HRP20230787T1 - Anti-muc1 antitijelo - Google Patents

Anti-muc1 antitijelo Download PDF

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Publication number
HRP20230787T1
HRP20230787T1 HRP20230787TT HRP20230787T HRP20230787T1 HR P20230787 T1 HRP20230787 T1 HR P20230787T1 HR P20230787T T HRP20230787T T HR P20230787TT HR P20230787 T HRP20230787 T HR P20230787T HR P20230787 T1 HRP20230787 T1 HR P20230787T1
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Croatia
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cancer
amino acid
antibody
acid sequence
seq
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HRP20230787TT
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English (en)
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Johanna Gellert
Anke FLECHNER
Doreen WEIGELT
Antje Danielczyk
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Glycotope Gmbh
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Publication of HRP20230787T1 publication Critical patent/HRP20230787T1/hr

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    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3076—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties
    • C07K16/3092—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells against structure-related tumour-associated moieties against tumour-associated mucins
    • 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
    • A61K47/6851—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 determinant of a tumour cell
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • 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
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    • 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
    • A61K47/54—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 organic compound
    • A61K47/545—Heterocyclic compounds
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • 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
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • 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
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • 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
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • 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
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    • 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

Claims (18)

1. Antitijelo sposobno za vezivanje za MUC1, naznačeno time što sadrži (i) varijabilnu regiju teškog lanca koja sadrži regije koje određuju komplementarnost (CDR) CDR-H1 koja ima amino-kiselinsku sekvencu SEQ ID NO: 1, CDR-H2 koji ima amino-kiselinsku sekvencu SEQ ID NO: 7 i CDR-H3 koji ima amino-kiselinsku sekvencu SEQ ID NO: 3, i (ii) varijabilnu regiju lakog lanca koja sadrži regije koje određuju komplementarnost (CDR) CDR-L1 koji ima amino-kiselinsku sekvencu SEQ ID NO: 4, CDR-L2 koji ima amino-kiselinsku sekvencu SEQ ID NO: 5 i CDR-L3 koji ima amino-kiselinsku sekvencu SEQ ID NO: 6.
2. Antitijelo prema patentnom zahtjevu 1, naznačeno time što varijabilna regija teškog lanca ima amino-kiselinsku sekvencu SEQ ID NO: 10 ili amino-kiselinsku sekvencu koja je najmanje 90% identična amino-kiselinskoj sekvenci SEQ ID NO: 10; i/ili varijabilna regija lakog lanca ima amino-kiselinsku sekvencu SEQ ID NO: 12 ili amino-kiselinsku sekvencu koja je najmanje 90% identična amino-kiselinskoj sekvenci SEQ ID NO: 12.
3. Antitijelo prema patentnom zahtjevu 1 ili 2, naznačeno time što varijabilna regija teškog lanca antitijela ima amino-kiselinsku sekvencu SEQ ID NO: 10 i varijabilna regija lakog lanca antitijela ima amino-kiselinsku sekvencu SEQ ID NO: 12.
4. Antitijelo prema bilo kojem od patentnih zahtjeva 1 do 3, naznačeno time što antitijelo sadrži Fc regiju i poželjno je antitijelo IgG1, IgG2 ili IgG4-tipa; poželjnije pri čemu antitijelo sadrži teški lanac koji ima amino-kiselinsku sekvencu SEQ ID NO: 22, i laki lanac koji ima amino-kiselinsku sekvencu SEQ ID NO: 16.
5. Antitijelo prema bilo kojem od patentnih zahtjeva 1 do 4, naznačeno time što se antitijelo može dobiti proizvodnjom u stanici sisavca, kao što je humana stanična linija odabrana iz grupe koja se sastoji od NM-H9D8 (DSM ACC 2806), NM-H9D8-E6 (DSM ACC 2807), NM-H9D8-E6Q12 (DSM ACC 2856) i staničnih linija porijeklom od njih, ili CHO stanična linija ili stanična linija porijeklom od nje.
6. Antitijelo prema bilo kojem od patentnih zahtjeva 1 do 5, naznačeno time što je antitijelo u kompeticiji za vezivanje za TA-MUC1 s antitijelom koje sadrži varijabilnu regiju teškog lanca koji ima amino-kiselinsku sekvencu SEQ ID NO: 10 i varijabilnu regiju lakog lanca koji ima amino-kiselinsku sekvencu SEQ ID NO: 12.
7. Nukleinska kiselina koja kodira antitijelo prema bilo kojem od patentnih zahtjeva 1 do 6.
8. Ekspresijska kazeta ili vektor naznačeni time što sadrže nukleinsku kiselinu prema patentnom zahtjevu 7 i promotor koji je operativno povezan s navedenom nukleinskom kiselinom.
9. Stanica domaćin naznačena time što sadrži nukleinsku kiselinu prema patentnom zahtjevu 7 ili ekspresijsku kazetu ili vektor prema patentnom zahtjevu 8.
10. Konjugat naznačen time što sadrži antitijelo prema bilo kojem od patentnih zahtjeva 1 do 6 konjugirano za dodatni agens, pri čemu je dodatni agens polipeptid ili protein, kao što je citokin, imunomodulatorni spoj, tumor-specifično antitijelo ili blokirajuće ili aktivirajuće antitijelo imunske kontrolne točke.
11. Pripravak naznačen time što sadrži antitijelo prema bilo kojem od patentnih zahtjeva 1 do 6, nukleinsku kiselinu prema patentnom zahtjevu 7, ekspresijsku kazetu ili vektor prema patentnom zahtjevu 8, stanicu domaćina prema patentnom zahtjevu 9, ili konjugat prema patentnom zahtjevu 10.
12. Antitijelo prema bilo kojem od patentnih zahtjeva 1 do 6, konjugat prema patentnom zahtjevu 10, ili pripravak prema patentnom zahtjevu 11 za uporabu u medicini.
13. Antitijelo, konjugat ili pripravak za uporabu u medicini prema patentnom zahtjevu 12 za uporabu u liječenju raka, infekcije, autoimune bolesti ili poremećaja imunodeficijencije.
14. Antitijelo, konjugat ili pripravak za uporabu u medicini prema patentnom zahtjevu 12 za uporabu u dijagnozi, detektiranju i/ili praćenju raka, infekcije, autoimune bolesti ili poremećaja imunodeficijencije.
15. Antitijelo, konjugat ili pripravak za uporabu u medicini prema patentnom zahtjevu 13 ili 14, pri čemu je rak naznačen ekspresijom TA-MUC1; i/ili pri čemu je rak odabran iz grupe koja se sastoji od raka jajnika, raka dojke, raka gušterače, raka pluća, raka debelog crijeva, raka želuca, raka jetre, raka bubrega, raka krvi, raka endometrija, raka štitne žlijezde, leukemije, seminoma, melanoma, karcinoma, teratoma, limfoma, sarkoma, mezotelioma, neuroblastoma, glioma, rektalnog raka, raka nadbubrežne žlijezde, raka kože, raka mozga, raka grlića maternice, intestinalnog raka, raka crijeva, raka glave i vrata, gastrointestinalnog raka, raka limfnih čvorova, raka jednjaka, kolorektalnog raka, raka uha, nosa i grla (ENT), raka prostate, raka mokraćnog mjehura, raka maternice i njihovih metastaza.
16. Antitijelo, konjugat ili pripravak za uporabu u medicini prema bilo kojem od patentnih zahtjeva 12 do 15, naznačeno time što se antitijelo upotrebljava u kombinaciji s dodatnim agensom.
17. Postupak proizvodnje antitijela s povećanim afinitetom vezivanja za MUC1, naznačen time što sadrži (a) osiguravanje nukleinske kiseline koja kodira antitijelo koje sadrži (i) varijabilnu regiju teškog lanca koja sadrži regije koje određuju komplementarnost (CDR) CDR-H1 koji ima amino-kiselinsku sekvencu SEQ ID NO: 1, CDR-H2 koji ima amino-kiselinsku sekvencu SEQ ID NO: 8 i CDR-H3 koji ima amino-kiselinsku sekvencu SEQ ID NO: 3, i (ii) varijabilnu regiju lakog lanca koja sadrži regije koje određuju komplementarnost (CDR) CDR-L1 koji ima amino-kiselinsku sekvencu SEQ ID NO: 4, CDR-L2 koji ima amino-kiselinsku sekvencu SEQ ID NO: 5 i CDR-L3 koji ima amino-kiselinsku sekvencu SEQ ID NO: 6; (b) uvođenje mutacije u navedenu nukleinsku kiselinu kako bi se proizvela mutirana nukleinska kiselina, pri čemu se mutacija uvodi u kodon koji kodira amino-kiselinski ostatak na poziciji 8 CDR-H2 tako da navedeni kodon kodira glutamin; i (c) proizvodnju antitijela s povećanim afinitetom vezivanja za MUC1 pomoću ekspresije mutirane nukleinske kiseline u stanici domaćinu.
18. Postupak prema patentnom zahtjevu 17, naznačen time što dodatno sadrži korak (d) obrade antitijela s povećanim afinitetom vezivanja za MUC1.
HRP20230787TT 2018-05-18 2019-05-17 Anti-muc1 antitijelo HRP20230787T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP18173253 2018-05-18
EP19724502.0A EP3794041B1 (en) 2018-05-18 2019-05-17 Anti-muc1 antibody
PCT/EP2019/062756 WO2019219889A1 (en) 2018-05-18 2019-05-17 Anti-muc1 antibody

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US (4) US20210221910A1 (hr)
EP (4) EP4249002A3 (hr)
JP (3) JP7257422B2 (hr)
KR (2) KR20210013107A (hr)
CN (3) CN112449641A (hr)
AU (2) AU2019270457A1 (hr)
BR (2) BR112020023373A2 (hr)
CA (2) CA3100745A1 (hr)
CO (2) CO2020013664A2 (hr)
DK (1) DK3794042T3 (hr)
ES (1) ES2951674T3 (hr)
HR (1) HRP20230787T1 (hr)
HU (1) HUE063066T2 (hr)
MX (2) MX2020011996A (hr)
PH (2) PH12020551969A1 (hr)
PL (1) PL3794041T3 (hr)
RS (1) RS64379B1 (hr)
SG (2) SG11202010493XA (hr)
TW (2) TW202402806A (hr)
WO (2) WO2019219891A1 (hr)
ZA (1) ZA202006684B (hr)

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