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公开(公告)号：US12053520B2
公开(公告)日：2024-08-06
申请号：US17587817
申请日：2022-01-28
IPC分类号： A61K39/21 , C07K14/005 , C07K14/16 , C12N7/00 , A61K39/00
CPC分类号： A61K39/21 , C07K14/005 , C07K14/162 , C12N7/00 , C12Y205/01078 , A61K2039/5258 , A61K2039/55555 , C07K2319/00 , C12N2740/16023 , C12N2740/16043 , C12N2740/16111 , C12N2740/16122 , C12N2740/16134 , C12N2740/16171
摘要： Embodiments of immunogens based on the outer domain of HIV-1 gp120 and methods of their use and production are disclosed. Nucleic acid molecules encoding the immunogens are also provided. In several embodiments, the immunogens can be used to prime an immune response to gp120 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.
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公开(公告)号：US20240197854A1
公开(公告)日：2024-06-20
申请号：US18274943
申请日：2022-01-28
申请人： Duke University
发明人： Rory Henderson , Barton F. Haynes
IPC分类号： A61K39/12 , A61K39/00 , A61K39/39 , A61P31/18 , C07K14/005
CPC分类号： A61K39/12 , A61K39/39 , A61P31/18 , C07K14/005 , A61K2039/55555 , A61K2039/575 , C12N2740/16122 , C12N2740/16134
摘要： This invention provides in general, a composition suitable for use in inducing anti-HIV-1 antibodies, such as immunogenic compositions comprising envelope proteins and nucleic acids to induce cross-reactive neutralizing antibodies and increase their breadth of coverage. The invention also provides methods of inducing such broadly neutralizing anti-HIV-1 antibodies using such compositions.
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公开(公告)号：US11845789B2
公开(公告)日：2023-12-19
申请号：US17376276
申请日：2021-07-15
申请人： THERACLONE SCIENCES, INC. , THE SCRIPPS RESEARCH INSTITUTE , INTERNATIONAL AIDS VACCINE INITIATIVE, INC.
发明人： Po-Ying Chan-Hui , Katherine Doores , Michael Huber , Stephen Kaminsky , Steven Frey , Ole Olsen , Jennifer Mitcham , Matthew Moyle , Sanjay K. Phogat , Dennis R. Burton , Laura Majorie Walker , Pascal Raymond Georges Poignard , Wayne Koff , Melissa Danielle De Jean De St. Marcel Simek-Lemos
CPC分类号： C07K16/1063 , A61K39/21 , C07K16/1045 , A61K2039/505 , A61P31/18 , C07K2317/21 , C07K2317/33 , C07K2317/34 , C07K2317/51 , C07K2317/515 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , C12N2740/16111 , C12N2740/16122
摘要： The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.
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公开(公告)号：US20230374078A1
公开(公告)日：2023-11-23
申请号：US18342949
申请日：2023-06-28
IPC分类号： C07K14/005 , A61K39/12
CPC分类号： C07K14/005 , A61K39/12 , C12N2740/16122 , C12N2740/16134 , A61K2039/55555
摘要： Human immunodeficiency virus (HIV) envelope proteins having specified mutations that stabilize the trimeric form of the envelope protein are provided. The HIV envelope proteins described herein have an improved percentage of trimer formation and/or an improved trimer yield. Also provided are particles displaying the HIV envelope proteins, nucleic acid molecules and vectors encoding the HIV envelope proteins, as well as compositions containing the HIV envelope proteins, particles, nucleic acid, or vectors.
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公开(公告)号：US11814413B2
公开(公告)日：2023-11-14
申请号：US16615768
申请日：2018-05-25
申请人： Duke University
CPC分类号： C07K14/005 , A61K39/21 , A61P31/18 , C12N7/00 , A61K2039/53 , A61K2039/55572 , C12N2740/16034 , C12N2740/16122
摘要： The invention is directed to immunogens and methods for inducing immune responses, comprising methods for germline B cell stimulation and maturation by reverse engineering of HIV-1 envelopes.
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公开(公告)号：US20230312658A1
公开(公告)日：2023-10-05
申请号：US18067525
申请日：2022-12-16
申请人： Centivax, Inc.
发明人： Jacob E. Glanville
IPC分类号： C07K14/005 , A61K39/12 , A61K39/21 , A61K38/46 , G16B30/10 , A61K39/00 , G16C20/60 , C12N7/00 , G16B35/00 , G16B20/30 , G16B30/00 , G16B35/10 , G16B20/00
CPC分类号： C07K14/005 , A61K38/46 , A61K39/0011 , A61K39/12 , A61K39/21 , C12N7/00 , G16B20/30 , G16B30/00 , G16B30/10 , G16B35/00 , G16B35/10 , G16C20/60 , A61K2039/515 , A61K2039/5154 , A61K2039/53 , A61K2039/575 , A61K2039/70 , C12N2740/16034 , C12N2740/16071 , C12N2740/16122 , C12N2740/16134 , C12N2760/16122 , C12N2760/16134 , C12Y306/05002 , G16B20/00
摘要： The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.
