THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Russell, Fraser
Ogbourne, Steven
Brooks, Peter
Hamilton, Karina
Tran, Trong
Gustafson, Kirk
Pauly, Gary
Boyle, Glen
Simmons, Jacinta
Moseley, Ryan
Abstract
Provided herein are methods and compounds for alleviating skin conditions. More particularly, provided herein are methods that include administering a compound derived or obtained from a natural source such as cerumen or a plant source. The compound may be tomentosenol A. Also provided are compositions for in the aforementioned methods.
The Government of the United States of America as Represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Stinchcomb, Dan T.
Kinney, Claire
Kinney, Richard M.
Livengood, Jill A.
Abstract
Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C07K 14/18 - Togaviridae, e.g. flavivirus, pestivirus, yellow fever virus, hepatitis C virus, japanese encephalitis virus
The Government of the United States of America as Represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Duan, Dongsheng
Hakim, Chady
Wasala, Nalinda B.
Yue, Yongping
Abstract
Disclosed herein are methods for systemically editing a gene in a subject and for systemically treating a genetic condition in a subject using a dual-vector CRISPR-Cas therapy. The methods comprise administering to the subject, via systemic administration, a gene editing AAV vector encoding a CRISPR effector protein (e.g., a Cas protein) and a targeting AAV vector providing one or more gRNAs targeted to the gene. In the methods, the ratio of the targeting AAV vector to the gene editing vector is greater than or equal to 2. Also provided are dual-vector systems for editing a gene or treating a genetic disease in a subject.
The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Chang, Gwong-Jen J.
Crill, Wayne D.
Hughes, Holly R.
Davis, Brent S.
Abstract
Described herein are dengue virus E-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes associated with immune enhancement. The disclosed dengue virus E-glycoproteins optionally further include mutations that introduce a strong CD4 T cell epitope. The disclosed E-glycoprotein polypeptides, or nucleic acid molecules encoding the polypeptides, can be used, for example, in monovalent or tetravalent vaccines against dengue virus.
The Government of the United States of America as Represented by The Secretary of the Department of Health and Human Services (USA)
Inventor
Bergamaschi, Cristina
Felber, Barbara K.
Pavlakis, George N.
Valentin, Antonio
Abstract
The present invention provides method for promoting the maturation and export of T cells from thymic tissue by contacting the thymic tissue with supraphysiological levels of interleukin (IL)-15. The present invention also provides methods for preventing, alleviating, reducing, and/or inhibiting lymphopenia or peripheral depletion of lymphocytes in a patient in need thereof by administering to the patient IL-15.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
The Trustees of The University of Pennsylvania (USA)
Trustees of Boston University (USA)
The Government of The United States of America as Represented by the Secretary of the Department of Health and Human Services (USA)
The Board of Trustees of the Leland Stanford Junior University (USA)
Inventor
Haynes, Barton F.
Liao, Hua-Xin
Lynch, Rebecca M.
Zhou, Tongqing
Gao, Feng
Boyd, Scott
Shaw, George M.
Hahn, Beatrice H.
Kepler, Thomas B.
Korber, Bette T.
Kwong, Peter
Mascola, John R.
Abstract
The present invention relates, in general, to HIV-1 and, in particular, to broadly neutralizing HIV-1 antibodies, and to HIV-1 immunogens and to methods of using such immunogens to induce the production of broadly neutralizing HIV-1 antibodies in a subject (e.g., a human).
The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Chang, Gwong-Jen J.
Crill, Wayne D.
Hughes, Holly R.
Davis, Brent S.
Abstract
Described herein are dengue virus E-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes associated with immune enhancement. The disclosed dengue virus E-glycoproteins optionally further include mutations that introduce a strong CD4 T cell epitope. The disclosed E-glycoprotein polypeptides, or nucleic acid molecules encoding the polypeptides, can be used, for example, in monovalent or tetravalent vaccines against dengue virus.
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
C12Q 1/6895 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for plants, fungi or algae
9.
Use of IL-15 to increase thymic output and to treat lymphopenia
The Government of the United States of America as Represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Pavlakis, George N.
Felber, Barbara K.
Valentin, Antonio
Bergamaschi, Cristina
Abstract
The present invention provides method for promoting the maturation and export of T cells from thymic tissue by contacting the thymic tissue with supraphysiological levels of interleukin (IL)-15. The present invention also provides methods for preventing, alleviating, reducing, and/or inhibiting lymphopenia or peripheral depletion of lymphocytes in a patient in need thereof by administering to the patient IL-15.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/10 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
A61K 39/00 - Medicinal preparations containing antigens or antibodies
11.
Compositions and methods for dengue virus chimeric constructs in vaccines
The Government of the United States of America as Represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Stinchcomb, Dan T.
Kinney, Claire
Kinney, Richard M.
Livengood, Jill A.
Abstract
Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
C07K 14/18 - Togaviridae, e.g. flavivirus, pestivirus, yellow fever virus, hepatitis C virus, japanese encephalitis virus
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
13.
QUINOLINONES AS INHIBITORS OF TRANSLATION INITIATION COMPLEX
THE ROYAL INSTITUTION FOR THE ADVANCEMENT OF LEARNING / MCGILL UNIVERSITY (Canada)
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Ronai, Ze'Ev
Pinkerton, Anthony B.
Feng, Yongmei
Topisirovic, Ivan
Brown, Kevin
Hassig, Christian A.
Abstract
Provided herein are compounds and pharmaceutical compositions comprising quinolinones. The quinolinones and compositions thereof are useful as eukaryotic translation initiation factor 4F (eIF4F) complex modulators.
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 215/227 - Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Defibaugh, Joseph
Camargo, Hugo
Yang, Junyi
Abstract
A cutter head for a mining machine includes a first end and a second end with a drum axis extending between the first and the second ends. The cutter head also includes a web coupled to the second end of the drum. The web includes a plurality of arcuate apertures. Each arcuate aperture extends through an angle about the drum axis. The cutter head further includes a plurality of first ribs coupled to the web. Each of the first ribs is positioned between adjacent arcuate apertures. The cutter head also includes a plurality of second ribs coupled to the web. Each of the second ribs extend across one of the plurality of arcuate apertures. A first angle that extends between one of the first ribs and an adjacent one of the second ribs is different than a second angle extending between the one first rib and another adjacent second rib.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
THE HONG KONG UNIVERSITY OF SCIENCE AND TECHNOLOGY (China)
Inventor
Ip, Nancy Yuk-Yu
Fu, Kit Yu
Fu, Wing Yu
Dimitrov, Dimiter S.
