WO2001090198A1 - Conjugues a composants multiples se liant a des molecules cibles et stimulant la lyse de cellules - Google Patents

Conjugues a composants multiples se liant a des molecules cibles et stimulant la lyse de cellules Download PDF

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Publication number
WO2001090198A1
WO2001090198A1 PCT/US2001/017184 US0117184W WO0190198A1 WO 2001090198 A1 WO2001090198 A1 WO 2001090198A1 US 0117184 W US0117184 W US 0117184W WO 0190198 A1 WO0190198 A1 WO 0190198A1
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WO
WIPO (PCT)
Prior art keywords
conjugate
cells
mhc
conjugates
fab
Prior art date
Application number
PCT/US2001/017184
Other languages
English (en)
Inventor
Jean-Pierre Mach
Bruno Robert
Pedro Romero
Immanuel Leuscher
Guillaume Philippe
Original Assignee
Ludwig Institute For Cancer Research
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ludwig Institute For Cancer Research filed Critical Ludwig Institute For Cancer Research
Priority to US10/276,764 priority Critical patent/US20040068100A1/en
Priority to AU2001271273A priority patent/AU2001271273A1/en
Publication of WO2001090198A1 publication Critical patent/WO2001090198A1/fr
Priority to US11/804,945 priority patent/US20070237771A1/en

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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
    • C07K16/30—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • 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
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70539—MHC-molecules, e.g. HLA-molecules
    • 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
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Definitions

  • HERCEPTIN ® is a recombinant, humanized mAb, of human IgGl ⁇ isotype, specific for the extracellular domain of the HER2 receptor. See Carter, et al, Proc. Natl. Acad. Sci USA 89:4285-9 (1992), incorporated by reference.
  • RITUXIMAB ® is a chimeric, murine/human mAb of IgGl human K subtype, directed against the CD20 molecule found on the surfaces of normal and malignant B lymphocytes. See Reff, et al, Blood 83:435-445 (1994), incorporated by reference.
  • HLA-A*0201 heavy chain and ⁇ 2M molecules were synthesized, using a commercially available prokaryotic expression system, using well known methodologies.
  • the heavy chain was modified by deleting the transmembrane cytosolic tail, and the C-terminal addition of a sequence containing the BirA enzymatic biotinylation site.
  • the heavy chain, ⁇ 2M, and the peptide of SEQ ID NO: 1 were refolded by dilution.
  • the molecular weight of the desired product was 45 kilodaltons.
  • Such products were isolated via FPLC, and then biotinylated in the presence of biotin, adenosine 5'-triphosphate, and Mg 2+ .
  • conjugates as described, in conjunction with other steps, to yield populations of T cells with desired features, such as specificity and phenotype. These include distinct cell surface phenotypes associated with antigen experienced, or memory cells, or naive cells, and so forth.
  • Such populations can be cultured, in the presence of either bifunctional Fab ' -MHC/peptide conjugate coated target cells, or free peptides in target cells to determine to what extent the deletion of MHC molecules are responsible for the lace of reactivity of T lymphocytes for CTLs.
  • This culturing can be carried out with a mitagen such as phytohemagluttinin, e.g., without peptides, for comparison.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne des immunoconjugués représentés par la formule: A-B-(C)n, dans laquelle B peut être présent ou absent, A est une protéine de liaison spécifique, par exemple, un anticorps ou un fragment de liaison d'anticorps, ou un ligand se liant à un récepteur présent sur les cellules cibles B, comprenant au moins une molécule à laquelle « A » et « C » se lient, par exemple, un complexe avidine/strepavidine, « C » est une molécule MHC, et « n » représente un nombre entier compris entre 1 et 10. Ces conjugués présentent une spécificité de liaison parfaite d'anticorps, associée à la capacité de stimuler les cellules T cytotoxiques pour identifier et détruire les cellules sur lesquelles se produisent la liaison et l'oligomérisation du conjugué. Par ailleurs, les conjugués sont utiles à la fois dans le domaine thérapeutique et diagnostique.
PCT/US2001/017184 2000-05-24 2001-05-24 Conjugues a composants multiples se liant a des molecules cibles et stimulant la lyse de cellules WO2001090198A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US10/276,764 US20040068100A1 (en) 2001-05-24 2001-05-24 Multicomponent conjugates which bind to target molecules and stimulate cell lysis
AU2001271273A AU2001271273A1 (en) 2000-05-24 2001-05-24 Multicomponent conjugates which bind to target molecules and stimulate cell lysis
US11/804,945 US20070237771A1 (en) 2001-05-24 2007-05-21 Multicomponent conjugates which bind to target molecules and stimulate T cell lysis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH10322000 2000-05-24
CH1032/00 2000-05-24

