HRP20140171T1 - Protutijela i od njih izvedene molekule koje se vežu na steap-1-proteine - Google Patents

Protutijela i od njih izvedene molekule koje se vežu na steap-1-proteine Download PDF

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HRP20140171T1
HRP20140171T1 HRP20140171TT HRP20140171T HRP20140171T1 HR P20140171 T1 HRP20140171 T1 HR P20140171T1 HR P20140171T T HRP20140171T T HR P20140171TT HR P20140171 T HRP20140171 T HR P20140171T HR P20140171 T1 HRP20140171 T1 HR P20140171T1
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Croatia
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antibody
fragment
agent
conjugate
steap
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HRP20140171TT
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Aya Jakobovits
Soudabeh Etessami
Pia M. Challita-Eid
Juan J. Perez-Villar
Karen J. Morrison
Xiao-Chi Jia
Mary Faris
Jean Gudas
Arthur B. Raitano
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Agensys, Inc.
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Publication of HRP20140171T1 publication Critical patent/HRP20140171T1/hr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • 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
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • 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
    • A61K47/50—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
    • A61K47/6861—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 the tumour determinant being from kidney or bladder cancer cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A61K51/106—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants the tumor cell being from kidney or bladder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1075—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody the antibody being against an enzyme
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • 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
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6887—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids from muscle, cartilage or connective tissue
    • 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
    • C07K2317/24—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
    • C07K2317/50—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]

Claims (36)