Ying, Tianlei
Abstract
The present invention provides new, fully human EphA4 monoclonal antibodies with distinct binding characteristics. Also disclosed are antigen binding fragments of these antibodies, bispecific forms of these antibodies, and conjugates of these antibodies. In addition, nucleic acids encoding these antibodies, antigen binding fragments, bispecific antibodies and conjugates are disclosed. These monoclonal antibodies, antigen binding fragments, bispecific antibodies, conjugates, nucleic acids and vectors are of use for identifying and treating a subject with a disease or condition involving abnormal EphA4-mediated signaling.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Lee, Richard
Andrew, Dick
Bowers, Lauren Schewitz
Nussenblatt, Robert
Gery, Igal
Wei, Lai
Abstract
The present invention relates to a conjugate that specifically targets a calcineurin inhibitor to T cells, such as Th17 cells, for use in a method for the treatment of an inflammatory disease. The invention also relates to a method for treating an inflammatory disease by administering a conjugate that specifically targets a calcineurin inhibitor to T cells, such as Th17 cells. In addition, the invention relates to a method for identifying a subject likely to be resistant to steroid treatment, as well as a subject likely to benefit from treatment with a calcineurin inhibitor.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Tong, Suxiang
Abstract
Disclosed herein are methods of detecting influenza virus in a sample from a subject. In some embodiments, the disclosed methods include contacting a sample with at least one primer 10-40 nucleotides in length wherein the at least one primer is capable of hybridizing to an influenza virus polymerase basic protein 1 (PB1) nucleic acid at least 70% identical to the nucleic acid sequence set forth as any one of SEQ ID NOs: 1-3, amplifying the PB1 nucleic acid or a portion thereof to produce an amplified PB1 nucleic acid, and detecting the amplified PB1 nucleic acid, wherein presence of the amplified PB1 nucleic acid indicates presence of influenza virus in the sample from the subject. In some examples, the primers comprise or consist of the nucleic acid sequence set forth as one of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 9, or SEQ ID NO: 10.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
19.
COMPOSITIONS AND METHODS FOR DETECTION AND DISCRIMINATION OF INFLUENZA VIRUSES
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Shu, Bo
Lindstrom, Stephen
Wu, Kai-Hui
Berman, Lashondra
Emery, Shannon, L.
Warnes, Christine
Mccord, Catharine
Abstract
The present disclosure relates to compositions and methods for detecting presence of an influenza virus in a sample, such as a biological sample obtained from a subject or an environmental sample. In some embodiments, the compositions and methods can be used to quickly identify particular subtypes of influenza virus (such as seasonal or variant influenza subtype H3, influenza subtype H5, Eurasian influenza subtype H7, North American influenza subtype H7, and/or influenza subtype H9) present in a sample. Probes and primers are provided herein that permit the rapid detection and/or discrimination of influenza virus subtype nucleic acids in a sample. Devices (such as arrays) and kits for detection and/or discrimination of influenza virus subtype nucleic acids are also disclosed herein.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
20.
METHODS AND COMPOSITIONS FOR DETECTION OF LEGIONELLA
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Winchell, Jonas, M.
Benitez, Alvaro, J.
Abstract
Methods for detecting Legionella (such as Legionella spp., Legionella pneumophila, Legionella pneumophila serogroup 1, Legionella bozemanii, Legionella dumoffii, Legionella feeleii, Legionella longbeachae, and/or Legionella micdadei) are disclosed. A sample suspected of containing one or more Legionella nucleic acids is screened for the presence or absence of that nucleic acid. Determining whether Legionella nucleic acid is present in the sample can be accomplished by detecting hybridization between a Legionella probe and a nucleic acid in a sample. Also disclosed are probes and primers for the detection of Legionella, and kits that contain the disclosed probes and/or primers.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Chiu, Charles
Swei, Andrea
Johnson, Barbara, J.B.
Abstract
This disclosure concerns the isolation, identification and sequencing of a unique Phlebovirus, the Lone Star Virus. Lone Star Virus nucleic acid molecules, proteins and antibodies are disclosed. Methods are also disclosed for the detection, diagnostic and treatment of the Lone Star Virus.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
TAKEDA VACCINES, INC. (USA)
Inventor
Stinchcomb, Dan T.
Kinney, Claire
Kinney, Richard M.
Livengood, Jill A.
Abstract
Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
TAKEDA VACCINES, INC. (USA)
Inventor
Stinchcomb, Dan T.
Kinney, Claire
Kinney, Richard M.
Livengood, Jill A.
Abstract
Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can in-clude constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be sub-sequently passaged in mammalian cells.Date Recue/Date Received 2022-09-29
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Stinchcomb, Dan, T.
Kinney, Claire,
Kinney, Richard, M.
Livengood, Jill, A.
Abstract
Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
TAKEDA VACCINES, INC. (USA)
Inventor
Stinchcomb, Dan T.
Kinney, Claire
Kinney, Richard M.
Livengood, Jill A.
Abstract
Embodiments herein report compositions, uses and rnanufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can in-clude constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be sub-sequently passaged in mammalian cells.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
TAKEDA VACCINES, INC. (USA)
Inventor
Stinchcomb, Dan T.
Kinney, Claire
Kinney, Richard M.
Livengood, Jill A.
Abstract
: Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can in-clude constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be sub-sequently passaged in mammalian cells.WO 2014/150939 A2 111111 1111111111 111111 111111111111 11E1111111E 11111 11111 11111 11111 1111 11111111111 DEMITM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Published:EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU,¨ without international search report and to be republishedLV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK,upon receipt of that report (Rule 48.2(g))SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ,GW, KM, ML, MR, NE, SN, TD, TG). ¨ with sequence listing part of description (Rule 5.2(a)) Declarations under Rule 4.17:¨ as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(ii))Date Recue/Date Received 2022-09-29
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Chiu, Charles
Patterson, Jean, L.
Leland, Mary, Michelle
Carey, Kenneth, Dee
Erdman, Dean
Abstract
Baboon Adenovirus (BaAdV)-2/4 and BaAdV-3 are disclosed herein. BaAdV-2/4 and BaAdV-3 polynucleotide, polypeptides and antibodies that specifically bind BaAdV-2/4 and/or BaAdV-3 are disclosed. Methods are disclosed for detecting BaAdV-2/4 and BaAdV-3. Methods are also disclosed for treating, preventing, and inducing an immune response to BaAdV-2/4 and/or BaAdV-3. Kits are also provided.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Livengood, Jill A.
Kinney, Claire
Powell, Timothy D.
Stinchcomb, Dan T.
Osorio, Jorge
Abstract
Embodiments herein report compositions, methods and uses for dengue-4 (DENV-4) virus constructs. Some embodiments concern a composition that includes, but is not limited to, DENV-4 virus constructs disclosed herein that alone or in combination with other constructs can be used in a vaccine composition to induce an immune response in a subject. In certain embodiments, compositions can include constructs of more than one serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, or dengue-3 (DEN-3) virus in combination with DENV-4 virus constructs disclosed herein. In other embodiments, DENV-4 constructs disclosed herein can be combined in a composition with other flavivirus constructs to generate a vaccine against more than one flavivirus. Other embodiments provide methods and uses for DENV-4 virus constructs in vaccine compositions that when administered to a subject induce an immune response in the subject against DENV-4 that is improved by modified constructs compared to other vaccine compositions.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
TRUSTEES OF BOSTON UNIVERSITY (USA)
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (USA)
Inventor
Haynes, Barton, F.
