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HRP20180352T1 - Protutijela anti-fcrh5 - Google Patents

Protutijela anti-fcrh5 Download PDF

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Publication number
HRP20180352T1
HRP20180352T1 HRP20180352TT HRP20180352T HRP20180352T1 HR P20180352 T1 HRP20180352 T1 HR P20180352T1 HR P20180352T T HRP20180352T T HR P20180352TT HR P20180352 T HRP20180352 T HR P20180352T HR P20180352 T1 HRP20180352 T1 HR P20180352T1
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HR
Croatia
Prior art keywords
seq
amino acid
acid sequence
sequence
hvr
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Application number
HRP20180352TT
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English (en)
Inventor
Allen J. Ebens
Meredith C. Hazen
Jo-Anne Hongo
Jennifer W. Johnston
Teemu T. Junttila
Ji Li
Andrew G. POLSON
Original Assignee
Genentech, Inc.
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Publication date
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Publication of HRP20180352T1 publication Critical patent/HRP20180352T1/hr

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    • 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
    • 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
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against Fc-receptors, e.g. CD16, CD32, CD64
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A—HUMAN NECESSITIES
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    • 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
    • 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
    • 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
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    • 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
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    • 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
    • A61K47/6875—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 being a hybrid immunoglobulin
    • A61K47/6879—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 being a hybrid immunoglobulin the immunoglobulin having two or more different antigen-binding sites, e.g. bispecific or multispecific immunoglobulin
    • 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
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • 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
    • 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
    • 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
    • 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
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • C07K2317/30—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
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL

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Claims (16)

