AU611381B2 - Monoclonal antibodies against tumour-associated glycoproteins, a process for their preparation and their use - Google Patents

Monoclonal antibodies against tumour-associated glycoproteins, a process for their preparation and their use Download PDF

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Publication number
AU611381B2
AU611381B2 AU62140/86A AU6214086A AU611381B2 AU 611381 B2 AU611381 B2 AU 611381B2 AU 62140/86 A AU62140/86 A AU 62140/86A AU 6214086 A AU6214086 A AU 6214086A AU 611381 B2 AU611381 B2 AU 611381B2
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Australia
Prior art keywords
mab
antibody
antigen
isotype
glycoprotein
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AU62140/86A
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AU6214086A (en
Inventor
Klaus Bosslet
Ernst-Jurgen Kanzy
Gerhard Luben
Hans-Harald Sedlacek
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Siemens Healthcare Diagnostics GmbH Germany
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Behringwerke AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • 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
    • A61K47/6851—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 a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Description

prescri Ied I)Y It p~ t lcollecior Of pubi~c MoVIOVs Re6gIste6r ed' *Pa.t Ie.nt Attorney THIE COMMISSIONER OF PATENTS.
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PATEN'I.
COMPLETE SPECIFICATION ORIG0IN AL) Class Int. Clasn Application Number: Lodged: Complete Specification Lodged: Accepted: Published: P~r,ij6rity flted Art: 97-14-0196 Name of Applicant: Address of Applicant: Actual Inventor: Address for Service: BEHRINGWERKE AKTIENGESELLSCHAFT D-3550 Marburg 1, Federal Republic of Germany KLAUS BOSSLET, GERHARD LUBEN, ERNST-JURGEN KANZY and H-ANS-HARALD SEDLACEK EDWD. WATERS SONS, 50 QUEEN STREET, MELBOURNE, AUSTRALIA, 3000.
Complete Specification for the invention entitled: MONOCLONAL ANTIBODIES AGAINST TUMOR-ASSOCIATED GLYCOPROTEINS, A PROCESS FOR THEIR PREPARATION AND THEIR USE The following statement is a full description of this invention, including the best method of performing it known to US
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-la- BEHRINGWERKE AKTIENGESELLSCHAFT 85 017 Ma 553 D Ha/Sd.
MonoclonaL antibodies against tumor-associated glycoproteins, a process for their preparation and their use The invention relates to monoclonal antibodies (MAb) which bind to defined cytoplasmic, membrane-associated or secreted antigens, and to a process for their preparation. These antibodies can be used as a diagnostic aid, an active compound or a carrier of an active compound.
0 0 0 Methods for immunization with defined, isolated antio, gens and for the production of antibodies against such antigens are known. It is also known to immunize with unpurified antigenic material and to select those antio" bodies which recognize a particular component of a o mixture of antigens of this type.
00 We have succeeded in selecting monoclonal antibodies having advantageous properties. These have the characl. teristic that they react with particular epitopes on protein antigens, as follows: MAb 436/15 reacts with a glycoprotein which has a molecular weight exceeding 200 kDa under non-reducing conditions (antigen The epitope recognized by this MAb is resistant to formaldehyde fixation or paraffin embedding in the same way as it is to neuraminidase treatment. However, this epitope is destroyed by periodate oxidation. MAb 436/15 belongs to the IgG 3 isotype with a kappa chain as the light chain.
MAb 494/32 recognizes an epitope on a glycoprotein (antigen 2) of molecular weight exceeding 200 koa under non-reducing or under reducing conditions, which is s .i 1; i AQ 2 resistant both to formaldehyde fixation or paraffin embedding and to neuraminidase treatment. Periodate oxidation results in destruction of this epitope. MAb 494/32 belongs to the IgG 1 isotype with a kappa chain as the Light chain.
MAb 495/19 and MAb -495/36 recognize an epitope on a glycoprotein (antigen 3) of a m.oLecuLar weight exceeding 200 kDa under non-reducing or under reducing conditions, which is resistant both to neuraminidase treatment and to periodate oxidation. In contrast to the epitopes on antigens 1 and 2, this epitope is not resistant to formaldehyde fixation or paraffin embed- 0 0 ding. MAb 495/19 and 495/36 are of the IgG 3 isotype 00 15 with a kappa chain.
0 o i o 0 MAb 494/32 and MAb 495/36 are able to promote the ADCC 0o reaction (see for methods: D. Herlyn et aL. The 0 0 0 0 Journal of Immunology 134, 2, 1,300-1,304 (1983)).
