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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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Применить Всего найдено 36538. Отображено 100.
23-02-2012 дата публикации

ANTI-lgSF4 ANTIBODY AND UTILIZATION OF THE SAME

Номер: US20120046451A1
Автор: Akihiko Takasaki, Atsushi Sugioka, Chiho Muramatsu, Gene Kurosawa, Kazuhiro Morishita, Kazuhiro Suzuki, Kazuki Matsuda, Keiko Ogawa, Mariko Sumitomo, Masachika Azuma, Miwa Morita, Nobuhiro Hayashi, Nobuhiro Takahashi, Sari Fujiyama, Susumu Tsutsumi, Yasushi Akahori, Yoshikazu Kurosawa, Yoshinori Ukai, Yoshitaka Iba
Принадлежит: Institute for Antibodies Co Ltd

It is intended to clarify a molecule which is available as a target in treating or diagnosing cancer and utilize the molecule in the medical field or the research field. By treating IgSF4, which has been identified as a molecule specifically expressed in lung cancer cells, with an antibody, and ADCC activity is exerted. Based on this finding, an anti-IgSF4 antibody is provided as a means efficacious in treating cancer, etc.

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Номер записи: 1
15-03-2012 дата публикации

Therapeutic use of anti-cs1 antibodies

Номер: US20120064083A1
Автор: Gao Liu, J. Yun Tso, Marna Williams, Nicholas F. Landolfi
Принадлежит: Abbott Biotherapeutics Corp

The present invention is directed to antagonists of CS1 that bind to and neutralize at least one biological activity of CS1. The invention also includes a pharmaceutical composition comprising such antibodies or antigen-binding fragments thereof. The present invention also provides for a method of preventing or treating disease states, including autoimmune disorders and cancer, in a subject in need thereof, comprising administering into said subject an effective amount of such antagonists.

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Номер записи: 2
05-04-2012 дата публикации

Cd33 binding agents

Номер: US20120082670A1
Автор: Eric Borges, Karl-Heinz Heider, Paul Adam, Renate Konopitzky
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to immunotherapies that are based on myeloid cell depletion. In particular, the present invention relates to CD33 binding agents for use in such therapies, e.g. in the treatment of myeloid cell malignancies and myelodysplastic syndrome (MDS).

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Номер записи: 3
26-04-2012 дата публикации

Compositions and methods for biological remodeling with frozen particle compositions

Номер: US20120101738A1
Автор: Daniel B. Cook, Edward S. Boyden, Elizabeth A. Sweeney, Eric C. Leuthardt, Lowell L. Wood, JR., Nathan P. Myhrvold, Roderick A. Hyde
Принадлежит: SEARETE LLC

Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

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Номер записи: 4
10-05-2012 дата публикации

Methods for inhibiting cutaneous inflammation and hyperpigmentation

Номер: US20120114575A1
Автор: B. Jack Longley
Принадлежит: Columbia University of New York

This invention provides a method of preventing or treating in a subject contact dermatitis which comprises administering to the subject an amount of a compound capable of inhibiting the stem cell factor signaling pathway effective to prevent or treating contact dermatitis so as to thereby prevent or treat contact dermatitis in the subject. This invention also provides a method of preventing or treating in a subject hyperpigmentation, asthma, cutaneous inflammation, anaphylaxis and bronchospasm, mastocytosis, tumors which express activated kit, and conception.

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Номер записи: 5
24-05-2012 дата публикации

Diagnosis and treatment of autoimmune demyelinating diseases

Номер: US20120128698A1
Автор: Menno Van Lookeren Campagne
Принадлежит: F Hoffmann La Roche AG

The present invention concerns the diagnosis and treatment of autoimmune demyelinating diseases, such as multiple sclerosis (MS), by means of a CLM-I agonist.

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Номер записи: 6
24-05-2012 дата публикации

Detection and treatment of autoimmune disorders

Номер: US20120130350A1
Автор: Anne M. Stevens, Neelufar Mozaffarian
Принадлежит: Seattle Childrens Hospital

Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand.

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Номер записи: 7
14-06-2012 дата публикации

Product and method for treatment of conditions associated with receptor-desensitization

Номер: US20120148566A1
Автор: Barbara J. Vilen, John C. Cambier
Принадлежит: NATIONAL JEWISH HEALTH

Particular members of the multisubunit immune recognition receptor (MIRR) family of receptors, specifically, the B cell antigen receptor (BCR), the pre-B cell receptor (pre-BCR), the pro-B cell receptor (pro-BCR), Ig Fc receptors (FcR), and NK receptors, can be physically uncoupled from their associated transducers. The invention describes regulatory compounds and methods for mimicking such dissociation/destabilization for the purposes of receptor desensitization and for treatment of conditions in which receptor desensitization or alternatively, enhanced or prolonged receptor sensitization, is desirable. Compounds and methods for enhancing or prolonging receptor sensitization are also disclosed, as are methods for identifying regulatory compounds suitable for use in the present methods.

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Номер записи: 8
19-07-2012 дата публикации

Aldehyde-Tagged Immunoglobulin Polypeptides and Methods of Use Thereof

Номер: US20120183566A1
Автор: David Rabuka, Gregory W. DEHART, Mark Alan Breidenbach, Robyn M. BARFIELD
Принадлежит: Redwood Bioscience Inc

The present disclosure provides aldehyde-tagged immunoglobulin (Ig) polypeptides that can be converted by a formylglycine-generating enzyme to produce a 2-formylglycine (FGly)-modified Ig polypeptide. An FGly-modified Ig polypeptide can be covalently and site-specifically bound to a moiety of interest to provide an Ig conjugate. The disclosure also encompasses methods of production of such aldehyde-tagged Ig polypeptides, FGly-modified Ig polypeptides, and Ig conjugates, as well as methods of use of same.

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Номер записи: 9
09-08-2012 дата публикации

Half immunoglobulin binding proteins and uses thereof

Номер: US20120201746A1
Автор: Charles W. Hutchins, Jijie Gu, Junjian Liu, Tariq Ghayur
Принадлежит: ABBOTT LABORATORIES

The invention provides compositions, methods, and kits related to half-Ig binding proteins that include a functional antibody binding site and a CH3 domain wherein the CH3 domain includes at least one mutation to inhibit CH3-CH3 dimerization.

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Номер записи: 10
16-08-2012 дата публикации

Human anti-kir antibodies

Номер: US20120208237A1
Автор: Alessandro Moretta, Anders Svensson, Francois Romagne, Ivan Svendsen, Kristian Kjaergaard, Laurent Gauthier, Mariella Della Chiesa, Matthias Thorolfsson, Michael Wilken, Pascale Andre, Peter Andreas Nicolai Reumert Wagtmann, Pieter Spee, Søren BERG PADKAER, Stefan Zahn
Принадлежит: Innate Pharma SAS, Novo Nordisk AS

Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.

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Номер записи: 11
25-10-2012 дата публикации

Anti-cd3 antibody dosing in autoimmune disease

Номер: US20120269826A1
Автор: Charlotte Mckee, Douglas Ringler, Lou Vaickus, Michael Rosenzweig, Paul Ponath
Принадлежит: Glaxo Group Ltd

Provided herein are methods of administering anti-CD3 antibodies or antigen-binding fragments thereof to an animal. In certain embodiments, the anti-CD3 antibody or fragment thereof does not bind or has reduced binding to at least one class of Fc (gamma) receptors. In certain embodiments, the animal has an immune-related disease.

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Номер записи: 12
08-11-2012 дата публикации

ROR1 as Therapeutic and Diagnostic Target

Номер: US20120282177A1
Автор: Alasdair Stamps, Christian Rohlff, Jonathan Alexander Terrett
Принадлежит: OXFORD BIOTHERAPEUTICS LTD

The present invention provides methods and compositions for treatment, screening, diagnosis and prognosis of cancer including bladder cancer, breast cancer, colorectal cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, skin cancer and thyroid cancer.

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Номер записи: 13
22-11-2012 дата публикации

Antibodies Reactive with B7-H3 and Uses Thereof

Номер: US20120294796A1
Автор: Deryk T. Loo, Francine Z. Chen, Leslie S. Johnson, Ling Huang, Paul A. Moore
Принадлежит: Macrogenics Inc

The present invention relates to antibodies that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers.

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Номер записи: 14
27-12-2012 дата публикации

Trispecific Therapeutics Against Acute Myeloid Leukaemia

Номер: US20120328619A1
Автор: Christian Kellner, Christoph Stein, Georg H. Fey, Markus Kugler
Принадлежит: Individual

The present invention relates to a molecule having binding specificities for (a) CD123; (b) CD16 and (c) CD33. The present invention further relates to the molecule of the invention, wherein the molecule comprises a first immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD123; a second immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD16; and a third immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD33. The present invention furthermore relates to a nucleic acid molecule encoding the molecule of the invention. In addition, the present invention relates to diagnostic and pharmaceutical compositions and the use of the molecule or the nucleic acid molecule of the invention in the treatment of acute myeloid leukaemia and/or myelodysplastic syndrome.

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Номер записи: 15
27-12-2012 дата публикации

Novel Lowered Affinity Antibodies And Methods of Making the Same

Номер: US20120329995A1
Автор: Hsiu-Ching Chang
Принадлежит: AB Biosciences Inc

The present invention provides methods for making novel, rationally designed lowered affinity antibodies. The methods of the present invention make antibodies that have variable domains that have been designed to reduce or eliminate the antigen binding activity of the parental antibody without altering the overall (3) dimensional antibody structure. Using the antibodies made using methods of the present invention in various assays allows researchers to distinguish effects that result from specific antigen-antibody interactions from other, non-specific antibody effects.

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Номер записи: 16
28-03-2013 дата публикации

Binding members-513

Номер: US20130078717A1
Автор: David Christopher Lowe, Donna Kirsty Finch, Duncan James Cochrane, Jamie Iain Campbell, Maria Anastasia Teresa Groves, Simon Charles Cruwys
Принадлежит: MedImmune Ltd

This invention relates to binding members, especially antibody molecules, specific for interleukin 1 receptor 1 (IL-1R1). For example, isolated binding members specific for IL-1R1 which competes with IL-1 and IL-1Ra for binding to IL-1R1 and binds Il-1R1 with a K D of 10 pM or less when measured by Kinexa™. The binding members are useful for, inter alia, treatment of disorders mediated by IL-1R1 including rheumatoid arthritis, athma and chronic obstructive pulmonary disease (COPD).

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Номер записи: 17
11-04-2013 дата публикации

Antibodies with Enhanced or Suppressed Effector Function

Номер: US20130089541A1
Автор: Anders Ohrn, David K.Y Poon, Dustin Bleile, Eric Escobar-Cabrera, Igor D'angelo, Paula I. Lario, Stacey A.L. Tom-Yew, Surjit B. Dixit
Принадлежит: Zymeworks Inc Canada

Rationally designed antibodies and polypeptides that comprise multiple Fc region amino acid substitutions that synergistically provide enhanced selectivity and binding affinity to a target Fc receptor are provided. The polypeptides are mutated at multiple positions to make them more effective when incorporated in antibody therapeutics than those having wild-type Fc components.

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Номер записи: 18
11-04-2013 дата публикации

ANTI-FcRH5 ANTIBODIES AND IMMUNOCONJUGATES AND METHODS OF USE

Номер: US20130089555A1
Автор: Allen Ebens, Andrew Polson, Bing Zheng, Camelia Adams, Jagath R. Junutula, Jo-Anne Hongo, Kristi Elkins, Yan Wu
Принадлежит: Genentech Inc

The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

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Номер записи: 19
18-04-2013 дата публикации

PD-1 ANTIBODY

Номер: US20130095098A1
Автор: Tyson Kerry Louise
Принадлежит: UCB PHARMA S.A.

A humanised agonistic antibody which binds human PD-1 comprising a heavy chain wherein the variable domain of the heavy chain comprises the sequence given in SEQ ID NO:1 for CDR-H1, the sequence given in SEQ ID NO: 2 for CDR-H2 and the sequence given in SEQ ID NO: 3 for CDR-H3 and the heavy chain framework region is derived from human sub-group sequence VH4 3-1 4-30.4+JH4 (SEQ ID NO: 33). The disclosure also extends to therapeutic uses of the antibody molecules, compositions and methods for producing said antibody molecules. 1. A humanised agonistic antibody which binds human PD-1 comprising a heavy chain wherein the variable domain of the heavy chain comprises the sequence given in SEQ ID NO:1 for CDR-H1 , the sequence given in SEQ ID NO:2 for CDR-H2 and the sequence given in SEQ ID NO:3 for CDR-H3 and the heavy chain framework region is derived from human sub-group sequence VH4 3-1 4-30.4+JH4 (SEQ ID NO: 33)2. A humanised antibody according to wherein the residue at at least one of positions 25 claim 1 , 44 claim 1 , 48 and 71 of the variable domain of the heavy chain is a donor residue.3. A humanised antibody according to having the heavy chain variable domain sequence given in SEQ ID NO:23.4. A humanised agonistic antibody which binds human PD-1 comprising a light chain wherein the variable domain of the light chain comprises the sequence given in SEQ ID NO:4 for CDR-L1 claim 2 , the sequence given in SEQ ID NO:5 for CDR-L2 and the sequence given in SEQ ID NO:6 for CDR-L3 and the light chain framework region is derived from human sub-group sequence VK2 4-1-1 A18+JK2 (SEQ ID NO:31)5. A humanised antibody according to wherein the residue at least one of positions 2 claim 4 , 3 claim 4 , 45 claim 4 , 62 claim 4 , and 87 of the variable domain of the light chain is a donor residue.6. A humanised antibody according to having the light chain variable domain sequence given in SEQ ID NO:15.7. A humanised agonistic antibody which binds human PD-1 having a heavy chain ...

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Номер записи: 20
25-04-2013 дата публикации

NOVEL GLYCOSYLATED PEPTIDE TARGET IN NEOPLASTIC CELLS

Номер: US20130101588A1
Автор: Vollmers Heinz Peter
Принадлежит: PATRYS LIMITED

The invention provides polypeptide, nucleic acid and other compositions. Polypeptide, nucleic acid and other compositions are useful in treatment and diagnostic methods. One treatment method includes inhibiting growth or proliferation of hyperproliferative cells or inducing regression of hyperproliferative cells, such as cells of a cellular hyperproliferative disorder, or reducing levels of LDL or oxLDL. 1117-. (canceled)118. An isolated or purified glycoprotein denoted as SAM-6 Receptor (SAM-6/R) , wherein said SAM-6/R glycoprotein is free of other proteins and has an apparent molecular weight in a range of about 80-82 kilodaltons (kDa) as determined by denaturing gel electrophoresis , has at least one oxygen (O)-linked carbohydrate moiety distinct from a carbohydrate moiety of Grp78 , and wherein an antibody comprising SEQ ID NOs:13 and 15 specifically binds to the glycoprotein , and wherein treatment of the glycoprotein with an O-glycosidase enzyme reduces binding of the antibody to the glycoprotein.119. An isolated or purified glycoprotein denoted as SAM-6 Receptor (SAM-6/R) , wherein said SAM-6/R glycoprotein is free of other proteins and has an apparent molecular weight in a range of about 80-82 kilodaltons (kDa) as determined by denaturing gel electrophoresis , has at least one oxygen (O)-linked carbohydrate moiety distinct from a carbohydrate moiety of Grp78 , and has at least 60% sequence homology to SEQ ID NO:1.120. The glycoprotein of claim 119 , wherein the glycoprotein comprises a sequence of about 655 amino acids.121. The glycoprotein of claim 119 , wherein the glycoprotein has a transmembrane domain of about 17 amino acids.122. The glycoprotein of claim 119 , wherein the glycoprotein has an extracellular domain of about 220 amino acids.123. The glycoprotein of claim 119 , wherein the glycoprotein has an intracellular domain of about 411 amino acids.124. The glycoprotein of claim 119 , wherein the carbohydrate moiety is linked to an asparagine claim ...

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Номер записи: 21
25-04-2013 дата публикации

Bcma-based stratification and therapy for multiple myeloma patients

Номер: US20130101599A1
Автор: Eric Borges, Jasmin Barbara Hebeis
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to methods for the stratification of a multiple myeloma (MM) patient comprising determining whether or not B-cells, preferably malignant B-cells of said patient express BCMA protein on their surface. Also, methods for selecting an antibody-based multiple myeloma (MM) therapy is based on whether or not BCMA is expressed on the cell surface of B-cells, preferably malignant B-cells of a patient. Furthermore, antibody-based therapies for patients who have BCMA positive malignant B-cells are provided.

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Номер записи: 22
02-05-2013 дата публикации

ANTIBODIES TO HUMAN PROGRAMMED DEATH RECEPTOR PD-1

Номер: US20130108651A1
Автор: Carven Gregory John, Dulos Gradus Johannes, Van Eenenneem Hans
Принадлежит: MSD Oss B.V.

Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed. 1. An isolated antibody or antibody fragment which binds to human PD-1 comprising:a. at least one CDR selected from the group consisting of SEQ ID NOs: 9, 10, 11, 15, 16 and 17, or a variant of any said sequence; and/orb. at least one CDR selected from the group consisting of SEQ ID NOs: 12, 13, 14, 18, 19 and 20, or a variant of any said sequence.2. The antibody or antibody fragment of claim 1 , comprising:a. light chain CDRs SEQ ID NOs: 9, 10 and 11, or variants of any said sequences; and heavy chain CDRs SEQ ID NOs: 12, 13 and 14, or variants of any said sequences; orb. light chain CDRs SEQ ID NOs: 15, 16 and 17 or variants of any said sequences; and heavy chain CDRs SEQ ID NOs: 18, 19 and 20 or variants of any said sequences.3. The antibody or antibody fragment of claim 2 , comprising: i. SEQ ID NO: 5 or a variant thereof;', 'ii. SEQ ID NO: 7 or a variant thereof;', 'iii. amino acid residues 20 to 139 of SEQ ID NO: 30 or a variant thereof; and', 'and further comprising', 'iv. an amino acid sequence having at least 90% homology to amino acid residues 20 to 139 of SEQ ID NO: 30;'}], 'a. a heavy chain variable region comprising an amino acid sequence selected from the group consisting of i. SEQ ID NO: 6 or a variant thereof;', 'ii. SEQ ID NO: 8 or a variant thereof;', 'iii. amino acid residues 20 to 130 of SEQ ID NO: 32 or a variant thereof;', 'iv. amino acid residues 20 to 130 of SEQ ID NO: 33 or a variant thereof;', 'v. amino acid residues 20 to 130 of SEQ ID NO: 34 or a variant thereof; and', 'vi. an amino acid sequence having at least 90% homology to amino acid residues 20 to 130 of SEQ ID NO: 32, 33 or 34., 'b. a light chain variable region comprising an amino acid sequence selected from the group consisting of4. The antibody ...

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Номер записи: 23
02-05-2013 дата публикации

ANTIBODIES TO HUMAN PROGRAMMED DEATH RECEPTOR PD-1

Номер: US20130109843A1
Автор: Carven Gregory John, Dulos Gradus Johannes, Van Eenenneem Hans
Принадлежит: MDS OSS B.V.

Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed. 1. An isolated antibody or antibody fragment which binds to human PD-1 comprising:a. at least one CDR selected from the group consisting of SEQ ID NOs: 9, 10, 11, 15, 16 and 17, or a variant of any said sequence; and/orb. at least one a CDR selected from the group consisting of SEQ ID NOs: 12, 13, 14, 18, 19 and 20, or a variant of any said sequence.2. The antibody or antibody fragment of claim 1 , comprising:a. light chain CDRs SEQ ID NOs: 9, 10 and 11, or variants of any said sequences; and heavy chain CDRs SEQ ID NOs: 12, 13 and 14, or variants of any said sequences; orb. light chain CDRs SEQ ID NOs: 15, 16 and 17 or variants of any said sequences; and heavy chain CDRs SEQ ID NOs: 18, 19 and 20 or variants of any said sequences.3. The antibody or antibody fragment of claim 2 , comprising: i. SEQ ID NO: 5 or a variant thereof;', 'ii. SEQ ID NO: 7 or a variant thereof;', 'iii. amino acid residues 20 to 139 of SEQ ID NO: 30 or a variant thereof; and', 'and further comprising', 'iv. an amino acid sequence having at least 90% homology to amino acid residues 20 to 139 of SEQ ID NO: 30;'}], 'a. a heavy chain variable region comprising an amino acid sequence selected from the group consisting of i. SEQ ID NO: 6 or a variant thereof;', 'ii. SEQ ID NO: 8 or a variant thereof;', 'iii. amino acid residues 20 to 130 of SEQ ID NO: 32 or a variant thereof;', 'iv. amino acid residues 20 to 130 of SEQ ID NO: 33 or a variant thereof;', 'v. amino acid residues 20 to 130 of SEQ ID NO: 34 or a variant thereof; and', 'vi. an amino acid sequence having at least 90% homology to amino acid residues 20 to 130 of SEQ ID NO: 32, 33 or 34., 'b. a light chain variable region comprising an amino acid sequence selected from the group consisting of4. The ...

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Номер записи: 24
16-05-2013 дата публикации

ANTIBODY AND METHODS FOR SELECTIVE INHIBITION OF T-CELL RESPONSES

Номер: US20130122015A1
Автор: Fokta Frank J., GETTS Daniel R., Herrmann James J., Puisis John J.
Принадлежит: Tolera Therapeutics, Inc.

The present invention provides compositions, methods, and assays for treating an inflammatory and/or autoimmune disease, and/or transplanted tissue rejection using anti-αβ TCR antibodies and antibody fragments. Anti-αβ TCR antibodies are antibodies which bind to a αβ TCR. Anti-αβ TCR antibodies produced by the hybridoma TOL101 MCB are also provided. Methods for treatment of an inflammatory disease, an autoimmune disease and for tissue transplant rejection using therapeutic dosing regimen of anti-αβ TCR antibodies and antibody fragments and for upregulating the numbers of Treg T-cells are also provided 1. An isolated antibody produced by the hybridoma TOL101 MCB.2. The isolated antibody according to claim 1 , wherein the antibody binds to αβ TCR and reduces the surface expression of αβ TCR and CD3 on the T cell claim 1 , and wherein the antibody does not deplete T cells.3. The isolated antibody according to claim 1 , wherein the antibody is coupled to a detectable label selected from the group consisting of a radioisotope claim 1 , enzyme claim 1 , fluorescent label claim 1 , luminescent label claim 1 , bioluminescent label claim 1 , biotin or toxin.4. A method for treating an inflammatory disease claim 1 , autoimmune disease claim 1 , or transplant tissue rejection comprising administering a therapeutically effective amount of the isolated antibody of to a human patient in need thereof.5. The method according to claim 4 , wherein the inflammatory disease claim 4 , autoimmune disease or transplanted tissue rejection is selected from the group consisting of: asthma claim 4 , allergy claim 4 , allergic airway inflammation claim 4 , allergic encephalomyelitis; autoimmune arthritis claim 4 , rheumatoid arthritis claim 4 , Juvenile rheumatoid arthritis claim 4 , reactive arthritis claim 4 , psoriatic arthritis claim 4 , sacroiliitis claim 4 , isolated acute anterior uveitis claim 4 , undifferentiated spondyloarthropathy claim 4 , Type I Diabetes Mellitus claim 4 , ...

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Номер записи: 25
23-05-2013 дата публикации

Heterodimer Binding Proteins and Uses Thereof

Номер: US20130129723A1
Автор: John W. Blankenship, Philip Tan
Принадлежит: Emergent Product Development Seattle LLC

The present disclosure provides polypeptide heterodimers formed between two different single chain fusion polypeptides via natural heterodimerization of an immunoglobulin CH1 region and an immunoglobulin light chain constant region (CL). The polypeptide heterodimer comprises two or more binding domains that specifically bind one or more targets (e.g., a receptor). In addition, both chains of the heterodimer further comprise an Fc region portion. The present disclosure also provides nucleic acids, vectors, host cells and methods for making polypeptide heterodimers as well as methods for using such polypeptide heterodimers, such as in directing T cell activation, inhibiting solid malignancy growth, and treating autoimmune or inflammatory conditions.

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Номер записи: 26
23-05-2013 дата публикации

CROSS-SPECIES-SPECIFIC PSMAxCD3 BISPECIFIC SINGLE CHAIN ANTIBODY

Номер: US20130129730A1
Автор: Carole Steiger, Doris Rau, Evelyne Schaller, Matthias Klinger, Patrick Hoffmann, Peter Kufer, Petra Fluhr, Ralf Lutterbuese, Roman Kischel, Susanne Hausmann, Susanne Mangold, Tobias Raum
Принадлежит: Amgen Research Munich GmbH

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.

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Номер записи: 27
06-06-2013 дата публикации

Anti-CD74 Immunoconjugates and Methods of Use

Номер: US20130142729A1
Автор: David M. Goldenberg, Hans J. Hansen, John C. Byrd
Принадлежит: Immunomedics Inc, Ohio State University

Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.

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Номер записи: 28
06-06-2013 дата публикации

Delivery System for Cytotoxic Drugs by Bispecific Antibody Pretargeting

Номер: US20130143296A1
Автор: Chien-Hsing Chang, Christopher A. D'Souza, David M. Goldenberg, William J. Mcbride
Принадлежит: Immunomedics Inc

The present invention relates to methods and compositions for pretargeting delivery of therapeutic agents. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody with a first binding site for a disease-associated antigen and a hapten on a targetable construct; b) administering a targetable construct comprising at least one therapeutic agent. In preferred embodiments, the bispecific antibody is made by the dock-and-lock (DNL) technique. In a more preferred embodiment, the targetable construct comprises one or more SN-38 moieties.

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Номер записи: 29
13-06-2013 дата публикации

Antibodies Reactive with B7-H3, Immunologically Active Fragments Thereof and Uses Thereof

Номер: US20130149236A1
Автор: Chen Francine Zhifen, Huang Ling, Johnson Leslie S., Loo Deryk T., Moore Paul A.
Принадлежит: MACROGENICS, INC.

The present invention relates to antibodies and their fragments that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies and their immunoreactive fragments that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers. 1. An isolated antibody or an immunoreactive fragment thereof , wherein said isolated antibody or said fragment comprises a variable domain that specifically binds an extracellular domain of B7-H3 , wherein said antibody competes for binding to said B7-H3 with any of antibodies: BRCA69D , BRCA84D , or PRCA157.2. The isolated antibody or immunoreactive fragment thereof of claim 1 , wherein said antibody or said fragment comprises a variable domain that comprises:{'sub': 1', '2', '3', '1', '2', '3, '(A) CDR(SEQ ID NO: 21), CDR(SEQ ID NO: 23) and CDR(SEQ ID NO: 25) of the light chain of BRCA69D and CDR(SEQ ID NO: 29), CDR(SEQ ID NO: 31) and CDR(SEQ ID NO: 33) of the heavy chain of BRCA69D;'}{'sub': 1', '2', '3', '1', '2', '3, '(B) CDR(SEQ ID NO: 5), CDR(SEQ ID NO: 7) and CDR(SEQ ID NO: 9) of the light chain of BRCA84D and CDR(SEQ ID NO: 13), CDR(SEQ ID NO: 15) and CDR(SEQ ID NO: 17) of the heavy chain of BRCA84D; or'}{'sub': 1', '2', '3', '1', '2', '3, '(C) CDR(SEQ ID NO: 37), CDR(SEQ ID NO: 39) and CDR(SEQ ID NO: 41) of the light chain of PRCA157 and CDR(SEQ ID NO: 45), CDR(SEQ ID NO: 47) and CDR(SEQ ID NO: 49) of the heavy chain of PRCA157.'}3. The isolated antibody or immunoreactive fragment thereof of claim 1 , wherein said antibody binds to B7-H3 that is endogenously expressed on the surface of a cancer cell.4. The isolated antibody or immunoreactive fragment thereof of claim 1 , wherein said antibody binds to B7-H3 that is internalized upon binding to B7-H3 ...

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Номер записи: 30
13-06-2013 дата публикации

MONOCLONAL ANTIBODIES WITH ALTERED AFFINITIES FOR HUMAN FCyRI, FCyRIIIa, AND C1q PROTEINS

Номер: US20130149300A1
Автор: Andrew Hiatt, Larry Zeitlin
Принадлежит: Icon Genetics AG, Mapp Biopharmaceutical Inc

Disclosed herein are GNGN and G1/G2 antibodies that recognize and bind various FcRs and C1 q. Also disclosed herein are glycan-optiminzed antibodies, predominantly of the GNGN or G 1 /G2 glycoform, with enhanced Fcγ receptor binding achieved through CHO, Nicotiana benthamiana and yeast manufacturing systems. Nucleic acids encoding these antibodies, as well as expression vectors and host cells including these nucleic acids are also disclosed herein. Methods and pharmaceutical compositions including the monoclonal antibodies are provided herein for the prevention and/or therapeutic treatment of viral infections, cancers and inflammatory diseases.

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Номер записи: 31
20-06-2013 дата публикации

Methods for identifying compounds that modulate lisch-like protein or c1orf32 protein activity and methods of use

Номер: US20130160150A1
Автор: Charles LeDuc, Marija Dokmanovic-Chouinard, Rudolph L. Leibel, Stuart G. Fischer, Wendy K. Chung
Принадлежит: Columbia University of New York

The invention provides methods for reducing diabetes susceptibility in a subject and methods for increasing the expression of LL or CLORF32 in a subject. The invention further provides a method for identifying an agent which modulates expression of an Ll RNA or Clorf32 RNA comprising contacting a cell with an agent; determining expression of the Ll RNA or Clorf32 RNA in the presence and the absence of the agent; and comparing expression of the Ll RNA or Clorf32 RNA in the presence and the absence of the agent, wherein a change in the expression of the Ll RNA or Clorf32 RNA in the presence of the agent is indicative of an agent which modulates the level of expression of the RNA.

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Номер записи: 32
27-06-2013 дата публикации

Methods and Compositions for Generating Bioactive Assemblies of Increased Complexity and Uses

Номер: US20130164816A1
Автор: Chien-Hsing Chang, David M. Goldenberg, Edmund A. Rossi, William J. Mcbride
Принадлежит: IBC Pharmaceuticals Inc

The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

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Номер записи: 33
04-07-2013 дата публикации

NCAM-VASE AND NEURODEGENERATION

Номер: US20130171139A1
Автор: Anderson Alexandra Antoinette, Delves Michael Jonathan, Saffell Jane Louise
Принадлежит:

Inhibitors of NCAM-VASE, compositions comprising said inhibitors, and methods of using said inhibitors for stimulation of neuroplasticity and/or neuroregeneration in the central nervous system, and for increasing neuronal cell response to agents that stimulate neuroplasticity and/or neuroregeneration in the central nervous system, are provided. The inhibitor or composition may be used, for example, for treating brain or spinal cord injury; schizophrenia, motor neurone disease; a neurodegenerative disorder such as Alzheimer's disease, multiple sclerosis or Parkinson's disease; ischaemia caused by stroke; or for improving learning and/or memory. 1. (canceled)2. (canceled)3. The method of wherein the inhibitor is an antisense RNA molecule or an interfering RNA that is capable of causing a reduction of NCAM-VASE mRNA transcription.4. The method of wherein the inhibitor is a soluble polypeptide comprising the Ig4 domain of NCAM-VASE.5. The method of wherein the inhibitor is a soluble polypeptide comprising a further sequence from NCAM-VASE in addition to the Ig4 domain.6. The method of wherein the inhibitor is an antibody or antibody fragment or derivative able to bind selectively to NCAM-VASE.7. The method of claim 12 , wherein the inhibitor is administered in combination with a second agent which promotes neuroplasticity and/or neuroregeneration.8. The method of claim 7 , wherein the second agent is selected from the list consisting of NGF claim 7 , BDNF claim 7 , FGF claim 7 , CNTF claim 7 , GDNF claim 7 , NT3 claim 7 , NT4/5 dbcAMP and forskolin.9. The method of claim 12 , wherein the method is for treating brain or spinal cord injury.10. The method of claim 12 , wherein the method is for treating schizophrenia claim 12 , motor neurone disease claim 12 , for treating a neurodegenerative disorder including Alzheimer's disease claim 12 , multiple sclerosis or Parkinson's disease; for treating ischaemia caused by stroke; or for improving learning and/or memory.11. ( ...

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Номер записи: 34
04-07-2013 дата публикации

ANTIBODIES TO OX-2/CD200 AND USES THEREOF

Номер: US20130172534A1
Автор: Bowdish Katherine S., Faas McKnight Susan, Kretz-Rommel Anke, Springhorn Jeremy P., Wu Dayang
Принадлежит: ALEXION PHARMACEUTICALS, INC.

This application provides methods and compositions for modulating and/or depleting CD200 positive cells. 1126-. (canceled)127. An isolated anti-CD200 antibody that:(i) inhibits the interaction between CD200 and CD200R; and(ii) comprises a variant Fc constant region that has ADCC activity or CDC activity equal to or less than the ADCC activity or CDC activity the anti-CD200 antibody would have if it had a G2/G4 Fc constant region consisting of amino acid residues 137-462 of SEQ ID NO:13.128. The isolated anti-CD200 antibody according to claim 127 , wherein the anti-CD200 antibody is a murine antibody claim 127 , a chimeric antibody claim 127 , a humanized antibody claim 127 , a deimmunized antibody claim 127 , or a human antibody.129. The isolated anti-CD200 antibody according to claim 127 , wherein the variant Fc constant region is an altered form of a native Fc constant region selected from the group consisting of IgG1 claim 127 , IgG2 claim 127 , IgG3 claim 127 , IgG4 claim 127 , IgM claim 127 , IgA1 claim 127 , IgA2 claim 127 , IgA claim 127 , IgD claim 127 , and IgE.130. The isolated anti-CD200 antibody according to claim 127 , wherein the variant Fc constant region was altered to comprise at least one amino acid substitution claim 127 , insertion claim 127 , or deletion relative to its corresponding native Fc constant region.131. The isolated anti-CD200 antibody according to claim 127 , wherein:(a) the variant Fc constant region is a G2/G4 constant region; (i) one or both of: (x) a phenylalanine to alanine substitution at position 234 and (y) a leucine to alanine substitution at position 235;', '(ii) a K322A mutation in the CH2 domain;', '(iii) the CH1 and hinge regions of an IgG2 antibody;', '(iv) the CH2 and CH3 regions of an IgG4 antibody; or, '(b) the variant Fc constant region comprises(v) the CH1 and hinge regions of an IgG2 antibody and the CH2 and CH3 regions of an IgG4 antibody; or(c) the variant Fc constant region lacks a hinge region.132. The ...

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Номер записи: 35
25-07-2013 дата публикации

THERAPEUTIC METHODS USING ANTI-CD200 ANTIBODIES

Номер: US20130189258A1
Автор: Rother Russell P., Yan Yan
Принадлежит: ALEXION PHARMACEUTICALS, INC.

