CN1315967A - Bifunctional antibodies and their use in targeting anti-tumour agents - Google Patents
Bifunctional antibodies and their use in targeting anti-tumour agents Download PDFInfo
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- CN1315967A CN1315967A CN99810368A CN99810368A CN1315967A CN 1315967 A CN1315967 A CN 1315967A CN 99810368 A CN99810368 A CN 99810368A CN 99810368 A CN99810368 A CN 99810368A CN 1315967 A CN1315967 A CN 1315967A
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- antibody
- radiolabeled
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- 230000000259 anti-tumor effect Effects 0.000 title description 3
- 230000008685 targeting Effects 0.000 title description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
- 229940127089 cytotoxic agent Drugs 0.000 claims abstract description 13
- 239000002254 cytotoxic agent Substances 0.000 claims abstract description 13
- 231100000599 cytotoxic agent Toxicity 0.000 claims abstract description 12
- 108090000790 Enzymes Proteins 0.000 claims abstract description 8
- 102000004190 Enzymes Human genes 0.000 claims abstract description 8
- 238000011282 treatment Methods 0.000 claims abstract description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 230000001225 therapeutic effect Effects 0.000 claims description 10
- 239000000427 antigen Substances 0.000 claims description 8
- 102000036639 antigens Human genes 0.000 claims description 8
- 108091007433 antigens Proteins 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 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 description 5
- 229930003756 Vitamin B7 Natural products 0.000 claims description 5
- 239000011735 vitamin B7 Substances 0.000 claims description 5
- 235000011912 vitamin B7 Nutrition 0.000 claims description 5
- 108060003951 Immunoglobulin Proteins 0.000 claims description 4
- 102000018358 immunoglobulin Human genes 0.000 claims description 4
- ZWVIEGKRECXIPC-UHFFFAOYSA-N n-(6-aminohexyl)-4-hydroxy-3,5-diiodobenzamide Chemical compound NCCCCCCNC(=O)C1=CC(I)=C(O)C(I)=C1 ZWVIEGKRECXIPC-UHFFFAOYSA-N 0.000 claims description 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N pentanoic acid group Chemical class C(CCCC)(=O)O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 3
- 239000003446 ligand Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 238000002405 diagnostic procedure Methods 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- QYFLDPNTDXMLRO-UHFFFAOYSA-N n-(6-aminohexyl)-2-hydroxy-3,5-diiodobenzamide Chemical compound NCCCCCCNC(=O)C1=CC(I)=CC(I)=C1O QYFLDPNTDXMLRO-UHFFFAOYSA-N 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 238000011275 oncology therapy Methods 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 abstract description 6
- 239000000651 prodrug Substances 0.000 abstract description 6
- 231100000433 cytotoxic Toxicity 0.000 abstract description 2
- 230000001472 cytotoxic effect Effects 0.000 abstract description 2
- 238000003745 diagnosis Methods 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000163 radioactive labelling Methods 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 239000002574 poison Substances 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010006303 Carboxypeptidases Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical class ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003327 cancerostatic effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- YDTFRJLNMPSCFM-YDALLXLXSA-M levothyroxine sodium anhydrous Chemical compound [Na+].IC1=CC(C[C@H](N)C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 YDTFRJLNMPSCFM-YDALLXLXSA-M 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Epidemiology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
A bifunctional antibody has affinity for a target site and affinity for an organic molecule covalently linked to a cytotoxic agent or an enzyme capable of converting a prodrug into its cytotoxic form. The antibody may be used in therapy or diagnosis, especially in the treatment of tumours.
Description
Invention field
The present invention relates to bifunctional antibody and the application in the targeting anti-tumour agents in vivo thereof.
Background of invention
Therapeutical agent is well-known to the internal guide of privileged site.Particularly, wish very much to tumor locus guiding carcinostatic agent, improving the concentration of this position medicament, thereby improve its in and usefulness in the tumour.The example of the medicament of guiding tumour is well-known, and the specificity of wherein many dependence monoclonal antibodies is carried diagnostic reagent or therapeutical agent to target site.A kind of method is to use the radionuclide-antibody coupling matter that is positioned in the target tissue, and radionuclide can be brought into play its cytotoxicity in target tissue.
Yet find out, use radionuclide-antibody coupling matter to exist problem, for example, because the high molecular of conjugate makes conjugate relatively poor to the infiltration of target site.In addition, for make this conjugate in treatment effectively, must give the regular hour to be positioned target site.Therefore there is the long time in vivo in radionuclide, and this causes the undesirable toxicity in non-target site.