0 0 4 The invention relates to a monoclonal antibody, which is called MAb 436/15, of the IgG 3 isotype with a kappa chain, which antibody reacts with a glycoprotein (antigen 1) which has a molecular weight (MW) exceeding 200 kDa under non-reducing conditions, to a monoclonal antibody, which is called MAb 494/32, of the IgG 1 isotype with a kappa chain, which antibody reacts with a gLycoprotein (antigen 2) which has a MW exceeding 200 kDa under non-reducing and under reducing conditions, and to two monoclonal antibodies, which are called MAb 495/19 and 495/36, of the IgG 3 isotype with a kappa chain, which antibodies react with a glycoprotein (antigen 3) which has a MW exceeding 200 kDa under nonreducing and under reducing conditions.
MAb 436/15 recognizes an epitope on antigen 1 with the following accessibility on human tissues, human tumor 3 xenotransplants on the nude mouse or in vitro cultivated cell Lines, where the epitope has been detected in the case of the cell lines by means of an indirect immunofluorescence method on live ceLLs immunol.
Methods 1977, 15, 57-66), and in the case of the xenotranspLant or human tumor tissue by means of the indirect immunopero-xidase method cLin. Path. 1979, 32, 971-978): The colon carcinoma cell Line DE-TA and the pancreas carcinoma cell line PaTul show a marked membrane fluorescence. The xenotranspLants of the pancreas carcinomas PaTuI and PaTulI and the small-cell xenotransplant of a lung carcinoma 8110 show a positive immune staining in particular tissue areas, whereas there is no detectable reaction to the lung carcinoma BroCa17 and the pancreas carcinoma tissue PaTuIII.
Q
The reaction of MAb 436/15 to human carcinomas is with 8 highly differentiated adenocarcinomas of the lung out of 55 other lung carcinomas tested (both secreted product staining and staining of the cytoplasm and S" membrane). A few squamous cell carcinomas of the lung o° likewise react. Furthermore, about 50% of colon car- S 25 cinomas and the Liver metastases derived therefrom, about 60% of pancreas carcinomas, 10-20% of the tumor areas in about 40% of ovarian carcinomas (strong reac- Stion with secretion), and a few cells in 50% of mammary *oo carcinomas are reactive.
0 0 MAb 436/15 shows no essential binding to lymph nodes, tonsils, peripheral blood leukocytes, normal liver and normal colon. The dysplastic epithelium of the lung, the inter- and intralobular ducts of the pancreas and a few acinar cells, and the gastric glands and a few cells in the spleen show a reaction.
4 MAb 494/32 recognizes an epitope on antigen 2 with the following accessibility on human tissues, human tumor xenotransplants on the nude mouse or in vitro cultivated cell lines, the binding having been detected as before: The colon carcinoma cell Line DE-TA shows a marked membrane fluorescence. The xenotransplants of the pancreas tumors PaTuI and II, I.W. and 14, and the xenotransplants of the colon carcinomas 4 and 5 show a marked cytoplasm and cell-membrane reaction.
The reaction of MAb 494/32 to human carcinomas is with about 80% of grade I and II adenocarcinomas of the pancreas, whereas no noteworthy reactions are observed with the grade III pancreas carcinomas. Furthermore, there is immunohistological staining of about 70% of liver metastases of colon carcinomas and about 30% of -a the primary tumors of colon carcinomas. A few tumor o.U 20 cells in about 40% of lung carcinomas are reactive.
Normal tissue from the lungs, Liver, breast, kidneys, S. spleen and lymph nodes, and bone marrow and connective o tissues, as well as muscles and peripheral blood leukocytes, show no noteworthy immune reactions with MAb S494/32. However, the mucus-producing cells of the stomach and of the colon (goblet cells) and a few cells of the outer mucous membrane of the colon do stain.
.0 The duct system in an inflamed pancreas shows a positive reaction, whereas the exocrine and endocrine pancreas tissue does not react.
The molecular weight of the antigen defined by MAb 494/ 32 (above 200 kDa) differs from that of the glycoproteins defined by the MAb AR2-20 and AR1-28, which is 190 kDa (Cancer Res., 1985, 45, 1,723-1,729). Furthermore, the epitope accessibility for MAb 494/32 is such that it preferentially reacts with the highly differentiated adenocarcinomas of the pancreas, whereas the MAb AR2-20 and AR1-28 react with all pancreas carcinomas tested.
There are marked differences between MAb 494/32 and the MAb DUPAN-2 (JNCI, .1985, 72, 999-1,003) in the epitope accessibility (DUPAN-2 reacts with all pancreas and gaLLbLadder carcinomas and many gLanduLar tissues) and the neuraminidase resistance (DUPAN-2 recognizes a neuraminidase-sensitive epitope). The MAb C54-0, C1-N3 and C1-P83 which are described in Cancer Res., 1985, 1,402-1,407 differ from MAb 494/32 in respect of the accessibility of the epitopes and the defined anti- 15 gen (molecuLar weight of 122 kDa for C54-0).
MAb 495/36 and 495/19 recognize an epitope on antigen 3 o o with the following accessibility on human tissues, 0 40 human tumor xenografts on the nude mouse and in vitro 20 cultivated cell Lines, a reaction having been detected as before: The colon carcinoma cell line DE-TA shows a marked membrane fluorescence. All the human tumor xenotransplants tested, such as the bronchial carcinomas BroCa- 11, GOT-1, MR-21E560Sp, BroCa-33, BroCa-53, 898, the pancreas carcinomas PaTul, PaTuIIl and the colon carcinomas Ca 4,5, Le-Met Co. Ca 2, DE-TA, Le-Met Co. Ca 9 and S Le-Met Co. Ca 3 show a strong cytoplasmic and membrane reaction.
