Patents Examined by Ram R. Shukla
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Patent number: 11624078Abstract: 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.Type: GrantFiled: April 9, 2020Date of Patent: April 11, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng Zhang, Omar O. Abudayyeh, James E. Dahlman, Patrick Hsu, David A. Scott
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Patent number: 11618881Abstract: Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and/or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.Type: GrantFiled: January 13, 2021Date of Patent: April 4, 2023Assignee: President and Fellows of Harvard CollegeInventors: Torsten B. Meissner, Leonardo M. R. Ferreira, Jack L. Strominger, Chad A. Cowan
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Patent number: 11617357Abstract: Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin ? light chain variable domain.Type: GrantFiled: December 30, 2019Date of Patent: April 4, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Cagan Gurer, Karolina A. Hosiawa, Sean Stevens, Andrew J. Murphy
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Patent number: 11612151Abstract: Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin ? light chain variable domain.Type: GrantFiled: December 30, 2019Date of Patent: March 28, 2023Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Cagan Gurer, Karolina A. Hosiawa, Sean Stevens, Andrew J. Murphy
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Patent number: 11597949Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.Type: GrantFiled: April 9, 2020Date of Patent: March 7, 2023Assignees: THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, PRESIDENT AND FELLOWS OF HARVARD COLLEGEInventors: Feng Zhang, Patrick Hsu, Chie-Yu Lin, Fei Ran
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Patent number: 11590171Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.Type: GrantFiled: April 20, 2022Date of Patent: February 28, 2023Assignee: The Regents of the University of CaliforniaInventors: Theodore Lee Roth, Eric Shifrut, Alexander Marson, Cristina Puig Saus, Antoni Ribas
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Patent number: 11578309Abstract: Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.Type: GrantFiled: December 31, 2021Date of Patent: February 14, 2023Assignee: CRISPR THERAPEUTICS AGInventors: Alireza Rezania, Valentin Sluch
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Patent number: 11525120Abstract: Provided herein are methods of producing ? cells and precursors thereof utilizing a Wnt signaling inhibitor or PKC activator, or both. Also provided herein are in vitro cultures comprising said cells, methods of treating a subject with a disease characterized by high blood sugar levels over a prolonged period of time by administering said cells, and devices for encapsulating said cells.Type: GrantFiled: September 10, 2021Date of Patent: December 13, 2022Assignee: Vertex Pharmaceuticals IncorporatedInventors: Felicia J. Pagliuca, George Harb, Lillian Ye
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Patent number: 11505783Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells and the products related to or resulting from such methods. In particular, the present invention provides an improved method for the formation of pancreatic hormone expressing cells and pancreatic hormone secreting cells. In addition, the present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer and the products related to or resulting from such methods. The present invention also provides methods to promote glucose-stimulated insulin secretion in insulin-producing cells derived from pluripotent stem cells.Type: GrantFiled: September 27, 2019Date of Patent: November 22, 2022Assignee: Janssen Biotech, Inc.Inventor: Alireza Rezania
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Patent number: 11499166Abstract: The present disclosure provides a variant AAV capsid protein that confers tropism to lung cells and recombinant adeno-associated viruses comprising the variant AAV and pharmaceutical compositions comprising same and their use in the delivery of heterologous nucleic acids to lung cells for the treatment of pulmonary disorders.Type: GrantFiled: April 26, 2021Date of Patent: November 15, 2022Assignee: 4D Molecular Therapeutics Inc.Inventors: Melissa Kotterman, Peter Francis, Melissa Calton, Johnny Gonzales, Roxanne Croze, Christopher Schmitt
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Patent number: 11477970Abstract: The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.Type: GrantFiled: February 21, 2019Date of Patent: October 25, 2022Assignee: NemaMetrix Inc.Inventors: Christopher E. Hopkins, Trisha J. Brock, Kathryn McCormick, Gongping He
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Patent number: 11433103Abstract: Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.Type: GrantFiled: July 23, 2021Date of Patent: September 6, 2022Assignee: CRISPR THERAPEUTICS AGInventors: Alireza Rezania, Rebeca Ramos-Zayas
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Patent number: 11311579Abstract: The present invention provides a method for producing a cell culture for promoting angiogenesis or axon outgrowth, particularly for the treatment of a cerebrovascular disease, an ischemic cardiac disease or traumatic brain injury and spinal cord injury, which comprises culturing a cell population containing microglia and/or monocytes under conditions of low oxygen concentration and/or low sugar concentration to produce the culture, a cell preparation obtained by the method, and a method for treating a cerebrovascular disease, an ischemic cardiac disease or traumatic cerebrospinal neuropathy by using the cell preparation.Type: GrantFiled: August 30, 2017Date of Patent: April 26, 2022Assignee: NIIGATA UNIVERSITYInventors: Takayoshi Shimohata, Masato Kanazawa