The present disclosure relates to anti-CD200 antibodies and to use of the antibodies in methods for treating autoimmune disorders and cancer. Also featured are biomarkers for use in selecting or prescribing a treatment modality for a patient with an autoimmune disorder and/or cancer. In addition, the disclosure features methods of treatment using an anti-CD200 antibody in combination with one or more additional therapeutic agents such as an anti-CD20 therapeutic agent. 177-. (canceled)78. A method for treating a human afflicted with a cancer , the method comprising administering to the human an anti-CD200 antibody , or a CD200-binding fragment thereof , in an amount that is sufficient to treat the cancer , wherein the cancer is resistant , or is suspected of being resistant , to therapy with an anti-CD20 therapeutic agent.79. The method of claim 78 , further comprising identifying the human as having the cancer that is resistant claim 78 , or is suspected to be resistant claim 78 , to treatment with an anti-CD20 therapeutic agent.80. The method of claim 78 , wherein the cancer comprises cancer cells that express CD5.81. The method of claim 80 , further comprising identifying the cancer as comprising cells that express CD5.82. The method of claim 78 , wherein the cancer is a solid tumor.83. The method of claim 78 , wherein the cancer is a liquid tumor.84. The method of claim 83 , wherein the liquid tumor is a chronic lymphocytic leukemia or multiple myeloma.85. The method of claim 84 , wherein the chronic lymphocytic leukemia is a B cell chronic lymphocytic leukemia.86. The method of claim 78 , further comprising administering to the human an anti-CD20 therapeutic agent.87. The method of claim 86 , wherein the anti-CD20 therapeutic agent is an anti-CD20 antibody or a CD20-binding fragment thereof.88. The method of claim 87 , wherein the anti-CD20 antibody is rituximab claim 87 , ofatumumab claim 87 , TRU-015 claim 87 , veltuzumab claim 87 , ocrelizumab claim 87 , or ...

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Номер записи: 36
08-08-2013 дата публикации

Method for the treatment of obesity

Номер: US20130202622A1
Автор: Christoph Rader, Michael Hudecek, Stanley R. Riddell
Принадлежит: Fred Hutchinson Cancer Research Center

The present invention relates to therapeutic compositions for treating or preventing obesity and obesity-related disorders in a subject using immunotherapy to target and eliminate adipocytes.

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Номер записи: 37
15-08-2013 дата публикации

Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (trem-1)

Номер: US20130211050A1
Автор: Anette Henriksen, Charlotte Wiberg, Christine Brender READ, Rune Salbo, Soeren Padkjaer, Susanne Nedergaard Grell, Vibeke Westphal Stennicke
Принадлежит: Novo Nordisk AS

The invention relates to antibodies that are capable of specifically binding TREM-1 and preventing the activation of TREM-1, a protein expressed on monocytes, macrophages and neutrophils. Such antibodies find utility in the treatment of individuals with an inflammatory disease, such as rheumatoid arthritis and inflammatory bowel disease.

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Номер записи: 38
29-08-2013 дата публикации

CD47 Antibodies and Methods of Use Thereof

Номер: US20130224188A1
Автор: Deveraux Quinn, Eckelman Brendan, JONES Kyle, NGUY Peter L., RAZAI Amir, Timmer John
Принадлежит: INHIBRX LLC

This invention relates generally to monoclonal antibodies that recognize CD47, more specifically to CD47 antibodies that do not cause a significant level of agglutination of cells, to methods of generating these antibodies, and to methods of using these monoclonal antibodies as therapeutics. 1. An isolated monoclonal antibody that binds to CD47 or an immunologically active fragment thereof , wherein the antibody does not cause a significant level of agglutination of cells after administration.2. The antibody of claim 1 , wherein the antibody is chimeric claim 1 , humanized claim 1 , or fully human.3. The antibody of claim 1 , wherein the CD47 is human CD47.4. The antibody of claim 1 , wherein the antibody or immunologically active fragment thereof prevents CD47 from interacting with signal-regulatory-protein a (SIRPα).5. The antibody of claim 4 , wherein the antibody or immunologically active fragment thereof promotes macrophage-mediated phagocytosis of a CD47-expressing cell.6. The antibody of claim 1 , wherein the antibody or immunologically active fragment thereof is an IgG isotype selected from the group consisting of IgG1 isotype claim 1 , IgG2 isotype claim 1 , IgG3 isotype claim 1 , and IgG4 isotype.7. The antibody of claim 1 , wherein the antibody or immunologically active fragment thereof comprises a variable heavy (VH) chain region selected from the group consisting of SEQ ID NOs: 5-30.8. The antibody of claim 1 , wherein the antibody or immunologically active fragment thereof comprises a variable light (VL) chain region selected from the group consisting of SEQ ID NOs: 31-47.9. The antibody of claim 1 , wherein the antibody or immunologically active fragment thereof comprises a VH region provided in any one of SEQ ID NOs: 5-30 and a VL region provided in any one of SEQ ID NOs: 31-47.10. The antibody of claim 9 , wherein the antibody or immunologically active fragment thereof comprises a VH region provided in any one of SEQ ID NOs: 5 claim 9 , 7 claim 9 , ...

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Номер записи: 39
05-09-2013 дата публикации

Engineered antibody-interferon mutant fusion molecules

Номер: US20130230517A1
Автор: Iqbal Grewal, Michael Gresser, Rashid Syed, Sanjay Khare
Принадлежит: IMMUNGENE INC

The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to fusion molecule constructs wherein a tumor associated antigen (TAA) antibody (Ab) serves as a targeting moiety to selectively deliver a cytokine to a tumor cell for purposes of killing or inhibiting the growth or proliferation of said tumor cell. In various embodiments, the engineered fusion molecules comprise a TAA Ab fused to an interferon-alpha (IFN-α) mutant molecule. The engineered Ab-IFN-α mutant fusion molecules of the present invention demonstrate improved therapeutic index and preserved or increased efficacy as compared to Ab-wildtype IFN-α fusion molecules, and/or demonstrate improved PK properties as compared to Ab-wildtype IFN-α fusion molecules.

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Номер записи: 40
05-09-2013 дата публикации

METHODS FOR DETECTING TH1 CELLS

Номер: US20130230523A1
Автор: Imai Toshio, Muramoto Kenzo, Yamaguchi Keiko
Принадлежит: Eisai R&D Management Co., Ltd.

The inventors discovered that the adhesion molecule CAR, known to be localized in intracellular adhesion sites, functioned as an adhesion molecule for activated lymphocytes. Further, the inventors identified CARL, a novel CAR ligand expressed in lymphocytes, and clarified that the ligand was expressed selectively in Th1 cells. In addition, they found that anti-CAR antibodies could inhibit the adhesion of activated lymphocytes to CAR molecules. Thus, the present invention provides methods for detecting Th1 cells using CAR or anti-CARL antibodies, and methods of screening for inhibitors suppressing the adhesion of Th1 cells using the binding between CAR and CARL as an index. Furthermore, the present invention relates to methods of screening for inhibitors of the binding between CAR and CARL, antibodies that inhibit the binding between CAR and CARL, and therapeutic compositions comprising these antibodies. These are expected to be useful in diagnosing diseases, such as inflammation, in which infiltration of Th1 cells is involved, and in providing pharmaceutical agents for alleviating such diseases. 123-. (canceled)24. An isolated antibody that specifically binds to a protein consisting of the amino acid sequence of SEQ ID NO:2 , wherein the antibody inhibits binding between the protein consisting of the amino acid sequence of SEQ ID NO:2 and a protein consisting of the amino acid sequence of SEQ ID NO:17.25. The antibody of claim 24 , wherein the antibody is a human antibody.26. The antibody of claim 24 , wherein the antibody is a humanized antibody.27. The antibody of claim 24 , wherein the antibody is a chimeric antibody.28. The antibody of claim 24 , wherein the antibody is a single chain antibody.29. The antibody of claim 24 , wherein the antibody is an antibody fragment selected from the group consisting of an Fab fragment claim 24 , an Fab′ fragment claim 24 , an F(ab′)fragment claim 24 , and an Fv fragment.30. A pharmaceutical composition comprising the antibody ...

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Номер записи: 41
05-09-2013 дата публикации

METHODS FOR DETECTING TH1 CELLS

Номер: US20130231466A1
Автор: Imai Toshio, Muramoto Kenzo, Yamaguchi Keiko
Принадлежит: Eisai R&D Management Co., Ltd.

The inventors discovered that the adhesion molecule CAR, known to be localized in intracellular adhesion sites, functioned as an adhesion molecule for activated lymphocytes. Further, the inventors identified CARL, a novel CAR ligand expressed in lymphocytes, and clarified that the ligand was expressed selectively in Th1 cells. In addition, they found that anti-CAR antibodies could inhibit the adhesion of activated lymphocytes to CAR molecules. Thus, the present invention provides methods for detecting Th1 cells using CAR or anti-CARL antibodies, and methods of screening for inhibitors suppressing the adhesion of Th1 cells using the binding between CAR and CARL as an index. Furthermore, the present invention relates to methods of screening for inhibitors of the binding between CAR and CARL, antibodies that inhibit the binding between CAR and CARL, and therapeutic compositions comprising these antibodies. These are expected to be useful in diagnosing diseases, such as inflammation, in which infiltration of Th1 cells is involved, and in providing pharmaceutical agents for alleviating such diseases. 122-. (canceled)23. An isolated antibody that specifically binds to a protein consisting of the amino acid sequence of SEQ ID NO:1 , wherein the antibody inhibits binding between the protein consisting of the amino acid sequence of SEQ ID NO:1 and a protein consisting of the amino acid sequence of SEQ ID NO:18.24. The antibody of claim 23 , wherein the antibody is an antibody fragment selected from the group consisting of an Fab fragment claim 23 , an Fab′ fragment claim 23 , an F(ab′)fragment claim 23 , and an Fv fragment.25. An antibody produced by the hybridoma @mCARL:#3.11 claim 23 , deposited under International Accession Number FERM BP-10319.26. Hybridoma @mCARL:#3.11 claim 23 , deposited under International Accession Number FERM BP-10319. The present application is divisional of U.S. application Ser. No. 11/568,435, filed Mar. 28, 2008, which is a U.S. National Phase ...

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Номер записи: 42
26-09-2013 дата публикации

Nk cell modulating treatments and methods for treatment of hematological malignancies

Номер: US20130251711A1
Автор: Jerome Tiollier, Marcel Rozencweig, Pascale Andre, Renaud Buffet
Принадлежит: Innate Pharma SAS

Compositions comprising compounds that neutralize NK cell inhibitory receptors and methods of using such compositions in the treatment of hematological malignancies are provided.

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Номер записи: 43
10-10-2013 дата публикации

Chimeric receptors with 4-1bb stimulatory signaling domain

Номер: US20130266551A1
Автор: Chihaya Imai, Dario Campana
Принадлежит: St Jude Childrens Research Hospital

The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

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Номер записи: 44
17-10-2013 дата публикации

ANTI-SSX-2 T CELL RECEPTORS AND RELATED MATERIALS AND METHODS OF USE

Номер: US20130274203A1
Автор: Chinnasamy Nachimuthu, Morgan Richard A., Rosenberg Steven A.
Принадлежит: The United States of America, as represented by the Secretary, Department of Health and Human Serv

The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for synovial sarcoma X Breakpoint (SSX)-2. The invention further provides related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells. Further provided by the invention are antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention. Methods of detecting the presence of cancer in a host and methods of treating or preventing cancer in a host are further provided by the invention. 1. An isolated or purified T cell receptor (TCR) having antigenic specificity for synovial sarcoma X Breakpoint (SSX)-2 (SEQ ID NO: 1).2. The TCR of claim 1 , wherein the TCR also recognizes any one or more of SSX-3 (SEQ ID NO: 3) claim 1 , SSX-4 (SEQ ID NO: 4) claim 1 , SSX-5 (SEQ ID NO: 5) claim 1 , SSX-9 (SEQ ID NO: 6) claim 1 , and SSX-10 (SEQ ID NO: 7).3. The TCR of claim 1 , wherein the TCR has antigenic specificity for an SSX-2 peptide comprising KASEKIFYV (SEQ ID NO: 2).4. The TCR of claim 1 , wherein the TCR recognizes any one or more of KVSEKIVYV (SEQ ID NO: 8) claim 1 , KSSEKIVYV (SEQ ID NO: 9) claim 1 , KASEKIIYV (SEQ ID NO: 10) claim 1 , KSSEKIIYV (SEQ ID NO: 11) claim 1 , and KASEKILYV (SEQ ID NO: 12).5. The TCR of claim 1 , wherein the TCR comprises amino acid sequences comprising SEQ ID NOs: 13-18.6. The TCR of claim 1 , wherein the TCR comprises SEQ ID NOs: 19 and 20.7. The TCR of claim 6 , wherein the TCR further comprises SEQ ID NOs: 21 and 22.8. The TCR of claim 1 , wherein the TCR comprises:a) SEQ ID NO: 23 and 24 orb) SEQ ID NO: 25 and 26.9. An isolated or purified polypeptide comprising a functional portion of the TCR of claim 1 , wherein the functional portion comprises the amino acid sequences of SEQ ID NOs: 13-18.10. The isolated or purified polypeptide of claim 9 , wherein the portion comprises the amino acid sequences of SEQ ID NOs ...

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Номер записи: 45
24-10-2013 дата публикации

Chimeric antigen receptor for bispecific activation and targeting of t lymphocytes

Номер: US20130280220A1
Автор: Donald R. Shaffer, Matthew Baker, Meenakshi HEDGE, Nabil Ahmed, Zakaria Grada
Принадлежит: Baylor College of Medicine

Embodiments of the invention include methods and compositions related to improved cells encoding a chimeric antigen receptor that is specific for two or more antigens. In certain aspects the receptor encompasses two or more non-identical antigen recognition domains. The antigens are tumor antigens, in particular embodiments.

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Номер записи: 46
31-10-2013 дата публикации

ANTIBODIES AND METHODS FOR MAKING AND USING THEM

Номер: US20130287766A1
Автор: Anderson Abraham, Frey Gehard, Kimmel Bruce E.
Принадлежит:

The invention provides antibodies, including chimeric human antibodies, recombinant antibodies, synthetic anti-bodies, and the nucleic acids encoding them, and methods for making and using these immunoglobulins. The invention provides recombinant and synthetic polypeptide and nucleic acid embodiments of these polypeptides and/or antibodies. The invention also provides polypeptides comprising, or consisting of, consensus human framework regions, or “Independently Consensused Frameworks (ICFs)”, nucleic acids encoding them, and libraries and kits comprising these ICFs and/or antibodies of the invention, individually and in combinatorial libraries and combinations. 1. An antibody or antigen-binding fragment thereof comprising at least one of the following combinations:(1) light chain BD22084 (SEQ ID NO:225) and heavy chain BD20332 (SEQ ID NO:138);(2) light chain BD22085 (SEQ ID NO:232) and heavy chain BD20335 (SEQ ID NO:143);(3) light chain BD22086 (SEQ ID NO:227) and heavy chain BD20335 (SEQ ID NO:143);(4) light chain BD22088 (SEQ ID NO:229) and heavy chain BD20337 (SEQ ID NO:148);(5) light chain BD22087 (SEQ ID NO:240) and heavy chain BD20335 (SEQ ID NO:143);(6) light chain BD22089 (SEQ ID NO:243) and heavy chain BD20335 (SEQ ID NO:143);(7) light chain BD22090 (SEQ ID NO:234) and heavy chain BD20337 (SEQ ID NO:148);(8) light chain BD22095 (SEQ ID NO:244) and heavy chain BD20337 (SEQ ID NO:148);(9) light chain BD22091 (SEQ ID NO:242) and heavy chain BD20337 (SEQ ID NO:148);(10) light chain BD22108 (SEQ ID NO:230) and heavy chain BD20337 (SEQ ID NO:148);(11) light chain BD22092 (SEQ ID NO:235) and heavy chain BD20338 (SEQ ID NO:149);(12) light chain BD22094 (SEQ ID NO:231) and heavy chain BD20337 (SEQ ID NO:148);(13) light chain BD22096 (SEQ ID NO:241) and heavy chain BD20337 (SEQ ID NO:148);(14) light chain BD22092 (SEQ ID NO:235) and heavy chain BD20337 (SEQ ID NO:148);(15) light chain BD22102 (SEQ ID NO:248) and heavy chain BD20337 (SEQ ID NO:148);(16) light chain ...

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Номер записи: 47
31-10-2013 дата публикации

Dock-and-Lock (DNL) Complexes for Delivery of Interference RNA

Номер: US20130289244A1
Автор: Chien-Hsing Chang, David M. Goldenberg
Принадлежит: IBC Pharmaceuticals Inc

Described herein are compositions and methods of use of targeted delivery complexes for delivery of siRNA to a disease-associated cell, tissue or pathogen. The targeted delivery complex comprises a targeting molecule, such as an antibody or fragment thereof, conjugated to one or more siRNA carriers. In preferred embodiments the siRNA carrier is a dendrimer or protamine and the targeting molecule is an anti-cancer antibody, such as hRS7. More preferably, the antibody or fragment is rapidly internalized into the target cell to facilitate uptake of the siRNA. Most preferably, the targeted delivery complex is made by the DNL technique. The compositions and methods are of use to treat a variety of disease states, such as cancer, autoimmune disease, immune dysfunction, cardiac disease, neurologic disease, inflammatory disease or infectious disease.