Liao, Hua-Xin
Lynch, Rebecca, M.
Zhou, Tongqing
Gao, Feng
Boyd, Scott
Shaw, George, M.
Hahn, Beatrice, H.
Kepler, Thomas, B.
Korber, Bette, T.
Kwong, Peter
Mascola, John
Abstract
The present invention relates, in general, to HIV-1 and, in particular, to broadly neutralizing HIV-1 antibodies, and to HIV-1 immunogens and to methods of using such immunogens to induce the production of broadly neutralizing HIV-1 antibodies in a subject (e.g., a human).
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (USA)
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
TRUSTEES OF BOSTON UNIVERSITY (USA)
DUKE UNIVERSITY (USA)
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Haynes, Barton F.
Liao, Hua-Xin
Lynch, Rebecca M.
Zhou, Tongqing
Gao, Feng
Boyd, Scott
Shaw, George M.
Hahn, Beatrice H.
Kepler, Thomas B.
Korber, Bette T.
Kwong, Peter
Mascola, John
Abstract
The present invention relates, in general, to HIV-1 and, in particular, to broadly neutralizing HIV-1 antibodies, and to HIV-1 immunogens and to methods of using such immunogens to induce the production of broadly neutralizing HIV-1 antibodies in a subject (e.g., a human).
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Leysath, Clinton Edward
Leppla, Stephen H.
Phillips, Damilola Daniel
Abstract
The present invention provides methods and systems for targeted delivery of a compound to a target cell that over-expresses two different proteinases. Specifically, two different modified protective antigen proteins, each comprising a cleavage site recognized by a distinct proteinase in place of the native proteinase cleavage site recognized by furin, are administered in combination with a compound that contains a protective antigen binding site. Upon cleavage by the two proteinases the two modified protective antigen proteins form a hetero-oligomer, allowing the compound to bind to the hetero-oligomer and subsequently to be translocated into the target cell.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 14/32 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Bacillus (G)
B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF (USA)
Inventor
Narayanan, Jothikumar
Jothikumar, Prithiviraj
Hill, Vincent
Abstract
This disclosure related to methods and reagents for isothermal amplification of nucleic acid molecules. In some embodiments, methods are provided for amplification of a nucleic acid molecule from a biological sample. Additional embodiments include identification of a target nucleic acid molecule in a biological sample using the disclosed amplification methods.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
CREARE, INCORPORATED (USA)
Inventor
Papania, Mark, J.
Barry, James, J.
Bagley, Mark, C.
Knaus, Darin, A.
Friets, Eric, M.
Moynihan, Edward
Abstract
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.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Dodd, Kimberly, A.
Bird, Brian, H.
Albarino, Cesar, G.
Nichol, Stuart, T.
Abstract
Disclosed herein is a robust system for the reverse genetics generation of a Rift Valley fever (RVF) virus replicon particle (VRPRVF) vaccine candidate. VRPRVF can actively synthesize viral RNA and proteins, but lack structural glycoprotein genes, preventing spread within immunized individuals and reducing the risk of vaccine-induced pathogenicity. Is it disclosed herein that VRPRVF immunization is both safe and efficacious, resulting in a robust immune response that is protective against RVF virus challenge within 24 hours of immunization. Provided herein are VRPRVF, methods of producing VRPRVF, and method of using VRPRVF for immunization against RVF virus infection.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
PDS BIOTECHNOLOGY CORPORATION (USA)
Inventor
Johnson, Kenya
Jacobson, Eric
Bedu-Addo, Frank
Mkrtichyan, Mikayel
Khleif, Samir N.
Abstract
The present disclosure provides vaccine compositions comprising at least one adjuvant and at least one therapeutic factor. The disclosure also provides methods of reducing an immune suppressor cell population in a mammal, methods of augmenting an immune response in a mammal, and methods of treating a disease in a mammal utilizing the vaccine compositions.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Winchell, Jonas, M.
Benitez, Alvaro, J.
Abstract
Methods for detecting Legionella (such as Legionella spp., Legionella pneumophila, Legionella pneumophila serogroup 1, Legionella bozemanii, Legionella dumoffii, Legionella feeleii, Legionella longbeachae, and/or Legionella micdadei) are disclosed. A sample suspected of containing one or more Legionella nucleic acids is screened for the presence or absence of that nucleic acid. Determining whether Legionella nucleic acid is present in the sample can be accomplished by detecting hybridization between a Legionella probe and a nucleic acid in a sample. Also disclosed are probes and primers for the detection of Legionella, and kits that contain the disclosed probes and/or primers.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Mcmullan, Laura, K.
Goldsmith, Cynthia
Kelly, Aubree
Nicholson, William, L.
Nichol, Stuart, T.
Abstract
Described herein are the clinical and laboratory characteristics of two patients bitten by ticks and infected with a unique member of the genus Phlebovirus (family Bunyaviridae) with a proposed name of Heartland virus (HRTLV). Provided herein are nucleotide and amino acid sequences of the Phlebovirus isolates, primers and probes that specifically hybridize with the Phlebovirus isolates, and antibodies specific for the Phlebovirus proteins. Also provided are detection assays using the Phlebovirus nucleic acid molecules, proteins, probes, primers and antibodies. Further provided are recombinant Phleboviruses and their use for eliciting an immune response in a subject.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Mcmullan, Laura K.
Goldsmith, Cynthia
Kelly, Aubree
Nicholson, William L.
Nichol, Stuart T.
Abstract
Described herein are the clinical and laboratory characteristics of two patients bitten by ticks and infected with a unique member of the genus Phlebovirus (family Bunyaviridae) with a proposed name of Heartland virus (HRTLV). Provided herein are nucleotide and amino acid sequences of the Phlebovirus isolates, primers and probes that specifically hybridize with the Phlebovirus isolates, and antibodies specific for the Phlebovirus proteins. Also provided are detection assays using the Phlebovirus nucleic acid molecules, proteins, probes, primers and antibodies. Further provided are recombinant Phleboviruses and their use for eliciting an immune response in a subject.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION (USA)
Inventor
Pavlakis, George
Felber, Barbara
Mullins, James
Abstract
The invention provides methods and compositions for eliciting broad immune responses. The methods employ nucleic acid vaccines that encodes highly conserved elements from a virus.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Chang, Gwong-Jen J.
Crill, Wayne D.
Hughes, Holly R.
Davis, Brent S.
Abstract
Described herein are dengue virus E-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes associated with immune enhancement. The disclosed dengue virus E-glycoproteins optionally further include mutations that introduce a strong CD4 T cell epitope. The disclosed E-glycoprotein polypeptides, or nucleic acid molecules encoding the polypeptides, can be used, for example, in monovalent or tetravalent vaccines against dengue virus. The dengue virus E-glycoprotein polypeptides have amino acid substitutions at residues corresponding to positions 106, 107, 310 and 311, and either position 364 or position 389 of dengue serotype 1 (DENV- 1) E- glycoprotein. The provided E-glycoprotein polypeptides optionally further include mutations corresponding to positions 468, 478, 482 and 487 of DENV-1 E-glycoprotein.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Chang, Gwong-Jen, J.
