EP0585224A1 - ANTICORPS MONOCLONAUX QUI SE LIENT A L'IgE SECRETEE ET LIEE AUX MEMBRANES MAIS QUI NE SE LIENT PAS A L'IgE SE TROUVANT SUR LES LEUCOCYTES BASOPHILES - Google Patents
ANTICORPS MONOCLONAUX QUI SE LIENT A L'IgE SECRETEE ET LIEE AUX MEMBRANES MAIS QUI NE SE LIENT PAS A L'IgE SE TROUVANT SUR LES LEUCOCYTES BASOPHILESInfo
- Publication number
- EP0585224A1 EP0585224A1 EP92901974A EP92901974A EP0585224A1 EP 0585224 A1 EP0585224 A1 EP 0585224A1 EP 92901974 A EP92901974 A EP 92901974A EP 92901974 A EP92901974 A EP 92901974A EP 0585224 A1 EP0585224 A1 EP 0585224A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- ige
- tesc
- tes
- cells
- mab
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
- C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
- C07K16/4291—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig against IgE
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6873—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting an immunoglobulin; the antibody being an anti-idiotypic antibody
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- immediate-type hypersensitivities such as extrinsic asthma, hay fever, and allergic responses to certain foods or drugs, are mediated
- the allergen binds to the IgE which is bound to receptors on the surfaces of mast cells and basophilic leukocytes (basophils).
- the binding of the allergen causes cross-linking of the surface IgE molecules and hence the underlying receptors (FceR) for the Fc portion of IgE, thereby triggering the release of pharmacologic mediators such as histamine, the slow-reacting substance of anaphylaxis (SRA), and serotonin.
- SRA slow-reacting substance of anaphylaxis
- IgE is secreted by a particular class of B cells, which also express IgE on their surface. In individuals sensitized to specific allergens, the allergen-
- the immune system's regulatory, cytolytic or cytotoxic mechanisms can be used to suppress or destroy the B cells which are bound by monoclonal antibodies. Other immune mechanisms can eliminate the secreted IgE which is bound by the monoclonal antibodies.
- IgE binds to the FceR receptors on the surface of basophils and mast cells very strongly, with an association constant, Ka, of about 1 x 10 10 liter/mole. Even though IgE is not synthesized by basophils and mast cells, the very strong and stable association of IgE with FceR means that IgE is virtually always present and exposed on the surface of these ceils. Thus, an immunotherapeutic agent which targets IgE must not react with the IgE on basophils and mast cells, in order to avoid cross-linking this IgE and the underlying FceR and thereby triggering an allergic reaction.
- TES-C21 is a murine monoclonal antibody
- TESC-2 is a chimeric mouse/human mAb with its variable regions derived from TES-C21, and with human ( ⁇ l, K) constant regions.
- Both TES-C21 and TESC-2 bind specifically to IgE and are not reactive with
- Both mAbs bind to IgE secreting B cells, and neither induces histamine release from human basophils. Both mAbs also inhibit the binding of IgE to the low affinity FceRII receptor, which is present on B cells producing all of the various heavy chain isotypes.
- these mAbs will bind specifically to secreted IgE, and the secreted IgE can then be eliminated by the immune system. They also bind specifically to IgE expressed on the surface of IgE-producing B cells, and these B cells
- Fig. 1 shows a comparison of the binding of TES-C21 and TESC-2 to
- IgE which is bound to microtiter plates.
- Fig. 2 shows a comparison of the relative affinity of the binding of TES-C21 and TESC-2 to IgE which is bound to microtiter plates.
- Fig.3 shows a comparison of the binding of TES-C21 and TESC-2 to
- Fig. 4 shows a comparison of the inhibition of the binding of IgE to FceRII by TES-C21 and TESC-2.
- the epitopes targeted by the TES-C21 and TESC-2 mAbs are unique in that they are present on IgE bearing B lymphocytes but not on mast cells or basophils. The epitopes are believed to be located at or near the binding site for FceR, and to be obscured when IgE is bound to FceR on basophils and mast cells. These mAbs are specific for the IgE-secreting B cells, and did not bind to B cell lines secreting other Ig isotypes, to a T cell line or a
- the TES-C21 and TESC-2 mAbs also do not bind to IgE on the low affinity FceRII receptors on B cells, thereby reducing the destruction or regulation of B cells which produce isotypes other than IgE.
