HRP20220631T1 - Supstrati koje mogu cijepati matrične metaloproteaze i serinske proteaze, te postupci njihove uporabe - Google Patents

Supstrati koje mogu cijepati matrične metaloproteaze i serinske proteaze, te postupci njihove uporabe Download PDF

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HRP20220631T1
HRP20220631T1 HRP20220631TT HRP20220631T HRP20220631T1 HR P20220631 T1 HRP20220631 T1 HR P20220631T1 HR P20220631T T HRP20220631T T HR P20220631TT HR P20220631 T HRP20220631 T HR P20220631T HR P20220631 T1 HRP20220631 T1 HR P20220631T1
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isolated polypeptide
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agent
polypeptide according
amino acid
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HRP20220631TT
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Stephen James Moore
Margaret Thy Luu Nguyen
Daniel R. Hostetter
Olga Vasiljeva
Jason Gary SAGERT
Jonathan Alexander Terrett
James William WEST
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Cytomx Therapeutics Inc.
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Publication of HRP20220631T1 publication Critical patent/HRP20220631T1/hr
Publication of HRP20220631T8 publication Critical patent/HRP20220631T8/hr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • 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
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • 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
    • A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
    • 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
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
    • A61K49/0058—Antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • 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
    • 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
    • C07K16/2863—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 growth factors, growth regulators
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • 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
    • 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
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Toxicology (AREA)
  • Peptides Or Proteins (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Detergent Compositions (AREA)
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Claims (27)