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Номер записи: 48
31-10-2013 дата публикации

HUMAN ANTI-PD-1, PD-L1, AND PD-L2 ANTIBODIES AND USES THEREFOR

Номер: US20130291136A1
Автор: Ahmed Rafi, CARR Francis J., FREEMAN Gordon J., GREGSON James P., JONES Timothy D.
Принадлежит:

The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-L1, and/or PD-L2 activity (e.g., persistent infectious diseases, autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein. 1. An isolated antibody , or an antigen-binding fragment thereof , comprising:a) a heavy chain CDR sequence selected from the group consisting of SEQ ID NOs: 7-9; orb) a light chain CDR sequence selected from the group consisting of SEQ ID NOs: 10-12,wherein the isolated antibody, or an antigen-binding fragment thereof, binds to a PD-1 protein having the amino acid sequence of SEQ ID NO: 2, and the isolated antibody, or antigen-binding fragment thereof, is chimeric, humanized, composite, or human.2. The isolated antibody or antigen-binding fragment of claim 1 , comprising:c) a heavy chain variable region sequence comprising SEQ ID NOs: 7-9; and/ord) a light chain variable region sequence comprising of SEQ ID NOs:10-12.3. The isolated antibody or antigen-binding fragment of claim 1 , wherein the isolated antibody comprises:e) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs: 25-29, or a sequence with at least about 95% homology to a heavy chain sequence selected from the group consisting of SEQ ID NOs: 25-29; and/orf) a light chain variable region sequence selected from the group consisting of SEQ ID NOs: 30-33, or a sequence with at least about 95% homology to a light chain sequence selected from the group consisting of SEQ ID NOs: 30-33.4. The isolated antibody or antigen-binding fragment of claim 3 , wherein the isolated antibody comprises:g) a heavy chain variable region sequence comprising SEQ ID NO: 27 or 28, or a sequence ...

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Номер записи: 49
14-11-2013 дата публикации

Anti-c epsilon mx antibodies capable of binding to human mige on b lymphocytes

Номер: US20130302314A1
Автор: Alfur F. Hung, Jiun-Bo Chen, Pheidias C. Wu, Tsewen Chang
Принадлежит: Academia Sinica

The invention pertains to the generation and utility of antibodies that can bind effectively to CεmX domain on membrane-bound IgE (mIgE) expressed on the surface of human B lymphocytes. The CεmX domain of 52 amino acid residues, located between the CH4 domain and the C-terminal membrane-anchor peptide on human membrane-bound epsilon chain, had been suggested as an antigenic site for immunological targeting of B cells expressing mIgE. Previous reported monoclonal antibodies, including a20, which bind to RADWPGPP (SEQ ID NO:1) peptide at the C-terminal of CεmX, have now been found to bind poorly to mIgE on human B cells. We have discovered that only monoclonal antibodies specific for certain segments, such as GLAGGSAQSQRAPDRVL (SEQ ID NO:2) and HSGQQQGLPRAAGGSVPHPR (SEQ ID NO:3), of CεmX can bind effectively to mIgE on human B cells and hence have the utility for targeting those B cells for the treatment of diseases mediated by IgE.

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Номер записи: 50
21-11-2013 дата публикации

CD33 Antibodies And Use Of Same To Treat Cancer

Номер: US20130309223A1
Автор: Django Sussman, Maureen Ryan, May Kung Sutherland, Patrick Burke, Scott Jeffrey
Принадлежит: Seattle Genetics Inc

The invention provides murine, chimeric, and humanized antibodies that specifically bind to CD33. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting CD33.

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Номер записи: 51
21-11-2013 дата публикации

ANTIBODIES THAT BIND AND BLOCK TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS-1 (TREM-1)

Номер: US20130309239A1
Автор: Grell Susanne Nedergaard, Henriksen Anette, Padkjaer Soeren, Read Christine Brender, Salbo Rune, Stennicke Vibeke Westphal, Wiberg Charlotte
Принадлежит: Novo Nordisk A/S

The invention relates to antibodies that are capable of specifically binding TREM-1 and preventing the activation of TREM-1, a protein expressed on monocytes, macrophages and neutrophils. Such antibodies find utility in the treatment of individuals with an inflammatory disease, such as rheumatoid arthritis and inflammatory bowel disease. 1. An antibody or fragment thereof that is capable of specifically binding to TREM-1 and which has an epitope comprising one , two , three , four , five , six , seven , eight , nine or all of the amino acid residues K40 , D42 , T44 , L45 , E46 , K47 , Y90 , H91 , D92 , H93 , G94 , L95 and R97 of SEQ ID NO: 1 (human TREM-1).2. The antibody or fragment thereof according to claim 1 , which has an epitope comprising amino acids K40 claim 1 , D42 claim 1 , T44 claim 1 , L45 claim 1 , E46 claim 1 , K47 claim 1 , Y90 claim 1 , H91 claim 1 , D92 claim 1 , H93 claim 1 , G94 claim 1 , L95 and R97 of SEQ ID NO: 1 (human TREM-1).3. The antibody or fragment thereof according to claim 1 , which is capable of blocking TREM-1.4. The antibody or fragment thereof according to claim 1 , which is capable of blocking PGLYRP1-induced activation of TREM-1.5. The antibody or fragment thereof according to claim 1 , which competes with mAb 0170 for binding to SEQ ID NO: 1 (human TREM-1).6. The antibody or fragment thereof according to claim 1 , which competes with mAb 0170 for binding to SEQ ID NO: 12 or SEQ ID NO: 21 (cynomolgus monkey TREM-1).7. The antibody or fragment thereof according to claim 1 , which is capable of specifically binding a polypeptide comprising amino acid residues E19 to L26 of SEQ ID NO: 12 (cynomolgus monkey TREM-1).8. The antibody according to claim 1 , which is capable of specifically binding SEQ ID NO: 13 (K20A-hTREM-1-Cmyc2-His6).9. The antibody according to claim 1 , which is capable of specifically binding SEQ ID NO: 14 (A24T/Y28F/N30S/R32Q/P70H-cTREM-1-Cmyc2-His6).10. The antibody according to claim 1 , which is capable of ...

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Номер записи: 52
21-11-2013 дата публикации

Antibody preparation method, and antibody and antibody library thus prepared

Номер: US20130310274A1
Автор: Guoxing Wang, Xiaoqing Wang, Xun Meng, Zeyong CHEN
Принадлежит: Individual

Provided is a method for preparing antibodies against a protein of interest, through which highly specific antibodies against all proteins can be effectively and rapidly prepared with low cost, and the epitope to which the antibody is directed can be determined, so that a library covering epitopes on the surface of the proteins of interest and a library of antibodies against all the epitopes can be established. The antibodies are proved to be useful in detection, protein function investigation and antibody pharmaceuticals.

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Номер записи: 53
05-12-2013 дата публикации

THERAPEUTIC ANTI-TIRC7 ANTIBODIES FOR USE IN IMMUNE RELATED AND OTHER DISEASES

Номер: US20130323254A1
Автор: UTKU Nalan
Принадлежит:

Provided are specific antibodies against T-cell immune response cDNA7 (TIRC7) costimulatory molecule, which are capable of inhibiting proliferation of peripheral blood mononuclear cells (PBMCs). In particular, high affinity monoclonal and chimeric anti-TIRC7 antibodies are described. Compositions comprising such antibodies and their use for the treatment of immune diseases are provided. 1. A monoclonal antibody or antigen binding fragment thereof that is capable of binding to an antigen comprising or consisting of the amino acid sequence of any one of SEQ ID NOs: 9 to 11.2. The antibody or antigen binding molecule of claim 1 , comprising in its variable region at least one complementarity determining region (CDR) of the Vand/or Vof the variable region comprising{'figref': [{'@idref': 'DRAWINGS', 'FIG. 4'}, {'@idref': 'DRAWINGS', 'FIG. 5'}], 'sub': H', 'L, '(a) the amino acid sequence depicted in (V) (SEQ ID NO: 2) and (V) (SEQ ID NO: 4); or'}{'figref': [{'@idref': 'DRAWINGS', 'FIG. 6'}, {'@idref': 'DRAWINGS', 'FIG. 7'}], 'sub': H', 'L, '(b) the amino acid sequence depicted in (V) (SEQ ID NO: 6) and (V) (SEQ ID NO: 8).'}3. The antibody of claim 1 , wherein said antibody is a chimeric or humanized antibody.4. The antibody of comprising the amino acid sequence of the Vand/or Vregion as depicted in any one of .5. An antigen or an epitope thereof that is recognized by the antibody of .6. A polynucleotide encoding at least a variable region of an immunoglobulin chain of the antibody of .7. A vector comprising the polynucleotide of .8. A host cell comprising a polynucleotide of .9. A method for preparing an antibody or a functional fragment or immunoglobulin chain(s) thereof comprising{'claim-ref': {'@idref': 'CLM-00008', 'claim 8'}, '(a) culturing the cell of ; and'}(b) isolating said antibody or functional fragment or immunoglobulin chain(s) thereof from the culture.10. An antibody claim 6 , an immunoglobulin chain thereof or an antigen binding fragment thereof encoded ...

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Номер записи: 54
12-12-2013 дата публикации

ANTIBODY AND METHODS FOR SELECTIVE INHIBITION OF T-CELL RESPONSES

Номер: US20130330351A1
Автор: Fokta Frank J., GETTS Daniel R., Herrmann James J., Puisis John J.
Принадлежит:

The present invention provides compositions, methods, and assays for treating an inflammatory and/or autoimmune disease, and/or transplanted tissue rejection using anti-αβ TCR antibodies and antibody fragments. Anti-αβ TCR antibodies are antibodies which bind to a αβ TCR. Anti-αβ TCR antibodies produced by the hybridoma TOL101 MCB are also provided. Methods for treatment of an inflammatory disease, an autoimmune disease and for tissue transplant rejection using therapeutic dosing regimen of anti-αβ TCR antibodies and antibody fragments and for upregulating the numbers of Treg T-cells are also provided 13.-. (canceled)4. A method for treating an inflammatory disease , autoimmune disease , or transplant tissue rejection comprising administering a therapeutically effective amount of an isolated antibody to a human patient in need thereof , wherein the isolated antibody is produced by the hybridoma TOL101 MCB deposited with the ATCC under the accession number PTA-13293.5. The method according to claim 4 , wherein the inflammatory disease claim 4 , autoimmune disease or transplanted tissue rejection is selected from the group consisting of: asthma claim 4 , allergy claim 4 , allergic airway inflammation claim 4 , allergic encephalomyelitis claim 4 , autoimmune arthritis claim 4 , rheumatoid arthritis claim 4 , Juvenile rheumatoid arthritis claim 4 , reactive arthritis claim 4 , psoriatic arthritis claim 4 , sacroiliitis claim 4 , isolated acute anterior uveitis claim 4 , undifferentiated spondyloarthropathy claim 4 , Type 1 Diabetes Mellitus claim 4 , Multiple Sclerosis claim 4 , Systemic Lupus Erythematosus claim 4 , glomerulonephritis claim 4 , Hashimoto's thyroiditis claim 4 , Graves' disease claim 4 , Scleroderma claim 4 , Celiac disease claim 4 , Crohn's disease claim 4 , inflammatory bowel disease claim 4 , ulcerative colitis claim 4 , ankylosing spondylitis claim 4 , Sjogren's syndrome claim 4 , psoriasis claim 4 , contact dermatitis claim 4 , Goodpasture's ...

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Номер записи: 55
19-12-2013 дата публикации

SINGLE-CHAIN MULTIVALENT BINDING PROTEINS WITH EFFECTOR FUNCTION

Номер: US20130336977A1
Автор: Brady William, Hayden-Ledbetter Martha Susan, Ledbetter Jeffrey A., Thompson Peter Armstrong
Принадлежит: Emergent Product Development Seattle, LLC

Multivalent binding peptides, including bi-specific binding peptides, having immunoglobulin effector function are provided, along with encoding nucleic acids, vectors and host cells as well as methods for making such peptides and methods for using such peptides to treat or prevent a variety of diseases, disorders or conditions, as well as to ameliorate at least one symptom associated with such a disease, disorder or condition. 181-. (canceled)82. A single-chain protein comprising from amino to carboxy terminus:(a) a first binding domain derived from an immunoglobulin-like molecule or the variable regions of an immunoglobulin;{'sub': 'H1', '(b) a Fc region, wherein said Fc region does not comprise a domain derived from an immunoglobulin Cdomain;'}(c) a linker peptide of at least 5 amino acids; and(d) a second binding domain derived from an immunoglobulin-like molecule or the variable regions of an immunoglobulin, wherein the first or second binding domain binds CD3.83. The protein of claim 82 , wherein the first and/or second binding domain is a single-chain variable antibody fragment (scFv).84. The protein of claim 82 , wherein the first and/or second binding domain comprises chimeric claim 82 , humanized claim 82 , or human immunoglobulin variable regions.85. The protein of claim 82 , wherein the first and/or second binding domain comprises a light chain immunoglobulin variable region (VL1) and a heavy chain immunoglobulin variable region (VH1) claim 82 , wherein said variable regions are positioned in a VH1-VL1 or a VL1-VH1 orientation.86. The protein of claim 82 , wherein the first or second binding domain comprises variable regions derived from the G19-4 antibody.87. The protein of claim 86 , wherein the first or second binding domain comprises the amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 109.88. The protein of claim 82 , wherein the immunoglobulin-like molecule is a receptor.89. The protein of claim 82 , wherein the other binding domain binds to a ...

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Номер записи: 56
02-01-2014 дата публикации

Anti-mesothelin binding proteins

Номер: US20140004121A1
Автор: Carl Kozlosky, Jean Marie Gudas, William Christian Fanslow, Iii
Принадлежит: AMGEN INC

The present disclosure provides compositions and methods relating to antigen binding proteins, in particular, antibodies and bispecific antibodies which specifically bind to mesothelin. The disclosure provides nucleic acids encoding such antigen binding proteins and antibodies and methods of making and using such antibodies, including methods of treating and preventing cancer or other hypoproliferative disorders and related disorders by administering such antigen binding proteins and antibodies to a subject in need of such treatment.

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Номер записи: 57
16-01-2014 дата публикации

FULLY HUMAN ANTIBODIES TO BTLA

Номер: US20140017255A1
Автор: Halk Edward L., Korman Alan J., Leblanc Heidi N., Mataraza Jennifer Marie, Selby Mark J., Sproul Timothy W., Thudium Kent B., Van Elsas Andrea
Принадлежит: Medarex, L.L.C.

The present invention relates to binding compounds specific for BTLA and uses thereof. More specifically, the invention relates to fully human antibodies that recognize human BTLA and modulate its activity in cancer, inflammatory, and autoimmune disorders. 1. An isolated antibody , or antigen binding fragment thereof , which binds BTLA and comprises:(a) heavy and/or light chain variable regions as set forth in SEQ ID NOs:11 and 18, respectively; or(b) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:5, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:6, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:7, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:12, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:13; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:14.2. An isolated antibody claim 1 , or antigen binding fragment thereof claim 1 , that competes for binding to BTLA with the antibody claim 1 , or antigen binding fragment thereof claim 1 , of .3. An isolated polypeptide comprising the Vdomain or the Vdomain of the antibody claim 1 , or antigen binding fragment claim 1 , of .4. An isolated nucleic acid encoding the Vdomain or the Vdomain of the antibody claim 1 , or antigen binding fragment claim 1 , of .5. An expression vector comprising the isolated nucleic acid of .6. A host cell comprising the expression vector of .7. A composition comprising one or more antibodies claim 1 , or antigen binding fragments claim 1 , of claim 1 , and a pharmaceutically acceptable carrier or diluent.8. A method of treating a condition caused by decreased expression and/or activity of BTLA in a subject claim 1 , comprising administering to the subject an effective amount of a composition comprising the antibody claim 1 , or antigen binding fragment claim 1 , of .9. A method of ...

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Номер записи: 58
13-02-2014 дата публикации

ANTI-TIM-3 ANTIBODY

Номер: US20140044728A1
Автор: AKASHI Koichi, Inagaki Yoshimasa, KIKUSHIGE Yoshikane, KUBOTA Tsuguo, TAKAYANAGI Shin-ichiro, Tawara Tomonori, TOMURA Hitomi
Принадлежит:

Disclosed are an anti-human TIM-3 antibody having high ADCC activity or antibody fragment thereof by screening a monoclonal antibody or antibody fragment thereof which binds to the amino acid sequence of the extracellular region of TIM-3 or its three-dimensional structure and exhibits ADCC activity; a hybridoma which produces the antibody; a DNA encoding the antibody; a vector comprising the DNA; a transformant which is obtainable by introducing the vector; a method for producing the antibody or the antibody fragment thereof which comprises using the hybridoma or the transformant; and a therapeutic agent and a diagnostic agent comprising the antibody or the antibody fragment thereof as an active ingredient. 1. A monoclonal antibody or an antigen-binding fragment , which binds to an extracellular region of human T-cell immunoglobulin and mucin domain containing molecule-3 (TIM-3) while competing with one antibody selected from the following (a) to (c):(a) an antibody or an antigen-binding fragment thereof, each comprising a heavy chain (H chain) and a light chain (L chain), wherein complementarity determining regions (CDRs) 1 to 3 of said H chain comprises the amino acid sequences of SEQ ID NOs: 1 to 3, respectively, and CDRs 1 to 3 of said L chain comprises the amino acid sequences of SEQ ID NOs: 4 to 6, respectively,(b) an antibody or an antigen-binding fragment thereof, each comprising an H chain and L chain, wherein CDRs 1 to 3 of said H chain comprises the amino acid sequences of SEQ ID NOs: 11 to 13, respectively, and CDRs 1 to 3 of said L chain comprises the amino acid sequences of SEQ ID NOs: 14 to 16, respectively, and(c) an antibody or an antigen-binding fragment thereof, each comprising an H chain and L chain, wherein CDRs 1 to 3 of said H chain comprises the amino acid sequences of SEQ ID NOs: 21 to 23, respectively, and CDRs 1 to 3 of said L chain comprises the amino acid sequences of SEQ ID NOs: 24 to 26, respectively.2. The monoclonal antibody or the ...