Crill, Wayne, D.
Hughes, Holly, R.
Davis, Brent, S.
Abstract
Described herein are dengue virus E-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes associated with immune enhancement. The disclosed dengue virus E-glycoproteins optionally further include mutations that introduce a strong CD4 T cell epitope. The disclosed E-glycoprotein polypeptides, or nucleic acid molecules encoding the polypeptides, can be used, for example, in monovalent or tetravalent vaccines against dengue virus. The dengue virus E-glycoprotein polypeptides have amino acid substitutions at residues corresponding to positions 106, 107, 310 and 31 1, and either position 364 or position 389 of dengue serotype 1 (DENV- l) E- glycoprotein. The provided E-glycoprotein polypeptides optionally further include mutations corresponding to positions 468, 478, 482 and 487 of DENV-1 E-glycoprotein.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
GEORGIA TECH RESEARCH CORPORATION (USA)
Inventor
Donlan, Rodney Martin
Lehman, Susan Marie
Garcia, Andres J.
Abstract
Medical devices that are resistant to biofilm development and methods of the manufacture of biofilm resistant medical devices are provided. One or more bacteriophages are tethered to the surface of a medical device or a hydrogei-type coating on the surface of the device by covalent bonding while maintaining bacteriophage infective or lytic activity. The presence of the bacteriophages on a medical device, such as an indwelling medical device, prevents biofilm formation or reduces existing biofilm formation on the surface of the device when in use. These devices address the long felt need for biofilm resistant devices that increase safety and reduce complications normally associated with prior indwelling or other medical devices.
A61F 2/00 - Filters implantable into blood vesselsProstheses, i.e. artificial substitutes or replacements for parts of the bodyAppliances for connecting them with the bodyDevices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
GEORGIA TECH RESEARCH CORPORATION (USA)
Inventor
Donlan, Rodney, Martin
Lehman, Susan, Marie
Garcia, Andres, J.
Abstract
Medical devices that are resistant to biofilm development and methods of the manufacture of biofilm resistant medical devices are provided. One or more bacteriophages are tethered to the surface of a medical device or a hydrogei-type coating on the surface of the device by covalent bonding while maintaining bacteriophage infective or lytic activity. The presence of the bacteriophages on a medical device, such as an indwelling medical device, prevents biofilm formation or reduces existing biofilm formation on the surface of the device when in use. These devices address the long felt need for biofilm resistant devices that increase safety and reduce complications normally associated with prior indwelling or other medical devices.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
A61F 2/00 - Filters implantable into blood vesselsProstheses, i.e. artificial substitutes or replacements for parts of the bodyAppliances for connecting them with the bodyDevices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
A61M 25/01 - Introducing, guiding, advancing, emplacing or holding catheters
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Basta, Milan
Chen, Xinzhi
Mattson, Mark
Abstract
Methods are disclosed for treating cerebral ischemia using a combination of C1-INH and immunoglobulin, such as human plasma derived immunoglobulin (IVIG).
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
45.
COMBINATION THERAPY USING IMMUNOGLOBULIN AND C1-INHIBITOR
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Basta, Milan
Chen, Xinzhi
Mattson, Mark
Abstract
Methods are disclosed for treating cerebral ischemia using a combination of C1-INH and immunoglobulin, such as human plasma derived immunoglobulin (IVIG).
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
46.
AMIDO COMPOUNDS AS RORϒTMODULATORS AND USES THEREOF
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF, HEALTH AND HUMAN SERVICES (USA)
Inventor
Littman, Dan
Huh, Jun, R.
Huang, Ruili
Huang, Wenwei
Englund, Erika, Elaine
Abstract
Amido compounds are disclosed that have a formula represented by the following:1 and wherein Cy1, Cy2, nl, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by¬ way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft- versus-host disease.
A61K 31/435 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
C07D 211/16 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
C07D 409/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
THE GOVERNMENT OF THE UNITED STATES AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Chang, Gwong-Jen, J.
Hughes, Holly, R.
Abstract
Described herein is the identification and of a potent West Nile virus (WNV) CD4 positive T cell epitope and its use for increasing the immunogenicity of heterologous flavivirus vaccines, such as dengue virus type 2 (DENV-2) DNA and virus-like particle (VLP) vaccines. Also described are methods for the identification of potent T cell epitopes to enhance immunogenicity of multivalent vaccines.
UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC. (USA)
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Champagne, Donald E.
Tsujimoto, Hitoshi
Francischetti, Ivo
Strand, Michael R.
Kotsyfakis, Michail
Abstract
The present invention includes a novel protein, also referred to herein as simukunin, that inhibits the function of several physiologically important enzymes. Simukunin is a potent inhibitor of the blood coagulation cascade, inhibiting Factor Xa and functioning as an efficient anticoagulant. Simukunin also inhibits the serine proteases elastase and cathepsin and demonstrates anti-inflammatory properties. Also included are methods of making and using simukunin.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Pastan, Ira H.
Weldon, John
Beers, Richard
Abstract
Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas and several other types of human cancers. Because among normal tissues, mesothelin is only present on mesothelial cells, it represents a good target for antibody mediated delivery of cytotoxic agents. The present invention is directed to improved recombinant immunotoxins comprising anti-mesothelin antibodies, including Fv molecules with particularly high affinity for mesothelin, and a Pseudomonas Exotoxin moiety which has been modified to reduce its immunogenicity and protease sensitivity and providing a better cytotoxicity for cells which expresss mesothelin. The RITs are well-suited for the treatment of cancers of the ovary, stomach, squamous cells, mesotheliomas and other malignant cells expressing mesothelin.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/21 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Pseudomonadaceae (F)
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
U.S. ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES` (USA)
Inventor
Kaplan, Gerardo
Konduru, Krishnamurthy
Jacques, Jerome
Bavari, Sina
Bradfute, Steven
Abstract
This invention provides fusion proteins comprising a Filovirus glycoprotein segment and an immunoglobulin polypeptide segment. The fusion proteins are useful in immunogenic compositions to protect against infections by Filoviruses, such as Ebola virus, in both humans and non-human animals. The fusion proteins are also useful in diagnostic assays to detect Filovirus infections.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Mascola, John, R.
Nabel, Gary
Haynes, Barton, F.
Wu, Xueling
Kepler, Thomas, B.
