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WO2008131575A2 - Anticorps anti-alk adaptés au traitement des cancers et tumeurs métastatiques - Google Patents

Anticorps anti-alk adaptés au traitement des cancers et tumeurs métastatiques Download PDF

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Publication number
WO2008131575A2
WO2008131575A2 PCT/CH2008/000193 CH2008000193W WO2008131575A2 WO 2008131575 A2 WO2008131575 A2 WO 2008131575A2 CH 2008000193 W CH2008000193 W CH 2008000193W WO 2008131575 A2 WO2008131575 A2 WO 2008131575A2
Authority
WO
WIPO (PCT)
Prior art keywords
antibody
alk
seq
anyone
sequence
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
PCT/CH2008/000193
Other languages
English (en)
Other versions
WO2008131575A3 (fr
Inventor
Adrian Auf Der Maur
Alcide Barberis
Peter Lichtlen
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.)
Esbatech a Novartis Co LLC
Original Assignee
Esbatech AG
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 Esbatech AG filed Critical Esbatech AG
Publication of WO2008131575A2 publication Critical patent/WO2008131575A2/fr
Publication of WO2008131575A3 publication Critical patent/WO2008131575A3/fr
Anticipated expiration legal-status Critical
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
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • 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
    • A61P35/04—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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • 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]
    • 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
    • C07K2317/567—Framework region [FR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • 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

  • ALK is highly similar to the RTK called Leukocyte Tyrosine Kinase (LTK) and belongs to the insulin receptor superfamily. ALK exhibits 57% aa identity and 71% aa similarity with LTK in their regions of overlap (Morris 2001). ALK is highly N-glycosylated and con- tains 21 putative N-glycosylation sites. Amino acids 687 to 1034 have significant similarity (50% aa identity) to LTK.
  • LTK Leukocyte Tyrosine Kinase
  • the amino acid sequence of the kinase domain of murine ALK shows 98% aa-identity to human ALK, 78% iden- tity to mouse LTK, 52% to mouse ros, 47% to human insulin-like growth factor receptor and 46% to human insulin receptor (Iwahara 1997; Ladanyi 2000) .
  • No splice variants of ALK have been described to date.
  • ALK is often associated with chromosomal translocations (see below) .
  • the ALK gene spans about 315kb and has 26 ex- ons. Much of the gene consists of two large introns that span about 170kb.
  • the ALK transcript is 6.5kb of length (Kutok 2002) .
  • NPM normally undergoes self-oligomerization (hexamers) as well as hetero- oligomerization with NPM-ALK (Duyster 2001).
  • the 2;5 translocation brings the ALK gene portion encoding the tyrosine kinase on chromosome 2 under the control of the strong NPM promoter on chromosome 5, producing permanent expression of the chimeric NPM-ALK protein (p80) (Duyster 2001) .
  • ALK kinase is deregulated and ectopic, both in terms of cell type (lymphoid) and cellular compartment (nucleus/nucleolus and cytoplasm) (Ladanyi 2000).
  • the antibody molecules are fully human.
  • Treatment of humans with human monoclonal antibodies offers several advantages.
  • the antibodies are likely to be less immunogenic in humans than non-human antibodies.
  • the therapy is also rapid because ALK inac- tivation can occur as soon as the antibody reaches a cancer site (where ALK is expressed) .
  • amino acids with basic side chains e.g., lysine, arginine, histidine
  • acidic side chains e.g., aspartic acid, glutamic acid
  • uncharged polar side chains e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan
  • nonpolar side chains e.g., alanine, valine, leucine, isoleucine, proline, phenyla- lanine, methionine
  • beta-branched side chains e.g., threonine, valine, isoleucine
  • aromatic side chains e.g., tyrosine, phenylalanine, tryptophan, histidine
  • the membranes were then incubated with the anti-Flag M2-HRP (Sigma-Aldrich Corporation; diluted according to the manufacturers' recommendations) and visualized using Su- perSignal West Pico Chemiluminescent Substrate (Pierce Biotechnology, Rockford, IL) .

