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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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02-02-2012 дата публикации

Antibody gene transfer and recombinant aav therefor

Номер: US20120027798A1
Автор: Kelly Reed Clark, Philip R. Johnson, Jr.
Принадлежит: Nationwide Childrens Hospital Inc

The present invention relates generally to the use of recombinant adeno-associated viruses (rAAV) for gene delivery and more specifically to the use of rAAV to deliver antibody genes to target cells in mammals. Administration of rAAV encoding antibodies that neutralize the HIV-1 virus is exemplified.

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Номер записи: 1
17-05-2012 дата публикации

Hiv cd4 binding site based covalent immunogen compositions

Номер: US20120121633A1
Автор: Richard J. Massey, Stephanie Planoue, Sudhir Paul, Yasuhiro Nishiyama
Принадлежит: Individual

Provided are immunogenic compositions based on the highly conserved, core CD4 binding site of the gp120 protein of the human immunodeficiency virus. One embodiment includes an antigenic conjugate of an electophilic derivative of HIV gp120 peptide 416-433, designated E-416-433, covalently linked to an immunogenic carrier protein. The compositions are effective in stimulating the production of HIV neutralizing antibodies in mammals. Provided also are related methods of immunization, methods of antibody production and antibodies obtained using the methods of the invention.

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Номер записи: 2
12-07-2012 дата публикации

Alphabodies for hiv entry inhibition

Номер: US20120177676A1
Автор: Ignace Joseph Isabella Lasters, Johan Desmet, Sophie Vanwetswinkel
Принадлежит: COMPLIX NV

The present invention relates to HIV-1 gp41-binding single-chain 3-stranded alpha-helical coiled coil molecules, denoted “Alphabodies”, nucleic acids encoding said Alphabodies, host cells comprising said nucleic acids, as well as pharmaceutical compositions comprising said Alphabodies, and methods for the treatment, prevention and diagnosis of HIV infection using said Alphabodies.

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Номер записи: 3
18-10-2012 дата публикации

Donor specific antibody libraries

Номер: US20120264647A1
Автор: Arun K. Kashyap, Lawrence Horowitz, Ramesh Bhatt
Принадлежит: Kashyap Arun K, Lawrence Horowitz, Ramesh Bhatt

The present invention concerns donor-specific antibody libraries derived from a patient donor who has suffered from, or is suffering from one or more diseases discussed herein. The present invention also concerns the method of making and using the donor-specific antibodies. The present invention further concerns the neutralizing antibodies obtained from the donor-specific antibody libraries and the methods of using these antibodies for the prevention/treatment of human disease.

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Номер записи: 4
21-03-2013 дата публикации

Methods and Compositions for Treatment of Human Immunodeficiency Virus Infection with Conjugated Antibodies or Antibody Fragments

Номер: US20130071406A1
Автор: Chien-Hsing Chang, David M. Goldenberg, Edmund A. Rossi, William J. Mcbride
Принадлежит: Immunomedics Inc

The present invention concerns methods and compositions for treatment of HIV infection in a subject. The compositions may comprise a targeting molecule against an HIV antigen, such as an anti-HIV antibody or antibody fragment. The anti-HIV antibody or fragment may be conjugated to a variety of cytotoxic agents, such as doxorubicin. In a preferred embodiment, the antibody or fragment is P4/D10. Other embodiments may concern methods of imaging, detection or diagnosis of HIV infection in a subject using an anti-HIV antibody or fragment conjugated to a diagnostic agent. In alternative embodiments, a bispecific antibody with at least one binding site for an HIV antigen and at least one binding site for a carrier molecule may be administered, optionally followed by a clearing agent, followed by administration of a carrier molecule conjugated to a therapeutic agent.

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Номер записи: 5
21-03-2013 дата публикации

PEPTIDES MIMICKING HIV-1 VIRAL EPITOPES IN THE V2 LOOP FOR THE GP120 SURFACE ENVELOPE GLYCOPROTEIN

Номер: US20130071424A1
Автор: CARDOZO Timothy, KONG Xiangpeng, ZOLLA-PAZNER Susan
Принадлежит: New York University

The present invention relates to an isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120. This peptide binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection, does not react with blood of matched patients who did not receive the vaccine, and can, therefore, elicit anti-HIV-1 antibodies which protect against HIV-1 infection. Other aspects of the present invention relate to an isolated immunogenic polypeptide comprising the peptide inserted into an immunogenic scaffold protein, a vaccine composition comprised of the immunogenic peptide and an immunologically or pharmaceutically acceptable vehicle or excipient as well as methods of inducing an immune response against HIV-1 and methods of detecting HIV-1. 1. An isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120 which binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection , does not react with blood of matched patients who did not receive the vaccine , and can , therefore , elicit anti-HIV-1 antibodies which protect against HIV-1 infection.2. The isolated immunogenic peptide of claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 1.3. The isolated immunogenic peptide of claim 2 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 7.4. The isolated immunogenic peptide of claim 2 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 11.5. The isolated immunogenic peptide of claim 2 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 12.6. The isolated immunogenic peptide of claim 2 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 13.7. The isolated immunogenic peptide of claim 2 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 14.8. The isolated immunogenic ...

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Номер записи: 6
02-05-2013 дата публикации

HIGH-AFFINITY FULLY FUNCTIONAL SOLUBLE SINGLE-DOMAIN HUMAN CD4, ANTIBODIES, AND RELATED FUSION PROTEINS

Номер: US20130108636A1
Автор: Chen Weizao, Dimitrov Dimiter S.
Принадлежит:

The invention provides engineered antibody domains (eAds), a polypeptide comprising a single domain CD4, as well as a fusion protein comprising the same. Nucleic acids encoding eAd and/or polypeptide or the fusion protein thereof, as well as compositions or cells comprising the eAd, polypeptide, fusion protein, or nucleic acid also are provided. 1. An isolated engineered antibody domain (eAd) comprising SEQ ID NO: 139 , wherein x-xcan be any amino acid , provided that the eAd does not comprise SEQ ID NO: 1.2. The eAd of claim 1 , wherein the eAd comprises SEQ ID NO: 2 claim 1 , SEQ ID NO: 3 claim 1 , SEQ ID NO: 4 claim 1 , or SEQ ID NO: 5.3. A composition comprising the isolated eAd of and a carrier.4. An isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 11.5. An isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 14.6. A composition comprising the polypeptide of .7. A fusion protein comprising (i) the eAd of and (ii) one or more fusion partners claim 1 , wherein the one or more fusion partners optionally is fused to (i) via a linker.8. The fusion protein of claim 7 , wherein the linker comprises the amino acid sequence of one of SEQ ID NOs: 36-40.9. The fusion protein of claim 7 , wherein the fusion partner is selected from an engineered antibody domain (eAd) claim 7 , an HIV envelope glycoprotein claim 7 , CD4 or a fragment or mimic thereof claim 7 , an Fc region or portion thereof claim 7 , an immunoglobulin heavy chain constant region claim 7 , an immunoglobulin light chain constant region claim 7 , or a combination thereof.10. A fusion protein comprising an engineered antibody domain (eAd) comprising (i) SEQ ID NO: 1 claim 7 , (ii) CD4 or a fragment or mimic thereof claim 7 , and (ii) an Fc region.11. The fusion protein of claim 9 , wherein the CD4 or fragment or mimic thereof is soluble CD4.12. The fusion protein of claim 9 , wherein the Fc region is an IgG1 Fc region.13. A fusion protein comprising SEQ ID ...

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Номер записи: 7
02-05-2013 дата публикации

BIVALENT MOLECULES FOR HIV ENTRY INHIBITION

Номер: US20130108653A1
Автор: Bahrami Shervin, Ostergaard Lars Jørgen, Pedersen Finn Skou, Ryttergmrd Mogens Duch, Tolstrup Martin
Принадлежит:

The present invention relates to a new class of virus fusion inhibitors or virus entry inhibitors. More specifically the present invention relates to bivalent molecules that are pre-fusion inhibitors of viruses that makes use of the type (1) fusion mechanism belonging to the groups consisting of Othomyxoviridae, Paramyxoviridae, Retroviridae, Filoviridae and Coronaviridae, in particular HIV. The bivalent molecules of the present invention are molecules that comprise a first part capable of mimicking the function of a mammalian cell receptor, and a second part capable of binding to a virus, preferably HIV, resulting in the neutralization of the virus which is thus rendered harmless. Further, the present invention relates to compositions comprising the pre-fusion inhibitors, as well as to methods for obtaining the pre-fusion inhibitors and the use of the pre-fusion inhibitors. 1161-. (canceled)162. A pre-fusion inhibitor molecule comprising:i) a first part that comprises or consists of a first virus binding moiety that binds to a first viral protein; and wherein said first part comprises or consists of an amino acid sequence of a mammalian membrane receptor or a fragment, mimic or functional homologue thereof;', 'or wherein said first or second part is an antibody or an antigen-binding fragment., 'ii) a second part that comprises or consists of a second virus binding moiety that binds to a second viral protein;'}163. The molecule according to claim 162 , wherein said fragment is at least 75 amino acids long; and wherein said functional homologue is at least 40 percent homologous with said mammalian membrane receptor.164. The molecule according to claim 162 , wherein said first viral protein is HIV gp120 claim 162 , said second viral protein is HIV gp41 claim 162 , andsaid first part is mammalian soluble CD4 (sCD4) or a fragment, or functional homologue thereof, oran amino acid sequence at least 80% identical to soluble CD4 (sCD4) or a fragment, or functional homologue ...

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Номер записи: 8
26-09-2013 дата публикации

Novel hiv -1 broadly neutralizing antibodies

Номер: US20130251726A1
Автор: Dennis R. Burton, Gary Nabel, John Mascola, Melissa Danielle De Jean St. Marcel Simek-Lemos, Pascal Raymond Georges Poignard, Peter Kwong, Sanjay K. Phogat, Tongqing Zhou, Wayne Koff, Xueling Wu, Zhi-Yong Yang
Принадлежит: International AIDS Vaccine Initiative Inc, National Institutes of Health NIH, Scripps Research Institute

The present application relates novel HIV-1 broadly neutralizing antibodies. The antibodies of the present invention are further characterized by their ability to bind epitopes from the Env proteins. The invention also provides light and heavy chain variable region sequences. Compositions for prophylaxis, diagnosis and treatment of HIV infection are provided.

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Номер записи: 9
06-02-2014 дата публикации

MIMOTOPES OF HIV ENV

Номер: US20140037619A1
Автор: Humbert Michael, Ruprecht Ruth M.
Принадлежит: DANA-FARBER CANCER INSTITUTE

The invention provides methods, compositions and kits for treating and or preventing an HIV infection. For example, HIV envelope-like polypeptides (wild-type HIV polypeptides and mimotopes) may be administered to an individual so as to induce a protective immune response to HIV. Alternatively, antibodies directed to the HIV envelope-like polypeptides may be administered to an individual to treat or prevent an HIV infection and/or one or more symptoms associated with the infection (e.g., AIDS). 1. An isolated HIV envelope-like polypeptide , wherein said polypeptide comprises an amino acid sequence which is 90% or more identical to an amino acid sequence selected from the group consisting of those recited in or .2. The isolated HIV envelope-like polypeptide of claim 1 , wherein said polypeptide is a mimotope having an amino acid sequence which is 90% or more identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-84.3. The isolated HIV envelope-like polypeptide of claim 1 , wherein said polypeptide is a mimotope of an HIV V3 envelope region and comprises an amino acid sequence which is 90% or more identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 21 claim 1 , 23 claim 1 , 25 claim 1 , 28 claim 1 , 29 and 31.4. The isolated HIV envelope-like polypeptide of claim 1 , wherein said polypeptide is a mimotope of an HIV C-terminal envelope region and comprises an amino acid sequence which is 90% or more identical to the amino acid sequence selected from the group consisting of SEQ ID NOs: 34 claim 1 , 35 claim 1 , 37 claim 1 , 38 and 39.5. The isolated HIV envelope-like polypeptide of claim 1 , wherein said polypeptide is a wild-type HIV envelope polypeptide consisting essentially of an amino acid sequence which is 90% or more identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 85-92.6. The isolated HIV envelope-like polypeptide of claim 3 , wherein said mimotope comprises ...

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Номер записи: 10
06-02-2014 дата публикации

RAPID SELECTION METHOD FOR HIV GP-120 VARIANTS

Номер: US20140037667A1
Автор: Ferreira Carolina, Sánchez Merino Víctor, Yuste Herranz María Eloísa
Принадлежит:

The invention relates to a method for rapid immunogen selection (RIS) based on the binding a library of recombinant viruses containing randomized HIV gp120 variants of a surface polypeptide displayed to said neutralizing antibodies. The invention relates as well to the use of the HIV gp120 immunogens isolated according to the RIS method of the invention in medicine for the treatment of diseases caused by a virus and in diagnosis for the identification of neutralizing antibodies in a patient. 127-. (canceled)28. A polypeptide capable of eliciting neutralizing antibodies against a virus , wherein the polypeptide comprises a variant HIV-1 gp120 polypeptide or an immunogenic fragment thereof , wherein the variant HIV-1 gp120 polypeptide or the immunogenic fragment thereof is selected from the group consisting of a polypeptide which comprises at least one mutation at a position selected from the group consisting of positions 88 , 131 , 132 , 138 , 160 , 191 , 203 , 226 , 479 , 507 , 604 , and 647 with respect to the numbering of SEQ ID NO:2.29. The polypeptide according to claim 28 , wherein the at least one mutation is selected from the group consisting of N88D claim 28 , C131Y claim 28 , T132N claim 28 , D138G claim 28 , N160Y claim 28 , N191D claim 28 , N203S claim 28 , A226V claim 28 , M479I claim 28 , R507W claim 28 , G604E claim 28 , and Y647N with respect to the numbering of SEQ ID NO:2.30. The polypeptide according to claim 29 , wherein the polypeptide comprises the C131Y claim 29 , T132N claim 29 , D138G claim 29 , and N160Y mutations or the polypeptide comprises the N203S and G604E mutations with respect to the numbering of SEQ ID NO:2.31. The polypeptide according to claim 30 , wherein the variant HIV gp120 polypeptide or the immunogenic fragment thereof comprises a sequence selected from the group consisting of SEQ ID NO:4 claim 30 , SEQ ID NO:17 claim 30 , SEQ ID NO:18 claim 30 , SEQ ID NO:19 claim 30 , SEQ ID NO:20 claim 30 , SEQ ID NO:21 claim 30 , SEQ ID ...

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Номер записи: 11
27-02-2014 дата публикации

Immunoconjugates with an Intracellularly-Cleavable Linkage

Номер: US20140058067A1
Автор: David M. Goldenberg, Serengulam V. Govindan, Sung-Ju Moon
Принадлежит: Immunomedics Inc

The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

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Номер записи: 12
06-01-2022 дата публикации

Broadly-Neutralizing ANTI-HIV Antibodies

Номер: US20220002390A1
Автор: Bjorkman Pamela J., Mouquet Hugo, Nussenzweig Michel, Scharf Louise
Принадлежит:

The present invention relates to anti-HIV antibodies. Also disclosed are related methods and compositions. HIV causes acquired immunodeficiency syndrome (AIDS), a condition in humans characterized by clinical features including wasting syndromes, central nervous system degeneration and profound immunosuppression that results in life-threatening opportunistic infections and malignancies. Since its discovery in 1981, HIV type 1 (HIV-1) has led to the death of at least 25 million people worldwide. 113-. (canceled)14. An isolated polynucleotide comprising a sequence encoding an anti-HIV antibody or antigen binding portion thereof , wherein the anti-HIV antibody or antigen binding portion comprises (i) a heavy chain variable region comprising CDRH 1 , CDRH 2 , and CDRH 3 , wherein the CDRH 1 , CDRH 2 and CDRH 3 comprise the respective sequences of SEQ ID NOs: 69-71 , and (ii) a light chain variable region comprising CDRL 1 , CDRL 2 and CDRL 3 , wherein the CDRL 1 , CDRL 2 and CDRL 3 comprise the respective sequences of SEQ ID NOs: 72-74.15. A vector comprising the polynucleotide of .16. A cultured cell comprising the vector of .1726-. (canceled)27. The isolated polynucleotide of claim 14 , wherein the heavy chain variable region comprises the sequence of SEQ ID NO: 13.28. The isolated polynucleotide of claim 14 , wherein the light chain variable region comprises the sequence of SEQ ID NO: 14.29. The isolated polynucleotide of claim 14 , wherein the heavy chain variable region and the light chain variable region comprise the respective sequences of SEQ ID NOs: 13-14.30. The isolated polynucleotide of claim 14 , wherein the antibody is a human antibody claim 14 , a humanized antibody claim 14 , or a chimeric antibody. This application is a Divisional of application Ser. No. 16/507,867 filed on Jul. 10, 2019, which is a Divisional of U.S. patent application Ser. No. 16/006,420, filed Jun. 12, 2018, issued as U.S. Pat. No. 10,392,433 on Aug. 27, 2019, which is a Divisional ...

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Номер записи: 13
05-01-2017 дата публикации

PRO-DRUG FORM (P2PDOX) OF THE HIGHLY POTENT 2-PYRROLINODOXORUBICIN CONJUGATED TO ANTIBODIES FOR TARGETED THERAPY OF CANCER

Номер: US20170000896A1
Автор: GOLDENBERG David M., Govindan Serengulam V., Mazza-Ferreira Christine, McBride William J., Sathyanarayan Nalini
Принадлежит:

Disclosed are methods, compositions and uses of conjugates of prodrug forms of 2-pyrrolinodoxorubicin (P2PDox) with antibodies or antigen-binding fragments thereof (ADCs), with targetable construct peptides or with other targeting molecules that are capable of delivering the P2PDox to a targeted cell, tissue or pathogen. Once delivered to the target cell, the ADC or peptide conjugate is internalized, a highly toxic 2-pyrrolinodoxorubicin (2-PDox) is released intracellularly. The P2PDox-peptide or ADC conjugates are of use to treat a wide variety of diseases, such as cancer, autoimmune disease or infectious disease. 1. A method of treating cancer comprising administering to a subject with cancer an antibody or antigen-binding antibody fragment that binds to a tumor-associated antigen (TAA) , wherein the antibody or antigen-binding antibody fragment is conjugated to pro-2-pyrrolinodoxorubicin (P2PDox) , wherein the antibody comprises human constant regions selected from the group consisting of IgG1 , IgG2 , IgG3 and IgG4.2. The method of claim 1 , wherein the TAA is selected from the group consisting of CTLA4 claim 1 , PD1 claim 1 , PD-L1 claim 1 , carbonic anhydrase IX claim 1 , CCL19 claim 1 , CCL21 claim 1 , CSAp claim 1 , CD1 claim 1 , CD1a claim 1 , CD2 claim 1 , CD3 claim 1 , CD4 claim 1 , CD5 claim 1 , CD8 claim 1 , CD11A claim 1 , CD14 claim 1 , CD15 claim 1 , CD16 claim 1 , CD18 claim 1 , CD19 claim 1 , IGF-1R claim 1 , CD20 claim 1 , CD21 claim 1 , CD22 claim 1 , CD23 claim 1 , CD25 claim 1 , CD29 claim 1 , CD30 claim 1 , CD32b claim 1 , CD33 claim 1 , CD37 claim 1 , CD38 claim 1 , CD40 claim 1 , CD40L claim 1 , CD45 claim 1 , CD46 claim 1 , CD47 claim 1 , CD52 claim 1 , CD54 claim 1 , CD55 claim 1 , CD59 claim 1 , CD64 claim 1 , CD66a-e claim 1 , CD67 claim 1 , CD70 claim 1 , CD70L claim 1 , CD74 claim 1 , CD79a claim 1 , CD80 claim 1 , CD83 claim 1 , CD95 claim 1 , CD126 claim 1 , CD133 claim 1 , CD138 claim 1 , CD147 claim 1 , CD154 claim 1 , AFP claim 1 ...

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Номер записи: 14
03-01-2019 дата публикации

THERAPEUTIC PEPTIDES AND VACCINES

Номер: US20190000964A1
Автор: Ruff Michael
Принадлежит: Creative Bio-Peptides Inc.

Compositions are disclosed that induce broadly HIV theraputic 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. 120-. (canceled)22. The therapeutic peptide of wherein said peptide overall length is five amino acids.23. The therapeutic peptide of wherein said peptide overall length is six amino acids.24. The therapeutic peptide of wherein said peptide overall length is seven amino acids.25. The therapeutic peptide of wherein said peptide overall length is eight amino acids.26. The therapeutic peptide of wherein said peptide overall length is nine amino acids. This application is a continuation of U.S. Ser. No. 12/688,862, filed Oct. 16, 2010, now U.S. Pat. No. 10,071,153; which is a divisional of U.S. Ser. No. 11/426,301, filed Jun. 23, 2006, now U.S. Pat. No. 7,700,115, issued Apr. 20, 2010; which claims priority to Provisional Application Ser No. 60/693,087, filed Jun. 23, 2005; Provisional Application Ser. No. 60/693,088, filed Jun. 23, 2005 and Provisional Application Ser. No. 60/693,089 filed Jun. 23,2005. This application is also related to application Ser. No. 11/474,049, filed Jun. 23, 2006, now U.S. Pat. No. 7,390,788, the contents of which are incorporated herein by reference.It is widely believed that a vaccine capable of protecting against HIV-1 infection and AIDS will require immunogens that induce high levels of antibodies with potent neutralization activity against primary isolates of the viruses, ...

