ME02377B - Anti-igf antitijela - Google Patents

Anti-igf antitijela

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Publication number
ME02377B
ME02377B MEP-2015-211A MEP21115A ME02377B ME 02377 B ME02377 B ME 02377B ME P21115 A MEP21115 A ME P21115A ME 02377 B ME02377 B ME 02377B
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ME
Montenegro
Prior art keywords
igf
antibody molecule
cancer
seq
molecule according
Prior art date
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MEP-2015-211A
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English (en)
French (fr)
Inventor
Paul Adam
Eric Borges
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Boehringer Ingelheim Int
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=40512371&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ME02377(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int
Publication of ME02377B publication Critical patent/ME02377B/me

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/575—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/5758—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites
    • G01N33/57595—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites involving intracellular compounds
    • 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
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • 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
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • 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
    • 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
    • C07K2317/70—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
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/475—Assays involving growth factors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Claims (31)

1.Izolovani molekul humanog antitjela, koji sea)vezuje za humani IGF-1 i IGF-2 tako da jei.vezivanje IGF-1 i IGF-2 za IGF-1 receptor spriječeno iii. signalizacija IGF-1 posredovanog receptora je inhibirana,b)vezuje za mišiji i pacovski IGF-1 i IGF-2,c)ne vezuje za humani insulin;pri čemu navedeni molekul antitjela je molekul antitjela koji ima teški lanac CDR koji sadrže amino kiselinske sekvence SEQ ID NO: 21 (CDR1), SEQ ID NO: 22 (CDR2) i SEQ ID NO: 23 (CDR3) i koji ima laki lanac CDR koji sadrže amino kiselinske sekvence SEQ ID NO: 24 (CDR1), SEQ ID NO: 25 (CDR2) i SEQ ID NO: 26 (CDR3).
2.Molekul antitjela prema zahtjevu 1, koji ima varijabilni teški lanac koji sadrži amino kiselinsku sekvencu SEQ ID NO: 28.
3.Molekul antitjela prema zahtjevu 1, koji ima varijabilni laki lanac koji sadrži amino kiselinsku sekvencu SEQ ID NO: 30.
4.Molekul antitjela prema bilo kom od zahtjeva 1 do 3, koji sadrži konstantni region teškog lanca odabranog između grupe koja se sastoji od konstantnih regiona IgG1, IgG2, IgG3, IgG4, IgM, IgA i IgE.
5.Molekul antitjela prema zahtjevu 4, gdje navedeni konstantni region teškog lanca je IgG1 koji sadrži amino kiselinsku sekvencu SEQ ID NO: 32.
6.Molekul antitjela prema bilo kom od zahtjeva 1 do 3, gdje konstanti region lakog lanca je Igλ.
7.Molekul antitjela prema zahtjevu 6, gdje konstanti region lakog lanca sadrži amino kiselinsku sekvencu SEQ ID NO: 34.
8.Molekul antitjela prema zahtjevu 2 ili 3 koji ima a)teški lanac koji sadrži amino kiselinsku sekvencu SEQ ID NO: 39 i b)laki lanac koji sadrži amino kiselinsku sekvencu SEQ ID NO: 40.
9.Molekul antitjela prema bilo kom od zahtjeva 1 do 3, koji je Fab, F(ab')2, ili pojedinačni lančani Fv fragment.