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Номер записи: 59
20-02-2014 дата публикации

T-Cell Redirecting Bispecific Antibodies for Treatment of Disease

Номер: US20140050660A1
Автор: Chang Chien-Hsing, GOLDENBERG David M., Rossi Diane, Rossi Edmund A.
Принадлежит: IBC PHARMACEUTICALS, INC.

The present invention concerns compositions and methods of use of T-cell redirecting complexes, with at least one binding site for a T-cell antigen and at least one binding site for an antigen on a diseased cell or pathogen. Preferably, the complex is a DNL™ complex. More preferably, the complex comprises a bispecific antibody (bsAb). Most preferably, the bsAb is an anti-CD3×anti-CD19 bispecific antibody, although antibodies against other T-cell antigens and/or disease-associated antigens may be used. The complex is capable of targeting effector T cells to induce T-cell-mediated cytotoxicity of cells associated with a disease, such as cancer, autoimmune disease or infectious disease. The cytotoxic immune response is enhanced by co-administration of interferon-based agents that comprise interferon-α, interferon-β, interferon-λ1, interferon-λ2 or interferon-λ3. 1. A method of treating a disease comprising:a) administering a T-cell redirecting complex to a subject with the disease to induce a T-cell mediated immune response against a target cell associated with the disease; andb) administering to the subject an interferon selected from the group consisting of interferon-α, interferon-β, interferon-λ1, interferon-λ2 and interferon-λ3.2. The method of claim 1 , further comprising:c) inducing a T-cell mediated cytotoxic immune response against a target cell associated with the disease.3. The method of claim 1 , wherein the interferon increases the efficacy of the T-cell redirecting complex.4. The method of claim 3 , wherein the combination of interferon and T-cell redirecting complex is more effective than interferon alone and T-cell redirecting complex alone.5. The method of claim 1 , wherein the interferon is administered before claim 1 , simultaneously with claim 1 , or after the T-cell redirecting complex.6. The method of claim 1 , wherein the interferon is administered as free interferon claim 1 , PEGylated interferon claim 1 , an interferon fusion protein or ...

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Номер записи: 60
20-02-2014 дата публикации

Readily Isolated Bispecific Antibodies with Native Immunoglobulin Format

Номер: US20140051833A1
Автор: Fischer Nicolas, Magistrelli Giovanni, Malinge Pauline, Mastemak Krzysztof, Rousseau Francois
Принадлежит:

The invention relates to antigen-binding proteins or antibodies having heterodimers of heavy chains, i.e., two immunoglobulin heavy chains that differ by at least one or two amino acid(s) that allows for isolation of the antigen-binding protein based on a differential affinity of an immunoglobulin heavy chain and a modified/mutated immunoglobulin heavy chain toward an affinity reagent. The invention also relates antigen-binding proteins, including bispecific antibodies, having IgG CH1 regions with different affinities with respect to affinity reagent(s) that allows rapid isolation by differential binding of the IgG regions to the affinity reagent(s). 2. The isolated multispecific antibody of claim 1 , wherein the first polypeptide and the second polypeptide comprise human IgG heavy chains or are derived from human IgG heavy chains.3. The isolated multispecific antibody of claim 1 , further comprising an immunoglobulin light chain.4. The isolated multispecific antibody of claim 3 , wherein the immunoglobulin light chain comprises a human immunoglobulin light chain or is derived from a human immunoglobulin light chain.5. The isolated multispecific antibody of claim 1 , wherein the first and the second polypeptides each comprise human IgG1 heavy chains or are derived from human IgG1 heavy chains.6. The isolated multispecific antibody of claim 1 , wherein the second CH1 region comprises the modification claim 1 , and wherein the modification in the second CH1 domain comprises a mutation modifying S40 in the IMGT exon numbering system claim 1 , a mutation modifying T47 in the IMGT exon numbering system or a combination thereof.7. The isolated multispecific antibody of claim 6 , wherein the modification in the second CH1 domain comprises an S40T mutation in the IMGT exon numbering system claim 6 , a T47S mutation in the IMGT exon numbering system or a combination thereof.8. The isolated multispecific antibody of claim 6 , wherein the first CH1 domain of the bispecific ...

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Номер записи: 61
27-02-2014 дата публикации

Binding Agents That Modulate the Hippo Pathway and Uses Thereof

Номер: US20140056890A1
Автор: Chartier-Courtaud Cecile, GURNEY AUSTIN L.
Принадлежит:

The present invention relates to agents that modulate the Hippo pathway and Hippo pathway signaling, such as antibodies and soluble receptors, as well as to methods of using the agents for the treatment of diseases such as cancer. 180-. (canceled)81. An agent that specifically binds the extracellular domain of one or more cell adhesion molecules of the immunoglobulin superfamily (IgCAM) , wherein the IgCAM is selected from the group consisting of: AMICA , CAR , CLMP , ESAM , GPA33 , VSIG1 , VSIG2 , VSIG3 , VSIG4 , VSIG8 , JAM1 , JAM2 , JAM3 , CADM1 , CADM2 , CADM3 , CADM4 , CRTAM , TMIGD1 , PVR , PVRL1 , PVRL2 , PVRL3 , PVRL4 , PVRIG , CD200 , CD200R1 , CD200R1L , CD226 , CD96 , TIGIT , and TMEM25.82. The agent of claim 81 , which is a soluble receptor.83. The agent of claim 82 , wherein the soluble receptor comprises:(a) the extracellular domain of an IgCAM or a portion thereof;(b) a sequence selected from the group consisting of: SEQ ID NOs:33-64; or(c) a portion of a sequence selected from the group consisting of: SEQ ID NOs:33-64.84. The agent of claim 82 , wherein the soluble receptor comprises the extracellular domain of CADM1 claim 82 , CADM3 claim 82 , PVRL1 claim 82 , PVRL2 claim 82 , or PVRL3 claim 82 , or a portion thereof.85. The agent of claim 82 , which further comprises a Fc region.86. The agent of claim 81 , which is an antibody.87. The agent of claim 86 , wherein the antibody is a monoclonal antibody claim 86 , a recombinant antibody claim 86 , a chimeric antibody claim 86 , a humanized antibody claim 86 , a human antibody claim 86 , an antibody fragment comprising an antigen-binding site claim 86 , or a bispecific antibody.88. The agent of claim 81 , which:(a) modulates the Hippo pathway;(b) activates or increases Hippo pathway signaling;(c) reduces YAP activity;(d) increases phosphorylated YAP;(e) decreases the expression of YAP-dependent genes; and/or(f) decreases the expression of at least one of the genes selected from the group consisting of: ...

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Номер записи: 62
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: 63
06-03-2014 дата публикации

THERAPEUTIC USE OF ANTI-CS1 ANTIBODIES

Номер: US20140065063A1
Автор: Landolfi Nicholas F., Liu Gao, Tso J. Yun, Williams Marna
Принадлежит:

The present invention is directed to antagonists of CS1 that bind to and neutralize at least one biological activity of CS1. The invention also includes a pharmaceutical composition comprising such antibodies or antigen-binding fragments thereof. The present invention also provides for a method of preventing or treating disease states, including autoimmune disorders and cancer, in a subject in need thereof, comprising administering into said subject an effective amount of such antagonists. 117-. (canceled)18. A method of treating myeloma , comprising administering to a patient suffering from myeloma but who has not developed clinical manifestations of myeloma , a therapeutically effective amount of a monoclonal anti-CS1 antibody or an anti-CS1 antigen binding fragment , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment binds to a protein encoded by SEQ ID NO:1.19. The method of claim 18 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment inhibits immunoglobulin secretion.20. The method of claim 18 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment is humanized.21. The method of claim 18 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment induces antibody-dependent cellular cytotoxicity (“ADCC”) of cells expressing said protein encoded by SEQ ID NO:1.22. The method of claim 21 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment induces at least 40% cytotoxicity of cells expressing said protein encoded by SEQ ID NO:1.23. The method of claim 21 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment induces at least 60% cytotoxicity of cells expressing said protein encoded by SEQ ID NO:1.24. The method of claim 18 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment is an IgG.25. The method of claim 18 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment ...

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Номер записи: 64
06-03-2014 дата публикации

ANTI-SIGLEC-15 ANTIBODY

Номер: US20140065146A1
Автор: Hiruma Yoshiharu, Nakayama Makiko, Takizawa Takeshi, Tsuda Eisuke
Принадлежит: Daiichi Sankyo Company, Limited

Provided is a pharmaceutical composition for treating and/or preventing abnormal bone metabolism targeting a protein encoded by a gene strongly expressed in osteoclasts. Specifically provided is a pharmaceutical composition containing an antibody which specifically recognizes human Siglec-15 and has an activity of inhibiting osteoclast formation, and the like. 1. An antibody or antigen binding fragment thereof comprising: a light chain sequence that comprises a light chain variable region having CDRL1 , CDRL2 , and CDRL3 , wherein CDRL1 , comprises the amino acid sequence of SEQ ID NO: 47 , CDRL2 , comprises the amino acid sequence of SEQ ID NO: 48 , and CDRL3 , comprises the amino acid sequence of SEQ ID NO: 49 , and a heavy chain sequence that comprises a heavy chain variable region having CDRH1 , CDRH2 , and CDRH3 , wherein CDRH1 comprises the amino acid sequence of SEQ ID NO: 44 , CDRH2 comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 45 and SEQ ID NO: 97 , and CDRH3 comprises the amino acid sequence of SEQ ID NO: 46 , wherein the antibody or antigen binding fragment thereof binds a Siglec-15 protein comprising the amino acid sequence of SEQ ID NO: 2 or 4.2. The antigen binding fragment of claim 1 , selected from the group consisting of Fab claim 1 , F(ab′)2 claim 1 , Fab′ and Fv.3. The antibody or antigen binding fragment of claim 1 , wherein the antigen binding fragment is an scFv.4. The antibody or antigen binding fragment of claim 1 , wherein the antibody is a chimeric antibody.5. The antibody or antigen binding fragment of claim 1 , wherein the antibody or antigen binding fragment is humanized.6. The antibody or antigen binding fragment of claim 1 , wherein CDRH2 comprises the amino acid sequence of SEQ ID NO: 45.7. The antibody or antigen binding fragment of claim 1 , wherein CDRH2 comprises the amino acid sequence of SEQ ID NO: 97.8. A polynucleotide encoding the antibody of antigen binding fragment of .9. A vector ...

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Номер записи: 65
06-03-2014 дата публикации

NOVEL LOWERED AFFINITY ANTIBODIES AND USES THEREFOR

Номер: US20140066600A1
Автор: Chang Hsiu-Ching
Принадлежит: AB BIOSCIENCES, INC.

The present invention provides novel, rationally designed lowered affinity antibodies for use in various in vivo and in vitro applications. The antibodies of the present invention have variable domains that have been designed to reduce or eliminate the antigen binding activity of the parental antibody without altering the overall 3 dimensional antibody structure. Using the antibodies of the present invention in various assays allows researchers to distinguish effects that result from specific antigen-antibody interactions from other, non-specific antibody effects. 120.-. (canceled)21. An isolated OKT3 modified antibody or antigen binding fragment thereof , comprising:non-CDR regions having OKT3 wild-type sequence, andCDR regions wherein no more than 3 of the CDR regions are mutated relative to the wild-type OKT3 sequence and the remaining CDR regions have wild-type OKT3 sequence,each mutated CDR having substitutions characterized by little discernable structural change relative to the wild-type but resulting in lowered binding affinity to a CD3 antigen relative to the wild-type CDR;{'sub': 'D', 'sup': '−7', 'wherein the OKT3 modified antibody or antigen binding fragment has a Kgreater than 10M.'}22. The isolated OKT3 modified antibody or antigen binding fragment of claim 21 , having a Kgreater than 10M.23. The isolated OKT3 modified antibody or antigen binding fragment of claim 21 , wherein each mutated CDR has no more than 4 amino acid substitutions.24. The isolated OKT3 modified antibody or antigen binding fragment of claim 21 , wherein CDRH1 comprises SEQ ID NO.: 2 claim 21 , and the antibody or antigen binding fragment further comprises at least one light chain CDR mutation.25. The isolated OKT3 modified antibody or antigen binding fragment of claim 21 , wherein CDRH2 comprises SEQ ID NO.: 4.26. The isolated OKT3 modified antibody or antigen binding fragment of claim 21 , wherein CDRH2 comprises SEQ ID NO.: 5 claim 21 , and the antibody or antigen binding ...

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Номер записи: 66
13-03-2014 дата публикации

Rsv-specific binding molecules and means for producing them

Номер: US20140072575A1
Автор: Etsuko Yasuda, Hergen Spits, Mark Jeroen KWAKKENBOS, Tim Beaumont
Принадлежит: MedImmune Ltd

The invention provides antibodies and functional equivalents thereof which are capable of specifically binding RSV, and means and methods for producing them.

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Номер записи: 67
20-03-2014 дата публикации

ANTI-CD147 ANTIBODIES, METHODS AND USES

Номер: US20140079711A1
Автор: Cunningham Mark, Swencki-Underwood Bethany, Tang Yi, Yan Li
Принадлежит: JANSSEN BIOTECH, INC.

The present invention provides antibodies immunospecific for human CD147 capable of blocking bioactivity of CD147 associated with malignant disease such as the stimulation of MMPs from fibroblast cells by tumor cells, the release of VEGF, and the promotion of angiogenesis. The antibodies of the present invention of are useful in treating malignant disease and those diseases in which CD147 activity is plays a pathogenic role, such as diseases of the eye, lung, and cardiovascular system. 1. An isolated monoclonal antibody or antigen-binding fragment thereof that competes for binding to the epitope on CD147 bound by the monoclonal antibody selected from the group consisting of 2H3 , 4A5 , and 5F6 having the amino acid sequences of the light chain complementarity determining regions (CDRs) of one of SEQ ID NOs: 9 , 11 , and 13 and the amino acid sequences of the heavy chain CDRs of one of SEQ ID NOs: 10 , 12 , and 14.2. An isolated antibody having heavy chain CDR1 , CDR 2 and CDR3 (Hc-CDR1 , Hc-CDR2 and Hc-CDR3) amino acid sequences selected from the sequences shown in SEQ ID NOs: 10 , 12 and 14 respectively and a light chain CDR3 (Lc-CDR3) as shown in Formula (I):{'br': None, 'sub': 1', '2', '3, 'Gln Gln XaaTyr Ser XaaPro XaaThr\u2003\u2003(I)'}{'sub': 1', '2', '3', '4, 'wherein Xaais Tyr or Asp; Xaais Tyr or Ser; Xaais Phe or Tyr or absent; and Xaais Thr or Phe; and light chain CDR1 (Lc-CDR1) and light chain CDR2 (Lc-CDR2) amino acid sequences selected from the sequences as shown in SEQ ID NOs: 9 and 11, respectively.'}3. An isolated antibody having Hc-CDR1 , Hc-CDR2 and Hc-CDR3 amino acid sequences shown in SEQ ID NOs: 10 and Lc-CDR1 Lc-CDR2 , and Lc-CDR3 amino acid sequences as shown in SEQ ID NOs: 9.4. An isolated antibody having Hc-CDR1 , Hc-CDR2 and Hc-CDR3 amino acid sequences shown in SEQ ID NOs: 12 and Lc-CDR1 Lc-CDR2 , and Lc-CDR3 amino acid sequences as shown in SEQ ID NOs: 11.5. An isolated antibody having Hc-CDR1 , Hc-CDR2 and Hc-CDR3 amino acid sequences ...

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Номер записи: 68
27-03-2014 дата публикации

ANTI-CD3 ANTIBODIES, BISPECIFIC ANTIGEN-BINDING MOLECULES THAT BIND CD3 AND CD20, AND USES THEREOF

Номер: US20140088295A1
Автор: PAPADOPOULOS Nicholas J., Smith Eric
Принадлежит: Regeneron Pharmaceuticals, Inc.

The present invention provides antibodies that bind to CD3 and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with high affinity and induce human T cell proliferation. The invention includes antibodies that bind CD3 and induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human CD20. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell tumors expressing CD20. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders. 152-. (canceled)53. A fully human bispecific antibody comprising a first antigen-binding domain that specifically binds human CD3 , and a second antigen-binding domain that specifically binds human CD20.54. The fully human bispecific antibody of claim 53 , wherein the fully human bispecific antibody binds to CD3-expressing human T-cells with an ECvalue of between 1×10M and 1×10M.55. The fully human bispecific antibody of claim 54 , wherein the fully human bispecific antibody binds to CD3-expressing human T-cells with an ECvalue of between 1×10M and 6×10M.56. The fully human bispecific antibody of claim 53 , wherein the fully human bispecific antibody binds human cells expressing human CD3 and cynomolgus monkey cells expressing cynomolgus CD3.57. The fully human bispecific antibody of claim 53 , wherein the fully human bispecific antibody induces proliferation of ...

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Номер записи: 69
03-04-2014 дата публикации

Novel modulators and methods of use

Номер: US20140093495A1
Автор: Johannes Hampl, Orit Foord, Robert A. Stull, Scott J. Dylla
Принадлежит: Stemcentrx inc

Novel modulators, including antibodies and derivatives thereof, and methods of such modulators to treat hyperproliferative disorders are provided.