1. Monoklonsko protutijelo, naznačeno time, da označava X120.545.1.1. i dodijeljen mu je ATCC-Pristupni broj PTA-5803 ili je to humanizirani oblik spomenutog protutijela; ili je to fragment spomenutog protutijela ili njegov humanizirani oblik koji sadrži domenu koja se veže na antigen od spomenutog protutijela ili njegovog humaniziranog oblika; pri čemu taj humanizirani oblik i taj fragment specifično vežu STEAP-1.
2. Modificirani oblik monoklonskog protutijela, naznačen time, da označava X120.545.1.1. i dodijeljen mu je ATCC-Pristupni broj PTA-5803, koji specifično veže STEAP-1 i pokazuje biološko djelovanje od X120.545.1.1.
3. Modificirani oblik prema zahtjevu 2, naznačen time, da je modifikacija odabrana od izbacivanja aminokiseline, dodavanja aminokiseline i zamjene aminokiseline.
4. Protutijelo ili njegov fragment prema zahtjevu 1, naznačen(o) time, da fragment je Fab-fragment, F(ab')2-fragment, Fv-fragment ili Sfv-fragment.
5. Rekombinantni protein, naznačen time, da obuhvaća područje vezanja antigena od protutijela prema bilo kojem od zahtjeva 1 do 4.
6. Protutijelo ili njegov fragment prema bilo kojem od zahtjeva 1 do 4, naznačen(o) time, da je protutijelo ili fragment spojen/o na marker koji se može otkriti, na toksin ili na terapeutsko sredstvo.
7. Protutijelo ili fragment prema zahtjevu 6, naznačen(o) time, da je protutijelo ili fragment spojen/o na marker koji se može otkriti, pri čemu je taj marker radioizotop, metalni kelator, enzim, fluorescentni spoj, bio-iluminacijski spoj ili kemijsko-iluminacijski spoj.
8. Protutijelo ili fragment prema zahtjevu 7, naznačen(o) time, da je radioizotop odabran od sljedećih: 212Bi, 131I, 111In, 90Y, 186Re, 211At, 125I, 188Re, 153Sm, 213Bi, 32P i 177Lu.
9. Protutijelo ili fragment prema zahtjevu 6, naznačen(o) time, da je protutijelo ili fragment spojen/o na toksin, pri čemu je taj toksin odabran od sljedećih: ricin, ricin A-lanca, doksorubicin, daunorubicin, majtansinoid, taksol, etidij-bromid, mitomicin, etopozid, tenopozid, vinkristin, vinblastin, kolhicin, dihidroksi-antracindion, aktinomicin, difterija- toksin, Pseudomonas-eksotoksin (PE) A, PE40, abrin, abrin A-lanca, modekcin A-lanca, alfa- sarcin, gelonin, mitogelin, retstriktocin, fenomicin, enomicin, kuricin, krotin, kaliheamicin, inhibitor sapaonaria officinalis, glukokortikoid, auristatin, auromicin, itrij, bizmut, kombrestatin, duokarmicin, dolostatin, cc1065 i cisplatin.
10. Protutijelo ili fragment prema zahtjevu 9, naznačen(o) time, da je protutijelo ili fragment spojen/o na auristatin.
11. Hibridom, naznačen time, da je deponiran pod ATCC-Pristupnim brojem PTA-5803.
12. Vektor, naznačen time, da obuhvaća polinukleotid koji kodira protutijelo ili fragment prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10.
13. Vektor prema zahtjevu 12, naznačen time, da kodira spomenuto protutijelo ili spomenuti fragment kao jednostruki lanac.
14. Farmaceutski sastav, naznačen time, da obuhvaća protutijelo ili fragment prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10 u humanom jedinstvenom doznom obliku.
15. Analiza za otkrivanje prisutnosti STEAP-1-proteina u biološkom uzorku, naznačena time, da obuhvaća stavljanje u doticaj uzorka s protutijelom ili fragmentom prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10, te otkrivanje vezanja STEAP-1-proteina u uzorku.
16. Analiza prema zahtjevu 15, naznačena time, da je biološki uzorak od pacijenta koji ima rak ili se sumnja da ga može imati, prema popisu vrsta raka u Tablici I.
17. Analiza prema zahtjevu 15 ili 16, naznačena time, da uzorak je serum.
18. Analiza prema zahtjevu 15 ili 16, naznačena time, da uzorak je prostata.
19. Vektor prema zahtjevu 13, naznačen time, da se upotrebljava u postupku medicinskog liječenja.
20. Vektor prema zahtjevu 19, naznačen time, da se upotrebljava u postupku inhibicije rasta stanica raka koje izražavaju STEAP-1 kod osobe, pri čemu postupak obuhvaća: primjenu vektora na spomenutoj osobi, tako da vektor prenosi na stanice raka sekvencu koja kodira protutijelo ili fragment jednostrukog lanca, i zatim ekspresiju unutar stanice tako kodiranog protutijela jednostrukog lanca.
21. Uporaba vektora prema zahtjevu 13, naznačena time, da je za proizvodnju lijeka, gdje je lijek za uporabu u postupku inhibicije rasta stanica raka koje izražavaju STEAP-1 kod osobe, pri čemu postupak obuhvaća: primjenu vektora na spomenutoj osobi, tako da vektor prenosi na stanice raka sekvencu koja kodira protutijelo ili fragment jednostrukog lanca, i zatim ekspresiju unutar stanice tako kodiranog protutijela jednostrukog lanca.
22. Protutijelo ili fragment prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10, naznačen(o) time, da se upotrebljava u postupku medicinskog liječenja.