- the TES-C21 and TESC-2 mAbs can be used in any way in which the mAbs described in published International Application PCT/US88/04706 can be used. These uses include diagnostic uses such as identifying and enumerating IgE-bearing B cells in mixed leukocyte populations, and
- TESC-2 chimeric TESC-2 mAb
- the mAbs can be systemically administered, preferably intravenously or intramuscularly, as free antibodies to patients afflicted with IgE-mediated allergy in amounts sufficient to down-regulate or eliminate IgE-producing cells, and/or amounts sufficient to bind to secreted IgE.
- TESC-2 is of IgGl subclass, and therefore mediates antibody dependent cellular cytotoxicity ("ADCC") of B cells expressing IgE on their surface. These IgE-expressing B cells also secrete IgE. Therefore, TESC-2
- TES-C21 could also be used to down-regulate B cells producing IgE through other regulatory immune mechanisms.
- TES-C21 and TESC-2 can be used for in vivo therapeutic applications, they may also be used in extra-corporeal ex-vivo applications.
- the IgE-bearing B cells in the circulation of the patients can be removed by an affinity matrix (antibody immobilized on a solid phase) which is conjugated with these mAbs.
- TESC-2 is also preferred for in vivo use because it is a humanized antibody, and it therefore less immunogenic than the wholly murine mAb TES-C21.
- Such humanized mAbs are less likely to evoke an immune or allergic response. It is noted that such a response could deplete the antibodies which are administered before such antibodies could function to bind to the secreted or membrane-bound forms of IgE, thereby reducing the
- the mAbs TES-C21 and TESC-2 can also be used as carrier agents of cytotoxic drugs or for delivering an effector substance, by conjugating the mAbs to these substances.
- a toxin-antibody conjugate will bind and directly kill B cells producing IgE, but not B cells producing other isotypes which do not express IgE on their surfaces.
- These toxins are cytolytic or cytotoxic agents, including cytotoxic steroids, gelonin, abrin, ricin, Pseudomonas toxin, diphtheria toxin, pokeweed antiviral peptide, tricathecums, radioactive nuclides, and membrane-lytic enzymes (such as phospholipase). The method of making these conjugates is described in International Application PCT/US88/04706.
- the TES-C21 and TESC-2 mAbs can also be used in combination with factors which enhance ADCC, such as granulocyte monocyte-colony stimulating factor ("GM-CSF 1 ) and monocyte-colony stimulating factor ("M-CSF 1 )
- GM-CSF 1 granulocyte monocyte-colony stimulating factor
- M-CSF 1 monocyte-colony stimulating factor
- Immunotherapies employing the mAbs of the invention can be used in combination with conventional desensitization immunotherapy.
- desensitization with allergen can be performed in conjunction with the administration of either the mAbs of the invention or antibody-toxin conjugates discussed above, to down-regulate or substantially eliminate IgE producing cells.
- Desensitization induces IgG production against the allergen/immunogen. Inducing such IgG production may be most effective as an allergy therapy when IgE-producing B cells are substantially depleted.
- the combination of antibody and desensitization therapy is attractive because although the IgE-producing B cells may only be temporarily depleted (for a few weeks or months) by the mAbs of the invention, and will eventually re-populate, the desensitization effect may last much longer.
- the TES-C21 and TESC-2 mAbs can also be used in making anti-
- the TES-C21 and TESC-2 mAbs can also be used in making derivative antibodies which draw cytotoxic cells such as macrophages or cytotoxic T cells toward the targeted IgE-expressing B cells.
- These derivative antibodies which are useful in allergy therapy, include bi-specific antibodies having a specificity for a receptor of a cytotoxic cell and a specificity for the IgE expressing cells.
- Such hybrid bi-specific antibodies can include two different Fab moieties, one Fab moiety having antigen specificity for the targeted B cells, and the other Fab moiety having antigen specificity
- the bi- specific antibodies of the invention can be a single antibody having two specificities, or a heteroaggregate of two or more antibodies or antibody fragments. See, e.g.. C. Reading, U.S. Patent Nos. 4,474,893 and 4,714,681;
- the mAbs TES-C21 and TESC-2 are made by techniques well-known in the art, which are described in International Application No.
- mice Male Balb/c mice were immunized several times with polyclonal human IgE from sera (provided by Ventrex), where the IgE was combined with a suitable adjuvant. Mice were sacrificed after the last injection of immunogen and the spleens were removed for preparing single cell suspensions for fusion with myeloma cells. The spleen cells were fused with Sp2/0 cells using a fusion mixture of polyethylene glycol 1450 (Kodak),
- hybridomas resulting from the fusion were then screened by enzyme-linked immunosorbent assay (ELISA) against human IgE bound to an Immulon 2 plate.