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Номер записи: 15
07-01-2016 дата публикации

HIV Antigens and Antibodies

Номер: US20160002319A1
Автор: Killian M. Scott, Szakal Evelin, Vyas Girish N.
Принадлежит:

The present invention relates to a method for reducing the occurance and/or severity of viral infections. The method embodies procedures for expanding HIV from the blood of HIV antibody negative donors and deriving a non-infectious virus particle product that is antigenic. The procedures for deriving the antigenic, non-infectious virus particle product are optimally designed to maintain the integrity of the envelope proteins while maximizing the depletion of capsid proteins and RNA. The resulting virus particle product, when introduced into humans or non-human animals, enables the production of antibodies that target the natural envelope macromolecular structure that is required for infectivity. The present invention can be applied to producing virus stocks from the blood of HIV-seronegative donors, for deriving non-infectious virus particles that retain intact envelope proteins, for producing anti-viral antibodies, and for administering anti-virus antibodies to patients. 1. A composition of matter comprising isolated antigen binding proteins (ABPs) , wherein said isolated ABPs selectively bind to an epitope on an HIV-1 trimeric envelope glycoprotein subunit (TEGS).2. The composition of matter of claim 1 , wherein said TEGS is prepared by a process comprising:obtaining infectious HIV-1 virus particles from human CD4+ cell culture grown in serum-free media;contacting said infectious HIV-1 virus particles with agents that selectively remove from said particle viral RNA and viral capsid protein while retaining viral envelope protein in a non-denatured conformation, wherein said agents do not chemically fix or cross-link said envelope protein; andisolating protein from said contacted infectious HIV-1 virus particles wherein said isolated protein comprises non-infectious complexes comprising a trimeric envelope glycoprotein subunit, said subunit comprising HIV-1 envelope, gp120, and gp41 proteins that are not chemically fixed or cross-linked and substantially free of HIV ...

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Номер записи: 16
07-01-2016 дата публикации

THERAPEUTIC AGENT

Номер: US20160002320A1
Автор: Cadogan Martin, Dalgleish Angus G., Heeney Jonathan, White Stanley D.T.
Принадлежит: AIMSCO LIMITED

Anti-HLA and other antibodies are present in goat serum after injection of HIV antigenic material, and form the basis for a most surprisingly effective treatment of HIV, multiple sclerosis and other conditions. 17.-. (canceled)8. A composition comprising: a goat serum isolate from a goat serum that is obtained following viral challenge of said goat with HIV or a lysate thereof , wherein said goat serum isolated is prepared by removing immunoglobulin fragments from and enriching for one or more antibodies in said goat serum.9. The composition of wherein said HIV is selected from HIV-1 and HIV-3B.10. The composition of wherein said goat serum isolate is enriched in one or more antibodies selected from the group consisting of an anti-HLA antibody claim 8 , an anti-FAS antibody claim 8 , an anti-NGFr antibody claim 8 , and an anti-CXCL10 antibody as compared to said purified goat serum.11. The composition of wherein one of said antibodies in an anti-HLA antibody.12. The composition of wherein one of said antibodies in an anti-FAS antibody.13. The composition of wherein one of said antibodies in an anti-NGFr antibody.14. The composition of wherein one of said antibodies in an anti-CXCL10 antibody.15. The composition of wherein said goat serum isolate is enriched for an anti-HLA antibody and an anti-FAS antibody as compared to said goat serum.16. The composition of wherein said goat serum isolate is enriched for an anti-HLA antibody and an anti-NGFr antibody as compared to said goat serum.17. The composition of wherein said goat serum isolate is enriched for an anti-HLA antibody and an anti-CXCL10 antibody as compared to said goat serum.18. The composition of wherein said goat serum isolate is enriched for an anti-HLA antibody claim 10 , an anti-FAS antibody claim 10 , and an anti-NGFr antibody as compared to said goat serum.19. The composition of wherein said goat serum isolate is enriched for an anti-HLA antibody claim 10 , an anti-FAS antibody claim 10 , an anti-NGFr ...

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Номер записи: 17
04-01-2018 дата публикации

NEUTRALIZING GP41 ANTIBODIES AND THEIR USE

Номер: US20180002406A1
Автор: Connors Mark, Georgiev Ivelin, Huang Jinghe, Kwong Peter, Laub Leo B., Mascola John R., Nabel Gary, Ofek Gilad, Rudicell Rebecca S., Yang Yongping, Zhang Baoshan, ZHU Jiang
Принадлежит: THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human

Monoclonal neutralizing antibodies are disclosed that specifically bind to the HIV-1 gp41 membrane-proximal external region (MPER). Also disclosed are compositions including the disclosed antibodies that specifically bind gp41, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of HIV-1 in a biological sample, or detecting an HIV-1 infection or diagnosing AIDS in a subject. In additional, the broad neutralization breadth of the disclosed antibodies makes them ideal for treating a subject with an HIV infection. Thus, disclosed are methods of treating and/or preventing HIV infection. 1. A method of inhibiting an HIV-1 infection in a subject , comprising administering to the subject an effective amount of a monoclonal antibody , the monoclonal antibody comprising:a heavy chain variable region comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 comprising amino acids 26-33, 51-60, and 99-120 of SEQ ID NO: 1, respectively; anda light chain variable region comprising a light chain complementarity determining region (LCDR)1, a LCDR2, and a LCDR3, comprising amino acids 26-31, 49-51, and 88-99 of SEQ ID NO: 2, respectively;wherein the monoclonal antibody specifically binds gp41 and neutralizes HIV-1.2. The method of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as one of SEQ ID NOs: 1 claim 1 , 3 claim 1 , 5 claim 1 , 149 claim 1 , 154 claim 1 , 189-192 claim 1 , 200-201 claim 1 , or 204 claim 1 , and further comprises at most ten amino acid substitutions in framework regions of the heavy chain variable region.3. The method of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 11 claim 1 , wherein Xis Q or R claim 1 , Xis V or A claim 1 , Xis S or Y claim ...

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Номер записи: 18
03-01-2019 дата публикации

BROADLY NEUTRALIZING ANTIBODIES AGAINST HIV-1 AND USE THEREOF

Номер: US20190002539A1
Автор: Chen Yajing, He Linling, JU Bin, Kong Leopold, Li Yuxing, LIU Jiandong, Ren Li, Shao Yiming, Wilson Ian A., ZHU Jiang
Принадлежит:

Broadly neutralizing antibodies against HIV-1 which specifically bind to gp120 of HIV-1, a method of preparing such antibodies and the use thereof are provided. 1. An isolated human monoclonal antibody comprising a heavy chain variable domain and a light chain variable domain , wherein the heavy chain variable domain comprises:(i) VHCDR1, VHCDR2, and VHCDR3 respectively corresponding to VHCDR1, VHCDR2, and VHCDR3 contained in the amino acid sequence of SEQ ID NO:2,(ii) VHCDR1, VHCDR2, and VHCDR3 respectively corresponding to VHCDR1, VHCDR2, and VHCDR3 contained in the amino acid sequence of SEQ ID NO:4, or(iii) VHCDR1, VHCDR2, and VHCDR3 respectively corresponding to VHCDR1, VHCDR2, and VHCDR3 contained in the amino acid sequence of SEQ ID NO:6, andwherein the light chain variable domain comprises VLCDR1, VLCDR2, and VLCDR3 respectively corresponding to VLCDR1, VLCDR2, and VLCDR3 contained in the amino acid sequence of SEQ ID NO:10, andwherein the antibody is a neutralizing antibody which specifically binds to gp120 of HIV-1.2. The antibody of claim 1 , wherein the heavy chain variable domain comprises:(i) VHCDR1, VHCDR2, and VHCDR3 respectively corresponding to amino acids 31-35, 50-66, and 99-109 of SEQ ID NO:2,(ii) VHCDR1, VHCDR2, and VHCDR3 respectively corresponding to amino acids 31-35, 50-66, and 99-109 of SEQ ID NO:4, or(iii) VHCDR1, VHCDR2, and VHCDR3 respectively corresponding to amino acids 31-35, 50-66, and 99-109 of SEQ ID NO:6.3. The antibody of or claim 1 , wherein the heavy chain variable domain comprises:(i) an amino acid sequence of SEQ ID NO:2 or an amino acid sequence at least 85% identical to SEQ ID NO:2,(ii) an amino acid sequence of SEQ ID NO:4 or an amino acid sequence at least 85% identical to SEQ ID NO:4, or(iii) an amino acid sequence of SEQ ID NO:6 or an amino acid sequence at least 85% identical to SEQ ID NO:6.4. The antibody of any one of - claim 1 , wherein the light chain variable domain comprises VLCDR1 claim 1 , VLCDR2 claim 1 , and ...

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Номер записи: 19
14-01-2016 дата публикации

Neutralizing antibodies to hiv-1 and their use

Номер: US20160009789A1
Автор: Carl-Magnus Hogerkorp, Gary Nabel, John Mascola, Mario Roederer, Mark Connors, Peter Kwong, Richard Wyatt, Tongqing Zhou, William Schief, Xueling Wu, Yuxing Li, Zhi-Yong Yang
Принадлежит: UNIVERSITY OF WASHINGTON, US Department of Health and Human Services

Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

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Номер записи: 20
14-01-2021 дата публикации

HIV Binding Agents

Номер: US20210009661A1
Автор: Lanzavecchia Antonio, Pantaleo Giuseppe
Принадлежит:

This disclosure relates to binding agents with specificity for HIV and to methods for using the same to treat, pre-vent and/or ameliorate HIV infection and/or AIDS. 1. A binding agent that neutralizes HIV in an in vitro HIV neutralization assay and/or in vivo , the binding agent at least one amino acid sequence selected from the group consisting of SEQ ID NOS. 1-32 and/or shown in Table 1.217-. cancelled18. The binding agent of comprising a conservative substitution of an amino acid residue of any one or more of SEQ ID NOS. 1-32.19. The binding agent of derived from a human antibody claim 1 , human IgG claim 1 , human IgG1 claim 1 , human IgG2 claim 1 , human IgG2a claim 1 , human IgG2b claim 1 , human IgG3 claim 1 , human IgG4 claim 1 , human IgM claim 1 , human IgA claim 1 , human IgAl claim 1 , human IgA2 claim 1 , human IgD claim 1 , human IgE claim 1 , canine antibody claim 1 , canine IgGA claim 1 , canine IgGB claim 1 , canine IgGC claim 1 , canine IgGD claim 1 , chicken antibody claim 1 , chicken IgA claim 1 , chicken IgD claim 1 , chicken IgE claim 1 , chicken IgG claim 1 , chicken IgM claim 1 , chicken IgY claim 1 , goat antibody claim 1 , goat IgG claim 1 , mouse antibody claim 1 , mouse IgG claim 1 , pig antibody claim 1 , and rat antibody.20. A derivative of a binding agent of .21. The derivative of selected from the group consisting of an F claim 20 , F claim 20 , Fab′ single chain antibody claim 20 , F claim 20 , single chain claim 20 , mono-specific antibody claim 20 , bispecific antibody claim 20 , trimeric antibody claim 20 , multi-specific antibody claim 20 , multivalent antibody claim 20 , chimeric antibody claim 20 , canine-human chimeric antibody claim 20 , canine-mouse chimeric antibody claim 20 , antibody comprising a canine Fc claim 20 , humanized antibody claim 20 , human antibody claim 20 , caninized antibody claim 20 , CDR-grafted antibody claim 20 , shark antibody claim 20 , nanobody claim 20 , and canelid antibody.2226-. canceled27. An ...

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Номер записи: 21
21-01-2016 дата публикации

Bispecific Molecules That are Immunoreactive with Immune Effector Cells That Express an Activating Receptor and an Antigen Expressed by a Cell Infected by a Virus and Uses Thereof

Номер: US20160017038A1
Автор: Scott Koenig
Принадлежит: Macrogenics Inc

The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections.

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Номер записи: 22
17-01-2019 дата публикации

BROADLY NEUTRALIZING HIV-1 ANTIBODIES THAT BIND TO THE CD4-BINDING SITE OF THE ENVELOPE PROTEIN

Номер: US20190016786A1
Автор: Chuang Gwo-Yu, Connors Mark, Georgiev Ivelin, KWON Young Do, Kwong Peter D., Mascola John, Nabel Gary J., Rudicell Rebecca S., Shi Wei, Wu Xueling, Yang Yongping, Yang Zhi-yong, Zhang Baoshan, Zhou Tongqing, ZHU Jiang
Принадлежит: The United States of America, as represented by the Secretary, Department of Health and Human Serv

Monoclonal neutralizing antibodies that specifically bind to HIV-1 gp120 and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV infection is disclosed. 1. An isolated monoclonal antibody , comprising a heavy chain variable domain and a light chain variable domain , wherein the heavy chain variable domain of the antibody comprises amino acids 26-33 (CDR1) , 51-58 (CDR2) and 97-114 (CDR3) of SEQ ID NO: 40 , and the light chain variable domain comprises a light chain variable domain from a VRC01-like monoclonal antibody , wherein the antibody specifically binds gp120 of HIV-1 , and wherein the antibody is neutralizing.2. An isolated VRC01-like monoclonal antibody , comprising a VRC01-like heavy chain and a VRC01-like light chain , wherein the heavy chain further comprises substitution of a histidine residue for the residue at position 54 of the heavy chain according to Kabat numbering , wherein the antibody specifically binds gp120 of HIV-1 and is neutralizing.3. An isolated antigen binding fragment of the antibody of .4. The isolated antigen binding fragment of claim 3 , wherein the fragment is a Fab fragment claim 3 , a Fab′ fragment claim 3 , a F(ab)′2 fragment claim 3 , a single chain Fv protein (scFv) claim 3 , or a disulfide stabilized Fv protein (dsFv).5. An isolated nucleic acid molecule encoding the antibody of or an antigen binding fragment of the antibody.6. An expression vector comprising the isolated nucleic acid molecule of operably linked to a promoter.7. An isolated host cell transformed with the nucleic acid molecule of .8. A composition comprising a therapeutically effective amount of the antibody of and a pharmaceutically acceptable carrier.9. A method for preventing or ...

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Номер записи: 23
17-01-2019 дата публикации

ANTIBODY AND ANTIBODY-CONTAINING COMPOSITION

Номер: US20190016788A1
Автор: TSUKAMOTO Yasuhiro
Принадлежит:

For many diseases due to microbes or the like, proliferation of microbes themselves is a cause of a symptom. However, there were cases where a substance released by the microbes is a cause of a symptom. In such cases, when attempting to treat a disease with an antibody, it was necessary to obtain an antibody against an antigen that is a substance causing the disease. However, it was difficult to find the underlying substance causing the disease among substances released by the microbes. An antibody (polyclonal) binding to not only an antigen but also to a substance, which is secreted by the antigen and accelerates the deterioration of a symptom, is obtained by immunizing birds with a lysis solution produced from lysing microbial cells as an antigen. Further, an antibody obtained with a surface protein of a virus as an antigen is expected to inhibit an infection by a virus. 1. An antibody against an antigen that is a lysis solution of a microbial cell.2. The antibody according to claim 1 , wherein the antibody is IgY obtained from an egg of a bird immunized with the lysis solution of the microbial cell as an antigen.3. The antibody according to claim 2 , wherein the bird is an ostrich.4Staphylococcus aureus.. The antibody according to any one of - claim 2 , wherein the microbial cell is5Propionibacterium acnes.. The antibody according to any one of - claim 2 , wherein the microbial cell is6. An antibody against an antigen that is a surface protein of a virus.7. The antibody according to claim 6 , wherein the antibody is IgY obtained from an egg of a bird immunized with the protein as an antigen.8. The antibody according to claim 7 , wherein the bird is an ostrich.9. The antibody according to any one of - claim 7 , wherein the protein comprises HIV gp120.10. The antibody according to any one of - claim 7 , wherein the protein comprises any one of HPV type 6 claim 7 , 11 claim 7 , 16 claim 7 , or 18.11. An antibody-containing composition comprising an antibody of any ...

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Номер записи: 24
17-01-2019 дата публикации

ANTI-PD-L1 ANTIBODIES, COMPOSITIONS AND ARTICLES OF MANUFACTURE

Номер: US20190016807A1
Автор: CHEUNG Jeanne, Chiu Henry, IRVING Bryan, LEHAR Sophie M., Maecker Heather, MARIATHASAN Sanjeev, Wu Yan
Принадлежит: Genentech, Inc.

The present application relates to anti-PD-L1 antibodies, nucleic acid encoding the same, therapeutic compositions thereof, and their use enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, including infection (e.g., acute and chronic) and tumor immunity. 195-: (canceled)96: An isolated nucleic acid encoding a heavy chain variable region of an anti-PD-L 1 antibody , wherein the antibody comprises the heavy chain variable region and a light chain variable region , wherein: (i) the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 15;', '(ii) the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 16; and', '(iii) the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 3; and, '(a) the heavy chain variable region comprises an HVR-H1, HVR-H2 and HVR-H3, wherein further (iv) the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 17;', '(v) the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 18; and', '(vi) the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 19., '(b) the light chain variable region comprises an HVR-L1, HVR-L2 and HVR-L3, wherein further97: The nucleic acid of claim 96 , wherein the antibody further comprises variable region light chain framework sequences juxtaposed between the HVRs according to the formula: (LC-FR1)-(HVR-L1)-(LC-FR2)-(HVR-L2)-(LC-FR3)-(HVR-L3)-(LC-FR4) claim 96 , wherein one or more of the framework sequences is the following:LC-FR1 comprises the amino acid sequence of SEQ ID NO: 11;LC-FR2 comprises the amino acid sequence of SEQ ID NO: 12;LC-FR3 comprises the amino acid sequence of SEQ ID NO: 13; orLC-FR4 comprises the amino acid sequence of SEQ ID NO: 14.98: The nucleic acid of claim 97 , wherein the antibody further comprises variable region heavy chain framework sequences juxtaposed between the HVRs according to the formula: (HC-FR1)-(HVR-H1)-(HC-FR2)-(HVR-H2)-(HC-FR3)-(HVR-H3)-(HC-FR4) claim 97 , wherein one or more of the ...

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Номер записи: 25
21-01-2021 дата публикации

CELL-TARGETING MOLECULES COMPRISING PROTEASE-CLEAVAGE RESISTANT, SHIGA TOXIN A SUBUNIT EFFECTOR POLYPEPTIDES AND CARBOXY-TERMINAL MOIETIES

Номер: US20210017512A1
Автор: HIGGINS Jack, KIM Jason, POMA Eric, WILLERT Erin
Принадлежит: Molecular Templates, Inc.

The present invention provides protease-cleavage resistant molecules comprising Shiga toxin effector polypeptides capable of exhibiting potent, Shiga toxin functions (e.g. subcellular routing and cytotoxicity). The present invention also provides protease-cleavage resistant, cell-targeting molecules for targeting specific cell types, e.g., infected or malignant cells. Certain molecules of the present invention are cytotoxic, and certain cell-targeting molecules of the present invention may be used for the targeted killing of specific cell types and the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections. Certain cell-targeting molecules of the invention exhibit improved, in vivo tolerability as compared to related cell-targeting molecules comprising protease-cleavage sensitive, wild-type, Shiga toxin effector polypeptides. The cell-targeting molecules of the invention can deliver additional materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, into the interiors of target cells. 1. A cell-targeting molecule comprisingi) a heterologous, binding region capable of specifically binding an extracellular target biomolecule; [ amino acids 75 to 251 of SEQ ID NO: 1 or SEQ ID NO: 2; or', 'amino acids 1 to 251 of SEQ ID NO: 1 or SEQ ID NO: 2;', 'and, '(a) a Shiga toxin A1 fragment region having a carboxy terminus, wherein said Shiga toxin A1 fragment region comprises an amino acid sequence that is at least 95% identical to, '(b) a disrupted furin-cleavage motif at the carboxy terminus of the A1 fragment region comprising one or more mutations in a minimal furin-cleavage site relative to a wild-type Shiga toxin A Subunit, the one or more mutations comprising a substitution mutation of an arginine residue natively positioned at 248 or 251 of SEQ ID NO: 1 or SEQ ID NO: 2 with a non-positively charged amino acid residue;', 'wherein the Shiga toxin ...

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Номер записи: 26
23-01-2020 дата публикации

BROADLY NEUTRALIZING HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) GP120-SPECIFIC MONOCLONAL ANTIBODY

Номер: US20200024330A1
Автор: Burton Dennis R., Chan-Hui Po-Ying, Doores Katherine, Frey Steven, HUBER Michael, Kaminsky Stephen, Koff Wayne, Mitchum Jennifer, Moyle Matthew, Olesen Ole, Phogat Sanjay K., Poignard Pascal Raymond Georges, Simek-Lemos Melissa Danielle De Jean De St. Marcel, Walker Laura Majorie
Принадлежит:

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 1. A non-naturally occurring PGT-121 monoclonal antibody or antigen binding portion thereof comprising (a) a light chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 150 , 151 and 152 and (b) a heavy chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 143 , 144 and 145.2. A non-naturally occurring PGT-121 monoclonal antibody or antigen binding portion thereof comprising (a) a light chain variable region comprising three complementarity determining regions having the amino acid sequences of SEQ ID NOS: 150 , 151 and 152 and (b) a heavy chain variable region comprising three complementarity determining regions having the amino acid sequences of SEQ ID NOS: 90 , 265 and 143.3. An immortalized B cell clone expressing the antibody or antigen binding portion thereof of or .4. One or more vectors containing and expressing a nucleic acid ...

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Номер записи: 27
28-01-2021 дата публикации

Antibody gene editing in b lymphocytes

Номер: US20210024889A1
Автор: Harald Hartweger, Michel Nussenzweig, Mila Jankovic
Принадлежит: ROCKEFELLER UNIVERSITY

Provided are compositions and methods that relate to engineering B cells that express heterologous antibodies. The B cells are modified using CRISPR-based approaches. The modified B cells maintain allelic exclusion, and are produced such that endogenous Ig genes are silenced, such as by insertion of a bi-cistronic cDNA into the Igh locus. Functional antibodies are produced by expression of the bi-cistronic cDNA. The modified B cells can be engineered to produce antibodies to any particular epitope. The modified B cells may be administered to an individual who is subsequently vaccinated with a composition comprising the epitope to stimulate production of the antibodies.

