WO1997008205B1 - Antibodies having two or more specificities for the selective elimination of cells in vivo - Google Patents
Antibodies having two or more specificities for the selective elimination of cells in vivoInfo
- Publication number
- WO1997008205B1 WO1997008205B1 PCT/EP1996/003734 EP9603734W WO9708205B1 WO 1997008205 B1 WO1997008205 B1 WO 1997008205B1 EP 9603734 W EP9603734 W EP 9603734W WO 9708205 B1 WO9708205 B1 WO 9708205B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibody
- antigen
- tumor
- antigens
- cell
- Prior art date
Links
- 238000001727 in vivo Methods 0.000 title claims abstract 3
- 230000008030 elimination Effects 0.000 title 1
- 238000003379 elimination reaction Methods 0.000 title 1
- 108091007433 antigens Proteins 0.000 claims abstract 28
- 102000036639 antigens Human genes 0.000 claims abstract 28
- 239000000427 antigen Substances 0.000 claims abstract 27
- 210000004881 tumor cell Anatomy 0.000 claims abstract 9
- 239000003814 drug Substances 0.000 claims abstract 4
- 239000000203 mixture Substances 0.000 claims abstract 2
- 210000004027 cell Anatomy 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 239000012636 effector Substances 0.000 claims 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims 2
- 238000009169 immunotherapy Methods 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 230000003211 malignant effect Effects 0.000 claims 2
- 102100022749 Aminopeptidase N Human genes 0.000 claims 1
- 208000003950 B-cell lymphoma Diseases 0.000 claims 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims 1
- 101150013553 CD40 gene Proteins 0.000 claims 1
- 108010058905 CD44v6 antigen Proteins 0.000 claims 1
- 241000189662 Calla Species 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 102100032768 Complement receptor type 2 Human genes 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 101710190709 Eukaryotic translation initiation factor 4 gamma 2 Proteins 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims 1
- 101000757160 Homo sapiens Aminopeptidase N Proteins 0.000 claims 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims 1
- 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 claims 1
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 claims 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 claims 1
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 claims 1
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 claims 1
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 claims 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 claims 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims 1
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 claims 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims 1
- 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 claims 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims 1
- 108010043496 Immunoglobulin Idiotypes Proteins 0.000 claims 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 claims 1
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 claims 1
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 claims 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 claims 1
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 claims 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims 1
- 102000003729 Neprilysin Human genes 0.000 claims 1
- 108090000028 Neprilysin Proteins 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 102100038081 Signal transducer CD24 Human genes 0.000 claims 1
- 206010042971 T-cell lymphoma Diseases 0.000 claims 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 claims 1
- 101710132062 Transitional endoplasmic reticulum ATPase Proteins 0.000 claims 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims 1
- 229960002685 biotin Drugs 0.000 claims 1
- 235000020958 biotin Nutrition 0.000 claims 1
- 239000011616 biotin Substances 0.000 claims 1
- 201000008275 breast carcinoma Diseases 0.000 claims 1
- -1 c-erb-B2 Proteins 0.000 claims 1
- 201000010989 colorectal carcinoma Diseases 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 150000002270 gangliosides Chemical class 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 208000029824 high grade glioma Diseases 0.000 claims 1
- 201000011614 malignant glioma Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 231100000617 superantigen Toxicity 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 238000000338 in vitro Methods 0.000 abstract 1
Abstract
The invention concerns antibodies having two or more specificities detecting two different antigens localized on a tumour cell. The invention further concerns medicaments and diagnostic compositions containing these antibodies. The antibodies and medicaments described are suitable in particular for specifically detecting and eliminating tumour cells in vivo or in vitro.
Claims
1. Antikörper mit mindestens drei Spezifitäten, dadurch ge¬ kennzeichnet, daß von mindestens zwei Antigenbindungs- stellen des Antikörpers mit unterschiedlicher Spezifität zwei unterschiedliche auf einer Tumorzelle lokalisierte Antigene erkannt werden und eine weitere Antigenbin- dungsstelle mit einer weiteren Spezifität ein auf einer Effektorzelle lokalisiertes Antigen erkennt.1. Antibody having at least three specificities, characterized ge indicates that are recognized by at least two antigen binding sites of the antibody with different specificity two different located on a tumor cell antigens and another antigen binding site with a further specificity an isolated on an effector cell antigen recognizes.