Therefore wish not rely on radiolabeled cytotoxic agent and administration of antibodies, thereby before using radiolabeled cytotoxic agent, make antibody be positioned target site.
US-A-5630996 has described a kind of method of using the vitamin H of antibody-Streptavidin conjugate guiding radioisotope labeling.Streptavidin has the high-affinity to vitamin H, and can make radionuclide be positioned target site by vitamin H-Streptavidin interaction.But Streptavidin is a kind of immunogenic protein that has in human body, therefore may be unsuitable for the multiple long-term treatment and use.
US-A-5591828 discloses the bi-specific antibody that has the avidity of metallo-chelate and specified protein epi-position.Yet, inner complex EDTA-Y
90And DTPA-Y
90Preferably need covalency add can with the fos-peptide of jun-peptide interaction on the antibody, with enough Y
90Be positioned target site.In addition, at sequestrant (EDTA) and radionuclide (Y
90) between may dissociate.Therefore, perhaps be not effectively in the location of tumor locus, and the method for generation fos-peptide-metal-chelating conjugate is tediously long, and is unsuitable for scale operation.
Summary of the invention
The present invention relates to the antigen that exists in the tumor locus and therapeutical agent or diagnostic reagent are all had the bifunctional antibody of avidity, wherein this medicament be a kind of radiolabeled or with the covalently bound organic molecule of cytotoxic agent.In an independent embodiment, this organic molecule combines with a kind of enzyme that prodrug can be converted into the cell toxicant form.
Therefore the invention provides a kind of by using the localized method of bifunctional antibody and organic molecule enhancing therapeutical agent in proper order at target site.The present invention can be used for treatment or diagnostic uses.
Generally speaking, this organic molecule is the good infiltration at vitamin H or a kind of display target position, otherwise bio distribution in vivo is the neutral organic molecule.
An advantage of the invention is and can use a kind of cytotoxic agent, the target position that it will be positioned to wish owing to interacting with antibody, but the toxicity of non-target tissue is reduced, because unconjugated medicament will be removed in body effectively.
In one embodiment, cytotoxic agent is a kind of radionuclide, and covalently bound with organic molecule, perhaps itself is the part of organic molecule.Can select radionuclide performance therapeutic action, for example as a kind of antineoplastic agent, or can be diagnostic purpose and use, as tumor imaging.
In another embodiment, this organic molecule is connected with a kind of enzyme that can be used for suitable prodrug is converted into active cells poison form.
Invention is described
Antibody of the present invention can produce with routine techniques, and for example hybridoma is synthetic, recombinant DNA technology or phage display.These antibody can derive from any kind, comprise rodent, but preferably antibody sources is in the Mammals except that rodent, and for example sheep, goat or cow are to produce high-affinity antibody.
These antibody generally have at least 10 to part separately
10L/mol, preferably 10
11L/mol, more preferably 10
12L/mol, most preferably 10
13The avidity of l/mol.
According to bifunctional antibody of the present invention can be complete antibody, perhaps can be its fragment, as f (a/b)
2In another embodiment, antibody can contain two strand fv fragments.The preparation of difunctional sFv is well-known.For example, people such as Carter, modern biotechnology viewpoint (Current Opinion in Biotechnology) 1997,8: 449-454 disclose to utilize and have bitten mattress body display library and produce difunctional sFv.
In addition, also can utilize the recombinant DNA technology modified antibodies, with " humanization " these antibody, making it has lower immunogenicity when the patient is used.Humanized antibody should comprise to come from least to be had the monoclonal antibody of avidity and organic molecule is had the hypervariable region of the monoclonal antibody of avidity target antigen.Remaining antibody variable region can be the variable region of human normal immunoglobulin.At complete antibody or fragment such as F (ab ')
2In can have the human normal immunoglobulin of higher proportion.When using strand Fv fragment, this fragment can contain aforesaid hypervariable region, and randomly is derived from the variable framework of human normal immunoglobulin.
Antibody can have the avidity to the particular target position.Usually, target site is a kind of tumour, and antibody has the avidity to tumor associated antigen.An example of tumor associated antigen is the carcinomebryonic antigen of finding in colorectal carcinoma and other gland cancer (CEA).
