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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 8332. Отображено 100.
19-04-2012 дата публикации

Mice That Make VL Binding Proteins

Номер: US20120096572A1
Автор: Andrew J. Murphy, Cagan Gurer, Karolina A. Hosiawa, Lynn Macdonald, Sean Stevens
Принадлежит: Regeneron Pharmaceuticals Inc

Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.

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Номер записи: 1
14-06-2012 дата публикации

Stable Heterodimeric Antibody Design with Mutations in the Fc Domain

Номер: US20120149876A1
Автор: David Kai Yuen Poon, Eric Escobar Cabrera, Igor Edmondo Paolo D'angelo, Paula Irene Lario, Surjit Bhimarao Dixit, Thomas SPRETER VON KREUDENSTEIN
Принадлежит: Zymeworks Inc Canada

The provided scaffolds have heavy chains that are asymmetric in the various domains (e.g. CH2 and CH3) to accomplish selectivity between the various Fc receptors involved in modulating effector function, beyond those achievable with a natural homodimeric (symmetric) Fc molecule, and increased stability and purity of the resulting variant Fc heterodimers. These novel molecules comprise complexes of heterogeneous components designed to alter the natural way antibodies behave and that find use in therapeutics.

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Номер записи: 2
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: 3
20-09-2012 дата публикации

Antigen Binding Proteins

Номер: US20120237506A1
Автор: Birgit Bossenmaier, Christian Klein, Claudio Sustmann, Hubert Kettenberger, Joerg-Thomas Regula, Klaus-Peter Kuenkele, Manfred Schwaiger, Wolfgang Schaefer
Принадлежит: Hoffmann La Roche Inc

The present invention relates to antigen binding proteins comprising two Fc parts, methods for their production, pharmaceutical compositions containing said antigen binding proteins, and uses thereof.

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Номер записи: 4
20-09-2012 дата публикации

Antibody Substituting for Function of Blood Coagulation Factor VIII

Номер: US20120237517A1
Автор: Hiroyuki Saito, Kunihiro Hattori, Taro Miyazaki, Tetsuhiro Soeda, Tetsuo Kojima
Принадлежит: Chugai Pharmaceutical Co Ltd

The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

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Номер записи: 5
14-02-2013 дата публикации

Dye Conjugated Peptides for Fluorescent Imaging

Номер: US20130039861A1
Автор: Celeste Aida S. Regino, Chien-Hsing Chang, David M. Goldenberg, William J. Mcbride
Принадлежит: Immunomedics Inc

The present application discloses compositions and methods of use of dye conjugated peptides for fluorescent detection, diagnosis and/or imaging. In preferred embodiments, the compositions comprise a DNL complex comprising an anti-hapten antibody or antigen-binding fragment thereof conjugated to an AD moiety and a DDD moiety conjugated to an antibody or antigen-binding fragment thereof that binds to the target antigen, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety to form the DNL complex. More preferably, the compositions comprise a targetable construct comprising at least one hapten and a fluorescent probe. Binding of the DNL complex to the target antigen and of the hapten on the targetable construct to the DNL complex results in fluorescent labeling of the target antigen. Most preferably, fluorescent imaging is of use in intraoperative, intraperitoneal, laparoscopic, endoscopic or intravascular procedures for detection of diseased tissues.

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Номер записи: 6
28-03-2013 дата публикации

BISPECIFIC BINDING MOLECULES BINDING TO DII4 AND ANG2

Номер: US20130078247A1
Автор: BOUCNEAU Joachim, BUYSE Marie-Ange, DEPLA Erik, GSCHWIND Andreas, OTT Rene Georg
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Bispecific binding molecules binding to both DII4 and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with DII4- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described. 1. A bispecific binding molecule comprising at least one Ang2-binding component and at least one DII4-binding component.2. The bispecific binding molecule of claim 1 , further comprising at least one serum albumin binding component.3. The bispecific binding molecule of claim 1 , comprising a DII4-binding component comprising at least a variable domain with four framework regions and three complementarity determining regions CDR1 claim 1 , CDR2 and CDR3 claim 1 , respectively claim 1 , wherein said CDR3 has an amino acid sequence selected from amino acid sequences shown ina. SEQ IDs NOs: 1 to 166 and 458,b. SEQ ID NOs: 333 to 353, orc. SEQ ID NOs: 375 to 395.4. The bispecific binding molecule of claim 3 , the DII4-binding component of which is an isolated immunoglobulin single variable domain or a polypeptide containing one or more of said immunoglobulin single variable domains claim 3 , wherein said immunoglobulin single variable domain consists of four framework regions and three complementarity determining regions CDR1 claim 3 , CDR2 and CDR3 claim 3 , respectively claim 3 , and wherein said CDR3 has an amino acid sequence selected from amino acid sequences shown ina. SEQ ID NOs: 1 to 166 and 458,b. SEQ ID NOs: 333 to 353, orc. SEQ ID NOs: 375 to 395.5. The bispecific binding molecule of claim 4 , wherein said one or more immunoglobulin single variable domain containa. a CDR3 with an amino acid sequence selected from a first group of amino acid sequences shown in SEQ ID NOs: 1 to 166;b. a CDR1 and a CDR2 with ...

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Номер записи: 7
28-03-2013 дата публикации

Bispecific binding molecules binding to vegf and ang2

Номер: US20130078248A1
Автор: Andreas Gschwind, Erik Depla, Joachim BOUCNEAU, Marie-Ange Buyse, Rene Georg OTT
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Bispecific binding molecules binding to both VEGF and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with VEGF- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.

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Номер записи: 8
28-03-2013 дата публикации

BISPECIFIC T CELL ACTIVATING ANTIGEN BINDING MOLECULES

Номер: US20130078249A1
Автор: Ast Oliver, Bruenker Peter, Fauti Tanja, Freimoser-Grundschober Anne, Jaeger Christiane, Klein Christian, Moessner Ekkehard, Umana Pablo
Принадлежит:

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1. A T cell activating bispecific antigen binding molecule comprising a first and a second antigen binding moiety , one of which is a Fab molecule capable of specific binding to an activating T cell antigen and the other one of which is a Fab molecule capable of specific binding to a target cell antigen , and an Fc domain composed of a first and a second subunit capable of stable association; (a) a single chain Fab molecule wherein the Fab light chain and the Fab heavy chain are connected by a peptide linker, or', '(b) a crossover Fab molecule wherein either the variable or the constant regions of the Fab light chain and the Fab heavy chain are exchanged., 'wherein the first antigen binding moiety is'}2. The T cell activating bispecific antigen binding molecule of claim 1 , comprising not more than one antigen binding moiety capable of specific binding to an activating T cell antigen.3. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the first and the second antigen binding moiety are fused to each other claim 1 , optionally via a peptide linker.4. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the second antigen binding moiety is fused at the C-terminus of the Fab heavy chain to the N-terminus of the Fab heavy chain of the first antigen binding moiety.5. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the first antigen binding moiety is fused at ...

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Номер записи: 9
28-03-2013 дата публикации

BISPECIFIC T CELL ACTIVATING ANTIGEN BINDING MOLECULES

Номер: US20130078250A1
Автор: Ast Oliver, Fauti Tanja, Jaeger Christiane, Klein Christian, Umana Pablo
Принадлежит:

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease. 1. A T cell activating bispecific antigen binding molecule comprising a first and a second single chain Fv (scFv) molecule fused to each other , wherein the first scFv molecule is capable of specific binding to a target cell antigen and the second scFv molecule is capable of specific binding to an activating T cell antigen;characterized in that the T cell activating bispecific antigen binding molecule further comprises an Fc domain composed of a first and a second subunit capable of stable association.2. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the first scFv molecule is fused at the C-terminus to the N-terminus of the second scFv molecule claim 1 , and the second scFv molecule is fused at the C-terminus to the N-terminus of the first or the second subunit of the Fc domain.3. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the second scFv molecule is fused at the C-terminus to the N-terminus of the first scFv molecule claim 1 , and the first scFv molecule is fused at the C-terminus to the N-terminus of the first or the second subunit of the Fc domain.4. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the Fc domain is an IgG claim 1 , specifically an IgGor IgG claim 1 , Fc domain.5. The T cell activating bispecific antigen binding molecule of claim 1 , wherein the Fc domain is a human Fc domain.6. The T cell activating bispecific antigen ...

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Номер записи: 10
11-04-2013 дата публикации

METHOD FOR MAKING HETEROMULTIMERIC POLYPEPTIDES

Номер: US20130089553A1
Автор: Carter Paul J., Presta Leonard G., Ridgway John B.
Принадлежит: Genentech, Inc.

The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins, heteromultimers and antibody-immunoadhesin chimeras. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis. 1. A method of preparing a heteromultimer comprising a first polypeptide and a second polypeptide which meet at an interface , wherein the interface of the first polypeptide comprises a protuberance which is positionable in a cavity in the interface of the second polypeptide , the method comprising the steps of:(a) culturing a host cell comprising nucleic acid encoding the first polypeptide and second polypeptide, wherein the nucleic acid encoding the first polypeptide has been altered from the original nucleic acid to encode the protuberance or the nucleic acid encoding the second polypeptide has been altered from the original nucleic acid to encode the cavity, or both, wherein the culturing is such that the nucleic acid is expressed, and wherein the host cell is a yeast cell; and(b) recovering the heteromultimer from the host cell culture.2. The method of wherein the nucleic acid encoding the first polypeptide has been altered from the original nucleic acid to encode the protuberance and the nucleic acid encoding the second polypeptide has been altered from the original nucleic acid to encode the cavity.3. The method of wherein step (a) is preceded by a step wherein nucleic acid encoding an original amino acid residue from the interface of the first polypeptide is replaced with nucleic acid encoding an import amino acid residue having a ...

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Номер записи: 11
11-04-2013 дата публикации

RON Binding Constructs and Methods of Use Thereof

Номер: US20130089554A1
Автор: Algate Paul A., Blankenship John W., Chenault Ruth A., Natarajan Sateesh Kumar, TAN Philip
Принадлежит: Emergent Product Development Seattle, LLC

This disclosure provides immunoglobulin binding molecules that specifically bind to human macrophage stimulating receptor (MST1 R, also referred to herein as recepteur d'origine Nantaise or RON), including antibodies and monospecific and multispecific single chain binding proteins having one or more other domains, such as one or more antibody constant region domains. Also provided are therapeutic applications of such binding proteins, such as for the treatment of cancer and inflammatory disorders. 135-. (canceled)36. A multi-specific fusion protein comprising (i) a RON binding domain , (ii) a CD3 binding domain and (iii) an immunoglobulin constant region or sub-region thereof between the RON and CD3 binding domains.37. The multi-specific fusion protein of claim 36 , wherein the immunoglobulin constant region or sub-region thereof comprises an immunoglobulin Fc region or an immunoglobulin CH2CH3 domain.38. The multi-specific fusion protein of claim 37 , wherein the immunoglobulin CH2CH3 domain is from an IgG1 claim 37 , IgG2 claim 37 , IgG3 claim 37 , IgG4 claim 37 , IgA1 claim 37 , IgA2 or IgD.39. The multi-specific fusion protein of claim 36 , wherein the multi-specific fusion protein does not comprise an immunoglobulin CH1 domain.40. The multi-specific fusion protein of claim 37 , wherein the immunoglobulin Fc region or CH2CH3 domain comprises(i) an amino acid substitution at the asparagine of position 297 and one amino acid substitution at position 234, 235, 236 or 237;(ii) an amino acid substitution at the asparagine of position 297 and amino acid substitutions at two of positions 234-237;(iii) an amino acid substitution at the asparagine of position 297 and amino acid substitutions at three of positions 234-237;(iv) an amino acid substitution at the asparagine of position 297, amino acid substitutions at positions 234, 235 and 237, and an amino acid deletion at position 236;(v) amino acid substitutions at three of positions 234-237 and amino acid substitutions ...

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Номер записи: 12
11-04-2013 дата публикации

BONE MORPHOGENETIC PROTEIN RECEPTOR BINDING AGENTS AND METHODS OF THEIR USE

Номер: US20130089560A1
Автор: Chartier-Courtaud Cecile, GURNEY AUSTIN L.
Принадлежит: OncoMed Pharmaceuticals Inc

The present invention provides bone morphogenetic protein receptor (BMPR) binding agents, such as antibodies, and compositions comprising said binding agents. The binding agents are useful to treat diseases such as cancer. 1106-. (canceled)107. An isolated monoclonal antibody that specifically binds an extracellular domain of at least one bone morphogenetic protein receptor (BMPR) selected from the group consisting of: BMPR1A , BMPR1B , BMPR2 , ACVR2A and ACVR2B , wherein the antibody is:(i) an agonist of the BMP pathway, or(ii) an antagonist of the BMP pathway.108. The antibody of claim 107 , which is a recombinant antibody claim 107 , a monoclonal antibody claim 107 , a chimeric antibody claim 107 , a bispecific antibody claim 107 , a humanized antibody claim 107 , a human antibody claim 107 , or an antibody fragment.109. The antibody of claim 107 , which:(i) modulates BMP pathway activity;(ii) stimulates BMP pathway activity,(iii) increases BMPR activation, and/or(iv) inhibits tumor growth.110. A pharmaceutical composition comprising the antibody of and a pharmaceutically acceptable carrier.111. A cell comprising or producing the antibody of .112. An isolated polynucleotide molecule comprising a polynucleotide that encodes the antibody of .113. A method of modulating BMP pathway signaling in a cell claim 107 , comprising contacting the cell with an effective amount of the antibody of .114. The method of claim 113 , wherein the modulation is a stimulation of BMP pathway signaling.115. A method of inhibiting tumor growth in a subject claim 107 , comprising administering to the subject a therapeutically effective amount of the antibody of .116. The method of claim 115 , wherein the tumor is a colorectal tumor claim 115 , a breast tumor claim 115 , a prostate tumor claim 115 , a pancreatic tumor claim 115 , a lung tumor claim 115 , a head and neck tumor claim 115 , a glioblastoma tumor or a melanoma tumor.117. The method of claim 115 , further comprising ...

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Номер записи: 13
18-04-2013 дата публикации

ANTIBODY POLYPEPTIDES THAT ANTAGONIZE CD40L

Номер: US20130095109A1
Автор: BRYSON James William, DREW Philip, GRANT Steven, Ignatovich Olga, Nadler Steven G., Price Laura, REHFUSS Robert P., Suchard Suzanne J., SURI Anish, TAMURA James K., YAMNIUK Aaron
Принадлежит:

Antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The antibody polypeptides are useful in the treatment of diseases involving CD40L activation, such as graft-related diseases and autoimmune diseases. The antibody polypeptides may be domain antibodies (dAbs) comprising a single Vor Vdomain. The half-life of the antibody polypeptides may be increased by modifying the antibody polypeptides to be dual specific reagents that can also bind human serum albumin (HSA) or another antigen. 1. An isolated antibody polypeptide comprising a first variable domain that specifically binds human CD40L , wherein CD40L comprises the amino acid sequence of SEQ ID NO: 1 , wherein the amino acid sequence of the first variable domain comprises(a) a CDR1 region which differs from the CDR1 region of BMS2h-572-633 by up to three amino acids,(b) a CDR2 region which differs from the CDR2 region of BMS2h-572-633 by up to three amino acids,(c) a CDR3 region which differs from the CDR3 region of BMS2h-572-633 by up to three amino acids,(d) a FR1 region which differs from the FR1 region of BMS2h-572-633 by up to three amino acids,(e) a FR2 region which differs from the FR2 region of BMS2h-572-633 by up to three amino acids,(f) a FR3 region which differs from the FR3 region of BMS2h-572-633 by up to three amino acids, and(g) a FR4 region which differs from the FR4 region of BMS2h-572-633 by up to three amino acids; andwherein the antibody polypeptide inhibits binding of CD40L to CD40 with an EC50 of 100 pM to 100 nM.2. The antibody polypeptide of claim 1 , wherein the amino acid sequence of the first variable domain comprises(a) a CDR1 region which differs from the CDR1 region of BMS2h-572-633 by up to three amino acids,(b) a CDR2 region which differs from the CDR2 region of BMS2h-572-633 by up to three amino acids, and(c) a CDR3 region which differs from the CDR3 region of BMS2h-572-633 by up to three amino acids.3. The ...

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Номер записи: 14
25-04-2013 дата публикации

Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) Single Chain FV Antibody Fragment Conjugates and Methods of Use Thereof

Номер: US20130101607A1
Автор: Kipps Thomas J., YU Jianqiang
Принадлежит:

Compositions including an antibody single-chain variable fragment (scFv) conjugate that specifically binds to ROR1 tumor-associated antigen are provided. The anti-ROR1 scFv antibody and conjugates may include a biologically-active molecule. Such conjugates may comprise a chimeric receptor to direct T cells to respond to ROR1 cancer cells, Methods to use the scFV conjugates to target cells expressing ROR1 for therapeutic and diagnostic purposes are also provided. 1. An antibody single-chain variable fragment (scFv) conjugate comprising ,an scFv having an amino acid sequence at least 90% identical to SEQ ID NO: 1 or SEQ ID NO: 2; anda biologically active molecule.2. The conjugate of claim 1 , wherein the amino acid sequence of the scFv is at least 95% identical to SEQ ID NO: 1 or SEQ ID NO: 2.3. The conjugate of claim 1 , wherein the amino acid sequence of the scFv is 100% identical to SEQ LD NO: 1 or SEQ LD NO: 2.4. The conjugate of claim 1 , wherein the scFv has a binding specificity of an antibody as produced by a hybridoma having Accession No. PTA 8634 by the American Type Culture Collection.5. The conjugate of claim 1 , wherein the biologically active molecule is selected from the group consisting of a polypeptide claim 1 , a peptidomimetic claim 1 , a nucleic acid molecule claim 1 , a lipid claim 1 , a drug compound claim 1 , chemotherapeutic agent claim 1 , an antagonist and an agonist.6. The conjugate of claim 5 , wherein the biologically active molecule is a polypeptide.7. The conjugate of claim 6 , wherein the polypeptide is an antibody or an antibody fragment.8. The conjugate of claim 7 , wherein the antibody fragment is selected from the group consisting of a Fab fragment claim 7 , a F(ab)2 fragment claim 7 , an FV fragment claim 7 , a single chain FV (scFV) fragment claim 7 , a dsFV fragment claim 7 , a CH fragment and a dimeric scFV.9. The conjugate of claim 8 , wherein the CH fragment is an IgG CH fragment.10. The conjugate of claim 9 , wherein the IgG ...

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Номер записи: 15
25-04-2013 дата публикации

Antibody Molecules Which Bind IL-17A and IL-17F

Номер: US20130102030A1
Автор: ADAMS RALPH, POPPLEWELL ANDREW GEORGE, Rapecki Stephen Edward
Принадлежит: UCB PHARMA S.A.