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne un anticorps spécifique pour l'ALK (kinase de lymphome anaplastique) humaine, en particulier un scFv, une séquence d'acide nucléique le codant, sa production et son utilisation à des fins pharmaceutiques ou diagnostiques. Ledit anticorps est adapté au traitement local de tumeurs, par exemple, le cancer ou les tumeurs métastatiques, en particulier le glioblastome.
PCT/CH2008/000193 2007-04-27 2008-04-28 Anticorps anti-alk adaptés au traitement des cancers et tumeurs métastatiques Ceased WO2008131575A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US92681007P 2007-04-27 2007-04-27
US60/926,810 2007-04-27

Publications (2)

Publication Number Publication Date
WO2008131575A2 true WO2008131575A2 (fr) 2008-11-06
WO2008131575A3 WO2008131575A3 (fr) 2009-01-29

Family

ID=39926146

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CH2008/000193 Ceased WO2008131575A2 (fr) 2007-04-27 2008-04-28 Anticorps anti-alk adaptés au traitement des cancers et tumeurs métastatiques

Country Status (1)

Country Link
WO (1) WO2008131575A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013033008A2 (fr) 2011-08-26 2013-03-07 Merrimack Pharmaceuticals, Inc. Anticorps bispécifiques à fc en tandem
WO2014138449A1 (fr) 2013-03-06 2014-09-12 Merrimack Pharmaceuticals, Inc. Anticorps bispécifiques anti-c-met à fc en tandem
EP2970495A4 (fr) * 2013-03-12 2017-02-22 Five Prime Therapeutics, Inc. Antagonistes fam150a, fam150b et fam150 et leurs utilisations
EP3341021A4 (fr) * 2015-08-27 2019-03-13 Celldex Therapeutics, Inc. Anticorps anti-alk et leurs procédés d'utilisation
WO2022235940A1 (fr) * 2021-05-06 2022-11-10 Dana-Farber Cancer Institute, Inc. Anticorps anti-alk et leurs procédés d'utilisation

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2399617T3 (es) * 2002-05-22 2013-04-02 Esbatech - A Novartis Company Llc Regiones de marco de inmunoglobulina que demuestran estabilidad potenciada en el entorno intracelulcar y métodos de identificación de las mismas
WO2007059300A2 (fr) * 2005-11-15 2007-05-24 Medimmune, Inc. Antagonistes et agonistes d'alk et applications
CN101443361B (zh) * 2006-04-28 2015-08-19 德勒尼克斯治疗股份公司 与受体酪氨酸激酶alk的胞外域结合的抗体

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013033008A2 (fr) 2011-08-26 2013-03-07 Merrimack Pharmaceuticals, Inc. Anticorps bispécifiques à fc en tandem
WO2014138449A1 (fr) 2013-03-06 2014-09-12 Merrimack Pharmaceuticals, Inc. Anticorps bispécifiques anti-c-met à fc en tandem
US9458245B2 (en) 2013-03-06 2016-10-04 Merrimack Pharmaceuticals, Inc. ANTI-C-MET tandem Fc bispecific antibodies
EP2970495A4 (fr) * 2013-03-12 2017-02-22 Five Prime Therapeutics, Inc. Antagonistes fam150a, fam150b et fam150 et leurs utilisations
EP3341021A4 (fr) * 2015-08-27 2019-03-13 Celldex Therapeutics, Inc. Anticorps anti-alk et leurs procédés d'utilisation
US11091559B2 (en) 2015-08-27 2021-08-17 Celldex Therapeutics, Inc. Anti-ALK antibodies and methods for use thereof
WO2022235940A1 (fr) * 2021-05-06 2022-11-10 Dana-Farber Cancer Institute, Inc. Anticorps anti-alk et leurs procédés d'utilisation

Also Published As

Publication number Publication date
WO2008131575A3 (fr) 2009-01-29

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