- ELISA enzyme-linked immunosorbent assay
- Sp 2/0 cells were co-transfected with the variable regions of TES-C21 H and L-chains,
- the transfectoma cells were adapted to growth in serum-free medium.
- TESC-2 was then purifed from medium of confluent cultures using an immobilized protein A column.
- the hybridoma cell line producing the mAb TESC-2 was deposited pursuant to the Budapest treaty at the American
- the mAb TES-C21 was found, on testing by ELISA, to be specific for human IgE, and not to react with IgG, IgM, IgA, IgD, human serum albumin, transferrin or insulin.
- TES-C21 bound equally well to various human IgE molecules.
- TES-C21 bound to the IgE-secreting cell lines SKO- 007, U266 and SE44 in a dose-dependent manner. But TES-C21 did not bind to human B cell lines bearing surface IgM, IgD, IgG, or IgA, or to a T cell line or to the parent murine cell line of SE44, or to a murine cell line secreting chimeric human IgG.
- TES-C21 does not bind to IgE on low affinity FceRII receptors, and does not induce histamine release from freshly prepared human blood basophils, on which the FceR are armed with IgE. At 10 ⁇ g/ml TES-C21 is able to inhibit completely the binding of IgE to FceRII.
- TESC-2 and TES-C21 bind equally well to IgE bound to microtiter plates by binding to antigen.
- Immulon 2 plates were coated with gpl20 peptide-ovalbumin conjugate and IgE-SE44 was bound to the immobilized antigen.
- TES-C21 or TESC-2 at the concentrations in Fig.
- TESC-2 and TES-C21 have the same relative affinity for IgE bound to microtiter plates by binding to antigen. Immulon
- TES-C21 was detected using horseradish peroxidase-conjugated streptavidin.
- TESC-2 and TES-C21 bind equally to IgE-secreting cells, as shown in Fig. 3.
- Cells were incubated at 2 x 10 6 cells/lOO l PBS-1% goat serum in the indicated antibody concentrations at 0° for 30 min. Binding of TES-
- FITC intensity gate was set to yield 10% ⁇ 0.5% positive cells in the absence of primary immunoglobulins.
- the data shown in Fig. 3 represents the net increase in percent positive cells.
- IM-9 IgG-secreting human lymphoblastoid line
- both chimeric TESC-2 and murine TES-C21 inhibit binding of IgE to FceRII.
- the mAb were preincubated at the indicated
- HEM7 is a control mAb that does not bind to serum IgE and does not affect IgE binding to FceRII.
- TESC-2 or FITC goat anti-human IgE (with TES-C21).
- TESC-2 nor TES-C21 induces histamine release from freshly prepared human blood basophils, on which the FceR are armed with IgE. Due to the variable release of mediators from basophils of different donors, the mAbs were examined at multiple concentrations on basophil preparations from multiple donors. No induction of histamine release by TESC-2 or TES-C21 was observed.
- TES-C21 did not induce histamine under these very permissive conditions.
- TESC-2 was further tested to determine whether it could block the binding of IgE to FceRI receptors, and whether immune complexes of IgE and TESC-2 would bind to these receptors.
- TESC-2 inhibits the binding of human IgE to FceRI
- human peripheral blood basophils that had been depleted of IgE by treatment at low pH were reloaded or sensitized with SE44-derived chimeric IgE reactive to a peptide antigen.
- Functional binding of SE44 IgE was tested by histamine release induced by the polyvalent R15K peptide-ovalbumin conjugate to which the variable region of IgE-SE44 binds.