The invention relates to antibody molecules having specificity for antigenic determinants of both IL-17A and IL-17F, therapeutic uses of the antibody molecules and methods for producing said antibody molecules. 128-. (canceled)29. An isolated DNA sequence encoding a neutralising antibody which binds human IL-17A and human IL-17F , 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 wherein the variable domain of the light chain comprises the sequence given in SEQ ID NO: 4 for CDR-L1 , the sequence given in SEQ ID NO: 5 for CDR-L2 and the sequence given in SEQ ID NO: 6 for CDR-L3 , or an antigen-binding fragment thereof.30. A cloning or expression vector comprising the DNA sequences according to .31. The vector according to claim 30 , wherein the vector comprises the sequences given in SEQ ID NO: 14 and SEQ ID NO: 18.32. A host cell comprising the vector according to .33. A process for the production of an antibody claim 32 , comprising culturing the host cell of and isolating the antibody.3437-. (canceled)38. A host cell comprising the vector according to .39. A process for the production of an antibody claim 38 , comprising culturing the host cell of and isolating the antibody.40. An isolated DNA sequence encoding a neutralising antibody which binds human IL-17A and human IL-17F claim 38 , wherein the heavy chain comprises the sequence given in SEQ ID NO: 15 and wherein the light chain comprises the sequence given in SEQ ID NO: 11 claim 38 , or an antigen-binding fragment thereof.41. A cloning or expression vector comprising the DNA sequences according to .42. A host cell comprising the vector according to .43. A process for the production of an antibody claim 42 , comprising culturing the host cell of and isolating the antibody.44. An isolated DNA sequence encoding a neutralising antibody which binds human IL- ...

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Номер записи: 16
02-05-2013 дата публикации

PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER

Номер: US20130108639A1
Автор: LEE Jae-il
Принадлежит: SAMSUNG ELECTRONICS CO., LTD.

The invention provides a fusion protein comprising (a) a first protein comprising a polypeptide which specifically binds to Annexin A1 and (b) a second protein comprising a polypeptide which induces a cytotoxic activity of a cytotoxic lymphocyte, pharmaceutical compositions comprising the fusion protein, and methods of treating or preventing cancer by administering the pharmaceutical compositions. 1. A fusion protein comprising:(a) a first protein comprising a polypeptide which specifically binds to Annexin A1 and(b) a second protein comprising a polypeptide which induces a cytotoxic activity of a cytotoxic lymphocyte.2. The fusion protein of claim 1 , wherein the fusion protein further comprises a linker which links the first protein with the second protein.3. The fusion protein of claim 1 , wherein the first protein is a full-length antibody or an antigen binding fragment thereof.4. The fusion protein of claim 1 , wherein the first protein comprises the amino acid sequence of X-Trp-Gly-His-X-X-Trp (SEQ ID NO: 119) claim 1 , wherein Xand Xare independently an amino acid selected from the group consisting of Ala claim 1 , Ile claim 1 , Leu claim 1 , Met claim 1 , Phe claim 1 , Pro claim 1 , Trp claim 1 , Val claim 1 , Asn claim 1 , Cys claim 1 , Gln claim 1 , Gly claim 1 , Ser claim 1 , Thr claim 1 , Tyr claim 1 , Asp claim 1 , Glu claim 1 , Arg claim 1 , His claim 1 , and Lys claim 1 , and{'sub': '3', 'wherein Xis an amino acid selected from the group consisting of Ala, Ile, Leu, Met, Phe, Pro, Trp, Val, Asn, Cys, Gln, Gly, Ser, Thr, and Tyr.'}5. The fusion protein of claim 4 , wherein the amino acid sequence is selected from the group consisting of SEQ ID NOS: 1 to 8.6. The fusion protein of claim 1 , wherein the first protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 9 to 42.7. The fusion protein of claim 1 , wherein the second protein specifically binds to a surface marker of the cytotoxic lymphocyte.8. The fusion protein ...

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Номер записи: 17
02-05-2013 дата публикации

ANTIKINE ANTIBODIES THAT BIND TO MULTIPLE CC CHEMOKINES

Номер: US20130108640A1
Автор: ALLISON Dan, Raport Carol
Принадлежит:

An antikine antibody binds to two, three, four, five or more CC chemokines, such as RANTES/CCL5, MIP-1α/CCL3, MIP-1β/CCL4, or MCP-1/CCL2. Methods for affinity maturation and humanization of antikine antibodies as well as the production of hybridoma cell lines producing antikine antibodies by sequential immunization are also disclosed. 146.-. (canceled)47. An isolated antibody or antigen binding fragment thereof that binds to at least three different CC chemokines.48. The isolated antibody or antigen binding fragment thereof of that binds to CCL3/MIP-1α.49. The isolated antibody or antigen binding fragment thereof of that binds to CCL4/MIP-1β.50. The isolated antibody or antigen binding fragment thereof of that binds to CCL5/RANTES.51. The isolated or purified monoclonal antibody of that is a chimeric monoclonal antibody or an antigen binding fragment thereof.52. The isolated or purified monoclonal antibody of that is a humanized monoclonal antibody or an antigen binding fragment thereof.53. The isolated or purified monoclonal antibody of that is a full-length monoclonal antibody.54. An antigen binding fragment of the isolated or purified monoclonal antibody of .55. The fragment of that is an Fab′ or F(ab′)2.56. The monoclonal antibody or fragment thereof of that has been conjugated to an effector moiety claim 47 , targeting moiety claim 47 , heterologous protein claim 47 , toxin claim 47 , enzyme claim 47 , cytokine claim 47 , chemical tag claim 47 , radiological tag claim 47 , a substance that increases its biological half-life or a substance that increases its biological availability.57. A composition comprising (i) the isolated or purified monoclonal antibody or the fragment thereof of and (ii) a carrier or excipient.58. A kit for use in a therapeutic or diagnostic procedure that comprises one more antikine antibodies claim 47 , at least one positive control antibody claim 47 , at least one negative control antibody claim 47 , at least one CC chemokine bound by ...

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Номер записи: 18
02-05-2013 дата публикации

AMINO ACID SEQUENCES OF NANOBODIES DIRECTED AGAINST P19 SUBUNIT OF THE HETERODIMERIC CYTOKINE IL-23

Номер: US20130109842A1
Автор: De Brabandere Veronique, Lauwereys Marc Jozef, Morizzo Erika, Rommelaere Heidi, Union Ann, Verheyden Gert
Принадлежит: Ablynx N.V.

The present invention relates to amino acid sequences that are directed against the p19 subunit of IL-23; as well as protein, constructs and compounds comprising the same; and also nucleic acids encoding the same. 1. Amino acid sequence that is a variant of PMP119A3 (SEQ ID NO:1) that comprises , compared to the amino acid sequence of PMP119A3 , (i) at least one and preferably both of the mutations H37Y and M43K; (ii) a valine residue at position 78; (iii) at least one , preferably at least two , and more preferably three , four of five humanizing substitutions; (iv) as well as optionally one or more further suitable amino acid substitutions.2. Amino acid sequence that is a variant of 119A3(H37Y-M43K) (SEQ ID NO:2) that comprises , compared to the amino acid sequence of PMP119A3(H37Y-M43K) , (i) a valine residue at position 78; (ii) at least one , preferably at least two , and more preferably three , four of five humanizing substitutions; (iii) as well as optionally one or more further suitable amino acid substitutions.3. Amino acid sequence that is a variant of 119A3v17 (SEQ ID NO:3) that comprises , compared to the amino acid sequence of 119A3v17 , (i) a valine residue at position 78; (ii) optionally 1 to 5 , such as one , two or three further amino acid differences compared to the sequence of 119A3v17.4. Amino acid sequence , chosen from 119A3v18(SEQ ID NO:4) , 119A3v20 (SEQ ID NO:5) , 119A3v21 (SEQ ID NO:6) or 119A3v22 (SEQ ID NO: 7).5. Protein or polypeptide that essentially consists of an amino acid sequence according to .6. Protein or polypeptide that comprises an amino acid sequence according to .7. Protein or polypeptide that comprises an amino acid sequence according to and one or more other groups claim 1 , residues claim 1 , moieties claim 1 , binding domains or binding units.8. Protein or polypeptide that comprises an amino acid sequence according to and one or more other immunoglobulin single variable domains claim 1 , VHH's claim 1 , (single) domain ...

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Номер записи: 19
09-05-2013 дата публикации

HETERODIMERIC PROTEINS AND METHODS FOR PRODUCING AND PURIFYING THEM

Номер: US20130115208A1
Автор: HO Wei-Hsien, Pons Jaume, RAJPAL ARVIND, STROP Pavel
Принадлежит: RINAT NEUROSCIENCE CORP.

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglobulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided. 1. A heterodimeric protein comprising:a hinge region comprising a first immunoglobulin-like hinge polypeptide and a second immunoglobulin-like hinge polypeptide which interact together to form a dimeric hinge interface, wherein electrostatic interactions between one or more charged amino acids within the hinge interface favor interaction between the first and second hinge polypeptides over interaction between two first hinge polypeptides or two second hinge polypeptides, thereby promoting heterodimer formation over homodimer formation.2. The heterodimeric protein of claim 1 , wherein the hinge region is an IgG hinge region.3. (canceled)4. The heterodimeric protein of claim 2 , wherein the first hinge polypeptide comprises at least one amino acid modification relative to a wild-type IgG hinge region; and the second hinge polypeptide comprises at least one amino acid modification relative to a wild-type IgG hinge region at the same position as the amino acid modification in the first hinge polypeptide claim 2 , wherein the wild-type amino acid in the second hinge polypeptide is replaced with an amino acid having an opposite charge to the corresponding amino acid modification in the first hinge polypeptide.5. The heterodimeric protein of claim 4 , wherein the amino acid modifications are selected from the group consisting of Lys claim 4 , Arg claim 4 , Asp claim 4 , and Glu.6. The heterodimeric protein of claim 4 , wherein the IgG hinge region comprises a human IgG hinge region.7. The heterodimeric protein of claim 6 , wherein the human IgG hinge region comprises a ...

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Номер записи: 20
09-05-2013 дата публикации

Domain insertion immunoglobulin

Номер: US20130115215A1
Автор: Hongxing Zhou
Принадлежит: AMGEN INC

Described herein is an antibody format, which is amenable to bispecific antibody creation. This format is referred to herein as “Domain Insertion Immunoglobulin G” or “(Di-IgG)”. The Di-IgG molecules are capable of specifically binding two different antigens simultaneously, show high level recombinant expression, and are sufficiently aggregation-free to be amenable to commercial production. Further described herein are, Di-IgG-encoding nucleic acids and vectors, host cells for making Di-IgGs, Di-IgG pharmaceutical compositions, and methods of treatment.

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Номер записи: 21
16-05-2013 дата публикации

Compositions and Methods for Increasing Muscle Mass and Muscle Strength by Specifically Antagonizing GDF8 and or Activin A

Номер: US20130122007A1
Автор: Latres Esther, Stitt Trevor
Принадлежит: Regeneron Pharmaceuticals, Inc.

The present invention provides compositions and methods which involve specifically antagonizing GDF8 and Activin A. In certain embodiments, compositions are provided which comprise a GDF8-specific binding protein and an Activin A-specific binding protein. For example, the invention includes compositions comprising an anti-GDF8 antibody and an anti-Activin A antibody. In other embodiments, antigen-binding molecules are provided which comprise a GDF8-specific binding domain and an Activin A-specific binding domain. For example, the invention includes bispecific antibodies that bind GDF8 and Activin A. The compositions of the present invention are useful for the treatment of diseases and conditions characterized by reduced muscle mass or strength, as well as other conditions which are treatable by antagonizing GDF8 and/or Activin A activity. 1. A composition comprising a GDF8-specific binding protein and an Activin A-specific binding protein.2. The composition of claim 1 , wherein the GDF8-specific binding protein is an anti-GDF-8 antibody or antigen-binding fragment thereof.3. The composition of claim 1 , wherein the Activin A-specific binding protein is an anti-Activin A antibody or antigen-binding fragment thereof.4. The composition of claim 1 , wherein the GDF8-specific binding protein is an anti-GDF-8 antibody or antigen-binding fragment thereof claim 1 , and wherein the Activin A-specific binding protein is an anti-Activin A antibody or antigen-binding fragment thereof.5. The composition of claim 2 , wherein the anti-GDF8 antibody or antigen-binding fragment thereof comprises the heavy chain complementarity determining regions (HCDRs) of a heavy chain variable region (HCVR) comprising SEQ ID NO:9 claim 2 , and the light chain complementarity determining regions (LCDRs) of a light chain variable region (LCVR) comprising SEQ ID NO:13 claim 2 ,6. The composition of claim 5 , wherein the anti-GDF8 antibody or antigen-binding fragment thereof comprises three HCDRs ...

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Номер записи: 22
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: 23
23-05-2013 дата публикации

COMPOSITIONS COMPRISING CROSS-SPECIES-SPECIFIC ANTIBODIES AND USES THEREOF

Номер: US20130129729A1
Автор: Cierpka Ronny, KISCHEL Roman, Kufer Peter, Rau Doris, Raum Tobias, Schlereth Bernd
Принадлежит:

The present invention relates to uses of bispecific antibodies exhibiting cross-species specificity for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of the same in non-human species and humans. The present invention moreover relates to methods for evaluating the in vivo safety and/or activity and/or pharmacokinetic profile of said bispecific antibodies exhibiting cross-species specificity. The present invention also relates to methods of measuring the biological activity and/or efficacy of such bispecific antibodies exhibiting cross-species specificity. In addition, the present invention relates to pharmaceutical compositions comprising bispecific single chain antibodies exhibiting cross-species specificity and to methods for the preparation of pharmaceutical compositions comprising said bispecific single chain antibodies exhibiting cross-species specificity for the treatment of diseases. 1. A bispecific single chain antibody which comprises(i) a first binding domain binding to an epitope of human and non-chimpanzee primate CD3, and(ii) a second binding domain binding to a cell surface antigen,wherein the epitope comprises the amino acid sequence “FSEXE” (SEQ ID NO. 204), wherein “X” represents L (Leucine) or M (Methionine).2. (canceled)3. The bispecific single chain antibody of claim 1 , wherein said first binding domain is located C-terminally or N-terminally to the second binding domain.4. The bispecific single chain antibody of claim 1 , wherein the second binding domain binds to a human cell surface antigen and to the non-chimpanzee primate homolog of said cell surface antigen.5. The bispecific single chain antibody of claim 1 , wherein the cell surface antigen is a tumor antigen.6. The bispecific single chain antibody of claim 1 , wherein the first binding domain comprises a VH region having an amino acid sequence as shown in any of SEQ ID NOs. 2 claim 1 , 110 or 6.7. The bispecific single chain antibody of claim 1 , wherein the ...

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Номер записи: 24
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: 25
23-05-2013 дата публикации

METHOD FOR PRESERVING FOOD

Номер: US20130129732A1
Автор: Lässker Rebecca, RITZER Edwin
Принадлежит: LANXESS DEUTSCHLAND GMBH

Method for producing microbially stabilized foods characterized in that a food containing a dialkyl dicarbonate is treated by means of electroporation. 1. Method for producing microbially stabilized foods , characterized in that a food containing a dialkyl dicarbonate is treated by means of electroporation.3. Method according to claim 1 , characterized in that the dialkyl dicarbonate is dimethyl dicarbonate.4. Method according to claim 1 , characterized in that the food is a drink.5. Method according to claim 1 , characterized in that the food is tea-based drinks including green tea claim 1 , black tea and other tea varieties claim 1 , and also acidified drinks having a pH≦4.2 claim 1 , carbonated and noncarbonated alcohol-free soft drinks claim 1 , fruit juices claim 1 , fruit nectars claim 1 , fruit juice-containing drinks claim 1 , fruit preparations claim 1 , wines claim 1 , alcohol-free drinks claim 1 , ciders claim 1 , ice teas claim 1 , alcoholic mixed drinks claim 1 , flavoured waters claim 1 , sports drinks or isotonic drinks.6. Method according to claim 1 , characterized in that a further antimicrobially active preservative is additionally added to the food that is to be treated.7. Method according to claim 1 , characterized in that at least one further antimicrobially active preservative from the group benzoic acid claim 1 , benzoates claim 1 , sorbic acid claim 1 , sorbates claim 1 , propionic acid claim 1 , propionates claim 1 , nisin claim 1 , sulphur dioxide claim 1 , EDTA and lysozyme is additionally added to the food that is to be treated.8. Method according to claim 1 , characterized in that the energy density introduced into the food drink by means of electroporation is 1 to 1000 J/ml.9. Method according to claim 1 , characterized in that claim 1 , as electroporation claim 1 , the pulsed electric field method is used.10. Method according to claim 1 , characterized in that the dialkyl dicarbonate is added in an amount of 10 to 250 ppm claim 1 , ...

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Номер записи: 26
23-05-2013 дата публикации

Humanized anti-egfl7 antibodies and methods using same

Номер: US20130129733A1
Автор: Jill Fredrickson, Mark S. Dennis, Weilan Ye
Принадлежит: Genentech Inc

The present invention concerns antibodies to EGFL7 and the uses of same.

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Номер записи: 27
23-05-2013 дата публикации

ANTI-SERUM ALBUMIN BINDING VARIANTS

Номер: US20130129746A1
Автор: De Angelis Elena, Enever Carolyn, Liu Haiqun, Pupecka-Swider Malgorzata, Schon Oliver
Принадлежит:

The invention relates to improved variants of the anti-serum albumin immunoglobulin single variable domain DOM7h-11, as well as ligands and drug conjugates comprising such variants, compositions, nucleic acids, vectors and hosts. 142-. (canceled)43. An anti-serum albumin (SA) immunoglobulin single variable domain variant of DOM7h-11 (SEQ ID NO: 438) , said variant having a Tm of at least 54° C.44. An anti-SA immunoglobulin as claimed in claim 43 , wherein said variant comprises at least one mutation at position 22 claim 43 , 42 or 91 (numbering according to Kabat) compared to DOM7h-11 claim 43 , and claim 43 , wherein said variant is a variant of DOM7h-11-15 (SEQ ID NO: 2) and comprises at least one mutation at position 22 claim 43 , 42 claim 43 , or 91 (numbering according to Kabat) compared to DOM7h-11-15.45. The variant of any of claim 43 , wherein the variant comprises at least one mutation selected from the following:Position 22=Ser, Phe, Thr, Ala or Cys;Position 42=Glu or Asp;Position 91=Thr or Ser.46. An anti-SA immunoglobulin single variable domain variant as claimed in wherein position 22 is Ser or Phe; or wherein position 42 is Glu and position 91 is Thr; or wherein position 91 is Thr; or wherein position 22 is Phe.47. The variant of claim 43 , wherein the variant comprises an amino acid sequence that is identical to the amino acid sequence of a single variable domain selected from DOM7h-11-56 (SEQ ID NO: 412) claim 43 , DOM7h-11-68 (SEQ ID NO: 416) claim 43 , DOM7h-11-79 (SEQ ID NO:418) claim 43 , DOM7h-11-80 (SEQ ID NO: 419) claim 43 , DOM7h-11-90 (SEQ ID NO: 420) claim 43 , DOM7h-11-86 (SEQ ID NO: 421) claim 43 , DOM7h-11-87 (SEQ ID NO: 422) claim 43 , and DOM7h-11-88 (SEQ ID NO: 423) or has up to 4 changes compared to the selected amino acid sequence.48. An anti-SA immunoglobulin single variable domain variant as claimed in wherein the variant comprises at least one mutation in the FW3 region (positions 57 to 88 claim 43 , numbering according to Kabat) ...