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公开(公告)号：US11767347B2
公开(公告)日：2023-09-26
申请号：US17553070
申请日：2021-12-16
发明人： Leopold Kong , Ian A. Wilson , Natalia De Val , Andrew B. Ward , Dennis Burton , Linling He , Jiang Zhu
CPC分类号： C07K14/162 , A61K39/21 , A61K47/6929 , C07K14/005 , A61K39/12 , A61K47/64 , A61K2039/5258 , A61K2039/6031 , A61K2039/645 , C12N2740/16122 , C12N2740/16134
摘要： The present invention provides HIV-1 vaccine immunogens. Some of the immunogens contain a soluble gp140-derived protein that harbors a modified N-terminus of the HR1 region in gp41. Some of the immunogens contain an HIV-1 Env-derived trimer protein that is presented on a nanoparticle platform. The invention also provides methods of using the HIV-1 vaccine immunogens for eliciting an immune response or treating HIV infections.
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公开(公告)号：US10076567B2
公开(公告)日：2018-09-18
申请号：US15024600
申请日：2014-09-29
发明人： Barton F. Haynes , Bette T. Korber , S. Munir Alam
IPC分类号： A61K39/21 , A61K38/16 , A61K38/21 , A61K9/127 , A61K9/00 , A61K39/12 , A61K47/48 , C07K14/005 , A61K39/39 , C12N7/00 , A61K39/00
CPC分类号： A61K39/21 , A61K9/0019 , A61K9/127 , A61K38/162 , A61K38/212 , A61K39/12 , A61K39/39 , A61K47/6911 , A61K2039/545 , A61K2039/55555 , A61K2039/55572 , A61K2039/575 , C07K14/005 , C12N7/00 , C12N2740/16022 , C12N2740/16034 , C12N2740/16122 , C12N2740/16134 , A61K2300/00
摘要： The present invention relates to peptides and compositions suitable for use in inducing anti-HIV-1 antibodies. The compositions comprise HIV-1 gp41 membrane proximal external region (MPER) peptide-liposome conjugates for induction of broadly reactive anti-HIV-1 antibodies. The invention also relates to methods of inducing neutralizing anti-HIV-1 antibodies using such compositions.
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公开(公告)号：US10071153B2
公开(公告)日：2018-09-11
申请号：US12688862
申请日：2010-01-16
申请人： Michael Ruff , Candace Pert
发明人： Michael Ruff , Candace Pert
IPC分类号： A61K39/21 , A61K38/16 , C07K14/005 , C07K16/10 , A61K39/12
CPC分类号： A61K39/21 , A61K38/162 , A61K39/12 , C07K14/005 , C07K16/1063 , C07K2317/76 , C12N2740/15022 , C12N2740/16122 , C12N2740/16134
摘要： Compositions are disclosed that induce broadly HIV therapeutic and vaccine inducing antibodies against diverse HIV clades and relate to the ability to identify HIV gp120-derived short peptide sequence immunogens and various therapeutic compositions made from the identified peptides which compose CCR5 binding sites. Also disclosed are methods of selecting peptide sequences that are likely candidates for drugs which will offer effective treatment in such areas as Alzheimer's disease, psoriasis, multiple sclerosis and other diseases associated with the human inflammatory cascade as well as related retroviruses such as HTLV-1, the cause of tropical spastic paraparesis.
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公开(公告)号：US20180194809A1
公开(公告)日：2018-07-12
申请号：US15844753
申请日：2017-12-18
发明人： William Schief , Sergey Menis , Daniel Kulp , Joseph Jardine
IPC分类号： C07K14/005 , C12N7/00 , C12N9/10 , A61K39/21 , A01K67/027 , A61K49/00
CPC分类号： C07K14/005 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2227/105 , A01K2267/03 , A61K39/12 , A61K39/21 , A61K49/0008 , C07K2319/00 , C07K2319/21 , C12N7/00 , C12N9/1085 , C12N2740/16122 , C12N2740/16134 , C12N2740/16171 , C12Y205/01078
摘要： The present invention relates to engineered outer domain (eOD) immunogens of HIV gp120 and mutants thereof and methods of making and using the same. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity. The mutant eODs bind to neutralizing antibody precursors. The mutant eODs can activate germline precursors on the pathway to eliciting a broadly neutralizing antibody (bnAb) response. The invention also relates to immunized knock-in mice expressing germline-reverted heavy chains. Induced antibodies showed characteristics of bnAbs and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate precursors. The invention also relates to rational epitope design that can prime rare B cell precursors for affinity maturation to desired targets.
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