23. Uporaba protutijela ili fragmenta prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10, naznačena time, da je za proizvodnju lijeka, gdje je lijek za uporabu u postupku inhibicije rasta stanica raka koje izražavaju STEAP-1 kod osobe, pri čemu postupak obuhvaća primjenu protutijela ili fragmenta na spomenutu osobu.
24. Uporaba prema zahtjevu 23, naznačena time, da su stanice raka iz raka koji pripada vrstama nabrojanim u Tablici I.
25. Uporaba prema zahtjevu 24, naznačena time, da su stanice raka iz maligne prostate.
26. Postupak in vitro prijenosa citotoksičnog sredstva ili dijagnostičkog sredstva u stanicu koja izražava STEAP-1-protein, naznačen time, da obuhvaća: dobavljanje citotoksičnog sredstva ili dijagnostičkog sredstva konjugiranog na protutijelo ili na fragment prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10, za tvorbu konjugata sredstva protutijela ili konjugata sredstva fragmenta; i izlaganje stanice navedenom konjugatu sredstva protutijela ili konjugatu sredstva fragmenta.
27. Konjugat sredstva protutijela ili konjugat sredstva fragmenta, naznačen time, da je stvoren od citotoksičnog sredstva ili dijagnostičkog sredstva konjugiranog na protutijelo ili na fragment prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10, te da se on upotrebljava u postupku in vivo za liječenje ili za dijagnosticiranje.
28. Konjugat prema zahtjevu 27, naznačen time, da se upotrebljava u postupku prijenosa citotoksičnog sredstva ili dijagnostičkog sredstva u stanicu koja izražava STEAP-1-protein, pri čemu taj postupak obuhvaća: dobavljanje citotoksičnog sredstva ili dijagnostičkog sredstva konjugiranog na protutijelo ili na fragment prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10, za tvorbu konjugata sredstva protutijela ili konjugata sredstva fragmenta; i izlaganje stanice navedenom konjugatu sredstva protutijela ili konjugatu sredstva fragmenta.
29. Uporaba konjugata, naznačena time, da je za proizvodnju lijeka, pri čemu je konjugat sredstvo protutijela ili sredstvo fragmenta stvoreno od citotoksičnog sredstva ili dijagnostičkog sredstva konjugiranog na protutijelo ili na fragment prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10, dok se lijek upotrebljava za prijenos citotoksičnog sredstva ili dijagnostičkog sredstva u stanicu koja izražava STEAP-1-protein.
30. Postupak, konjugat ili uporaba prema bilo kojem od zahtjeva 26 do 29, naznačen(a) time, da je citotoksično sredstvo ili dijagnostičko sredstvo odabrano iz skupine koja se sastoji od markera koji se može otkriti, toksina i terapeutskog sredstva.
31. Postupak, konjugat ili uporaba prema zahtjevu 30, naznačen(a) time, da je protutijelo ili fragment konjugiran/o na marker koji se može otkriti, pri čemu marker koji se može otkriti je radioizotop, metalni kelator, enzim, fluorescentni spoj, bio-iluminacijski spoj ili kemijsko- iluminacijski spoj.
32. Postupak, konjugat ili uporaba prema zahtjevu 31, naznačen(a) time, da je radioizotop odabran od sljedećih: 212Bi, 131I, 111In, 90Y, 186Re, 211At, 125I, 188Re, 153Sm, 213Bi, 32P i 177Lu.
33. Postupak, konjugat ili uporaba prema zahtjevu 30, naznačen(a) time, da je protutijelo ili fragment konjugiran/o na toksin, pri čemu je taj toksin odabran od sljedećih: ricin, ricin A- lanca, doksorubicin, daunorubicin, majtansinoid, taksol, etidij-bromid, mitomicin, etopozid, tenopozid, vinkristin, vinblastin, kolhicin, dihidroksi-antracindion, aktinomicin, difterija- toksin, Pseudomonas-eksotoksin (PE) A, PE40, abrin, abrin A-lanca, modekcin A-lanca, alfa- sarcin, gelonin, mitogelin, retstriktocin, fenomicin, enomicin, kuricin, krotin, kaliheamicin, inhibitor sapaonaria officinalis, glukokortikoid, auristatin, auromicin, itrij, bizmut, kombrestatin, duokarmicin, dolostatin, cc1065 i cisplatin.
34. Postupak, konjugat ili uporaba prema zahtjevu 33, naznačen(a) time, da je protutijelo ili fragment spojen/o na auristatin.
35. Postupak in vitro otkrivanja STEAP-1-proteina u biološkom uzorku, naznačen time, da obuhvaća sljedeće korake: dobavljanje biološkog uzorka i kontrolnog uzorka; stavljanje u doticaj biološkog uzorka i kontrolnog uzorka s protutijelom ili fragmentom prema bilo kojem od zahtjeva 1 do 4 ili 6 do 10, koji se specifično veže na STEAP-1-protein; i određivanje količine kompleksa protutijela ili fragmenta sa STEAP-1-proteinom, koji je prisutan u biološkom uzorku i u kontrolnom uzorku.
36. Postupak prema zahtjevu 35, naznačen time, da su biološki uzorak i kontrolni uzorak od pacijenta koji ima rak ili za kojega se sumnja da ima rak od nabrojenih vrsta u Tablici I.
HRP20140171TT 2004-04-22 2014-02-25 Protutijela i od njih izvedene molekule koje se vežu na steap-1-proteine HRP20140171T1 (hr)

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