On human lung carcinoma tissues MAb 495/36 shows a marked membrane reaction with about 100% of the tested cases of various histologies. Furthermore, about of pancreas carcinomas, Liver metastases of colon carcinomas, and ovarian and bladder carcinomas and mammary carcinomas show a strong membrane reaction. No
I!
,i i ti- 6 immunohistological staining is found with peripheral blood leukocytes, lymphocytes, spleen, blood vessels, connective tissue or muscle. There is a positive reaction of the mucous membrane and the crypts of the normal colon, the bile duct epithelium in the Liver, and the glandular tissue in the stomach. The epithelium of the lung and the exocrine and endocrine pancreas tissue show a strong reaction.
The method used for the production of the above monoclonal antibodies is described in German Offenlegungsschrift 3,329,184 on pages 3 to o The invention also relates to 3 process for the pre- 000 15 paration of one of the monoclonal antibodies described o 0o0 o above, which comprises immunization of a mammal with cells of the lung carcinoma cell Line MR22E572 or of f0 0 I the colon carcinoma cell line DE-TA, removal of spleen cells from an animal which has been immunized in this 0 0 0 20 way, fusion with the cell line X63 Ag8.653,.selection of the hybridomas, and obtaining of the MAb.
The immunogen used for the induction of MAb 436/15 is the cell line MR22E572, and that for the induction of MAb 494/32, 495/36 and 495/19 is the DE-TA cell line.
Mammals, preferably mice, are immunized with cells of one of these cell lines, and the spleen cells from such animals are fused with the X63 Ag8.653 cell line.
The resulting hybridomas are tested for the presence of antibodies of the desired specificity. Among the hybridoma supernatants which are tested there are a few which contain the antibodies having the specificities described above. The hybridomas secreting these antibodies are cloned, and the monoclonal antibodies obtained from these hybridoma clones are used for the immunochemical characterization of the antigen which 6 I ii ii -I 7 they recognize. The molecular weight is determined by comparison with commercially obtainable markers. The antigens can be purified by affinity chromatography.
In addition, the binding of the monoclonal antibodies to histological specimens is measured using the indirect immunoperoxidase technique clin. Pathol., 1979, 32, 971).
Furthermore, the molecular characterization of the antigens or subpopulations of antigenic molecules which are recognized by the monoclonal antibodies is carried out in addition to Western blot analysis by radioo immunoprecipitation (Behring Institute Mitteilungen, o 15 1984, 74, 27-34).
o
O
0 .o By reason of their reactivity with various epitopes on o human tissues, the MAb 436/15, 494/32 and 495/36 or 0 0* o 495/19 can be used for the immunohistological differen- S 20 tiation between epitope-positive and epitope-negative tissues or body fluids. The MAb described above are furthermore able, in a radiolabeled form, to bind to tumors in vivo (436/15, 494/32) and with their aid it is possible to detect early metastases in draining lymph nodes by immunoscintigraphy (495/36, 495/19).
In addition, these monoclonal antibodies can be employed as carriers of active compounds and used for the t therapy of malignant diseases. Further possible uses are represented by the inhibition of tumor cell metastasis after in vivo administration or the binding of the monoclonal antibodies to antigen-carrying, metastasizing tumor cells. Furthermore, these monoclonal antibodies may be toxic, without cooperation from other toxins, for the antigen-carrying tumor cells, or may result, after binding to the tumor cell membrane, in differentiation processes which cause malignant tumor -8cells to become benign cells.
Furthermore, the MAb 494/32 and 495/36 which promote ADCC can be used, in a non-radiolabeled form, for the tumor therapy of epitope-positive tumors after systemic or regional administration.
However, the monoclonal antibodies which have been described can also be used in a labeled form as diagnostic aids or for the analysis of tissues and body fluids and for radioimmunoscintigraphy or as therapeutic agents for radioimmunotherapy or for chemoimmunotherapy.
0 0 0 0 o~ 15 For diagnostic purposes the monoclonal antibodies are used in a concentration of 0.001 jg/mL to 100 pg/ml, o depending on the test.
0 o0 S Therapeutic effects are achieved in amounts of 200 ag- 20 100 mg/kg of body weight.
Apart from the intact antibodies according to the S" invention, it is also possible to make use of their products of cleavage by enzymes (in particular papain, plasmin or pepsin), which are prepared by processes known to those skilled in the art, such as, for example, F(ab') 2 or Fab.
0 0i s a o c

