Abstract: HIV-1 Env ectodomain trimers stabilized in a prefusion mature closed conformation and methods of their use and production are disclosed. In several embodiments, the HIV-1 Env ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject. In additional embodiments, the therapeutically effective amount of the HIV-1 Env ectodomain trimers can be administered to a subject in a method of treating or preventing HIV-1 infection.
Type:
Application
Filed:
August 30, 2019
Publication date:
December 26, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Inventors:
Peter Kwong, Marie Pancera, Tongqing Zhou, Ivelin Georgiev, Michael Gordon Joyce, Priyamvada Acharya, Jason Gorman, Yongping Yang, Guillaume Stewart-Jones, Rita Chen, Gwo-Yu Chuang, John Mascola, Baoshan Zhang, Cheng Cheng, Mallika Sastry
Abstract: Chimeric antigen receptors containing human CD19 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.
Type:
Grant
Filed:
September 14, 2018
Date of Patent:
December 10, 2019
Assignees:
Lentigen Technology Inc., The U.S.A., as Represented By The Secretary, Department of Health and Human Services
Inventors:
Dina Schneider, Rimas J. Orentas, Boro Dropulic, Dimiter S. Dimitrov, Zhongyu Zhu
Abstract: Recombinant viruses, such as adeno-associated virus (rAAV) or lentivirus, for the treatment of glycogen storage disease type Ib (GSD-Ib) are described. The recombinant viruses use either the human glucose-6-phosphatase (G6PC) promoter/enhancer (GPE) or the minimal human G6PT promoter/enhancer (miGT) to drive expression of human glucose-6-phosphate transporter (G6PT). The disclosed vectors are capable of delivering the G6PT transgene to the liver and correcting metabolic abnormalities in a murine model of GSD-Ib. The recombinant virus-treated mice maintained glucose homeostasis, tolerated a long fast, and did not elicit anti-G6PT antibodies. Methods of treating a subject diagnosed with GSD-Ib using the recombinant viruses is further described.
Type:
Application
Filed:
January 30, 2018
Publication date:
December 5, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Abstract: Human monoclonal antibodies that specifically bind Fms-like tyrosine kinase 3 (FLT3) are described. Chimeric antigen receptors (CARs) and other antibody conjugates that include the FLT3-specific monoclonal antibodies are also described. Methods for the diagnosis and treatment of FLT3-associated cancer, such as acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), are further described.
Type:
Application
Filed:
December 21, 2017
Publication date:
November 21, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Inventors:
Dimiter S. Dimitrov, Weizao Chen, Terry J. Fry, Christopher Chien
Abstract: Modified G6PC (glucose-6-phosphatase, catalytic subunit) nucleic acids and glucose-6-phosphatase-? (G6Pase-?) enzymes with increased phosphohydrolase activity are described. Also described are vectors, such as adeno-associated virus (AAV) vectors, and recombinant AAV expressing modified G6Pase-?. The disclosed AAV vectors and rAAV can be used for gene therapy applications in the treatment of glycogen storage disease, particularly glycogen storage disease type Ia (GSD-Ia), and complications thereof.
Type:
Application
Filed:
July 30, 2019
Publication date:
November 14, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Abstract: Antibodies and antigen binding fragments that specifically bind to IL-7R? are disclosed. Nucleic acids encoding the antibodies and antigen binding fragments, and vectors including the nucleic acid molecules are also provided. Methods for detecting a ca cancer or a cell that expresses IL-7R? using the antibodies and antigen binding fragments are disclosed, as is the use of the antibodies and antigen binding fragments to prevent and/or treat a subject with a cancer that expresses IL-7R?, such as acute lymphoblastic leukemia.
Type:
Application
Filed:
July 1, 2019
Publication date:
October 17, 2019
Applicants:
The U.S.A., as represented by the Secretary, Department of Health and Human Services, University of Maryland, College Park
Inventors:
Scott Durum, Julie Hixon, Wen Qing Li, Scott Walsh, Lila Kashi
Abstract: Transcriptional units encoding Zika virus (ZIKV) premembrane (prM) and envelope (E) proteins, which upon translation form Zika virus-like particles (VLPs), are described. Use of the transcriptional units and VLPs in three different ZIKV vaccine platforms is described. Immunoassay-based detection methods using ZIKV VLPs are described for the diagnosis of ZIKV infection.