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Номер записи: 70
03-04-2014 дата публикации

Fc mutants

Номер: US20140093959A1
Автор: Jeffrey V. Ravetch, Rene G. Ott
Принадлежит: ROCKEFELLER UNIVERSITY

The present invention provides reagents, methods and systems for predicting the inhibitory activity of an antibody or variant thereof comprising: determining a binding affinity of the antibody or variant thereof to a Fc activating receptor; determining a binding affinity of the antibody or variant thereof to a Fc inhibitory receptor, and calculating the ratio of said activating binding affinity to said inhibitory binding affinity (A/I ratio), wherein the magnitude of said ratio is less than one (1).

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Номер записи: 71
10-04-2014 дата публикации

CD3-Binding Molecules Capable of Binding to Human and Non-Human CD3

Номер: US20140099318A1
Автор: Huang Ling, Johnson Leslie S.
Принадлежит: MACROGENICS, INC.

CD3-binding molecules capable of binding to human and non-human CD3, and in particular to such molecules that are cross-reactive with CD3 of a non-human mammal (e.g., a cynomolgus monkey) are presented. Uses of such antibodies and antigen-binding fragments in the treatment of cancer, autoimmune and/or inflammatory diseases and other conditions are presented. 1. A CD3-binding molecule comprising an antigen-binding fragment of an antibody , wherein said antigen-binding fragment comprises an antibody CD3-specific VL domain and an antibody CD3-specific VH domain , wherein said CD3-specific VL domain and said CD3-specific VH domain form an antigen-binding domain capable of immunospecifically binding to both an epitope of human CD3 and to an epitope of the CD3 of a non-human mammal , wherein:(I) said CD3-specific VL domain is selected from the group consisting of h-mab2 VL-1 (SEQ ID NO:16), h-mab2 VL-2 (SEQ ID NO:18), h-mab2 VL-3 (SEQ ID NO:20), h-mab2 VL-4 (SEQ ID NO:22), h-mab2 VL-5 (SEQ ID NO:24), h-mab2 VL-6 (SEQ ID NO:26), h-mab2 VL-7 (SEQ ID NO:28), h-mab2 VL-8 (SEQ ID NO:30), h-mab2 VL-9 (SEQ ID NO:32), and h-mab2 VL-10 (SEQ ID NO:34), and said CD3-specific VH domain is selected from the group consisting of h-mab2 VH-1 (SEQ ID NO:36), h-mab2 VH-2 (SEQ ID NO:38), h-mab2 VH-3 (SEQ ID NO:40), h-mab2 VH-4 (SEQ ID NO:42), h-mab2 VH-5 (SEQ ID NO:44), h-mab2 VH-6 (SEQ ID NO:46), h-mab2 VH-6L (SEQ ID NO:54), h-mab2 VH-7 (SEQ ID NO:48), h-mab2 VH-8 (SEQ ID NO:50), h-mab2 VH-8L (SEQ ID NO:55), h-mab2 VH-8 di-1 (SEQ ID NO:56), h-mab2 VH-8 di-2 (SEQ ID NO:57), h-mab2 VH-6M (SEQ ID NO:72), h-mab2 VH-8M (SEQ ID NO:74), h-mab2 VH-2k (SEQ ID NO:87), and h-mab2 VH-5k (SEQ ID NO:88); or(II) said CD3-specific VL domain is selected from the group consisting of h-mab1 VL-1 (SEQ ID NO:10) and h-mab1 VL-2 (SEQ ID NO:12), and said CD3-specific VH domain is h-mab1 VH (SEQ ID NO:14).2. The CD3-binding molecule of claim 1 , wherein said CD3-specific VL domain is h-mab2 VL-6 (SEQ ID NO:26).3. ...

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Номер записи: 72
10-04-2014 дата публикации

Non-naturally occurring t cell receptors

Номер: US20140099699A1
Автор: Bent Karsten Jakobsen, Naomi Harwood, Nathaniel Ross Liddy
Принадлежит: Immunocore Ltd

A T cell receptor (TCR) having the property of binding to the gp100 YLEPGPVTA peptide-HLA-A2 complex and comprising a TCR alpha variable domain and/or a TCR beta variable domain, characterized in that the domains are mutated relative to a TCR having the extracellular alpha and beta chain sequences SEQ ID NOs: 2 and that the TCR has a binding affinity for, and/or a binding half-life for, the YLEPGPVTA-HLA-A2 complex at least double that of a reference TCR. Embodiments of the invention such as the use of such TCRs in adoptive therapy, and fusions of such TCRs with therapeutic agents are also described.

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Номер записи: 73
10-04-2014 дата публикации

Dual Variable Domain Immunoglobulin and Uses Thereof

Номер: US20140100359A1
Автор: DIXON Richard W., Ghayur Tariq, SALFELD Jochen G., Wu Chengbin
Принадлежит: AbbVie Inc.

The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases. 175-. (canceled)76. A binding protein comprising first and second polypeptide chains , each independently comprising VD1-(X1)n-VD2-C-(X2)n , whereinVD1 is a first variable domain;VD2 is a second variable domain;C is a constant domain;X1 is a linker;X2 is an Fc region; andn is 0 or 1;wherein the VD1 domains on the first and second polypeptide chains form a functional target binding site and the VD2 domains on the first and second polypeptide-chains form a functional target binding site, and wherein at least one functional target site binds to TNF.77. The binding protein of claim 76 , wherein the variable domains that form the functional target binding site for TNF comprise variable domains from adalimumab (HUMIRA®) claim 76 , infliximab (REMICADE®) claim 76 , HUMICADE® claim 76 , CNTO 148 (Medarex/Centocor) or etenercept (ENBREL®).78. The binding protein of claim 76 , wherein the binding protein also binds to a cytokine claim 76 , cytokine receptor claim 76 , or a cytokine related protein.79. The binding protein of claim 76 , wherein the binding protein also binds to a target selected from the group consisting of ABCF1 claim 76 , ACVRI claim 76 , ACVR1B claim 76 , ACVR2 claim 76 , ACVR2B claim 76 , ACVRL1 claim 76 , AMH claim 76 , AMHR2 claim 76 , BMPR1A claim 76 , BMPR1B claim 76 , BMPR2 claim 76 , BCL6 claim 76 , C19orf10 (IL27w) claim 76 , C3 claim 76 , C4A claim 76 , C5 claim 76 , CNR1 claim 76 , CRP claim 76 , CTLA4 claim 76 , CYSLTR1 claim 76 , BLR1 claim 76 , CCL1 (1-309) claim 76 , CCL2 (mcp-1) claim 76 , CCL3 (MIP-1a) claim 76 , CCL4 (MIP-1b) claim 76 , CCL5 (RANTES) claim 76 , CCL7 (mcp-3) claim 76 , CCL8 (mcp-2) claim 76 , CCL11 (eotaxin) claim 76 , CCL13 (mcp-4) claim 76 , CCL15 (MIP-Id) claim 76 ,CCL16 (HCC-4) claim 76 , CCL17 ...

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Номер записи: 74
06-01-2022 дата публикации

Modified Cell Expressing Therapeutic Agent and Uses thereof

Номер: US20220000921A1
Автор: Cao Zhiyuan, Pu Chengfei, Xiao Lei
Принадлежит: Innovative Cellular Therapeutics Holdings, Ltd.

Compositions and methods for enhancing T cell response which increases the efficacy of CAR T cell therapy for treating cancer are described. Embodiments include a modified cell comprising an isolated nucleic acid comprising a first nucleic acid and a second nucleic acid, the first nucleic acid encoding a chimeric antigen receptor (CAR), the second nucleic acid encoding a therapeutic agent comprising at least one of IFN-, IL-2, IL-6, IL-7, IL-15, IL-17, and IL-23. The modified cell expresses and secretes the therapeutic agent. 119-. (canceled)20. A pharmaceutical composition comprising modified T cells , wherein the modified T cells comprise chimeric antigen receptor (CAR) and an exogenous polynucleotide encoding one or more proteins , the one or more proteins comprising IFNγ.21. The pharmaceutical composition of claim 20 , wherein the exogenous polynucleotide comprises SEQ ID NO: 469 and a polynucleotide encoding SEQ ID NO: 328.22. The pharmaceutical composition of claim 20 , wherein the modified T cells express and secrete the one or more proteins in response to activation of the modified T cells claim 20 , hypoxia claim 20 , or a combination thereof.23. The pharmaceutical composition of claim 20 , wherein the exogenous polynucleotide is present in the modified T cell in a recombinant DNA construct claim 20 , in an mRNA claim 20 , or in a viral vector.24. The pharmaceutical composition of claim 20 , wherein the one or more proteins further comprise IL-6.25. The pharmaceutical composition of claim 24 , wherein the exogenous polynucleotide comprises a polynucleotide encoding SEQ ID NOS: 287 and a polynucleotide encoding SEQ ID NO: 328.26. The pharmaceutical composition of claim 20 , wherein the exogenous polynucleotide comprises a promoter comprising a binding site for a transcription modulator that modulates the expression and/or secretion of the one or more proteins in the modified T cells.27. The pharmaceutical composition of claim 26 , wherein the transcription ...

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Номер записи: 75
06-01-2022 дата публикации

ANTI-HUMAN PAPILLOMAVIRUS (HPV) ANTIGEN-BINDING PROTEINS AND METHODS OF USE THEREOF

Номер: US20220001000A1
Автор: Bray Kevin A., Delfino Frank, Franklin Matthew C., Garnova Elena S., Kirshner Jessica, MacDONALD Douglas, Olson William, THURSTON Gavin
Принадлежит:

The present invention provides antigen-binding proteins that specifically bind to an HLA-displayed human papillomavirus (HPV) peptide, and therapeutic and diagnostic methods of using those binding proteins. 1. A method of treating a subject having an HPV16E7-associated disease or disorder , comprising administering to the subject a therapeutically effective amount of an isolated antigen-binding protein that binds specifically to a conformational epitope of an HLA-A2 presented human papillomavirus (HPV) 16 E7 peptide (HPV16E7 peptide) ,wherein the conformational epitope comprises one or more amino acids of SEQ ID NO: 537 selected from the group consisting of Y11, D14, L15, P17 and E18,wherein the antigen-binding protein comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3); and three light chain CDRs (LCDR1, LCDR2 and LCDR3), wherein(a) the HCDR1 domain comprises an amino acid sequence having at least 90% amino acid sequence identity to the entire amino acid sequence of an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 20, 36, 52, 68, 84, 100, 116, 132, 148, 164, 180, 196, 212, 220, 236, 252, 268, 284, 300, 316, 332, 348, 364, 380, 396, 412, 428, 444, 460, 476, 492, 508, and 524;(b) the HCDR2 domain comprises an amino acid sequence having at least 90% amino acid sequence identity to the entire amino acid sequence of an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 22, 38, 54, 70, 86, 102, 118, 134, 150, 166, 182, 198, 214, 222, 238, 254, 270, 286, 302, 318, 334, 350, 366, 382, 414, 430, 446, 462, 478, 494, 510, and 526;(c) the HCDR3 domain comprises an amino acid sequence having at least 90% amino acid sequence identity to the entire amino acid sequence of an amino acid sequence selected from the group consisting of SEQ ID NOs: 8, 24, 40, 56, 72, 88, 104, 120, 136, 152, 168, 184, 200, 216, 224, 240, 256, 272, 288, 304, 320, 336, 352, 368, 384, 400, 416, 432, 448, 464, 480, ...

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Номер записи: 76
07-01-2021 дата публикации

CD19 SPECIFIC CHIMERIC ANTIGEN RECEPTOR AND USES THEREOF

Номер: US20210000869A9
Автор: Galetto Roman, Scharenberg Andrew, SCHIFFER-MANNIOUI Cecile, Smith Julianne
Принадлежит:

The present invention relates to chimeric antigen receptors (CAR). CARs are able to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties. In particular, the present invention relates to a Chimeric Antigen Receptor in which extracellular ligand binding is a scFV derived from a CD19 monoclonal antibody, preferably 4G7. The present invention also relates to polynucleotides, vectors encoding said CAR and isolated cells expressing said CAR at their surface. The present invention also relates to methods for engineering immune cells; expressing 4G7-CAR at their surface which confers a prolonged “activated” state on the transduced cell. The present invention is particularly useful for the treatment of B-cells lymphomas and leukemia. 1. (canceled)2. A combination therapy comprising:(a) an engineered T-cell expressing a CD19-specific chimeric antigen receptor (CAR); and(b) an antibody.3. The combination therapy of claim 2 , wherein the antibody is the CAMPATH antibody.4. The combination therapy of claim 2 , wherein the CD19-specific CAR comprises at least one extracellular ligand binding domain claim 2 , a transmembrane domain claim 2 , and at least one intracellular signaling domain.5. The combination therapy of claim 4 , wherein the extracellular ligand binding of the CD19-specific CAR comprises an amino acid sequence of SEQ ID NOs: 7 or 8.6. The combination therapy of claim 4 , wherein the at least one intracellular signaling domain of the CD19-specific CAR is a CD3 zeta signaling domain comprising the amino acid sequence of SEQ ID NO: 10.7. The combination therapy of claim 4 , wherein the transmembrane domain of the CD19-specific CAR comprises a human CD8 alpha chain transmembrane and stalk domain comprising the amino acid sequence of SEQ ID NO: 13.8. The combination therapy of claim 4 , wherein the CD19-specific CAR comprises a second intracellular signaling domain.9. The combination therapy of claim 8 , ...

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Номер записи: 77
07-01-2021 дата публикации

Prostate Cancer Specific Marrow Infiltrating Lymphocytes and Uses Thereof

Номер: US20210000876A1
Автор: Borrello Ivan, Noonan Kimberly A.
Принадлежит: WINDMIL THERAPEUTICS, INC.

The disclosure provides for compounds comprising prostate cancer specific marrow infiltrating lymphocytes and methods for making and using the same. 1. A method for treating a subject having prostate cancer with marrow infiltrating lymphocytes , the method comprising the steps of:(a) culturing a bone marrow sample obtained from the subject having prostate cancer with an anti-CD3 antibody and an anti-CD28 antibody in a hypoxic environment to produce hypoxic-activated marrow infiltrating lymphocytes;(b) culturing the hypoxic-activated marrow infiltrating lymphocytes in a normoxic environment to produce the therapeutic activated marrow infiltrating lymphocytes; and(c) administering the therapeutic activated marrow infiltrating lymphocytes to the subject having prostate cancer.2. The method of claim 1 , wherein the hypoxic environment has an oxygen content of about 0% to about 5% oxygen.3. The method of claim 1 , wherein the lymphocytes are cultured in the presence of IL-2.4. The method of claim 1 , wherein the culturing the hypoxic-activated marrow infiltrating lymphocytes in a normoxic environment is performed in the presence of IL-2.5. The method of claim 1 , wherein the bone marrow sample is cultured in the hypoxic environment for about 24 hours.6. The method of claim 1 , wherein the bone marrow sample is cultured in the hypoxic environment for about 2 days.7. The method of claim 1 , wherein the bone marrow sample is cultured in the hypoxic environment for about 3 days.8. The method of claim 1 , wherein the bone marrow sample is cultured in the hypoxic environment for about 2 to about 5 days.9. The method of claim 1 , wherein the hypoxic environment is about 1% to about 2% oxygen.10. The method of claim 1 , wherein the hypoxic-activated marrow infiltrating lymphocytes are cultured in the normoxic environment for about 2 to about 12 days.11. The method of claim 1 , wherein the hypoxic-activated marrow infiltrating lymphocytes are cultured in the normoxic environment ...

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Номер записи: 78
07-01-2016 дата публикации

ONCOLYTIC VIRUS

Номер: US20160000842A1
Автор: Gottschalk Stephen M. G., Song Xiao-Tong, Yu Feng
Принадлежит:

Embodiments of the present disclosure concern oncolytic viruses, such as vaccinia virus, for example, for the treatment of cancer, wherein the viruses encode an engager molecule having an activation domain that recognizes a cell molecule, such as CD3, for example, on T cells and an antigen recognition domain that recognizes a tumor antigen, such as EphA2, HER2, GD2, or Glypican-3, for example. In some embodiments, the engager molecules further comprise a cytokine or co-stimulatory domain, for example. Methods of treating cancer using one or more of the compositions are encompassed in the disclosure. 1. An oncolytic virus that encodes a bipartite molecule comprising a single chain variable fragment (scFv) specific for a cell surface molecule and a scFv specific for a tumor antigen.2. The virus of claim 1 , wherein the cell surface molecule is on effector cells.3. The virus of claim 2 , wherein the effector cells are T lymphocytes.4. The virus of claim 1 , wherein the tumor antigen is selected from the group consisting of EphA2 claim 1 , HER2 claim 1 , or GD2.5. The virus of claim 1 , wherein the cell surface molecule is selected from the group consisting of CD3 claim 1 , CD4 claim 1 , CD5 claim 1 , CD8 claim 1 , CD16 claim 1 , CD28 claim 1 , CD40 claim 1 , CD134 claim 1 , CD137 claim 1 , and NKG2D.6. The virus of claim 1 , wherein the cell surface molecule is CD3.7. The virus of claim 1 , wherein the oncolytic virus is vaccinia virus claim 1 , adenovirus claim 1 , Herpes simplex virus 1 (HSV1) claim 1 , myxoma virus claim 1 , reovirus claim 1 , poliovirus claim 1 , vesicular stomatitis virus (VSV) claim 1 , measles virus (MV) claim 1 , or Newcastle disease virus (NDV).8. A method of treating an individual for cancer claim 1 , comprising the step of delivering to the individual a therapeutically effective amount of the virus of .9. The method of claim 8 , wherein the amount of the virus comprises 10-10pfu of the virus.10. The method of claim 8 , further comprising the ...