1. Izolirano protutijelo anti-FcRH5, naznačeno time, da veže izoformno c-specifično područje izvanstanične domene od FcRH5c, prikazano kao aminokiseline 743-850 od SEQ ID NO: 1, pri čemu protutijelo ne veže značajno niti jednu drugu domenu od FcRH5, koja je nalik na Ig.
2. Protutijelo anti-FcRH5 prema zahtjevu 1, naznačeno time, da protutijelo anti-FcRH5 obuhvaća sljedeće: (a) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 39, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 63, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 87, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 3, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 15, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 27; (b) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 38, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 62, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 86, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 2, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 14, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 26; (c) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 40, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 64, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 88, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 4, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 16, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 28; (d) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 41, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 65, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 89, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 5, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 17, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 29; (e) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 42, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 66, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 90, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 6, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 18, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 30; (f) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 43, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 67, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 91, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 7, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 19, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 31; (g) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 44, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 68, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 92, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 8, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 20, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 32; (h) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 45, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 69, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 93, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 9, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 21, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 33; (i) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 46, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 70, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 94, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 10, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 22, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 34; (j) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 47, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 71, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 95, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 11, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 23, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 35; (k) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 48, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 72, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 96, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 12, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 24, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 36; ili (l) teški lanac koji obuhvaća HVR-H1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 49, HVR-H2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 73, i HVR-H3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 97, te laki lanac koji obuhvaća HVR-L1 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 13, HVR-L2 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 25, i HVR-L3 koje sadrži aminokiselinsku sekvencu od SEQ ID NO: 37.
3. Protutijelo anti-FcRH5 prema zahtjevu 1 ili 2, naznačeno time, da protutijelo anti-FcRH5 obuhvaća sljedeće: (a) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 113 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 112; (b) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 135 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 134; (c) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 111 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 110; (d) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 115 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 114; (e) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 117 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 116; (f) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 119 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 118; (g) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 121 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 120; (h) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 123 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 122; (i) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 125 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 124; (j) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 127 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 126; (k) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 129 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 128; (l) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 131 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 130; ili (m) VH sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 133 i VL sekvencu koja ima najmanje 95% identiteta sekvence od aminokiselinske sekvence SEQ ID NO: 132.
4. Protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 3, naznačeno time, da protutijelo anti-FcRH5 obuhvaća sljedeće: (a) VH sekvencu od SEQ ID NO: 111 i VL sekvencu od SEQ ID NO: 110; (b) VH sekvencu od SEQ ID NO: 135 i VL sekvencu od SEQ ID NO: 134; (c) VH sekvencu od SEQ ID NO: 113 i VL sekvencu od SEQ ID NO: 112; (d) VH sekvencu od SEQ ID NO: 115 i VL sekvencu od SEQ ID NO: 114; (e) VH sekvencu od SEQ ID NO: 117 i VL sekvencu od SEQ ID NO: 116; (f) VH sekvencu od SEQ ID NO: 119 i VL sekvencu od SEQ ID NO: 118; (g) VH sekvencu od SEQ ID NO: 121 i VL sekvencu od SEQ ID NO: 120; (h) VH sekvencu od SEQ ID NO: 123 i VL sekvencu od SEQ ID NO: 122; (i) VH sekvencu od SEQ ID NO: 125 i VL sekvencu od SEQ ID NO: 124; (j) VH sekvencu od SEQ ID NO: 127 i VL sekvencu od SEQ ID NO: 126; (k) VH sekvencu od SEQ ID NO: 129 i VL sekvencu od SEQ ID NO: 128; (l) VH sekvencu od SEQ ID NO: 131 i VL sekvencu od SEQ ID NO: 130; ili (m) VH sekvencu od SEQ ID NO: 133 i VL sekvencu od SEQ ID NO: 132.
5. Protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 4, naznačeno time, da je protutijelo anti-FcRH5 sljedeće: (a) monoklonalno protutijelo; (b) ljudsko, humanizirano, ili kimerno protutijelo; (c) fragment protutijela koji veže FcRH5; (d) protutijelo IgG1, IgG2a, ili IgG2b; (e) bispecifično protutijelo, opcijski gdje to bispecifično protutijelo veže FcRH5 i CD3; i/ili (f) konjugirano na oznaku, pri čemu je opcijski ta oznaka sredstvo za emitiranje pozitrona, te opcijski gdje sredstvo za emitiranje pozitrona je 89Zr.
6. Protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 5, naznačeno time, da protutijelo anti-FcRH5 ima jednu ili više od sljedećih karakteristika: (a) jest unakrsno-reaktivno s ljudskim i psećim FcRH5 pune duljine, (b) nije unakrsno-reaktivno s FcRH1, FcRH2, FcRH3 i/ili FcRH4, (c) veže se na endogeni FcRH5, i (d) nije unakrsno-reaktivno s FcRH5a.
7. Izolirana nukleinska kiselina, naznačena time, da kodira protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 6.
8. Stanica domaćina, naznačena time, da obuhvaća nukleinsku kiselinu prema zahtjevu 7.
9. Postupak za proizvodnju protutijela anti-FcRH5, naznačen time, da obuhvaća kultiviranje stanice domaćina prema zahtjevu 8, tako, da se proizvede protutijelo anti-FcRH5.
10. Imunokonjugat, naznačen time, da obuhvaća protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 6 i jedno citotoksično sredstvo, opcijski pritom imunokonjugat ima formulu Ab-(L-D)p, pri čemu: (a) Ab je protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 6; (b) L je poveznica; (c) D je lijek odabran od majtanzinoida, auristatina, kaliheamicina, pirolobenzodiazepina, i derivata nemorubicina; i (d) p iznosi u rasponu od 1 do 8, i poželjno od 2 do 5.
11. Imunokonjugat prema zahtjevu 10, naznačen time, da se poveznica može cijepati pomoću proteaze ili je kiselolabilna.
12. Farmaceutska formulacija, naznačena time, da obuhvaća protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 6 i /ili imunokonjugat prema zahtjevu 10 ili 11 i jedan farmaceutski prihvatljiv nosač, te opcijski nadalje obuhvaća jedno dodatno terapeutsko sredstvo.
13. Protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 6 i/ili imunokonjugat prema zahtjevu 10 ili 11, naznačen/o time, da se upotrebljava u postupku liječenja pojedinca koji ima rak pozitivan na FcRH5, pri čemu taj postupak obuhvaća davanje pojedincu učinkovite količine protutijela anti-FcRH5 i/ili imunokonjugata, gdje se kod raka pozitivnog na FcRH5, radi opcijski o proliferativnom poremećaju B-stanice, te postupak opcijski nadalje obuhvaća davanje dodatnog terapeutskog sredstva pojedincu.
14. Protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 6 i/ili imunokonjugat prema zahtjevu 10 ili 11, naznačen/o time, da se upotrebljava u postupku inhibiranja proliferacije stanice koja je pozitivna na FcRH5, pri čemu taj postupak obuhvaća izlaganje stanice koja je pozitivna na FcRH5, protutijelu anti-FcRH5 i/ili imunokonjugatu, pod uvjetima koji su tolerantni za vezanje protutijela anti-FcRH5 i/ili imunokonjugata na FcRH5, na površini stanice koja je pozitivna na FcRH5, čime se inhibira proliferacija stanice pozitivne na FcRH5, dok se opcijski kod stanice koja je pozitivna na FcRH5, radi o B-stanici.
15. Protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 6, naznačeno time, da se upotrebljava u postupku otkrivanja ljudskog FcRH5 u biološkom uzorku, pri čemu taj postupak obuhvaća stavljanje u doticaj biološkog uzorka s protutijelom anti-FcRH5, pod uvjetima koji su tolerantni za vezanje protutijela anti-FcRH5 na ljudski FcRH5 koji se pojavljuje prirodno, te otkrivanja činjenice, da li se stvara kompleks u biološkom uzorku, između protutijela anti-FcRH5 i ljudskog FcRH5 koji se pojavljuje prirodno, dok se opcijski kod biološkog uzorka radi o uzorku krvi.
16. Protutijelo anti-FcRH5 prema bilo kojem od zahtjeva 1 do 6, naznačeno time, da se upotrebljava u postupku otkrivanja raka pozitivnog na FcRH5, pri čemu taj postupak obuhvaća (i) davanje protutijela anti-FcRH5 pojedincu koji ima ili se sumnja da ima rak pozitivan na FcRH5, dok se kod protutijela anti-FcRH5 radi o označenom protutijelu anti-FcRH5, i (ii) otkrivanje označenog protutijela anti-FcRH5 kod pojedinca, gdje otkrivanje označenog protutijela anti-FcRH5, pokazuje postojanje raka pozitivnog na FcRH5 kod pojedinca, dok opcijski označeno protutijelo anti-FcRH5 obuhvaća protutijelo anti-FcRH5 konjugirano na sredstvo za emitiranje pozitrona, te time, da se opcijski kod sredstva za emitiranje pozitrona radi o 89Zr.
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