- IgE-SE44 was not preincubated 37 66 with TESC-2
- IgE-SE44 was preincubated with 3 68
- TESC-2 IgE-SE44 was preincubated with 0 63
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Abstract
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/US1991/001991 WO1992017207A1 (fr) | 1991-03-26 | 1991-03-26 | ANTICORPS MONOCLONAUX QUI SE LIENT A L'IgE SECRETEE ET LIEE AUX MEMBRANES MAIS QUI NE SE LIENT PAS A L'IgE SE TROUVANT SUR LES LEUCOCYTES BASOPHILES |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0585224A1 true EP0585224A1 (fr) | 1994-03-09 |
EP0585224A4 EP0585224A4 (en) | 1994-09-14 |
Family
ID=22225411
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP9292901974A Withdrawn EP0585224A4 (en) | 1991-03-26 | 1992-10-22 | Monoclonal antibodies which bind to secreted and membrane-bound ige, but not to ige on basophils |
Country Status (2)
Country | Link |
---|---|
EP (1) | EP0585224A4 (fr) |
WO (1) | WO1992017207A1 (fr) |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1452542A3 (fr) * | 1992-09-24 | 2007-05-02 | Novartis AG | Anticorps monoclonaux humains transformés contre l'IgE |
US5958708A (en) * | 1992-09-25 | 1999-09-28 | Novartis Corporation | Reshaped monoclonal antibodies against an immunoglobulin isotype |
US6066718A (en) * | 1992-09-25 | 2000-05-23 | Novartis Corporation | Reshaped monoclonal antibodies against an immunoglobulin isotype |
WO1997010004A1 (fr) * | 1995-09-13 | 1997-03-20 | Genentech, Inc. | Procedes de traitement de la cystite interstitielle |
DE19643427C1 (de) * | 1996-10-22 | 1998-02-12 | Bundesrep Deutschland | Verfahren zur Bestimmung von Allergenen in der Luft |
US6893636B2 (en) * | 1997-02-20 | 2005-05-17 | Biogen Idec Ma Inc. | Gamma-1 and gamma-3 anti-human CD23 monoclonal antibodies and use thereof as therapeutics |
US7033589B1 (en) | 1997-02-20 | 2006-04-25 | Biogen Idec Ma Inc. | γ-1 anti-human CD23 monoclonal antibodies and use thereof as therapeutics |
US6011138A (en) * | 1997-02-20 | 2000-01-04 | Idec Pharmaceuticals Corporation | Gamma-1 anti-human CD23 monoclonal antibodies |
US6172213B1 (en) | 1997-07-02 | 2001-01-09 | Genentech, Inc. | Anti-IgE antibodies and method of improving polypeptides |
US5994511A (en) | 1997-07-02 | 1999-11-30 | Genentech, Inc. | Anti-IgE antibodies and methods of improving polypeptides |
CN1289253A (zh) * | 1998-01-29 | 2001-03-28 | 泰诺士公司 | 以lgE拮抗剂治疗特应性皮炎 |
US6787524B2 (en) | 2000-09-22 | 2004-09-07 | Tanox, Inc. | CpG oligonucleotides and related compounds for enhancing ADCC induced by anti-IgE antibodies |
US8703126B2 (en) | 2000-10-12 | 2014-04-22 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
ES2332402T5 (es) | 2000-10-12 | 2018-05-14 | Genentech, Inc. | Formulaciones de proteína concentradas de viscosidad reducida |
WO2004070010A2 (fr) * | 2003-02-01 | 2004-08-19 | Tanox, Inc. | Procede destine a produire des anticorps a affinite elevee |
SI2335725T1 (sl) | 2003-04-04 | 2017-01-31 | Genentech, Inc. | Visokokoncentrirane formulacije protiteles in proteinov |
UA102994C2 (ru) | 2007-03-22 | 2013-09-10 | Дженентек, Инк. | АНТИТЕЛО, КОТОРОЕ СПЕЦИФИЧНО СВЯЗЫВАЕТСЯ С IgE/M1' И ИНДУЦИРУЕТ АПОПТОЗ В ЭКСПРЕССИРУЮЩИХ IgE В-КЛЕТКАХ |
MX2009010765A (es) * | 2007-04-02 | 2009-10-26 | Amgen Fremont Inc | Anticuerpos anti-ige. |
SG174258A1 (en) | 2009-03-06 | 2011-10-28 | Genentech Inc | Antibody formulation |
SI2494356T1 (sl) | 2009-10-26 | 2017-07-31 | Genentech, Inc. | Preizkusi za detektiranje protiteles, specifičnih za terapevtska protitelesa proti IgE, in njihova uporaba pri anafilaksi |
KR101413689B1 (ko) * | 2010-11-15 | 2014-07-01 | 한국생명공학연구원 | 인간 tesc 단백질에 특이적으로 결합하는 단일클론항체 및 이의 용도 |
AR089434A1 (es) | 2011-12-23 | 2014-08-20 | Genentech Inc | Procedimiento para preparar formulaciones con alta concentracion de proteinas |