Kwong, Peter
Abstract
Antibody VRC01 represents a human immunoglobulin that neutralizes -∼90% of diverse HIV-1 isolates. To understand how such broadly neutralizing HIV-1 antibodies develop and recognize the viral envelope, we used X-ray crystallography and 454 pyrosequencing to characterize additional antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding of different antibodies to the same CD4-binding-site epitope. Antibody recognition was achieved through the evolution of complementary contact domains that were generated in diverse ways. Phylogenetic analysis of expressed heavy and light chains determined by deep sequencing revealed a common pathway of antibody heavy chain maturation confined to IGHV1-2*02 lineage that could pair with different light chains. The maturation pathway inferred by antibodyomics reveals that diverse antibodies evolve to a highly affinity-matured state to recognize an invariant viral structure, providing insight into the development and evolution of broadly neutralizing HIV-1 immunity.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Pastan, Ira H.
Weldon, John
Beers, Richard
Abstract
Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas and several other types of human cancers. Because among normal tissues, mesothelin is only present on mesothelial cells, it represents a good target for antibody mediated delivery of cytotoxic agents. The present invention is directed to improved recombinant immunotoxins comprising anti-mesothelin antibodies, including Fv molecules with particularly high affinity for mesothelin, and a Pseudomonas Exotoxin moiety which has been modified to reduce its immunogenicity and protease sensitivity and providing a better cytotoxicity for cells which expresss mesothelin. The RITs are well-suited for the treatment of cancers of the ovary, stomach, squamous cells, mesotheliomas and other malignant cells expressing mesothelin.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/21 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Pseudomonadaceae (F)
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
53.
FOCUSED EVOLUTION OF HIV-1 NEUTRALIZING ANTIBODIES REVEALED BY CRYSTAL STRUCTURES AND DEEP SEQUENCING
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
DUKE UNIVERSITY (USA)
Inventor
Mascola, John R.
Nabel, Gary
Haynes, Barton F.
Wu, Xueling
Kepler, Thomas B.
Kwong, Peter
Abstract
Antibody VRC01 represents a human immunoglobulin that neutralizes -~90% of diverse HIV-1 isolates. To understand how such broadly neutralizing HIV-1 antibodies develop and recognize the viral envelope, we used X-ray crystallography and 454 pyrosequencing to characterize additional antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding of different antibodies to the same CD4-binding-site epitope. Antibody recognition was achieved through the evolution of complementary contact domains that were generated in diverse ways. Phylogenetic analysis of expressed heavy and light chains determined by deep sequencing revealed a common pathway of antibody heavy chain maturation confined to IGHV1-2*02 lineage that could pair with different light chains. The maturation pathway inferred by antibodyomics reveals that diverse antibodies evolve to a highly affinity-matured state to recognize an invariant viral structure, providing insight into the development and evolution of broadly neutralizing HIV-1 immunity.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Bachran, Christopher H.
Leppla, Stephen H.
Liu, Shihui
Morley, Thomas
Abstract
The present invention provides chimeric molecules having a ubiquitin moiety attached to a cytosol-targeting moiety and an effector moiety. The ubiquitin can be modified to replace one or more lysine residues with another amino acid to reduce the amount of ubiquitination and proteasomal degradation of the chimeric molecule. The modified ubiquitin results in increased stability of the effector moiety in the cytosol of the target cell. The invention also provides methods of using the ubiquitin-containing chimeric molecules to target diseased cells, such as tumor cells and HIV-infected cells.
C12N 15/62 - DNA sequences coding for fusion proteins
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/87 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
C12P 21/02 - Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Thomas, Jennifer Dolan
Wang, Xin
Hatcher, Cynthia
Anderson, Raydel
Theodore, Mary Jordan
Mayer, Leonard W.
Abstract
A process for detecting Haemophilus influenzae nucleic acid in a sample includes producing an amplification product by amplifying a Haemophilus influenzae nucleotide sequence and measuring the amplification product to detect Haemophilus influenzae in the sample. Some embodiments allow direct serotype determination in a single step assay. Also provided are reagents and methods for detecting and distinguishing Haemophilus influenzae from other infectious agents. A kit is provided for detecting and quantifying Haemophilus influenzae in a sample.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C12N 15/31 - Genes encoding microbial proteins, e.g. enterotoxins
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C40B 40/06 - Libraries containing nucleotides or polynucleotides, or derivatives thereof
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Thomas, Jennifer, Dolan
Wang, Xin
Hatcher, Cynthia
Anderson, Raydel
Theodore, Mary, Jordan
Mayer, Leonard, W.
Abstract
A process for detecting Haemophilus influenzae nucleic acid in a sample includes producing an amplification product by amplifying a Haemophilus influenzae nucleotide sequence and measuring the amplification product to detect Haemophilus influenzae in the sample. Some embodiments allow direct serotype determination in a single step assay. Also provided are reagents and methods for detecting and distinguishing Haemophilus influenzae from other infectious agents. A kit is provided for detecting and quantifying Haemophilus influenzae in a sample.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12Q 1/04 - Determining presence or kind of microorganismUse of selective media for testing antibiotics or bacteriocidesCompositions containing a chemical indicator therefor
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE (USA)
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Zhao, Rui
Ford, Heide, L.
Southall, Noel
Englund, Erika
Patnaik, Samarjit
Ferrer, Marc
Zhang, Wei
Dehdashti, Seameen
Marugan, Juan
Abstract
The invention provides small molecule inhibitors of EYA2 phosphatase activity and EYA2 binding to Six1. These inhibitors are proposed for use in methods of treating cancer in a subject, such as those involving Six1 and/or EYA2 disregulation. In some embodiments, the invention further provides for the administration of a second cancer therapy to the subject.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
JANSSEN VACCINES & PREVENTION B.V. (USA)
Inventor
Sullivan, Nancy J.
Nabel, Gary J.
Asiedu, Clement
Cheng, Cheng
Pau, Maria Grazia
Goudsmit, Jaap
Abstract
The present invention provides recombinant adenovirus vectors (serotype 26 and serotype 35) encoding filovirus antigens. The adenovirus vectors can be used to induce protective immune responses against filovirus infection.
THE GOVERMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
CRUCELL HOLLAND B.V. (Netherlands)
Inventor
Sullivan, Nancy J.
Nabel, Gary J.
Asiedu, Clement
Cheng, Cheng
Pau, Maria Grazia
Goudsmit, Jaap
Abstract
The present invention provides recombinant adenovirus vectors (serotype 26 and serotype 35) encoding filovirus antigens. The adenovirus vectors can be used to induce protective immune responses against filovirus infection.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Boyer, Anne E.
Lins, Renato C.
Kuklenyik, Zsuzsanna
Gallegos-Candela, Maribel
Quinn, Conrad P.
Barr, John R.