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Номер записи: 28
23-05-2013 дата публикации

AMINO ACID SEQUENCES DIRECTED AGAINST GPCRS AND POLYPEPTIDES COMPRISING THE SAME FOR THE TREATMENT OF GPCR-RELATED DISEASES AND DISORDERS

Номер: US20130130379A1
Автор: Adams Hendrik, BLANCHETOT Christophe, DE HAARD Johannes Joseph Wilhelmus, Descamps Francis, Jähnichen Sven, Leurs Regorius, Maussang-Detaille David Andre Baptiste, Merchiers Pascal Gerard, PAJUELO MARIA GONZALEZ, SAUNDERS Michael John Scott, Smit Martine, Stortelers Catelijne, Van Rompaey Philippe, Van Roy Maarten, Vanlandschoot Peter
Принадлежит: Ablynx N.V.

The present invention relates to amino acid sequences that are directed against G-protein coupled receptors (GPCRs), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences. The invention also relates to nucleic acids encoding such amino acid sequences and; to methods for preparing such amino acid sequences and polypeptides; to host cells expressing or capable of expressing such amino acid sequences or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such amino acid sequences, polypeptides, nucleic acids and/or host cells; and to uses of such amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes. 1. A polypeptide comprising two or more amino acid sequences which are directed against GPCRs , whereina) at least one “first” amino acid sequence is directed against a first antigenic determinant, epitope, part, domain, subunit or conformation of a GPCR; and wherein,b) at least one “second” amino acid sequence is directed against a second antigenic determinant, epitope, part, domain, subunit or conformation of said GPCR different from the first antigenic determinant epitope, part, domain, subunit or conformation, respectively.2. The polypeptide according to claim 1 , wherein said at least one “first” amino acid sequence and/or said at least one “second” amino acid sequence consists of a domain antibody claim 1 , an amino acid sequence that is suitable for use as a domain antibody claim 1 , a single domain antibody claim 1 , an amino acid sequence that is suitable for use as a single domain antibody claim 1 , a “dAb” claim 1 , an amino acid sequence that is suitable for use as a dAb claim 1 , a Nanobody or a VHH sequence.3. The polypeptide according to claim 1 , wherein said at least one “first” amino acid sequence and/or said ...

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Номер записи: 29
20-06-2013 дата публикации

BINDING MOLECULES FOR BCMA AND CD3

Номер: US20130156769A1
Автор: ADAM Paul, BORGES Eric, Hebeis Barbara, Hipp Susanne, Hoffmann Patrick, KISCHEL Roman, Kufer Peter, Lutterbuese Ralf, Rau Doris, Raum Tobias
Принадлежит:

The present invention relates to a binding molecule which is at least bispecific comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope cluster 3 of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 1. A binding molecule which is at least bispecific comprising a first and a second binding domain , wherein(a) the first binding domain is capable of binding to epitope cluster 3 of BCMA (CQLRCSSNTPPLTCQRYC); and(b) the second binding domain is capable of binding to the T cell CD3 receptor complex; andwherein epitope cluster 3 of BCMA corresponds to amino acid residues 24 to 41 of the sequence as depicted in SEQ ID NO: 1002.2. The binding molecule according to claim 1 , wherein the first binding domain is further capable of binding to epitope cluster 3 of macaque BCMA (CQLRCSSTPPLTCQRYC).3. The binding molecule according to wherein the second binding domain is capable of binding to CD3 epsilon.4. The binding molecule according to claim 1 , wherein the second binding domain is capable of binding to human CD3 and to macaque CD3.5. The binding molecule according to claim 1 , wherein the first and/or the second binding domain are derived from an antibody.6. The binding molecule according to claim 5 , which is selected from the group consisting of (scFv) claim 5 , (single domain mAb) claim 5 , scFv-single domain mAb claim 5 , diabodies and oligomers thereof.7. The binding molecule according to claim 1 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 1 , CDR-H2 and ...

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Номер записи: 30
20-06-2013 дата публикации

BINDING MOLECULES FOR BCMA AND CD3

Номер: US20130156770A1
Автор: ADAM Paul, BORGES Eric, Hebeis Barbara, Hipp Susanne, Hoffmann Patrick, KISCHEL Roman, Kufer Peter, Lutterbuese Ralf, Rau Doris, Raum Tobias
Принадлежит:

The present invention relates to a binding molecule comprising a first and a second binding domain, wherein the first binding domain is capable of binding to epitope clusters of BCMA, and the second binding domain is capable of binding to the T cell CD3 receptor complex. Moreover, the invention provides a nucleic acid sequence encoding the binding molecule, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention provides a process for the production of the binding molecule of the invention, a medical use of said binding molecule and a kit comprising said binding molecule. 2. The binding molecule of claim 1 , wherein the first binding domain is not capable of binding to the chimeric extracellular domain of BCMA as depicted in SEQ ID NO: 1015.3. The binding molecule according to claim 1 , wherein the first binding domain is further capable of binding to macaque BCMA.4. The binding molecule according to claim 1 , wherein the second binding domain is capable of binding to CD3 epsilon.5. The binding molecule according to claim 1 , wherein the second binding domain is capable of binding to human CD3 and to macaque CD3.6. The binding molecule according to claim 1 , wherein the first and/or the second binding domain are derived from an antibody.7. The binding molecule according to claim 6 , which is selected from the group consisting of (scFv) claim 6 , (single domain mAb) claim 6 , scFv-single domain mAb claim 6 , diabodies and oligomers thereof.8. The binding molecule according to claim 1 , wherein the first binding domain comprises a VH region comprising CDR-H1 claim 1 , CDR-H2 and CDR-H3 and a VL region comprising CDR-L1 claim 1 , CDR-L2 and CDR-L3 selected from the group consisting of:(a) CDR-H1 as depicted in SEQ ID NO: 231, CDR-H2 as depicted in SEQ ID NO: 232, CDR-H3 as depicted in SEQ ID NO: 233, CDR-L1 as depicted in SEQ ID NO: 234, CDR-L2 as depicted in SEQ ID NO: 235 and CDR-L3 as ...

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Номер записи: 31
27-06-2013 дата публикации

BISPECIFIC T-CELL ACTIVATOR ANTIBODY

Номер: US20130165629A1
Автор: CHANG Ming-Chuan, Chang Mingi, Hsu Yu-Shen, Sheu Show-Shan, Yuan Ta-Tung
Принадлежит:

This invention relates to bispecific antibodies having combinations of linker and hinge sequences to create linker-hinge interface domains with biological significance. Such linker-hinge interface domains covalently join two molecules, maintain the biological activities of linked molecules (target binding), stabilize the biological characteristics of new molecule (solubility and 4° C. stability), maintain the chemical, biochemical and physical properties (cytotoxicity) of the linked molecules, and modulate the biological characteristics of the linked molecules (activating T-lymphocytes without significant sign of proliferations). Both linker (GGGGS) and hinge (CPPCP) sequences are required to establish functional linker-hinge interface domains as deletion of any of the component resulted in significant lost of T-lymphocyte mediated activity. 1. A protein domain (LHD) comprising a linker sequence and a hinge sequence , wherein the linker sequence comprises glycine-glycine-glycine-glycine-serine , and the hinge sequence comprises cysteine-proline-proline-cysteine-proline.2. The protein domain of claim 1 , wherein the protein domain comprises two or more linker sequences.3. The protein domain of claim 1 , wherein the protein domain comprises the sequence of SEQ ID NO: 1 claim 1 , SEQ ID NO: 2 claim 1 , SEQ ID NO: 3 claim 1 , SEQ ID NO: 4 claim 1 , SEQ ID NO: 5 claim 1 , or SEQ ID NO: 6.4. A protein comprising the protein domain of claim 1 , further comprising an N-terminal moiety fused to the N-terminus of the protein domain via a peptide bond and a C-terminal moiety fused to the C-terminus for the protein domain via a peptide bond.5. The protein of claim 4 , wherein the N-terminal moiety and the C-terminal moiety are each independently a full-length immunoglobulin or a single-chain variable region fragment (ScFv) of an antibody.6. The protein of claim 4 , wherein one of the N-terminal moiety and the C-terminal moiety comprises a T-lymphocyte activating domain that ...

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Номер записи: 32
04-07-2013 дата публикации

Method for Purifying Antibodies

Номер: US20130171095A1
Автор: Bernett Matthew J., Desjarlais John, Moore Gregory L., Rashid Rumana
Принадлежит: Xencor, Inc.

The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains. 1. A composition comprising a heterodimer protein comprising: i) a first variant heavy chain constant region;', 'ii) a first fusion partner; and, 'a) a first monomer comprising i) a second variant heavy chain constant region;', 'ii) a second fusion partner;, 'b) a second monomer comprisingwherein the pIs of said first and second variant heavy chain constant regions are at least 0.5 logs apart.2. A composition according to wherein the pIs of said first and second monomer are at least 0.5 logs apart.3. A composition according to or wherein said first monomer comprises a third fusion partner.4. A composition according to claim 1 , or wherein said second monomer comprises a fourth fusion partner.5. A composition according to claim 1 , and wherein said fusion partners are independently selected from the group consisting of an immunoglobulin component claim 1 , a peptide claim 1 , a cytokine claim 1 , a chemokine claim 1 , an immune receptor and a blood factor.6. A composition according to wherein said immunoglobulin component is selected from the group consisting of Fab claim 5 , VH claim 5 , VL claim 5 , scFv claim 5 , scFv2 claim 5 , dAb.7. A composition according to wherein said cytokine is selected from the group consisting of IL-2 claim 5 , IL-10 claim 5 , IL-12 and GM-CSF.8. A composition according to wherein said chemokine is selected from the group consisting of RANTES claim 5 , CXCL9 claim 5 , CXCL10 and CXCL12.9. A composition according to wherein said immune receptor is selected from the group consisting of CTLA-4 claim 5 , TNFRI claim 5 , TNFRII claim 5 , a TNFSF protein claim 5 , and TNFRSF10. A composition according to wherein said blood factor is selected from the group consisting of Factor VII claim 5 , Factor ...

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Номер записи: 33
04-07-2013 дата публикации

Dual-specific il-1a/ il-1b antibodies

Номер: US20130171146A1
Автор: Bradford L. McRae, Carrie Enever, Chung-Ming Hsieh, Ian Tomlinson, John E. Memmott, Michael Roguska, Mihriban Tuna, Steven Grant, Yuliya Kutskova
Принадлежит: ABBOTT LABORATORIES

The invention provides an isolated, dual-specific antibody, or an antigen-binding portion thereof, which is specific for human IL-1α and human IL-1β. The dual specific antibodies of the invention also neutralize both human IL-1α and human IL-1β. The invention also provides domain antibodies (dAbs) specific for human IL-1α and human IL-1β.

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Номер записи: 34
25-07-2013 дата публикации

ANTIGEN-BINDING MOLECULE AND USES THEREOF

Номер: US20130189263A1
Автор: Le Gall Fabrice, LITTLE Melvyn
Принадлежит:

In one aspect, the present invention relates to an antigen-binding molecule specific for albumin and CD3 which may comprise two polypeptide chains, each polypeptide chain having at least four variable domains in an orientation preventing Fv formation and the two polypeptide chains are dimerized with one another thereby forming a multivalent antigen-binding molecule. On each of the two polypeptide chains the four variable domains may be arranged in the order VA-VB-VB-VA from the N-terminal to the C-terminal of the polypeptide. Compositions of the antigen-binding molecule and the methods of using the antigen-binding molecule or the compositions thereof for treatment of various diseases are also provided herein. 19-. (canceled)10. A method for immunotherapy comprising administering a pharmaceutical composition comprising a dimeric antigen-binding molecule being specific for albumin and CD3 comprising a first and a second polypeptide chain , each of the first and the second polypeptide chains comprising{'sub': 'L', 'a first domain VA being a light chain variable domain specific for albumin;'}{'sub': 'H', 'a second domain VB being a heavy chain variable domain s ecific for CD3;'}{'sub': 'L', 'a third domain VB being a light chain variable domain specific for CD3; and'}{'sub': 'H', 'a fourth domain VA being a heavy chain variable domain specific for albumin,'}wherein{'sub': L', 'H', 'L', 'H, 'said domains are arranged in each of said first and second polypeptide chains in the order VA-VB-VB-VA from the N-terminus to the C-terminus of said polypeptide chains, and'}{'sub': L', 'H, 'the first domain VA of the first polypeptide chain is in association with the fourth domain VA of the second polypeptide chain to form an antigen binding site for the albumin;'}{'sub': H', 'L, 'the second domain VB of the first polypeptide chain is in association with the third domain VB of the second polypeptide chain to form an antigen binding site for the CD3;'}{'sub': L', 'H, 'the third ...

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Номер записи: 35
01-08-2013 дата публикации

PROTEIN COMPLEX AND METHOD OF PREPARING SAME

Номер: US20130196377A1
Автор: Choi Yoon-aa, LEE Jae-il, Suh Hye-young
Принадлежит: SAMSUNG ELECTRONICS CO., LTD.

A protein complex including at least two monoclonal antibodies is provided. By using the protein complex, a system for simultaneously targeting at least two antigens is effectively constructed. 1. A protein complex comprising at least two polypeptides each comprising an antigen binding site; and a linker that links the at least two polypeptides to each other , wherein the linker comprises a linking group and a tag attached to at least one terminus thereof , wherein the tag also is linked to a terminus of one of the at least two polypeptides and includes a cleavable amino acid sequence.2. The protein complex of claim 1 , wherein the antigen binding site of each polypeptide is located at an N-terminus of the polypeptide.3. The protein complex of claim 1 , wherein the at least two polypeptides have antigen binding sites that are different from one another.4. The protein complex of claim 1 , wherein the protein complex comprises a first polypeptide having a first antigen binding site at an N-terminus thereof; a second polypeptide having a second antigen binding site at an N-terminus thereof; and a linker that links the first and second polypeptides to each other claim 1 , wherein the linker comprises a linking group and a first tag and a second tag at both termini thereof claim 1 , wherein the first tag is linked to a C-terminus of the first polypeptide claim 1 , the second tag is linked to an N-terminus of the second polypeptide claim 1 , and the first tag and the second tag each comprise a cleavable amino acid sequence.5. The protein complex of claim 1 , wherein the protein complex comprises a first polypeptide having a first antigen binding site at an N-terminus thereof; a second polypeptide having a second antigen binding site at an N-terminus thereof; and a linker that links the first and second polypeptides to each other claim 1 , wherein the linker comprises a linking group and a tag at one terminus thereof claim 1 , wherein the tag is linked to a C-terminus of ...

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Номер записи: 36
15-08-2013 дата публикации

Antibodies that bind both il-17a and il-17f and methods of using the same

Номер: US20130209470A1
Автор: Scott R. Presnell, Stephen R. Jaspers
Принадлежит: Zymogenetics Inc

The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-17A and IL-17F. IL-17A and IL-17F are cytokines that are involved in inflammatory processes and human disease. The present invention includes antibodies that bind both IL-17A and IL-17F, as well as methods of using the same in inflammation.

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Номер записи: 37
22-08-2013 дата публикации

Anti-GD2 Antibodies

Номер: US20130216528A1
Автор: Ahmed Mahiuddin, Cheung Nai-Kong
Принадлежит:

In this application are described chimeric, humanized, affinity matured, stability enhanced, and bispecific Anti-GD2 antibodies and fragments thereof. Also provided are methods of using individual antibodies or compositions thereof for the detection, prevention, and/or therapeutical treatment of GD2-related diseases, in particular, neuroblastoma. 1. A humanized or chimeric antibody or fragment thereof capable of binding to GD2 , wherein the antibody or fragment thereof comprises at least one of the amino acid sequences of CDR1 , CDR2 and CDR3 of the murine antibody m3F8 variable light chain and/or at least one of the amino acid sequences of CDR1 , CDR2 and CDR3 of the murine antibody m3F8 variable heavy chain.2. A chimeric antibody or fragment thereof according to claim 1 , wherein the antibody comprises any of the following:(i) a variable heavy chain domain of SEQ ID NO:1 and a variable light chain domain of SEQ ID NO:2(ii) a variable heavy chain domain of SEQ ID NO:3 and a variable light chain domain of SEQ ID NO:2;(iii) a variable heavy chain domain of SEQ ID NO:4 and a variable light chain domain of SEQ ID NO:5;(iv) a variable heavy chain domain of SEQ ID NO:6 and a variable light chain domain of SEQ ID NO:7;(v) a variable heavy chain domain of SEQ ID NO:8 and a variable light chain domain of SEQ ID NO:5; and(vi) a variable heavy chain domain of SEQ ID NO:9 and a variable light chain domain of SEQ ID NO:10.37-. (canceled)8. The antibody of claim 1 , wherein said antibody is glycosylated with terminal mannose claim 1 , N-acetylglucose or glucose claim 1 , but no fucose.9. The antibody of claim 2 , wherein said antibody comprises at least one of the following amino acid substitutions in said heavy chain domain sequence of said antibody claim 2 , said substitutions consisting of S239D claim 2 , A330L claim 2 , 1332E claim 2 , and G54I.10. The antibody of claim 2 , wherein said antibody comprises an amino acid substitution in said light chain of said antibody claim ...

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Номер записи: 38
22-08-2013 дата публикации

Compositions and Methods for Treating Inflammatory Disorders

Номер: US20130216538A1
Автор: Basran Amrik, Brewis Neil, De Wildt Rudolf Maria Theodora, GRANT Steven, Ignatovich Olga, Jones Philip C., Woolven Benjamin
Принадлежит: Domantis Limited

The invention relates to compositions and methods for treating inflammatory disorders. More specifically, the invention relates to antibody compositions and their use in the treatment of inflammatory disorders. 1. A composition comprising a first and a second anti-TNFα antibody single variable domain and an anti-serum albumin antibody single variable domain , wherein said first and second anti-TNFα antibody single variable domains have the same TNFα epitope binding specificity.2. The composition of claim 1 , wherein said first and second anti-TNFα antibody single variable domains are identical.3. The composition of claim 1 , wherein the anti-TNFα antibody single variable domains have a monomer surface plasmon resonance Kof about 300 nM to about 5 pM.4. The composition of claim 3 , wherein said monomer surface plasmon resonance Kis about 50 nM to about 20 pM.5. The composition of claim 4 , wherein said monomer surface plasmon resonance Kis about 1 nM to about 100 pM.6. The composition of claim 1 , wherein said composition has a tβ half-life of at least 24 hours.7. The composition of claim 1 , wherein said composition has a tβ half-life of 12 hours to 48 hours.8. The composition of claim 1 , wherein said composition has a tβ half-life of 12 hours to 26 hours.9. A composition comprising a first and a second anti-TNFα antibody single variable domain and an anti-serum albumin antibody single variable domain claim 1 , wherein said composition has a tβ half-life of at least 12 hours.10. The composition of claim 9 , wherein said composition has a tβ half-life of at least 24 hours.11. The composition of claim 9 , wherein said composition has a tβ half-life of 12 hours to 48 hours.12. The composition of claim 9 , wherein said composition has a tβ half-life of 12 hours to 26 hours.13. The composition of claim 9 , comprising one anti-serum albumin antibody single variable domain.14. The composition of claim 9 , wherein said first and second anti-TNFα antibody single variable ...