In preferred embodiments, antibody has ligand affinity to radiolabeled organic molecule.The present invention includes in the independent covalent attachment of radionuclide and organic molecule and the organic molecule itself the suitably simple radio-labeling of atom.For example, organic molecule can comprise radiolabeled phosphorus or iodine atom and become a kind of cytotoxicity organic molecule.Using of this molecule will make radionuclide by being positioned tumor locus with antibodies, to tumour performance cytotoxicity.Radionuclide with cytotoxicity is well-known.A kind of preferred radionuclide that can use in the present invention is the radio isotope of iodine, as can be used for the I of diagnostic uses
123, I
124And I
125And the I that can be used for treating
131Can be used for the preferred radionuclide of another kind of the present invention is P
32
Cytotoxic agent also can be a cytotoxic drug, as ricin or calicheamycin.
In another embodiment, organic molecule is connected (coupling) with a kind of enzyme.This enzyme can be converted into suitable prodrug active cells poison form.This with term " prodrug " definition medicine inactive form, its can be cut by the enzyme effect and discharge the treatment effective form.Suitable enzyme-prodrug system is known by those skilled in the art, comprises the yperite derivative of carboxypeptidase and modification.
Useful in the present invention organic molecule must interact specifically with antibody.Therefore these molecules must have enough sizes to cause immunne response, with the protein carrier coupling time, to produce antibody, perhaps have enough sizes be beneficial to from as produce antibody thread biting the antibody library that the mattress body shows.Preferably, the organic molecule that is connected with cytotoxic agent or enzyme can arrive target site by the lining of vasculature.The molecular weight of these organic molecules is preferably lower than 1500, more preferably is lower than 1000.Organic molecule is preferably nontoxic when radio-labeling not.In addition, the organic molecule of mark should have the neutral bio distribution when the patient uses under no bi-specific antibody situation, and the molecule of selecting not accumulate in Tiroidina and can be removed fast by kidney is preferred.If these molecules are easy to be derived by cold parental generation molecule, and the deutero-tagged molecule is stable after using, and then also is favourable.Conjugate is preferably water miscible, is beneficial to prepare in suitable vehicle.Suitable organic molecule comprises non-toxic compound, and is Cytotoxic but these molecules can become by radio-labeling.
In a preferred embodiment, radiolabeled organic molecule is radiolabeled vitamin H.In another preferred embodiment, this molecule has formula I
Promptly 4, two (4-hydroxyl-3, the 5-diiodo-phenyl) valeric acids of 4-.
In another preferred embodiment, this molecule has the general formula II
R wherein
1And R
2Be radiolabeled part independently of one another, as radiolabeled iodine, methyl or phenyl, X
1And X
2Be H or OH independently of one another.
Preferred radiolabeled molecule is N-(4-hydroxyl-3,5-diiodo-benzene formyl)-1,6-hexanediamine and N-(2-hydroxyl-3,5-diiodo-benzene formyl)-1, the 6-hexanediamine, wherein in two iodine atoms any or each can be radio isotope I
123, I
125, I
124And I
131One of.
Be used for when of the present invention, bi-specific antibody and cytotoxic agent can be contained in the test kit, for example, and comprise packing respectively or two kinds of compositions in the container that separates.According to route of administration, to use as oral or intravenously, every kind of composition can be prepared with appropriate carriers or vehicle, and the example is well-known.
Two kinds of compositions are used usually in proper order.The technician can easily determine the significant quantity of every kind of composition, and it depends on following typical factor, as position, seriousness and the diffusion of tumour, patient's the state of an illness etc.The amount of required cytotoxic agent will be lower than amount when not containing antibody yes a feature of the present invention.
Claims (20)
1. one kind has to tumour and to the bifunctional antibody of the avidity of therapeutical agent or diagnostic reagent, and wherein this medicament is an organic molecular species.
2. one kind has to tumour and to the bifunctional antibody of the avidity of therapeutical agent, and wherein this medicament is a kind of and the covalently bound organic molecule of enzyme.
3. according to the antibody of claim 1 or claim 2, wherein ligand affinity is at least 10
10L/ml.
4. according to the antibody of aforementioned arbitrary claim, wherein this organic molecule molecular weight is lower than 1500.
5. according to the antibody of aforementioned arbitrary claim, wherein this organic molecule is water miscible, and has bio distribution in the neutral body.
6. according to a kind of antibody of claim 1, wherein radioactively labelled substance is I
123, I
124, I
125, P
32Or I
131
7. according to the antibody of aforementioned arbitrary claim, wherein this molecule is radiolabeled 4, two (4-hydroxyl-3, the 5-diiodo-phenyl) valeric acids of 4-.