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Номер записи: 28
02-02-2017 дата публикации

Immunoconjugates with an Intracellularly-Cleavable Linkage

Номер: US20170028081A1
Автор: GOLDENBERG David M., Govindan Serengulam V., Moon Sung-Ju
Принадлежит:

The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates. 2. The composition of claim 1 , wherein n is between 1 and 12.3. The composition of claim 1 , wherein n is between 6 and 12.4. The composition of claim 1 , wherein n is 8.5. The composition of claim 1 , wherein AA is a lysine residue.6. The composition of claim 1 , wherein the MAb is a murine claim 1 , chimeric claim 1 , humanized claim 1 , or human monoclonal antibody or antigen binding fragment thereof.7. The composition of claim 6 , wherein said fragment is selected from the group consisting of Fab claim 6 , Fab′ claim 6 , F(ab) claim 6 , F(ab′) claim 6 , and scFv.8. The composition of claim 6 , wherein the MAb has constant domains and a hinge domain of a human IgG1 or a human IgG4 antibody.9. The composition of claim 6 , wherein the MAb has constant domains and a hinge domain of a human IgG4 antibody claim 6 , wherein serine 228 of the hinge is replaced with proline.10. The composition of claim 6 , wherein the antibody has constant domains and a hinge domain of a human IgG1 antibody and wherein one or more Fc amino acids are mutated to increase the half-life of the antibody in the blood claim 6 , or wherein one or more sugar moieties of the Fc have been deleted claim 6 , or one or more sugar moieties added to increase the blood half-life of the antibody.11. The composition of claim 1 , wherein said MAb is selected from the group consisting of hLL1 claim 1 , hLL2 claim 1 , RFB4 claim 1 , hA19 claim 1 , hA20 claim 1 , hRS7 claim 1 , hPAM4 claim 1 , KC4 claim 1 , hMN-3 claim 1 , hMN-14 claim 1 , hMN-15 claim 1 , hMu-9 claim 1 , hR1 claim 1 , CC49 claim 1 , hL243 claim 1 , D2/B and hIMMU-31.12. The composition of claim 1 , wherein said MAb binds to a tumor-associated antigen (TAA) ...

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Номер записи: 29
31-01-2019 дата публикации

Monoclonal antibodies directed against trimeric forms of the hiv-1 envelope glycoprotein with broad and potent neutralizing activity

Номер: US20190031742A1
Автор: Dennis R. Burton, Jennifer Mitcham, Laura Marjorie Walker, Matthew Moyle, Melissa Danielle De Jean De St. Marcel Simek-Lemos, Ole Olsen, Pascal Raymond Georges Poignard, Po-Ying Chan-Hui, Sanjay K. Phogat, Stephen Kaminsky, Steven Frey, Wayne Koff
Принадлежит: International AIDS Vaccine Initiative Inc, Scripps Research Institute, Theraclone Sciences Inc

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 are 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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Номер записи: 30
30-01-2020 дата публикации

METHODS TO IDENTIFY IMMUNOGENS BY TARGETING IMPROBABLE MUTATIONS

Номер: US20200031908A1
Автор: BONSIGNORI Mattia, Haynes Barton F., WIEHE Kevin J.
Принадлежит: Duke University

The invention is directed to methods to identify improbable mutations in the heavy or light chain variable domain of an antibody, methods to identify antigens which bind to antibodies comprising such improbable mutations, and methods of using such antigens to induce immune responses. 1. A method for identifying improbable mutations in the heavy or light chains of broadly neutralizing anti-HIV-1 antibodies comprising:(a) identifying at least one somatic mutation in the heavy or light chain variable domain of a broadly neutralizing anti-HIV-1 antibody, wherein if before antigenic selection the somatic mutation occurs at a frequency of less than 2%, then the somatic mutation is classified as an improbable mutation;(b) selecting the amino acid sequence of the broadly neutralizing anti-HIV-1 antibody of step (a) and reverting the at least one somatic mutation identified in step (a) to its germline-encoded amino acid(s) to thereby provide a recombinant antibody;(c) expressing the recombinant antibody of step (b) and testing the expressed recombinant antibody for neutralizing activity against an HIV-1 virus or for binding ability against the envelope of an HIV-1 virus, and(d) determining whether the improbable mutation identified in step (a) is functionally significant by testing whether the expressed recombinant antibody of step (c) exhibits a reduction of neutralizing activity or reduction of envelope binding as compared to an antibody with the same amino acid sequence but for the reverted amino acid sequence.2. A method to identify HIV-1 antigens that specifically or preferentially bind antibodies with an improbable mutation comprising:(a) identifying at least one somatic mutation in the heavy or light chain variable domain of a broadly neutralizing anti-HIV-1 antibody, wherein if before antigenic selection the somatic mutation occurs at a frequency of less than 2%, then the somatic mutation is classified as an improbable mutation;(b) selecting the amino acid sequence ...

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Номер записи: 31
30-01-2020 дата публикации

METHODS FOR INCREASING THE DIVERSITY OF MONOCLONAL ANTIBODIES PRODUCED AGAINST AN ANTIGEN

Номер: US20200032246A1
Автор: Cumming Dale Anthony
Принадлежит:

The present invention relates to methods for increasing the diversity of monoclonal antibodies produced against an antigen. The methods of the invention utilize immunization of a murine host defective in one or more enzymes involved in a post-translational modification of a polypeptide or a modification of a lipid, wherein said modification is exposed on a cell surface. The invention also relates to monoclonal antibodies produced by these methods and which are not produced when a normal mouse is immunized with the same antigen. The invention further relates to compositions comprising these monoclonal antibodies, as well as to such monoclonal antibodies bound or conjugated to a toxin, a detectable marker or to a solid support. 120-. (canceled)21. A method of producing an antibody library that comprises an antibody that binds to an epitope on a molecule of interest , wherein the epitope is not present naturally in a wild-type host , the method comprising the steps of:(a) immunizing a knockout host with an antigen that comprises the epitope present on said molecule of interest in a manner sufficient for said knockout host to develop antibodies against said epitope, wherein when the wild-type host is immunized with the antigen it does not produce an antibody that binds to the epitope, wherein said knockout host comprises a knockout mutation in an enzyme involved in post-translational glycosylation of a polypeptide;(b) isolating splenocytes or B cells from said immunized host;(c) extracting ribonucleic acid (RNA) from the isolated splenocytes or B cells; and(d) generating an antibody library from the extracted RNA.22. The method of claim 21 , wherein the library is a phage display library.23. The method of claim 21 , wherein the library is a yeast display library.24. The method of further comprising the step of amplifying the RNA by polymerase chain reaction (PCR).25. The method of claim 21 , wherein the B cells are isolated from blood claim 21 , bone marrow claim 21 , ...

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Номер записи: 32
04-02-2021 дата публикации

ANTI-PD-L1 ANTIBODIES, COMPOSITIONS AND ARTICLES OF MANUFACTURE

Номер: US20210032345A1
Автор: CHEUNG Jeanne, Chiu Henry, IRVING Bryan, LEHAR Sophie M., Maecker Heather, MARIATHASAN Sanjeev, Wu Yan
Принадлежит: Genentech, Inc.

The present application relates to anti-PD-L1 antibodies, nucleic acid encoding the same, therapeutic compositions thereof, and their use enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, including infection (e.g., acute and chronic) and tumor immunity. 295-. (canceled) This application is a continuation of U.S. patent application Ser. No. 15/075,616, filed Mar. 21, 2016, now abandoned, which is a continuation of U.S. patent application Ser. No. 14/825,779, filed Aug. 13, 2015, now abandoned, which is a continuation of U.S. patent application Ser. No. 13/954,796, filed Jul. 30, 2013, now abandoned, which is a U.S. patent application Ser. No. 13/478,511 filed May 23, 2012, now abandoned, which is a division of U.S. application Ser. No. 12/633,339 filed Dec. 8, 2009, now issued as U.S. Pat. No. 8,217,149, issued Jul. 10, 2012, which claims the benefit of priority under 35 USC 119(e) of U.S. Provisional Application No. 61/121,092 filed Dec. 9, 2008, the disclosures of which are incorporated herein by reference in their entirety.This application contains a Sequence Listing submitted via EFS-Web and hereby incorporated by reference in its entirety. Said ASCII copy, created on Oct. 25, 2016, is named 146392637402SeqList.txt, and is 28 KB in size.This invention relates generally to immune function and to enhancing T-cell function, including the upregulation of cell-mediated immune responses and to the treatment of T cell dysfunctional disorders.Co-stimulation or the provision of two distinct signals to T-cells is a widely accepted model of lymphocyte activation of resting T lymphocytes by antigen-presenting cells (APCs). Lafferty et al., 53: 27-42 (1975). This model further provides for the discrimination of self from non-self and immune tolerance. Bretscher et al. 169: 1042-1049 (1970); Bretscher, P. A. 96: 185-190 (1999); Jenkins et al., 165: 302-319 (1987). The primary signal, or antigen ...

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Номер записи: 33
11-02-2016 дата публикации

STABILIZED SINGLE HUMAN CD4 DOMAINS AND FUSION PROTEINS

Номер: US20160039904A1
Автор: Chen Weizao, Dimitrov Dimiter S., Ponraj Prabakaran
Принадлежит:

The invention provides a polypeptide comprising a single domain CD4, as well a fusion protein comprising the single domain CD4 and one or more fusion partners. A nucleic acid encoding the polypeptide or fusion protein, as well as compositions or cells comprising the polypeptide, fusion protein, or nucleic acid also are provided. 1. A polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2.2. A composition comprising the polypeptide of and a carrier.3. A fusion protein comprising (i) the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 and (ii) one or more fusion partners claim 1 , wherein the one or more fusion partners optionally is fused to the amino acid sequence of (i) via a linker.4. (canceled)5. The fusion protein of claim 3 , wherein the one or more fusion partners is an engineered antibody domain (eAd) claim 3 , an HIV envelope glycoprotein claim 3 , an Fc region or portion thereof claim 3 , an immunoglobulin heavy chain constant region claim 3 , an immunoglobulin light chain constant region claim 3 , or a combination thereof.6. (canceled)7. The fusion protein of claim 5 , wherein the one or more fusion partners is an eAd and the eAd binds to an HIV envelope glycoprotein.8. The fusion protein of claim 7 , wherein the eAd comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-16.9. (canceled)10. The fusion protein of claim 5 , wherein the one or more fusion partners is an HIV envelope glycoprotein and the HIV envelope glycoprotein is gp120.1112.-. (canceled)14. The fusion protein of claim 13 , wherein the antibody or antibody fragment of A comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-16.1512. The fusion protein of claim claim 13 , wherein the Fc region or portion thereof is an IgG1 Fc region.16. The fusion protein of claim 15 , wherein the Fc region or portion thereof comprises SEQ ID NO: 7 or SEQ ID NO: 8.17. The fusion protein of claim 3 , wherein the linker ...

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Номер записи: 34
08-02-2018 дата публикации

STRUCTURED VIRAL PEPTIDE COMPOSITIONS AND METHODS OF USE

Номер: US20180037636A1
Автор: Bird Gregory, Walensky Loren D.
Принадлежит: Dana-Farber Cancer Institute, Inc.

The invention provides structurally constrained viral peptides for use as therapeutic and vaccination agents, and for the production of antibodies for use in a number of applications including as therapeutic agents. The invention further provides methods and kits for use of the structurally constrained peptides and antibodies of the instant invention. The invention is based, at least in part, on the result provided herein demonstrating the viral hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides. 113.-. (canceled)14. A structurally constrained peptide comprising 3 to 38 amino acids of an HR-2 sequence , wherein the peptide comprises at least 3 contiguous amino acids of an HR-2 peptide , or at least two amino acids on a single face of a helix of an HR-2 peptide , or at least two interacting face amino acids of an HR-2 peptide; or a conservative substitution thereof.1533.-. (canceled)34. The structurally constrained peptide of claim 14 , wherein the HR-2 domain comprises at least one modification from the group consisting of: hydrocarbon staple claim 14 , amino acid mutation claim 14 , and non-natural amino acid incorporation.35. The structurally constrained peptide of claim 34 , herein the HR-2 domain comprises two hydrocarbon staples.36. The structurally constrained peptide of claim 35 , wherein one of the hydrocarbon staples is positioned so as to link amino acid residues i and i+3 relative to amino acid positions of a first helix of the polypeptide claim 35 , and wherein one of said hydrocarbon staples is positioned so as to link amino acid residues i and i+4 relative to amino acid positions of a second helix of the polypeptide.37. The structurally constrained peptide of claim 14 , wherein a single ...

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Номер записи: 35
12-02-2015 дата публикации

Neutralizing antibodies to hiv-1 and their use

Номер: US20150044137A1
Автор: John R. Mascola, Joseph Casazza, Mark Connors, Peter D. Kwong, Rebecca M. Lynch, Tongqing Zhou, Xueling Wu
Принадлежит: US Department of Health and Human Services

Neutralizing antibodies that specifically bind to HIV-1 gp120 and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV infection is disclosed.

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Номер записи: 36
14-02-2019 дата публикации

HIV ANTIBODY COMPOSITIONS AND METHODS OF USE

Номер: US20190048067A1
Автор: Briggs Adrian Wrangham, Goldfless Stephen J., Timberlake Sonia, VIGNEAULT Francois
Принадлежит:

This invention relates to novel anti-HIV antibodies that can be used in the treatment and detection of human immunodeficiency virus (HIV). These antibodies exhibit a high degree of sensitivity and can provide a broad range of specificity. 1. An anti-HIV antibody , wherein the anti-HIV antibody binds to or is capable of binding to an N-glycan epitope of an HIV with an affinity of 1 nM or less.2. The antibody of claim 1 , wherein the antibody neutralizes or is capable of neutralizing HIV.3. The antibody of claim 1 , wherein the antibody inhibits the infectivity of two or more strains or subtypes of HIV.4. The antibody of claim 1 , wherein the HIV is HIV-1.5. The antibody of claim 1 , wherein the HIV is group M HIV-1.6. (canceled)7. The antibody of claim 1 , wherein the antibody is glycoengineered to modify the oligosaccharides in the Fc region claim 1 , and wherein the antibody has increased ADCC effector function as compared to a non-glycoengineered antibody.8. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.9. The antibody of claim 1 , wherein the antibody is a human antibody claim 1 , a humanized antibody claim 1 , or a chimeric antibody.1011-. (canceled)12. The antibody of claim 9 , wherein the antibody is a full-length IgG class antibody.13. The antibody of claim 1 , wherein the antibody is an antibody fragment.14. The antibody of claim 13 , wherein the antibody is a single chain variable fragment (scFv).15. The antibody of claim 1 , wherein the antibody comprises(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 17, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 18, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 19, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 20, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 21, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 22;(b) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 23, a CDR-H2 comprising the amino acid ...

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Номер записи: 37
21-02-2019 дата публикации

TRISPECIFIC AND/OR TRIVALENT BINDING PROTEINS FOR PREVENTION OR TREATMENT OF HIV INFECTION

Номер: US20190054182A1
Автор: Asokan Mangaiarkarasi, Beil Christian, BENINGA Jochen, Connors Mark, DORIA-ROSE Nicole A., Huang Jinghe, KOUP Richard A., Kruip Jochen, KWON Young Do, Kwong Peter D., Lange Christian, LEUSCHNER Wulf Dirk, Mascola John R., Nabel Gary J., Pegu Amarendra, Qiu Huawei, Rao Ercole, Wei Ronnie, Xu Ling, Yang Zhi-yong, Zhou Tongqing
Принадлежит:

Provided herein are compositions comprising trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, where in a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins for the treatment and/or prevention of HIV/AIDS. 1. A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins , wherein a first polypeptide chain comprises a structure represented by the formula:{'br': None, 'sub': L2', '1', 'L1', '2', 'L, 'V-L-V-L-C\u2003\u2003[I];'} {'br': None, 'sub': H1', '3', 'H2', '4', 'H1, 'V-L-V-L-C\u2003\u2003[II];'}, 'a second polypeptide chain comprises a structure represented by the formula {'br': None, 'sub': H3', 'H1, 'V-C\u2003\u2003[III],'}, 'a third polypeptide chain comprises a structure represented by the formula {'br': None, 'sub': L3', 'L, 'V-C\u2003\u2003[IV];'}, 'and a fourth polypeptide chain comprises a structure represented by the formulawherein{'sub': 'L1', 'Vis a first immunoglobulin light chain variable domain;'}{'sub': 'L2', 'Vis a second immunoglobulin light chain variable domain;'}{'sub': 'L3', 'Vis a third immunoglobulin light chain variable domain;'}{'sub': 'H1', 'Vis a first immunoglobulin heavy chain variable domain;'}{'sub': 'H2', 'Vis a second immunoglobulin heavy chain variable domain;'}{'sub': 'H3', 'Vis a third immunoglobulin heavy chain variable domain;'}{'sub': 'L', 'Cis an immunoglobulin light chain constant domain;'}{'sub': H1', 'H1, 'Cis an immunoglobulin Cheavy chain constant domain; and'}{'sub': 1', '2', '3', '4, 'L, L, ...

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Номер записи: 38
01-03-2018 дата публикации

COMPOSITIONS FOR PREVENTING AND/OR TREATING AN INFECTION BY AN HIV-1 VIRUS

Номер: US20180057535A1
Автор: Debre Patrice, Vieillard Vincent
Принадлежит:

The present invention relates to an immunogenic composition comprising an antigenic peptide of formula (I) below: Nt-S-X1-X2-X3-K-X4-Ct (I) [SEQ ID N° 1], wherein Nt consists of a peptide having from 0 to 50 amino acids in length, Ct consists of a peptide having from 0 to 50 amino acids in length, each of X1 to X4 consists of an amino acid residue, wherein: (i) X1 means the specific amino acid W or (ii) X1 means any amino acid residue excepted W, (i) X2 means the specific amino acid S or (ii) X2 means any amino acid residue excepted S, (i) X3 means the specific amino acid N or (ii) X3 means any amino acid residue excepted N, (i) X4 means the specific amino acid S or (ii) X4 means any amino acid residue excepted S, with the proviso that three out of the four amino acid residues X1, X2, X3 and X4 mean the specific amino acid defined in their respective meaning (i) above, and the remaining amino acid residue among X1 to X4 means any amino acid residue excepted the specific amino acid residue defined in its meaning (i), for preventing and/or treating an infection of an individual with an HIV-1 virus. 116-. (canceled)20. The antibody according to claim 17 , wherein Nt is an amino acid sequence of 1 to 10 amino acid residues in length.21. The antibody according to claim 17 , wherein Nt comprises the amino acid sequence PWNA [SEQ ID N° 10].22. The antibody according to claim 17 , wherein Ct is an amino acid sequence of 1 to 10 amino acid residues in length.23. The antibody according to claim 17 , wherein Ct comprises the amino acid sequence LDDIW [SEQ ID N° 11].24. The antibody according to claim 17 , wherein meaning (ii) of each of X1 claim 17 , X2 claim 17 , X3 and X4 is selected from the group consisting of Alanine (Ala or A) claim 17 , Cysteine (Cys or C) claim 17 , Glycine (Gly or G) claim 17 , Proline (Pro or P) and Valine (Val or V).26. The antibody according to claim 17 , wherein the antigenic peptide of formula (I) is covalently linked to a carrier molecule.27. ...

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Номер записи: 39
01-03-2018 дата публикации

BROADLY NEUTRALIZING HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) GP120-SPECIFIC MONOCLONAL ANTIBODY

Номер: US20180057570A1
Автор: Burton Dennis R., Chan-Hui Po-Ying, Doores Katherine, Frey Steven, HUBER Michael, Kaminsky Stephen, Koff Wayne, Mitcham Jennifer, Moyle Matthew, Olsen Ole, Phogat Sanjay K., Poignard Pascal Raymond Georges, Simek-Lemos Melissa Danielle De Jean De St. Marcel, Walker Laura Majorie
Принадлежит:

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. 1. A non-naturally occurring PGT-121 monoclonal antibody or antigen binding portion thereof comprising (a) a light chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 150 , 151 and 152 and (b) a heavy chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 143 , 144 and 145.2. A non-naturally occurring PGT-121 monoclonal antibody or antigen binding portion thereof comprising (a) a light chain variable region comprising three complementarity determining regions having the amino acid sequences of SEQ ID NOS: 150 , 151 and 152 and (b) a heavy chain variable region comprising three complementarity determining regions having the amino acid sequences of SEQ ID NOS: 90 , 265 and 143.3. An immortalized B cell clone expressing the antibody or antigen binding portion thereof of or .4. One or more vectors containing and expressing a nucleic acid ...

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Номер записи: 40
20-02-2020 дата публикации

TRISPECIFIC AND/OR TRIVALENT BINDING PROTEINS FOR PREVENTION OR TREATMENT OF HIV INFECTION

Номер: US20200054765A1
Автор: Asokan Mangaiarkarasi, Beil Christian, BENINGA Jochen, Connors Mark, DORIA-ROSE Nicole A., Huang Jinghe, KOUP Richard A., Kruip Jochen, KWON Young Do, Kwong Peter D., Lange Christian, LEUSCHNER Wulf Dirk, Mascola John R., Nabel Gary J., Pegu Amarendra, Qiu Huawei, Rao Ercole, Wei Ronnie, Xu Ling, Yang Zhi-yong, Zhou Tongqing
Принадлежит:

Provided herein are compositions comprising trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins for the treatment and/or prevention of HIV/AIDS. 1. A binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins , wherein a first polypeptide chain comprises a structure represented by the formula:{'br': None, 'sub': L2', '1', 'L1', '2', 'L, 'V-L-V-L-C\u2003\u2003[I];'} {'br': None, 'sub': H1', '3', 'H2', '4', 'H1, 'V-L-V-L-C\u2003\u2003[II];'}, 'a second polypeptide chain comprises a structure represented by the formula {'br': None, 'sub': H3', 'H1, 'V-C\u2003\u2003[III];'}, 'a third polypeptide chain comprises a structure represented by the formula {'br': None, 'sub': L3', 'L, 'V-C\u2003\u2003[IV];'}, 'and a fourth polypeptide chain comprises a structure represented by the formulawherein{'sub': 'L1', 'Vis a first immunoglobulin light chain variable domain;'}{'sub': 'L2', 'Vis a second immunoglobulin light chain variable domain;'}{'sub': 'L3', 'Vis a third immunoglobulin light chain variable domain;'}{'sub': 'H1', 'Vis a first immunoglobulin heavy chain variable domain;'}{'sub': 'H2', 'Vis a second immunoglobulin heavy chain variable domain;'}{'sub': 'H3', 'Vis a third immunoglobulin heavy chain variable domain;'}{'sub': 'L', 'Cis an immunoglobulin light chain constant domain;'}{'sub': H1', 'H1, 'Cis an immunoglobulin Cheavy chain constant domain; and'}{'sub': 1', '2', '3', '4, 'L, L, L ...

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Номер записи: 41
28-02-2019 дата публикации

NON-HUMAN ANIMALS HAVING A MUTANT KYNURENINASE GENE

Номер: US20190062410A1
Автор: Kyratsous Christos, Mujica Alexander O.
Принадлежит: Regeneron Pharmaceuticals, Inc.