Abstract
One major problem in diagnosis methods presently available for anthrax is that these methods require several days to produce a result, are rendered unusable after antibiotic use, or are not quantifiable. The only existing treatment for anthrax requires administration soon after infection at a time when patients are exhibiting only mild flu-like symptoms. Thus, by the time a diagnosis is made a patient may be days beyond the time when treatment would be effective. The present invention reduces diagnosis time to as little as four hours providing same day identification of anthrax radically increasing the odds of delivering proper treatment and patient recovery. The rapid identification of anthrax edema factor activity exhibited by the invention is also amenable to in vivo screening protocols for the discovery and development of anthrax vaccines, anti-toxins and edema factor inhibitors. The invention isolates and concentrates edema factor and edema toxin from nearly any sample. By capitalizing on the adenylate cyclase activity of edema factor the invention amplifies output signals producing reliable detection of low concentrations of edema factor previously unachievable. The invention involves novel purification and detection techniques and substrates for rapid, reproducible, and quantitative measurements of anthrax edema factor, and other adenylate cyclases in biological samples.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving enzymes not classifiable in groups
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses
61.
TREATMENT OF INFLAMMATORY DISEASES BY TARGETING THE ADAPTOR PROTEIN CIKS
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Siebenlist, Ulrich
Soender, Soeren
Saret, Sun
Abstract
The invention provides compositions and methods employing such compositions, for the treatment of inflammatory disorders that involve activation of NF- B. The compositions inhibit the CIKS binding to TRAF6 via an N-terminal CIKS domain.
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
62.
LEISHMANIA CANINE CHALLENGE MODEL BY SAND FLY BITES
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Fischer, Laurent Bernard
Kamahwi, Shaden
Valenzuela, Jesus
Suau, Hamide Aslan
Abstract
The present invention provides a method for effectively and reproducibly infecting canines with Leishmania infantum using sand flies to vector the parasite. The inventive method comprises several steps, including ensuring canines are naive to Leishmania, infecting the canines using bites of Leishmania-infected sand fly bites, and evaluating successful transmission of the Leishmania parasites.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Smith, Todd G.
Wu, Xianfu
Abstract
Described herein is a method of identifying a monoclonal antibody (or antigen- binding fragment thereof) that specifically binds a plurality of lyssaviruses for use in post-exposure rabies prophylaxis or in the treatment of clinical rabies. The method includes using a naive antibody phage display library to screen for phage clones that bind whole recombinant rabies virus or cells expressing glycoprotein from multiple lyssaviruses (such as RABV, MOKV and WCBV) and/or specifically bind recombinant glycoprotein from different lyssaviruses.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Smith, Todd, G.
Wu, Xianfu
Abstract
Described herein is a method of identifying a monoclonal antibody (or antigen- binding fragment thereof) that specifically binds a plurality of lyssaviruses for use in post-exposure rabies prophylaxis or in the treatment of clinical rabies. The method includes using a naive antibody phage display library to screen for phage clones that bind whole recombinant rabies virus or cells expressing glycoprotein from multiple lyssaviruses (such as RABV, MOKV and WCBV) and/or specifically bind recombinant glycoprotein from different lyssaviruses.
THE GOVERMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Harris, Curtis C.
Horikawa, Izumi
Fujita, Kaori
Mondal, Abdul M.
Park, Kye-Yoon
Pine, Sharon R.
Serrano, Manuel
Abstract
This invention provides methods and compositions for increasing the efficiency of obtaining pluripotent stem cells, the method comprising expressing a 133p53 in cells that are being re-programmed to obtain pluripotent cells. The invention also provides method of inhibiting the proliferation of cancer stem cells, the method comprising suppressing expression of 133p53 in the cells.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Dimitrov, Dimiter, S.
Feng, Yang
Abstract
The present invention provides antibodies and antibody fragments that specifically recognize and agonize the death receptor 4 (DR4). Also provided in the invention are polynucleotides and vectors that encode such molecules and host cells that harbor the polynucleotides or vectors.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
OKAIROS AG (Italy)
Inventor
Sullivan, Nancy J.
Nabel, Gary J.
Clement, Asiedu
Cheng, Cheng
Nicosia, Alfredo
Cortese, Riccardo
Ammendola, Virginia
Colloca, Stefano
Abstract
This invention provides vaccines for inducing an immune response and protection against filovirus infection for use as a preventative vaccine in humans. In particular, the invention provides chimpanzee adenoviral vectors expressing filovirus proteins from different strains of Ebolavirus (EBOV) or Marburg virus (MARV).
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
69.
AMIDO COMPOUNDS AS RORγt MODULATORS AND USES THEREOF
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Littman, Dan
Huh, Jun, R.
Huang, Ruili
Huang, Wenwei
Englund, Erika, Elaine
Abstract
Amido compounds are disclosed that have a formula represented by the following (I) and wherein n l, n2, Rla, Rlb, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.
A61K 31/535 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Klinman, Dennis
Zeuner, Rainald
Verthelyi, Daniela
Gursel, Ihsan
Gursel, Mayda
Abstract
The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for preventing or treating inflammatory arthropathies by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Fitzgerald, David J.
Pastan, Ira H.
Onda, Masanori
O'Shea, John
Thomas, Craig
Jiang, Jian-Kang
Abstract
The present invention provides methods and compositions for reducing, inhibiting or preventing the development and/or production of neutralizing antibodies against therapeutic foreign proteins by co-administering the therapeutic foreign protein with a Janus kinase 3 (JAK3) inhibitor.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Judge, Adam
Lee, Yun-Han
Maclachlan, Ian
Thorgeirsson, Snorri, S.
Abstract
The present invention provides therapeutic nucleic acids such as interfering RNA (e.g., siRNA) that target the expression of genes associated with tumorigenesis and/or cell transformation, lipid particles (e.g., nucleic acid-lipid particles) comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles, e.g., for the treatment of a cell proliferative disorder such as cancer.
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
75.
IMPROVED PSEUDOMONAS EXOTOXIN A WITH REDUCED IMMUNOGENICITY
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Pastan, Ira H.
Beers, Richard
Onda, Masanori
Abstract
The present invention provides improved Pseudomonas Exotoxin A (PE) molecules with high cytotoxicity and reduced immunogenicity, compositions containing the improved (PE), and methods of use.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Fitzgerald, David, J.
Abstract
The present invention provides compositions comprising a chimeric molecule comprising a cytotoxin that inhibits protein synthesis and an agent that inactivates an anti-apoptotic BCL-2 family member protein and methods of inhibiting the growth of or promoting the apoptosis of an aberrantly proliferating cell population by co-administering the chimeric molecule and the agent that inactivates an anti-apoptotic BCL-2 family member protein.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Pastan, Ira H.
Beers, Richard
Onda, Masanori
Abstract
The present invention provides improved Pseudomonas Exotoxin A (PE) molecules with high cytotoxicity and reduced immunogenicity, compositions containing the improved (PE), and methods of use.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 14/21 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Pseudomonadaceae (F)
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Backus, Keriann Marie
Davis, Benjamin
Barry Iii, Clifton B.
