CA2510180A1 - Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2 - Google Patents

Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2 Download PDF

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Publication number
CA2510180A1
CA2510180A1 CA002510180A CA2510180A CA2510180A1 CA 2510180 A1 CA2510180 A1 CA 2510180A1 CA 002510180 A CA002510180 A CA 002510180A CA 2510180 A CA2510180 A CA 2510180A CA 2510180 A1 CA2510180 A1 CA 2510180A1
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Prior art keywords
variable region
antibody variable
fusion protein
seq
amino acid
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CA002510180A
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French (fr)
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CA2510180C (en
Inventor
Stephen D. Gillies
Kin-Ming Lo
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Merck Patent GmbH
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • C07K16/3076Immunoglobulins [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
    • C07K16/3084Immunoglobulins [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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46Hybrid immunoglobulins
    • C07K16/461Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/467Igs with modifications in the FR-residues only
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732Antibody-dependent cellular cytotoxicity [ADCC]

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

The invention provides humanized antibody H14.18 binding the human cell surface glycosphingolipid GD2. The antibody comprises modified variable regions, more specially, modified framework regions, which reduce their immunogenitity when administered to a human. The antibody may be coupled to the therapeutic agent such as IL-2 and used in the treatment of cancer.

Claims (25)

1. ~An antibody variable region comprising the amino acid sequence set forth in SEQ
ID NO: 1.
2. ~An antibody variable region comprising the amino acid sequence set forth in SEQ
ID NO: 2.
3. ~The antibody variable region of claim 2 further comprising the amino acid sequence set forth in SEQ ID NO: 1.
4. ~The antibody variable region of claim 3, wherein the amino acid sequences are~
linked by a disulfide bond.
5. ~The antibody variable region of claim 3, wherein the amino acid sequences are linked by a peptide bond.
6. ~An antibody variable region comprising an amino acid sequence selected from the group consisting of amino acids 1-23 of SEQ ID NO: 1, amino acids 1-25 of SEQ
ID NO:
2, and amino acids 67-98 of SEQ ID NO: 2, wherein the antibody variable region specifically binds to GD2.
7. ~The antibody variable region of claim 6, wherein the amino acid sequence includes amino acids 1-23 of SEQ ID NO: 1.
8. ~The antibody variable region of claim 6, wherein the amino acid sequence includes amino acids 1-25 of SEQ ID NO: 2.
9. ~The antibody variable region of claim 6, wherein the amino acid sequence includes amino acids 67-98 of SEQ ID NO: 2.
10. ~A polypeptide comprising an antibody variable region according to any of the preceding claims and an Fc portion comprising at least a CH2 domain.
11. ~The polypeptide of claim 10, wherein the Fc portion is derived from IgG1.
12. ~A nucleic acid encoding an antibody variable region according to any one of claims 1-9 or a polypeptide according to claim 10 or 11.
13. ~A cell comprising the nucleic acid of claim 12.
14. ~A method for targeting a cell with GD2 on its surface, the method comprising:
administering an antibody variable region according to any one of claims 1-9 or a~
polypeptide according to claim 10 or 11.
15. ~The method of claim 14, wherein the cell is a tumor cell.
16. ~A fusion protein comprising an antibody variable region according to any one of claims 1-9 or a polypeptide according to claim 10 or 11 linked to a non-immunoglobulin moiety.
17. ~The fusion protein of claim 16, wherein the non-immunoglobulin moiety is a cytokine.
18. ~The fusion protein of claim 17, wherein the cytokine is selected from the group consisting of an interleukin, a hematopoietic factor, a lymphokine, an interferon, and a chemokine.
19. ~The fusion protein of claim 18, wherein the interleukin is selected from the group consisting of interleukin-2 (IL-2) and interleukin-12 (IL-12).
20. ~The fusion protein of claim 18, wherein the hematopoietic factor is granulocyte-macrophage colony stimulating factor (GM-CSF).
21. ~The fusion protein of claim 18, wherein the lymphokine is a lymphotoxin.
22. ~The fusion protein of claim 18, wherein the interferon is selected from the group consisting of interferon-.alpha., interferon-.beta., and interferon-.gamma..
23. ~The fusion protein of claim 16 further comprising a second non-immunoglobulin moiety.
24. ~The fusion protein of claim 23, wherein the fusion protein comprises IL-2 and IL-12.
25. ~Use of nucleic acid of claim 12 or a cell of claim 13 for the manufacture of a medicament.
CA2510180A 2002-12-17 2003-12-16 Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2 Expired - Lifetime CA2510180C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US43394502P 2002-12-17 2002-12-17
US60/433,945 2002-12-17
PCT/EP2003/014295 WO2004055056A1 (en) 2002-12-17 2003-12-16 Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2

Publications (2)

Publication Number Publication Date
CA2510180A1 true CA2510180A1 (en) 2004-07-01
CA2510180C CA2510180C (en) 2012-09-11

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CA2510180A Expired - Lifetime CA2510180C (en) 2002-12-17 2003-12-16 Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2

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US (3) US7169904B2 (en)
EP (1) EP1572748B1 (en)
JP (1) JP4494977B2 (en)
KR (1) KR101086660B1 (en)
CN (1) CN100432105C (en)
AT (1) ATE471946T1 (en)
AU (1) AU2003298187B2 (en)
BR (1) BRPI0317376B8 (en)
CA (1) CA2510180C (en)
DE (1) DE60333121D1 (en)
DK (1) DK1572748T3 (en)
ES (1) ES2346205T3 (en)
MX (1) MXPA05006384A (en)
PL (1) PL211180B1 (en)
PT (1) PT1572748E (en)
RU (1) RU2366664C2 (en)
WO (1) WO2004055056A1 (en)
ZA (1) ZA200505681B (en)

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