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Номер записи: 39
29-08-2013 дата публикации

COMPOSITIONS AND METHODS FEATURING IL-6 AND IL-21 ANTAGONISTS

Номер: US20130224109A1
Автор: KOULMANDA Maria, Strom Terry
Принадлежит: BETH ISRAEL DEACONESS MEDICAL CENTER, INC.

The present invention features compositions for inhibiting both the IL-6 and the IL-21 pathways and methods of making and using such compositions. Our work to date indicates the importance of the redundancy of IL-6 and IL-21 to perform certain crucial functions. The pathways can be inhibited by inhibiting the ligands (i.e., IL-6 and IL-21) and/or their respective receptors (i.e., the IL-6 receptor and IL-21 receptor). Alternatively, or in addition, upstream and downstream effectors in the IL-6 and IL-21 pathways can be blocked. The agents used can be antibody or antibody-based proteins or peptides including circulating receptors, optionally coupled to an immunoglobulin or a portion thereof (e.g., the Fc region). Also provided are methods for using the compositions, for example, in organ transplantation, tissue grafting, or autoimmune disorders. 1. A bi-specific immunoglobulin comprising a first portion that specifically binds an IL-6 or an IL-6 receptor and a second portion that specifically binds an IL-21 or an IL-21 receptor.2. The bispecific immunoglobulin of claim 1 , wherein the first portion specifically binds an IL-6 and the second portion specifically binds an IL-21; the first portion specifically binds an IL-6 receptor and the second portion specifically binds an IL-21 receptor; the first portion specifically binds an IL-6 and the second portion specifically binds an IL-21 receptor; or the first portion specifically binds an IL-6 receptor and the second portion specifically binds an IL-21.3. The bi-specific immunoglobulin of claim 1 , wherein the antibody is a bi-specific monoclonal antibody or a biologically active variant thereof claim 1 , a chemically linked F(ab′)or a biologically active variant thereof claim 1 , or a bi-specific T cell engager or a biologically active variant thereof.45-. (canceled)6. The bi-specific immunoglobulin of claim 1 , wherein the immunoglobulin further comprises a toxin or radioisotope.7. The bi-specific immunoglobulin of ...

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Номер записи: 40
05-09-2013 дата публикации

ANTI-SERUM ALBUMIN BINDING VARIANTS

Номер: US20130230519A1
Автор: De Angelis Elena, Enever Carolyn, Liu Haiqun, Pupecka-Swider Malgorzata, Schon Oliver
Принадлежит:

The invention relates to improved variants of the anti-serum albumin immunoglobulin single variable domain DOM7h-14-10, as well as ligands and drug conjugates comprising such variants, compositions, nucleic acids, vectors and hosts. 1. An anti-serum albumin (SA) immunoglobulin single variable domain selected from the group consisting of: DOM7h-14-56 (SEQ ID NO: 72) , DOM7h-14-65 (SEQ ID NO: 73) , DOM7h-14-74 (SEQ ID NO: 74) , DOM7h-14-76 (SEQ ID NO: 75) , DOM7h-14-82 (SEQ ID NO: 76) , DOM7h-14-100 (SEQ ID NO: 77) , DOM7h-14-101 (SEQ ID NO: 78) , DOM7h-14-109 (SEQ ID NO: 79) , DOM7h-14-115 (SEQ ID NO: 80) , DOM7h-14-116 (SEQ ID NO: 81) , DOM7h-14-119 (SEQ ID NO: 82) , DOM7h-14-120 (SEQ ID NO: 83) , DOM7h-14-121 (SEQ ID NO: 84) , DOM7h-14-122 (SEQ ID NO: 85) and DOM7h-14-123 (SEQ ID NO: 86).2. A multispecific ligand comprising the anti-SA single variable domain of claim 1 , and a binding moiety that specifically binds a target antigen other than SA.3. The anti-SA single variable domain of claim 1 , wherein the variable domain is conjugated to an NCE drug.4. A fusion protein comprising a polypeptide or peptide drug fused to the single variable domain according to .5. A composition comprising the variable domain of claim 1 , and a pharmaceutically acceptable diluent claim 1 , carrier claim 1 , excipient or vehicle.6. A nucleic acid comprising a nucleotide sequence encoding the single variable domain according to .7. A nucleic acid comprising a nucleotide sequence that is at least 80% identical to a nucleotide sequence selected from the group consisting of: SEQ ID NO: 87 claim 1 , SEQ ID NO: 88 claim 1 , SEQ ID NO: 89 claim 1 , SEQ ID NO: 90 claim 1 , SEQ ID NO: 91 claim 1 , SEQ ID NO: 92 claim 1 , SEQ ID NO: 93 claim 1 , SEQ ID NO: 94 claim 1 , SEQ ID NO: 95 claim 1 , SEQ ID NO: 96 claim 1 , SEQ ID NO: 97 claim 1 , SEQ ID NO: 98 claim 1 , SEQ ID NO: 99 claim 1 , SEQ ID NO: 100 claim 1 , and SEQ ID NO: 101.8. A vector comprising the nucleic acid of .9. An isolated host ...

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Номер записи: 41
05-09-2013 дата публикации

PROTEIN COMPLEXES FOR ANTIGEN BINDING AND METHODS OF USE

Номер: US20130230525A1
Автор: Bao Jun, Chen Bo, Li Zijuan, Wu Chun
Принадлежит: ALTIMAB THERAPEUTICS, INC.

Provided herein in certain embodiments are polypeptide complexes capable of binding to an antigen. Pharmaceutical compositions, method of using the polypeptide complexes are also provided. 1. A polypeptide complex comprising:a first polypeptide comprising a first protein monomer and a first antigen-binding domain, anda second polypeptide comprising a second protein monomer and a second antigen-binding domain,wherein the first protein monomer forms a dimmer with the second protein monomer;wherein the C-terminal of the first protein monomer is operably linked to the N-terminal of the first antigen-binding domain; andwherein the C-terminal of the second protein monomer is operably linked to the N-terminal of the second antigen-binding domain.2. The polypeptide complex of wherein the formation of the dimmer substantially reduces the simultaneous binding of the first antigen-binding domain and the second antigen-binding domain to an antigen.3. The polypeptide complex of claim 1 , whereinthe first polypeptide further comprises a first thiol residue-containing peptide linker,the second polypeptide further comprises a second thiol residue-containing peptide linker;the N-terminal of the first peptide linker is covalently linked to the C-terminal of the first protein monomer;the C-terminal of the first peptide linker is covalently linked to the N-terminal of the first antigen-binding domain;the N-terminal of the second peptide linker is covalently linked to the C-terminal of the second protein monomer;the C-terminal of the second peptide linker is covalently linked to the N-terminal of the second antigen-binding domain; andthe first peptide linker and the second peptide linker forms a disulfide bond.4. The polypeptide complex of wherein the disulfide bond substantially reduces the simultaneous binding of the first antigen-binding domain and the second antigen-binding domain to an antigen.5. The polypeptide complex of wherein the first protein monomer is the same or not the ...

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Номер записи: 42
12-09-2013 дата публикации

DUAL SPECIFIC BINDING PROTEINS DIRECTED AGAINST IL-13 AND/OR IL-17

Номер: US20130236458A1
Автор: Ghayur Tariq, Goodreau Carrie L., HSIEH Chung-Ming
Принадлежит: AbbVie Inc.

Engineered multivalent and multispecific binding proteins that bind IL-13 and/or IL-17 are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease. 125-. (canceled)28. The binding protein according to claim 26 , wherein the binding protein is capable of binding IL-13 and IL-17 claim 26 , wherein SEQ ID NOs: 30 and 31,', 'SEQ ID NOs: 32 and 33, or', 'SEQ ID NOs: 33 and 34;, '(a) the variable domains that form a functional target binding site for IL-13 comprise'}and SEQ ID NOs: 36 and 37,', 'SEQ ID NOs: 38 and 39,', 'SEQ ID NOs: 40 and 41,', 'SEQ ID NOs: 42 and 52,', 'SEQ ID NOs: 42 and 53,', 'SEQ ID NOs: 43 and 50,', 'SEQ ID NOs: 44 and 51,', 'SEQ ID NOs: 45 and 54,', 'SEQ ID NOs: 46 and 51,', 'SEQ ID NOs: 47 and 54,', 'SEQ ID NOs: 48 and 51, or', 'SEQ ID NOs: 49 and 51., '(b) the variable domains that form a functional target binding site for IL-17 comprise'}30. The binding protein according to claim 26 , comprising two first polypeptide chains and two second polypeptide chains claim 26 , forming four functional target binding sites.31. The binding protein according to claim 26 , wherein X1 is any one of SEQ ID NOs: 1-29 or a G4S (SEQ ID NO: 29) repeating sequence.32. The binding protein according to claim 26 , wherein the Fc region is a variant sequence Fc region.33. The binding protein according to claim 26 , wherein the Fc region is an Fc region from IgG1 claim 26 , IgG2 claim 26 , IgG3 claim 26 , IgG4 claim 26 , IgA claim 26 , IgM claim 26 , IgE claim 26 , or IgD.34. The binding protein according to claim 26 , wherein the binding protein is a crystallized binding protein.35. A binding protein capable of binding IL-13 and IL-17 claim 26 , wherein the binding protein comprises any one of:DVD2148H (comprising SEQ ID NO: 30 and 36) and DVD2148L (comprising SEQ ID NOs: 31 and 37);DVD2149H (comprising SEQ ID NO: 36 and 30) and DVD2149L (comprising SEQ ID NOs: 37 and 31);DVD2150H (comprising SEQ ID NOs: 30 and 36) and ...

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Номер записи: 43
12-09-2013 дата публикации

MONOSPECIFIC AND BISPECIFIC ANTI-IGF-1R AND ANTI-ERBB3 ANTIBODIES

Номер: US20130236459A1
Автор: Adams Sharlene, Baum Jason, FITZGERALD Jonathan Basil, JOHNSON Bryan, KOHLI Neeraj, LUGOVSKOY Alexey Alexandrovich, XU Lihui
Принадлежит: Merrimack Pharmaceuticals, Inc.

Provided are monospecific and bispecific antibodies that are useful as anti-neoplastic agents and that bind specifically to human IGF-1R and human ErbB3. Exemplary antibodies inhibit signal transduction through either or both of IGF-1R and ErbB3. Exemplary polyvalent proteins comprise at least one anti-IGF-1R binding site and at least one anti-ErbB3 binding site. In certain embodiments the binding sites may be linked through an immunoglobulin constant region. AntiErbB3 and anti-IGF-1R antibodies (e.g., monoclonal antibodies) are also provided. 1194-. (canceled)196. A polyvalent bispecific antibody that is: two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:212; and', 'two light chains, each comprising a light chain sequence of SEQ ID NO:202, or;, 'a. an SF-G1-P1 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:214; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:202, or;, 'b. an SF-G1-M1.3 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:216; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:202, or;, 'c. an SF-G1-M27 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:218; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:202, or;, 'd. an SF-G1-P6 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:220; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:202, or;, 'e. an SF-G1-B69 polyvalent bispecific antibody comprising two heavy chains, each comprising a heavy chain amino acid sequence of SEQ ID NO:224; and', 'two light chains, each comprising a light chain amino acid sequence of SEQ ID NO:204, or;, ...

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Номер записи: 44
12-09-2013 дата публикации

ANTI-CLTA4, ANTI-GLUT2 PROTEIN FOR THE TREATMENT OF TYPE 1 DIABETES

Номер: US20130236464A1
Автор: BHATTACHARYA Palash, PRABHAKAR Bellur S., VASU Chenthamarakshan
Принадлежит:

The disclosure relates to a protein composed of a first polypeptide or polypeptide domain having a first specific binding activity for Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) expressed on a T-cell cell surface and a second specific binding activity for Glucose Transporter 2 (GLUT2) or an extracellular ectodomain thereof expressed on a pancreatic β-cell surface, wherein binding of the first polypeptide or polypeptide domain to CTLA-4 induces a CTLA-4 specific agonist response in the T-cell, and binding of the second polypeptide or polypeptide domain to GLUT2 or an ectodomain thereof does not inhibit GLUT2 glucose transporter function, wherein said agonist response in the T-cell induces a response that reduces immunoreactivity against pancreatic β-cells. 1. A protein comprising a first polypeptide or polypeptide domain having a first specific binding activity for Cytotoxic T-lymphocyte Antigen 4 (CTLA-4) expressed on a T-cell cell surface and a second specific binding activity for Glucose Transporter 2 (GLUT2) or an extracellular ectodomain thereof expressed on a pancreatic beta-cell surface , wherein binding of the first polypeptide or polypeptide domain to CTLA-4 induces a CTLA-4 specific agonist response in the T cell , and binding of the second polypeptide or polypeptide domain to GLUT2 or an ectodomain thereof does not inhibit GLUT2 glucose transporter function , wherein said agonist response in the T cell reduces immunoreactivity against pancreatic beta cells.2. The protein of claim 1 , wherein the first and second polypeptide or polypeptide domain are independently an antibody molecule or a specific-binding fragment thereof.3. The protein of wherein the first and second polypeptide or polypeptide domain independently comprise at least one immunoglobulin heavy chain and one immunoglobulin light chain.4. The protein of claim 2 , wherein the first and second polypeptide or polypeptide domain independently comprise a monovalent antibody fragment claim 2 , an F(ab ...

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Номер записи: 45
19-09-2013 дата публикации

ANTIBODIES THAT BIND IL-4 AND/OR IL-13 AND THEIR USES

Номер: US20130243777A1
Автор: DAVISON Matthew, Kruip Jochen, LI Danxi, MIKOL Vincent, Rao Ercole
Принадлежит: SANOFI

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis. 149-. (canceled)50. A bispecific antibody or bispecific antibody fragment thereof that specifically binds to IL-13 and IL-4;wherein the bispecific antibody or bispecific antibody fragment thereof comprises a first pair of polypeptides and a second pair of polypeptides;{'sub': L', 'H1, 'wherein the first pair of polypeptides comprise an outer (N-terminal) variable light chain domain linked to an inner (C-terminal) variable light chain domain which is linked to a constant light chain domain (C), and the second pair of polypeptides comprise an outer (N-terminal) variable heavy chain domain linked to an inner (C-terminal) variable heavy chain domain which is linked to a constant heavy chain domain (C); and'}wherein:(a) the outer (N-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 4;(b) the outer (N-terminal) variable light chain domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises an ...

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Номер записи: 46
19-09-2013 дата публикации

ANTIBODIES THAT BIND IL-4 AND/OR IL-13 AND THEIR USES

Номер: US20130243778A1
Автор: DAVISON Matthew, Kruip Jochen, LI Danxi, MIKOL Vincent, Rao Ercole
Принадлежит: SANOFI

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis. 149-. (canceled)50. A bispecific antibody or bispecific antibody fragment thereof that specifically binds to IL-13 and IL-4;wherein the bispecific antibody or bispecific antibody fragment thereof comprises four polypeptide chains that form four antigen binding sites; {'br': None, 'sub': L1', '1', 'L2', 'L, 'V-L-V-C\u2003\u2003[I]'}, 'wherein two polypeptide chains have a structure represented by the formula {'br': None, 'sub': H1', '2', 'H2', 'H1, 'V-L-V-C\u2003\u2003[II]'}, 'and two polypeptide chains have a structure represented by the formulawherein:{'sub': 'L1', 'Vis a first immunoglobulin light chain variable domain;'}{'sub': 'L2', 'Vis a second immunoglobulin light chain variable domain;'}{'sub': 'H1', 'Vis a first immunoglobulin heavy chain variable domain;'}{'sub': 'H2', 'Vis a second immunoglobulin heavy chain variable domain;'}{'sub': 'L', 'Cis an immunoglobulin light chain constant domain;'}{'sub': H1', 'H1, 'Cis the immunoglobulin Cheavy chain constant domain;'}{'sub': 1', '2, 'Land Lare amino acid linkers; and'}wherein:{'sub': L1', 'L2', 'H1', 'H2, '(a) Vcomprises the amino acid sequence of SEQ ID NO: 1, Vcomprises the amino acid sequence of SEQ ID NO: 3, Vcomprises the amino acid sequence of SEQ ID NO: 2, and Vcomprises the amino acid sequence of SEQ ID NO: 4;'}{'sub': L1', 'L2', 'H1', 'H2, '(b) Vcomprises the amino acid sequence of SEQ ID NO: 1, Vcomprises the amino acid sequence of SEQ ID NO: 3, Vcomprises the amino acid sequence of SEQ ID NO: 2, and Vcomprises the amino acid sequence of SEQ ID NO: 5;'}{'sub': L1', 'L2', 'H1', 'H2, '(c) Vcomprises the amino acid sequence of SEQ ID NO: 3, ...

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Номер записи: 47
19-09-2013 дата публикации

Multispecific Molecules

Номер: US20130245233A1
Автор: Jing Li, Li Zhou, Ming Lei, Zhenping Zhu
Принадлежит: Individual

The present invention is directed to multi-specific/multivalent molecules of novel formats. The molecules with the formats of the present invention have desired yield and thermostability. The present invention also includes methods of producing and using the molecules described herein.

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Номер записи: 48
26-09-2013 дата публикации

Method for Making Heteromultimeric Molecules

Номер: US20130253172A1
Автор: Aaron K. Sato, Austin L. Gurney
Принадлежит: OncoMed Pharmaceuticals Inc

The present invention provides methods for making heteromultimeric molecules, such as bispecific antibodies, and compositions comprising said molecules. The method includes introducing mutations in amino acids that are in contact at the interface of two polypeptides, such that the electrostatic interaction between the ion pairs is altered.

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Номер записи: 49
10-10-2013 дата публикации

ACTIVATABLE BISPECIFIC ANTIBODIES

Номер: US20130266568A1
Автор: Brinkmann Ulrich, Croasdale Rebecca, METZ SILKE, Schanzer Juergen Michael, Sustmann Claudio, Umana Pablo
Принадлежит:

The current invention relates to bispecific antibodies wherein the binding affinity to one of the two antigens is reduced and which can be activated by tumor- or inflammation-specific proteases, and the preparation and use of such bispecific antibodies. 1. A bispecific antibody comprising{'sup': 1', '1, 'a) a first antibody that binds to a first antigen comprising a VHdomain and a VLdomain, and'}b) a second antibody that binds to a second antigen,{'sup': 1', '1, 'wherein the VHdomain is fused N-terminally via a first peptide linker to the second antibody, and the VLdomain is fused N-terminally via a second peptide linker to the second antibody, and'}characterized in thatone of the linkers comprises a tumor- or inflammation-specific protease cleavage site, and the other linker does not comprise a protease cleavage site; andthe binding affinity of the bispecific antibody to the first antigen is reduced 5 times or more compared to the corresponding bispecific antibody in which the protease cleavage site is cleaved.2. The bispecific antibody according to characterized in that the second antibody is a whole antibody; and{'sup': '1', 'the VHdomain is fused N-terminally via the first linker to the C-terminus of the first heavy chain of the second antibody, and'}{'sup': '1', 'the VLdomain is fused N-terminally via the second linker to the C-terminus of the second heavy chain of the second antibody.'}3. The bispecific antibody according to characterized in comprising from C- to N-terminus the following polypeptide chains{'sup': 1', '2, 'one VH-peptide linker-CH3-CH2-CH1-VHchain'}{'sup': '2', 'two CL-VLchains'}{'sup': 1', '2, 'one VL-peptide linker-CH3-CH2-CH1-VHchain.'}4. The bispecific antibody according to characterized in thatthe first CH3 domain of the heavy chain of the whole antibody and the second CH3 domain of the whole antibody each meet at an interface which comprises an alteration in the original interface between the antibody CH3 domains;wherein i) in the CH3 ...