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10/276,764 A-371-Of-International US20040068100A1 (en) 2001-05-24 2001-05-24 Multicomponent conjugates which bind to target molecules and stimulate cell lysis
US10/632,663 Continuation-In-Part US20040143094A1 (en) 2001-05-24 2003-08-01 Multicomponent conjugates which bind to target molecules and stimulate T cell lysis

Publications (1)

Publication Number Publication Date
WO2001090198A1 true WO2001090198A1 (fr) 2001-11-29

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Country Status (2)

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AU (1) AU2001271273A1 (fr)
WO (1) WO2001090198A1 (fr)

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1409547A2 (fr) * 2001-06-19 2004-04-21 Technion Research and Development of Foundation, Ltd. Procedes et compositions pharmaceutiques permettant la falsification immunitaire, particulierement utiles pour le traitement du cancer
EP1413316A1 (fr) * 2002-09-27 2004-04-28 Bruno Robert Conjugués bifonctionnels ou protéines de fusions
WO2005035567A1 (fr) * 2003-10-06 2005-04-21 Proimmune Limited Proteine mhc chimere et son oligomere pour ciblage specifique
GB2422834A (en) * 2005-02-04 2006-08-09 Proimmune Ltd Oligomers of MHC complexes
US7977457B2 (en) 2006-05-19 2011-07-12 Teva Pharmaceutical Industries Ltd. Fusion proteins, uses thereof and processes for producing same
US8022190B2 (en) 2001-06-19 2011-09-20 Technion Research & Development Foundation Ltd. Immuno-molecules containing viral proteins, compositions thereof and methods of using
US9139809B2 (en) 2009-01-08 2015-09-22 Albert Einstein College Of Medicine Of Yeshiva University Bacterial vaccines with cell wall-associated ceramide-like glycolipids and uses thereof
US9371352B2 (en) 2013-02-08 2016-06-21 Vaccinex, Inc. Modified glycolipids and methods of making and using the same
US9404916B2 (en) 2008-09-20 2016-08-02 University College Cardiff Consultants Limited Use of a protein kinase inhibitor to detect immune cells, such as T cells
US9603922B2 (en) 2007-02-21 2017-03-28 Vaccinex, Inc. Modulation of NKT cell activity with antigen-loaded CD1d molecules
US9616112B2 (en) 2003-03-26 2017-04-11 Technion Research & Development Foundation Limited Compositions capable of specifically binding particular human antigen presenting molecule/pathogen-derived antigen complexes and uses thereof
US9809654B2 (en) 2002-09-27 2017-11-07 Vaccinex, Inc. Targeted CD1d molecules
WO2017214456A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-cd98 et conjugués anticorps-médicament
WO2017214339A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
WO2017214322A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
US10030065B2 (en) 2007-07-03 2018-07-24 Dako Denmark A/S MHC multimers, methods for their generation, labeling and use
WO2018195302A1 (fr) 2017-04-19 2018-10-25 Bluefin Biomedicine, Inc. Anticorps anti-vtcn1 et conjugués anticorps-médicament
US10336808B2 (en) 2007-03-26 2019-07-02 Dako Denmark A/S MHC peptide complexes and uses thereof in infectious diseases
US10369204B2 (en) 2008-10-02 2019-08-06 Dako Denmark A/S Molecular vaccines for infectious disease
US10611818B2 (en) 2007-09-27 2020-04-07 Agilent Technologies, Inc. MHC multimers in tuberculosis diagnostics, vaccine and therapeutics
EP2651442B1 (fr) 2010-12-14 2020-04-22 University of Maryland, Baltimore Lymphocytes t exprimant un récepteur d'antigène chimérique anti-étiquette universel et méthodes de traitement du cancer
US10640563B2 (en) 2016-06-08 2020-05-05 Abbvie Inc. Anti-B7-H3 antibodies and antibody drug conjugates
US10722562B2 (en) 2008-07-23 2020-07-28 Immudex Aps Combinatorial analysis and repair
US10968269B1 (en) 2008-02-28 2021-04-06 Agilent Technologies, Inc. MHC multimers in borrelia diagnostics and disease
EP4218929A1 (fr) 2014-03-21 2023-08-02 AbbVie Inc. Anticorps anti-egfr et conjugués anticorps-médicament
US11759527B2 (en) 2021-01-20 2023-09-19 Abbvie Inc. Anti-EGFR antibody-drug conjugates
US11992518B2 (en) 2008-10-02 2024-05-28 Agilent Technologies, Inc. Molecular vaccines for infectious disease

