EP2297206A1 - Anticorps anti-cxcr4 - Google Patents

Anticorps anti-cxcr4

Info

Publication number
EP2297206A1
EP2297206A1 EP09747210A EP09747210A EP2297206A1 EP 2297206 A1 EP2297206 A1 EP 2297206A1 EP 09747210 A EP09747210 A EP 09747210A EP 09747210 A EP09747210 A EP 09747210A EP 2297206 A1 EP2297206 A1 EP 2297206A1
Authority
EP
European Patent Office
Prior art keywords
seq
antibody
cancer
cxcr4
human
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
EP09747210A
Other languages
German (de)
English (en)
Inventor
Cindy Takeuchi Dickerson
David Matthew Marquis
Victor Obungu
Sheng-Bin Peng
Peter Edward Vaillancourt
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eli Lilly and Co
Original Assignee
Eli Lilly and Co
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 Eli Lilly and Co filed Critical Eli Lilly and Co
Publication of EP2297206A1 publication Critical patent/EP2297206A1/fr
Ceased legal-status Critical Current

Links

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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • 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
    • C07K2317/90—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

Definitions

  • the present invention preferably provides a human engineered antibody or a binding fragment thereof, that binds human CXCR4, and which exhibits anti- tumorigenesis activity by preventing tumor growth in a tumor xenograft model as described herein when administered at 1 mg/kg.
  • inhibitor means the ability to substantially antagonize, prohibit, prevent, restrain, slow, disrupt, eliminate, stop, reduce or reverse the biological effects of binding to the CXCR4 receptor.
  • an antibody of the present invention wherein all six CDRs, the HCVR, the LCVR, the HCVR and the LCVR, the entire heavy chain, the entire light chain, or the entire heavy chain and light chain are limited by a particular sequence as shown by a SEQ ID NO: herein is further characterized by having an IC50 in a human CXCR4/ 125 I-SDF-l ⁇ binding inhibition assay as described herein of about of 10 nM or less, more preferably about 5.0 nM or less, and most preferably of 0.5 nM or less.
  • an antibody of the present invention wherein all six CDRs, the HCVR, the LCVR, the LCVR, the
  • an antibody of the present invention wherein all six CDRs, the HCVR, the LCVR, the HCVR and the LCVR, the entire heavy chain, the entire light chain, or the entire heavy chain and light chain are limited by a particular sequence as shown by a SEQ ID NO: herein is further characterized by having an IC50 in a chemotaxis assay as described herein of about 30 nM or less, more preferably about 15 nM or less, and even more preferably 3.0 nM or less.
  • Antibody I inhibits tumor growth in this assay when administered at lO ⁇ g/mouse, which is approximately 0.4 mg/kg.
  • the data demonstrate that Antibody I has tumorigenesis activity by preventing tumor growth.
  • annexin V changes are investigated by flow cytometry in Namalwa cells after treatment with test antibody or isotype IgG control.
  • Antibody I induces a dose-dependent increase of annexin V, while isotype IgG has no effect.
  • Antibody I induces apoptosis which is also observed in CEM xenograft tumors by TUNEL staining.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Dermatology (AREA)
  • Neurosurgery (AREA)
  • Pulmonology (AREA)
  • Neurology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne des anticorps de liaison au CXCR4 humain caractérisés en ce qu’ils présentent une haute affinité et de fortes propriétés de neutralisation. Les anticorps selon l’invention sont utiles dans le traitement de la genèse tumorale, comprenant la croissance, l’invasion, l’angiogenèse, ou la métastase tumorales.
EP09747210A 2008-05-14 2009-05-07 Anticorps anti-cxcr4 Ceased EP2297206A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US5319208P 2008-05-14 2008-05-14
PCT/US2009/043063 WO2009140124A1 (fr) 2008-05-14 2009-05-07 Anticorps anti-cxcr4

Publications (1)

Publication Number Publication Date
EP2297206A1 true EP2297206A1 (fr) 2011-03-23

Family

ID=40852496

Family Applications (1)

Application Number Title Priority Date Filing Date
EP09747210A Ceased EP2297206A1 (fr) 2008-05-14 2009-05-07 Anticorps anti-cxcr4

Country Status (11)