Non-human animals, methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a mutant L-kynurenine hydrolase (or kynureninase) gene. Said non-human animals may be described, in some embodiments, as having a genetic modification in an endogenous kynureninase gene so that said non-human animals express a kynureninase polypeptide that includes an amino acid substitution that results in the elimination of an epitope in said kynureninase polypeptide that is present in the membrane proximal external region of human immunodeficiency virus-1 gp41. 1. A rodent whose genome comprises a mutant kynureninase (Kynu) gene ,wherein the mutant Kynu gene comprises one or more point mutations in exon three and encodes a mutant Kynu polypeptide comprising the amino acid sequence of ELEKWA (SEQ ID NO: 36);wherein the mutant Kynu polypeptide is expressed in the rodent; andwherein the rodent is a mouse or a rat.2. The rodent of claim 1 , wherein the genome of the rodent comprises a disruption of an endogenous Kynu gene.3. The rodent of claim 2 , wherein the rodent is homozygous for the disruption of the endogenous Kynu gene.4. The rodent of claim 1 , wherein the mutant Kynu gene further comprises one or more site-specific recombinase recognition sites.5. The rodent of claim 4 , wherein the mutant Kynu gene comprises a recombinase gene and a selection marker flanked by recombinase recognition sites claim 4 , which recombinase recognition sites are oriented to direct an excision.6. The rodent of claim 5 , wherein the recombinase gene is operably linked to a promoter that drives expression of the recombinase gene in differentiated cells and does not drive expression of the recombinase gene in undifferentiated cells claim 5 , or is transcriptionally competent and developmentally regulated.7. The rodent of claim 6 , wherein the promoter is or comprises SEQ ID NO:37 claim 6 , SEQ ID NO:38 claim 6 , or SEQ ID NO:39.8. The rodent of claim 1 , ...

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Номер записи: 42
28-02-2019 дата публикации

Immunological Reagents

Номер: US20190062431A1
Автор: Craig Fenwick, Giuseppe Pantaleo
Принадлежит: MabQuest SA

This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) and to methods for using the same to treat, prevent and/or ameliorate an infectious disease (e.g., human immunodeficiency virus (HIV)), cancer and/or autoimmunity. In addition, this disclosure identifies a novel binding patch (“P2”) on PD-1 that is linked with a previously unidentified functional activity of PD-1 that is distinct from the interaction site involved with either the PD-L1 or PD-L2 ligands. Furthermore, we demonstrate that antibodies that interact with this region of PD-1 are able to act as antagonists of PD-1 and that this antagonism is further enhanced with the addition of antibodies that act through the blockade of the PD-1/PD-L1/L2 interaction.

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Номер записи: 43
08-03-2018 дата публикации

ANTIBODY AND ANTIBODY-CONTAINING COMPOSITION

Номер: US20180066042A1
Автор: TSUKAMOTO Yasuhiro
Принадлежит:

For many diseases due to microbes or the like, proliferation of microbes themselves is a cause of a symptom. However, there were cases where a substance released by the microbes is a cause of a symptom. In such cases, when attempting to treat a disease with an antibody, it was necessary to obtain an antibody against an antigen that is a substance causing the disease. However, it was difficult to find the underlying substance causing the disease among substances released by the microbes. An antibody (polyclonal) binding to not only an antigen but also to a substance, which is secreted by the antigen and accelerates the deterioration of a symptom, is obtained by immunizing birds with a lysis solution produced from lysing microbial cells as an antigen. Further, an antibody obtained with a surface protein of a virus as an antigen is expected to inhibit an infection by a virus. 112-. (canceled)13Staphylococcus aureusPropionibacterium acnes.. A method of treating skin of a subject , comprising administering a composition comprising ostrich polyclonal antibodies against antigens from a lysis solution of a microbial cell to the subject , wherein the antigens comprises enterotoxin , super antigen TSST-1 , coagulase , or protease , and the microbial cell comprises and/or14. The method of claim 13 , wherein the antibodies are polyclonal IgY antibodies.15. The method of claim 14 , wherein the antibodies are produced by immunizing an ostrich with the lysis solution of the microbial cell claim 14 , and obtaining the antibodies from an egg of the ostrich.16Staphylococcus aureus.. The method of claim 13 , wherein the microbial cell comprises17. The method of claim 16 , wherein the subject has atopy.18. The method of claim 16 , wherein the subject has acne.19. The method of claim 16 , wherein the subject has atopy and acne.20Propionibacterium acnes.. The method of claim 13 , wherein the microbial cell comprises21. The method of claim 20 , wherein the subject has atopy.22. The method ...

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Номер записи: 44
15-03-2018 дата публикации

HIV-1 NEUTRALIZING ANTIBODIES AND USES THEREOF (V3 ANTIBODIES)

Номер: US20180072797A1
Автор: BONSIGNORI Mattia, Bradley Todd, Haynes Barton F., Liao Hua-Xin, MEYERHOFF Ryan, Moody M. Anthony
Принадлежит:

The invention is directed to HIV-1 neutralizing antibodies, CD4 binding site and V3 glycan antibodies, and methods for their uses. 1. A recombinant antibody or fragment thereof with the binding specificity of the V3 glycan binding antibody DH542 , DH542_L4 or DH5422_QSA.2. The antibody or fragment thereof of wherein the antibody or fragment thereof comprises:a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VH chain of antibody DH542 anda VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of antibody DH542 or a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of antibody DH429, ora VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of antibody DH542_QSA.3. The antibody or fragment thereof of wherein the antibody comprises:{'figref': {'@idref': 'DRAWINGS', 'FIGS. 8, 20B'}, 'a VH chain of an antibody selected from the group of antibodies in the DH270 lineage () and'}{'figref': {'@idref': 'DRAWINGS', 'FIGS. 8, 16'}, 'a VL chain of an antibody selected from the group of antibodies in the in the DH270 lineage ().'}4. The antibody or fragment thereof of wherein the antibody or fragment thereof comprises:a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VH chain of antibody DH542 anda VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of antibody DH542.5. The antibody or fragment thereof of wherein the antibody or fragment thereof comprises:a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VH chain of antibody DH542 anda VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of antibody DH429.6. The antibody or fragment thereof of wherein the antibody or fragment thereof comprises a VH chain that is 90% ...

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Номер записи: 45
24-03-2022 дата публикации

ANTIBODIES THAT TARGET HIV GP120 AND METHODS OF USE

Номер: US20220089698A1
Автор: Balakrishnan Mini, Carr Brian A., Hung Magdeleine S., Kanwar Manu, Pace Craig S., Rehder Doug, Schenauer Matthew Robert, Serafini Loredana, Stephenson Heather Theresa, Thomsen Nathan D., Yu Helen, ZHANG Xue
Принадлежит:

Antibodies that bind to HIV gp120 and neutralize HIV are disclosed. Also disclosed are methods of using such antibodies alone or in combination with other therapeutic agents to treat or prevent HIV infection. 197-. (canceled)98. A nucleic acid molecule or nucleic acid molecules encoding an antibody or an antigen-binding fragment thereof that binds to human immunodeficiency virus-1 (HIV-1) Envelope glycoprotein gp120 , the antibody or antigen-binding fragment thereof comprising (i) a heavy chain variable region (VH) comprising VH complementary determining regions 1-3 (CDRs 1-3) and (ii) a light chain variable region (VL) comprising VL CDRs 1-3 , wherein the VH CDRs 1-3 and VL CDRs 1-3 have the sequences set forth in:(i) SEQ ID NOs.: 159, 138, 139, 140, 141, and 142, respectively;(ii) SEQ ID NOs.: 137, 160, 139, 140, 141, and 142, respectively;(iii) SEQ ID NOs.: 137, 161, 139, 140, 141, and 142, respectively;(iv) SEQ ID NOs.: 137, 162, 139, 140, 141, and 142, respectively;(v) SEQ ID NOs.: 137, 163, 139, 140, 141, and 142, respectively;(vi) SEQ ID NOs.: 137, 138, 164, 140, 141, and 142, respectively;(vii) SEQ ID NOs.: 159, 138, 164, 140, 141, and 142, respectively;(viii) SEQ ID NOs.: 137, 138, 139, 140, 165, and 142, respectively;(ix) SEQ ID NOs.: 137, 138, 139, 140, 166, and 142, respectively;(x) SEQ ID NOs.: 137, 138, 139, 140, 167, and 142, respectively;(xi) SEQ ID NOs.: 137, 138, 139, 140, 168, and 142, respectively;(xii) SEQ ID NOs.: 137, 138, 154, 140, 141, and 142, respectively; or{'claim-text': 'wherein the antibody or antigen-binding fragment thereof includes in framework region 3 (FR3) of the VH at position corresponding to 74a, 74b, 74c, and 74d (Kabat numbering) the amino acid sequence set forth in SEQ ID NO: 62.', '#text': '(xiii) SEQ ID NOs.: 137, 138, 139, 140, 141, and 142, respectively; and'}99. The nucleic acid molecule or nucleic acid molecules of claim 98 , wherein the nucleic acid or nucleic acids comprise DNA claim 98 , cDNA or mRNA.100. The ...

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Номер записи: 46
18-03-2021 дата публикации

NEUTRALIZING ANTIBODIES TO HIV-1 ENV AND THEIR USE

Номер: US20210079070A1
Автор: KWON Young Do, Kwong Peter, Liu Qingbo, LUSSO Paolo, Mascola John
Принадлежит: The United States of America, as represented by the Secretary, Department of Health and Human Servic

Antibodies and antigen binding fragments that specifically bind to HIV-1 Env and neutralize HIV-1 are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed. 1. A monoclonal antibody , comprising:{'sub': 'H', 'a heavy chain variable region (V) comprising a heavy chain complementarity determining region (HCDR) 1, a HCDR2, and a HCDR3 of a parent VRC01-class antibody;'}{'sub': 'L', 'a light chain variable region (V) comprising a light chain complementarity determining region (LCDR) 1, a LCDR2, and a LCDR3 of the parent VRC01-class antibody;'}a modification of a heavy chain framework region (HFR) 3 compared to the parent VRC01-class antibody, wherein the modification is a substitution of the amino acids of Kabat positions 72-76 of the parent VRC01-class antibody with the sequence set forth as QLSQDPDDPDWG (SEQ ID NO: 36);wherein the parent VRC01-class antibody does not contain an amino acid insertion between Kabat positions 75 and 76 compared to an IGHV1-2*02 germline sequence; andwherein the antibody specifically binds to HIV-1 Env and neutralizes HIV-1.2. The monoclonal antibody of claim 1 , whereina HFR 1, a HFR2, the HFR3, and a HFR4 of the monoclonal antibody comprise, in aggregate and not including the modification, no more than 10 amino acid substitutions compared to the corresponding sequences of the parent VRC01-class antibody; anda light chain framework region (LFR) 1, a LFR2, a LFR3, and a LFR4 of the monoclonal antibody comprise, in aggregate, no more than 10 amino acid substitutions compared to the corresponding sequences of the parent VRC01-class antibody.3. The monoclonal antibody of claim 2 , wherein the amino acid substitutions are conservative amino acid substitutions.4. The monoclonal antibody of ...

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Номер записи: 47
14-03-2019 дата публикации

NEUTRALIZING ANTIBODIES TO HIV-1 GP41 AND THEIR USE

Номер: US20190077849A1
Автор: "ODell Sijy", Asokan Mangaiarkarasi, Bailer Robert, Bender Michael, Carlton Kevin, Chuang Gwo-Yu, Connors Mark, Cooper Jonathan, Georgiev Ivelin, Gindin Tatyana, Kueltzo Lisa, KWON Young Do, Kwong Peter, Louder Mark, Mascola John, McKee Krisha, Ofek Gilad, Pegu Amarendra, Schwartz Richard, Shapiro Lawrence, Zhang Baoshan
Принадлежит:

Neutralizing antibodies that specifically bind to HIV-1 Env and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed. 1. An isolated antibody , comprising:{'sub': H', 'H', 'L', 'L, 'a heavy chain variable region (V) comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 of the Vset forth as SEQ ID NO: 75, and a light chain variable region (V) comprising a light chain complementarity determining region (LCDR)1, a LCDR2, and a LCDR3 of the Vset forth as SEQ ID NO: 6, wherein the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2, and the LCDR3 comprise the amino acid sequences set forth as: SEQ ID NOs; 7, 8, 77, 10, 11, and 12, respectively (10E8v4 S100cF CDRs); and'}wherein the antibody specifically binds to gp41 and neutralizes HIV-1.2. (canceled)3. The isolated antibody of claim 1 , wherein{'sub': 'H', 'the Vcomprises arginine, glutamate, serine, lysine, aspartate, threonine, lysine, threonine, valine, threonine, threonine, tyrosine, glutamine, and isoleucine residues at kabat positions 3, 61, 62, 64, 72, 74, 75, 77, 82c, 84, 87, 89, 105, and 110, respectively; and'}{'sub': 'L', 'the Vcomprises alanine, serine, aspartate, proline, alanine, lysine, glutamine, valine, isoleucine, threonine, glutamate, and aspartate residues at kabat positions 1, 2, 7, 8, 9, 16, 17, 45, 58, 76, 83, and 85, respectively.'}4. The isolated antibody of any of claim 1 , comprising an arginine residue at kabat position 5.5. The isolated antibody of any of claim 1 , wherein the Vand the Vcomprise amino acid sequences at least 90% identical to SEQ ID NOs: 75 and 6 claim 1 , respectively (10E8v4 S100cF).6. The isolated antibody of any of claim 1 , wherein the ...

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Номер записи: 48
22-03-2018 дата публикации

Human Immunodeficiency Virus Neutralizing Antibodies and Methods of Use Thereof

Номер: US20180079800A1
Автор: Bjorkman Pamela J., Diskin Ron, Nussenzweig Michel, Scheid Johannes
Принадлежит:

The invention provides broadly neutralizing antibodies directed to epitopes of Human Immunodeficiency Virus, or HIV. The invention further provides compositions containing HIV antibodies used for prophylaxis, and methods for diagnosis and treatment of HIV infection. 125-. (canceled)26. A therapeutic composition comprising:i. a recombinantly produced monoclonal anti-HIV antibody or an HIV gp120-derived antigen-binding fragment thereof comprising the CDR1, CDR2, and CDR3 regions of the sequence of SEQ ID NO: 896 and the CDR1, CDR2, and CDR3 regions of SEQ ID NO: 910 andii. a pharmaceutically acceptable carrier.27. The therapeutic composition of wherein the anti-HIV antibody or an HIV gp120-derived antigen-binding fragment thereof neutralizes HIV virus SM53M.PB12 at an ICconcentration of less than 1.0 μg/mL claim 26 , or an HIV virus R1166.c1 at an ICconcentration of less than 1.0 μg/mL.28. The therapeutic composition of wherein the anti-HIV antibody or an HIV gp120-derived antigen-binding fragment thereof neutralizes a VRC01-resistant HIV virus at an ICconcentration of less than 30 μg/mL.29. A method of preventing or treating an HIV infection in a patient in need thereof comprising the steps of:i. identifying a patient in need of such prevention or treatment, and{'claim-ref': {'@idref': 'CLM-00026', 'claim 26'}, 'ii. administering to said patient a therapeutically effective amount of the therapeutic composition of .'}30. The method of claim 29 , additionally comprising the administration of a second therapeutic agent.31. The method of claim 30 , wherein said second therapeutic agent is an antiviral agent.32. A method for making an anti-HIV antibody or fragment thereof according to claim 26 , said method comprising culturing a cell comprising a vector comprising a nucleic acid encoding the heavy and light chains of said antibody under conditions whereby the nucleic acid is expressed claim 26 , and isolated said anti-HIV antibody or fragment thereof.33. A method to ...

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Номер записи: 49
22-03-2018 дата публикации

HIV-1 NEUTRALIZING ANTIBODIES AND USES THEREOF (CD4bs ANTIBODIES)

Номер: US20180079801A1
Автор: BONSIGNORI Mattia, Haynes Barton F., Liao Hua-Xin
Принадлежит:

The invention relates to the identification of monoclonal HIV-1 neutralizing antibodies, such as, but not limited to, antibodies that bind to the CD4 binding site (CD4bs) of HIV-1 gp120, their recombinant expression and purification and uses. In certain aspects, the invention provides a pharmaceutical composition comprising anyone of the antibodies of the invention or fragments thereof or any combination thereof. In certain aspects the invention provides methods to treat or prevent HIV-1 infection in a subject comprising administering to the subject a pharmaceutical composition comprising any one of the inventive antibodies or fragments thereof. 1. A recombinant antibody or fragment thereof with the binding specificity of the CD4 binding site antibody CH557.2. The antibody or fragment thereof of wherein the antibody or fragment thereof is fully human.3. A recombinant antibody or fragment thereof comprising: a variable heavy chain (VH) amino acid sequence claim 1 , or fragment thereof claim 1 , selected from the group of VH amino acid sequences of an antibody CH490 claim 1 , CH491 claim 1 , CH492 claim 1 , CH493 claim 1 , CH555 claim 1 , CH556 and CH557 and a variable light chain (VL) amino acid sequence or fragment thereof claim 1 , selected from the group of VL amino acid sequences of an antibody CH490 claim 1 , CH491 claim 1 , CH492 claim 1 , CH493 claim 1 , CH555 claim 1 , CH556 and CH557 claim 1 , wherein the recombinant antibody or fragment thereof binds to the CD4 binding site of the HIV-1 envelope.4. The antibody or fragment thereof of wherein the antibody or fragment thereof comprises a VH chain that is 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% claim 1 , 94% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% or 100% identical to the VH chain of antibody CH557 and comprises a VL chain that is 90% claim 1 , 91% claim 1 , 92% claim 1 , 93% claim 1 , 94% claim 1 , 95% claim 1 , 96% claim 1 , 97% claim 1 , 98% claim 1 , 99% or 100% ...

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Номер записи: 50
23-03-2017 дата публикации

ENGINEERED ANTIBODY CONSTANT DOMAIN MOLECULES

Номер: US20170081393A1
Автор: Dimitrov Dimiter S.
Принадлежит: The U.S.A., as represented by the Secretary, Department of Health and Human Services

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. 1. A polypeptide comprising an immunoglobulin CH2 domain of IgG , IgA or IgD , or a CH3 domain of IgE or IgM , wherein the CH2 domain or CH3 domain comprises an N-terminal truncation of about 1 to about 7 amino acids , and wherein (i) at least one of the loops of the CH2 or CH3 domain is mutated; (ii) at least a portion of a loop region of the CH2 domain or CH3 domain is replaced by a complementarity determining region (CDR) , or a functional fragment thereof , from a heterologous immunoglobulin variable domain; or (iii) both , wherein the polypeptide has a molecular weight of less than about 15 kD , and wherein the polypeptide specifically binds an antigen.2. The polypeptide of claim 1 , wherein Loop 1 of the CH2 or CH3 domain is mutated.3. The polypeptide of claim 2 , wherein the CH2 domain or CH3 domain further comprises a mutated Loop 2 claim 2 , a mutated Loop 3 claim 2 , a mutated Loop A-B claim 2 , a mutated Loop C-D claim 2 , a mutated Loop E-F claim 2 , or any combination thereof.4. The polypeptide of claim 2 , wherein the mutated Loop 1 comprises random substitutions of any combination of alanine claim 2 , tyrosine claim 2 , aspartic acid or serine residues.5. The polypeptide of claim 4 , wherein all Loop 1 residues are replaced by alanine claim 4 , tyrosine claim 4 , aspartic acid or serine residues.6. The polypeptide of claim 4 , wherein the mutated Loop 1 further comprises an extra glycine residue on the C-terminus of Loop 1.7. The polypeptide of claim 2 , wherein the CH2 domain or CH3 domain further comprises a mutated Loop 3 claim 2 , ...

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Номер записи: 51
31-03-2022 дата публикации

Neutralizing antibodies to hiv-1 gp41 and their use

Номер: US20220098286A1
Автор: Amarendra PEGU, Baoshan Zhang, Gilad Ofek, Gwo-yu CHUANG, Ivelin Georgiev, John Mascola, Jonathan Cooper, Kevin Carlton, Krisha McKee, Lawrence Shapiro, Lisa Kueltzo, Mangaiarkarasi ASOKAN, Mark Connors, Mark Louder, Michael Bender, Peter Kwong, Richard Schwartz, Robert Bailer, Sijy O'Dell, Tatyana Gindin, Young Do Kwon
Принадлежит: Columbia University of New York, US Department of Health and Human Services

Neutralizing antibodies that specifically bind to HIV-1 Env and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed.

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Номер записи: 52
25-03-2021 дата публикации

BISPECIFIC HIV-1-NEUTRALIZING ANTIBODIES

Номер: US20210087259A1
Автор: HO David D., Huang Yaoxing, Yu Jian
Принадлежит:

In various embodiments, the present invention relates generally to using bispecific antibodies in the prevention and treatment of HIV. 1. A bispecific antibody in a CrossMab format capable of neutralizing HIV , wherein the antibody comprises a light chain and heavy chain portion of a first antibody 10E8 , or a variant thereof , that binds to a HIV envelope protein , and a light chain and heavy chain portion of a second antibody ibalizumab , or a variant thereof , that binds to a cell membrane receptor protein or a cell membrane co-receptor protein , whereinthe light chain portion of the first antibody 10E8 comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 33, wherein SEQ ID NO: 33 incorporates 1-4 mutations and the heavy chain portion of the first antibody 10E8 comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 34, wherein SEQ ID NO: 34 incorporates 4-12 mutations; andthe light chain portion of the second antibody ibalizumab comprises an amino acid sequence having at least 97% identity with SEQ ID NO: 1, and the heavy chain portion of the second antibody ibalizumab comprises an amino acid sequence having at least 97% with SEQ ID NO: 2; andwherein any amino acid alterations relative to SEQ ID NOS: 1, 2, 33, and 34 are within the variable regions.2. The bispecific antibody of claim 1 , wherein the mutations to SEQ ID NO: 33 are amino acid positions selected from L15 claim 1 , P40 claim 1 , I45 claim 1 , and/or P112.3. The bispecific antibody of claim 1 , wherein the mutations to SEQ ID NO: 33 are amino acid positions selected from P40 and I45.4. The bispecific antibody of claim 1 , wherein the mutations to SEQ ID NO: 33 are P4OT and I45K.5. The bispecific antibody of claim 1 , wherein the mutations to SEQ ID NO: 34 are amino acid positions selected from L72 claim 1 , I75 claim 1 , F77 claim 1 , L89 claim 1 , Y98 claim 1 , F100a claim 1 , W100b claim 1 , Y100e claim 1 , P100f claim 1 , P100g claim 1 , L108 claim 1 ...