Boshoff, Helena
Abstract
A method for determining the presence of mycobacteria species in an organism or biological sample, the method comprising adding to the organism or biological sample a probe molecule comprising a substrate and a label, which probe molecule can be incorporated into mycobacteria, the presence of mycobacteria being determined by a detector responsive to the presence of the label, optionally after applying a stimulus; suitable probe molecules include compounds comprising a label and a substrate, which label is can be detected by a detector responsive to the presence of the label, optionally after applying a stimulus, characterised by compound being able to engage with the active site of Antigen 85B (Ag85B) such that it can form simultaneous hydrogen bonds with two or more amino acids in the active site selected from Arg 43, Trp 264, Ser126, His 262 and Leu 42, or the corresponding amino acids in Antigen 85A (Ag85A) or Antigen 85C (Ag85C), at least one of which is with Ser126.
A61K 31/351 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
A61K 51/00 - Preparations containing radioactive substances for use in therapy or testing in vivo
C07D 309/02 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Fletcher, Paul L.
Fletcher, Maryann D.
Martin, Brian M.
Abstract
The present invention relates to metalloprotease enzymes isolated from scorpion venom, their nucleic acid and amino acid sequences, and methods of use thereof in the treatment of various diseases, disorders and cosmetic conditions.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
FLETCHER, PAUL L. (USA)
MARYANN D. FLETCHER (USA)
Inventor
Fletcher, Paul L.
Fletcher, Maryann D.
Martin, Brian M.
Abstract
The present invention relates to metalloprotease enzymes isolated from scorpion venom, their nucleic acid and amino acid sequences, and methods of use thereof in the treatment of various diseases, disorders and cosmetic conditions.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Pavlakis, George N.
Felber, Barbara K.
Valentin, Antonio
Bergamaschi, Cristina
Abstract
The present invention provides method for promoting the maturation and export of T cells from thymic tissue by contacting the thymic tissue with supraphysiological levels of interleukin (IL)-15. The present invention also provides methods for preventing, alleviating, reducing, and/or inhibiting lymphopenia or peripheral depletion of lymphocytes in a patient in need thereof by administering to the patient IL-15.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Pavlakis, George N.
Felber, Barbara K.
Valentin, Antonio
Bergamaschi, Cristina
Abstract
The present invention provides method for promoting the maturation and export of T cells from thymic tissue by contacting the thymic tissue with supraphysiological levels of interleukin (IL)-15. The present invention also provides methods for preventing, alleviating, reducing, and/or inhibiting lymphopenia or peripheral depletion of lymphocytes in a patient in need thereof by administering to the patient IL-15.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Ho, Mitchell
Pastan, Ira
Abstract
The present invention provides monoclonal anti-mesothelin antibodies and antibody fragments and meth-ods for their use. The antibodies can be completely human.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Ho, Mitchell
Pastan, Ira
Abstract
The present invention provides monoclonal anti-mesothelin antibodies and antibody fragments and methods for their use. The antibodies can be completely human.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
85.
METHOD AND COMPOSITIONS FOR HOST CELL-FREE GROWTH OF PATHOGENS
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the secretary of the department of health and human services (USA)
Inventor
Heinzen, Robert
Omsland, Anders
Cockrell, Diane C.
Howe, Dale
Abstract
The disclosure provides compositions comprising Coxiella burnetii substantially free of eukaryotic host cells, and methods of making and using such compositions.
C12N 1/38 - Chemical stimulation of growth or activity by addition of chemical compounds which are not essential growth factorsStimulation of growth by removal of a chemical compound
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Gershengorn, Marvin, C.
Neumann, Susanne
Raaka, Bruce, M.
Thomas, Craig, J.
Inglese, James
Southall, Noel, T.
Titus, Steven
Zheng, Wei
Huang, Wenwei
Krause, Gerd
Kleinau, Gunnar
Abstract
Disclosed are oxo-hydroquinazolines of formula I that are useful as selective TSHR agonists. The compounds may be used for detecting or treating thyroid cancer, or treating a bone degenerative disorder.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE, SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Zhu, Wenge
Depamphilis, Melvin, L.
Abstract
Disclosed herein are methods of selectively killing cancer cells. The methods include contacting a cancer cell with a compound that inhibits geminin. Disclosed herein are methods that selectively induce apoptosis in cancer cells in the absence of a cell cycle checkpoint inhibitor. Also disclosed are methods for identifying a compound that selectively kills cancer cells, including contacting a cancer cell with a test compound, determining the cell cycle status of the cancer cell, and determining geminin activity in the cancer cell, wherein a compound that induces DNA re-replication, cell cycle arrest, or apoptosis and inhibits geminin activity is a compound that selectively induces apoptosis of cancer cells.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Kaler, Stephen, G.
Abstract
Disclosed herein are methods of identifying a subject as a candidate for treatment with copper. The described methods include determining the presence of at least one mutation in an ATP7 A gene and the presence of at least one biochemical marker of abnormal copper metabolism, wherein the presence of at least one ATP7A mutation and at least one biochemical marker of abnormal copper metabolism identifies an individual likely to benefit from copper treatment. The mutation in ATP7A is one or more mutation selected from the group consisting of Gln197Ter; Arg201Ter; Ala629Pro; Ser637Leu; Gly666Arg; Gly727Arg; Ser833Gly; Gly1019Asp; Asn1304Ser; Ala1362Asp; IVS8,AS,dup5; IVS9,DS,+6T>G; IVS21,DS,+3A>T; Del4246-4260; and Del 4284-4315. The biochemical marker of abnormal copper metabolism includes copper level, ceruloplasmin level, placental copper level, catecholamine level, or cellular copper egress.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Verthelyi, Daniela
Tami, Maria, Cecilia
Puig, Montserrat
Abstract
The invention relates to novel methods for detecting and/or quantifying oversulfated or persulfated glycosaminoglycans based on inhibition of nucleic acid polymerases. The methods can be utilized to detect and quantify oversulfated or persulfated glycosaminoglycans in pharmaceutical preparations, such as heparin preparations or therapeutic medical devices. When used to detect or quantify oversulfated glycosaminoglycans in heparin containing solutions, the samples are prepared by treatment with heparinases to degrade the heparin. Titration of the inhibition of the activity of the polymerases allows quantitation of the oversulfated glycosaminoglycans in the sample.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/86 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood coagulating time
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Grivel, Jean-Charles
Chen, Silvia, S.
Biancotto, Angelique
Abstract
The present invention provides compositions, kits, systems, and methods for detecting antigens in a biological sample, preferably HIV antigens and in particular a HIV-1 p24 antigen. A preferred p24 immuosystem has a wide dynamic range together with a high sensitivity. A preferred assay of the present invention uses a solid support coupled to a high affinity first antibody directed against an antigen together with a labeled second antibody binding to the same antigen.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
THE OHIO STATE UNIVERSITY RESEARCH FOUNDATION (USA)
FUDAN UNIVERSITY (China)
Inventor
Wang, Xin, W.
Ji, Junfang
Croce, Carlo, M.
