October 2015 patents
Generating pancreatic cells, identifying Cas9 targets, and more
Professors Tobias Ritter, David Liu, Donald Ingber, Stuart Schreiber, Lee Rubin, Ronald Walsworth, and Greg Verdine were among the faculty members issued U.S. patents this October. The patents include:
Fluorination of organic compounds
U.S. Patent 9,150,516 (October 6, 2015)
Tobias Ritter and Pingping Tang
Abstract: Methods for fluorinating organic compounds are described herein.
Protein surface remodeling
U.S. Patent 9,150,626 (October 6, 2015)
David R. Liu, Kevin John Phillips, and Michael S. Lawrence
Abstract: Aggregation is a major cause of the misbehavior of proteins. A system for modifying a protein to create a more stable variant is provided. The method involves identifying non-conserved hydrophobic amino acid residues on the surface of a protein, suitable for mutating to more hydrophilic residues (e.g., charged amino acids). Any number of residues on the surface may be changed to create a variant that is more soluble, resistant to aggregation, has a greater ability to re-fold, and/or is more stable under a variety of conditions. The invention also provides GFP, streptavidin, and GST variants with an increased theoretical net charge created by the inventive technology. Kits are also provided for carrying out such modifications on any protein of interest.
Engineered opsonin for pathogen detection and treatment
U.S. Patent 9,150,631 (October 6, 2015)
Michael Super, Jeffrey Charles Way, and Donald E. Ingber
Abstract: The present invention provides for engineered molecular opsonins that may be used to bind biological pathogens or identify subclasses or specific pathogen species for use in devices and systems for treatment and diagnosis of patients with infectious diseases, blood-borne infections or sepsis. An aspect of the invention provides for mannose-binding lectin (MBL), which is an abundant natural serum protein that is part of the innate immune system. The ability of this protein lectin to bind to surface molecules on virtually all classes of biopathogens (viruses, bacteria, fungi, protozoans) make engineered forms of MBL extremely useful in diagnosing and treating infectious diseases and sepsis.
Compositions and methods for promoting the generation of PDX1+ pancreatic cells
U.S. Patent 9,157,062 (October 13, 2015)
Shuibing C. Chen, Douglas A. Melton, Malgorzata Borowiak, Julia Lamenzo Fox, Stuart L. Schreiber, Lee F. Peng, Lance Davidow, Kelvin Lam, and Lee L. Rubin
Abstract: Certain embodiments disclosed herein are directed to a method of producing pancreatic cells or pancreatic cell precursors by exposing human embryonic stem cells to an effective amount of at least one compound listed in Table I to differentiate the human embryonic stem cells into the pancreatic cells or the pancreatic cell precursors. Kits and pancreatic cell lines produced using the methods are also described.
Efficient fluorescence detection in solid state spin systems
U.S. Patent 9,157,859 (October 13, 2015)
Ronald Walsworth and David Lesage
Abstract: Efficient fluorescence detection is achieved by optically guiding fluorescence light generated by color centers within a sample to photodetectors outside the sample. A fluorescence detection system may use a sample containing one or more fluorescence color centers that emit fluorescent light when irradiated with excitation light from an optical source. The sample has an index of refraction greater than its surrounding medium. The sample may include one or more output faces and further include at least two opposing faces configured to internally reflect the fluorescent light emitted by the fluorescent color centers, and to optically guide the emitted fluorescent light to the one or more output faces. The fluorescence detection system may include one or more optical detector configured to receive fluorescent light emitted through the one or more output faces, and a microwave source configured to manipulate the electronic spin of the fluorescent color centers.
Methods and compositions for the treatment of proliferative and pathogenic diseases
U.S. Patent 9,163,086 (October 20, 2015)
Xuebin Qin and Weiguo Hu
Abstract: The invention features proteins including an antibody, or functional derivatives thereof, that bind hCD59 and have the activity of domain 4 of the Streptococcus intermedins intermedilysin (ILY) protein. In order to prevent the independent induction of CDC and ADCC, the antibodies of the invention can bind the same hCD59 epitope as ILYd4 and/or contain modifications that disrupt the interaction between the antibody and complement.
Methods for identifying a target site of a Cas9 nuclease
U.S. Patent 9,163,284 (October 20, 2015)
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.
Bifunctional stapled polypeptides and uses thereof
U.S. Patent 9,163,330 (October 20, 2015)
Gregory L. Verdine, Tom N. Grossmann, Raymond E. Moellering, Tsung-Han Johannes Yeh, Yue Rebecca Yue Liang, and Youbean Oak
Abstract: The invention relates to bifunctional stapled or stitched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stitched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stitched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stitched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Uses of the inventive bifunctional stapled or stitched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.