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Номер записи: 53
29-03-2018 дата публикации

STABILIZED SINGLE HUMAN CD4 DOMAINS AND FUSION PROTEINS

Номер: US20180086812A1
Автор: Chen Weizao, Dimitrov Dimiter S., Ponraj Prabakaran
Принадлежит: The United States of America, as represented by the Secretary, Department of Health and Human Serv

The invention provides a polypeptide comprising a single domain CD4, as well as a fusion protein comprising the single domain CD4 and one or more fusion partners. A nucleic acid encoding the polypeptide or fusion protein, as well as compositions or cells comprising the polypeptide, fusion protein, or nucleic acid also are provided. 124.-. (canceled)25. A construct comprising{'br': None, 'two fusion proteins of A-(optional linker)-C\u2003\u2003(Formula (III)), and'}{'br': None, 'two fusion proteins of B-(optional linker)-D-(optional linker)-E\u2003\u2003(Formula (IV)),'}wherein A is an antibody or antibody fragment, B is a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, C is an immunoglobulin light chain constant region, D is an immunoglobulin heavy chain constant region, and E is an Fc region or portion thereof,wherein the fusion protein of Formula (III) comprises SEQ ID NO: 19 and the fusion protein of Formula (IV) comprises SEQ ID NO: 18.26. (canceled)27. A construct comprising{'br': None, 'two fusion proteins of A-(optional linker)-C\u2003\u2003(Formula (III)), and'}{'br': None, 'two fusion proteins of B-(optional linker)-D-(optional linker)-E-(optional linker)-B\u2003\u2003 (Formula (II)),'}wherein A is an antibody or antibody fragment, B is a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, C is an immunoglobulin light chain constant region, D is an immunoglobulin heavy chain constant region, and E is an Fc region or portion thereof,wherein the fusion protein of Formula (III) comprises SEQ ID NO: 21 and the fusion protein of Formula (II) comprises SEQ ID NO: 20.28. (canceled)29. A construct comprising{'br': None, 'two fusion proteins of A-(optional linker)-C-(optional linker)-B\u2003\u2003(Formula (I)), and'}{'br': None, 'two fusion proteins of B-(optional linker)-D-(optional linker)-E-(optional linker)-B\u2003\u2003 (Formula (II)),'}wherein A is an antibody or antibody fragment, B is a polypeptide comprising the amino acid ...

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Номер записи: 54
21-03-2019 дата публикации

DNA Antibody Constructs And Method Of Using Same

Номер: US20190085058A1
Автор: FLINGAI Seleeke, Muthumani Karuppiah, Sardesai Niranjan, Weiner David
Принадлежит:

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating disease in a subject using said composition and method of generation. 1. A nucleic acid molecule encoding a synthetic antibody comprising one or more nucleic acid sequences selected from the group consisting of:(a)(b) a nucleic acid sequence that is at least 90% homologous to a nucleotide sequence that encodes SEQ ID NO: 67, a fragment of a nucleotide sequence that encodes SEQ ID NO: 67, a nucleic acid sequence that is at least 90% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 67;(c) a nucleic acid sequence that is at least 90% homologous to a nucleotide sequence that encodes SEQ ID NO: 69, a fragment of a nucleotide sequence that encodes SEQ ID NO: 69, a nucleic acid sequence that is at least 90% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 69;(d) a nucleic acid sequence that is at least 90% homologous to a nucleotide sequence that encodes SEQ ID NO: 71, a fragment of a nucleotide sequence that encodes SEQ ID NO: 71, a nucleic acid sequence that is at least 90% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 71;(e) a nucleic acid sequence that is at least 90% homologous to a nucleotide sequence that encodes SEQ ID NO: 73, a fragment of a nucleotide sequence that encodes SEQ ID NO: 73, a nucleic acid sequence that is at least 90% homologous to a fragment of a nucleotide sequence that encodes SEQ ID NO: 73;(f) a nucleic acid sequence that is at least 90% homologous to a nucleotide sequence that encodes SEQ ID NO: 75, a fragment of a nucleotide sequence that encodes SEQ ID NO: 75, a nucleic acid sequence that is at least 90% homologous to a fragment of a nucleotide sequence that encodes ...

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Номер записи: 55
19-06-2014 дата публикации

Methods and Compositions for Treatment of Human Immunodeficiency Virus Infection with Conjugated Antibodies or Antibody Fragments

Номер: US20140170065A1
Автор: Chang Chien-Hsing, GOLDENBERG David M., McBride William J., Rossi Edmund A.
Принадлежит: IMMUNOMEDICS, INC.

The present invention concerns methods and compositions for treatment of HIV infection in a subject. The compositions may comprise a targeting molecule against an HIV antigen, such as an anti-HIV antibody or antibody fragment. The anti-HIV antibody or fragment may be conjugated to a variety of cytotoxic agents, such as doxorubicin. In a preferred embodiment, the antibody or fragment is P4/D10. Other embodiments may concern methods of imaging, detection or diagnosis of HIV infection in a subject using an anti-HIV antibody or fragment conjugated to a diagnostic agent. In alternative embodiments, a bispecific antibody with at least one binding site for an HIV antigen and at least one binding site for a carrier molecule may be administered, optionally followed by a clearing agent, followed by administration of a carrier molecule conjugated to a therapeutic agent. 1. A method for treating HIV infection in a subject , comprising:a) administering to the subject a bispecific antibody or fragment thereof, the bispecific antibody comprising one or more binding sites specific for an HIV surface envelope antigen and one or more binding sites for a carrier;b) administering to the subject a carrier conjugated to a therapeutic agent, said administration of said carrier effective to reduce, eliminate or prevent HIV infection or to prevent the intercellular transmission of HIV to uninfected cells in the subject.2. The method of claim 1 , further comprising administering a clearing agent to the subject3. The method of claim 1 , wherein the therapeutic agent is selected from the group consisting of a cytotoxic drug claim 1 , virostatic agent claim 1 , toxin claim 1 , radioisotope claim 1 , oligonucleotide claim 1 , immunomodulator claim 1 , small interfering RNA (siRNA) and enzyme.4. The method of claim 3 , wherein the therapeutic agent is doxorubicin.5. The method of claim 1 , wherein the subject is a human subject.6. The method of claim 2 , wherein the antibody or fragment is a ...

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Номер записи: 56
19-06-2014 дата публикации

Bispecific antibodies against her2 and cd3

Номер: US20140170149A1
Автор: Aran Frank Labrijn, Bart De Goeij, Janine Schuurman, Joost J. Neijssen, Joyce I. MEESTERS, Paul Parren
Принадлежит: Genmab AS

Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

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Номер записи: 57
19-03-2020 дата публикации

HIV Antigens and Antibodies

Номер: US20200087382A1
Автор: Killian M. Scott, Szakal Evelin, Vyas Girish N.
Принадлежит:

The present invention relates to a method for reducing the occurrence and/or severity of viral infections. The method embodies procedures for expanding HIV from the blood of HIV antibody negative donors and deriving a non-infectious virus particle product that is antigenic. The procedures for deriving the antigenic, non-infectious virus particle product are optimally designed to maintain the integrity of the envelope proteins while maximizing the depletion of capsid proteins and RNA. The resulting virus particle product, when introduced into humans or non-human animals, enables the production of antibodies that target the natural envelope macromolecular structure that is required for infectivity. The present invention can be applied to producing virus stocks from the blood of HIV-seronegative donors, for deriving non-infectious virus particles that retain intact envelope proteins, for producing anti-viral antibodies, and for administering anti-virus antibodies to patients. 168.-. (canceled)69. A composition comprising polyclonal antibodies , wherein the polyclonal antibodies selectively bind to an epitope on an HIV-1 trimeric envelope glycoprotein subunit (TEGS) of an infectious HIV-1 virus.70. The composition of claim 69 , wherein the TEGS is prepared by a process comprising:obtaining infectious HIV-1 virus particles from human CD4+ cell culture grown in serum-free media;contacting the infectious HIV-1 virus particles with agents that selectively remove from the particle viral RNA and viral capsid protein while retaining viral envelope protein in a non-denatured conformation, wherein the agents do not chemically fix or cross-link the envelope protein; andisolating protein from the contacted infectious HIV-1 virus particles wherein the isolated protein comprises non-infectious complexes comprising a trimeric envelope glycoprotein subunit, the subunit comprising HIV-1 envelope, gp120, and gp41 proteins that are not chemically fixed or cross-linked and substantially ...

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Номер записи: 58
01-04-2021 дата публикации

Bispecific Molecules That Are Immunoreactive With Immune Effector Cells That Express An Activating Receptor And An Antigen Expressed By A Cell Infected By A Virus And Uses Thereof

Номер: US20210095021A1
Автор: Ferrari Guido, Haynes Barton F., Johnson Leslie S., Koenig Scott, Lam Chia-Ying Kao, Liu Liqin, NORDSTROM Jeffrey Lee
Принадлежит:

The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections. 130-. (canceled)31. A bispecific diabody comprising first and second polypeptide chains , wherein: (i) a domain (A) comprising a binding region of a light chain variable domain of a first immunoglobulin (VL1) specific for an HIV epitope;', '(ii) a domain (B) comprising a binding region of a heavy chain variable domain of a second immunoglobulin (VH2) specific for a CD3 epitope; and', '(iii) a domain (C);, '(A) the first polypeptide chain comprises, in the N-terminal to C-terminal direction (i) a domain (D) comprising a binding region of a light chain variable domain of the second immunoglobulin (VL2) specific for the CD3 epitope;', '(ii) a domain (E) comprising a binding region of a heavy chain variable domain of the first immunoglobulin (VH1) specific for the HIV epitope;', '(iii) a domain (F);, '(B) the second polypeptide chain comprises, in the N-terminal to C-terminal direction (ii) domains (D) and (E) do not associate with one another to form an epitope-binding domain;', '(iii) domains (A) and (E) associate to form an epitope-binding domain that binds the HIV epitope, and domains (B) and (D) associate to form an epitope-binding domain that binds the CD3 epitope,', '(iv) domains (C) and (F) are covalently associated ...

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Номер записи: 59
12-05-2022 дата публикации

METHODS OF IDENTIFYING HIV PATIENTS SENSITIVE TO THERAPY WITH gp120 CD4 BINDING SITE-DIRECTED ANTIBODIES

Номер: US20220144923A1
Автор: Martin Stephen R., Moldt Brian, Parvangada Aiyappa
Принадлежит:

Provided are methods for identifying patient populations infected with HIV that can be targeted by antibodies that bind to HIV gp120 CD4 binding site (CD4bs) region. 1. A method of treating or preventing HIV in a human subject in need thereof , the method comprising:a) Identifying a human subject who is infected with an HIV or a population of HIV expressing a gp120 comprising the following amino acid residues: I201 and one or more of the amino acid residues selected from the group consisting of E102, I108, A281, Y318 and F353, wherein the amino acid positions are with reference to SEQ ID NO: 3; andb) Administering to the subject an effective amount of an antibody or antigen-binding fragment thereof that competes with or comprises VH and VL regions that bind to an epitope of gp120 comprising the CD4 binding site (CD4bs).2. The method of claim 1 , comprising identifying a subject infected with an HIV or a population of HIV expressing a gp120 comprising the following amino acid residues:i. I201 and F353;ii. I201, I108 and F353;iii. I201, I108, A281 and F353;iv. I201, E102, I108, A281 and F353; orv. I201, E102, I108, A281, Y318 and F353.3. The method of claim 1 , comprising identifying a subject infected with an HIV or a population of HIV expressing a gp120 comprising the following amino acid residues:i. I201, I108 and F353;ii. I201, I108, A281 and F353;iii. I201, E102, I108, A281 and F353; oriv. I201, E102, I108, A281, Y318 and F353.4. The method of claim 1 , comprising identifying a subject infected with an HIV or a population of HIV expressing a gp120 comprising the following amino acid residues:i. I201, I108, A281 and F353;ii. I201, E102, I108, A281 and F353; oriii. I201, E102, I108, A281, Y318 and F353.5. The method of claim 1 , wherein at least 90% claim 1 , e.g. claim 1 , at least 91% claim 1 , at least 92% claim 1 , at least 93% claim 1 , at least 94% claim 1 , at least 95% claim 1 , at least 96% claim 1 , at least 97% claim 1 , at least 98% claim 1 , at least ...

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Номер записи: 60
14-04-2016 дата публикации

CROSSLINKED ANTI-HIV-1 COMPOSITIONS FOR POTENT AND BROAD NEUTRALIZATION

Номер: US20160102137A1
Автор: Bjorkman Pamela J., Galimidi Rachel P., Nussenzweig Michel C., West Anthony P.
Принадлежит:

An anti-HIV-1 spike composition includes a first anti-HIV-1 antibody Fab and a second anti-HIV-1 antibody Fab linked by a DNA or protein linker molecule to form a crosslinked homo-diFab or hetero-diFab having improved viral potency and neutralization. The anti-HIV-1 antibody Fabs include anti-gp120 CD4, anti-gp120 V1V2, anti-gp120 V3, and anti-gp41. 1. A composition comprising:a first anti-HIV-1 antibody Fab;a second anti-HIV-1 antibody Fab; anda linker molecule conjugated between the C-terminus of the first anti-HIV-1 antibody Fab and the C-terminus of the second anti-HIV-1 antibody Fab.2. The composition of claim 1 , wherein the linker molecule is selected from the group consisting of single stranded nucleic acids claim 1 , double stranded nucleic acids claim 1 , amino acids claim 1 , and combinations thereof.3. The composition of claim 1 , wherein the first anti-HIV-1 antibody Fab and the second anti-HIV-1 antibody Fab are each independently selected from the group consisting of anti-gp120 V1V2 Fabs claim 1 , anti-gp120 V3 Fabs claim 1 , anti-gp120 CD4 Fabs claim 1 , and anti-gp41 Fabs.4. The composition of claim 3 , wherein the anti-gp120 V1V2 Fab comprises:a heavy chain comprising anti-gp120 V1V2 binding residues corresponding to 57-59, 61, 64, 100, 100B, 100D, 100E, 100F, 100G, 100H, 100I, 100J, 100K, 100L, 100O, 100P, 100Q, 100R according to PDB 4DQO; anda light chain comprising gp120 V1V2 binding residues corresponding to 31, 32, 50, 91, 94, 95A according to PDB 4DQO.5. The composition of claim 3 , wherein the anti-gp120 V1V2 Fab comprises:a heavy chain comprising anti-gp120 V1V2 binding residues corresponding to 31, 53, 55, 100, 100B, 100E, 100F, 100G, 100H, 100I, 100J, 100K, 100L, 100O, 100P, 100Q, 100R according to PDB 3U2S; anda light chain comprising anti-gp120 V1V2 binding residues corresponding to 31, 32, 50, 91, 94, and 95A according to PDB 3U2S.6. The composition of claim 3 , wherein the anti-gp120 CD4 Fab comprises:a heavy chain comprising anti- ...

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Номер записи: 61
08-04-2021 дата публикации

Hiv antibody compositions and methods of use

Номер: US20210101963A1
Автор: Adrian Wrangham Briggs, Francois Vigneault, Sonia TIMBERLAKE, Stephen J. Goldfless
Принадлежит: AbVitro LLC

This invention relates to novel anti-HIV antibodies that can be used in the treatment and detection of human immunodeficiency virus (HIV). These antibodies exhibit a high degree of sensitivity and can provide a broad range of specificity.

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Номер записи: 62
13-04-2017 дата публикации

Antiretroviral Drug Targeting Human Endogenous Retrovirus

Номер: US20170101461A1
Автор: Curtin Francois, Faucard Raphaël, Gehin Nadege, Lang Alois, Madeira Alexandra, MEDINA Julie, PERRON Herve
Принадлежит:

The invention relates to an antibody, a fragment or a derivative thereof, for use as an antiretroviral drug targeting a virus belonging to human endogenous retroviruses type W (HERV-W), wherein said antibody, fragment or derivative thereof is directed against HERV-W Envelope protein (HERV-W Env). The invention also relates to a composition comprising said antibody and a retroviral reverse-transcriptase inhibitory drug, for use as an antiretroviral drug targeting a virus belonging to HERV-W. 1. A method for inhibiting the expression and/or the replication of a virus belonging to human endogenous retroviruses (HERV) in a patient comprising administering to said patient an antibody , a fragment or a derivative thereof , wherein said antibody , fragment or derivative is directed against HERV-W Envelope protein (HERV-W Env).2. The method according to claim 1 , wherein said antibody claim 1 , fragment or derivative is able to:suppress or inhibit totally or partially the replication of a virus belonging to the human endogenous retroviruses type W (HERV-W) family; orsuppress or inhibit totally or partially the expression of a virus belonging to human endogenous retroviruses type W family, or the expression of the envelope protein of said virus.3. The method according to claim 1 , wherein said virus belongs to the MSRV subtype of human endogenous retrovirus family (HERV-W).4. The method according to claim 1 , wherein said virus is MSRV.5. The method according to claim 1 , for preventing and/or treating an HERV-W associated disease.6. The method according to claim 1 , wherein said method is for preventing and/or treating an HERV-W associated disease selected from the group consisting of multiple sclerosis (MS) claim 1 , schizophrenia (SZ) claim 1 , bipolar disorder (BP) claim 1 , unipolar or psychotic depression claim 1 , clinically isolated syndrome (CIS claim 1 , with neurological symptom) claim 1 , chronic inflammatory demyelinating polyneuropathy (CIDP) claim 1 , epilepsy ...

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Номер записи: 63
13-04-2017 дата публикации

PROTEASE-CLEAVAGE RESISTANT, SHIGA TOXIN A SUBUNIT EFFECTOR POLYPEPTIDES AND CELL-TARGETED MOLECULES COMPRISING THE SAME

Номер: US20170101636A1
Автор: HIGGINS Jack, KIM Jason, POMA Eric, WILLERT Erin
Принадлежит: Molecular Templates, Inc.

The present invention provides protease-cleavage resistant molecules comprising Shiga toxin effector polypeptides capable of exhibiting potent, Shiga toxin functions (e.g. subcellular routing and cytotoxicity). The present invention also provides protease-cleavage resistant, cell-targeting molecules for targeting specific cell types, e.g., infected or malignant cells. Certain molecules of the present invention are cytotoxic, and certain cell-targeting molecules of the present invention may be used for the targeted killing of specific cell types and the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections. Certain cell-targeting molecules of the invention exhibit improved, in vivo tolerability as compared to related cell-targeted molecules comprising protease-cleavage sensitive, wild-type, Shiga toxin effector polypeptides. The cell-targeting molecules of the invention can deliver additional materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, into the interiors of target cells. 150-. (canceled)52. The cytotoxic cell-targeting molecule of claim 51 , wherein the molecular moiety has a mass of at least 4.5 kDa claim 51 , 6 kDa claim 51 , 9 kDa claim 51 , 12 kDa claim 51 , 15 kDa claim 51 , 20 kDa claim 51 , 25 kDa claim 51 , 28 kDa claim 51 , 30 kDa claim 51 , 41 kDa claim 51 , or 50 kDa.53. The cytotoxic cell-targeting molecule of claim 52 , wherein the molecular moiety comprises the heterologous claim 52 , binding region.54. The cytotoxic cell-targeting molecule of claim 52 , wherein the molecular moiety comprises at least one amino acid residue and the Shiga toxin effector polypeptide is fused to at least one amino acid residue of the molecular moiety.55. The cytotoxic cell-targeting molecule of claim 52 , wherein the disrupted furin-cleavage motif comprises one or more mutations relative to a wild-type claim 52 , Shiga toxin A ...

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Номер записи: 64
02-06-2022 дата публикации

ANTIBODIES TARGETING HIV ESCAPE MUTANTS

Номер: US20220169707A1
Автор: Bjorkman Pamela J., Diskin Ron, Nussenzweig Michel, West Anthony P.
Принадлежит:

Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) broadly neutralizing antibodies having improved potency and breadth for neutralizing a range of HIV strains. Combinations of broadly neutralizing antibodies can also improve potency over a single antibody composition. 1. A composition comprising:an isolated anti-CD4 binding site (anti-CD4bs) potentVRC01-like (PVL) antibody having a heavy chain and a light chain, a first substitution at a position equivalent to Phe43 of a CD4 receptor protein, the first substitution being selected from the group consisting of glycine, histidine, arginine, glutamine, asparagine, lysine, glutamic acid, and aspartic acid; and', 'a second substitution of tryptophan at position 47 of the heavy chain, the second substitution being selected from valine, isoleucine, and threonine; and, 'the heavy chain comprisingthe light chain comprising a light chain substitution of tyrosine at position 28 of the light chain for serine.2. The composition of claim 1 , wherein the first substitution is tryptophan claim 1 , tyrosine claim 1 , phenylalanine claim 1 , glycine claim 1 , histidine claim 1 , arginine claim 1 , glutamine claim 1 , or asparagine.3. The composition of claim 1 , wherein the position equivalent to Phe43 of the CD4 receptor protein is position 54 of the heavy chain.4. The composition of claim 1 , wherein the heavy chain is selected from the group consisting of SEQ ID NOs: 2 claim 1 , 4 claim 1 , 6 claim 1 , 8 claim 1 , 10 claim 1 , 12 claim 1 , 14 claim 1 , 16 claim 1 , 18 claim 1 , 20 claim 1 , 22 claim 1 , 24 claim 1 , 26 claim 1 , 28 claim 1 , 30 claim 1 , 32 claim 1 , 34 claim 1 , 36 claim 1 , 38 claim 1 , 40 claim 1 , 42 claim 1 , 44 claim 1 , 45 claim 1 , and 46.5. The composition of claim 1 , wherein the light chain is selected from the group consisting of SEQ ID NOs: 1 claim 1 , 3 claim 1 , 5 claim 1 , 7 claim 1 , 9 claim 1 , 11 claim 1 , 13 claim 1 , 15 claim 1 , ...

