Classifications

• • 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
  • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
• • 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
• • 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
• • 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
• • 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
• • 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]

Definitions

• CXCR4 receptor is over-expressed in a large number of cancers including but not limited to lymphoma, leukemia, multiple myeloma, colon (Ottaiano A. et al., 2004), breast (Kato M. et al., 2003), prostate (Sun Y.X. et al., 2003), lungs [small-cell- and non-small-cell- carcinoma (Phillips R.J. et al., 2003)], ovary (Scotton C.J. et al., 2002), pancreas (Koshiba T. et al., 2000), kidneys, brain (Barbero S et al., 2002), glioblastoma and lymphomas.
• lymphoma including lymphoma, leukemia, multiple myeloma, colon (Ottaiano A. et al., 2004), breast (Kato M. et al., 2003), prostate (Sun Y.X.
• CXCR4+ tumors that may derive from the normal CXCR4+ tissue/organ-specific stem cells such as leukemias, brain tumors, small cell lung cancer, breast cancer, hepatoblastoma, ovarian and cervical cancers (Kucia M. et al., 2005).
• constitutive heterodimers include studies showing CXCR1 and CXCR2 interact as well as forming respective homodimers. No interactions were noted for either of them with another GPCR (alpha(lA)- adrenoreceptor), indicating the specificity of CXCR1 and CXCR2 interaction (Wilson S. et al., 2005).
• the present invention aims at providing at least one reagent, devoid of any in vivo activity in cancer models, which can be used as a diagnosis or prognosis tool for oncogenic disorders, especially those characterized by expression of CXCR4 or those that are mediated by aberrant CXCR4 expression.
• the published patent application WO 2010/125162 discloses two anti-CXCR4 monoclonal antibodies, referred as 515H7 and 301 aE5, and their uses in the field of the HIV treatment.
• the inventors have found that the said antibody can be used for identifying CXCR4-expressing cells and, in particular, CXCR4-expressing tumor cells.
• CDR or CDRs are used here in order to indicate, according to the case, one of these regions or several, or even the whole, of these regions which contain the majority of the amino acid residues responsible for the binding by affinity of the antibody for the antigen or the epitope which it recognizes.
• the invention can also be described as an antibody, or an antigen-binding fragment or derivative thereof, comprising:
• amino acid sequence exhibiting at least 80%, preferably 85%, 90%, 95% and 98% identity with a reference amino acid sequence
• preferred examples include those containing the reference sequence, certain modifications, notably a deletion, addition or substitution of at least one amino acid, truncation or extension.
• substitutions are preferred in which the substituted amino acids are replaced by "equivalent” amino acids.
• the expression “equivalent amino acids” is meant to indicate any amino acids likely to be substituted for one of the structural amino acids without however modifying the biological activities of the corresponding antibodies and of those specific examples defined below.
• the invention relates to an antibody of the invention, or an antigen- binding fragment or derivative thereof, for the in vitro or ex vivo diagnosis or prognosis of an oncogenic disorder associated with expression of CXCR4.
• the results of a test or assay according to the invention can be presented in any of a variety of formats.
• the results can be presented qualitatively.
• the test report may indicate only whether or not a particular polypeptide was detected, perhaps also with an indication of the limits of detection.
• the results may be displayed as semi-quantitative.
• various ranges may be defined, and the ranges may be assigned a score (e.g., 0 to 3+ or 0 to 8 depending on the used scale) that provides a certain degree of quantitative information.
• a score may reflect various factors, e.g., the number of cells in which CXCR4 is detected, the intensity of the signal (which may indicate the level of expression of CXCR4 or CXCR4-bearing cells), etc.
• the results may be displayed in a quantitative way, e.g., as a percentage of cells in which the polypeptide (CXCR4) is detected, as a protein concentration, etc.
• tumor aggressiveness refers to a tumor quickly growing and tending to spread rapidly.
• An increase or a decrease in the level of CXCR4 is indicative of the evolution of a cancer associated with CXCR4.
• said cancer is selected among prostate cancer, osteosarcoma, lung cancer, breast cancer, endometrial cancer, leukemia, lymphoma, multiple myeloma, ovarian cancer, pancreatic cancer and colon cancer.
• said cancer comprises lymphoma cell, leukemia cell or multiple myeloma cell.
• the invention concerns a kit for the determination of the CXCR4 status of a tumor by the methods of the invention.
• the invention relates to a kit for the determination of the CXCR4 status of a tumor by IHC and/or FACS methods.
• the invention consists in a kit comprising at least the antibody 1-3859, or an antigen-binding fragment or derivative thereof, as above described, said antibody being labeled.
• MDA-MB-231 cells from ECACC were routinely cultured in DMEM medium

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• Health & Medical Sciences (AREA)
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• Life Sciences & Earth Sciences (AREA)
• Immunology (AREA)
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• Engineering & Computer Science (AREA)
• General Health & Medical Sciences (AREA)
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• Urology & Nephrology (AREA)
• Biomedical Technology (AREA)
• Hematology (AREA)
• Genetics & Genomics (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Biophysics (AREA)
• Pathology (AREA)
• General Physics & Mathematics (AREA)
• Analytical Chemistry (AREA)
• Cell Biology (AREA)
• Food Science & Technology (AREA)
• Physics & Mathematics (AREA)
• Biotechnology (AREA)
• Microbiology (AREA)
• Hospice & Palliative Care (AREA)
• Oncology (AREA)
• Veterinary Medicine (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Public Health (AREA)
• Pharmacology & Pharmacy (AREA)
• Peptides Or Proteins (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Investigating Or Analysing Biological Materials (AREA)
• Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Priority Applications (14)

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Publications (1)

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Cited By (2)

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Citations (7)

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• 2012
  • 2012-07-27 AR ARP120102745A patent/AR087363A1/es unknown
  • 2012-07-30 BR BR112014001979A patent/BR112014001979A2/pt not_active IP Right Cessation
  • 2012-07-30 JP JP2014522119A patent/JP6138780B2/ja not_active Expired - Fee Related
  • 2012-07-30 CN CN201280037703.0A patent/CN103717620A/zh active Pending
  • 2012-07-30 CA CA2842552A patent/CA2842552A1/en not_active Abandoned
  • 2012-07-30 US US14/235,235 patent/US20140170677A1/en not_active Abandoned
  • 2012-07-30 EP EP12740374.9A patent/EP2736926A1/en not_active Ceased
  • 2012-07-30 AU AU2012292116A patent/AU2012292116A1/en not_active Abandoned
  • 2012-07-30 KR KR1020147003605A patent/KR20140047127A/ko not_active Ceased
  • 2012-07-30 WO PCT/EP2012/064876 patent/WO2013017562A1/en not_active Ceased
  • 2012-07-30 MX MX2014001160A patent/MX2014001160A/es unknown
  • 2012-07-30 RU RU2014103054A patent/RU2636032C2/ru not_active IP Right Cessation
• 2014
  • 2014-01-22 ZA ZA2014/00500A patent/ZA201400500B/en unknown
  • 2014-01-28 IL IL230693A patent/IL230693A0/en unknown
• 2017
  • 2017-06-15 AU AU2017204043A patent/AU2017204043A1/en not_active Abandoned

Patent Citations (9)

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