Type:
Application
Filed:
June 9, 2017
Publication date:
October 10, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Abstract: Chimeric flaviviruses that include non-coding regions, non-structural proteins, a capsid (C) protein and a portion of a premembrane (prM) signal sequence from West Nile virus (WNV), and a portion of a prM signal sequence, a prM protein and an E protein from Zika virus (VIKV) are described. Also described are compositions and methods for eliciting an immune response in a subject, such as an immune response directed against ZIKV. Diagnostic assays that utilize chimeric West Nile/Zika viruses are further described.
Type:
Application
Filed:
July 6, 2017
Publication date:
October 3, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Abstract: Chimeric antigen receptors containing ROR1 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.
Type:
Grant
Filed:
November 2, 2018
Date of Patent:
October 1, 2019
Assignees:
LENTIGEN TECHNOLOGY, INC., The U.S.A., as represented by the Secretary, Department of Health and Human Services
Inventors:
Rimas J. Orentas, Dina Schneider, Boro Dropulic, Dimiter S. Dimitrov, Zhongyu Zhu
Abstract: A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay that utilizes multiplex primers and probes with degenerate nucleotides to detect divergent species of lyssavirus is described. The probes used in the RT-PCR assay target a highly conserved region at the 5? end of the lyssavirus genome and are modified with either a minor groove binder (MGB) or locked nucleic acid (LNA) nucleotides to increase their melting temperature. The described assay detects all known lyssavirus species with a sensitivity and specificity superior to traditional hemi-nested PCR and the direct fluorescent antibody (DFA) test.
Type:
Application
Filed:
May 8, 2017
Publication date:
September 19, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Abstract: Biomarkers associated with neuroimmunological disease are described. The disclosed biomarkers are secreted proteins identified in cerebral spinal fluid (CSF) samples of patients with neurological disease. The disclosed biomarkers identify patients with intrathecal inflammation, distinguish multiple sclerosis (MS) patients from patients with other types of inflammatory neurological diseases and from subjects without MS, distinguish progressive MS patients from patients with relapsing-remitting MS, identify subjects with non-MS inflammatory neurological diseases, differentiate healthy subjects from patients with any type of neurological disease, and/or identify subjects with increased disability, CNS tissue damage and/or neurodegeneration. Process-specific biomarkers that can be used in place of a brain biopsy to identify immune cell infiltration and/or activation in the CNS are also described.
Type:
Application
Filed:
February 25, 2019
Publication date:
August 29, 2019
Applicants:
The U.S.A., as represented by the Secretary, Department of Health and Human Services, Montana State University
Inventors:
Bibiana Bielekova, Mika Komori, Peter Kosa, Mark C. Greenwood, Christopher Barbour
Abstract: Methods of inducing an immune response in a subject to the Middle East respiratory syndrome coronavirus (MERS-CoV) are provided. In several embodiments, the immune response is a protective immune response that inhibits or prevents MERS-CoV infection in the subject. Recombinant MERS-CoV polypeptides and nucleic acid molecules encoding same are also provided. Additionally, neutralizing antibodies that specifically bind to MERS-CoV S protein and antigen binding fragments thereof are disclosed. The antibodies and antigen binding fragments are useful, for example, in methods of detecting MERS-CoV S protein in a sample or in a subject, as well as methods of preventing and treating a MERS-CoV infection in a subject.
Type:
Application
Filed:
May 3, 2019
Publication date:
August 22, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Inventors:
Barney Graham, Wing-Pui Kong, Kayvon Modjarrad, Lingshu Wang, Wei Shi, Michael Gordon Joyce, Masaru Kanekiyo, John Mascola
Abstract: The disclosure provides recombinant herpes virus with diminished latency. In embodiments, the recombinant herpes virus comprises a latency gene or transcript linked to an altered or heterologous promoter. The disclosure also provides compositions and methods for inducing immunity in animals using the recombinant herpes viruses.
Type:
Application
Filed:
November 19, 2018
Publication date:
June 6, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Abstract: Embodiments of the present disclosure include anti-inflammatory compositions and methods of use thereof. The compositions include purified lipids from Francisella, for example, virulent strains of Francisella. Other features and advantages of the invention will be apparent from the detailed description, and from the claims.
Type:
Application
Filed:
April 6, 2017
Publication date:
March 28, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Inventors:
Catharine Mans Bosio, Robin M. Ireland, Glenn A. Nardone
Abstract: Neutralizing antibodies and antigen binding fragments that specifically bind to Ebola virus glycoprotein are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting Ebola virus using the antibodies and antigen binding fragments are disclosed. The antibodies, antigen binding fragments, nucleic acids, and vectors, can be used, for example, to prevent and/or treat Ebola virus infection in a subject.