Claims (8)

1. A monoclonal antibody, MAb 436/15 as herein defined, of the IgG 3 isotype with a kappa chain, which antibody reacts with a glycoprotein (antigen 1) which has a molecular weight (MW) exceeding 200 kDa under non-reducing conditions, a monoclonal antibody, MAb 494/32 as herein defined, of the IgG 1 isotype with a kappa chain, which antibody reacts with a glycoprotein (antigen 2) which has an MW exceeding 200 kDa under non-reducing and under reducing conditions, and two monoclonal anti-bodies, MAb 495/19 and 495/36 as herein defined, of the IgG 3 isotype with a kappa 0 0 chain, which antibodies react with a glycoprotein (antigen o[ 3) which has an MW exceeding 200 kDa under non-reducing and S, under reducing conditions. o 0 o 0.
2. A process for the preparation of the monoclonal 00 o antibody, MAb 436/15, of the IgG 3 isotype with a kappa chain, which antibody reacts with a glycoprotein (antigen 1) which has a molecular weight (MW) exceeding 200 kDa under non-reducing conditions, of the monoclonal antibody 494/32, of the IgG 1 isotype with a kappa chain, which antibody S.reacts with a glycoprotein (antigen 2) which has an MW a exceeding 200 kDa under non-reducing and under reducing Sconditions, and of two monoclonal antibodies, MAb495/19 and 495/36, of the IgG 3 isotype with a kappa chain, which two antibodies react with a glycoprotein (antigen 3) which has an MW exceeding 200 kDa under non-reducing and under reducing conditions, which comprises immunization of a mammal with cells of the lung carcinoma cell line MR22E572 or of the colon carcinoma cell line DE-TA, removal of spleen cells from an animal which has been immunized in this way, fusion with 1R!- p t- 1 1 i 10 the cell line X63 Ag8.653, selection of the hyb- ridomas, and obtaining of the MAb.
3. The process as claimed in claim 2, wherein the mammal is the iouse.
4. The use of a monQclonal antibody as claimed in claim 1 in an in vitro diagnostic aid. The use of a monoclonal antibody as claimed in claim 1 as a carrier for a pharmaceutical active compound.
S o
6. The use of a monoclonal antibody as claimed in 0 0 o claim 1 as a therapeutic agent. 0 o 0
7. The use of a monoclonal antibody as claimed in o. o claim 1 in a Labeled form as a diagnostic aid or 0° for the analysis of tissues and body fluids and for 00 Sradioimmunoscintigraphy. 6000
8. The use of a monoclonal antibody as claimed in S claim 1 in a labeled form as a therapeutic agent 0 for radioimmunotherapy or for chemoimmunotherapy. DATED this 29th day of August 1986. BEHRINGWERKE AKTIENGESELLSCHAFT S'EDWD. WATERS SONS PATENT ATTORNEYS QUEEN STREET MELBOURNE. VIC.3000.
AU62140/86A 1985-09-02 1986-09-01 Monoclonal antibodies against tumour-associated glycoproteins, a process for their preparation and their use Ceased AU611381B2 (en)