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Номер записи: 50
10-10-2013 дата публикации

BISPECIFIC ANTIBODIES COMPRISING A DISULFIDE STABILIZED - FV FRAGMENT

Номер: US20130267686A1
Автор: Brinkmann Ulrich, Haas Alexander, METZ SILKE, Schanzer Juergen Michael
Принадлежит:

The present invention relates to bispecific antibodies, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof. 1. A bispecific antibody comprisinga) a full length antibody specifically binding to a first antigen and consisting of two antibody heavy chains and two antibody light chains;{'sup': 2', '2, 'b) a Fv fragment specifically binding to a second antigen comprising a VHdomain and a VLdomain, wherein both domains are connected via a disulfide bridge, and'}{'sup': 2', '2, 'wherein only either the VHdomain or the VLdomain is fused via a peptide linker to the heavy or light chain of the full length antibody specifically binding to a first antigen.'}2. The bispecific antibody according to characterized in that the bispecific antibody is trivalent and{'sup': 2', '2, 'either the VHdomain or the VLdomain is fused via a peptide linker to the heavy chain of the full length antibody specifically binding to a first antigen.'}3. The bispecific antibody according to characterized in that the VHdomain or VLdomain is N-terminally fused via a peptide linker to the C-terminus of the full length antibody specifically binding to a first antigen.4. The bispecific antibody according to claim 2 , characterized in that the VHdomain or VLdomain is C-terminally fused via a peptide linker to the N-terminus of the full length antibody specifically binding to a first antigen.5. The bispecific antibody according to claim 1 , characterized in that the VHdomain or VLdomain is N-terminally fused via a peptide linker to the C-terminus of the heavy or light chain of the full length antibody specifically binding to a first antigen.6. The bispecific antibody according to claim 1 , characterized in that the VHdomain or VLdomain is C-terminally fused via a peptide linker to the N-terminus of the heavy or light chain of the full length antibody specifically binding to a first antigen.7. The bispecific antibody according to claim 1 , characterized in ...

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Номер записи: 51
17-10-2013 дата публикации

Compositions and Methods of Inhibiting MASP-1 and/or MASP-2 and/or MASP-3 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria

Номер: US20130273053A1
Автор: Demopulos Gregory A., Schwaeble Hans-Wilhelm
Принадлежит:

In one aspect, the invention provides methods and compositions for inhibiting MASP-3-dependent complement activation in a subject suffering from paroxysmal nocturnal hemoglobinuria by administering to the subject a composition comprising an amount of a MASP-3 inhibitory agent in an amount effective to inhibit MASP-3-dependent complement activation. In another aspect, the invention provides methods and compositions for increasing the survival of red blood cells in a subject suffering from paroxysmal nocturnal hemoglobinuria by administering to the subject a composition comprising an amount of at least one of a MASP-1 inhibitory agent and/or a MASP-3 inhibitory agent effective to increase the survival of red blood cells. In some embodiments, the subject is administered a MASP-2 inhibitory agent and a MASP-1 inhibitory agent, a MASP-2 inhibitory agent and a MASP-3 inhibitory agent administered, a MASP-3 inhibitory agent and a MASP-1 inhibitory agent, or a MASP-1 inhibitory agent, a MASP-2 inhibitory agent and a MASP-3 inhibitory agent. 1. A method of inhibiting MASP-3-dependent complement activation in a subject suffering from paroxysmal nocturnal hemoglobinuria (PNH) , comprising administering to the subject a composition comprising an amount of a MASP-3 inhibitory agent effective to inhibit MASP-3-dependent complement activation.2. The method of claim 1 , wherein the MASP-3 inhibitory agent is a MASP-3 monoclonal antibody claim 1 , or fragment thereof that specifically binds to a portion of SEQ ID NO:8.3. The method of claim 1 , further comprising administering to the subject a composition comprising a MASP-1 inhibitory agent.4. The method of claim 3 , wherein the MASP-1 inhibitory agent is a MASP-1 monoclonal antibody claim 3 , or fragment thereof claim 3 , that specifically binds to a portion of SEQ ID NO:10.5. The method of claim 1 , further comprising administering to the subject a composition comprising a MASP-2 inhibitory agent.6. The method of claim 5 , ...

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Номер записи: 52
17-10-2013 дата публикации

Bispecific Anti ErbB2/Anti cMet Antibodies

Номер: US20130273054A1
Автор: Bossenmaier Birgit, Brinkmann Ulrich, Klein Christian, Niederfellner Gerhard, Schaefer Wolfgang, Schanzer Juergen Michael, Sustmann Claudio, Umana Pablo
Принадлежит: ROCHE GLYCART AG

The present invention relates to bispecific antibodies against human ErbB-2 and against human C-met, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof. 1. A bispecific antibody that specifically binds to human ErbB-2 and human c-Met comprising a first antigen-binding site that specifically binds to human ErbB-2 and a second antigen-binding site that specifically binds to human c-Met , wherein the bispecific antibody causes an increase in internalization of c-Met on OVCAR-8 cells of no more than 15% when measured after 1 hour of OVCAR-8 cell-antibody incubation as measured by a flow cytometry assay , as compared to internalization of c-Met on OVCAR-8 cells in the absence of antibody.2. The bispecific antibody according to wherein the antibody is a bivalent or trivalent bispecific antibody comprising one or two antigen-binding sites that specifically bind to human ErbB-2 and a third antigen-binding site that specifically binds to human c-Met.3. The antibody according to comprising:a) a full length antibody that specifically binds to ErbB-2 consisting of two antibody heavy chains and two antibody light chains; andb) one single chain Fab fragment that specifically binds to human c-Met,wherein the single chain Fab fragment under b) is fused to the full length antibody under a) via a peptide connector to the C- or N-terminus of the heavy or light chain of the full length antibody.4. A bispecific antibody that specifically binds to human ErbB-2 and human C-met comprising a first antigen-binding site that specifically binds to human ErbB-2 and a second antigen-binding site that specifically binds to human c-Met claim 2 , whereinthe first antigen-binding site comprises in the heavy chain variable domain a CDR3H region with the amino acid sequence of SEQ ID NO: 15, a CDR2H region with the amino acid sequence of SEQ ID NO: 16, and a CDR1H region with the amino acid sequence of SEQ ID NO:17, and in the light chain variable ...

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Номер записи: 53
24-10-2013 дата публикации

ANTI-BAFF-ANTI-IL-17 BISPECIFIC ANTIBODIES

Номер: US20130280256A1
Автор: Allan Barrett, Benschop Robert Jan, Lu Jirong
Принадлежит: ELI LILLY AND COMPANY

Bispecific antibodies are provided that specifically bind B-cell Activating Factor of the TNF Family (BAFF) and Interleukin-17A (IL-17) and are characterized as having high affinity and strong neutralizing properties to both BAFF and IL-17. The bispecific antibodies of the invention are expected to be useful in treating Lupus Nephritis (LN), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Psoriasis (Ps), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PA), primary Sjögren's Syndrome (pSS), or Multiple Myeloma (MM). 1. A bispecific antibody comprising two first polypeptides and two second polypeptides wherein the amino acid sequence of the first polypeptide is SEQ ID NO:1 and the amino acid sequence of the second polypeptide is SEQ ID NO:2.2. The bispecific antibody of claim 1 , wherein an intra-chain disulfide bond between cysteine residue 507 of SEQ ID NO: 1 and cysteine residue 707 of SEQ ID NO: 1.3. A DNA molecule comprising a polynucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO:1.4. A DNA molecule comprising a polynucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO:2.5. A DNA molecule comprising a polynucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO:1 and comprising a polynucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO:2.6. A mammalian cell comprising a polynucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO:1 and a polynucleotide encoding a polypeptide having the amino acid sequence of SEQ ID NO:2 claim 1 , which cell is capable of expressing a bispecific antibody comprising a first polypeptide having an amino acid sequence of SEQ ID NO:1 and a second polypeptide having an amino acid sequence of SEQ ID NO:2.7. A mammalian cell transformed with the DNA molecule of claim 5 , which cell is capable of expressing a bispecific antibody comprising a first polypeptide whose amino ...

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Номер записи: 54
31-10-2013 дата публикации

Humanized anti-egfl7 antibodies and methods using same

Номер: US20130287779A1
Автор: Jill Fredrickson, Mark S. Dennis, Weilan Ye
Принадлежит: Genentech Inc

The present invention concerns antibodies to EGFL7 and the uses of same.

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Номер записи: 55
31-10-2013 дата публикации

DETECTION OF A POSTTRANSLATIONALLY MODIFIED POLYPEPTIDE BY A BI-VALENT BINDING AGENT

Номер: US20130288266A1
Автор: Gerg Michael, Heindl Dieter, Klein Christian, Mertens Alfred, Schmid Volker, Schraeml Michael, Soukupova Monika, Tacke Michael
Принадлежит: ROCHE DIAGNOSTICS OPERATIONS, INC.

A bi-valent binding agent having a first monovalent binder that binds to a polypeptide epitope of a target polypeptide, a second monovalent binder that binds to a posttranslational polypeptide modification on the target polypeptide and a linker. Further disclosed are methods for the detection of a posttranslationally modified target polypeptide, for making the disclosed bi-valent binding agent, and for use of the disclosed bi-valent binding agent in histological staining procedures. 1. A bi-valent binding agent for binding a posttranslationally modified target polypeptide consisting of:{'sup': −3', '−4, 'a first monovalent binder which binds to a polypeptide epitope of a target polypeptide and having a Kdiss in the range of 5×10/sec to 10/sec;'}{'sup': −3', '−4, 'a second monovalent binder which binds to a posttranslational polypeptide modification of the target polypeptide and having a Kdiss in the range of 5×10/sec to 10/sec; and'}{'sup': '−5', 'a linker linking the first monovalent binder to the second monovalent binder, the bi-valent binding agent having a Kdiss of 3×10/sec or less.'}2. The bi-valent binding agent of claim 1 , wherein one of the first and the second monovalent binders comprises one of a single chain antibody claim 1 , a Fab-fragment claim 1 , and a Fab′-fragment of a monoclonal antibody.3. The bi-valent binding agent of claim 1 , wherein the first and second monovalent binders are derived from monoclonal antibodies and are one of Fab-fragments claim 1 , Fab′-fragments claim 1 , a Fab-fragment claim 1 , and a Fab′-fragment.4. The bi-valent binding agent of claim 1 , wherein said bi-valent binding agent has a Kdiss of 10/sec or less.5. The bi-valent binding agent of claim 1 , wherein the linker has a length of 6 to 100 nm.6. The bi-valent binding agent of claim 5 , wherein the linker further comprises a label.7. The bi-valent binding agent of claim 6 , wherein the label is a digoxigenin molecule.8. The bi-valent binding agent of claim 5 , wherein ...

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Номер записи: 56
31-10-2013 дата публикации

DETECTION OF A POLYPEPTIDE DIMER BY A BIVALENT BINDING AGENT

Номер: US20130288267A1
Автор: Gerg Michael, Heindl Dieter, Mertens Alfred, Rutz Christoph, Schraeml Michael, Soukupova Monika, Sustmann Claudio, Tacke Michael, van Dieck Jan
Принадлежит: ROCHE DIAGNOSTICS OPERATIONS, INC.

A bivalent binding agent, capable of binding a polypeptide dimer, consisting of two monovalent binders linked to each other via a linker, the first monovalent binder binds an epitope of a first target polypeptide comprised in said dimer and the second monovalent binder binds to an epitope of a second target polypeptide comprised in said dimer. Each monovalent binder has a Kdiss in the range of 5×10/sec to 10/sec, and the bivalent binding agent has a Kdiss of 3×10/sec or less. Methods of making and using such bivalent binding agent in histological staining procedures are also disclosed. 1. A bivalent binding agent capable of binding a polypeptide dimer consisting of:{'sup': −3', '−4, 'a first monovalent binder which binds to an epitope of a first target polypeptide comprising a polypeptide dimer, the first monovalent binder having a Kdiss in the range of 5×10/sec to 10/sec;'}{'sup': −3', '−4, 'a second monovalent binder which binds to an epitope of a second target polypeptide comprising the polypeptide dimer, the second monovalent binder having a Kdiss in the range of 5×10/sec to 10/sec; and'}{'sup': '−5', 'a linker linking the first monovalent binder to the second monovalent binder, the bivalent binding agent having a Kdiss of 3×10/sec or less.'}2. The bi-valent binding agent of claim 1 , wherein one of the first and the second monovalent binders comprises one of a single chain antibody claim 1 , a Fab-fragment claim 1 , and a Fab′-fragment of a monoclonal antibody.3. The bi-valent binding agent of claim 1 , wherein the first and second monovalent binders are derived from monoclonal antibodies and are one of Fab-fragments claim 1 , Fab′-fragments claim 1 , a Fab-fragment claim 1 , and a Fab′-fragment.4. The bi-valent binding agent of claim 1 , wherein the linker has a length of 6 to 100 nm.5. The bivalent binding agent of claim 1 , wherein the linker is an L-DNA-linker.6. The bi-valent binding agent of claim 1 , wherein the linker further comprises a label.7. The bi ...

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Номер записи: 57
31-10-2013 дата публикации

Polynucleotides encoding antibodies that bind both il-17a and il-17f

Номер: US20130288304A1
Автор: Monica J. Huber, Scott R. Presnell, Stephen R. Jaspers
Принадлежит: Zymogenetics Inc

The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-17A and IL-17F. IL-17A and IL-17F are cytokines that are involved in inflammatory processes and human disease. The present invention includes antibodies that bind both IL-17A and IL-17F, hybridomas that produce the antibodies, and methods of using the same in inflammation.

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Номер записи: 58
31-10-2013 дата публикации

Polynucleotide construct capable of displaying fab in a cell-free translation system, and method for manufacturing and screening fab using same

Номер: US20130288908A1
Автор: Kotomi Oda, Kouichi Wada, Risako Fujita, Takashi Kanamori, Takuya Ueda, Yasuhiro Fujino, Yoshihiro Shimizu
Принадлежит: Mitsubishi Tanabe Pharma Corp, University of Tokyo NUC

The polynucleotide construct of (1) or (2) below is used to perform ribosome display, CIS display and/or mRNA display in order to screen a Fab against an antigen of interest: (1) a polynucleotide construct which monocistronically comprises a ribosome-binding sequence, Fab first chain-coding sequence, linker peptide-coding sequence, Fab second chain-coding sequence and scaffold-coding sequence in this order, and further comprises at its 3′-end a structure necessary for maintaining a complex with the Fab encoded by itself, and (2) a polynucleotide construct which comprises a Fab first chain-expressing cistron and a Fab second chain-expressing cistron each containing a ribosome-binding sequence, a Fab first chain-coding sequence or Fab second chain-coding sequence, and a scaffold-coding sequence in this order, the first Fab-expressing cistron further comprising at its 3′-end a ribosome stall sequence, said Fab second chain-expressing cistron further comprising at its 3′-end a structure necessary for maintaining a complex with the Fab encoded by itself.

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Номер записи: 59
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: 60
07-11-2013 дата публикации

BINDING PROTEINS HAVING TETHERED LIGHT CHAINS

Номер: US20130295084A1
Автор: Hunter Michael, Swanson Ronald
Принадлежит: JANSSEN BIOTECH, INC.

The present invention relates to binding proteins having tethered light chains and methods of making and using them. 1. A binding protein comprising a tethered light chain , a first heavy chain and a second heavy chain that specifically binds at least one antigen.2. The binding protein of wherein the tethered light chain is an inside-out tethered light chain claim 1 , the first heavy chain is a first inside-out heavy chain and the second heavy chain is a second inside-out heavy chain.3. The binding protein of claim 2 , wherein the inside-out tethered light chain comprises VH1-CL-linker-VH2-CL claim 2 , the first inside-out tethered heavy chain comprises VL1-CH claim 2 , and the second inside-out tethered heavy chain comprises VL2-CH claim 2 , whereini) VL1 is a first light chain variable region;ii) VL2 is a second light chain variable region;iii) CL is a light chain constant region;iv) VH1 is a first heavy chain variable region;v) VH2 is a second heavy chain variable region;vi) CH is a heavy chain constant region; andvii) linker is a polypeptide linker.4. The binding protein of claim 3 , wherein the VL1 and the VL2 comprise identical or substantially identical amino acid sequences.5. The binding protein of claim 3 , which is bispecific.6. The binding protein of claim 3 , wherein the VL1 claim 3 , the VL2 claim 3 , the VH1 and the VH2 comprise human claim 3 , humanized claim 3 , human-adapted or murine polypeptide sequences.7. The binding protein of claim 3 , wherein the CL is of kappa (κ) or lambda (λ) type and the CH is of IgG1 claim 3 , IgG2 claim 3 , IgG3 claim 3 , or IgG4 type.8. The binding protein of claim 3 , wherein the CL and CH are of human origin.9. The binding protein of claim 3 , wherein the linker is about 5-50 amino acids long.10. The binding protein of claim 9 , wherein the linker is (GS)(SEQ ID NO: 1) claim 9 , (GS)(SEQ ID NO: 2) claim 9 , (GS)(SEQ ID NO: 3) or (GS)(SEQ ID NO: 4).11. The binding protein of claim 3 , wherein the binding protein binds ...

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Номер записи: 61
07-11-2013 дата публикации

Human Antibodies to Fel d1 and Methods of Use Thereof

Номер: US20130295097A1
Автор: MURPHY Andrew J., Orengo Jamie
Принадлежит: Regeneron Pharmaceuticals, Inc.

The present invention provides antibodies that bind to the cat allergen, Fel d1, compositions comprising the antibodies, nucleic acids encoding the antibodies and methods of use of the antibodies. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to Fel d1. The antibodies of the invention are useful for binding to the Fel d1 allergen in vivo, thus preventing binding of the Fel d1 allergen to pre-formed IgE on the surface of mast cells or basophils. In doing so, the antibodies act to prevent the release of histamine and other inflammatory mediators from mast cells and/or basophils, thus ameliorating the untoward response to the cat allergen in sensitized individuals. The antibodies of the invention may also be useful for diagnostic purposes to determine if a patient is allergic to the Fel d1 cat allergen. 1. An isolated human monoclonal antibody or antigen-binding fragment thereof that binds specifically to Fel d1 , wherein the antibody or antigen binding fragment thereof is an isotype other than an IgA isotype.2. The isolated human monoclonal antibody or antigen-binding fragment thereof of having an isotype selected from the group consisting of an IgG1 claim 1 , an IgG2 and an IgG4.3. The isolated human monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the human antibody or antigen-binding fragment thereof binds specifically to Fel d1 with a Kequal to or less than 10M claim 1 , as measured by surface plasmon resonance.4. The isolated human monoclonal antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody comprises the three heavy chain CDRs (HCDR1 claim 1 , HCDR2 and HCDR3) contained within any one of the heavy chain variable region (HCVR) sequences selected from the group consisting of SEQ ID NOs: 2 claim 1 , 18 claim 1 , 34 claim 1 , 50 claim 1 , 66 claim 1 , 82 claim 1 , 98 claim 1 , 114 claim 1 , 130 claim 1 , 146 claim 1 , 162 claim 1 , 178 claim 1 , 194 ...