2. Antikörper nach Anspruch 1, dadurch gekennzeichnet, daß von den Antigenbindungsstellen, die zwei unterschiedli¬ che auf der Tumorzelle lokalisierte Antigene erkennen, zwei verschiedene tumorassoziierte Antigene erkannt wer¬ den.2. Antibody according to claim 1, characterized in that two different tumor-associated antigens wer¬ recognized by the antigen binding sites that recognize two unterschiedli¬ che located on the tumor cell antigens.
3. Antikörper nach Anspruch 1, dadurch gekennzeichnet, daß von den Antigenbindungsstellen, die zwei unterschiedli¬ che auf der Tumorzelle lokalisierte Antigene erkennen, mindestens eine Antigenbindungsstelle ein tumorassozi¬ iertes Antigen erkennt und mindestens eine weitere Anti¬ genbindungsstelle ein Antigen erkennt, das auch von nicht-malignen Zellen exprimiert wird.3. Antibody according to claim 1, characterized in that of the antigen binding sites which recognize two unterschiedli¬ che on the tumor cell localized antigens, at least one antigen binding site recognizes a tumorassozi¬ iert antigen and at least one further anti¬ gene binding site recognizes an antigen that also from non-malignant cells is expressed.
4. Antikörper nach Anspruch 3, wobei das Antigen, das auch von nicht-malignen Zellen exprimiert wird, ein Antigen ist, das spezifisch für den Zeil- oder Gewebetyp des Tu¬ mors ist.4. The antibody of claim 3, wherein the antigen also expressed by non-malignant cells is an antigen specific to the cell or tissue type of the tumor.
5. Antikörper nach Anspruch 1, dadurch gekennzeichnet, daß von den Antigenbindungsstellen, die zwei unterschiedli¬ che auf einer Tumorzelle lokalisierte Antigene erkennen, zwei nicht-tumorspezifische Antigene erkannt werden, die in Kombination ausschließlich oder fast ausschließlich auf der Tumorzelle vorkommen. 5. An antibody according to claim 1, characterized in that two non-tumor-specific antigens are detected by the antigen binding sites that recognize two unterschiedli¬ che on a tumor cell located antigens that occur in combination exclusively or almost exclusively on the tumor cell.
6. Antikörper nach einem der Ansprüche 1 bis 5, wobei die auf der Tumorzelle lokalisierten Antigene die Antigene CD1, CD2, CD4, CD6, CD7, CD8, CD10, CDU, CD13 , CD14 , CD23, CD24, einen Ig-Idiotyp, CD30, CD33, CD37, CD40, CD41, c-erb-B2, CALLA (CD10) , MHCII, CD44v3 , CD44v6, CD71, p97, Gangliosid-GD_2, GD3 , C215, das von dem mono¬ clonalen Antikörper 17-IA-erkannte Antigen, das von dem monoclonalen Antikörper 9.2.27 erkannte Antigen, das von dem monoclonalen Antikörper NE150 erkannte Antigen, das von dem monoclonalen Antikörper L6 erkannte Antigen, das von dem monoclonalen Antikörper CA125 erkannte Antigen6. An antibody according to any one of claims 1 to 5, wherein the tumor cell located on the antigens antigens CD1, CD2, CD4, CD6, CD7, CD8, CD10, CDU, CD13, CD14, CD23, CD24, an Ig idiotype, CD30 , CD33, CD37, CD40, CD41, c-erb-B2, CALLA (CD10), MHCII, CD44v3, CD44v6, CD71, p97, ganglioside G D _ 2, GD3, C215, that of the monoethylenically clonal antibody 17- IA-recognized antigen, the antigen recognized by the monoclonal antibody 9.2.27, the antigen recognized by the monoclonal antibody NE150, the antigen recognized by the monoclonal antibody L6, the antigen recognized by the monoclonal antibody CA125
(Mucin) , das Antigen Lewis y, CD19, CD20, CD21, CD22, B220 oder CD5 sind.(Mucin), the antigen is Lewis y, CD19, CD20, CD21, CD22, B220 or CD5.
