WO2008131575A2 - Anticorps anti-alk adaptés au traitement des cancers et tumeurs métastatiques - Google Patents
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Classifications
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- 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
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- 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) .
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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.
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 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CH2008/000193 WO2008131575A2 (fr) | 2007-04-27 | 2008-04-28 | Anticorps anti-alk adaptés au traitement des cancers et tumeurs métastatiques |
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| WO (1) | WO2008131575A2 (fr) |
Cited By (5)
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8853362B2 (en) * | 2002-05-22 | 2014-10-07 | Esbatech, An Alcon Biomedical Research Unit Llc | Immunoglobulin frameworks which demonstrate enhanced stability in the intracellular environment and methods of identifying same |
| 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 |
-
2008
- 2008-04-28 WO PCT/CH2008/000193 patent/WO2008131575A2/fr active Application Filing
Cited By (7)
| 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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