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Номер записи: 62
07-11-2013 дата публикации

MULTISPECIFIC EPITOPE BINDING PROTEINS AND USES THEREOF

Номер: US20130295098A1
Автор: Dimasi Nazzareno, GAO CHANGSHOU, Hay Carl, WU HERREN
Принадлежит:

The present invention relates to multispecific epitope binding proteins, methods of making, and uses thereof in the prevention, management, treatment or diagnosis of acute or chronic diseases. 1139-. (canceled)140. An inverted antibody protein comprising at least a first and a second polypeptide chain wherein said first chain is a “light-like” chain comprising at least one antibody heavy chain variable region (VH) linked to a CH1 domain and said second chain is a “heavy-like” chain comprising an antibody light chain variable region (VL) linked to a Ckappa/lambda domain , said Ckappa/lambda region further linked to an Fc region wherein said variable region in said first chain associates with the variable region in said second chain to form an epitope binding site.141. The inverted antibody protein of claim 140 , wherein said first light-like chain is disulphide linked to said second heavy-like chain.142. An inverted antibody protein of comprising at least four polypeptide chains claim 140 , with at least two chains being “light-like” chains and at least two chains being “heavy-like” chains.143. The inverted antibody protein of claim 140 , wherein the heavy-like chain comprises all or part of a hinge region.144. The inverted antibody protein of claim 140 , wherein the light-like chain comprises all or part of a hinge region.145. The inverted antibody protein of claim 143 , wherein the inverted antibody protein is a multimer of four polypeptide chains wherein the heavy-like chains comprise a second VL (VL2) linked to a second Ckappa/lambda region linked N-terminal to the VL domain (VL1) claim 143 , and wherein the light-like chains comprise a second VH domain (VH2) linked to a second CH1 domain linked N terminal to the VH domain (VH1).146. The inverted antibody protein of claim 143 , wherein the inverted antibody protein is a multimer of six polypeptide chains claim 143 , wherein the heavy-like chains comprise a second VL (VL2) linked to a second Ckappa/lambda region ...

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Номер записи: 63
14-11-2013 дата публикации

DISULFIDE STABILIZED DVD-IG MOLECULES

Номер: US20130302336A1
Автор: Heywood Sam Philip, Humphreys David Paul
Принадлежит: UCB PHARMA S.A.

A re-epoxidized polyfunctional epoxy resin composition comprising the reaction product of: (I) an epoxidized polyfunctional epoxy resin oligomeric composition comprising a polyfunctional aliphatic or cycloaliphatic epoxy resin which has been isolated from an epoxy resin product formed as a result of an epoxidation process comprising the reaction of: (i) an aliphatic or cycloaliphatic hydroxyl-containing material; (ii) an epihalohydrin, (iii) a basic-acting substance, in the presence of (iv) a non-Lewis acid catalyst; and (v) optionally, one or more solvents; (II) an epihalohydrin; (III) a basic acting substance; in the presence of (IV) a non-Lewis acid catalyst; and (V) optionally, one or more solvents. A curable epoxy resin composition of the re-epoxidized polyfunctional epoxy resin composition and a thermoset of the curable composition is also disclosed. 1. A re-epoxidized polyfunctional epoxy resin composition comprising the reaction product of: (A) an aliphatic or cycloaliphatic hydroxyl-containing material;', '(B) an epihalohydrin,', '(C) a basic-acting substance,', '(D) a non-Lewis acid catalyst; and', '(E) optionally, one or more solvents;, '(I) an epoxidized polyfunctional epoxy resin oligomeric composition comprising a polyfunctional aliphatic or cycloaliphatic epoxy resin which has been isolated from an epoxy resin product formed as a result of an epoxidation process comprising the reaction of(II) an epihalohydrin;(III) a basic acting substance;(IV) a non-Lewis acid catalyst; and(V) optionally, one of more solvents.2. The composition of wherein the aliphatic or cycloaliphatic hydroxyl containing material claim 1 , component (A) claim 1 , comprises one or more of cyclohexanedialkanols claim 1 , cyclohexenedialkanols claim 1 , cyclohexanolmonoalkanols claim 1 , cyclohexenolmonoalkanols claim 1 , decahydronaphthalenedialkanols claim 1 , octahydronaphthalenedialkanols; 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthalenedialkanols; or bridged cyclohexanols ...

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Номер записи: 64
14-11-2013 дата публикации

Multispecific Antibody Targeting and Multivalency Through Modular Recognition Domains

Номер: US20130303733A1
Автор: Barbas Carlos F.
Принадлежит:

Antibodies containing one or more modular recognition domains (MRDs) that can be used to target the antibodies to specific sites are described. The use of antibodies containing one or more modular recognition domains to treat disease, and methods of making antibodies containing one or more modular recognition domains are also described. 1. A complex comprising an antibody and at least one modular recognition domain (MRD) , wherein the antibody is (a) murine , (b) chimeric , (c) humanized , or (d) human.2. The complex of claim 1 , wherein the antibody is multispecific.3. The complex of claim 1 , wherein the antibody is an IgG.4. The complex of claim 1 , wherein the MRD binds to a target selected from the group consisting of: an integrin claim 1 , a cytokine claim 1 , an angiogenic cytokine claim 1 , vascular endothelial growth factor (VEGF) claim 1 , insulin-like growth factor-I receptor (IGF-IR) claim 1 , a tumor antigen claim 1 , CD20 claim 1 , an epidermal growth factor receptor (EGFR) claim 1 , the ErbB2 receptor claim 1 , the ErbB3 receptor claim 1 , tumor associated surface antigen epithelial cell adhesion molecule (Ep-CAM) claim 1 , an angiogenic factor claim 1 , an angiogenic receptor claim 1 , cell surface antigen claim 1 , soluble ligand claim 1 , vascular homing peptide claim 1 , and nerve growth factor.5. The complex of claim 4 , wherein the target is a human protein.6. The complex of claim 1 , wherein the antibody binds to a target selected from the group consisting of an integrin claim 1 , a cyokine claim 1 , an angiogenic cytokine claim 1 , vascular endothelial growth factor (VEGF) claim 1 , insulin-like growth factor-I receptor (IGF-IR) claim 1 , a tumor antigen claim 1 , CD20 claim 1 , an epidermal growth factor receptor (EGFR) claim 1 , the ErbB2 receptor claim 1 , the ErbB3 receptor claim 1 , tumor associated surface antigen epithelial cell adhesion molecule (Ep-CAM) claim 1 , an angiogenic factor claim 1 , an angiogenic receptor claim 1 , cell ...

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Номер записи: 65
28-11-2013 дата публикации

BISPECIFIC ANTIBODIES AND METHODS OF USING THE SAME

Номер: US20130315911A1
Автор: Cardarelli Josephine M., CHAKRABORTY Indrani, Chen Guodong, Kempe Thomas D., KRYSTEK Stanley R., PRESNELL Scott R., RIXON Mark W., Schneeweis Lumelle A., Sheppard Paul O., SRINIVASAN Mohan, Stevens Brenda L., Wei Hui, Witte Alison, Wong Susan C.
Принадлежит: BRISTOL-MYERS SQUIBB COMPANY

The present invention relates to antagonizing the activity of IL-17A, IL-17F and IL-23 using bispecific antibodies that comprise a binding entity that is cross-reactive for IL-17A and IL-17F and a binding entity that binds IL-23p19. The present invention relates to novel bispecific antibody formats and methods of using the same. 1. A bispecific antibody comprising an IL-17A/F binding entity and an IL-23 binding entity , wherein the IL-23 binding entity comprises two pairs of immunoglobulin chains , each pair having one light and one heavy chain , and the IL-17A/F binding entity comprises two Fab fragments each comprising a light chain and the Cand variable regions of a heavy chain , and the Fab fragments of the IL-17A/F binding entity are linked to the C-termini of the heavy chains of the IL-23 binding entity.2. The bispecific antibody of wherein the light chains of the IL-17A/F binding entity and the IL-23 binding entity comprise a variable domain comprising a CDR1 having the amino acid sequence of SEQ ID NO:22 claim 1 , a CDR2 having the amino acid sequence of SEQ ID NO:23 claim 1 , and a CDR3 having the sequence of SEQ ID NO:24.3. The bispecific antibody of wherein the light chains of the IL-17A/F binding entity and the IL-23 binding entity comprise a variable domain comprising the amino acid sequence of SEQ ID NO:9.4. The bispecific antibody of wherein the light chains of the IL-17A/F binding entity and the IL-23 binding entity comprise a constant domain comprising the amino acid sequence of SEQ ID NO:10.5. The bispecific antibody of wherein the light chains of the IL-17A/F binding entity and the IL-23 binding entity comprise a variable domain comprising the amino acid sequence of SEQ ID NO:9 and a constant domain comprising the amino acid sequence of SEQ ID NO:10.6. The bispecific antibody of wherein the heavy chains of the IL-17A/F binding entity comprise a variable domain comprising a CDR1 having the amino acid sequence of SEQ ID NO:25 claim 1 , a CDR2 having ...

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Номер записи: 66
28-11-2013 дата публикации

Methods of Purifying Antibodies

Номер: US20130317200A1
Автор: Depoisier Jean-Francois, Elson Greg, Fischer Nicolas, Fouque Nicolas, Magistrelli Giovanni
Принадлежит: Novlmmune S.A.

The invention provides methods of purifying antibodies using various antibody-specific purification media to rapidly and efficiently separate mixtures of antibodies, antibody fragments and/or antibody components to isolate a desired antibody product from the mixture. The invention relates to the purification of bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, e.g., antibodies composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other a Lambda constant domain, including antibodies of different specificities that share a common heavy chain. The invention also provides the methods of efficiently purifying intact antibodies by separating the intact antibody from non-intact antibodies including free light chains. 1. A method of purifying a bispecific monoclonal antibody carrying a different specificity in each combining site and consisting of two copies of a single heavy chain polypeptide and a first light chain comprising a kappa constant region and a second light chain comprising a lambda constant region , the method comprising the steps of:(a) providing a mixed antibody composition that comprises one or more of the bispecific monoclonal antibodies carrying a different specificity in each combining site and consisting of two copies of a single heavy chain polypeptide and a first light chain comprising a kappa constant region and a second light chain comprising a lambda constant region (bispecific MAb); one or more monospecific monoclonal antibodies having two lambda light chains or portions thereof (λ-MAb); and one or more monospecific monoclonal antibodies having two kappa light chains or portions thereof (κ-MAb);(b) providing a separation means that has a specific affinity for a kappa light chain constant region or a lambda light chain constant region;(c) contacting the separation means with the mixed antibody composition under conditions ...

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Номер записи: 67
12-12-2013 дата публикации

Chemokine receptor binding polypeptides

Номер: US20130330346A1
Автор: Bruno DOMBRECHT, Carlo Boutton, Gino Anselmus Van Heeke, Judith Baumeister, Karen Cromie, Marie-Ange Buyse, Marie-Paule Bouche, Michelle Bradley, Soren Steffensen, Stephanie Staelens, Steven John Charlton, Veerle Snoeck, Zarin Brown
Принадлежит: Individual

The present invention relates to polypeptides directed against or specifically binding to chemokine receptor CXCR2 and in particular to polypeptides capable of modulating signal transduction from CXCR2. The invention also relates to nucleic acids, vectors and host cells capable of expressing the polypeptides of the invention, pharmaceutical compositions comprising the polypeptides and uses of said polypeptides and compositions for treatment of diseases involving aberrant functioning of CXCR2.

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Номер записи: 68
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: 69
26-12-2013 дата публикации

Human antibodies to the glucagon receptor

Номер: US20130344538A1
Автор: Haruka Okamoto, Joyce Harp, Mark Sleeman
Принадлежит: Regeneron Pharmaceuticals Inc

The present invention provides antibodies that bind to the human glucagon receptor, designated GCGR and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human GCGR. The antibodies of the invention are useful for lowering blood glucose levels and blood ketone levels and are also useful for the treatment of diseases and disorders associated with one or more GCGR biological activities, including the treatment of diabetes, diabetic ketoacidosis and long-term complications associated with diabetes, or other metabolic disorders characterized in part by elevated blood glucose levels.

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Номер записи: 70
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: 71
09-01-2014 дата публикации

Dual Variable Region Antibody-Like Binding Proteins Having Cross-Over Binding Region Orientation

Номер: US20140011238A1
Автор: Baurin Nicolas, Biel Chirstian, Corvey Carsten, Lange Christian, LI Danxi, MIKOL Vincent, Rao Ercole, Steinmetz Anke
Принадлежит: SANOFI

The invention provides antibody-like binding proteins comprising four polypeptide chains that form four antigen binding sites, wherein each pair of polypeptides forming an antibody-like binding protein possesses dual variable domains having a cross-over orientation. The invention also provides methods for making such antigen-like binding proteins. 132-. (canceled)33. An isolated nucleic acid molecule comprising a nucleotide sequence encoding an antibody-like binding protein comprising four polypeptide chains that form four antigen binding sites , wherein two polypeptide chains have a structure represented by the formula:{'br': None, 'sub': L1', '1', 'L2', '2', 'L, 'V-L-V-L-C\u2003\u2003[I]'} {'br': None, 'sub': H2', '3', 'H1', '4', 'H1, 'V-L-V-L-C-Fc\u2003\u2003[II]'}, 'and two polypeptide chains have a structure represented by the formula [{'sub': 'L1', 'Vis a first immunoglobulin light chain variable domain;'}, {'sub': 'L2', 'Vis a second immunoglobulin light chain variable domain;'}, {'sub': 'H1', 'Vis a first immunoglobulin heavy chain variable domain;'}, {'sub': 'H2', 'Vis a second immunoglobulin heavy chain variable domain;'}, {'sub': 'L', 'Cis an immunoglobulin light chain constant domain;'}, {'sub': H1', 'H1, 'Cis the immunoglobulin Cheavy chain constant domain;'}, {'sub': H2', 'H3, 'Fc is the immunoglobulin hinge region and C, Cimmunoglobulin heavy chain constant domains; and'}, {'sub': 1', '2', '3', '4, 'L, L, L, and Lare amino acid linkers;'}], 'whereinand wherein the polypeptides of formula I and the polypeptides of formula II form a cross-over light chain-heavy chain pair.34. An expression vector comprising the nucleic acid molecule of either or .35. An isolated host cell comprising the nucleic acid molecule of either or .36. An isolated host cell comprising the expression vector of .37. The host cell of claim 35 , wherein the host cell is a mammalian cell or an insect cell.38. (canceled)39. A method for making an antibody-like binding protein ...

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Номер записи: 72
16-01-2014 дата публикации

Anti-CD19 Antibodies

Номер: US20140017197A1
Автор: GOLDENBERG David M., HANSEN Hans J., Qu Zhengxing
Принадлежит: IMMUNOMEDICS, INC.

The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hA19 VH sequence. 1. A bispecific antibody comprising:a) a first anti-CD19 antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises (i) the light chain complementarity determining region CDR sequences CDR1 of SEQ ID NO: 16 (KASQSVDYDGDSYLN); CDR2 of SEQ ID NO: 17 (DASNLVS); and CDR3 of SEQ ID NO: 18 (QQSTEDPWT); (ii) the heavy chain CDR sequences CDR1 of SEQ ID NO: 19 (SYWMN); CDR2 of SEQ ID NO: 20 (QIWPGDGDTNYNGKFKG) and CDR3 of SEQ ID NO: 21 (RETTTVGRYYYAMDY), and (iii) human antibody framework (FR) and constant region sequences with one or more framework region amino acid residues substituted from the corresponding framework region sequences of the parent murine antibody, wherein said substituted FR residues comprise the substitution of serine for phenylalanine at Kabat residue 91 of the heavy chain variable region; andb) a second antibody or humanized antibody or antigen-binding fragment thereof.2. The bispecific antibody of claim 1 , wherein the anti-CD19 antibody or antigen-binding fragment thereof comprises the sequences of SEQ ID NO:7 (hA19VK) and SEQ ID NO:10 (hA19VH).3. The bispecific antibody of claim 1 , wherein the bispecific antibody is an anti-CD19 X anti-CD3 antibody.4. The bispecific antibody of claim 1 , wherein the second antibody ...

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Номер записи: 73
16-01-2014 дата публикации

Il-17 binding proteins

Номер: US20140017246A1
Автор: Anca Clabbers, Anwar Murtaza, Bradford L. McRae, Chung-Ming Hsieh, Craig Wallace, Edit Tarcsa, Jennifer M. Perez, John E. Memmott, Margaret Hugunin, Mary R. Leddy, Shaughn H. Bryant, Suju Zhong, Yuliya Kutskova
Принадлежит: AbbVie Inc

Proteins that bind IL-17 and/or IL-17F are described along with there use in composition and methods for treating, preventing, and diagnosing IL-17 related diseases and for detecting IL-17 in cells, tissues, samples, and compositions.

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Номер записи: 74
23-01-2014 дата публикации

ANTIBODIES THAT BIND IL-4 AND/OR IL-13 AND THEIR USES

Номер: US20140023649A1
Автор: DAVISON Matthew, Kruip Jochen, LI Danxi, MIKOL Vincent, Rao Ercole
Принадлежит: SANOFI

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis. 149-. (canceled)50. A bispecific antibody or bispecific antibody fragment thereof that specifically binds to IL-13 and IL-4;{'sub': L1', '1', 'L2', 'L', 'H1', '2', 'H2', 'H1, 'wherein the bispecific antibody or bispecific antibody fragment thereof comprises two light chains having the structure V-L-V-C, and two heavy chains having the structure V-L-V-C;'}{'sub': L', 'H1, 'wherein Cis a constant light chain domain and Cis a constant heavy chain domain;'}{'sub': 1', '2, 'wherein Land Lare amino acid linkers; and'}wherein:{'sub': L1', 'L2', 'H1', 'H2, '(a) Vcomprises the amino acid sequence of SEQ ID NO: 1, Vcomprises the amino acid sequence of SEQ ID NO: 3, Vcomprises the amino acid sequence of SEQ ID NO: 2, and Vcomprises the amino acid sequence of SEQ ID NO: 4;'}{'sub': L1', 'L2', 'H1', 'H2, '(b) Vcomprises the amino acid sequence of SEQ ID NO: 1, Vcomprises the amino acid sequence of SEQ ID NO: 3, Vcomprises the amino acid sequence of SEQ ID NO: 2, and Vcomprises the amino acid sequence of SEQ ID NO: 5;'}{'sub': L1', 'L2', 'H1', 'H2, '(c) Vcomprises the amino acid sequence of SEQ ID NO: 3, Vcomprises the amino acid sequence of SEQ ID NO: 1, Vcomprises the amino acid sequence of SEQ ID NO: 4, and Vcomprises the amino acid sequence of SEQ ID NO: 2;'}{'sub': L1', 'L2', 'H1', 'H2, '(d) Vcomprises the amino acid sequence of SEQ ID NO: 3, Vcomprises the amino acid sequence of SEQ ID NO: 1, Vcomprises the amino acid sequence of SEQ ID NO: 5, and Vcomprises the amino acid sequence of SEQ ID NO: 2;'}{'sub': L1', 'L2', 'H1', 'H2, '(e) Vcomprises the amino acid sequences RASESVDSYGQSYMH (SEQ ID NO: 8), LASNLES (SEQ ID NO: ...

