NZ764875B2 - Human monoclonal antibodies to ganglioside gd2 - Google Patents
Human monoclonal antibodies to ganglioside gd2 Download PDFInfo
- Publication number
- NZ764875B2 NZ764875B2 NZ764875A NZ76487515A NZ764875B2 NZ 764875 B2 NZ764875 B2 NZ 764875B2 NZ 764875 A NZ764875 A NZ 764875A NZ 76487515 A NZ76487515 A NZ 76487515A NZ 764875 B2 NZ764875 B2 NZ 764875B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- antibody
- polypeptide
- conjugate
- exemplified
- domain
- Prior art date
Links
- CXQCLLQQYTUUKJ-ALWAHNIESA-N beta-D-GalpNAc-(1->4)-[alpha-Neup5Ac-(2->8)-alpha-Neup5Ac-(2->3)]-beta-D-Galp-(1->4)-beta-D-Glcp-(1<->1')-Cer(d18:1/18:0) Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@@H](CO)O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 CXQCLLQQYTUUKJ-ALWAHNIESA-N 0.000 title 1
- 239000003814 drug Substances 0.000 claims abstract 7
- 239000012634 fragment Substances 0.000 claims abstract 6
- 206010028980 Neoplasm Diseases 0.000 claims abstract 5
- 229940124597 therapeutic agent Drugs 0.000 claims abstract 5
- 201000011510 cancer Diseases 0.000 claims abstract 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract 3
- 238000004519 manufacturing process Methods 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims abstract 3
- 102000040430 polynucleotide Human genes 0.000 claims abstract 3
- 108091033319 polynucleotide Proteins 0.000 claims abstract 3
- 239000002157 polynucleotide Substances 0.000 claims abstract 3
- 239000000032 diagnostic agent Substances 0.000 claims abstract 2
- 229940039227 diagnostic agent Drugs 0.000 claims abstract 2
- 229920001184 polypeptide Polymers 0.000 claims 14
- 102000004196 processed proteins & peptides Human genes 0.000 claims 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims 14
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 206010003571 Astrocytoma Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 208000000172 Medulloblastoma Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 206010039491 Sarcoma Diseases 0.000 claims 1
- 206010041067 Small cell lung cancer Diseases 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 201000008968 osteosarcoma Diseases 0.000 claims 1
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- FFILOTSTFMXQJC-QCFYAKGBSA-N (2r,4r,5s,6s)-2-[3-[(2s,3s,4r,6s)-6-[(2s,3r,4r,5s,6r)-5-[(2s,3r,4r,5r,6r)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2r,3s,4r,5r,6r)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(e)-3-hydroxy-2-(octadecanoylamino)octadec-4-enoxy]oxan-3-yl]oxy-3-hy Chemical compound O[C@@H]1[C@@H](O)[C@H](OCC(NC(=O)CCCCCCCCCCCCCCCCC)C(O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 FFILOTSTFMXQJC-QCFYAKGBSA-N 0.000 abstract 1
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
- 230000036952 cancer formation Effects 0.000 abstract 1
- 230000005740 tumor formation Effects 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K16/3076—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 against structure-related tumour-associated moieties
- C07K16/3084—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 against structure-related tumour-associated moieties against tumour-associated gangliosides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- 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
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2405/00—Assays, e.g. immunoassays or enzyme assays, involving lipids
- G01N2405/08—Sphingolipids
- G01N2405/10—Glycosphingolipids, e.g. cerebrosides, gangliosides
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
Abstract
The present invention provides compositions for the production of an antibody or functional fragment thereof directed against disialoganglioside-GD2. The compositions of the invention include polynucleotides encoding a heavy chain and/or a light chain variable domain that binds to GD2. The invention also provides an isolated antibody or functional fragment thereof and methods of treating or preventing a disease, such as cancer or tumor formation, wherein the antibody or functional fragment includes a variable heavy chain domain and a variable light chain domain that has an amino acid sequence provided herein. The invention further provides a conjugate of an antibody or functional fragment thereof conjugated or recombinantly fused to a diagnostic agent, detectable agent or therapeutic agent, and methods of treating, preventing or diagnosing a disease in a subject in need thereof.