JP2015506950A (ja) | 2012-01-31 | 2015-03-05 | ジェネンテック, インコーポレイテッド | 抗ig−em1’抗体およびそれを用いる方法 |
US10196458B2 (en) * | 2013-07-26 | 2019-02-05 | The Regents Of The University Of California | Anti-immunoglobulin E antibodies and methods of using thereof |
CN105722539B (zh) | 2013-11-13 | 2021-01-15 | 豪夫迈·罗氏有限公司 | 辅助式手动注射装置和方法 |
CA3226165A1 (fr) | 2018-02-09 | 2019-08-15 | Genentech, Inc. | Procedes therapeutiques et de diagnostic pour des maladies inflammatoires mediees par des mastocytes |
Citations (3)
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WO1989006138A1 (fr) * | 1987-12-31 | 1989-07-13 | Tanox Biosystems, Inc. | Epitopes antigeniques uniques sur des lymphocytes b porteurs d'immunoglobuline e |
US4940782A (en) * | 1987-06-08 | 1990-07-10 | G. D. Searle & Co. | Monoclonal antibodies against IgE-associated determinants, hybrid cell lines producing these antibodies, and use therefore |
EP0396505A2 (fr) * | 1989-05-04 | 1990-11-07 | Ciba-Geigy Ag | Anticorps monoclonaux spécifiques pour un isotype d'immunoglobuline |
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US4865980A (en) * | 1982-12-29 | 1989-09-12 | University Of Hawaii | Monoclonal antibodies for DNA-RNA hybrid complexes and their uses |
US5053224A (en) * | 1983-11-07 | 1991-10-01 | Hilary Koprowski | Induction of antibody response to solid tumors with anti-idiotype antibodies |
GB2160312B (en) * | 1984-04-13 | 1987-09-16 | South African Inventions | Adjuvant for immunisation |
US5026545A (en) * | 1984-09-17 | 1991-06-25 | Baxter International, Inc. | Treatment of allergy and composition therefor |
US5017489A (en) * | 1985-06-28 | 1991-05-21 | Massachusetts Institute Of Technology | Cytotoxic T lymphocte serine esterase and method for stimulation and inhibition |
US4714759A (en) * | 1985-12-02 | 1987-12-22 | Whitaker Jr Robert B | Immunotoxin therapy of allergy |
-
1991
- 1991-03-26 WO PCT/US1991/001991 patent/WO1992017207A1/fr not_active Application Discontinuation
-
1992
- 1992-10-22 EP EP9292901974A patent/EP0585224A4/en not_active Withdrawn
Patent Citations (3)
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US4940782A (en) * | 1987-06-08 | 1990-07-10 | G. D. Searle & Co. | Monoclonal antibodies against IgE-associated determinants, hybrid cell lines producing these antibodies, and use therefore |
WO1989006138A1 (fr) * | 1987-12-31 | 1989-07-13 | Tanox Biosystems, Inc. | Epitopes antigeniques uniques sur des lymphocytes b porteurs d'immunoglobuline e |
EP0396505A2 (fr) * | 1989-05-04 | 1990-11-07 | Ciba-Geigy Ag | Anticorps monoclonaux spécifiques pour un isotype d'immunoglobuline |
Non-Patent Citations (6)
Title |
---|
BIO/TECHNOLOGY vol. 8, no. 2 , February 1990 , NEW YORK NY, USA pages 122 - 126 T. CHANG ET AL. 'Monoclonal antibodies specific for human IgE-producing B cells: A potential therapeutic for IgE-mediated allergic diseases.' * |
See also references of WO9217207A1 * |
THE FASEB JOURNAL vol. 4, no. 7 , 26 April 1990 , BETHESDA MD, USA page A1808 F. DAVIS ET AL. 'Monoclonal antibodies specific for the transmembrane anchor peptide og IgE.' * |
THE FASEB JOURNAL vol. 5, no. 4 , 11 March 1991 , BETHESDA MD, USA page A605 F. DAVIS ET AL. 'Two isoforms of membrabe-bound human IgE.' * |
THE JOURNAL OF CELL BIOLOGY vol. 109, no. 4(2) , October 1989 , NEW YORK NY, USA page 163A F. DAVIS ET AL. 'Monoclonal antibodies that bind to IgE on B cells but not to IgE on high and low affinity IgE receptors.' * |
THE JOURNAL OF CELL BIOLOGY vol. 109, no. 4(2) , October 1989 , NEW YORK NY, USA page 164A L. GOSSETT ET AL. 'Reactivity of IgE on FcepsilonRII with various IgE-specific monoclonal antibodies.' * |
Also Published As
Publication number | Publication date |
---|---|
EP0585224A4 (en) | 1994-09-14 |
WO1992017207A1 (fr) | 1992-10-15 |
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