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Номер записи: 75
06-02-2014 дата публикации

ANTIGEN BINDING FORMATS FOR USE IN THERAPEUTIC TREATMENTS OR DIAGNOSTIC ASSAYS

Номер: US20140037631A1
Автор: Baty Daniel, Chames Patrick, Kerfelec Brigitte, Mansais Martine, Rozan Caroline
Принадлежит: UNIVERSITE D'AIX-MARSEILLE

The present invention relates to antigen binding formats for use in therapeutic treatments or diagnostic assays. The present invention relates to an antigen-binding format consisting of: a first fusion protein wherein the CH1 constant domain of an antibody is fused i) by its N-terminal end to the C-terminal end of a variable domain of an antibody and ii) by its C-terminal end to the N-terminal end of a variable domain of an antibody and, a second fusion protein wherein the CL constant domain of an antibody is fused by its N-terminal end to the C-terminal end of a variable domain of an antibody. 1. An antigen-binding format comprising:a first fusion protein wherein a CH1 constant domain of an antibody is fused i) by its N-terminal end to a C-terminal end of a first variable domain of an antibody and ii) by its C-terminal end to an N-terminal end of a second variable domain of an antibody and,a second fusion protein wherein a CL constant domain of an antibody is fused by its N-terminal end to a C-terminal end of a third variable domain of an antibody, wherein said first, second and third variable domains of an antibody may be the same or different.2. The antigen binding format according to wherein said CL domain is from a lambda (λ) or a kappa (κ) light chain.3. The antigen binding format according to claim 1 , wherein said CH1 domain is an IgG claim 1 , an IgA claim 1 , an IgD claim 1 , an IgE or an IgM.4. The antigen binding format according to claim 1 , wherein the first claim 1 , second and third variable domains are selected from the group consisting of VH domains claim 1 , VL domains claim 1 , and single domain antibodies (sdAbs).5. The antigen binding format according to claim 1 , wherein one or more of the first claim 1 , second and third variable domains is specific for an immune cell regulatory molecule or for a cancer antigen.6. The antigen binding format according to claim 1 , wherein the CH1 constant domain of the first fusion protein is fused by its C- ...

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Номер записи: 76
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: 77
27-02-2014 дата публикации

Dual Variable Region Antibody-Like Binding Proteins Having Cross-Over Binding Region Orientation

Номер: US20140056895A1
Автор: Baurin Nicolas, Biel Chirstian, Corvey Carsten, Lange Christian, LI Danxi, MIKOL Vincent, Rao Ercole, Steinmetz Anke
Принадлежит: SANOFI

The invention provides antibody-like binding proteins comprising four polypeptide chains that form four antigen binding sites, wherein each pair of polypeptides forming an antibody-like binding protein possesses dual variable domains having a cross-over orientation. The invention also provides methods for making such antigen-like binding proteins. 1. An antibody-like binding protein comprising four polypeptide chains that form four antigen binding sites , wherein two polypeptide chains have a structure represented by the formula:{'br': None, 'sub': L1', '1', 'L2', '2', 'L, 'V-L-V-L-C\u2003\u2003[I]'} {'br': None, 'sub': H2', '3', 'H1', '4', 'H1, 'V-L-V-L-C-Fc\u2003\u2003[II]'}, 'and two polypeptide chains have a structure represented by the formula [{'sub': 'L1', 'Vis a first immunoglobulin light chain variable domain;'}, {'sub': 'L2', 'Vis a second immunoglobulin light chain variable domain;'}, {'sub': 'H1', 'Vis a first immunoglobulin heavy chain variable domain;'}, {'sub': 'H2', 'Vis a second immunoglobulin heavy chain variable domain;'}, {'sub': 'L', 'Cis an immunoglobulin light chain constant domain;'}, {'sub': H1', 'H1, 'Cis the immunoglobulin Cheavy chain constant domain;'}, {'sub': H2', 'H3, 'Fc is the immunoglobulin hinge region and C, Cimmunoglobulin heavy chain constant domains; and'}, {'sub': 1', '2', '3', '4, 'L, L, L, and Lare amino acid linkers;'}], 'wherein{'sub': 2', '4, 'claim-text': [{'sub': 2', '4, '(a) the length of Lis at least twice the length of L; or'}, {'sub': 4', '2, '(b) the length of Lis at least twice the length of L;'}], 'wherein Land Lare both at least one amino acid in length, and'}and wherein the polypeptides of formula I and the polypeptides of formula II form a cross-over light chain-heavy chain pair.210-. (canceled)11. The antibody-like binding protein of claim 1 , wherein the binding protein is capable of specifically binding one or more antigen targets.12. The antibody-like binding protein of claim 11 , wherein the one or more ...

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Номер записи: 78
27-02-2014 дата публикации

BISPECIFIC THREE-CHAIN ANTIBODY-LIKE MOLECULES

Номер: US20140056897A1
Автор: Buelow Roland, van Schooten Wim
Принадлежит: HCO Antibody, Inc.

The present invention relates to novel bispecific three-chain antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific three-chain antibody-like molecules (TCAs) capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases. 1. A bispecific three-chain antibody-like molecule (TCA) comprising(a) an antibody heavy and light chain pair, or a functional fragment thereof, comprising at antigen-binding region specifically binding to a first binding target and at least one heavy chain constant region sequence; and(b) a heavy chain antibody comprising an antigen-binding region specifically binding to a second binding target, and a CH2, CH3 and/or CH3 region, in the absence of a CH1 region.2. The bispecific TCA of claim 1 , wherein the antibody heavy and light chain pair comprises an antigen-binding region specifically binding to a first binding target and a CH1 sequence.3. The bispecific TCA of claim 1 , wherein the antibody heavy and light chain pair comprises an antigen-binding region specifically binding to a first binding target and a CH1 and a CH2 sequence.4. The bispecific TCA of claim 1 , wherein the antibody heavy and light chain pair comprises an antigen-binding region specifically binding to a first binding target and a CH1 claim 1 , a CH2 claim 1 , and a CH3 sequence.54. The bispecific TCA of claim 1 , claim 1 , claim 1 , or claim 1 , wherein the antibody heavy and light chain pair further comprises a hinge region.6. The bispecific TCA of claim 1 , wherein the antibody heavy and light chain claim 1 , or functional fragments thereof claim 1 , are covalently linked to each other.7. The bispecific TCA of claim 6 , wherein the antibody heavy and light chain claim 6 , or functional fragments thereof claim 6 , are linked by a disulfide bond.8. The bispecific TCA of claim 1 , wherein the heavy chain antibody comprises an antigen-binding ...

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Номер записи: 79
13-03-2014 дата публикации

PROTEIN COMPLEXES AND METHODS OF MANUFACTURING BISPECIFIC ANTIBODIES USING THE PROTEIN COMPLEXES

Номер: US20140073767A1
Автор: KIM Min-kyung, LEE Jae-il, LEE Jung-Wook, SHIM Seon-hui
Принадлежит:

A protein complex comprising (i) a first fusion protein comprising (a) a first polypeptide that comprises a first antigen-binding site and (b) a first binding protein linked to a terminus of the first polypeptide; and (ii) a second fusion protein comprising (a) a second polypeptide that comprises a second antigen-binding site and (b) a second binding protein linked to a terminus of the second polypeptide, wherein the protein complex comprises an amino acid sequence that enables cleavage between the first polypeptide and the first binding protein, and/or between the second polypeptide and the second binding protein, as well as a method for preparing a bi-specific antibody and related methods and compositions. 1. A protein complex comprising:(i) a first fusion protein comprising (a) a first polypeptide that comprises a first antigen-binding site and (b) a first binding protein linked to a terminus of the first polypeptide; and(ii) a second fusion protein comprising (a) a second polypeptide that comprises a second antigen-binding site and (b) a second binding protein linked to a terminus of the second polypeptide,wherein the protein complex comprises an amino acid sequence that enables cleavage between the first polypeptide and the first binding protein, or between the second polypeptide and the second binding protein, or wherein the protein complex comprises both an amino acid sequence that enables cleavage between the first polypeptide and the first binding protein, and an amino acid sequence that enables cleavage between the second polypeptide and the second binding protein.2. The protein complex of claim 1 , wherein the first antigen-binding site and the second antigen-binding site are positioned at the N-terminus of the first polypeptide and the second polypeptide claim 1 , respectively.3. The protein complex of claim 1 , wherein an antigen specifically binding to the first antigen-binding site and an antigen specifically binding to the second antigen-binding site ...

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Номер записи: 80
20-03-2014 дата публикации

COMBINATION THERAPIES COMPRISING ANTI-ERBB3 AGENTS

Номер: US20140079703A1
Автор: Huhalov Alexandra, McDonagh Charlotte, ZHANG BO
Принадлежит: Merrimack Pharmaceuticals, Inc.

Disclosed are methods and compositions for inhibiting the growth of a tumor (e.g., a malignant tumor) in a subject. In particular, combination therapies for treating a tumor in a subject by co-administering an agent selected from i) an effective amount of an anti-estrogen agent; ii) an effective amount of a receptor tyrosine kinase inhibitor; iii) an effective amount of a MEK/PI3 kinase/AKT inhibitor; iv) an effective amount of MM-151; v) an effective amount of an mTOR inhibitor; and/or vi) an effective amount of trastuzumab or TMD1, and/or combinations thereof; and an effective amount of a bispecific anti-ErbB2/anti-ErbB3 antibody. Also disclosed is a bispecific anti-ErbB2/anti-ErbB3 antibody for use in the therapy of a tumor in combination with an agent selected from i) an effective amount of an anti-estrogen agent; ii) an effective amount of a receptor tyrosine kinase inhibitor; iii) an effective amount of a MEK/PI3 kinase/AKT inhibitor; iv) an effective amount of MM-151; v) an effective amount of an mTOR inhibitor; and/or vi) an effective amount of trastuzumab or TMD1, and/or combinations thereof. 1. A method of treating a subject with a malignant tumor , the method comprising co-administering to the subject an agent selected from one or more of i) an effective amount of an anti-estrogen agent; ii) an effective amount of a receptor tyrosine kinase inhibitor; iii) an effective amount of a MEK/PI3 kinase/AKT inhibitor; iv) an effective amount of MM-151; v) an effective amount of an mTOR inhibitor; and/or vi) an effective amount of trastuzumab or ado-trastuzumab emtanstine; and an effective amount of a bispecific anti-ErbB2/anti-ErbB3 antibody.28.-. (canceled)9. The method of claim 1 , wherein the co-administration to the subject does not create a drug-drug interaction-mediated toxicity in the subject.10. The method of claim 1 , wherein the co-administration to the subject creates a substantially additive or superadditive effect.11. (canceled)12. The method of ...

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Номер записи: 81
20-03-2014 дата публикации

BISPECIFIC IMMUNOBINDERS DIRECTED AGAINST TNF AND IL-17

Номер: US20140079705A1
Автор: Benatuil Lorenzo, Brito Alyssa, Clabbers Anca, Eaton Lucia, HSIEH Chung-Ming, Hugunin Margaret, Kutskova Yuliya, Memmott John, Perez Jennifer, Zhong Suju
Принадлежит:

Engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease are provided. 1. A binding protein capable of binding TNF , the binding protein comprising a polypeptide chain , wherein the polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n , wherein;VD1 is a first heavy chain variable domain;VD2 is a second heavy chain-variable domain;C is a heavy chain constant domain;X1 is a linker with the proviso that it is not CH1;X2 is an Fc region;(X1)n, wherein n is 0 or 1;(X2)n, wherein n is 0 or 1; andwherein(a) VD1 or VD2 comprises three CDRs from SEQ ID NO: 541, 551, 561, 571, 581, 591, 601, 606, 611, 616, 621, 626, 631, 636, 643, 653, 661, 671, 681, 691, 701, 711, 721, 731, 741, 753, 763, 771, 776, 781, 786, 791, 796, 801, 805, 807, 809, or any one of 36-41, 48-72, or 88-97;(b) VD1 and VD2 independently comprise three CDRs from SEQ ID NO: 541, 551, 561, 571, 581, 591, 601, 606, 611, 616, 621, 626, 631, 636, 643, 653, 661, 671, 681, 691, 701, 711, 721, 731, 741, 753, 763, 771, 776, 781, 786, 791, 796, 801, 805, 807, or 809, or any one of 36-41, 48-72, or 88-97;(c) VD1 comprises three CDRs from SEQ ID NO: 541, 551, 561, 571, 581, 591, 601, 606, 611, 616, 621, 626, 631, 636, 643, 653, 661, 671, 681, 691, 701, 711, 721, 731, 741, 753, 763, 771, 776, 781, 786, 791, 796, 801, 805, 807, or 809, or any one of 36-41, 48-72, or 88-97, and VD2 comprises three CDRs from SEQ ID NO: 30, 32, 34, 108, 109, 110, 111, 112, 113, 114, 115, 121-317, 527-534, 543, 553, 563, 573, 583, 593, 603, 608, 613, 618, 623, 628, 633, 638, 641, 651, 663, 673, 683, 693, 703, 713, 723, 733, 743, 751, 761, 773, 778, 783, 788, 793, 798, 803 or 811; or(d) VD2 comprises three CDRs from SEQ ID NO: 541, 551, 561, 571, 581, 591, 601, 606, 611, 616, 621, 626, 631, 636, 643, 653, 661, 671, 681, 691, 701, 711, 721, 731, 741, 753, 763, 771, 776, 781, 786, 791, 796, 801, 805, 807, or 809, or any one of 36-41, 48-72, ...

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Номер записи: 82
20-03-2014 дата публикации

PROTEIN COMPLEX INCLUDING BI-SPECIFIC ANTIBODY

Номер: US20140081002A1
Автор: Choi Yoon-aa, KIM Min-kyung, LEE Jae-il
Принадлежит:

Provided is a protein complex including a bi-specific antibody, and a method of preparing the protein complex, which can provide a system that simultaneously targets two antigens. 1. A protein complex comprising:a first polypeptide comprising a first antigen-binding site at the N-terminus thereof;a second polypeptide comprising a second antigen-binding site at the N-terminus thereof; anda linker that links the first and second polypeptides to each other,wherein the first polypeptide and second polypeptide each comprises a domain including at least one knob or hole on a region other than the first or second antigen-binding site,wherein, if the first polypeptide comprises at least one knob, then the second polypeptide comprises a domain including at least one hole on a region other than the second antigen-binding site,wherein, if the first polypeptide comprises at least one hole, then the second polypeptide comprises a domain including at least one knob on a region other than the second antigen-binding site,wherein the knob and the hole bind to each other so that the first and second polypeptides form dimers,wherein a tag is bound to a terminus of the linker, andwherein the tag is linked to the C-terminus of the first polypeptide or the N-terminus of the second polypeptide and comprises a cleavable amino acid sequence.2. The protein complex of claim 1 , wherein a first tag and a second tag are bound at both termini of the linker claim 1 , andwherein the first tag is linked to the C-terminus of the first polypeptide, the second tag is linked to the N-terminus of the second polypeptide, and the first tag and the second tag each comprise a cleavable amino acid sequence.3. The protein complex of claim 1 , wherein the first and second antigen-binding sites are antigen-binding sites that are identical to or different from each other.4. The protein complex of claim 1 , wherein the region other than the first and second antigen-binding sites is a CH3 domain of a Fc region of ...

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Номер записи: 83
10-04-2014 дата публикации

Il-1 binding proteins

Номер: US20140099671A1
Автор: Chengbin Wu, Chung-Ming Hsieh, Dominic J. Ambrosi, Tariq Ghayur
Принадлежит: AbbVie Inc

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

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Номер записи: 84
06-01-2022 дата публикации

PRODUCTION OF HETEROMULTIMERIC PROTEINS USING MAMMALIAN CELLS

Номер: US20220002386A1
Автор: NG Domingos, SCHEER JUSTIN, SHATZ WHITNEY
Принадлежит: Genentech, Inc.

Described herein are methods for the efficient production of antibodies and other multimeric protein complexes (collectively referred to herein as heteromultimeric proteins) capable of specifically binding to more than one target. The targets may be, for example, different epitopes located on a single molecule or located on different molecules. 164-. (canceled)65. A method of preparing a heteromultimeric protein comprising i) a first hinge-containing polypeptide having a first heterodimerization domain , wherein the first hinge-containing polypeptide is associated with a first light chain , and ii) a second hinge-containing polypeptide having a second heterodimerization domain , wherein the second hinge-containing polypeptide is associated with a second light chain , wherein the second heterodimerization domain interacts with the first heterodimerization domain at an interface , and wherein the first and second hinge-containing polypeptides are linked by at least one interchain disulfide bond , the method comprising the steps of:(a) culturing a first host cell capable of expressing a first hinge-containing polypeptide and a first light chain;(b) culturing a second host cell capable of expressing a second hinge-containing polypeptide and a second light chain; and,(c) obtaining a combined culture medium for the first host cell and the second host cell without disrupting cell membrane of the first and second host cells, wherein the combined culture medium comprises the heteromultimeric protein, and wherein the first host cell and the second host cell are each a mammalian cell.66. The method of claim 65 , wherein obtaining the combined culture medium comprises: (2) harvesting a second culture medium for the second host cell; and', '(3) combining the first culture medium and the second culture medium to obtain the combined culture medium, or, '(A) (1) harvesting a first culture medium for the first host cell;'}(B) harvesting culture medium of a combined cell culture ...