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DE19853531301 DE3531301A1 (en) 1985-09-02 1985-09-02 MONOCLONAL ANTIBODIES AGAINST TUMOR ASSOCIATED GLYCOPROTEINS, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE
DE3531301 1985-09-02

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AU611381B2 true AU611381B2 (en) 1991-06-13

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JP (1) JP2526217B2 (en)
AU (1) AU611381B2 (en)
DE (1) DE3531301A1 (en)
DK (1) DK415586A (en)
ES (1) ES2000615A6 (en)
GR (1) GR862238B (en)
MX (1) MX3601A (en)
PT (1) PT83285B (en)
ZA (1) ZA866614B (en)

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DE3629640A1 (en) * 1986-08-30 1988-03-03 Behringwerke Ag USE OF MONOCLONAL ANTIBODIES FOR THE TREATMENT OF TUMORS
DE3584280D1 (en) * 1984-10-26 1991-11-07 Wakunaga Seiyaku Kk MONOCLONAL ANTIBODY AGAINST HUMAN CANCER.
AU601379B2 (en) * 1985-11-07 1990-09-13 Trustees Of Columbia University In The City Of New York, The Antigen indicative of human breast cancer and assays based thereon
US4926869A (en) * 1986-01-16 1990-05-22 The General Hospital Corporation Method for the diagnosis and treatment of inflammation
GB8800078D0 (en) * 1988-01-05 1988-02-10 Ciba Geigy Ag Novel antibodies
DE3825615A1 (en) * 1988-07-28 1990-02-01 Behringwerke Ag ANTIGENT CONSTRUCTS OF "MAJOR HISTOCOMPATIBILITY COMPLEX" CLASS I ANTIGENS WITH SPECIFIC CARRIER MOLECULES, THEIR PRODUCTION AND USE
JPH0266456A (en) * 1988-08-31 1990-03-06 Saikin Kagaku Kenkyusho:Kk Primary diagnostic method for disease animal and diagnostic reagent used therein and its production
DE3909799A1 (en) 1989-03-24 1990-09-27 Behringwerke Ag MONOCLONAL ANTIBODIES (MAK) AGAINST TUMOR ASSOCIATED ANTIGENS, THEIR PRODUCTION AND USE

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU4976585A (en) * 1985-05-10 1986-11-13 Nihon Medi-Physics Co., Ltd. Monoclonal antibody to human adenocarcinoma cells, and its preparation and use
AU6927287A (en) * 1986-02-26 1987-08-27 Bristol-Myers Squibb Company Monoclonal antibodies and antigen for human non-small cell lung carcinoma and certain other human carcinomas

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3329184A1 (en) * 1983-08-12 1985-02-21 Behringwerke Ag, 3550 Marburg MONOCLONAL ANTIBODIES WITH SPECIFICITY FOR MEMBRANE-ASSOCIATED ANTIGENS
DE3416774A1 (en) * 1984-05-07 1985-11-14 Behringwerke Ag, 3550 Marburg MONOCLONAL ANTIBODIES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE
US4585742A (en) * 1983-12-14 1986-04-29 Dana-Farber Cancer Institute, Inc. Monoclonal antibody with specificity to human small cell carcinoma and use thereof
DK276185D0 (en) * 1984-11-09 1985-06-19 Novo Industri As MONOCLONAL ANTIBODIES, METHOD OF PREPARING THESE AND THEIR DIAGNOSTIC USES

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU4976585A (en) * 1985-05-10 1986-11-13 Nihon Medi-Physics Co., Ltd. Monoclonal antibody to human adenocarcinoma cells, and its preparation and use
AU6927287A (en) * 1986-02-26 1987-08-27 Bristol-Myers Squibb Company Monoclonal antibodies and antigen for human non-small cell lung carcinoma and certain other human carcinomas

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DE3531301A1 (en) 1987-03-05
DK415586D0 (en) 1986-09-01
PT83285A (en) 1986-10-01
AU6214086A (en) 1987-03-05
EP0213581A2 (en) 1987-03-11
EP0213581A3 (en) 1988-05-25
GR862238B (en) 1986-12-31
JPS6269997A (en) 1987-03-31
MX3601A (en) 1993-05-01
ES2000615A6 (en) 1988-03-01
ZA866614B (en) 1987-04-29
JP2526217B2 (en) 1996-08-21
PT83285B (en) 1989-05-12
DK415586A (en) 1987-03-03

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