Patents Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Serv
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Publication number: 20190038627Abstract: Adenosine kinase inhibitors, including pharmaceutical compositions containing the adenosine kinase inhibitors, and their use for preventing epilepsy and its progression in patients. The adenosine kinase inhibitors have the formula: where the moieties J and K, considered in combination, are —CH2—, or K and L, considered in combination, are —CH2—. The R1 moiety can be —NH2, C1-C6 alkyl, C1-C6 alkoxy, or C1-C6 hydroxyalkyl. The R2 and R3 moieties are each independently C1-C6 alkyl. The R4 moiety is hydrogen or C1-C6 alkyl. The R5 and R6 moieties are each independently C6-C12 aryl, C3-C8 cycloalkyl, or C3-C8 heteroaryl, that is optionally further substituted.Type: ApplicationFiled: July 9, 2018Publication date: February 7, 2019Applicants: Legacy Emanuel Hospital & Health Center, The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Kenneth Alan Jacobson, Detlev Boison, Kiran Shambhu Toti
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Publication number: 20190016786Abstract: Monoclonal neutralizing antibodies that specifically bind to HIV-1 gp120 and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV infection is disclosed.Type: ApplicationFiled: July 24, 2018Publication date: January 17, 2019Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Peter D. Kwong, Gary J. Nabel, Rebecca S. Rudicell, John Mascola, Mark Connors, Ivelin Georgiev, Jiang Zhu, Young Do Kwon, Tongqing Zhou, Yongping Yang, Baoshan Zhang, Gwo-Yu Chuang, Xueling Wu, Zhi-yong Yang, Wei Shi
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Publication number: 20190009040Abstract: A nasal delivery device can include air-receiving section that has a first passageway therethrough to allow air to pass through the air-receiving section, a powder-reservoir receiving section sized to receive a powder reservoir, and a powder-delivery section that has a second passageway therethrough to allow aerosolized powder from the powder reservoir to pass through the powder-delivery section. The first passageway can have a first end and a second end, with the first end being further from the powder-reservoir receiving section and the second end being at or near the powder-reservoir receiving area. The second end of the air-receiving section can include a flattened region so that air exiting the air-receiving section has a generally flattened profile.Type: ApplicationFiled: September 7, 2018Publication date: January 10, 2019Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Serv, Creare LLCInventors: Mark J. Papania, James J. Barry, Mark C. Bagley, Darin A. Knaus, Eric M. Friets, Edward Moynihan
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Publication number: 20190000781Abstract: This disclosure concerns the discovery of the use of fenoterol analogues for regulating cannabinoid (CB) receptor activity-related disorders and disease, such as dysregulated CB receptors, including treating a disorder or disease, such as a glioblastoma, hepatocellular carcinoma, liver cancer, colon cancer, and/or lung cancer, which is associated with altered cannabinoid receptor activity. In one example, the method includes administering to a subject having or at risk of developing a disorder or disease regulated by CB receptor activity an effective amount of a fenoterol analogue to reduce one or more symptoms associated with the disorder or disease regulated by CB receptor activity.Type: ApplicationFiled: September 12, 2018Publication date: January 3, 2019Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Irving W. Wainer, Michel Bernier, Rajib K. Paul
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Publication number: 20180353623Abstract: The present invention provides a synthetic MMACHC polynucleotide comprising a polynucleotide encoding MMACHC that is codon-optimized for expression in a human. Also provided is a polypeptide encoded by a synthetic MMACHC polynucleotide, an expression vector comprising a MMACHC gene sequence under the control of a chicken beta actin (CBA) promoter, and an expression vector comprising a synthetic MMACHC polynucleotide. Methods of treating cobalamin C deficiency and for detecting or tracking exogenous MMACHC are also provided.Type: ApplicationFiled: April 27, 2016Publication date: December 13, 2018Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Charles P. Venditti, Jennifer L. Sloan
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Publication number: 20180311374Abstract: Some embodiments of the present disclosure are directed to methods that include delivering to a subject a papillomavirus particle or soluble papillomavirus protein that targets a tumor, and delivering to the subject an immune cell expressing a receptor that binds to a surface antigen of the papillomavirus particle or soluble papillomavirus protein, respectively.Type: ApplicationFiled: October 28, 2016Publication date: November 1, 2018Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Serv, Aleta Biotherapeutics, Inc.Inventors: Roy Lobb, Paul David Rennert, John Todd Schiller
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Publication number: 20180303906Abstract: Methods are provided for treating ocular surface inflammation and/or uveitis in a subject. The methods can include selecting a subject with uveitis and/or ocular surface disease. The methods can then include administering to the subject a therapeutically effective amount of an interleukin 24 (IL-24) polypeptide or nucleic acid encoding the IL-24 polypeptide. In some examples, the administered IL-24 polypeptide suppresses production of effector cytokines by Th17 cells. A pharmaceutical composition is further provided here that includes an IL-24 polypeptide or nucleic acid encoding the polypeptide. In some examples, the IL-24 polypeptide is a variant of IL-24 or an Fc fusion protein that includes IL-24. The pharmaceutical composition can be used in any of the methods provided herein to treat ocular surface inflammation and/or uveitis.Type: ApplicationFiled: April 19, 2018Publication date: October 25, 2018Applicant: THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human ServInventors: Rachel R. Caspi, Wai Po Chong, Reiko Yamane (nee Horai), Mary Mattapallil