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Patent number: 10905742Abstract: The present invention provides an agent for protecting the liver and/or promoting liver regeneration, which contains a heparin-binding EGF-like growth factor-like growth factor (HB-EGF) or a partial peptide thereof, or a nucleic acid that encodes same, and an agent for the prophylaxis or treatment of liver diseases. The present invention further provides a method for producing a cell for liver protection and/or promoting liver regeneration, and for the prophylaxis/treatment of a liver disease, which includes introducing a nucleic acid that encodes HB-EGF or a partial peptide thereof into a cell collected from an animal.Type: GrantFiled: September 28, 2006Date of Patent: February 2, 2021Assignee: KAGOSHIMA UNIVERSITYInventors: Ken-ichiro Kosai, Cin Khai Ngin, Tomoyuki Takahashi
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Patent number: 10330690Abstract: The application describes methods for determining the concentration and/or particle number of a lipoprotein(a) subform in a biological sample using capillary isotachophoresis laser induced fluorescence (CE-ITP-LIF) and compositional analysis of lipoprotein(a) particles. The ability to measure the concentration and/or particle number of a lipoprotein(a) subform in a biological sample provides a useful diagnostic tool for assessing cardiovascular risk in a subject.Type: GrantFiled: October 27, 2015Date of Patent: June 25, 2019Assignee: HELENA LABORATORIES CORPORATIONInventors: Philip Guadagno, Erin Grace (Summers) Bellin
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Patent number: 10288627Abstract: The invention relates to a method for detection of abnormal PrP in a sample of blood or urine, said method comprising: (a) diluting the sample with buffer to comprise final concentrations of (i) 10 mM to 500 mM buffer agent; (ii) 1% to 10% w/v bovine serum albumin; and (iii) 1% to 8% w/v CHAPS; (b) adding steel particles and incubating to allow PrP binding; (c) washing the steel particles to remove diluted sample; and (d) detecting abnormal PrP captured on the steel particles using antibody capable of binding said abnormal PrP. The invention also provides compositions and kits.Type: GrantFiled: September 13, 2011Date of Patent: May 14, 2019Assignee: D-Gen LimitedInventors: Graham Stuart Jackson, John Collinge, Julie Ann Edgeworth
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Patent number: 10161928Abstract: A panel for monitoring levels of biomarkers, including an assay having at least one inflammation monitoring test, at least one oxidative stress monitoring test, and at least one antioxidant activity monitoring test. A method of monitoring an individual's health, by collecting a sample from the individual, applying the sample to an assay panel, performing at least one inflammation monitoring test, at least one oxidative stress monitoring test, and at least one antioxidant activity monitoring test in the panel, and determining levels of biomarkers related to inflammation, oxidative stress, and antioxidant activity and therefore providing information regarding the individual's relative health and/or risk of developing one or more diseases.Type: GrantFiled: July 21, 2011Date of Patent: December 25, 2018Assignee: Wellmetris, LLCInventors: Andrew A. Dahl, Denis M. Callewaert
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Patent number: 10145853Abstract: The present invention aims to present methods to detect nonalcoholic fatty liver disease including nonalcoholic steatohepatitis by using a protein or its partial peptide that differs in presence or absence, or in quantity between healthy human subjects and patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis or between patients with fatty liver and nonalcoholic steatohepatitis and further aims to present biomarkers comprising said protein and said partial peptide to be used to detect nonalcoholic fatty liver disease including nonalcoholic steatohepatitis. Specifically, 35 kDa protein fragment consisting of amino acid sequence expressed by Sequence No. 2 and its partial peptide consisting of amino acid sequence expressed by Sequence No. 3 (including its glycated form) of inter-alpha-trypsin inhibitor heavy chain H4 precursor consisting of amino acid sequence expressed by Sequence No.Type: GrantFiled: April 6, 2015Date of Patent: December 4, 2018Assignee: MCBI, Inc.Inventors: Kohji Meno, Hideaki Suzuki
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Patent number: 10041951Abstract: An imaging probe can include a photoluminescent carbon nanostructure configured to emit a wavelength of light detectable through living tissue, and a targeting moiety including a first binding partner configured to interact with a second binding partner.Type: GrantFiled: January 31, 2013Date of Patent: August 7, 2018Assignee: Massachusetts Institute of TechnologyInventors: Hyunjung Yi, Debadyuti Ghosh, Jifa Qi, Angela M. Belcher, Michael S. Strano, Neelkanth M. Bardhan
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Patent number: 10001440Abstract: An observation apparatus and an observation method are provided. The observation apparatus includes a light source that emits illumination light used to observe a specimen to which a fluorescent substance that specifically binds to or is expressed in a stimulus target has been supplied, an illumination optical system that radiates the illumination light emitted from the light source 11 onto the specimen, a deflecting device that changes an area of the specimen to be irradiated with the illumination light, a wavelength selecting section that selects the wavelength of illumination light to be radiated onto the specimen, an observation optical system that collects light from the specimen, a detector that detects the light collected by the observation optical system, an image processing section that generates an image from the light detected by the detector, and a control section that controls these components.Type: GrantFiled: March 7, 2014Date of Patent: June 19, 2018Assignee: OLYMPUS CORPORATIONInventor: Susumu Honda