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Номер записи: 79
06-01-2022 дата публикации

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

Номер: US20220002376A1
Автор: GILL Saar, June Carl H., KLICHINSKY Michael
Принадлежит:

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 144-. (canceled)45. A pharmaceutical composition comprising: (i) at least 50% of the cells in the population of cells are CD14+ or CD11b+, and', '(ii) the population of cells has been depleted for cells expressing CD3 and CD19 and, '(a) a population of modified human cells comprising a chimeric antigen receptor (CAR), wherein(b) a pharmaceutically acceptable excipient.46. The pharmaceutical composition of claim 45 , wherein the CAR comprises an antigen binding domain claim 45 , a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule.47. The pharmaceutical composition of claim 46 , wherein the antigen binding domain comprises an anti-HER2 antigen binding domain claim 46 , an anti-mesothelin antigen binding domain claim 46 , an anti-CD19 antigen binding domain or an anti-PSMA antigen binding domain.48. The pharmaceutical composition of claim 46 , wherein the antigen binding domain of the CAR comprises an antibody selected from the group consisting of a monoclonal antibody claim 46 , a polyclonal antibody claim 46 , a synthetic antibody claim 46 , human antibody claim 46 , humanized antibody claim 46 , single domain antibody claim 46 , single chain variable fragment claim 46 , and antigen-binding fragments thereof.49. The pharmaceutical composition of claim 46 , wherein the transmembrane domain of the CAR comprises a CD8 or CD28 transmembrane domain.50. The ...

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Номер записи: 80
06-01-2022 дата публикации

Modified Monocytes/Macrophage Expressing Chimeric Antigen Receptors and Uses Thereof

Номер: US20220002377A1
Автор: GILL Saar, June Carl H., KLICHINSKY Michael
Принадлежит:

The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. 144-. (canceled)45. A pharmaceutical composition comprising: wherein at least 70% of the cells in the population of cells express the CAR,', 'wherein the modified human cells are modified human macrophages and/or modified human monocytes, and, '(a) a population of modified human cells comprising a chimeric antigen receptor (CAR),'}(b) a pharmaceutically acceptable excipient.46. The pharmaceutical composition of claim 45 , wherein the CAR comprises an antigen binding domain claim 45 , a transmembrane domain and an intracellular domain of a stimulatory and/or co-stimulatory molecule.47. The pharmaceutical composition of claim 45 , wherein the antigen binding domain comprises an anti-HER2 antigen binding domain claim 45 , an anti-mesothelin antigen binding domain claim 45 , an anti-PSMA antigen binding domain claim 45 , or an anti-CD19 antigen binding domain.48. The pharmaceutical composition of claim 46 , wherein the antigen binding domain of the CAR comprises an antibody selected from the group consisting of a monoclonal antibody claim 46 , a polyclonal antibody claim 46 , a synthetic antibody claim 46 , human antibody claim 46 , humanized antibody claim 46 , single domain antibody claim 46 , single chain variable fragment claim 46 , and antigen-binding fragments thereof.49. The pharmaceutical composition of claim 46 , wherein the transmembrane domain of the CAR comprises a CD8 or CD28 transmembrane domain.50. ...

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Номер записи: 81
06-01-2022 дата публикации

ANTI-oxMIF/ANTI-CD3 ANTIBODY FOR CANCER TREATMENT

Номер: US20220002398A1
Автор: Kerschbaumer Randolf, Schinagl Alexander, THIELE Michael Robert
Принадлежит:

The invention refers to an anti-ox MIF/anti-CD3 antibody comprising at least one binding site specifically recognizing ox MIF and at least one binding site specifically recognizing CD3 and its use in the treatment of hyperproliferative diseases, specifically in the treatment of cancers. 1. An anti-oxMIF/anti-CD3 antibody comprising at least one binding site specifically recognizing oxMIF and at least one binding site specifically recognizing CD3.2. The anti-oxMIF/anti-CD3 antibody of claim 1 , wherein the binding site specifically recognizing oxMIF comprises(a) a heavy chain variable region comprisinga CDR1-H1 sequence which has at least 70% sequence identity to any of the sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 7, SEQ ID NO: 13, SEQ ID NO: 19 and SEQ ID NO: 26, anda CDR2-H1 sequence which has at least 70% sequence identity to any of the sequences selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 8, SEQ ID NO: 14, SEQ ID NO: 20 and SEQ ID NO: 27, anda CDR3-H1 sequence which has at least 70% sequence identity to any of the sequences selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 9, SEQ ID NO: 15 and SEQ ID NO: 21, and(b) a light chain variable region comprisinga CDR1-L1 sequence which has at least 70% sequence identity to any of the sequences selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 10, SEQ ID NO: 16, SEQ ID NO: 22 and SEQ ID NO: 28, anda CDR2-L1 sequence which has at least 70% sequence identity to any of the sequences selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 17, SEQ ID NO: 23 and SEQ ID NO: 25, anda CDR3-L1 sequence which has at least 70% sequence identity to any of the sequences selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 12, SEQ ID NO: 18 and SEQ ID NO: 24.3. The anti-oxMIF/anti-CD3 antibody of claim 2 , comprising 0 claim 2 , 1 claim 2 , or 2 point mutations in each CDR sequences claim 2 , wherein the CDR sequences area CDR1- ...

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Номер записи: 82
06-01-2022 дата публикации

Chimeric antigen receptor and its use

Номер: US20220002401A1
Автор: Andreas Hombach, Hinrich Abken
Принадлежит: Individual

In a first aspect, the present invention relates to a recombinant polypeptide containing a domain comprising at least two antibody units whereby the first antibody unit is an an anti-CD30 single chain antibody unit while the second antibody unit is a antibody unit being specific for an antigen present on the surface of a pre-determined target cell. In particular, the present invention relates to a recombinant polypeptide containing at least the following domains starting from the N-terminus to the C-terminus: a first domain containing an anti-CD30 single chain anti-body unit, in particular, HRS3 scFv of SEQ ID No. 2 or homologs thereof having at least 70% identity with SEQ ID No. 2 binding specifically to CD30, and an antibody unit said antibody unit being specific for an antigen present on the surface of a predetermined target cell, in particular, being specific for a tumor-associated antigen; optionally a spacer domain; a trans-membrane domain; and a cytoplasmatic signalling domain. In a further aspect, the present invention relates to a nucleic acid molecule encoding the polypeptide according to the present invention, as well as vectors and cells containing the same. Moreover, lymphocytes are provided, in particular T-cells like CD8′ or a CD4* T-cell expressing on its surface chimeric antigen receptors containing an anti-CD30 single chain antibody unit and an antibody unit whereby said antibody unit being specific for an antigen present on the surface of a predetermined target cell. Immune cells modified with the polypeptide show improved functions, in particular in the treatment of cancer, in particular CD30− cancer. That is, the cells are for use in adapted cell therapy for treating cancer in a subject in need thereof.

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Номер записи: 83
06-01-2022 дата публикации

ANTI-ILT4 ANTIBODIES AND ANTIGEN-BINDING FRAGMENTS

Номер: US20220002403A1
Автор: Blanusa Milan, Joyce-Shaikh Barbara, Schultze Kornelia, Schuster Andrea Claudia, Zuniga Luis A.
Принадлежит:

The present invention provides antibodies and antigen-binding fragments thereof that bind to ILT4 (immunoglobulin-like transcript 4) and combinations thereof, e.g., with an anti-PD1 antibody. Also provided are methods of use thereof, for example, for treating or preventing cancer in a subject; and methods of making such antibodies and fragments. 1. An antibody or antigen-binding fragment thereof that binds one or more amino acid residues in a human immunoglobulin-like transcript 4 (ILT4) epitope selected from the group consisting of LYREKKSASW (SEQ ID NO:59) , TRIRPEL (SEQ ID NO:60) , NGQF (SEQ ID NO:61) , and HTGRYGCQ (SEQ ID NO:62) and protects the epitope from deuterium exchange in the presence of a deuterium source.2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the ILT4 epitope is LYREKKSASW (SEQ ID NO:59).3. The antibody or antigen-binding fragment thereof of claim 1 , wherein the ILT4 epitope is TRIRPEL (SEQ ID NO:60).4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the ILT4 epitope is NGQF (SEQ ID NO:61).5. The antibody or antigen-binding fragment thereof of claim 1 , wherein the ILT4 epitope is HTGRYGCQ (SEQ ID NO:62).6. An antibody or antigen-binding fragment thereof that competes with a reference antibody for binding to a human ILT4 epitope selected from the group consisting of LYREKKSASW (SEQ ID NO:59) claim 1 , TRIRPEL (SEQ ID NO:60) claim 1 , NGQF (SEQ ID NO:61) claim 1 , and HTGRYGCQ (SEQ ID NO:62) claim 1 , wherein the reference antibody comprises a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO:2 and a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO:7.7. The antibody or antigen-binding fragment thereof of claim 6 , wherein the ILT4 epitope is LYREKKSASW (SEQ ID NO:59).8. The antibody or antigen-binding fragment thereof of claim 6 , wherein the ILT4 epitope is TRIRPEL (SEQ ID NO:60).9. The antibody or antigen-binding fragment ...

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Номер записи: 84
06-01-2022 дата публикации

Homodimer-type bispecific antibody targeting cd19 and cd3, and preparation method therefor and application thereof

Номер: US20220002407A1
Автор: Guimin Zhang, Lili Zhao, QIANG LI, Shixiang Jia, Xinlu Ma, Xuemei Liu, Xueyuan Cui, Yuhua Zhang
Принадлежит: Ampsource Biopharma Shanghai Inc

Provided is a tetravalent, homodimer-type bispecific antibody molecule that targets both immune effector cell antigen CD3 and tumor-related antigen CD19. The bispecific antibody molecule comprises first and second single-chain Fv and Fc fragments in sequence from the N-terminus to the C-terminus, wherein the first single-chain Fv can specifically bind to CD19, the second single-chain Fv can specifically bind to CD3, the first and second single-chains Fv are connected by means of a linker peptide, the second single-chain Fv and Fc fragments are directly connected to each other or connected by means of a linker peptide; and the Fc fragment does not have effector functions such as CDC, ADCC, and ADCP. The bispecific antibody can significantly inhibit or kill tumor cells, and has toxic and side effects that may be caused by excessive activation of effector cells; in addition, such bispecific antibody is of homodimer type, without the problem of heavy chain and light chain mismatch; the purification step is simple and efficient, the expression is high, and the physical and chemical properties as well as in vivo stability of the antibody are significantly improved.

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Номер записи: 85
06-01-2022 дата публикации

BISPECIFIC ANTIBODY, PREPARATION METHOD THEREOF AND APPLICATION THEREOF

Номер: US20220002408A1
Автор: BAI Lili, LI Yanhu, MENG Qingwu, YUAN Andy Qingan, ZHAO Likun
Принадлежит:

A bispecific antibody, a preparation method therefor and an application thereof. The bispecific antibody includes a monoclonal antibody unit and a single-chain antibody unit. The single-chain antibody unit includes two complete light chain-heavy chain pairs, and is specifically bound to a surface antigen of a tumor cell. The single-chain antibody unit includes two single-chain antibodies. The single-chain antibody includes a heavy chain variable region and a light chain variable region, and is specifically bound to a surface antigen of an immunocyte. The bispecific antibody can be simultaneously bound to the immunocyte and the tumor cell, can mediate a directed immune response, and can effectively kill the tumor cell. 1. A bispecific antibody that binds to CD19 and CD3 , wherein the bispecific antibody comprises (a) a monoclonal antibody unit and (b) a single-chain antibody unit; the monoclonal antibody unit consists of two complete light chain-heavy chain pairs , and can specifically bind to CD19; the single-chain antibody unit comprises two single-chain antibodies; the single-chain antibody comprises a heavy chain variable region and a light chain variable region , and can specifically bind to CD3; the bispecific antibody has a symmetric structure formed by linkage in any one of the following modes:(1) the C-ends of the two single-chain antibodies are respectively linked to the N-ends of two heavy chains of the monoclonal antibody through a linker peptide; and(2) N-ends of the two single-chain antibodies are respectively linked to C-ends of the two heavy chains of the monoclonal antibody through a linker peptide.2. The bispecific antibody according to claim 1 , wherein the amino acid sequence of the linker peptide is (GGGGX)n claim 1 , wherein X is Gly or Ser claim 1 , and n is a natural number selected from 1 to 4;preferably, the amino acid sequence of the linker peptide is represented by SEQ ID NO. 13.3. The bispecific antibody according to claim 1 , wherein ...

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Номер записи: 86
06-01-2022 дата публикации

Bispecific antibody against bcma and cd3 and an immunological drug for combined use in treating multiple myeloma

Номер: US20220002427A1
Автор: Bruno David Lourenço PAIVA, Jesus Fernado San Miguel Izquierdo, Klaus Strein, Minh Diem Vu
Принадлежит: Bristol Myers Squibb Co, Universidad De Navarra

The invention relates to a bispecific antibody specifically binding to human B cell maturation antigen (BCMA) and to human CD3ε (CD3) together with an immunotherapeutic drug for combined use in treating multiple myeloma.

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Номер записи: 87
07-01-2021 дата публикации

HUMANIZED CC CHEMOKINE RECEPTOR 4 (CCR4) ANTIBODIES AND METHODS OF USE THEREOF

Номер: US20210000950A1
Автор: CHANG De-Kuan, Marasco Wayne A., ZHU Quan
Принадлежит:

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4-IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. 1. An isolated humanized monoclonal antibody that binds to the human CC chemokine receptor 4 (CCR4) and has an IgG4 heavy chain constant region.2. The antibody of claim 1 , wherein{'sub': H', 'L, 'a. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 2 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 4;'}{'sub': H', 'L, 'b. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 16 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 18;'}{'sub': H', 'L, 'c. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 20 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 22;'}{'sub': H', 'L, 'd. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 24 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 25;'}{'sub': H', 'L, 'e. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 28 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 30'}{'sub': H', 'L, 'claim-text': 'the heavy chain constant region comprises SEQ ID NO: 6 or SEQ ID: 8;', 'f. the variable heavy chain region (V) comprises the amino acid sequence of SEQ ID NO: 44 and variable light chain region (V) comprises the amino acid sequence of SEQ ID NO: 46; and'}3. The antibody of claim 2 , wherein said antibody ...

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Номер записи: 88
07-01-2021 дата публикации

COMBINATION THERAPIES

Номер: US20210000951A1
Автор: Cao Zhu Alexander, Lee Benjamin Hyun, Longmire Tyler, Pinzon-Ortiz Maria Consuelo, Rong Xianhui
Принадлежит:

Combination therapies are disclosed. The combination therapies can be used to treat or prevent cancerous conditions and/or disorders. 12.-. (canceled)3. A method of treating a cancer in a subject , comprising administering to the subject an immunomodulator and a second therapeutic agent , wherein:(i) the immunomodulator is an inhibitor of an immune checkpoint molecule or an activator of a costimulatory molecule, or a combination thereof,wherein the inhibitor of an immune checkpoint molecule is chosen from an inhibitor of one or more of PD-1, PD-L1, PD-L2, CTLA-4, TIM-3, LAG-3, CEACAM, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, or TGFR beta, andwherein the activator of the costimulatory molecule is chosen from an agonist of one or more of OX40, CD2, CD27, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, or CD83 ligand; and(ii) the second therapeutic agent is chosen from one or more of 1) an IAP inhibitor; 2) a HDM2 ligase inhibitor; 1 a PIM kinase inhibitor; 4) a HER3 kinase inhibitor; or 5) an FGF receptor inhibitor, as provided in Table 1,thereby treating the cancer.4. A method of treating a cancer in a subject , comprising administering to the subject an immunomodulator and a second therapeutic agent , wherein:(i) the immunomodulator is an inhibitor of an immune checkpoint molecule or an activator of a costimulatory molecule, or a combination thereof,wherein the inhibitor of an immune checkpoint molecule is chosen from an inhibitor of one or more of PD-1, PD-L1, PD-L2, CTLA-4, TIM-3, LAG-3, CEACAM, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, or TGFR beta, andwherein the activator of the costimulatory molecule is chosen from an agonist of one or more of OX40, CD2, CD27, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, or CD83 ligand; and(ii) the second therapeutic agent is chosen from one or ...

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Номер записи: 89
07-01-2021 дата публикации

ANTI-TIGIT ANTIBODIES, ANTI-PVRIG ANTIBODIES AND COMBINATIONS THEREOF

Номер: US20210000952A1
Автор: Chan Christopher, Cheng Hsin-Yuan, Cojocaru Gad S., Dassa Liat, Desai Radhika, Drake Andrew W., Giladi David Nisim, Gozlan Yosi, Hansen Kyle, Kotturi Maya, Kumar Sandeep, Liang Spencer, Ophir Eran, PRESTA Leonard, Safyon Einav, Sameah-Greenwald Shirley, Stapleton Lance, Theolis Richard, Tiran Zohar, Vaknin Ilan, Wall Patrick, White Mark
Принадлежит:

Anti-PVRIG and anti-TIGIT antibodies are provided. 1. A method of activating T-cells of a patient with cancer comprising administering an anti-PD-L1 antibody and an anti-PVRIG antibody to said patient , wherein said anti-PVRIG antibody comprises:i) a heavy chain comprising SEQ ID NO: 9, andii) a light chain comprising SEQ ID NO: 14.2. The method according to wherein said T-cells are cytotoxic T-cells (CTLs).3. The method according to wherein said T-cells are selected from the group consisting of CD4 T-cells and CD8 T-cells.4. The method according to wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.5. The method according to claim 1 , wherein the anti-PD-L1 antibody is selected from the group consisting of atezolizumab claim 1 , avelumab claim 1 , and durvalumab.6. The method according to claim 5 , wherein the anti-PD-L1 antibody is atezolizumab.7. The method according to claim 5 , wherein the anti-PD-L1 antibody is avelumab.8. The method according to claim 5 , wherein the anti-PD-L1 antibody is durvalumab.9. A method of activating T-cells of a patient with cancer comprising administering an anti-PD-L1 antibody and an anti-PVRIG antibody to said patient claim 5 , wherein said anti-PVRIG antibody comprises:i) a heavy chain comprising SEQ ID NO: 19, andii) a light chain comprising SEQ ID NO: 24.10. The method according to wherein said T-cells are cytotoxic T-cells (CTLs).11. The method according to wherein said T-cells are selected from the group consisting of CD4 T-cells and CD8 T-cells.12. The method according to wherein said activation is measured as an increase in interferon-γ production and/or an increase in cytokine secretion.13. The method according to claim 1 , wherein the anti-PD-L1 antibody is selected from the group consisting of atezolizumab claim 1 , avelumab claim 1 , and durvalumab.14. The method according to claim 13 , wherein the anti-PD-L1 antibody is atezolizumab.15. The method ...