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5525338A (en) * 1992-08-21 1996-06-11 Immunomedics, Inc. Detection and therapy of lesions with biotin/avidin conjugates
WO1999050637A2 (fr) * 1998-03-27 1999-10-07 Ludwig Institute For Cancer Research Complexes multicomposants isoles servant a l'analyse des lymphocytes t, peptides utiles a la fabrication de ces complexes et utilisations de ces complexes
WO1999064464A2 (fr) * 1998-06-05 1999-12-16 Philip Michael Savage Procede de production ou d'amelioration d'une reponse des lymphocytes t contre une cellule cible a l'aide d'un complexe comprenant une molecule hla de classe i et un dispositif d'attache

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5525338A (en) * 1992-08-21 1996-06-11 Immunomedics, Inc. Detection and therapy of lesions with biotin/avidin conjugates
WO1999050637A2 (fr) * 1998-03-27 1999-10-07 Ludwig Institute For Cancer Research Complexes multicomposants isoles servant a l'analyse des lymphocytes t, peptides utiles a la fabrication de ces complexes et utilisations de ces complexes
WO1999064464A2 (fr) * 1998-06-05 1999-12-16 Philip Michael Savage Procede de production ou d'amelioration d'une reponse des lymphocytes t contre une cellule cible a l'aide d'un complexe comprenant une molecule hla de classe i et un dispositif d'attache

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ROBERT BRUNO ET AL: "Antibody-conjugated MHC class I tetramers can target tumor cells for specific lysis by T lymphocytes.", EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 30, no. 11, November 2000 (2000-11-01), pages 3165 - 3170, XP001021944, ISSN: 0014-2980 *

Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1409547A4 (fr) * 2001-06-19 2007-05-02 Technion Res And Dev Of Founda Procedes et compositions pharmaceutiques permettant la falsification immunitaire, particulierement utiles pour le traitement du cancer
EP1409547A2 (fr) * 2001-06-19 2004-04-21 Technion Research and Development of Foundation, Ltd. Procedes et compositions pharmaceutiques permettant la falsification immunitaire, particulierement utiles pour le traitement du cancer
US8022190B2 (en) 2001-06-19 2011-09-20 Technion Research & Development Foundation Ltd. Immuno-molecules containing viral proteins, compositions thereof and methods of using
US8449889B2 (en) 2001-06-19 2013-05-28 Technion Research & Development Foundation Limited Immuno-molecules containing viral proteins, compositions thereof and methods of using
EP1413316A1 (fr) * 2002-09-27 2004-04-28 Bruno Robert Conjugués bifonctionnels ou protéines de fusions
EP1551448A2 (fr) * 2002-09-27 2005-07-13 Vaccinex, Inc. Molecules cd1d ciblees
EP1551448A4 (fr) * 2002-09-27 2008-12-24 Vaccinex Inc Molecules cd1d ciblees
US9809654B2 (en) 2002-09-27 2017-11-07 Vaccinex, Inc. Targeted CD1d molecules
US9616112B2 (en) 2003-03-26 2017-04-11 Technion Research & Development Foundation Limited Compositions capable of specifically binding particular human antigen presenting molecule/pathogen-derived antigen complexes and uses thereof
WO2005035567A1 (fr) * 2003-10-06 2005-04-21 Proimmune Limited Proteine mhc chimere et son oligomere pour ciblage specifique
GB2422834A (en) * 2005-02-04 2006-08-09 Proimmune Ltd Oligomers of MHC complexes
GB2422834B (en) * 2005-02-04 2007-01-03 Proimmune Ltd MHC oligomer and method of making the same
US7977457B2 (en) 2006-05-19 2011-07-12 Teva Pharmaceutical Industries Ltd. Fusion proteins, uses thereof and processes for producing same
US9603922B2 (en) 2007-02-21 2017-03-28 Vaccinex, Inc. Modulation of NKT cell activity with antigen-loaded CD1d molecules
US10336808B2 (en) 2007-03-26 2019-07-02 Dako Denmark A/S MHC peptide complexes and uses thereof in infectious diseases
US10030065B2 (en) 2007-07-03 2018-07-24 Dako Denmark A/S MHC multimers, methods for their generation, labeling and use
US10611818B2 (en) 2007-09-27 2020-04-07 Agilent Technologies, Inc. MHC multimers in tuberculosis diagnostics, vaccine and therapeutics
US10968269B1 (en) 2008-02-28 2021-04-06 Agilent Technologies, Inc. MHC multimers in borrelia diagnostics and disease
US10722562B2 (en) 2008-07-23 2020-07-28 Immudex Aps Combinatorial analysis and repair
US9404916B2 (en) 2008-09-20 2016-08-02 University College Cardiff Consultants Limited Use of a protein kinase inhibitor to detect immune cells, such as T cells
US10369204B2 (en) 2008-10-02 2019-08-06 Dako Denmark A/S Molecular vaccines for infectious disease
US11992518B2 (en) 2008-10-02 2024-05-28 Agilent Technologies, Inc. Molecular vaccines for infectious disease
US9139809B2 (en) 2009-01-08 2015-09-22 Albert Einstein College Of Medicine Of Yeshiva University Bacterial vaccines with cell wall-associated ceramide-like glycolipids and uses thereof
EP2651442B1 (fr) 2010-12-14 2020-04-22 University of Maryland, Baltimore Lymphocytes t exprimant un récepteur d'antigène chimérique anti-étiquette universel et méthodes de traitement du cancer
US10111950B2 (en) 2013-02-08 2018-10-30 Vaccinex, Inc. Modified glycolipids and methods of making and using the same
US9371352B2 (en) 2013-02-08 2016-06-21 Vaccinex, Inc. Modified glycolipids and methods of making and using the same
EP4218929A1 (fr) 2014-03-21 2023-08-02 AbbVie Inc. Anticorps anti-egfr et conjugués anticorps-médicament
WO2017214456A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-cd98 et conjugués anticorps-médicament
WO2017214322A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
US10640563B2 (en) 2016-06-08 2020-05-05 Abbvie Inc. Anti-B7-H3 antibodies and antibody drug conjugates
WO2017214339A1 (fr) 2016-06-08 2017-12-14 Abbvie Inc. Anticorps anti-b7-h3 et conjugués anticorps-médicaments
WO2018195302A1 (fr) 2017-04-19 2018-10-25 Bluefin Biomedicine, Inc. Anticorps anti-vtcn1 et conjugués anticorps-médicament
US11759527B2 (en) 2021-01-20 2023-09-19 Abbvie Inc. Anti-EGFR antibody-drug conjugates

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