Sun, Hui-Chuan
Tang, Zhao-You
Abstract
It is disclosed herein that expression of microRNA-26 is decreased in hepatocellular (HCC) tumor tissue relative to non-cancerous tissue, and that a low level of microRNA-26 is associated with a poor clinical outcome. It is also disclosed herein that a low expression level of microRNA-26 is correlated with a favorable response to interferon (IFN) - α therapy in HCC patients. Thus, provided herein is a method of predicting the clinical outcome of a patient diagnosed with HCC comprising detecting the level of microRNA-26 expression in a sample obtained from the patient. Also provided is a method of selecting a patient diagnosed with HCC as a candidate for IFN-α therapy, comprising detecting the level of microRNA-26 expression in a sample obtained from the patient. A method of identifying therapeutic agents for the treatment of HCC, comprising screening candidate agents in vitro to select an agent that increases expression of microRNA-26 in HCC cells are also provided. Further provided are methods of treating a patient diagnosed with HCC and expressing a low level of miR-26, wherein treatment comprises IFN-α therapy.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Fitzgerald, David, J.
Sarnovsky, Robert
Abstract
The invention provides novel recombinant immunotoxins comprising domain III of cholix toxin and exotoxin from Vibrio cholerae. The present invention further provides methods for using the compositions of the present invention to (i) induce apoptosis in a cell bearing one or more surface markers (ii) inhibit unwanted growth, hyperproliferation or survival of a cell bearing one or more cell surface markers, (iii) treat a condition, such as a cancer, (iv) provide therapy for a mammal having developed antibodies to Pseudomonas exotoxin A, and (v) provide therapy for a mammal having developed a disease caused by the presence of cells bearing one or more cell surface marker.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 14/28 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Vibrionaceae (F)
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
93.
METHOD OF TREATING PNEUMOCONIOSIS WITH OLIGODEOXYNUCLEOTIDES
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Klinman, Dennis, M.
Sato, Takashi
Abstract
Methods are disclosed for treating, preventing or reducing the risk of developing occupational lung diseases, such as pneumoconiosis. In several embodiments, the methods include administering a therapeutically effective amount of the suppressive ODN to a subject having or at risk of developing a pneumoconiosis, thereby treating or inhibiting the pneumoconiosis. In several examples, thee subject can have or be at risk of developing silicosis, asbestosis or berryliosis. The method can include selecting a subject exposed to, or at risk of exposure to, inorganic particles, including, but not limited to silica, asbestos, berrylium, coal dust, or bauxite.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
THE UNITED STATES OF AMERICA, AS REPRESENTED BY, THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN, SERVICES (USA)
Inventor
Pike, Victor, W.
Donohue, Sean, R.
Halldin, Christer
Abstract
Imaging of cannabinoid subtype-1 (CB1) receptors in vivo is important for understanding their role in neuropsychiatric disorders and for drug development. Radioligands for imaging with PET or SPECT are required for this purpose. The present invention provides new ligands, including (-)-3-(4-chlorophenyl)-N'-[(4-cyanophenyl)sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine) and 1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate, which were found to have high affinity and selectivity for binding to CB1 receptors. These compounds were labeled and evaluated as a PET and SPECT radioligands for use in mammals. After injection of [11C] (-)-3-(4-chlorophenyl)-N'-[(4-cyanophenyl)sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine) into mammals, high uptake and retention of radioactivity across brain according to the rank order of CB1 receptor densities was observed. Likewise 125I-labeled 1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate showed a distinct regional distribution of radioactivity in brain tissue according to the known CB1 receptor densities. Ligands of the present invention are useful for in vivo imaging CB1 receptor function in mammals.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Dimitrov, Dimiter, S.
Feng, Yang
Pastan, Ira, H.
Abstract
Disclosed herein are isolated human monoclonal antibodies that specifically bind human mesothelin with a binding affinity of about 25 nM or less. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. The antibodies can be used to detect human mesothelin in a sample. Methods of diagnosing cancer, or confirming a diagnosis of cancer, are disclosed herein that utilize these antibodies. Methods of treating a subject with cancer are also disclosed.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
NATIONAL RESEARCH COUNCIL OF CANADA (Canada)
Inventor
Kubler-Kielb, Joanna
Vinogradov, Evguenii
Schneerson, Rachel
Hu, Haijing
Leppla, Stephen, H.
Robbins, John, B.
Abstract
Provide are immunogen c compositions and methods or el c t ng an immune response against B. anthracis and other bacteria that contain 3-methyl-3- hydroxybutyrate- or 3-hydroxybutryate-substituted saccharides. Conjugates of 3- methyl-3-hydroxybutyrate- or 3-hydroxybutryate-substituted saccharides elicit an effective immune response against B. anthracis spores in mammalian hosts to which the conjugates are administered.
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services (USA)
Inventor
Berzofsky, Jay A.
Oh, Sangkon
Pastan, Ira
Abstract
Immunogenic T-cell receptor gamma Alternate Reading Frame Protein (TARP) polypeptides are disclosed herein. These immunogenic TARP polypeptides include nine consecutive amino acids of the amino acid sequence set forth as SEQ ID NO: 9 and do not comprise amino acids 1-26 or amino acids 38-58 of SEQ ID NO: 1. Several specific, non-limiting examples of these polypeptides are set forth as SEQ ID NOs: 3-7. Nucleic acids encoding these polypeptides, and host cells transfected with these nucleic acids, are also disclosed. Methods of using these polypeptides, and polynucleotides encoding these polypeptides, for the treatment of breast and prostate cancer are also disclosed.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
INSTITUTE OF ENZYMOLOGY, BIOLOGICAL RESEARCH CENTER, HUNGARIAN ACADEMY OF SCIENCES (Hungary)
Inventor
Hall, Matthew, D.
Gottesman, Michael, M.
Hellawell, Jennifer, L.
Ludwig, Joseph, A.
Fales, Henry, M.
Salam, Noeris, K.
Szakács, Gergely
Abstract
Disclosed herein are drug compounds that have MDR-inverse activity and thus are effective against multidrug-resistant cells. Exemplary compounds disclosed herein have the following structure: (I). Examples of the disclosed compounds have been found to have, inter alia, efficacy in directly treating multidrug resistant cells, rendering multidrug resistant cells susceptible to other chemotherapeutics and in some instances reversing multidrug resistance.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Dimitrov, Dimiter, S.
Abstract
Described herein are engineered antibody constant domain molecules, such as CH2 or CH3 domain molecules, comprising at least one mutation, or comprising at least one complementarity determining region (CDR), or a functional fragment thereof, engrafted in a loop region of the CH2 domain. The CH2 domain molecules described herein are small, stable, soluble, exhibit little to no toxicity and are capable of binding antigen.
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Dimitrov, Dimiter S.
Abstract
Described herein are engineered antibody constant domain molecules, such as CH2 or CH3 domain molecules, comprising at least one mutation, or comprising at least one complementarity determining region (CDR), or a functional fragment thereof, engrafted in a loop region of the CH2 domain. The CH2 domain molecules described herein are small, stable, soluble, ex-hibit little to no toxicity and are capable of binding antigen.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 39/42 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum viral
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment