WO2006088464A2 - Procede d'utilisation d'un anticorps anti-cd137 en tant qu'agent de radio-immunotherapie ou radio-immunodetection - Google Patents

Procede d'utilisation d'un anticorps anti-cd137 en tant qu'agent de radio-immunotherapie ou radio-immunodetection Download PDF

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Publication number
WO2006088464A2
WO2006088464A2 PCT/US2005/005405 US2005005405W WO2006088464A2 WO 2006088464 A2 WO2006088464 A2 WO 2006088464A2 US 2005005405 W US2005005405 W US 2005005405W WO 2006088464 A2 WO2006088464 A2 WO 2006088464A2
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WO
WIPO (PCT)
Prior art keywords
antibody
human
antibodies
cell
transgenic
Prior art date
Application number
PCT/US2005/005405
Other languages
English (en)
Other versions
WO2006088464A3 (fr
Inventor
Scott E. Strome
Daniel Schindler
Lieping Chen
Harry Meade
Yann Echelard
Original Assignee
Gtc Biotherapeutics, Inc.
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
Priority claimed from US11/058,458 external-priority patent/US20060182744A1/en
Priority claimed from PCT/US2005/004739 external-priority patent/WO2006088447A1/fr
Application filed by Gtc Biotherapeutics, Inc. filed Critical Gtc Biotherapeutics, Inc.
Priority to EP05723386A priority Critical patent/EP1850872A4/fr
Publication of WO2006088464A2 publication Critical patent/WO2006088464A2/fr
Publication of WO2006088464A3 publication Critical patent/WO2006088464A3/fr

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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
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • 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
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • A61K47/6829—Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
    • 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
    • A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
    • 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
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1027—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants
    • 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
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/12—Immunoglobulins specific features characterized by their source of isolation or production isolated from milk
    • 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
    • C07K2317/74—Inducing 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
    • C07K2317/75—Agonist effect on antigen

Definitions

  • FIG. 1 Shows a graph of the spleen size of sacrificed mice after treatment with the antibodies of the current invention.
  • FIG. 8 Shows a histological representation of the tissues after various treatment regimens according to the antibodies of the invention.
  • Binding affinity were measured semi-quantitatively by the dose range over which chimeric anti-CD 137 inhibits binding by the original GW mAb, compared to control IgG. The glycosylated and aglycosylated chimeric preparations were compared to the original GW mAb. Dose-dependent Co-stimulation of T-ceII growth and cytokine production by immobilized anti-CD137.
  • Suitable mammalian sources for oocytes include goats, sheep, cows, pigs, rabbits, guinea pigs, mice, hamsters, rats, primates, etc.
  • the oocytes were obtained from ungulates, and most preferably goats or cattle. Methods for isolation of oocytes are well known in the art.
  • Preparations for oral administration may be suitably formulated to give controlled release of the active compound.
  • the composition may take the form of tablets or lozenges formulated in conventional manner.
  • Humanization also called Reshaping or CDR-grafting
  • mAbs monoclonal antibodies
  • the radionuclide with energy emission characteristics most suitable for use with current nuclear medicine cameras is technetium-99, which has gamma emissions of 140 KeV.
  • This transitional element has no particulate emission; its short half-life further reduces radiation dose to the patient, permitting use of relatively large amounts of radioactivity.
  • Radioiodinated MAbs are relatively stable in vivo; and,

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Toxicology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne le développement et des procédés d'utilisation d'un anticorps agoniste recombiné anti-humain CD137, et de variantes de glycosylation correspondantes. Ces anticorps agissent en tant qu'agents anticancéreux et/ou modulateurs du système immunitaire qui sont efficaces pour réduire des tumeurs solides et/ou d'autres manifestations cancéreuses, ainsi que pour empêcher la récurrence de celles-ci. Parmi les types de cancer efficacement traités au moyen de l'anticorps selon l'invention figurent en outre les leucémies et les lymphomes. Dans un mode de réalisation préféré de cette invention, les anticorps recombinés sont produits dans le lait d'animaux transgéniques, puis extraits de ce lait par purification. Dans un autre mode de réalisation préféré de la présente invention, les anticorps agonistes anti-CD137 peuvent être conjugués à des radionucléides à des fins de radio-immunodétection ou de radio-immunothérapie, ou être conjugués à une toxine pour mieux traiter divers cancers.
PCT/US2005/005405 2005-02-15 2005-02-18 Procede d'utilisation d'un anticorps anti-cd137 en tant qu'agent de radio-immunotherapie ou radio-immunodetection WO2006088464A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP05723386A EP1850872A4 (fr) 2005-02-15 2005-02-18 Procede d'utilisation d'un anticorps anti-cd137 en tant qu'agent de radio-immunotherapie ou radio-immunodetection

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
USPCT/US2005/04739 2005-02-15
US11/058,458 US20060182744A1 (en) 2005-02-15 2005-02-15 Anti-CD137 antibody as an agent in the treatment of cancer and glycosylation variants thereof
PCT/US2005/004739 WO2006088447A1 (fr) 2005-02-15 2005-02-15 Anticorps anti-cd137 en tant qu'agent dans le traitement de cancers et variante de glycosylation dudit anticorps
US11/058,458 2005-02-17

Publications (2)

Publication Number Publication Date
WO2006088464A2 true WO2006088464A2 (fr) 2006-08-24
WO2006088464A3 WO2006088464A3 (fr) 2007-11-15

