used in various applications, e.g., but not limited to assays for detection of a microbe or microbial matter, diagnostic and/or therapeutic agents for diagnosis and/or treatment of an infection caused by microbes in a subject or any environmental surface, and/or devices for removal of a microbe or microbial matter from a fluid.

Protected guide RNAS (PGRNAS)
U.S. Patent 10,696,986 (June 30, 2020)

Feng Zhang, Omar O. Abudayyeh, James E. Dahlman, Patrick Hsu, and David A. Scott

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5' additions to the guide sequence.

Methods and compositions for protein identification
U.S. Patent 10,697,974 (June 30, 2020)

Sungwook Woo and Peng Yin

Abstract: Provided herein, in some embodiments, are methods and compositions for protein identification.

Method and apparatus for using gait analysis to determine a health quality measure
U.S. Patent 10,699,205 (June 30, 2020)

Saeed S. Ghassemzadeh, Lusheng Ji, Robert Raymond Miller II, Manish Gupta, and Vahid Tarokh

Abstract: A method, computer-readable storage device and apparatus for calculating a health quality measure are disclosed. For example, a method receives characteristics of motion information, wherein the characteristics of motion information is based upon gait information, monitors the characteristics of motion information over a time period to determine a plurality of different modes of motion within the time period, and calculates the health quality measure based upon the plurality of different modes of motion.