Claims (24)
1. An isolated antibody, or a polypeptide that binds to GD2 and ses a functional fragment of the antibody, wherein said antibody or polypeptide comprises a combination of heavy chain variable domain (VH) and light chain variable domain (VL), the VH domain comprising VH CDR1, CDR2 and CDR3 ing to residues 26-33, residues 51-58, and residues 97-110 of SEQ ID NO: 34, and the VL domain comprising VL CDR1, CDR2 and CDR3 according to residues 27-32, es 50-52, and residues 89-97 of SEQ ID NO: 38.
2. The isolated antibody or polypeptide of claim 1, said antibody or polypeptide comprising the VH domain of SEQ ID NO: 34 and a VL domain of SEQ ID NO: 38.
3. The isolated antibody or ptide of claim 1 or 2, wherein said dy is a human antibody.
4. The isolated antibody or polypeptide of of claim 1 or 2, wherein said antibody functional fragment is selected from the group consisting of a Fab, a Fab', a F(ab')2, a scFV, a diabody, a triabody, and a minibody.
5. The isolated antibody or polypeptide of any one of claims 1-3, wherein said antibody is a onal antibody.
6. The isolated antibody or polypeptide of any one of claims 1-3 or 5, wherein said antibody is an IgG or IgM isotope.
7. The isolated antibody or polypeptide of claim 6, wherein said IgG is an IgG 1subclass.
8. A conjugate comprising an isolated antibody or polypeptide of any one of claims 1-7 conjugated or recombinantly fused to a diagnostic agent, or detectable agent or therapeutic agent.
9. The conjugate of claim 8, wherein said antibody or polypeptide is conjugated or recombinantly fused to a detectable agent.
10. The use of a ate of claim 9, in the manufacture of a medicament for detecting a tumor in a subject in need f.
11. The conjugate of claim 8, wherein said antibody or ptide is conjugated or inantly fused to a therapeutic agent.
12. A pharmaceutical composition comprising the antibody or polypeptide of any one of claims 1-7, or the conjugate of claim 11, and a pharmaceutically acceptable carrier.
13. The use of an antibody or polypeptide according to any one of claims 1-7, the conjugate of claim 11 or the ceutical composition of claim 12, in the manufacture of a medicament for use in treating cancer, wherein the cells of said cancer express GD2.
14. The use of claim 13, wherein said cancer is selected from the group consisting of neuroblastoma, osteosarcomas and other subsets of sarcomas, melanomas, gliomas, small cell lung cancer, breast , medulloblastoma, and astrocytoma.
15. The use of claim 13 or 14, wherein said treatment comprises administering concurrently or successively a second therapeutic agent.
16. The use of claim 15, wherein said second therapeutic agent is a chemotherapeutic agent or an immunotherapeutic agent.
17. An isolated polynucleotide encoding the dy or polypeptide of any one of claims 1-7.
18. An antibody or polypeptide according to claim 1, substantially as herein described or exemplified.
19. A conjugate according to claim 8, substantially as herein described or ified.
20. A use according to claim 10, substantially as herein described or exemplified.
21. A pharmaceutical composition according to claim 12, substantially as herein described or exemplified.
22. A use according to claim 13, substantially as herein bed or exemplified.
23. A use according to claim 14, substantially as herein described or exemplified.
24. An isolated polynucleotide according to claim 17, substantially as herein described or exemplified.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462007874P | 2014-06-04 | 2014-06-04 | |
| NZ726501A NZ726501B2 (en) | 2014-06-04 | 2015-06-03 | Human monoclonal antibodies to ganglioside gd2 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ764875A NZ764875A (en) | 2024-07-26 |
| NZ764875B2 true NZ764875B2 (en) | 2024-10-30 |
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