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Номер записи: 90
07-01-2021 дата публикации

ANTI-CD3 ANTIBODY FORMULATIONS

Номер: US20210000957A1
Автор: Shailubhai Kunwar
Принадлежит: Tiziana Life Sciences PLC

This invention relates to therapeutic, diagnostic and/or prophylactic formulations and dosages and dosing regimens of anti-CD3 antibodies, as well as to methods for using such formulations and dosages and dosing regimens. 1. A method of treating or alleviating a symptom of autoimmune disease , an inflammatory disorder , a neurodegenerative disease or cancer comprising orally administering to a subject in need thereof an anti-CD3 antibody formulation comprising a heavy chain amino acid sequence comprising the amino acid sequence of SEQ ID NO: 10 and a light chain amino acid sequence comprising the amino acid sequence of SEQ ID NO: 11 , sodium acetate , trihydrate , sodium chloride , polysorbate 80 , trehalose and methionine.2. The method of claim 1 , wherein the autoimmune disease is nonalcoholic steatohepatitis (NASH) claim 1 , Crohn's disease claim 1 , primary biliary cirrhosis (PBC) claim 1 , Type 1 diabetes claim 1 , Type 2 diabetes claim 1 , or ulcerative colitis (UC).3. The method of claim 1 , wherein the formulation further comprises EDTA.4. The method of claim 1 , wherein the formulation is a liquid.5. The method of claim 1 , wherein the formulation is a lyophilized powder.6. The method of claim 5 , wherein the liquid is in an enteric coated oral capsule.7. The method of claim 4 , wherein the lyophilized powder is in an enteric coated oral capsule.8. The method of claim 1 , wherein the formulation comprising a unit dose of the anti-CD3 antibody.9. The method of claim 8 , wherein claim 8 , the unit dose is about 0.1 mg to 10 mg.10. The method of claim 9 , wherein claim 9 , the unit dose is 0.5 mg claim 9 , 2.5 mg or 5.0 mg.11. The method of claim 4 , wherein the concentration of:a. sodium acetate trihydrate is about 10 mM to 500 mM;b. sodium chloride is about 10 mM to 500 mM;c. polysorbate 80 is about 0.01% to 1% (w/v);d. trehalose is about 5% to 50% (w/v); ande. methionine is 0.01% to 1% (w/v).12. The method of claim 11 , where the concentration of EDTA is ...

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Номер записи: 91
07-01-2016 дата публикации

REDUCING SYSTEMIC REGULATORY T CELL LEVELS OR ACTIVITY FOR TREATMENT OF DISEASE AND INJURY OF THE CNS

Номер: US20160000909A1
Автор: BARUCH Kuti, Eisenbach-Schwartz Michal, ROSENZWEIG Neta
Принадлежит:

A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session. 1. A method for treating a disease , disorder , condition or injury of the Central Nervous System (CNS) that does not include the autoimmune neuroinflammatory disease relapsing-remitting multiple sclerosis (RRMS) , said method comprising administering to an individual in need thereof an active agent that causes reduction of the level of systemic immunosuppression , wherein said active agent is administered by a dosage regime comprising at least two courses of therapy , each course of therapy comprising in sequence a treatment session followed by an interval session.2. The method according to claim 1 , wherein said active agent causes reduction of the level of systemic immunosuppression by release of a restraint imposed on the immune system by one or more immune checkpoints.3. The method according to claim 2 , wherein said reduction of the level of systemic immunosuppression is associated with an increase in systemic presence or activity of IFNγ-producing leukocytes.4. The method according to claim 2 , wherein said active agent causes reduction of the level of systemic immunosuppression and thereby an increase in the systemic presence or activity of effector T cells.5. The method according to claim 2 , wherein said active agent causes release from immunosuppression by blockade of said one or more immune checkpoints.6. The method according to claim 5 , wherein said one or more checkpoints is selected from the group consisting of ...

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Номер записи: 92
05-01-2017 дата публикации

CD300A RECEPTORS AS VIRUS ENTRY COFACTORS

Номер: US20170000849A1
Автор: AMARA Ali, CARNEC Xavier, MEERTENS Laurent
Принадлежит:

The present invention concerns an inhibitor of an interaction between CD300a and an aminophospholipid for use in preventing or treating a virus infection by inhibition of the interaction between CD300a and viral aminophospholipid. 1. A method for preventing or treating a viral infection comprising administering to an individual in need hereof a therapeutically effective amount of an inhibitor of an interaction between CD300a and viral aminophospholipid.2. The method according to claim 1 , whereinthe aminophospholipid is phosphatidylserine and/or phosphatidylethanolamine.3. The method according to claim 1 , wherein the inhibitor is(i) a CD300a inhibitor, and/or(iii) an aminophospholipid binding protein.4. The method according to claim 3 , wherein said CD300a inhibitor is an anti-CD300a antibody claim 3 , an antisense nucleic acid claim 3 , a mimetic or a variant CD300a.5. The method according to claim 3 , wherein said aminophospholipid binding protein is a phosphatidylserine binding protein and/or a phosphatidylethanolamine binding protein.6. The method according to claim 5 , wherein said phosphatidylserine binding protein is an anti-phosphatidylserine antibody or Annexin 5.7. The method according to claim 5 , wherein said phosphatidylethanolamine binding protein is an anti-phosphatidylethanolamine antibody or Duramycin.8. The method according to claim 1 , wherein said virus is an aminophospholipid harboring virus.9flavivirus.. The method according to claim 8 , wherein said aminophospholipid harboring virus is an aminophospholipid harboring10. The method according to claim 9 , wherein said aminophospholipid harboring virus is a West-Nile Virus claim 9 , Yellow Fever Virus or Dengue Virus.11. The method according to claim 1 , wherein said inhibitor is formulated for administration in combination with at least one other antiviral compound claim 1 , either sequentially or simultaneously.12. (canceled) The present invention concerns the use of an inhibitor of an ...

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Номер записи: 93
04-01-2018 дата публикации

Anti-hsp70 specific chimeric antigen receptors (cars) for cancer immunotherapy

Номер: US20180000914A1
Автор: Alexandre Juillerat, Arvind Rajpal, Barbra Johnson SASU, Julianne Smith, Julien Valton, Philippe Duchateau
Принадлежит: CELLECTIS SA

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from an anti-HSP70 monoclonal antibody, conferring specific immunity against HSP70 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating in particular leukemia.

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Номер записи: 94
04-01-2018 дата публикации

METHODS OF TREATING CEA-POSITIVE CANCERS USING PD-1 AXIS BINDING ANTAGONISTS AND ANTI-CEA/ANTI-CD3 BISPECIFIC ANTIBODIES

Номер: US20180000931A1
Автор: Bacac Marina, Colombetti Sara, Klein Christian, Sam Johannes, Saro Jose, Umana Pablo
Принадлежит: Hoffmann-La Roche Inc.

The invention provides compositions and methods for treating CEA-positive cancers. The method comprising administering a PD-1 axis binding antagonist and a bispecific antibody that targets CEA and CD3. 1. A method for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of a human PD-1 axis binding antagonist and an anti-CEA/anti-CD3 antibody.2. The method of claim 1 , wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-1 binding antagonist claim 1 , a PD-L1 binding antagonist and a PD-L2 binding antagonist.3. The method of or claim 1 , wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.4. The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to its ligand binding partners.5. The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1.6. The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L2.7. The method of claim 3 , wherein the PD-1 binding antagonist inhibits the binding of PD-1 to both PD-L1 and PD-L2.8. The method of claim 3 , wherein the PD-1 binding antagonist is an antibody.9. The method of claim 3 , wherein the PD-1 binding antagonist is selected from the group consisting of MDX 1106 (nivolumab) claim 3 , MK-3475 (pembrolizumab) claim 3 , CT-011 (pidilizumab) claim 3 , MEDI-0680 (AMP-514) claim 3 , PDR001 claim 3 , REGN2810 claim 3 , and BGB-108.10. The method of claim 2 , wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.11. The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to PD-1.12. The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to B7-1.13. The method of claim 10 , wherein the PD-L1 binding antagonist inhibits the binding of PD-L1 to both PD-1 and B7-1.14. The method of claim 10 , wherein the PD-L1 binding ...

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Номер записи: 95
04-01-2018 дата публикации

CD19 BINDING AGENTS AND USES THEREOF

Номер: US20180000961A9
Автор: Benjamin Dennis, Carter Paul, CERVENY Charles G., McDonagh Charlotte
Принадлежит:

This invention, inter alia, relates to CD19 binding agents and methods of using such CD19 binding agents for treating disease. 1. A method for treating a CD19-associated disorder in a mammalian subject comprising administering an antibody or antigen-binding fragment that specifically binds to human CD19 in an amount effective to treat the disorder in the mammalian subject; the antibody or antigen-binding fragment comprising a heavy chain variable region amino acid sequence as set forth in SEQ ID NO:29 with 0 , 1 or 2 substitutions relative to SEQ ID NO:9 and a light chain variable region amino acid sequence as set forth in SEQ ID NO:30 with 0 , 1 or 2 substitutions relative to SEQ ID NO:17; wherein the antibody or antigen-binding fragment binds to CD19 with a dissociation constant of 1×10M.2. The method of claim 1 , wherein the CD19-associated disorder is a CD19 expressing cancer.3. The method of claim 1 , wherein the heavy chain variable region has the amino acid sequence of SEQ ID NO:9.4. The method of claim 1 , wherein the light chain variable region has the amino acid sequence of SEQ ID NO:24.5. The method of claim 1 , wherein the antibody comprises a human IgG constant region and is administered.6. The method of claim 5 , wherein the isotype of the IgG constant region is IgG1 claim 5 , IgG2 claim 5 , or IgG1V1.7. The method of claim 1 , wherein the antibody or antigen-binding fragment is conjugated to an anti-tubulin agent.8. The method of claim 7 , wherein the anti-tubulin agent is an auristatin.9. The method of claim 1 , wherein the antibody or antigen-binding fragment as a ligand-drug conjugate compound claim 1 , wherein the ligand drug conjugate compound is of the following formula:{'br': None, 'sub': 'p', 'L-(LU-D)\u2003\u2003(I)'}or a pharmaceutically acceptable salt or solvate thereof;wherein:L is a ligand unit wherein the ligand unit is the antibody or antigen-binding fragment; and(LU-D) is a Linker unit-Drug unit moiety, wherein:LU- is a Linker unit, ...

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Номер записи: 96
04-01-2018 дата публикации

Antibody-urease conjugates for therapeutic purposes

Номер: US20180000963A1
Автор: Baomin Tian, Heman Chao, Kimberly Jayne GASPAR, Praveen Kumar, Wah Yau Wong
Принадлежит: Helix Biopharma Corp

Pharmaceutical compositions comprising antibody-urease conjugates and substantially free of unconjugated urease are disclosed. These compositions are prepared by a method that does not require chromatographic purification. These pharmaceutical compositions have utility in the treatment of cancer by antibody-directed enzyme prodrug therapy wherein the urease converts endogenous urea into ammonia in situ to induce cytotoxicity.

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Номер записи: 97
04-01-2018 дата публикации

BLOOD BRAIN BARRIER RECEPTOR ANTIBODIES AND METHODS OF USE

Номер: US20180000964A1
Автор: Chen Xiaocheng, Dennis Mark S., Tan Christine, Watts Ryan J., Zuchero Joy Yu
Принадлежит: Genentech, Inc.

The present invention relates to antibodies that bind to receptors expressed on the blood brain barrier and methods of using the same. 1. A method of transporting an agent across the blood-brain barrier , wherein the method comprises exposing the blood-brain barrier to an antibody which (i) binds to a blood-brain barrier receptor (BBB-R); and (ii) is coupled to the agent; wherein:the antibody, upon binding to the BBB-R, transports the agent coupled thereto across the blood-brain barrier; andthe BBB-R is a member selected from the group consisting of CD98 heavy chain (CD98hc), basigin, and Glucose Transporter Type 1 (Glut1).2. The method of claim 1 , wherein the blood-brain barrier is in a mammal.3. The method of claim 2 , wherein the mammal has a neurological disease or disorder.4. A method of treating a neurological disease or disorder in a mammal claim 2 , wherein the method comprises administering to the mammal an antibody which (i) binds to a BBB-R selected from the group consisting of CD98hc claim 2 , basigin claim 2 , and Glut1; and (ii) is coupled to a therapeutic agent which is effective for treating the neurological disease or disorder.5. The method of claim 4 , wherein the neurological disease or disorder is selected from the group consisting of Alzheimer's disease (AD) claim 4 , stroke claim 4 , dementia claim 4 , muscular dystrophy (MD) claim 4 , multiple sclerosis (MS) claim 4 , amyotrophic lateral sclerosis (ALS) claim 4 , cystic fibrosis claim 4 , Angelman's syndrome claim 4 , Liddle syndrome claim 4 , Parkinson's disease claim 4 , Pick's disease claim 4 , Paget's disease claim 4 , cancer claim 4 , and traumatic brain injury.6. The method of claim 2 , wherein the mammal is a human.7. The method of claim 1 , wherein the agent is an imaging agent.8. The method of claim 1 , wherein the agent is a neurological disorder drug.9. The method of claim 1 , wherein binding of the antibody to the BBB-R does not impair binding of the BBB-R to one or more of its ...

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Номер записи: 98
03-01-2019 дата публикации

ANTI-HUMAN PAPILLOMAVIRUS (HPV) ANTIGEN-BINDING PROTEINS AND METHODS OF USE THEREOF

Номер: US20190000956A1
Автор: Bray Kevin A., Delfino Frank, Franklin Matthew C., Garnova Elena S., Kirshner Jessica R., MacDONALD Douglas, Olson William, THURSTON Gavin
Принадлежит:

The present invention provides antigen-binding proteins that specifically bind to an HLA-displayed human papillomavirus (HPV) peptide, and therapeutic and diagnostic methods of using those binding proteins. 1. An isolated antigen-binding protein that binds specifically to a conformational epitope of an HLA-A2 presented human papillomavirus (HPV) 16 E7 peptide (HPV16E7 peptide) , wherein the conformational epitope comprises one or more amino acids of SEQ ID NO: 537 selected from the group consisting of Y11 , D14 , L15 , P17 and E18.2. The isolated antigen-binding protein of claim 1 , wherein the antigen-binding protein has a property selected from the group consisting of:{'sub': 'D', '(a) binds monomeric HLA-A2:HPV16E7 11-19 peptide with a binding dissociation equilibrium constant (K) of less than about 20 nM as measured in a surface plasmon resonance assay at 25° C.;'}{'sub': 'D', '(b) binds monomeric HLA-A2:HPV16E7 82-90 peptide with a binding dissociation equilibrium constant (K) of less than about 25 nM as measured in a surface plasmon resonance assay at 25° C.;'}{'sub': '50', '(c) binds to HLA-A2:HPV16E7 11-19 peptide expressing cells with an ECless than about 6 nM and do not bind to cells expressing predicted off-target peptides as determined by luminescence assay;'}{'sub': '50', '(d) binds to HLA-A2:HPV16E7 82-90 peptide expressing cells with an ECless than about 1 nM and do not substantially bind to cells expressing predicted off-target peptides as determined by luminescence assay;'}{'sub': '50', '(e) binds to HLA-A2:HPV16E7 11-19 peptide expressing cells with an ECless than about 30 nM as determined by flow cytometry assay; and'}{'sub': '50', '(f) binds to HLA-A2:HPV16E7 82-90 peptide expressing cells with an ECless than about 75 nM as determined by flow cytometry assay.'}3. The isolated antigen-binding protein of claim 1 , wherein the HPV16E7 peptide comprises the amino acid sequence of YMLDLQPET (SEQ ID NO: 538).4. The isolated antigen-binding protein of ...

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Номер записи: 99
07-01-2016 дата публикации

Bispecific CD33 and CD3 Binding Proteins

Номер: US20160002333A1
Автор: Claudia Wall, Erich Rajkovic, Eugene Zhukovsky, Ivica FUCEK, Jeanmarie Guenot, Judith A. Fox, Kristina Ellwanger, Lori Kunkel, Luke Evnin, Melvyn Little, Michael WEICHEL, Stefan Knackmuss, Uwe Reusch, Vera Molkenthin
Принадлежит: Amphivena Therapeutics Inc

Described herein are binding proteins that specifically bind to human CD33, and in particular to bispecific binding proteins that specifically bind to human CD33 and human CD3. Also described herein are bispecific tandem diabodies that bind to CD33 and CD33, and their uses for immunotherapy of CD33 + cancers, diseases and conditions such as acute myeloid leukemia (AML).

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Номер записи: 100