10.DNK molekul koji kodira varijabilni teški lanac i varijabilni laki lanac molekula antitjela prema bilo kom od zahtjeva 1 do 9.
11.DNK molekul prema zahtjevu 10 koji ima nukleotidnu sekvencu SEQ ID NO: 27, koji enkodira varijabilni teški lanac antitjela definisanog prema zahtjevu 2, i koji ima nukleotidnu sekvencu SEQ ID NO: 29, koji kodira varijabilni laki lanac antitjela definisanog prema zahtjevu 3.
12.Ekspresioni vektor koji sadrži DNK molekul koji obuhvata nukleotidnu sekvencu koja kodira varijabilni teški lanac i varijabilni laki lanac molekula antitjela prema bilo kom od zahtjeva 1 do 9.
13.Ekspresioni vektor prema zahtjevu 12 koji sadrži DNK molekul koji obuhvata nukleotidnu sekvencu SEQ ID NO: 27 i/ili SEQ ID NO: 29.
14.Ekspresioni vektor prema zahtjevu 12 ili 13, koji sadrži, dodatno, DNK molekul koji kodira konstantni teški lanac i/ili konstantni laki lanac, respektivno, povezan za DNK molekulom koji kodira varijabilni teški lanac i/ili varijabilni laki lanac, respektivno.
15.Ćelija domaćina koja nosi jedan ili više ekspresionih vektora prema zahtjevu 12, 13, ili 14.
16.Ćelija domaćina prema zahtjevu 15, koja je ćelija sisara.
17.Postupak za dobijanje antitjela prema bilo kom od zahtjeva 1 do 9, koji sadrži transfektovanje ćelije domaćina sisara sa jednim ili više vektora prema zahtjevu 12 do 14, kultivisanje ćelije domaćina i obnavljanje i prečišćavanje antitjela.
18.Postupak za proizvodnju antitjela prema bilo kom od zahtjeva 1 do 9, koji sadrži dobijanje ćelije domaćina sisara koji sadrži jedan ili više vektora prema zahtjevu 12 do 14, i kultivisanje ćelije domaćina.
19.Postupak prema zahtjevu 18, dalje obuhvata obnavljanje i prečišćavanje antitjela.
20.Molekul antitjela prema bilo kom od zahtjeva 1 do 9 za korišćenje u medicini.
21.Molekul antitjela prema bilo kom od zahtjeva 1 do 9 za korišćenje u liječenju oboljenja raka odabranih između raka hematopoetičnog sistema koji obuhvata leukemije, limfome i mijelome, rak gastrointestinalnog trakta koji obuhvata esofagalni, gastritični, kolorektalni, pankreatski, jetreni i rak žučne kese i rak žučnog kanala, prvenstveno hepatocelularni karcinom; rak bubrega, prostate i bešike; ginekološki kanceri koji obuhvataju rak dojke, jajnika, cerviksa i endometrijuma; rak kože i glave i vrata koji obuhvata malignantne melanome; pedijatrijski karcinomi kao što su Wilm-ov tumor, neuroblastoma i Ewing-ova sarkoma; tumor mozga kao što je glioblastoma; sarkome kao što su osteosarkoma, sarkoma mekog tkiva, rabdomiosarkoma, hemangiosarkoma; rak pluća, prvenstveno rak ne malih ćelija pluća; mezotelioma i rak tiroidne žlezde.
22.Molekul antitjela prema zahtjevu 21, gdje se medikament koristi u kombinaciji sa hemoterapijom na bazi platinuma, prvenstveno dvostrukom terapijom paclitaksel/karboplatin ili gemcitabin/cisplatin platinum, sorafenibom, ili jedinjenjem odabranim između grupe inhibitora EGFR, VEGF, HER2-neu, AuroraB, Plkl, PI3 kinaze, ili mTor.
23.Molekul antitjela prema zahtjevu 22, gdje inhibitor mTor je rapamicin, temsirolimus, deforolimus, ili everolimus.
24.Farmaceutska kompozicija koja sadrži molekul antitjela prema bilo kom od zahtjeva 1 do 9 i farmaceutski prihvatljivi nosač.
25.Farmaceutska kompozicija prema zahtjevu 24, dalje sadrži jedan ili više dodatnih terapeutskih agenasa odabranih između a)agenasa za oštećenje DNK, b)terapeutskih aktivnih jedinjenja koja inhibiraju signalni transdukcioni prelaz ili mitotičnu kontrolnu tačku u ćelijama raka, c)antidiabeticima.