Type:
Application
Filed:
November 14, 2018
Publication date:
March 7, 2019
Applicants:
The U.S.A., as represented by the Secretary, Department of Health and Human Services, Institute for Research in Biomedicine, The Government of the United States, as represented by the Secretary of the Army, Humabs BioMed SA
Inventors:
Nancy Sullivan, Sabue Malangu, Davide Corti, Antonio Lanzavecchia, Barney Graham, Jean-Jacques Muyembe-Tamfun, John Trefry, Julie Ledgerwood, Daphne Stanley
Abstract: Disclosed herein are methods of treating a malignant adrenocortical tumor, including a locally advanced and metastatic adrenocortical carcinoma. In some examples, methods of treating a malignant adrenocortical tumor include administering an effective amount of niclosamide alone or in combination with other therapeutic agents to a subject in need thereof, thereby treating the malignant adrenocortical tumor.
Type:
Application
Filed:
January 18, 2017
Publication date:
February 21, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Inventors:
Electron Kebebew, Lisa Zhang, Ya-Qin Zhang, Min Shen
Abstract: The present disclosure describes improved adeno-associated virus (AAV) vectors for gene therapy applications in the treatment of glycogen storage disease, particularly glycogen storage disease type Ia (GSD-Ia). Described are recombinant nucleic acid molecules, vectors and recombinant AAV that include a G6PC promoter/enhancer, a synthetic intron, a G6PC coding sequence (such as a wild-type or codon-optimized G6PC coding sequence), and stuffer nucleic acid sequence situated between the G6PC promoter/enhancer and the intron, as well as between the intron and the G6PC coding sequence. The recombinant AAVs disclosed herein exhibit highly efficient liver transduction and are capable of correcting metabolic abnormalities in an animal model of GSD-Ia.
Type:
Application
Filed:
October 1, 2018
Publication date:
January 17, 2019
Applicant:
The U.S.A., as represented by the Secretary, Department of Health and Human Services
Abstract: The finding that human immunodeficiency virus (HIV) envelope glycans bind CD62L (L-selectin) on central memory T cells is described. HIV infection is also shown to induce shedding of CD62L and this shedding is required for efficient release of HIV from infected cells. Methods of inhibiting HIV release from infected cells using inhibitors of CD62L sheddase are described. Methods of treating HIV infection with a CD62L sheddase, such as in combination with antiretroviral therapy, is also described.
Type:
Application
Filed:
December 27, 2016
Publication date:
January 10, 2019
Applicant:
The U.S.A., as represented by the Secretary Department of Health and Human Services
Inventors:
Peter D. SUN, Joseph P. KONONCHIK, Joanna L. IRELAND
Abstract: Described herein is the discovery that cancer stem cells (CSCs) can be induced to differentiate by altering CD47 signaling. Provided herein are methods and compositions for inducing differentiation of cancer stem cells, for instance irreversible differentiation, including methods of treating subjects with cancer such as breast cancer, colon cancer, lung cancer, ovarian cancer, or melanoma, and including metastatic as well as primary cancer. Also provided are methods for treating subjects with triple negative breast cancers involving forcing differentiation of bCSCs of the subjects through targeting of CD47.
Type:
Application
Filed:
October 9, 2015
Publication date:
December 13, 2018
Applicant:
The U.S.A, as represented by the Secretary, Department of Health and Human Services
Inventors:
David D. Roberts, Sukhbir Kaur, Chengyu Liu
Abstract: Recombinant adenoviruses expressing the extracellular (EC) and transmembrane (TM) domains of human HER2 (HER2ECTM) are described. The recombinant adenoviruses express a chimeric fiber protein having the adenovirus type 35 (Ad5) shaft and knob domains, which facilitates transduction of human dendritic cells by the recombinant HER2ECTM expressing adenovirus. Compositions that include dendritic cells transduced by the recombinant adenovirus and their use for treating HER-positive tumors is described.
Type:
Application
Filed:
October 31, 2016
Publication date:
December 6, 2018
Applicants:
The U.S.A., as represented by the Secretary, Department of Health and Human Services, Baylor College of Medicine
Inventors:
Lauren V. Wood, Brenda D. Roberson, Jay A. Berzofsky, John C. Morris, Jason C. Steel, Masaki Terabe, Malcolm K. Brenner