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Номер записи: 65
02-06-2022 дата публикации

Immunological Reagents

Номер: US20220169733A1
Автор: Fenwick Craig, Pantaleo Giuseppe
Принадлежит: MabQuest SA

This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) and to methods for using the same to treat, prevent and/or ameliorate an infectious disease (e.g., human immunodeficiency virus (HIV)), cancer and/or autoimmunity. 154-. (canceled)55. A combination of binding agents , the combination comprising a first binding agent that blocks a first binding agent that blocks the interaction of PD-1 and PD-L1 and a second binding agent that does not block the interaction of PD-1 and PD-L1.561. The combination of claim wherein the second binding agent comprises a variable heavy chain region comprising SEQ ID NOS. 17 , 40 , 63 and a variable light chain region comprising SEQ ID NOS. 86 , 109 , and 132. This application is a continuation application of U.S. Ser. No. 15/981,977 filed May 17, 2018, now U.S. Pat. No. 11,130,807, which is a continuation application of U.S. Ser. No. 15/329,760 filed Jan. 27, 2017, now U.S. Pat. No. 9,982,053 B2, which was filed under 35 U.S.C. § 371 and claims priority to International Application No. PCT/IB2015/055943 filed Aug. 5, 2015, and claims priority to U.S. Ser. No. 62/033,177 filed Aug. 5, 2014; U.S. Ser. No. 62/053,366 filed Sep. 22, 2014; and U.S. Ser. No. 62/093,368 filed Dec. 17, 2014; each of which is hereby incorporated by reference into this disclosure in their entirety.This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) (e.g., human PD-1) and to methods for using the same to treat and/or prevent infection (e.g., by human immunodeficiency virus (HIV)), cancer and/or autoimmunity.As we enter the fourth decade of the HIV epidemic, significant advances have been made in the understanding of HIV pathogenesis and in the development of potent and safe antiviral drugs. More than 30 antiviral drugs have been registered and the impact of combination antiretroviral therapy (ART) on both morbidity and mortality has been remarkable. However, despite the long-term ...

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Номер записи: 66
23-04-2015 дата публикации

ANTIBODY COMPOSITION-PRODUCING CELL

Номер: US20150112046A1
Автор: HANAI Nobuo, HOSAKA Emi, Kanda Yutaka, NAKAMURA Kazuyasu, Satoh Mitsuo, SHINKAWA Toyohide, UCHIDA Kazuhisa, YAMANE Naoko, YAMANO Kazuya, YAMASAKI Motoo
Принадлежит: KYOWA HAKKO KIRIN CO., LTD

The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependant cell-mediated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof. 161-. (canceled)62. An antibody composition comprising antibody molecules , wherein the antibody composition has a higher ratio of a non-fucosylated antibody molecule than an antibody composition produced by a YB2/0 rat myeloma cell.63. The antibody composition according to claim 62 , wherein the non-fucosylated antibody molecule has an Fc region comprising two complex-type and/or hybrid-type N-glycoside-linked sugar chains bound to the Fc region claim 62 , wherein said sugar chains comprise a reducing terminal which contains an N-acetylglucosamine claim 62 , and wherein said at least one sugar chain does not contain fucose bound to the 6-position of the N-acetylglucosamine in the reducing terminal of the sugar chain.64. The antibody composition according to claim 62 , wherein the ratio of the non-fucosylated antibody molecule is 80% or more.65. The antibody composition according to claim 62 , wherein the antibody molecules in said composition consist essentially of the non-fucosylated antibody molecule.66. The antibody composition according to claim 62 , wherein the antibody molecules in said composition consist of the non-fucosylated antibody molecule.67. The antibody composition according to claim 62 , wherein said antibody molecules bind to an antigen selected from the group consisting of: ganglioside GD3 claim 62 , ganglioside GM2 claim 62 , CD4 claim 62 , CD20 claim 62 , CD52 claim 62 , HER-2 claim 62 , HM1.24 claim 62 , PTHrP claim 62 , bFGF claim 62 , an insulin-like growth factor receptor claim 62 , a vascular endothelial cell growth factor receptor claim 62 , CCR4 ...

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Номер записи: 67
02-04-2020 дата публикации

METHODS AND COMPOSITIONS FOR TREATING AND PREVENTING HIV

Номер: US20200101152A1
Автор: Flamar Anne-Laure, Levy Yves, Zurawski Gerard, Zurawski Sandra
Принадлежит:

Methods and compositions are provided that can be used to vaccinate against and treat HIV. Specifically contemplated are vaccine compositions and methods of using these compositions treat HIV in patients. Aspects of the disclosure relate to an anti-CD40 antibody-HIV antigen fusion protein comprising (i) an anti-CD40 heavy chain (HCD40)-HIV antigen (Ag) fusion protein comprising the formula: HCD40-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and (ii) an anti-CD40 light chain (LCD40). 1. A polynucleotide encoding a fusion protein , wherein said fusion protein is an anti-Dendritic Cell (DC) receptor antibody-HIV antigen fusion protein comprising ,(i) an anti-DC receptor heavy chain (HDCR)-HIV antigen (Ag) fusion protein comprising the formula: HDCR-Ag, wherein Ag is a polypeptide with at least 80% sequence identity to SEQ ID NO:1; and(ii) an anti-DC receptor light chain (LDCR).2. The polynucleotide of claim 1 , wherein the fusion protein further comprises one or more peptide linkers (PL).3. The fusion protein of claim 1 , wherein the fusion protein comprises:(i) HDCR-PL-Ag; and(ii) LDCR.4. The polynucleotide of claim 1 , wherein the fusion protein further comprises one or more joining sites (JS) claim 1 , wherein the joining site comprises alanine and serine residues.5. The polynucleotide of claim 1 , wherein the fusion protein further comprises one or more joining sites (JS) claim 1 , wherein the joining site consists of alanine and serine residues.6. The polynucleotide of claim 1 , wherein the fusion protein comprises:(i) HDCR-JS-PL-JS-Ag-JS; and(ii) LCD40;wherein JS is a joining site and PL is a peptide linker, and LCD40 is an anti-CD40 light chain.7. The polynucleotide of claim 2 , wherein the peptide linker comprises a polypeptide with at least 80% sequence identity to SEQ ID NO:2.8. The polynucleotide of claim 3 , wherein PL-Ag comprises a polypeptide with at least 80% identity to SEQ ID NO:3.9. The polynucleotide of claim 3 ...

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Номер записи: 68
02-04-2020 дата публикации

DIRECTED EVOLUTION OF MULTIVALENT GLYCOPEPTIDES THAT TIGHTLY BIND TO TARGET PROTEINS

Номер: US20200102555A1
Автор: Guillen Schlippe Yollete V., Horiya Satoru, KRAUSS Isaac J.
Принадлежит:

The invention relates to a method for selecting a glycopolypeptide that binds to a target protein, the method including the steps of providing a pool of glycopolypeptides fused via puromycin linker to an encoding mRNA-cDNA duplex; combining the pool with a target protein to form a mixture; incubating the mixture for a period of time sufficient to allow any target protein to bind to one or more of the glycopolypeptides, thereby forming glycopolypeptide-target protein complexes; and isolating from the mixture the glycopolypeptide-target protein complexes, thereby identifying a plurality of selected glycopolypeptides. 1. A method for selecting a glycopolypeptide that binds to a target protein comprising:{'sup': '11', 'providing a pool of glycopolypeptides fused via puromycin linker to an encoding mRNA-cDNA duplex, wherein the provided pool comprises greater than 10glycopolypeptides fused via puromycin linker to an encoding mRNA-cDNA duplex;'}combining the pool with a target protein to form a mixture;incubating the mixture for a period of time sufficient to allow any target protein to bind to one or more of the glycopolypeptides, thereby forming glycopolypeptide-target protein complexes; andisolating from the mixture the glycopolypeptide-target protein complexes, thereby identifying a plurality of selected glycopolypeptides.23-. (canceled)4. The method according to claim 1 , wherein the provided pool comprises greater than 10glycopolypeptides fused via puromycin linker to an encoding mRNA-cDNA duplex.5. The method according to claim 1 , wherein the provided pool comprises about 10glycopolypeptides fused via puromycin linker to an encoding mRNA-cDNA duplex.67-. (canceled)8. The method according to claim 1 , wherein said incubating is carried out at a temperature from about 32° C. to about 42° C.9. The method according to claim 1 , wherein said isolating comprises:exposing the mixture to magnetic beads labeled with an affinity reagent that binds to a portion of the target ...

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Номер записи: 69
11-04-2019 дата публикации

Immunological Reagents

Номер: US20190106493A1
Автор: Fenwick Craig, Pantaleo Giuseppe
Принадлежит: MabQuest SA

This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) and to methods for using the same to treat, prevent and/or ameliorate an infectious disease (e.g., human immunodeficiency virus (HIV)), cancer and/or autoimmunity. 154-. (canceled)55. A combination of binding agents , the combination comprising a first binding agent that blocks the interaction of PD-1 and PD-L1 and a second binding agent that does not block the interaction of PD-1 and PD-L1. This application is a continuation application of U.S. Ser. No. 15/329,760 filed Jan. 27, 2017, now U.S. Pat. No. 9,982,053 B2, which was filed under 35 U.S.C. § 371 and claims priority to International Application No. PCT/IB2015/055943 filed Aug. 5, 2015, and claims priority to U.S. Ser. No. 62/033,177 filed Aug. 5, 2014; U.S. Ser. No. 62/053,366 filed Sep. 22, 2014; and U.S. Ser. No. 62/093,368 filed Dec. 17, 2014; each of which is hereby incorporated by reference into this disclosure in their entirety.This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) (e.g., human PD-1) and to methods for using the same to treat and/or prevent infection (e.g., by human immunodeficiency virus (HIV)), cancer and/or autoimmunity.As we enter the fourth decade of the HIV epidemic, significant advances have been made in the understanding of HIV pathogenesis and in the development of potent and safe antiviral drugs. More than 30 antiviral drugs have been registered and the impact of combination antiretroviral therapy (ART) on both morbidity and mortality has been remarkable. However, despite the long-term suppression of HIV replication achieved in patients with optimal adherence to ART, HIV invariably rebounds after interruption of therapy. Furthermore, successful therapy does not induce or allow restoration/development of virus-specific immune responses capable of controlling HIV replication in the absence of ART. Thus, life-long ART is needed to control HIV ...

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Номер записи: 70
13-05-2021 дата публикации

EPITOPE RESTRICTION FOR ANTIBODY SELECTION

Номер: US20210139542A1
Автор: Kim Peter S., Weidenbacher Payton
Принадлежит:

Provided are methods of producing antigenic proteins and antigenic protein complexes and compositions and vaccines produced from such methods. Also provided are methods of immunizing a subject using such compositions and vaccines. The antigenic proteins and protein complexes of this disclosure are useful as vaccine immunogens that can direct the immune system of a subject immunized with such vaccine immunogens to generate antibodies against a specific region, or epitope, of a protein that is known to be productive or neutralizing in the case of an infection. Also provided are methods of screening for B cells expressing antibodies that bind specifically to a particular, desired epitope (target region). Compositions and kits comprising one or more antigenic protein, protein complexes, binding partners, and polynucleotides encoding any thereof, are also described. 1. A method of making a modified antigenic protein , the method comprising the steps of:(a) providing an antigenic protein comprising a target region and a non-target region;(b) providing a binding partner, wherein the binding partner binds specifically to the target region of the antigenic protein;(c) contacting the antigenic protein with the binding partner under conditions in which the binding partner binds specifically to the antigenic protein thereby forming a protein complex comprising the antigenic protein and the binding partner;(d) contacting amino acid residues of the antigenic protein in the protein complex with a modifying reagent under conditions sufficient to form a modified antigenic protein thereby forming a modified antigenic protein in the protein complex, wherein each of a plurality of amino acid residues in the non-target region of the antigenic protein have a modifying component covalently attached thereto, and wherein amino acid residues of the target region of the antigenic protein do not have a modifying component attached thereto; and(e) separating the modified antigenic protein from ...

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Номер записи: 71
03-05-2018 дата публикации

Bispecific multivalent fusion proteins

Номер: US20180118815A1
Автор: Dimiter S. Dimitrov, Tianlei Ying, Weizao Chen
Принадлежит: FUDAN UNIVERSITY, US Department of Health and Human Services

The invention provides a construct comprising two or more fusion proteins of Formulas (I)-(IV): A-(optional linker)-C-(optional linker)-B (Formula I), B-(optional linker)-D-(optional linker)-E-(optional linker)-B (Formula II), A-(optional linker)-C (Formula III), and B-(optional linker)-D-(optional linker)-E (Formula IV), wherein A denotes an antibody or antibody fragment, B denotes a single domain CD4, C denotes an immunoglobulin light chain constant region D denotes an immunoglobulin heavy chain constant region, and E denotes an Fc region or a portion thereof that is optionally defucosylated.

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Номер записи: 72
03-05-2018 дата публикации

MULTI-VALENT HUMAN IMMUNODEFICIENCY VIRUS ANTIGEN BINDING MOLECULES AND USES THEREOF

Номер: US20180118816A1
Автор: Keyt Bruce, Olsen Ole A., Stinchcomb Dan T.
Принадлежит:

This disclosure provides a multimeric human immunodeficiency virus (HIV) protein binding molecule, e.g., an dimeric IgA or a pentameric or hexameric IgM binding molecule, comprising at least two bivalent binding units, or variants or fragments thereof, each comprising at least two antibody heavy chain constant regions or fragments thereof, wherein each heavy chain constant region or fragment thereof is associated with an HIV antigen binding domain. Also provided are compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules. 1. A multimeric binding molecule comprising at least two bivalent binding units , or variants or fragments thereof; wherein each binding unit comprises at least two antibody heavy chain constant regions or fragments thereof , each associated with an antigen binding domain , wherein at least one antigen binding domain specifically binds to a human immunodeficiency virus (HIV) antigen expressed on the surface of HIV viral particles , on the surface of HIV-infected cells , or a combination thereof , and wherein the binding molecule is more potent than a reference single binding unit molecule comprising the at least one antigen binding domain that specifically binds to an HIV antigen.2. The binding molecule of claim 1 , wherein the reference single binding unit molecule is an IgG antibody.3. The binding molecule of or claim 1 , which is a dimeric binding molecule comprising two bivalent IgA binding units or fragments thereof and a J-chain or fragment thereof or variant thereof claim 1 , wherein each binding unit comprises two IgA heavy chain constant regions or fragments thereof each associated with an antigen binding domain.4. The binding molecule of claim 3 , further comprising a secretory component claim 3 , or fragment or variant thereof.5. The binding molecule of or claim 3 , wherein the IgA heavy chain constant regions or ...

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Номер записи: 73
03-05-2018 дата публикации

SENSOR SYSTEMS FOR TARGET LIGANDS AND USES THEREOF

Номер: US20180118818A1
Автор: CEPKO Constance, Drokhlyansky Eugene, Tang Chung Yiu Jonathan, Wang Sui
Принадлежит: President and Fellows of Harvard College

Disclosed herein are sensor systems, compositions comprising the sensor systems, and methods of using the same. In particular aspects, disclosed herein are sensor systems for a target intracellular ligand and uses thereof, e.g., in detection assays or in cell manipulation or therapeutic applications. 1. A sensor system comprising (i) in the absence of the target ligand, the target ligand-binding recognition domain is destabilized and such that the fusion protein is destabilized and the effector domain is not active, or', '(ii) in the presence of the target ligand, the target ligand-binding recognition domain is stabilized upon binding of the target ligand, and the effector domain is active., 'a fusion molecule comprising at least one target ligand-binding recognition domain linked to an effector domain, wherein the target ligand-binding recognition domain specifically binds an intracellular target ligand and is configured such that'}2. The sensor system of claim 1 , wherein the target ligand is a polypeptide claim 1 , a nucleic acid claim 1 , or a combination thereof.3. The sensor system of claim 1 , wherein the target ligand-binding recognition domain is a protein claim 1 , a peptide claim 1 , a nucleic acid claim 1 , an antibody claim 1 , an antibody fragment claim 1 , a nanobody claim 1 , a single-domain antibody claim 1 , a scaffold protein claim 1 , or combinations thereof.4. The sensor system of claim 1 , wherein the target ligand-binding recognition domain is a nanobody.5. The sensor system of claim 1 , wherein the target ligand-binding recognition domain is configured to comprise at least one intracellular target ligand-dependent destabilizing mutation claim 1 , as compared to a wild-type target ligand-binding recognition domain.6. The sensor system of claim 1 , wherein the effector domain is a protein claim 1 , an enzyme claim 1 , a nucleic acid claim 1 , a therapeutic agent claim 1 , a detectable agent claim 1 , or a combination thereof.710.-. (canceled)11 ...

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Номер записи: 74
25-08-2022 дата публикации

HIV BINDING AGENTS

Номер: US20220267416A1
Автор: Fenwick Craig, Pantaleo Giuseppe
Принадлежит: Lausanne University Hospital

This disclosure relates to LN02M binding agents with specificity for HIV and to methods for using the same to treat, prevent and/or ameliorate HIV infection and/or AIDS. In some embodiments, this disclosure provides a binding agent(s) comprising a variable region shown in FIGS. A through E; amino acid sequence of any mutant of FIGS. A through D and/or FIGS. A through F, and any effective (e.g., HIV neutralization) combination thereof; any one or more of SEQ ID NOS. 3-92, 95-233, 248-482, or 491-699; and/or combinations thereof. 1. A binding agent comprising:{'figref': [{'@idref': 'DRAWINGS', 'FIG. 1'}, {'@idref': 'DRAWINGS', 'FIGS. 6A through 6E'}, {'@idref': 'DRAWINGS', 'FIGS. 7A-7E'}, {'@idref': 'DRAWINGS', 'FIGS. 8A-F'}], 'a) at least one CDR illustrated in , , , or ;'}b) an amino acid sequence selected from the group consisting of SEQ ID NOS. 3-92 or 491-699;c) an amino acid sequence selected from the group consisting of SEQ ID NOS. 95-233 or 248-482;d) a variable heavy chain region comprising MH01 (SEQ ID NO. 95), MH16 (SEQ ID NO. 110), MH22 (SEQ ID NO. 116), MH26 (SEQ ID NO. 120), MH30 (SEQ ID NO. 124), MH32 (SEQ ID NO. 126), MH35 (SEQ ID NO. 129), MH36 (SEQ ID NO. 130), MH37 (SEQ ID NO. 131), MH43 (SEQ ID NO. 136), MH44 (SEQ ID NO. 137), MH48 (SEQ ID NO. 141), MH49 (SEQ ID NO. 142), MH50 (SEQ ID NO. 143), MH51 (SEQ ID NO. 144), MH53 (SEQ ID NO. 146), MH59 (SEQ ID NO. 151), MH61 (SEQ ID NO. 153), MH64 (SEQ ID NO. 156), MH68 (SEQ ID NO. 159), MH73 (SEQ ID NO. 163), MH84 (SEQ ID NO. 174), MH89 (SEQ ID NO. 177), MH91 (SEQ ID NO. 178), MH92 (SEQ ID NO. 179), MH106 (SEQ ID NO. 193), MH107 (SEQ ID NO. 194), MH108 (SEQ ID NO. 195), MH111 (SEQ ID NO. 198), MH112 (SEQ ID NO. 199), MH115 (SEQ ID NO. 202), MH119 (SEQ ID NO. 206), MH120 (SEQ ID NO. 207), MH124 (SEQ ID NO. 211), MH 131 (SEQ ID NO. 218), MH135 (SEQ ID NO. 222), MH136 (SEQ ID NO. 223), MH138 (SEQ ID NO. 225), and/or MH146 (SEQ ID NO. 232);e) a variable light chain region comprising ML01 (SEQ ID NO. 3), ML02 ...

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Номер записи: 75
24-07-2014 дата публикации

FOCUSED EVOLUTION OF HIV-1 NEUTRALIZING ANTIBODIES REVEALED BY CRYSTAL STRUCTURES AND DEEP SEQUENCING

Номер: US20140205607A1
Автор: Haynes Barton F., Kepler Thomas B., Kwong Peter, Mascola John R., Nabel Gary, Wu Xueling
Принадлежит:

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. 1. An antibody against the CD4 binding site of HIV-1 comprising a heavy or light chain amino acid sequence of CH30 , CH31 or CH32 as shown in , or fragment of said antibody.2. The antibody according to wherein said fragment is an antigen-binding fragment.3. The antibody according to wherein said fragment comprises a complementarity determining region (CDR) of said heavy or light chain amino acid sequence of CH30 claim 1 , CH31 or CH 32.4. A composition comprising the antibody according to claim 1 , or said fragment thereof claim 1 , and a carrier.5. An isolated nucleic acid encoding the antibody according to claim 1 , or said fragment thereof.6. A vector comprising the nucleic acid according to claim 5 , wherein said nucleic acid is present in said vector in operable linkage with a promoter.7. An isolated host cell comprising the vector according to .8. A composition comprising the vector according to and a carrier.9. A method of ...

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Номер записи: 76
24-07-2014 дата публикации

HUMAN IMMUNODEFICIENCY VIRUS (HIV)-NEUTRALIZING ANTIBODIES

Номер: US20140205612A1
Автор: Burton Dennis R., Chan-Hui Po-Ying, Doores Katherine, Frey Steven, HUBER Michael, Kaminsky Stephen, Koff Wayne, Marcel Simek-Lemos Melissa Danielle De Jean De St., Mitcham Jennifer, Moyle Matthew, Olsen Ole, Phogat Sanjay K., Poignard Pascal Raymond Georges, Walker Laura Marjorie
Принадлежит:

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. 12-. (canceled)3. A monoclonal antibody selected from the group consisting of 1443_C16 (PG16) (TCN-116) , 1503 H05 (PG16) (TCN-119) , 1456 A12 (PG16) (TCN-117) , 1469 M23 (PG16) (TCN-118) , 1489_I13 (PG16) (TCN-120) , 1480_I08 (PG16) , 1456_P20 (PG20) , 1460_G14 (PGG14) , 1495_C14 (PGC14) , 1496_C09 (PG9) (TCN-109) , 4838_L06 (PGT-121) , 4873_E03 (PGT-121) , 4877_D15 (PGT-122) , 4858_P08 (PGT-123) , 6123_A06 (PGT-125) , 5141_B17 (PGT-126) , 5145_B14 (PGT-127) , 5114_A19 (PGT-128) , 5147_N06 (PGT-130) , 5136_H01 (PGT-131) , 5343_B08 (PGT-135) , 5344_E16 (PGT-135) , 5329_C19 (PGT-136) , 5366_P21 (PGT-136) , 4964_G22 (PGT-141) , 5345_I01 (PGT-137) , 4993_K13 (PGT-141) , 4995_E20 (PGT-142) , 4980_N08 (PGT-143) , 4970_K22 (PGT-144) , 4995_P16 (PGT-145) , 4835_F12 (PGT-124) , 4869-K15 (PGT-133) , 4876_M06 (PGT-134) , 5131_A17 (PGT-132) , 5138_G07 (PGT-138) , 5120_N10 (PGT-139) , 6831_A21 (PGT-151) , 6889_I17 (PGT-152) , 6891_F06 (PGT-153) , 6843_G20 (PGT-154) , 6892_D19 (PGT-155) , ...