Country Link
EP (1) EP2297206A1 (fr)
JP (1) JP2011520885A (fr)
KR (1) KR20100133012A (fr)
CN (1) CN102027015A (fr)
AU (1) AU2009246683A1 (fr)
CA (1) CA2724409A1 (fr)
EA (1) EA201071300A1 (fr)
IL (1) IL208869A0 (fr)
MX (1) MX2010012435A (fr)
WO (1) WO2009140124A1 (fr)
ZA (1) ZA201007955B (fr)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2172485A1 (fr) * 2008-10-01 2010-04-07 Pierre Fabre Medicament Nouveaux anticorps anti CXCR4 et leur utilisation dans le traitement contre le cancer
WO2010092571A2 (fr) 2009-02-11 2010-08-19 Yeda Research And Development Co. Ltd. Peptides courts dérivés de bêta-défensine
EP2246364A1 (fr) * 2009-04-29 2010-11-03 Pierre Fabre Médicament Anticorps anti CXCR4 pour le traitement du VIH
GB201002238D0 (en) 2010-02-10 2010-03-31 Affitech As Antibodies
EP2371863A1 (fr) * 2010-03-30 2011-10-05 Pierre Fabre Médicament Anticorps humanisé anti CXCR4 pour le traitement du cancer
CA2814908A1 (fr) * 2010-10-27 2012-05-03 Pierre Fabre Medicament Anticorps utilises pour traiter le vih
US20140120555A1 (en) * 2011-06-20 2014-05-01 Pierre Fabre Medicament Anti-cxcr4 antibody with effector functions and its use for the treatment of cancer
US11492383B2 (en) 2011-06-24 2022-11-08 Stephen D. Gillies Light chain immunoglobulin fusion proteins and methods of use thereof
JP2014523745A (ja) * 2011-07-20 2014-09-18 メディミューン リミテッド 抗ｃｘｃｒ４抗体及び使用方法
AR087364A1 (es) 2011-07-29 2014-03-19 Pf Medicament Anticuerpo anti-cxcr4 y su uso para la deteccion y dianostico de canceres
SG11201401386XA (en) * 2011-11-09 2014-10-30 Bristol Myers Squibb Co Treatment of hematologic malignancies with an anti-cxcr4 antibody
JO3580B1 (ar) * 2013-03-15 2020-07-05 Lilly Co Eli أجسام مضادة لكيموكين elr+ cxc شامل
EA201792522A1 (ru) 2015-06-12 2018-05-31 Бристол-Майерс Сквибб Компани Лечение злокачественной опухоли с помощью комбинированной блокады сигнальных путей pd-1 и cxcr4
CN109475603B (zh) 2016-06-20 2023-06-13 科马布有限公司 抗pd-l1抗体
US20230181635A1 (en) 2018-03-13 2023-06-15 Fundación Para La Investigación Biomédica Del Hospital Universitario La Paz Anti-cxcr4 antibody combined with activated and expanded natural killer cells for cancer immunotherapy
EP3774840A1 (fr) 2018-03-27 2021-02-17 Bristol-Myers Squibb Company Surveillance en temps réel de la concentration de protéines à l'aide d'un signal ultraviolet
US20220135619A1 (en) 2019-02-24 2022-05-05 Bristol-Myers Squibb Company Methods of isolating a protein
EP3973274A1 (fr) 2019-05-23 2022-03-30 Bristol-Myers Squibb Company Méthodes de surveillance de milieu
EP4225770A1 (fr) 2020-10-05 2023-08-16 Bristol-Myers Squibb Company Procédés pour concentrer des protéines
CN112661845B (zh) * 2020-12-25 2022-06-21 暨南大学 与cxcr4结合的亲和力成熟结合蛋白及其应用
CN112521500B (zh) * 2020-12-25 2022-06-24 暨南大学 与cxcr4结合的亲和力成熟结合蛋白及应用
WO2023173011A1 (fr) 2022-03-09 2023-09-14 Bristol-Myers Squibb Company Expression transitoire de protéines thérapeutiques

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19801265C1 (de) * 1998-01-15 1999-08-12 Deutsches Krebsforsch Inhibierung von CD95-unabhängiger Apoptose bei AIDS
US20050002939A1 (en) * 2002-12-23 2005-01-06 Albert Zlotnik Tumor killing/tumor regression using CXCR4 antagonists
CA2597717C (fr) * 2005-02-18 2014-10-21 Dana-Farber Cancer Institute Anticorps contre cxcr4 et leurs procedes d'utilisation
CN101528259B (zh) * 2006-10-02 2014-04-09 梅达雷克斯有限责任公司 结合cxcr4的人类抗体及其用途
FR2915102B1 (fr) * 2007-04-23 2014-05-16 Pf Medicament Utilisation d'un anticorps anti-cxcr4 pour le traitement du cancer

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ROBERTS S ET AL: "Generation of an antibody with enhanced affinity and specificity for its antigen by protein engineering", NATURE: INTERNATIONAL WEEKLY JOURNAL OF SCIENCE, NATURE PUBLISHING GROUP, UNITED KINGDOM, vol. 328, 20 August 1987 (1987-08-20), pages 731 - 734, XP002987280, ISSN: 0028-0836, DOI: 10.1038/328731A0 *

Also Published As

Publication number Publication date
EA201071300A1 (ru) 2011-06-30
CN102027015A (zh) 2011-04-20
CA2724409A1 (fr) 2009-11-19
KR20100133012A (ko) 2010-12-20
MX2010012435A (es) 2011-05-03
ZA201007955B (en) 2012-04-25
IL208869A0 (en) 2011-01-31
JP2011520885A (ja) 2011-07-21
WO2009140124A1 (fr) 2009-11-19
AU2009246683A1 (en) 2009-11-19

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