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PCT/US2005/005405 WO2006088464A2 (fr) 2005-02-15 2005-02-18 Procede d'utilisation d'un anticorps anti-cd137 en tant qu'agent de radio-immunotherapie ou radio-immunodetection

Country Status (2)

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EP (1) EP1850872A4 (fr)
WO (1) WO2006088464A2 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007048077A3 (fr) * 2005-10-21 2007-07-05 Gtc Biotherapeutics Inc Anticorps ayant une meilleure activite cytotoxique cellulaire dependant des anticorps et leurs procedes de production et leur utilisation
EP2279003A2 (fr) * 2008-05-01 2011-02-02 GTC Biotherapeutics, Inc. Anticorps anti-cd137 en tant qu'agent dans le traitement d'états inflammatoires
CN103713125A (zh) * 2014-01-08 2014-04-09 滨州医学院 一种用于检测恶性血液疾病cd137l突变的试剂盒及其应用
AU2012201010B2 (en) * 2005-10-21 2015-01-22 Genzyme Corporation Antibodies with enhanced antibody-dependent cellular cytoxicity activity, methods of their production and use
WO2017009842A2 (fr) 2015-07-16 2017-01-19 Biokine Therapeutics Ltd. Compositions et méthodes pour le traitement du cancer
US10174110B2 (en) 2013-02-13 2019-01-08 Laboratoire Français Du Fractionnement Et Des Biotechnologies Highly galactosylated anti-TNF-α antibodies and uses thereof
WO2022074206A1 (fr) 2020-10-08 2022-04-14 Affimed Gmbh Lieurs trispécifiques
WO2023007023A1 (fr) 2021-07-30 2023-02-02 Affimed Gmbh Corps duplex
WO2024056862A1 (fr) 2022-09-15 2024-03-21 Avidicure Ip B.V. Protéines multispécifiques de liaison à l'antigène pour le ciblage tumoral de cellules nk et leur utilisation

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4361544A (en) * 1980-03-03 1982-11-30 Goldenberg Milton David Tumor localization and therapy with labeled antibodies specific to intracellular tumor-associated markers
WO2003049755A1 (fr) * 2001-10-09 2003-06-19 Mayo Foundation For Medical Education And Research Amelioration des reponses immunitaires par des agents liant 4-1bb

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of EP1850872A4 *

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2388272A1 (fr) * 2005-10-21 2011-11-23 GTC Biotherapeutics, Inc. Anticorps avec activité cytotoxique cellulaire améliorée dépendant des anticorps, leurs procédés de production et utilisation
EP2388273A1 (fr) * 2005-10-21 2011-11-23 GTC Biotherapeutics, Inc. Anticorps avec activité cytotoxique cellulaire améliorée dépendant des anticorps, leurs procédés de production et utilisation
CN101484470B (zh) * 2005-10-21 2014-07-23 阿伊沃生物制剂有限公司 具有增强的抗体依赖性细胞毒性活性的抗体及其生产方法和用途
AU2012201010B2 (en) * 2005-10-21 2015-01-22 Genzyme Corporation Antibodies with enhanced antibody-dependent cellular cytoxicity activity, methods of their production and use
WO2007048077A3 (fr) * 2005-10-21 2007-07-05 Gtc Biotherapeutics Inc Anticorps ayant une meilleure activite cytotoxique cellulaire dependant des anticorps et leurs procedes de production et leur utilisation
EP2279003A2 (fr) * 2008-05-01 2011-02-02 GTC Biotherapeutics, Inc. Anticorps anti-cd137 en tant qu'agent dans le traitement d'états inflammatoires
EP2279003A4 (fr) * 2008-05-01 2013-04-03 Gtc Biotherapeutics Inc Anticorps anti-cd137 en tant qu'agent dans le traitement d'états inflammatoires
US10174110B2 (en) 2013-02-13 2019-01-08 Laboratoire Français Du Fractionnement Et Des Biotechnologies Highly galactosylated anti-TNF-α antibodies and uses thereof
CN103713125A (zh) * 2014-01-08 2014-04-09 滨州医学院 一种用于检测恶性血液疾病cd137l突变的试剂盒及其应用
WO2017009842A2 (fr) 2015-07-16 2017-01-19 Biokine Therapeutics Ltd. Compositions et méthodes pour le traitement du cancer
EP3744340A2 (fr) 2015-07-16 2020-12-02 Biokine Therapeutics Ltd. Compositions et procédés pour le traitement du cancer
EP3943098A2 (fr) 2015-07-16 2022-01-26 Biokine Therapeutics Ltd. Compositions et procédés pour le traitement du cancer
WO2022074206A1 (fr) 2020-10-08 2022-04-14 Affimed Gmbh Lieurs trispécifiques
WO2023007023A1 (fr) 2021-07-30 2023-02-02 Affimed Gmbh Corps duplex
WO2024056862A1 (fr) 2022-09-15 2024-03-21 Avidicure Ip B.V. Protéines multispécifiques de liaison à l'antigène pour le ciblage tumoral de cellules nk et leur utilisation
WO2024056861A1 (fr) 2022-09-15 2024-03-21 Avidicure Ip B.V. Protéines de liaison à un antigène multispécifiques pour stimuler des cellules nk et utilisation associée

Also Published As

Publication number Publication date
EP1850872A4 (fr) 2008-10-15
EP1850872A2 (fr) 2007-11-07
WO2006088464A3 (fr) 2007-11-15

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