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Номер записи: 77
27-05-2021 дата публикации

HUMAN IMMUNODEFICIENCY VIRUS NEUTRALIZING ANTIBODIES

Номер: US20210155676A1
Автор: Balakrishnan Mini, Carr Brian A., Corbin John, Pace Craig S., Thomsen Nathan D., ZHANG Xue
Принадлежит:

The present invention provides novel anti-HIV antibodies with improved therapeutic properties, related pharmaceutical compositions, and methods of use thereof. 129-. (canceled)30. An isolated monoclonal antibody , or an antigen-binding fragment thereof , that binds to human immunodeficiency virus (HIV) gp120 , comprising a heavy chain variable region having at least 95% , at least 98% , or at least 99% sequence identity to the heavy chain variable region set forth in SEQ ID NO: 451 , and a light chain variable region having at least 95% , at least 98% , or at least 99% sequence identity to the light chain variable region set forth in SEQ ID NO: 452; wherein the heavy chain variable region comprises Asn at position 60 , His at position 68 , Thr-Gly-Val at positions 82a-82c and Thr at position 105 , using Kabat numbering; and wherein the light chain variable region comprises Arg at position 67b and Pro at position 67c , using Kabat numbering.31. The isolated monoclonal antibody of claim 30 , comprising a heavy chain constant region comprising one or more of the following amino acid substitutions: Ala at position 236 claim 30 , Asp at position 239 claim 30 , Leu at position 330 claim 30 , Glu at position 332 claim 30 , Leu at position 428 claim 30 , and Ser at position 434 claim 30 , using EU numbering.32. The isolated monoclonal antibody of claim 30 , comprising a IgG1m17 allotype heavy chain.33. The isolated monoclonal antibody of claim 30 , comprising a Lambda2 light chain.34. A pharmaceutical composition comprising the monoclonal antibody or fragment thereof of claim 30 , and a pharmaceutically acceptable carrier claim 30 , excipient or diluent.35. The pharmaceutical composition of claim 34 , wherein the pharmaceutically acceptable carrier claim 34 , excipient or diluent comprises an aqueous pH-buffered solution and a sugar.36. The pharmaceutical composition of claim 34 , wherein the pharmaceutically acceptable carrier claim 34 , excipient or diluent comprises an ...

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Номер записи: 78
12-05-2016 дата публикации

Pathogen Binding Agents Conjugated to Radioisotopes and Uses in Imaging and Therapeutic Applications

Номер: US20160130328A1
Автор: Santangelo Philip, VILLINGER Francois
Принадлежит:

This disclosure relates to binding agents specific for the envelope protein of a virus, e.g., lentivirus, wherein the binding agent is conjugated to a molecule with a radioisotope or positron-emitting radionuclide. In certain embodiments, the disclosure relates to methods of imaging a virus or other pathogen within the body of a subject using binding agents disclosed herein. In certain embodiments, the disclosure relates to methods of treating or preventing a viral or other pathogenic infection by administering pharmaceutical composition containing radioactive binding agents disclosed herein. 1. A binding agent specific for pathogenic antigen , wherein the binding agent is conjugated to a molecule with a positron-emitting radionuclide.2. A binding agent of claim 1 , wherein the pathogenic antigen is a virus particle surface antigen.3. The binding agent of which is an antibody claim 1 , antibody fragment claim 1 , aptamer claim 1 , or antibody mimetic.4. The binding agent of claim 3 , wherein the antibody epitope is on a gp120 protein of a lentivirus.5. The binding agent of claim 3 , wherein the antibody epitope is on the V3 loop of a gp120 protein of a lentivirus.6. The binding agent of claim 3 , wherein the antibody is a humanized antibody or human chimera.7. The binding agent of claim 6 , wherein the human chimera comprises a polypeptide sequence selected froma) a variable domain of the light chain from an antibody conjugated to a human immunoglobulin;b) a variable domain of the heavy chain from an antibody conjugated to a human immunoglobulin; orc) a variable domain of the light chain and heavy chain from an antibody conjugated to a human immunoglobulin.8. The binding agent of claim 6 , wherein the humanized antibody comprises polypeptide sequences of complementarity determining region one (CDR-1) claim 6 , CDR-2 claim 6 , and CDR-3 on the light (VL) chain of an antibody and polypeptide sequences of CDR-1 claim 6 , CDR-2 claim 6 , and CDR-3 heavy (VH) chains of ...

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Номер записи: 79
11-05-2017 дата публикации

POLYPEPTIDE DERIVED FROM gp41, A VACCINE COMPOSITION COMPRISING SAID POLYPEPTIDE, AND USES FOR TREATING AN INFECTION BY AN HIV VIRUS IN AN INDIVIDUAL

Номер: US20170128564A1
Автор: Debre Patrice, Vieillard Vincent
Принадлежит:

The present invention relates to the field of the in vitro diagnosis of the progression status of an infection of an individual with a virus belonging to the family of the Human Immunodeficiency Viruses (HIV) as well as with the therapeutical treatment of this infectious disease. The invention also relates to immunological compounds and vaccine compositions comprising a polypeptide derived from gp41. 1. A method for treating an HIV infected patient , comprising administering to an individual an effective amount of an antigenic polypeptide of the following formula (III):{'br': None, 'sub': 2', 'n', 'n', 'n, 'NH-PepNt-[(I)-PepX]-PepCt-COOH\u2003\u2003(III),'} “PepNt” consists of a polypeptide having an amino acid length from 4 to 6 amino acid residues and located at the N-terminal end of the polypeptide of formula (III);', {'sub': n', 'n, 'claim-text': [{'sub': 1', 'n, '“(I)” to −“(I)” each consists of, one independently from each other, a polypeptide of formula “SWSNKS”, with n being an integer of 1; and'}, {'sub': 1', 'n, '“PepX” to “PepX” each consists of, one independently from the other, a spacer polypeptide having an amino acid length of 0 amino acid residues, with n being an integer of from 1 to 12;'}], '“[(I)-PepX]” consists of a polypeptide unit wherein, {'sub': n', 'n, 'n is the number of [(I)-PepX] polypeptide units in said polypeptide, with n being an integer of from 1 to 12; and'}, '“PepCt” consists of a polypeptide having an amino acid length of 5 amino acid residues and located at the C-terminal end of the polypeptide of formula (III),, 'whereinwherein the said antigenic polypeptide raises an antibody response that does not neutralize the HIV virus and that inhibits the cytotoxicity of NK cells towards CD4+ T cells in patients infected by HIV.2. The method according to claim 1 , wherein:“PepNt” consists of a polypeptide having an amino acid length of 6 amino acid residues and located at the N-terminal end of the polypeptide of formula (III);{'sub': n', ...

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Номер записи: 80
23-04-2020 дата публикации

Immunoconjugates with an Intracellularly-Cleavable Linkage

Номер: US20200121805A1
Автор: David M. Goldenberg, Serengulam V. Govindan, Sung-Ju Moon
Принадлежит: Immunomedics Inc

The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

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Номер записи: 81
01-09-2022 дата публикации

DE-IMMUNIZED SHIGA TOXIN A SUBUNIT EFFECTOR POLYPEPTIDES FOR APPLICATIONS IN MAMMALS

Номер: US20220275030A1
Автор: Brieschke Brigitte, POMA Eric, Rajagopalan Sangeetha, Robinson Garrett Lee, WILLERT Erin
Принадлежит:

The present invention relates to Shiga toxin effector polypeptides with reduced antigenic and/or immunogenic potential. Immunogenicity can be a limitation for the repeated administration to mammals of proteins and polypeptides derived from Shiga toxins. The Shiga toxin effector polypeptides of the present invention have uses as components of therapeutics, diagnostics, and immunization materials. The cytotoxic proteins of the present invention have uses for selective killing of specific cell types and as therapeutics for the treatment of a variety of diseases, including cancers, immune disorders, and microbial infections. The proteins of the present invention also have uses for detecting specific cell types, collecting diagnostic information, and monitoring the treatment of a variety of diseases, such as, e.g., cancers, immune disorders, and microbial infections. 1. A Shiga toxin effector polypeptide comprising an amino acid sequence having at least 90% identity to amino acids 1 to 251 of SEQ ID NO: 1 ,wherein the amino acid sequence comprises at least four endogenous B-cell epitope regions, and further comprises:i) a plurality of disrupted endogenous B-cell epitope regions, wherein the disrupted endogenous B-cell epitope regions contain the following amino acid substitutions: S45 of SEQ ID NO: 1 to I, R55 of SEQ ID NO: 1 to L, 157 of SEQ ID NO: 1 to F, P59 of SEQ ID NO: 1 to F, E60 of SEQ ID NO: 1 to T, E61 of SEQ ID NO: 1 to L, G110 of SEQ ID NO: 1 to A, R188 of SEQ ID NO: 1 to A, R248 of SEQ ID NO: 1 to A and R251 of SEQ ID NO: 1 to A;and ii) the amino acid substitution C242 of SEQ ID NO: 1 to S; andwherein the amino acid sequence comprises an asparagine at the amino acid residue corresponding to position 75 of SEQ ID NO: 1, a tyrosine at the amino acid residue corresponding to position 77 of SEQ ID NO: 1, a tyrosine at the amino acid residue corresponding to position 114 of SEQ ID NO: 1, a glutamate at the amino acid residue corresponding to position 167 of SEQ ...

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Номер записи: 82
02-05-2019 дата публикации

HIV-1 VACCINE

Номер: US20190127466A1
Автор: Arts Eric J., Burkhouse Annette
Принадлежит:

A method for inducing an immune response against HIV in a subject includes the step of preparing an HIV-1 gp120 envelope protein coding sequence particle having an N425K mutation, introducing the HIV-1 gp120 protein coding sequence particle having an N425K mutation into an expression construct using yeast homologous recombination, transfecting a cell with the expression construct, wherein the HIV-1 particle is secreted by the cell, and administering the secreted HIV-1 particle and a pharmaceutically acceptable carrier to the subject, wherein the secreted HIV-1 particle stimulates an immune response in the subject. 1. A method for inducing an immune response against HIV in a subject , the method comprising the steps:preparing an HIV-1 gp120 envelope protein coding sequence particle having an N425K mutation;introducing the HIV-1 gp120 protein coding sequence particle having an N425K mutation into an expression construct using yeast homologous recombination;transfecting a cell with the expression construct, wherein the HIV-1 particle is secreted by the cell; andadministering the secreted HIV-1 particle and a pharmaceutically acceptable carrier to the subject, wherein the secreted HIV-1 particle stimulates an immune response.2. The method of claim 1 , the immune response comprising the generation of broadly neutralizing CD4i HIV-1 antibodies directed to a CD4 coreceptor biding site of HIV-1.3. The method of claim 2 , the CD4 coreceptor binding site comprising a CCR5 CD4 coreceptor binding site.4. The method of claim 1 , wherein the HIV protein coding sequences is prepared from HIV-1 RNA.5. The method of claim 1 , wherein the HIV-1 particle secreted by the cell is a replication defective HIV-1 particle including N425K env claim 1 , gag and pol proteins in the correct stoichometry and is morphologically indistinguishable from a wild type HIV-1.6. The method of claim 1 , further comprising the step of harvesting the HIV-1 particle.7. The method of claim 4 , wherein the ...

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Номер записи: 83
23-04-2020 дата публикации

MULTISPECIFIC ANTIBODIES TARGETING HUMAN IMMUNODEFICIENCY VIRUS AND METHODS OF USING THE SAME

Номер: US20200123236A1
Автор: Guenaga Javier, Li Yuxing, Mascola John R., STEINHARDT James
Принадлежит:

The present disclosure relates to multispecific antibodies targeting the human immunodeficiency virus-1 (HIV-1) envelope, methods for their production, pharmaceutical compositions containing said antibodies and uses thereof in treatment and prevention of HIV infection. 1. A multispecific antibody , or an antigen-binding fragment thereof , comprising:a) a first light chain comprising a first light chain variable region (VL) and a first heavy chain comprising a first heavy chain variable region (VH), wherein the first light chain and the first heavy chain are derived from a first antibody or an antigen-binding fragment thereof; andb) a second light chain comprising a second light chain variable region (VL) and a second heavy chain comprising a second heavy chain variable region (VH), wherein the second light chain and the second heavy chain are derived from a second antibody or an antigen-binding fragment thereof,wherein the first light chain and the second light chain bind non-overlapping epitopes of the envelope protein of human immunodeficiency virus-1 (HIV-1), andwherein the VH from the first light chain and the VL from the second light chain are connected by one or more linkers or wherein the VL from the first light chain and the VH from the second light chain are connected by one or more linkers.2. (canceled)3. The multispecific antibody claim 1 , or antigen binding fragment thereof claim 1 , of claim 1 , wherein the linker is not a single glycine (Gly) residue; a diglycine peptide (Gly-Gly); a tripeptide (Gly-Gly-Gly); a peptide with four glycine residues (Gly-Gly-Gly-Gly); a peptide with five glycine residues (Gly-Gly-Gly-Gly-Gly); a peptide with six glycine residues (Gly-Gly-Gly-Gly-Gly-Gly); a peptide with seven glycine residues (Gly-Gly-Gly-Gly-Gly-Gly-Gly); a peptide with eight glycine residues (Gly-Gly-Gly-Gly-Gly-Gly-Gly-Gly) claim 1 , the peptide Gly-Gly-Gly-Gly-Ser claim 1 , the peptide Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser claim 1 , the peptide Gly- ...

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Номер записи: 84
23-04-2020 дата публикации

HUMANIZED OR CHIMERIC CD3 ANTIBODIES

Номер: US20200123255A1
Автор: Labrijn Aran Frank, MEESTERS Joyce, Neijssen Joost J., PARREN Paul, SCHUURMAN Janine, VAN DEN BRINK Edward
Принадлежит:

The present invention relates to humanized or chimeric antibodies binding CD3. It furthermore relates to bispecific antibodies, compositions, pharmaceutical compositions, use of said antibodies in the treatment of a disease, and method of treatment. 149-. (canceled)50. A nucleic acid construct encoding the heavy and/or light chain variable region of a humanized or chimeric antibody which binds to human CD3 , wherein said antibody comprises heavy chain variable (VH) region CDR1 , CDR2 , and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NOs: 1 , 2 , and 3 , respectively , and light chain variable (VL) region CDR1 , CDR2 , and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NO: 4 , GTN , and SEQ ID NO: 5 , respectively.51. An expression vector comprising the nucleic acid of .52. A host cell comprising the expression vector of .53. A method for producing an anti-CD3 antibody comprising: (a) culturing the host cell of claim 52 , and (b) purifying the antibody from the culture media.54. A method of diagnosing a disease characterized by involvement or accumulation of CD3-expressing cells claim 52 , comprising administering a humanized or chimeric antibody which binds to human CD3 claim 52 , wherein said antibody comprises heavy chain variable (VH) region CDR1 claim 52 , CDR2 claim 52 , and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NOs: 1 claim 52 , 2 claim 52 , and 3 claim 52 , respectively claim 52 , and light chain variable (VL) region CDR1 claim 52 , CDR2 claim 52 , and CDR3 domains comprising the amino acid sequences set forth in SEQ ID NO: 4 claim 52 , GTN claim 52 , and SEQ ID NO: 5 claim 52 , respectively claim 52 , optionally wherein the antibody is labeled with a detectable agent.55. A method for detecting the presence of CD3 antigen claim 52 , or a cell expressing CD3 claim 52 , in a sample comprising the steps of;a) contacting the sample with a humanized or chimeric antibody which binds to ...

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Номер записи: 85
17-05-2018 дата публикации

METHODS AND COMPOSITIONS FOR INHIBITING HIV TRANSMISSION

Номер: US20180134768A1
Автор: Purcell Damian Francis John
Принадлежит: Reef Pharmaceuticals Pty Ltd

The present invention provides methods and compositions useful in the field of medicine, and particularly in the treatment of viral infections. More particularly, the invention relates to the use of methods and compositions for the inhibition of human immunodeficiency virus (HIV) transmission. 1. A composition for inhibiting transmission of HIV comprising polyclonal antibodies or fragments thereof capable of binding to a human immunodeficiency virus (HIV) viral envelope (Env) protein or a fragment thereof , wherein the polyclonal antibodies or fragments thereof are capable of binding to a Env protein from a heterologous clade of HIV2. A composition according to wherein the Env protein or fragment thereof is gp140.3. A composition according to or wherein the Env protein or fragment thereof is a gp140 oligomer4. A composition according to wherein the Env protein or fragment thereof is a stabilized gp140 trimer.5. A composition according to wherein the gp140 trimer is stabilized by way of covalent bond between residues of any two or more of the gp140 trimer.6. A composition according to wherein the covalent bond is formed between a residue of gp120 and a residue of gp41.7. A composition according to wherein the covalent bond is an intermolecular disulphide bond formed between gp120 and gp41.8. A composition according to wherein the stabilized gp140 trimer comprises one or more mutations in gp41 and/or gp120 configured to enhance stability of the trimer.9. A composition according to wherein the mutation is a substitution of a residue in the N-terminal heptad repeat region of gp41.10. A composition according to wherein the mutation is an isoleucine-to-proline substitution at position 559 in the N-terminal heptad repeat region of gp41.11. A composition according to claim 10 , wherein the Env protein is SOSIP gp140 claim 10 , or functional equivalent thereof.12. A composition according to wherein the polyclonal antibodies or fragments thereof are obtained from a milk or a ...

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Номер записи: 86
30-04-2020 дата публикации

ANTIBODY THERAPIES FOR HUMAN IMMUNODEFICIENCY VIRUS (HIV)

Номер: US20200129618A1
Автор: BAROUCH Dan H.
Принадлежит:

This invention relates to antibody therapies for human immunodeficiency virus (HIV). In particular, the invention provides methods of curing subjects infected with HIV and blocking HIV infections in subjects at risk of HIV transmission using a N332 glycan-dependent antibody (e.g., PGT121). 189-. (canceled)90. A method for treating a human immunodeficiency virus type 1 (HIV-1) infection in a subject , wherein said subject has been previously administered antiretroviral therapy (ART) or has plasma viral RNA levels below 3500 copies/mL , comprising administering:(a) at least one dose of a first composition comprising one or more N332 glycan-dependent antibodies; and (i) after at least about twenty-eight days after administration of the first composition and prior to a decline in a blood titer of the one or more N332 glycan-dependent antibodies of the first composition below about 1 μg/ml;', '(ii) at least two months after administration of the first composition; or', {'sup': '6', '(iii) after proviral DNA level in tissue of the subject is below about 1000 DNA copies/10cells.'}], '(b) at least one dose of a second composition comprising one or more N332 glycan-dependent antibodies, wherein the second composition is administered91. The method of claim 90 , wherein said N332 glycan-dependent antibody is selected from the group consisting of: (i) a heavy chain complementarity determining region (CDR-H) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a light chain complementarity determining region (CDR-L) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6; or', '(ii) a heavy chain variable domain having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 7, and a light chain variable ...

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Номер записи: 87
08-09-2022 дата публикации

ANTIBODIES AND THE USES THEREOF

Номер: US20220281959A1
Автор: POTHLICHET JULIEN, THEZE JACQUES
Принадлежит:

The present invention relates to antibodies and their use. The invention particularly relates to antibodies against a particular domain of gp41, pharmaceutical compositions or kits or any device comprising the same, as well as the uses thereof. The invention is particularly useful for treating (e.g., curing or preventing), detecting or monitoring AIDS in a subject, either, alone or in combination with other treatments/agents. 126-. (canceled)27. An isolated monoclonal antibody , or a variant or fragment thereof , said isolated monoclonal antibody , or a variant or fragment thereof binding:a) to an epitope of a HIV gp41 protein, wherein the epitope includes at least one amino acid residues of PEP3 domain of gp41 protein, and wherein the monoclonal antibody or variant or fragment thereof inhibits the binding of gp41 to C1qR; orb) to an HIV gp41 protein at one or more amino acid residues of PEP3 domain of gp41 protein, and wherein the monoclonal antibody or variant or fragment thereof inhibits the binding of gp41 to C1qR.28. The monoclonal antibody of claim 27 , which essentially does not bind HIV gp120 protein.29. A monoclonal antibody comprising a light chain variable region claim 27 , wherein the light chain variable region comprises (i) a CDR-L1 consisting essentially of SEQ ID NO: 15 claim 27 , 21 claim 27 , 27 claim 27 , 33 claim 27 , 39 claim 27 , or 45 claim 27 , and/or (ii) a CDR-L2 consisting essentially of SEQ ID NO: 16 claim 27 , 22 claim 27 , 28 claim 27 , 34 claim 27 , 40 claim 27 , or 46 claim 27 , and/or (iii) a CDR-L3 consisting essentially of SEQ ID NO: 17 claim 27 , 23 claim 27 , 29 claim 27 , 35 claim 27 , 41 claim 27 , or 47.30. The monoclonal antibody of claim 29 , wherein the light chain variable region comprises a CDR-L1 claim 29 , a CDR-L2 and a CDR-L3 as follows:SEQ ID NOs: 15, 16 and 17; orSEQ ID NOs: 21, 22 and 23; orSEQ ID NOs: 27, 28, and 29; orSEQ ID NOs: 33, 34 and 35; orSEQ ID NOs: 39, 40 and 41; orSEQ ID NOs: 45, 46 and 47.31. The ...