7. Antikörper nach einem der Ansprüche 1 bis 6, dadurch ge¬ kennzeichnet, daß das auf der Effektorzelle lokalisierte Antigen nicht auf der Tumorzelle vorhanden ist.7. Antibody according to one of claims 1 to 6, characterized ge indicates that the localized on the effector cell antigen is not present on the tumor cell.
8. Antikörper nach einem der Ansprüche 1 bis 7, dadurch ge¬ kennzeichnet, daß es sich bei dem auf der Effektorzelle lokalisierten Antigen um das Antigen CD3 , CD16, CD28, CD32 oder CD64 handelt.8. Antibody according to one of claims 1 to 7, characterized ge indicates that it is the antigen located on the effector cell to the antigen CD3, CD16, CD28, CD32 or CD64.
9. Antikörper nach einem der Ansprüche 1 bis 8, wobei es sich um einen monoclonalen Antikörper, einen durch re¬ kombinante DNA-Technologie hergestellten Antikörper, eine halbsynthetischen oder synthetischen Antikörper, um einen chemisch modifizierten Antikörper oder um ein Fragment eines solchen Antikörpers handelt.9. An antibody according to any one of claims 1 to 8, wherein it is a monoclonal antibody, an antibody produced by re¬ combinant DNA technology, a semisynthetic or synthetic antibody, a chemically modified antibody or a fragment of such an antibody.
10. Antikörper nach einem der Ansprüche 1 bis 9, wobei der Antikörper gekoppelt ist mit einem Enzym, einer toxi¬ schen Substanz, einem Radionuclid, Biotin oder einem Superantigen.10. An antibody according to any one of claims 1 to 9, wherein the antibody is coupled with an enzyme, a toxi¬'s substance, a radionuclide, biotin or a superantigen.
11. Arzneimittel enthaltend mindestens einen Antikörper nach einem der Ansprüche 1 bis 10. 11. A medicament containing at least one antibody according to any one of claims 1 to 10.
12. Verwendung eines Antikörpers nach einem der Ansprüche 1 bis 10 zur Herstellung eines Arzneimittels zur in vivo Immuntherapie .12. Use of an antibody according to any one of claims 1 to 10 for the manufacture of a medicament for in vivo immunotherapy.
13. Verwendung nach Anspruch 12, wobei die Immuntherapie eine Therapie zur Behandlung eines Tumors ist.13. Use according to claim 12, wherein the immunotherapy is a therapy for the treatment of a tumor.
14. Verwendung nach Anspruch 13, wobei der Tumor eine Leukämie, ein kolorektales Karzinom, ein Melanom, ein Ovarialkarzinom, ein Glioblastom (malignes Gliom) oder ein Mamma-Karzinom ist.14. Use according to claim 13, wherein the tumor is a leukemia, a colorectal carcinoma, a melanoma, an ovarian carcinoma, a glioblastoma (malignant glioma) or a mammary carcinoma.
15. Verwendung nach Anspruch 14, wobei die Leukämie ein B- Zell-Lymphom oder ein T-Zell-Lymphom ist.Use according to claim 14, wherein the leukemia is a B-cell lymphoma or a T-cell lymphoma.