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Номер записи: 85
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: 86
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: 87
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: 88
06-01-2022 дата публикации

BISPECIFIC ANTIBODY BINDING TO CD20 AND CD3 AND USES THEREOF

Номер: US20220002431A1
Автор: Chen Si, Cui Xueyuan, Jia Shixiang, Li Qiang, MA Xinlu, Zhang Yuhua
Принадлежит:

Disclosed is a bispecific antibody that specifically binds to surface antigens CD3 of immune cells and CD20 antigens on the surfaces of tumor cells, and that can bind to human CD3 with high affinity, inducing T cell proliferation, and mediating tumor cell killing. The bispecific antibody in an in vitro test was able to mediate the specific killing of target cells by T cells. The construction method thereof is simple, avoiding the possibility of mismatch between two sets of light chains and heavy chains of heterobispecific antibodies, thereby reducing the difficulty of antibody purification. The affinity of the obtained antibody is high, the side effects caused by cytokines are small, and safety is high. 1. A bispecific antibody , which is a tetravalent homodimer formed by two identical polypeptide chains that bind to each other by a covalent bond , wherein each of the polypeptide chains comprises a first single-chain Fv that specifically binds to tumor antigen CD20 , a second single-chain Fv that specifically binds to effector cell antigen CD3 and an Fc fragment in sequence from N-terminus to C-terminus; wherein the first single-chain Fv is linked to the second single-chain Fv by a linker peptide , the second single-chain Fv is linked to the Fc fragment directly or by a linker peptide , and the Fc fragment has no effector functions comprising CDC , ADCC and ADCP.2. The bispecific antibody according to claim 1 , wherein the first single-chain Fv comprises a VH domain and a VL domain that are linked by a linker peptide which has an amino acid sequence of (GGGGX)n claim 1 , wherein X comprises Ser or Ala claim 1 , and n is a natural number from 1 to 5.3. The bispecific antibody according to claim 1 , wherein the first single-chain Fv is selected from the group consisting of:(1) a VH domain comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NOs: 1, 2 and 3, respectively or having sequences that are least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or more similar to or ...

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Номер записи: 89
03-01-2019 дата публикации

MULTISPECIFIC ANTIGEN-BINDING MOLECULES AND USES THEREOF

Номер: US20190000984A1
Автор: ANDREEV Julian, CYGNAR Katherine, Delfino Frank, Martin Joel, PAPADOPOULOS Nicholas, THAMBI Nithya, THURSTON Gavin
Принадлежит:

The present disclosure provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present disclosure can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the disclosure, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present disclosure results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the disclosure, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present disclosure causes or facilitates the targeted killing of tumor cells. 1. A method of inhibiting the growth of a tumor or promoting tumor regression in a cancer patient , the method comprising administering to the patient an antibody drug conjugate (ADC) and a multispecific antigen-binding protein , wherein the ADC comprises a drug , toxin or radioisotope conjugated to an antigen-binding protein that specifically binds a tumor target (T) , and wherein the multispecific antigen-binding protein comprises a first antigen-binding domain that specifically binds T , and a second antigen-binding domain that specifically binds an internalizing effector protein (E); wherein the patient is afflicted with a tumor comprising cells that express both T and E.2. The method of wherein the antigen-binding portion of the ADC binds an epitope on T that does not overlap with the epitope on T ...

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Номер записи: 90
03-01-2019 дата публикации

BISPECIFIC TARGETING AGENTS AND METHODS FOR THEIR PREPARATION

Номер: US20190000989A1
Автор: Ganley-Leal Lisa, Leszczyniecka Magdalena, Schneider Thomas J.
Принадлежит:

The present invention is directed to a platform for new bispecific targeting agents using liposomes or nanoparticles as linkers. The bispecific targeting agent can bind two different cell types, each via a separate targeting moiety. Said targeting agents can be used to induce specific biological effects in the cells such as cell proliferation or cell activation which can be used in some instances to destroy the other bound cells. Any cell that can be targeted can be subject to targeting. For example, the cell types that may be recruited by the bispecific targeting agent may be both human or one of the cells may be human and the other an infected cell or it can be an infectious agent. The platform is based on an empty nanoparticle or liposome conjugated to two or more targeting moieties, bound to the nanoparticle/liposome at defined ratios that may be other than 1:1. Such, compositions provide for specific binding to each cell type. This bispecific targeting agent can further be linked to growth factors or cytokines to further potentiate the effect of the bispecific targeting agent as a therapeutic or to exert a specific biologic effect on one or both cells being targeted. 138-. (canceled)39. A multispecific targeting agent comprising at least two targeting arms linked together by a liposome wherein:a first targeting arm of the targeting agent binds a first cell by binding to an antigen expressed on the cell,a second targeting arm of the targeting agent binds a target antigen expressed on a second cell, andfurther comprising a recombinant protein with stimulatory or inhibitory activity that is capable of stimulating or inhibiting the biological activity of the cells being targeted by the bispecific targeting agent.40. The targeting agent of wherein the recombinant protein is a growth factor.41. The targeting agent of wherein the recombinant protein is a cytokine.42. The targeting agent of wherein the recombinant protein is IL-15.43. The targeting agent of wherein the ...

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Номер записи: 91
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: 92
07-01-2016 дата публикации

COILED COIL AND/OR TETHER CONTAINING PROTEIN COMPLEXES AND USES THEREOF

Номер: US20160002356A1
Автор: Christensen Erin H., Eaton Dan L., Vendel Andrew C., Wranik Bernd
Принадлежит:

The invention provides engineered protein complexes constructed using a coiled coil and/or a tether and methods for making, using, and purifying such complexes, such as multispecific antibodies or other multispecific Fc containing complexes. 1. An antibody comprising: {'br': None, 'sub': 1', '2', '3', '4', '5', '6', '7', 'n, '(XXXXXXX)\u2003\u2003(Formula I)'}, '(a) a first polypeptide comprising a VH domain and a first coiled coil domain (CC), wherein the first CC comprises a heptad repeat of Formula I{'sub': '1', 'claim-text': [{'sub': 2', '3', '6, 'X, X, and Xare each any amino acid residue,'}, {'sub': '4', 'Xis a hydrophobic amino acid residue, and'}, {'sub': 5', '7, 'Xand Xare each a charged amino acid residue; and'}], 'Xis a hydrophobic amino acid residue or Asparagine,'} {'br': None, 'sub': 1', '2', '3', '4', '5', '6', '7', 'n, '(X′X′X′X′X′X′X′)\u2003\u2003(Formula II)'}, '(b) a second polypeptide comprising a VH domain and a second coiled coil domain (CC), wherein the second CC comprises a heptad repeat of Formula II{'sub': '1', 'claim-text': [{'sub': 2', '3', '6, 'X′, X′, and X′are each any amino acid residue,'}, {'sub': '4', 'X′is a hydrophobic amino acid residue, and'}, {'sub': 5', '7, 'X′and X′are each a charged amino acid residue;'}], 'X′is a hydrophobic amino acid residue or Asparagine,'}wherein n in Formula I and II is greater than or equal to 2; and{'sub': 5', '7', '7', '5, 'wherein, in each heptad repeat, the first CC comprises an Xresidue that is opposite in charge to the X′residue in the second CC and the first CC comprises an Xresidue that is opposite in charge to the X′residue in the second CC.'}2. The antibody of claim 1 , wherein the first and second polypeptides each comprise a VH and a CH1 domain.3. The antibody of claim 2 , wherein the first and second polypeptides each further comprise a hinge domain.4. The antibody of claim 1 , wherein said first and second polypeptides each further comprise a CH2 and a CH3 domain.5. The antibody of claim ...

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Номер записи: 93
07-01-2016 дата публикации

BISPECIFIC HETERODIMERIC DIABODIES AND USES THEREOF

Номер: US20160002357A1
Автор: BLOOM Laird, Brady William A., Johnson Leslie S., May Chad Michael, Moore Paul A., MOSYAK Lidia, Root Adam Reid, Tchistiakova Lioudmila Gennadievna
Принадлежит: PFIZER INC.

Bispecific heterodimeric diabody molecules and uses thereof in the treatment of cancer. The bispecific heterodimeric diabody molecules comprise two polypeptide chains that associate to form two epitope binding sites recognizing the P-cadherin tumor cell associated antigen and the CD3 T cell antigen. 1. A bispecific heterodimeric diabody capable of specific binding to an epitope of P-cadherin and to an epitope of CD3 comprising a first polypeptide chain and a second polypeptide chain , wherein: i. a Domain 1, comprising a sub-Domain 1A and a sub-Domain 1B, and', 'ii. a first heterodimer-promoting domain; and, 'a. the first polypeptide comprises, in the N-terminal to C-terminal direction i. a Domain 2, comprising a sub-Domain 2A and a sub-Domain 2B and', 'ii. a second heterodimer-promoting domain, and, 'b. the second polypeptide chain comprises, in the N-terminal to C-terminal directionwherein sub-Domain 1A and sub-Domain 2A form a P-cadherin VL/VH binding domain comprising a variable heavy (VH) domain of an anti-P-cadherin antibody (P-CAD VH) and a variable light (VL) domain of an anti-P-cadherin antibody (P-CAD VL), and sub-Domain 1B and sub-Domain 2B form a CD3 VL/VH binding domain comprising a VL domain of an anti-CD3 antibody (CD3 VL) and a VH binding domain of an anti-CD3 antibody (CD3 VH); orwherein sub-Domain 1A and sub-Domain 2A form a CD3 VL/VH binding domain comprising a CD3 VL and a CD3 VH, and sub-Domain 1B and sub-Domain 2B form a P-cadherin VL/VH binding domain comprising a P-CAD VH and a P-CAD VL.2. The bispecific heterodimeric diabody of claim 1 , wherein the sub-Domain 1A comprises a P-CAD VL or a CD3 VL claim 1 , and the sub-Domain 1B comprises a P-CAD VH claim 1 , if the sub-Domain 1A comprises CD3 VL claim 1 , or aCD3 VH claim 1 , if the sub-Domain 1A comprises P-CAD VL; and wherein the sub-Domain 2B comprises a P-CAD VL or a CD3 VL depending on the VL domain selected for sub-Domain 1A claim 1 , and the sub-Domain 2A comprises P-CAD VH claim 1 , ...

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Номер записи: 94
05-01-2017 дата публикации

MULTI-SPECIFIC BINDING PROTEINS

Номер: US20170002097A1
Автор: GANESAN Rajkumar, SHAABAN Abdulsalam, Singh Sanjaya
Принадлежит:

This invention generally relates to multi-specific binding proteins. The invention also relates to methods of making such proteins and to methods of using such proteins. Pharmaceutical compositions and kits comprising such proteins are also disclosed. 1. A protein comprising:a) a first heavy chain and a first light chain forming a first binding unit specific for a first epitope, andb) a second heavy chain and a second light chain forming a second binding unit specific for a second epitope,wherein said first heavy chain comprises a tyrosine (Y) at position 366 [T366Y], wherein said second heavy chain comprises a threonine (T) at position 407 [Y407T], and wherein said first or said second heavy chain further comprises an arginine at position 435 [H435R] and a phenylalanine at position 436 [Y436F], or wherein said first heavy chain comprises a tryptophan (W) at position 366 [T366W], wherein said second heavy chain comprises a serine (S) at position 366 [T366S], an alanine (A) at position 368 [L368A] and a valine (V) at position 407 [Y407V], and wherein said first or said second heavy chain further comprises an arginine at position 435 [H435R] and a phenylalanine at position 436 [Y436F].2. The protein of claim 1 , wherein said second heavy chain further comprises an arginine at position 435 [H435R] and a phenylalanine at position 436 [Y436F].3. The protein of claim 1 , wherein said first and said second heavy chains further comprises YTE mutations (M252Y/S254T/T256E).4. The protein of claim 1 , wherein said first heavy chain comprises a tryptophan (W) at position 366 [T366W] claim 1 , wherein said second heavy chain comprises a serine (S) at position 366 [T366S] claim 1 , an alanine (A) at position 368 [L368A] and a valine (V) at position 407 [Y407V] claim 1 , wherein said second heavy chain further comprises an arginine at position 435 [H435R] and a phenylalanine at position 436 [Y436F] claim 1 , and wherein said heavy chains are derived from the heavy chain of an ...

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Номер записи: 95
04-01-2018 дата публикации

ANTIBODY SUBSTITUTING FOR FUNCTION OF BLOOD COAGULATION FACTOR VIII

Номер: US20180002443A1
Автор: Hattori Kunihiro, Kojima Tetsuo, MIYAZAKI Taro, Saito Hiroyuki, Soeda Tetsuhiro
Принадлежит: Chugai Seiyaku Kabushiki Kaisha

The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII. 228.-. (canceled) This application is a continuation of U.S. application Ser. No. 15/402,580, filed Jan. 10, 2017, which is a continuation of U.S. application Ser. No. 15/172,727, filed Jun. 3, 2016, which is a continuation of U.S. application Ser. No. 14/921,590, filed Oct. 23, 2015, which is a continuation of U.S. application Ser. No. 13/434,643, filed Mar. 29, 2012, which is a continuation of U.S. application Ser. No. 11/910,836, filed Oct. 5, 2007, which is the National Stage of International Application Serial No. PCT/JP2006/306821, filed Mar. 31, 2006, which claims the benefit of Japanese Patent Application Serial No. 2005-112514, filed Apr. 8, 2005. The contents of all of the foregoing applications are incorporated by reference in their entireties in this application.The present invention relates to multispecific antibodies that functionally substitute for coagulation factor VIII, a cofactor that enhances enzymatic reactions, methods for producing such antibodies, and pharmaceutical compositions comprising such an antibody as an active ingredient.Antibodies are highly stable in blood and have low antigenicity; therefore, they ...

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Номер записи: 96
02-01-2020 дата публикации

ANTITUMOR IMMUNE CHECKPOINT REGULATOR ANTAGONISTS

Номер: US20200002417A1
Автор: Karow Margaret, LIU Bo, SHENG Jackie, TRUONG Khue, ZHANG Wei
Принадлежит:

Antitumor antagonists that bind specifically to immune checkpoint regulator are disclosed. Also disclosed is a method of treating proliferative disorders with the antitumor antagonists. 1. An antitumor antagonist comprising:a first targeting domain that specifically binds to PD-1 or LAG-3;a second targeting domain comprising an scFv that specifically binds to TIGIT, wherein the scFv comprises an immunoglobulin heavy chain variable region (HCVR) linked to an immunoglobulin light chain variable region (LCVR) via a peptide linker comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 189-191; andan immunoglobulin scaffold having an amino terminus and a carboxyl terminus,wherein the first targeting domain is linked to the amino terminus of the immunoglobulin scaffold, wherein the second targeting domain is linked to the carboxyl terminus of immunoglobulin scaffold,wherein the first targeting domain is selected from the group consisting of(1) a PD-1 targeting domain comprising an HCVR comprising an HCDR1 having an amino acid sequence of SEQ ID NO:79, an HCDR2 having an amino acid sequence of SEQ ID NO:80, and an HCDR3 having an amino acid sequence of SEQ ID NO:81, and an LCVR comprising an LCDR1 having an amino acid sequence of SEQ ID NO:93, an LCDR2 having an amino acid sequence of SEQ ID NO:94, and an LCDR3 having an amino acid sequence of SEQ ID NO:95, and(2) an LAG-3 targeting domain comprising an HCDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:163, 166, and 169, an HCDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 164, 167, and 170, an HCDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 165, 168, and 171, and an LCVR comprising an LCDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:172, 175, and 177, an LCDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:173 and 178, ...

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Номер записи: 97
04-01-2018 дата публикации

Antibody Constructs For CDH19 and CD3

Номер: US20180002450A1
Автор: Blümel Claudia, Hoffmann Patrick, Kufer Peter, Lutterbüse Ralf, Nahrwold Elisabeth, PAN Zheng, Raum Tobias, Wickramasinghe Dineli, Xiao Shouhua
Принадлежит:

The present invention provides to a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct. 114-. (canceled)15. A method for treating or ameliorating a melanoma disease , comprising the step of administering to a subject in need thereof a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell ,wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:(a)(i) CDR-H1 as set forth in SEQ ID NO: 14, CDR-H2 as set forth in SEQ ID NO: 15, CDR-H3 as set forth in SEQ ID NO: 16, CDR-L1 as set forth in SEQ ID NO: 17, CDR-L2 as set forth in SEQ ID NO: 18 and CDR-L3 as set forth in SEQ ID NO: 19;(a)(ii) CDR-H1 as set forth in SEQ ID NO: 27, CDR-H2 as set forth in SEQ ID NO: 28, CDR-H3 as set forth in SEQ ID NO: 29, CDR-L1 as set forth in SEQ ID NO: 30, CDR-L2 as set forth in SEQ ID NO: 31 and CDR-L3 as set forth in SEQ ID NO: 32;(a)(iii) CDR-H1 as set forth in SEQ ID NO: 40, CDR-H2 as set forth in SEQ ID NO: 41, CDR-H3 as set forth in SEQ ID NO: 42, CDR-L1 as set forth in SEQ ID NO: 43, CDR-L2 as set forth in SEQ ID NO: 44 and CDR-L3 as set forth in SEQ ID NO: 45;(a)(iv) CDR-H1 as set forth in SEQ ID NO: 53, CDR-H2 as set forth in SEQ ID NO: 54, CDR-H3 as set ...

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Номер записи: 98
02-01-2020 дата публикации

Antitumor antagonists

Номер: US20200002426A1
Автор: BO LIU, Jackie SHENG, Margaret Karow
Принадлежит: Gensun Biopharma Inc

Antitumor antagonists that bind specifically to immune checkpoint regulators, angiogenesis pathway regulators and/or TGF pathway regulators are disclosed. Also disclosed are methods for treating proliferative disorders, infections, and immunological disorders with the antitumor antagonists described herein.

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Номер записи: 99
02-01-2020 дата публикации

TRISPECIFIC ANTAGONISTS

Номер: US20200002439A1
Автор: LIU Bo, SHENG Jackie
Принадлежит:

Antitumor antagonists that bind specifically to immune checkpoint regulator and/or components of the angiogenesis pathways and/or components of the TGF pathway are disclosed. Also disclosed is a method of treating proliferative disorders with the antitumor antagonists. 1. A trispecific antagonist , comprising:an immunoglobulin scaffold comprising a CHI domain, a CH2 domain and a CH3 domain;a first targeting domain comprising one or more immunoglobulin variable domains selected from the group consisting of(1) an anti-PD-1 variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and HCDR3, and three light chain complementary regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 is selected from the group consisting of SEQ ID NOS:48, 51, 54, 56 and 59, the HCDR2 is selected from the group consisting of SEQ ID NOS:49, 52, 57 and 60, HCDR3 is selected from the group consisting of SEQ ID NOS:50, 53, 55, 58 and 61, the LCDR1 is selected from the group consisting of SEQ ID NOS:62, 65, 68, 69, 70 and 73, the LCDR2 is selected from the group consisting of SEQ ID NOS:63, 66, 71 and 74, and the LCDR3 is selected from the group consisting of SEQ ID NOS:64, 67, 72 and 75,(2) an anti-PD-L1 variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and HCDR3, and three light chain complementary regions LCDR1, LCDR2 and LCDR3, wherein the HCDR1 is selected from the group consisting of SEQ ID NOS:76, 79, 85 and 88, the HCDR2 is selected from the group consisting of SEQ ID NOS:77, 80, 82, 84, 86 and 89, the HCDR3 is selected from the group consisting of SEQ ID NOS:78, 81, 83, 87 and 90, the LCDR1 is selected from the group consisting of SEQ ID NOS:91, 94, 98, 101 and 104, the LCDR2 is selected from the group consisting of SEQ ID NOS:92, 95, 99, 102, 105, and the LCDR3 is selected from the group consisting of SEQ ID NOS:93, 96, 97, 100 and 106,(3) an anti-TIGIT variable domain comprising three heavy chain complementary regions HCDR1, HCDR2 and ...

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Номер записи: 100