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Номер записи: 88
10-06-2021 дата публикации

Bispecific CD16-Binding Molecules and Their Use in the Treatment of Disease

Номер: US20210171630A1
Автор: Diedrich Gundo, Johnson Leslie S., Li Hua Watson, Liu Liqin
Принадлежит: MACROGENICS, INC.

The present invention is directed to molecules (e.g., an antibody, a diabody, an scFv, an antibody, a TandAb, etc.) capable of binding an epitope of human CD16 (a “CD16 Binding Molecule”). The present invention is further directed to CD 16 Binding Molecules that are capable of binding an epitope of human CD16 and one or more epitope(s) of a Disease Antigen (“DA”) (e.g., a “CD16 x DA Binding Molecule”). The present invention is particularly directed to such CD16 x DA Binding Molecules that are antibodies, or that comprise an Epitope Binding Domain thereof, or are diabodies (including DART® diabodies), bispecific antibodies, TandAbs, other multispecific binding molecules (e.g., trivalent TRIDENT™ molecules), etc. The invention particularly concerns CD16 x DA Binding Molecules that are capable of binding a Disease Antigen that is a Cancer Antigen or a Pathogen-Associated Antigen in addition to being able to bind CD 16. The invention particularly concerns the use of such CD16 and CD16 x DA Binding Molecules in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s). 1. A CD16 x Disease Antigen (CD16 x DA) Binding Molecule comprising a CD16 Binding Domain capable of binding an epitope of CD16 and also a Disease Antigen-Binding Domain capable of binding an epitope of a Disease Antigen , wherein said CD16 Binding Domain comprises one or more of:{'sub': 'H', 'claim-text': [{'sub': 'H', '(B) a CDR2 Domain comprising the amino acid sequence of SEQ ID NO:67;'}, {'sub': 'H', '(C) a CDR3 Domain comprising the amino acid sequence of SEQ ID NO:68 or SEQ ID NO:60;'}, {'sub': 'L', '(D) a CDR1 Domain comprising the amino acid sequence of SEQ ID NO:69 or SEQ ID NO:74;'}, {'sub': 'L', '(E) a CDR2 Domain comprising the amino acid sequence of SEQ ID NO:70; and'}, {'sub': 'L', '(F) a CDR3 Domain comprising the amino acid sequence of SEQ ID NO:71 or SEQ ID NO:61;'}], '(I) (A) a CDR1 ...

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Номер записи: 89
04-06-2015 дата публикации

HIV-1-NEUTRALIZING ANTIBODY POTENCY AND BREADTH VIA CELL RECEPTOR ANCHORING USING BISPECIFIC ANTIBODIES WITH NATIVE ARCHITECTURE

Номер: US20150152167A1
Автор: HO David D., Huang Yaoxing, Yu Jian
Принадлежит:

In various embodiments, the present invention relates generally to using bispecific antibodies in the prevention and treatment of HIV. 1. A bispecific antibody capable of neutralizing HIV , wherein the antibody includes portions of a first and a second antibody and wherein the first antibody binds to a HIV envelope protein.2. The bispecific antibody of claim 1 , wherein the bispecific antibody has a CrossMab format.3. The bispecific antibody of claim 1 , wherein the first antibody is selected from PGT145 claim 1 , PG9 claim 1 , PGT128 claim 1 , PGT121 claim 1 , 10-1074 claim 1 , 3BNC117 claim 1 , VRC01 claim 1 , PGT151 claim 1 , 4E10 claim 1 , 10E8 claim 1 , or a variant thereof.4. The bispecific antibody of claim 3 , wherein the first antibody is an anti-gp41 antibody.5. The bispecific antibody of claim 4 , wherein the first antibody binds to the membrane proximal external region (MPER) of HIV gp41.6. The bispecific antibody of claim 5 , wherein the first antibody is 10E8 or a variant thereof.7. The bispecific antibody of claim 5 , wherein the first antibody is 4E10 or a variant thereof.8. The bispecific antibody of claim 1 , wherein the second antibody binds to a cell membrane protein.9. The bispecific antibody of claim 8 , wherein the second antibody binds to a cell membrane receptor protein or a cell membrane co-receptor protein.10. The bispecific antibody of claim 9 , wherein the second antibody is selected from a CD4 antibody claim 9 , a CCR5 antibody or a CXCR4 antibody.11. The bispecific antibody of claim 10 , wherein the second antibody is selected from Pro 140 claim 10 , ibalizumab claim 10 , 515H7 claim 10 , or a variant thereof.12. A bispecific antibody including portions of a first antibody and a second antibody claim 10 , wherein the first antibody binds to a HIV envelope protein and the second antibody binds to a cell membrane protein.13. The bispecific antibody of claim 12 , wherein the bispecific antibody has a CrossMab format.14. The bispecific ...

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Номер записи: 90
25-05-2017 дата публикации

METHODS FOR INCREASING THE DIVERSITY OF MONOCLONAL ANTIBODIES PRODUCED AGAINST AN ANTIGEN

Номер: US20170145407A1
Автор: Cumming Dale Anthony
Принадлежит:

The present invention relates to methods for increasing the diversity of monoclonal antibodies produced against an antigen. The methods of the invention utilize immunization of a murine host defective in one or more enzymes involved in a post-translational modification of a polypeptide or a modification of a lipid, wherein said modification is exposed on a cell surface. The invention also relates to monoclonal antibodies produced by these methods and which are not produced when a normal mouse is immunized with the same antigen. The invention further relates to compositions comprising these monoclonal antibodies, as well as to such monoclonal antibodies bound or conjugated to a toxin, a detectable marker or to a solid support. 1. A method of producing an antibody library that comprises an antibody that binds to an epitope on a molecule of interest , wherein the epitope is not present naturally in a wild-type host , the method comprising the steps of:(a) immunizing a knockout host with an antigen that comprises the epitope present on said molecule of interest in a manner sufficient for said knockout host to develop antibodies against said epitope, wherein when the wild-type host is immunized with the antigen it does not produce an antibody that binds to the epitope, wherein said knockout host comprises a knockout mutation in an enzyme involved in post-translational glycosylation of a;(b) isolating splenocytes or B cells from said immunized host;(c) extracting ribonucleic acid (RNA) from the isolated splenocytes or B cells; and(d) generating an antibody library from the extracted RNA.2. The method of claim 1 , wherein the library is a phage display library.3. The method of claim 1 , wherein the library is a yeast display library.4. The method of further comprising the step of amplifying the RNA by polymerase chain reaction (PCR).5. The method of wherein the B cells are isolated from blood claim 1 , bone marrow claim 1 , or lymph node.6. The method of wherein the ...

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Номер записи: 91
02-06-2016 дата публикации

COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS

Номер: US20160152667A1
Автор: Bird Gregory H., Walensky Loren D.
Принадлежит:

The invention provides compositions, kits and methods utilizing polypeptides having a viral alpha-helix heptad repeat domain in a stabilized α-helical structure (herein also referred to as SAH). The compositions are useful for treating and/or preventing viral infections. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled alpha helical peptides display excellent proteolytic, acid, and thermal stability, restore the native alpha-helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides. 1. A modified polypeptide comprising a stabilized alpha helix of HIV gp41 heptad repeat domain.261.-. (canceled)62. A method for inhibiting transmission of HIV to a cell comprising contacting the virus in the presence of the cell with an effective dose of a modified polypeptide comprising a stabilized alpha helix of HIV gp41 heptad repeat domain , so that the infection of the cell by the virus is inhibited.6370.-. (canceled)71. A method for treating or delaying the onset of AIDS in an HIV infected individual , comprising administering to the individual an effective dose of a pharmaceutical composition comprising a modified polypeptide comprising a stabilized alpha helix of HIV gp41 heptad repeat domain.7285.-. (canceled) This application is a continuation of U.S. application Ser. No. 12/864,375, filed on Jul. 23, 2010, which is a continuation of International Application No. PCT/US2009/000438 (WO2009/108261) filed on Jan. 23, 2009, which claims priority to U.S. Provisional Patent Application Ser. No. 61/062,007 filed on Jan. 23, 2008, each of which is incorporated herein by reference in its entirety.The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web, and is hereby incorporated by reference in its entirety. Said ASCII copy, ...

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Номер записи: 92
16-05-2019 дата публикации

Immunoglobulins Directed to Bacterial, Viral and ENDOGENOUS Polypetides

Номер: US20190144528A1
Автор: Brown Eric L., Nishiyama Yasuhiro, Paul Sudhir, Planque Stephanie, Smith Keri C., TAGUCHI Hiroaki
Принадлежит:

Disclosed are antibodies (immunoglobulins) and fragments thereof that hydrolyze or bind polypeptide antigens belonging to , hepatitis C virus, human immunodeficiency virus and Alzheimer's disease. Also disclosed are novel methods to improve the antigen reactivity of the immunoglobulins and to treat a pathophysiological condition using the immunoglobulins as therapeutics. 143-. (canceled)44: An isolated or purified immunoglobulin (Ig) variable (V) domain of a light chain subunit (VL) or heavy chain subunit (VH) of an immunoglobulin having a specific , defined antigenic-directed activity ,wherein the antigen of said IgV is an amyloid protein or a superantigen other than gp120, said IgV catalyzes the hydrolysis of said amyloid protein or superantigen; and said IgV is obtained from an organism without prior immunization with said antigen, andwherein said IgV comprises a nucleophilic site.45: The IgV domain of claim 44 , wherein said IgV domain is covalently linked to a second IgV domain to form a dimer claim 44 , andwherein said dimer comprises two VL domains or two VH domains.46: The IgV domain of claim 45 , wherein the two IgV domains of the VL dimer are covalently linked by a peptide linker between the termini of the VL domains.47: The IgV domain of claim 44 , further comprising a peptide tag.48: The IgV domain of claim 47 , wherein said peptide tag is effective to reduce or to eliminate intermolecular V domain aggregation reactions.49: The IgV domain of claim 47 , wherein said peptide tag facilitates delivery of the IgV domain(s) to an anatomic site of interest.50: The IgV domain of claim 49 , wherein the anatomic site of interest is the blood-brain barrier.51: The IgV domain of claim 50 , wherein said peptide tag is putrescine claim 50 , TAT peptide or an antibody to a molecule expressed on cells forming the blood-brain barrier.52: The IgV domain of claim 44 , wherein said hydrolysis of said amyloid protein or superantigen by said IgV is inhibited by a serine ...

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Номер записи: 93
07-05-2020 дата публикации

Broadly Neutralizing Anti-HIV Antibodies and Epitope Therefor

Номер: US20200140528A1
Автор: Bjorkman Pamela J., Nussenzweig Michel, Scharf Louise, Scheid Johannes
Принадлежит: THE ROCKEFELLER UNIVERSITY

The present invention relates to broadly neutralizing anti-HIV-1 antibodies and isolated antigens. Also disclosed are related methods and compositions. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. An isolated nucleic acid encoding the an isolated anti-HIV-1 antibody comprising one or both of a heavy chain comprising the sequence of any one of SEQ ID NOs: 1-18 and a light chain comprising the sequence of any one of SEQ ID NOs: 19-33 or an isolated polypeptide comprising the sequence of any one of SEQ ID NOs: 1-33.7. A vector comprising the isolated nucleic acid of .8. A cultured cell comprising the vector of .9. (canceled)10. (canceled)11. An isolated antigen comprising an epitope-scaffold that mimics the HIV-1 envelope spike epitope of broadly neutralizing antibody 8ANC195.12. The antigen of wherein the epitope-scaffold comprises a discontinuous epitope and a scaffold claim 11 , wherein the epitope is derived from HIV-1 gp120 and gp41 claim 11 , and wherein at least part of the scaffold is not derived from gp120 or gp41.13. The antigen of wherein the discontinuous epitope comprises amino acids corresponding to amino acid numbers 44-47 claim 12 , 90-94 claim 12 , 97 claim 12 , 234 claim 12 , 236-238 claim 12 , 240 claim 12 , 274-278 claim 12 , 352-354 claim 12 , 357 claim 12 , 456 claim 12 , 463 claim 12 , 466 claim 12 , 487 claim 12 , and 625-641 of gp140 from HIV strain 93TH057 numbered using standard numbering for HIV strain HXBC2.14. The antigen of wherein the amino acids corresponding to amino acid numbers 234 and 276 are glycosylated.15. An isolated nucleic acid encoding the antigen of .16. A vector comprising the isolated nucleic acid of .17. A cultured cell comprising the vector of .18. A composition comprising the antigen of .19. A method for inducing an HIV antigen-specific immune response in a subject in need thereof claim 18 , comprising administering to said subject the composition of in an amount effective to generate an immune ...

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Номер записи: 94
07-05-2020 дата публикации

Methods and compositions for inhibiting hiv transmission

Номер: US20200140529A1
Автор: Damian Francis John Purcell
Принадлежит: Reef Pharmaceuticals Pty Ltd

The present invention provides methods and compositions useful in the field of medicine, and particularly in the treatment of viral infections. More particularly, the invention relates to the use of methods and compositions for the inhibition of human immunodeficiency virus (HIV) transmission.

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Номер записи: 95
31-05-2018 дата публикации

BISPECIFIC MOLECULES COMPRISING AN HIV-1 ENVELOPE TARGETING ARM

Номер: US20180148497A1
Автор: Ferrari Guido, Haynes Barton F., Johnson Leslie S., Koenig Scott, Lam Chia-Ying Kao, Liu Liqin, MARGOLIS David M., NORDSTROM Jeffrey Lee, SUNG Julia A.
Принадлежит:

The invention is directed to bispecific molecules comprising an HIV-1 envelope targeting arm and an arm targeting an effector cell, compositions comprising these bispecific molecules and methods of use. In certain aspects, the bispecific molecules of the present invention can bind to two different targets or epitopes on two different cells wherein the first epitope is expressed on a different cell type than the second epitope, such that the bispecific molecules can bring the two cells together. In certain aspects, the bispecific molecules of the present invention can bind to two different cells, wherein the bispecific molecules comprises an arm with the binding specificity of A32, 7B2, CH27, CH28, or CH44. 132-. (canceled)33. A bispecific molecule comprising a first polypeptide chain , a second polypeptide chain , and a third polypeptide chain covalently bonded to one another , wherein: (i) a domain (A) comprising a binding region of the light chain variable domain of a first immunoglobulin (VL1) comprising the VL CDR3, CDR2 and CDR1 of the A32, 7B2, CH28, or CH44 HIV-1 antibody;', '(ii) a domain (B) comprising a binding region of a heavy chain variable domain of a second immunoglobulin (VH2) comprising the VH CDR3, CDR2 and CDR1 of an antibody specific for an epitope of CD3 or CD16, wherein domains (A) and (B) are separated from one another by a peptide linker 1;', '(iii) a domain (C) comprising a heterodimer promoting domain including a K coil or E coil; wherein the heterodimer promoting domain (C) and domain (B) are separated by a peptide linker 2; and', '(iv) a CH2-CH3 domain, wherein the CH2-CH3 domain and domain (C) are separated by a peptide linker 3 or a spacer-linker 3;, '(I) the first polypeptide chain comprises in the N- to C-terminal direction (i) a domain (D) comprising a binding region of a light chain variable domain of the second immunoglobulin (VL2) comprising the VL CDR3, CDR2 and CDR1 of an antibody specific for the epitope of CD3 or CD16;', '(ii) ...

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Номер записи: 96
07-05-2020 дата публикации

MULTIVALENT GLYCOPEPTIDES THAT TIGHTLY BIND TO TARGET PROTEINS

Номер: US20200140853A1
Автор: Horiya Satoru, KRAUSS Isaac J.
Принадлежит:

The invention relates to a glycopolypeptide that includes one or more modified amino acid residues having a sidechain comprising a monosaccharide or an oligosaccharide, wherein the glycopolypeptide binds specifically to a carbohydrate-binding monoclonal antibody with an affinity of less than 100 nM. Immunogenic conjugates that include the glycopolypeptide, and pharmaceutical compositions that include the glycopolypeptide or the immunogenic conjugate are also disclosed. Various method of using the glycopolypeptides, immunogenic conjugates, and pharmaceutical compositions are disclosed, including inducing an immune response, inhibiting viral or bacterial infection, treating a cancerous condition, and detecting a neutralizing antibody. 143.-. (canceled)44. A method of inducing an immune response in an individual comprising:administering to an individual: (i) a glycopolypeptide comprising one or more modified amino acid residues having a sidechain comprising a monosaccharide or an oligosaccharide, wherein the glycopolypeptide binds specifically to a carbohydrate-binding monoclonal antibody with an affinity of less than 100 nM, (ii) an immunogenic conjugate, comprising said glycopolypeptide covalently or non-covalently bound to an immunogenic carrier molecule; or (iii) a pharmaceutical composition comprising a pharmaceutically acceptable carrier and said glycopolypeptide or said immunogenic conjugate, wherein said administering is effective to induce an immune response against the glycopolypeptide.45. The method according to claim 44 , wherein said administering is effective to induce a carbohydrate-binding claim 44 , neutralizing antibody response.46. The method according to claim 45 , wherein the induced carbohydrate-binding claim 45 , neutralizing antibody response is protective against a virus.4751.-. (canceled)52. The method according to claim 44 , wherein said administering is carried out orally claim 44 , parenterally claim 44 , subcutaneously claim 44 , ...

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Номер записи: 97
16-05-2019 дата публикации

HIV DIAGNOSTIC METHOD USING CD4 AND CD8 CELL INFORMATION

Номер: US20190145951A1
Автор: LIM Taekyu, SUNG Yeon-Moon
Принадлежит: GLORY BIOTECH CORP.

Provided is a method of diagnosing HIV using an HIV diagnostic apparatus comprising a nanofilter comprising an upper body for collecting cells, wherein the upper body has a plurality of filtration holes formed through a substrate, any one filtration hole of the plurality of filtration holes is adjacent to other filtration holes, and an interval between a center of any one filtration hole and those of the other filtration holes adjacent thereto is 23 μm to 27 μm, the method comprising: collecting leukocytes, among the cells, using the nanofilter, radiating light toward the entire area of the nanofilter using a light source unit, sensing the light passing through the nanofilter using a light-sensing unit, outputting an image of the entire area of the nanofilter through a display means based on information obtained by the light-sensing unit, and analyzing the image outputted through the display means using an analyzing means. 1100100120110120. A method of diagnosing HIV using an HIV diagnostic apparatus comprising a nanofilter , which comprises an upper body () for collecting cells , the upper body () having a plurality of filtration holes () formed through a substrate () , and in which any one filtration hole of the plurality of filtration holes () is adjacent to other filtration holes and an interval between a center of any one filtration hole and centers of the other filtration holes adjacent thereto is 23 μm to 27 μm , the method comprising:(a) collecting leukocytes among the cells using the nanofilter;{'b': '500', '(b) radiating light toward an entire area of the nanofilter using a light source unit ();'}{'b': '600', '(c) sensing light passing through the nanofilter using a light-sensing unit ();'}{'b': 700', '600, '(d) outputting an image of the entire area of the nanofilter through a display means () based on information obtained by the light-sensing unit (); and'}{'b': 700', '800, '(e) analyzing the image outputted through the display means () using an ...

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Номер записи: 98
21-08-2014 дата публикации

Antibody and antibody-containing composition

Номер: US20140234337A1
Автор: Yasuhiro Tsukamoto
Принадлежит: IMMORTAL SPIRIT Ltd, OSTRICH PHARMA KK

For many diseases due to microbes or the like, proliferation of microbes themselves is a cause of a symptom. However, there were cases where a substance released by the microbes is a cause of a symptom. In such cases, when attempting to treat a disease with an antibody, it was necessary to obtain an antibody against an antigen that is a substance causing the disease. However, it was difficult to find the underlying substance causing the disease among substances released by the microbes. An antibody (polyclonal) binding to not only an antigen but also to a substance, which is secreted by the antigen and accelerates the deterioration of a symptom, is obtained by immunizing birds with a lysis solution produced from lysing microbial cells as an antigen. Further, an antibody obtained with a surface protein of a virus as an antigen is expected to inhibit an infection by a virus.

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Номер записи: 99
11-06-2015 дата публикации

BROADLY NEUTRALIZING VHH AGAINST HIV-1

Номер: US20150158934A1
Автор: McCoy Laura Ellen Fleet, RUTTEN Lucy, STROKAPPE Nika Mindy, VERRIPS CORNELIS THEODORUS, Webb Benjamin Lucian John, Weiss Robert Anthony
Принадлежит:

The invention relates to a novel class of broadly neutralizing anti-HIV antibodies, more specifically to broadly neutralizing heavy chain variable domain antibodies (VHH) and variants and modifications thereof. The invention further relates to methods for producing these antibodies and to the use of the antibodies for diagnostic and therapeutic and/or prophylactic treatment of individuals that are infected with HIV, or are at risk of becoming infected. 1. A broadly neutralizing anti-HIV single heavy chain variable domain antibody (VHH) that neutralizes at least 70% of individual viruses of 5 or more different subgroups of viruses.2. A broadly neutralizing anti-HIV single heavy chain variable domain antibody (VHH) according to claim 1 , which neutralizes at least 75% of individual viruses of at least 5 different subgroups.3. The heavy chain variable domain antibody of claim 1 , wherein said antibody binds nearly exclusively to a CD4 binding site on HIV.4. The heavy chain variable domain antibody of claim 1 , wherein the CDR2 region as defined by amino acid residues 52-58 (according to the Kabat numbering) consists of 5 amino acids.5. The heavy chain variable domain antibody of claim 1 , comprising CDR1 claim 1 , CDR2 and CDR3 amino acid sequences as depicted in table 2 claim 1 , table 3 claim 1 , and/or table 6.6. The heavy chain variable domain antibody of claim 1 , comprising CDR1 claim 1 , CDR2 and CDR3 amino acid sequences as depicted in table 11.7. The heavy chain variable domain antibody of claim 1 , wherein said antibody is fused to an immunoglobulin Fc region or functional part thereof.8. The heavy chain variable domain antibody of claim 7 , wherein the Fc region or functional part thereof is derived from IgGl claim 7 , IgG2 claim 7 , IgG3 claim 7 , or IgG4.9. The antibody of claim 7 , wherein the Fc region or functional part thereof is human or a humanized lama Fc or functional part thereof.10. A bi- or multispecific antibody comprising a heavy chain ...

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Номер записи: 100