8. according to each antibody of claim 1-6, wherein this molecule has general formula
R wherein
1And R
2Be a kind of radioactively labelled substance independently, as radiolabeled iodine, methyl or phenyl, X
1And X
2Be H or OH independently.
9. a kind of antibody according to Claim 8, wherein this molecule is radiolabeled N-(4-hydroxyl-3,5-diiodo-benzene formyl)-1,6-hexanediamine or N-(2-hydroxyl-3,5-diiodo-benzene formyl)-1,6-hexanediamine.
10. according to a kind of antibody of claim 1 or claim 2, wherein this molecule is a vitamin H.
11. according to the antibody of aforementioned arbitrary claim, wherein the affinity of antibody to tumour is to pass through tumor associated antigen.
12. according to a kind of antibody of claim 11, wherein this antigen is carcinomebryonic antigen.
13. according to the antibody of aforementioned arbitrary claim, wherein this antibody contains two strand Fv.
14. according to the antibody of aforementioned arbitrary claim, wherein this antibody contains the constant region that derives from human normal immunoglobulin at least.
15. a radiolabeled compound, wherein this compound is 4, two (4-hydroxyl-3, the 5-diiodo-phenyl) valeric acids of 4-, N-(4-hydroxyl-3,5-diiodo-benzene formyl)-1,6-hexanediamine or N-(2-hydroxyl-3,5-diiodo-benzene formyl)-1,6-hexanediamine.
16. radiolabeled 4, two (4-hydroxyl-3, the 5-diiodo-phenyl) valeric acids of 4-, radiolabeled N-(4-hydroxyl-3,5-diiodo-benzene formyl)-1,6-hexanediamine or radiolabeled N-(2-hydroxyl-3,5-diiodo-benzene formyl)-1, the 6-hexanediamine is used for the treatment of or diagnostic method.
17. be used for the application of the composition of cancer therapy in production according to each antibody of claim 1-14.
18. be used for the application of the composition of diagnostic method in production according to each antibody of claim 1-14.
19. product, it is included in the oncotherapy simultaneously, order or having of separately using be to tumour and to bifunctional antibody and the therapeutical agent or the diagnostic reagent of the avidity of organic molecule, and described treatment or diagnostic reagent are and covalently bound organic molecule of cytotoxic agent or radiolabeled organic molecule.
20. the treatment or the method for diagnosing tumour relative disease comprise that order uses:
(ⅰ) a kind of bifunctional antibody, it has to tumour with to the specificity of therapeutical agent or diagnostic reagent;
(ⅱ) a kind of therapeutical agent or diagnostic reagent, wherein this medicament be a kind of radiolabeled or with the covalently bound organic molecule of cytotoxic agent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9819411.1 | 1998-09-04 | ||
| GBGB9819411.1A GB9819411D0 (en) | 1998-09-04 | 1998-09-04 | Antibodies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1315967A true CN1315967A (en) | 2001-10-03 |
Family
ID=10838416
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99810368A Pending CN1315967A (en) | 1998-09-04 | 1999-09-06 | Bifunctional antibodies and their use in targeting anti-tumour agents |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP1107995A2 (en) |
| JP (1) | JP2002524470A (en) |
| KR (1) | KR20010072988A (en) |
| CN (1) | CN1315967A (en) |
| AU (1) | AU5641299A (en) |
| BG (1) | BG105293A (en) |
| BR (1) | BR9913429A (en) |
| CA (1) | CA2341753A1 (en) |
| EA (1) | EA200100311A1 (en) |
| GB (1) | GB9819411D0 (en) |
| HR (1) | HRP20010154A2 (en) |
| HU (1) | HUP0104091A2 (en) |
| ID (1) | ID28873A (en) |
| IL (1) | IL141524A0 (en) |
| MX (1) | MXPA01002349A (en) |
| NO (1) | NO20011102L (en) |
| PL (1) | PL346861A1 (en) |
| TR (2) | TR200103405T2 (en) |
| WO (1) | WO2000014119A2 (en) |
| ZA (1) | ZA200101574B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020019232A1 (en) * | 2018-07-26 | 2020-01-30 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and methods for imaging |