1. Izolirani polipeptid koji sadrži supstrat CM1-CM2, koji sadrži najmanje prvi ostatak kojeg se može cijepati (CM1), koji je supstrat za najmanje jednu matričnu metaloproteazu (MMP), i najmanje drugi ostatak kojeg se može cijepati (CM2), koji je supstrat za najmanje jednu serinsku proteazu (SP), pri čemu supstrat CM1-CM2 sadrži aminokiselinski slijed kojeg se bira iz skupine koju čine: SEQ ID NO: 1, 7, 555, te 557.
2. Izolirani polipeptid u skladu s patentnim zahtjevom 1, pri čemu je MMP MMP2, MMP9 ili MMP14.
3. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, pri čemu je SP uPA ili matriptaza.
4. Izolirani polipeptid koji sadrži antitijelo ili njegov fragment koji se veže na antigen (AB), koji se veže na metu, te najmanje prvi ostatak kojeg se može cijepati (CM1), koji je supstrat za najmanje jednu matričnu metaloproteazu (MMP), i najmanje drugi ostatak kojeg se može cijepati (CM2), koji je supstrat za najmanje jednu serinsku proteazu (SP), pri čemu supstrat CM1-CM2 sadrži aminokiselinski slijed kojeg se bira iz skupine koju čine: SEQ ID NO: 1, 7, 555, te 557.
5. Izolirani polipeptid u skladu s patentnim zahtjevom 4, pri čemu MMP, SP, ili su i MMP i SP kolokalizirani u tkivu s metom.
6. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-5, pri čemu se njegov fragment koji se veže na antigen bira iz skupine koju čine fragment Fab, fragment F(ab’)2, scFv, scAb, dAb, antitijelo s jednodomenskim teškim lancem, te antitijelo s jednodomenskim lakim lancem.
7. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-6, pri čemu je AB spojen s CM1; i/ili izborno pri čemu je AB spojen izravno s CM1 i/ili izborno; pri čemu je AB spojen s CM1 putem spojnog peptida.
8. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-7, pri čemu je AB spojen s CM2; i/ili izborno pri čemu je AB spojen izravno s CM2; i/ili izborno pri čemu je AB spojen s CM2 putem spojnog peptida.
9. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-8, pri čemu je MMP MMP2, MMP9 ili MMP14; i/ili izborno pri čemu je SP uPA ili matriptaza.
10. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-9, pri čemu izolirani polipeptid sadrži prikrivajući ostatak (MM); i/ili izborno pri čemu MM ima konstantu disocijacije za vezanje na AB veću od konstante disocijacije AB za vezanje na metu; i/ili izborno pri čemu je MM polipeptid dug najviše 40 aminokiselina.
11. Izolirani polipeptid u skladu s patentnim zahtjevom 10, pri čemu je MM tako spojen s CM1 da izolirani polipeptid u nerascijepljenom stanju ima strukturni raspored od N-kraja do C-kraja kao što slijedi: MM-CM1-CM2-AB ili AB-CM2-CM1-MM; i/ili izborno pri čemu izolirani polipeptid sadrži spojni peptid između MM i CM1; i/ili izborno pri čemu izolirani polipeptid sadrži spojni peptid između CM2 i AB.
12. Izolirani polipeptid u skladu s patentnim zahtjevom 10, pri čemu je MM tako spojen s CM2 da izolirani polipeptid u nerascijepljenom stanju ima strukturni raspored od N-kraja do C-kraja kao što slijedi: MM-CM2-CM1-AB ili AB-CM1-CM2-MM; i/ili izborno pri čemu izolirani polipeptid sadrži spojni peptid između MM i CM2; i/ili izborno pri čemu izolirani polipeptid sadrži spojni peptid između CM1 i AB.
13. Izolirani polipeptid u skladu s patentnim zahtjevom 10, pri čemu izolirani polipeptid sadrži prvi spojni peptid (LP1) i drugi spojni peptid (LP2), te pri čemu izolirani polipeptid ima strukturni raspored od N-kraja do C-kraja kao što slijedi u nerascijepljenom stanju: MM-LP1-CM1-CM2-LP2-AB, AB-LP2-CM2-CM1-LP1-MM, MM-LP1- CM2-CM1-LP2-AB ili AB-LP2-CM1-CM2-LP1-MM; i/ili izborno pri čemu dva spojna peptida ne moraju biti međusobno istovjetni; i/ili izborno pri čemu je svaki od LP1 i LP2 peptid dug otprilike 1 do 20 aminokiselina.
14. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 10-13, pri čemu aminokiselinski slijed MM se razlikuje od slijeda mete, te je najviše 10 % istovjetan aminokiselinskom slijedu prirodnog vežućeg partnera AB.
15. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 10-14, pri čemu MM ne ometa niti konkurira s AB za vezanje na metu u rascijepljenom stanju.
16. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-15, pri čemu izolirani polipeptid sadrži aminokiselinski slijed lakog lanca kojeg se bira iz skupine koju čine SEQ ID NO: 420, 432, 561, te 562, te aminokiselinski slijed teškog lanca koji sadrži SEQ ID NO: 67; i/ili izborno pri čemu izolirani polipeptid sadrži aminokiselinski slijed lakog lanca kojeg se bira iz skupine koju čine SEQ ID NO: 449, 559, te 560, te aminokiselinski slijed teškog lanca koji sadrži SEQ ID NO: 108.
17. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 1-15, pri čemu izolirani polipeptid sadrži aminokiselinski slijed kojeg se bira iz skupine koju čine SEQ ID NO: 420, 432, 561, te 562; i/ili izborno pri čemu izolirani polipeptid sadrži aminokiselinski slijed kojeg se bira iz skupine koju čine SEQ ID NO: 449, 559, te 560.
18. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 10-17, pri čemu je MMP MMP2, MMP9 ili MMP14; i/ili izborno pri čemu je SP uPA ili matriptaza.
19. Konjugirano antitijelo kojeg se može aktivirati koje sadrži izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-18 konjugiran sa sredstvom; i/ili izborno pri čemu je sredstvo konjugirano s AB putem spojnice; i/ili izborno pri čemu spojnica je spojnica koju se može cijepati ili spojnica koju se ne može cijepati.
20. Konjugirano antitijelo kojeg se može aktivirati u skladu s patentnim zahtjevom 19, pri čemu je sredstvo toksin; i/ili izborno pri čemu je sredstvo inhibitor mikrotubula; i/ili izborno pri čemu je sredstvo sredstvo koje oštećuje nukleinske kiseline; i/ili izborno pri čemu se sredstvo bira iz skupine koju čine dolastatin, auristatin, maitansinoid, duokarmicin, te kalikeamicin; i/ili izborno pri čemu je sredstvo auristatin E; i/ili izborno pri čemu je sredstvo monometilauristatin E (MMAE); i/ili izborno pri čemu je sredstvo monometilauristatin D (MMAD); i/ili izborno pri čemu je sredstvo maitansinoid kojeg se bira iz skupine koju čine DM1 i DM4.
21. Konjugirano antitijelo kojeg se može aktivirati u skladu s bilo kojim od patentnog zahtjeva 19 ili patentnog zahtjeva 20, pri čemu je sredstvo dokazivi ostatak; i/ili izborno pri čemu je dokazivi ostatak dijagnostičko sredstvo.
22. Farmaceutski pripravak koji sadrži izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-18 i nosač; i/ili može sadržavati dodatno sredstvo; i/ili izborno pri čemu je dodatno sredstvo terapijsko sredstvo.
23. Izolirana molekula nukleinske kiseline koja kodira izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 1-18.
24. Vektor koji sadrži izoliranu molekulu nukleinske kiseline u skladu s patentnim zahtjevom 23.
25. Postupak proizvodnje antitijela ili antitijela kojeg se može aktivirati uzgojem stanice u uvjetima koji dovode do eksprimiranja izoliranog polipeptida u skladu s bilo kojim od patentnih zahtjeva 4-18, pri čemu stanica sadrži molekulu nukleinske kiseline u skladu s patentnim zahtjevom 23.
26. Postupak proizvodnje antitijela kojeg se može aktivirati, koje se, u aktiviranom stanju, veže na metu, gdje se postupak sastoji u: (a) uzgoju stanice koja sadrži nukleinskokiselinski konstrukt koji kodira izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-18; i (b) prikupljanju antitijela kojeg se može aktivirati.
27. Izolirani polipeptid u skladu s bilo kojim od patentnih zahtjeva 4-18, konjugirano antitijelo kojeg se može aktivirati u skladu s bilo kojim od patentnih zahtjeva 19-21, ili farmaceutski pripravak u skladu s patentnim zahtjevom 22, namijenjeni uporabi u liječenju raka, izborno uz dodatno sredstvo, koje može biti terapijsko sredstvo.
HRP20220631TT 2015-01-20 2016-01-20 Supstrati koje mogu cijepati matrične metaloproteaze i serinske proteaze, te postupci njihove uporabe HRP20220631T8 (hr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201562105490P 2015-01-20 2015-01-20
US201562258015P 2015-11-20 2015-11-20
US201662278713P 2016-01-14 2016-01-14
EP16704511.1A EP3247393B1 (en) 2015-01-20 2016-01-20 Matrix metalloprotease-cleavable and serine protease cleavable substrates and methods of use thereof
PCT/US2016/014132 WO2016118629A1 (en) 2015-01-20 2016-01-20 Matrix metalloprotease-cleavable and serine protease cleavable substrates and methods of use thereof

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