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Publication number: 20180291448Abstract: High efficiency methods for producing retinal pigment epithelial cells from induced pluripotent stem cells (iPSCs) are disclosed herein. The iPSCs are produced from somatic cells, including retinal pigment epithelial (RPE) cells, such as fetal RPE stem cells. In some embodiments, the iPSC include a tyrosinase promoter operably linked to a marker. Methods are disclosed for using the RPE cells, such as for treatment. Methods for screening for agents that affect RPE differentiation are also disclosed.Type: ApplicationFiled: May 2, 2018Publication date: October 11, 2018Applicant: THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human ServInventors: Kapil Bharti, Janine Davis, Arvydas Maminishkis, Marc Ferrer-Alegre, Sheldon S. Miller
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Publication number: 20180275013Abstract: Described are systems, devices, and methods related to a confocal laser method (CLM) for accurately measuring dioptric powers and other critical optical properties of intraocular lenses (IOLs), such as toric IOLs. Described test results demonstrate that the described CLM systems and methods can be used to measure the spherical equivalent and cylinder powers of toric IOLs with high accuracy. Furthermore, some described systems include a rotating rectangular slit aperture that can be used for precise differentiation of the two focal planes and isolation of the two focal points, and thus, for accurate measurement of the anterior cylinder axis of toric IOLs.Type: ApplicationFiled: January 27, 2016Publication date: September 27, 2018Applicant: THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human ServInventors: Ilko Kolev Ilev, Bennett Neave Walker, Robert Harold James, Don Calogero
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Publication number: 20180273485Abstract: A compound, or a pharmaceutically acceptable salt or ester thereof, comprising (i) a CB1 receptor mediating scaffold conjugated to (ii) a second therapeutic scaffold.Type: ApplicationFiled: June 1, 2016Publication date: September 27, 2018Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: George Kunos, Malliga Iyer, Resat Cinar
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Publication number: 20180251527Abstract: Isolated VHH monoclonal antibodies are disclosed that specifically bind to a Norovirus polypeptide. In some embodiments, the Norovirus is a Genogroup I Norovirus or a Genogroup II Norovirus. In other embodiments, the Norovirus is Norwalk or MD2004 virus. In some embodiments, the monoclonal antibodies specifically bind VP1. Also disclosed are compositions including the disclosed antibodies, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of a Norovirus in a biological sample, or detecting a Norovirus infection. Also disclosed are methods of treating and/or preventing a NoV infection.Type: ApplicationFiled: May 17, 2018Publication date: September 6, 2018Applicants: THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Serv, INSTITUTO NACIONAL DE TECNOLOGIA AGROPECUARIAInventors: Karin Bok, Lorena Laura Garaicoechea, Viviana Parreno, Andrea Pamela Aguilar, Marina Bok, Lisbeth Kim Green, Stanislav Vladimirovich Sosnovtsev
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Publication number: 20180237835Abstract: Described herein are massively parallel sequencing methods for virus-derived therapeutics such as viral vaccines, including the PVS-RIPO vaccine. The methods allow for the determination of micro-heterogeneity and quantitation of low frequency sequence variants and in the case of PVS-RIPO, are expected to replace the monkey neurovirulence safety test (MNVT) and the mutant analysis by PCR and restriction enzyme cleavage (MAPREC) methods that are currently used to screen lots of RNA virus-derived therapeutics.Type: ApplicationFiled: July 29, 2016Publication date: August 23, 2018Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Serv, American International Biotechnology, LLCInventors: Trevor Lane Broadt, Michael D. Harwich, William T. Budd, Gregory A. Meyers
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Publication number: 20180230150Abstract: Disclosed are compounds of the formula (I) and (II): which are A3 adenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X, Y, Z, R2-R6, and R103-R106 are as defined in the specification. These compounds are selective to the A3 receptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, neuropathic pain.Type: ApplicationFiled: April 10, 2018Publication date: August 16, 2018Applicants: The United States of America, as represented by the Secretary, Department of Health and Human Serv, Saint Louis UniversityInventors: Kenneth A. Jacobson, Dilip K. Tosh, Daniela Salvemini
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Publication number: 20180188254Abstract: Disclosed herein are methods of diagnosing and treating a malignant adrenocortical tumor, including adrenocortical carcinoma. In some examples, methods of diagnosing a malignant adrenocortical tumor include measuring creatine riboside, L-tryptophan, N?,N?,N?-trimethyl-L-lysine and 3-methylhistidine in a biological sample obtained from a subject with an adrenocortical tumor and identifying an increase in creatine riboside and a decrease in L-tryptophan, N?,N?,N?-trimethyl-L-lysine and 3-methylhistidine in the biological sample when compared to a control or reference value for each molecule indicates a malignant adrenocortical tumor. Methods of treatment and evaluating the effectiveness of an agent for treating a malignant adrenocortical tumor are also disclosed. Additionally, kits, assays and devices for characterizing adrenocortical tumors are provided.Type: ApplicationFiled: June 29, 2016Publication date: July 5, 2018Applicant: The United States of America, as Represented by the Secretary, Department of Health and Human ServInventors: Dhaval T. Patel, Kristopher W. Krausz, Frank J. Gonzalez, Electron Kebebew, Matthew Thompson