| US11987629B2 (en) | 2018-06-01 | 2024-05-21 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and uses thereof for treating disease or condition |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110811820B (en) * | 2019-12-11 | 2022-07-12 | 江西华晨医疗设备有限公司 | Straight rod type flushing and suction electrocoagulation cutter |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4474893A (en) * | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
| IL89491A0 (en) * | 1988-11-17 | 1989-09-10 | Hybritech Inc | Bifunctional chimeric antibodies |
| US5217713A (en) * | 1988-12-27 | 1993-06-08 | Takeda Chemical Industries, Ltd. | Cytotoxic bispecific monoclonal antibody, its production and use |
| WO1991009134A1 (en) * | 1989-12-15 | 1991-06-27 | Takeda Chemical Industries, Ltd. | Biospecific antibody to cancer cell and enzyme with prodrug-activating characteristics |
| JPH05184383A (en) * | 1990-06-19 | 1993-07-27 | Dainabotsuto Kk | Bispecific antibody |
| US6451980B1 (en) * | 1997-02-26 | 2002-09-17 | Ban-An Khaw | Signal enhancement of bispecific antibody-polymer probe for immunoassay use |
-
1998
- 1998-09-04 GB GBGB9819411.1A patent/GB9819411D0/en not_active Ceased
-
1999
- 1999-09-06 HU HU0104091A patent/HUP0104091A2/en unknown
- 1999-09-06 WO PCT/GB1999/002938 patent/WO2000014119A2/en not_active Application Discontinuation
- 1999-09-06 JP JP2000568876A patent/JP2002524470A/en active Pending
- 1999-09-06 KR KR1020017002437A patent/KR20010072988A/en not_active Application Discontinuation
- 1999-09-06 PL PL99346861A patent/PL346861A1/en not_active Application Discontinuation
- 1999-09-06 TR TR2001/03405T patent/TR200103405T2/en unknown
- 1999-09-06 CA CA002341753A patent/CA2341753A1/en not_active Abandoned
- 1999-09-06 EA EA200100311A patent/EA200100311A1/en unknown
- 1999-09-06 MX MXPA01002349A patent/MXPA01002349A/en not_active Application Discontinuation
- 1999-09-06 CN CN99810368A patent/CN1315967A/en active Pending
- 1999-09-06 EP EP99943138A patent/EP1107995A2/en not_active Withdrawn
- 1999-09-06 ID IDW20010752A patent/ID28873A/en unknown
- 1999-09-06 IL IL14152499A patent/IL141524A0/en unknown
- 1999-09-06 TR TR2001/00651T patent/TR200100651T2/en unknown
- 1999-09-06 AU AU56412/99A patent/AU5641299A/en not_active Abandoned
- 1999-09-06 BR BR9913429-2A patent/BR9913429A/en not_active IP Right Cessation
-
2001
- 2001-02-26 BG BG105293A patent/BG105293A/en unknown
- 2001-02-26 ZA ZA200101574A patent/ZA200101574B/en unknown
- 2001-03-02 NO NO20011102A patent/NO20011102L/en unknown
- 2001-03-02 HR HR20010154A patent/HRP20010154A2/en not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11987629B2 (en) | 2018-06-01 | 2024-05-21 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and uses thereof for treating disease or condition |
| WO2020019232A1 (en) * | 2018-07-26 | 2020-01-30 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and methods for imaging |
Also Published As
| Publication number | Publication date |
|---|---|
| PL346861A1 (en) | 2002-03-11 |
| HRP20010154A2 (en) | 2002-02-28 |
| BR9913429A (en) | 2001-09-25 |
| HUP0104091A2 (en) | 2002-03-28 |
| AU5641299A (en) | 2000-03-27 |
| NO20011102D0 (en) | 2001-03-02 |
| JP2002524470A (en) | 2002-08-06 |
| TR200103405T2 (en) | 2002-06-21 |
| EP1107995A2 (en) | 2001-06-20 |
| MXPA01002349A (en) | 2003-10-15 |
| NO20011102L (en) | 2001-03-05 |
| BG105293A (en) | 2001-12-29 |
| ZA200101574B (en) | 2002-02-26 |
| CA2341753A1 (en) | 2000-03-16 |
| WO2000014119A2 (en) | 2000-03-16 |
| KR20010072988A (en) | 2001-07-31 |
| ID28873A (en) | 2001-07-12 |
| IL141524A0 (en) | 2002-03-10 |
| TR200100651T2 (en) | 2001-07-23 |
| EA200100311A1 (en) | 2001-08-27 |
| GB9819411D0 (en) | 1998-10-28 |
| WO2000014119A3 (en) | 2000-11-30 |
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