26.Farmaceutska kompozicija prema zahtjevu 25, gdje navedeno jedno ili više jedinjenja b) je odabrano iz grupe inhibitora EGFR, VEGF, HER2-neu, AuroraB, Plkl, PI3 kinaze, ili mTor.
27.Farmaceutska kompozicija prema bilo kom od zahtjeva 24 do 26 za korišćenje u lečenju oboljenja raka odabranih između raka hematopoetičnog sistema koji obuhvata leukemije, limfome i mijelome, rak gastrointestinalnog trakta koji obuhvata esofagalni, gastritični, kolorektalni, pankreatski, jetreni i rak žučne kese i rak žučnog kanala, prvenstveno hepatocelularni karcinom; rak bubrega, prostate i bešike; ginekološki kanceri koji obuhvataju rak dojke, jajnika, cerviksa i endometrijuma; rak kože i glave i vrata koji obuhvata malignantne melanome; pedijatrijski karcinomi kao što su Wilm.ov tumor, neuroblastoma i Ewing-ova sarkoma; tumor mozga kao što je glioblastoma; sarkome kao što su osteosarkoma, sarkoma mekog tkiva, rabdomiosarkoma, hemangiosarkoma; rak pluća, prvenstveno rak ne malih ćelija pluća; mezotelioma i rak tiroidne žlezde.
28.Farmaceutska kompozicija prema zahtjevu 27, se dalje koristi u kombinaciji sa hemoterapijom na bazi platinuma, prvenstveno dvostrukom terapijom paclitaksel/karboplatin ili gemcitabin/cisplatin platinum, sorafenibom, ili jedinjenjem odabranim između grupe inhibitora EGFR, VEGF, HER2-neu, AuroraB, Plkl, PI3 kinaze, ili mTor.
29.In vitro postupak za inhibiranje vezivanja IGF-1 i IGF-2 za IGF-1 receptor kod ćelije sisara, obuhvata primjenu na navedenu ćeliju molekula antitjela prema bilo kom od zahtjeva 1 do 9, gdje je posredovanje signalizacijom od strane IGF-1 receptora i proliferacija i anti-apoptozno posredovanje od strane IGF-1 i IGF-2 inhibirano.
30.In vitro postupak za inhibiranje vezivanja IGF-2 za insulin receptor IR-A kod ćelije sisara, obuhvata primjenu molekula antitjela na navedenu ćeliju prema bilo kom od zahtjeva 1 do 9, gdje je posredovanje signalizacijom od strane IR-A inhibirano i gdje je proliferacija i anti-apoptozno posredovanje od strane IGF-2 inhibirano.
31.In vitro postupak za praćenje efektivnosti liječenja pacijenta obolelih od raka sa molekulom antitjela koji se vezuje za IGF-1 i IGF-2, pri čemu navedeni molekul antitela je molekul antitjela prema bilo kom od zahtjeva 1 do 9, gdje navedni postupak obuhvata (a)mjerenje, u biloškom uzorku navedenog pacijenta, nivoa ukupnog IGF-1, (b)mjerenje, u biloškom uzorku navedenog pacijenta, nivoa ukupnog IGF-1 poslije primjene navedenog molekula anti-IGF antitjela na navedenog pacijenta, gdje količina povećanja u nivou ukupnog IGF-1, kada se poredi sa nivoom ukupnog IGF-1 izmerenog u koraku (a), ukazuje na to u kolikoj mjeri pacijent odgovara na liječenje sa navedenim molekulom anti-IGF antitjela. 1/25 2/25 3/25 4/25 5/25 6/25 7/25 8/25 9/25 10/25 11/25 12/25 13/25 14/25 15/25 16/25 17/25 18/25 19/25 20/25 21/25 22/25 23/25 24/25 25/25 1
MEP-2015-211A 2008-12-12 2009-12-11 Anti-igf antitijela ME02377B (me)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP08171554 2008-12-12
PCT/EP2009/066894 WO2010066868A2 (en) 2008-12-12 2009-12-11 Anti-igf antibodies
EP09771361.4A EP2376116B1 (en) 2008-12-12 2009-12-11 Anti-igf antibodies

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ME02377B true ME02377B (me) 2016-06-20

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US (4) US8318159B2 (me)
EP (2) EP3064219A3 (me)
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