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Publication number: 20180172709Abstract: The present disclosure relates to methods and compositions for the detection of infectious proteins or prions in samples, including the diagnosis of prion related diseases. One embodiment is an ultrasensitive method for detecting PrP-res (PrPSc) that allows the use of recombinant PrP-sen (rPrP-sen) as a substrate for seeded polymerization. A sample is mixed with purified rPrP-sen to make a reaction mix which is incubated to permit aggregation of the rPrP-sen with the PrP-res that may be present in the sample. Any aggregates are intermittently disaggregated by agitation and the reaction allowed to proceed to amplify target substrate. Any rPrP-res(Sc) in the reaction mix is detected to indicate the presence of PrP-res in the original sample. In the QUIC method in, the reaction mixture is shaken intermittently. The surprising speed and efficiency of the method permits the rapid identification and diagnosis of prion disease.Type: ApplicationFiled: July 31, 2017Publication date: June 21, 2018Applicant: THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human ServInventors: Byron W. Caughey, Ryuichiro Atarashi, Roger A. Moore
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Publication number: 20180153978Abstract: A lymphoma cell line was engineered to express surface IgG1 Fc. These tumor cells were taken up rapidly by DCs, leading to enhanced cross-presentation of tumor-derived antigen to CD8 T cells. IgG1-Fc tumors failed to grow in vivo and prophylactic vaccination in an animal model resulted in rejection of unmanipulated tumor cells. Furthermore, IgG1-Fc tumor cells were able to slow the growth of an unmanipulated primary tumor when used as a therapeutic tumor vaccine. This demonstrates that engagement of Fc receptors by tumors expressing the Fc region of IgG1 can induce efficient and protective anti-tumor CD8+ T cell responses without prior knowledge of tumor-specific antigen.Type: ApplicationFiled: February 2, 2018Publication date: June 7, 2018Applicants: The Board of Regents of the University of Texas System, Yale University, The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Chandrashekhar PASARE, Scott N. FURLAN, Noah W. PALM, Arun UNNI
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Publication number: 20180141894Abstract: This disclosure concerns the discovery of (R,R)- and (R,S)-fenoterol analogues which are highly effective at binding ?2-adrenergic receptors. Exemplary chemical structures for these analogues are provided. Also provided are pharmaceutical compositions including the disclosed (R,R)-fenoterol and fenoterol analogues, and methods of using such compounds and compositions for the treatment of cardiac disorders such as congestive heart failure and pulmonary disorders such as asthma or chronic obstructive pulmonary disease.Type: ApplicationFiled: January 18, 2018Publication date: May 24, 2018Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Irving William Wainer, Weizhong Zhu, Khalid Chakir, Rui-Ping Xiao, Darrell R. Abernethy, Farideh M. Beigi Abhari
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Publication number: 20180100157Abstract: Methods of inhibiting metastasis in cancer patients are provided, wherein the methods comprise reducing TGF? signaling, for example, by reducing TGF? receptor II expression in myeloid cells. Vectors comprising a TGF? receptor II RNAi nucleic acid sequence operably linked to a myeloid specific promoter also are provided. A method of diagnosing cancer in an individual by determining TGF? receptor II expression in myeloid cells in the individual is provided. Additionally, a method of modulating TGF? activity in myeloid cells in a cancer patient comprising administering a regulator of at least one of the GSK3 and PI3K pathways to the patient is provided.Type: ApplicationFiled: December 11, 2017Publication date: April 12, 2018Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventor: Li Yang
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Publication number: 20180093995Abstract: Embodiments of small molecule inhibitors of hypoxia inducible factor 1 (HIF-1) and pharmaceutical compositions thereof are disclosed. The disclosed compounds suppress HIF-1 activity by inhibiting the interaction between the HIF-1 a subunit and transcriptional co-activator protein p300. Embodiments of methods for making and using the small molecule inhibitors are also disclosed.Type: ApplicationFiled: April 6, 2016Publication date: April 5, 2018Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Kirk R. Gustafson, Martin J. Schnermann, Susanna T. S. Chan, Paresma R. Patel, William D. Figg, James B. McMahon
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Publication number: 20180094041Abstract: Disclosed is a T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of human papillomavirus (HPV) 16 E6, E629-38. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of a condition in a mammal and methods of treating or preventing a condition in a mammal, wherein the condition is cancer, HPV 16 infection, or HPV-positive premalignancy.Type: ApplicationFiled: October 18, 2017Publication date: April 5, 2018Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Christian S. Hinrichs, Steven A. Rosenberg