16. Diagnostische Zusammensetzung enthaltend mindestens einen Antikörper nach einem der Ansprüche 1 bis 10. 16. A diagnostic composition comprising at least one antibody according to any one of claims 1 to 10.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1995131348 DE19531348A1 (en) | 1995-08-25 | 1995-08-25 | Antibodies with two or more specificities for the selective elimination of cells in vivo |
| DE19531348.8 | 1995-08-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1997008205A1 WO1997008205A1 (en) | 1997-03-06 |
| WO1997008205B1 true WO1997008205B1 (en) | 1997-05-15 |
Family
ID=7770410
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1996/003734 WO1997008205A1 (en) | 1995-08-25 | 1996-08-23 | Antibodies having two or more specificities for the selective elimination of cells in vivo |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE19531348A1 (en) |
| WO (1) | WO1997008205A1 (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2753368B1 (en) | 1996-09-13 | 1999-01-08 | Chauvin Jean Luc | EXPANSIONAL OSTEOSYNTHESIS CAGE |
| BRPI9909860B8 (en) | 1998-04-21 | 2021-05-25 | Amgen Res Munich Gmbh | multifunctional single-chain polypeptide, polynucleotide, vector, prokaryotic, yeast or unicellular cell, composition, uses of polypeptide and polynucleotide, and methods for preparing said polypeptide and for identifying activators or inhibitors of activation or stimulation of t cells |
| DE10034607A1 (en) | 2000-07-20 | 2002-02-07 | Gundram Jung | Multi-specific reagent for the selective stimulation of cell surface receptors |
| DE10043437A1 (en) | 2000-09-04 | 2002-03-28 | Horst Lindhofer | Use of trifunctional bispecific and trispecific antibodies for the treatment of malignant ascites |
| AT413486B (en) * | 2002-07-03 | 2006-03-15 | Igeneon Krebs Immuntherapie | USE OF AN ANTIBODY DIRECTED AGAINST LEWIS ANTIGENE |
| AT500648B1 (en) | 2002-08-12 | 2010-03-15 | Igeneon Krebs Immuntherapie | SET FOR THE TREATMENT OF CANCER PATIENTS |
| KR20060015602A (en) | 2003-05-31 | 2006-02-17 | 마이크로메트 에이지 | Pharmaceutical composition comprising a bispecific antibody against EVCA |
| CN100509850C (en) | 2003-05-31 | 2009-07-08 | 麦克罗梅特股份公司 | Pharmaceutical compositions comprising bispecific anti-cd3, anti-cd19 antibody constructs for the treatment of b-cell related disorders |
| EP3151788A4 (en) | 2014-06-04 | 2018-01-17 | Wenzel Spine, Inc. | Bilaterally expanding intervertebral body fusion device |
| JP7229176B2 (en) | 2017-02-07 | 2023-02-27 | オブリーク セラピューティクス アーベー | Hydrocarbylsulfonyl-substituted pyridines and their use in treating cancer |
| US11219531B2 (en) | 2019-04-10 | 2022-01-11 | Wenzel Spine, Inc. | Rotatable intervertebral spacing implant |
| WO2020236792A1 (en) | 2019-05-21 | 2020-11-26 | Novartis Ag | Cd19 binding molecules and uses thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4978745A (en) * | 1987-11-23 | 1990-12-18 | Centocor, Inc. | Immunoreactive heterochain antibodies |
| AU6290090A (en) * | 1989-08-29 | 1991-04-08 | University Of Southampton | Bi-or trispecific (fab)3 or (fab)4 conjugates |
| ZA914625B (en) * | 1990-06-22 | 1993-02-24 | Lilly Co Eli | In vivo targeting with bifunctional antibodies |
| DE4028955A1 (en) * | 1990-09-12 | 1992-03-19 | Boehringer Mannheim Gmbh | MONOCLONAL ANTIBODIES AGAINST THE INTERLEUKIN 2 RECEPTOR |
| FR2672291A1 (en) * | 1991-01-31 | 1992-08-07 | Inst Nat Sante Rech Med | COMPOSITION OF ANTIBODIES DIRECTED AGAINST HUMAN OR ANIMAL INTERLEUKIN-2 RECEPTOR. |
| AU2400692A (en) * | 1991-07-19 | 1993-02-23 | Hybritech Incorporated | Trifunctional compounds having specificity for multi-drug resistant cells |
| WO1994024163A2 (en) * | 1993-04-09 | 1994-10-27 | Chiron Corporation | Bispecific antigen-binding molecules |
-
1995
- 1995-08-25 DE DE1995131348 patent/DE19531348A1/en not_active Withdrawn
-
1996
- 1996-08-23 WO PCT/EP1996/003734 patent/WO1997008205A1/en active Application Filing
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