HRP20150591T1 - Smanjenje broja b-stanica koristeä†i cd37-specifiäśne i cd20-specifiäśne vezne molekule - Google Patents
Smanjenje broja b-stanica koristeä†i cd37-specifiäśne i cd20-specifiäśne vezne molekule Download PDFInfo
- Publication number
- HRP20150591T1 HRP20150591T1 HRP20150591TT HRP20150591T HRP20150591T1 HR P20150591 T1 HRP20150591 T1 HR P20150591T1 HR P20150591T T HRP20150591T T HR P20150591TT HR P20150591 T HRP20150591 T HR P20150591T HR P20150591 T1 HRP20150591 T1 HR P20150591T1
- Authority
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- Croatia
- Prior art keywords
- binding protein
- seq
- humanized
- specific binding
- agent
- Prior art date
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- 230000009870 specific binding Effects 0.000 title claims 22
- 210000003719 b-lymphocyte Anatomy 0.000 title claims 4
- 102000023732 binding proteins Human genes 0.000 claims 26
- 108091008324 binding proteins Proteins 0.000 claims 26
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims 24
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims 21
- 239000003795 chemical substances by application Substances 0.000 claims 12
- 239000002246 antineoplastic agent Substances 0.000 claims 9
- 229940127089 cytotoxic agent Drugs 0.000 claims 9
- 108060003951 Immunoglobulin Proteins 0.000 claims 7
- 102000018358 immunoglobulin Human genes 0.000 claims 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims 7
- 125000003275 alpha amino acid group Chemical group 0.000 claims 6
- 235000001014 amino acid Nutrition 0.000 claims 6
- 150000001413 amino acids Chemical class 0.000 claims 6
- 230000008512 biological response Effects 0.000 claims 6
- 239000003607 modifier Substances 0.000 claims 6
- 230000027455 binding Effects 0.000 claims 5
- 238000004519 manufacturing process Methods 0.000 claims 5
- 229920001184 polypeptide Polymers 0.000 claims 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims 5
- 208000023275 Autoimmune disease Diseases 0.000 claims 3
- 208000012526 B-cell neoplasm Diseases 0.000 claims 3
- 102000048426 human CD37 Human genes 0.000 claims 3
- 208000011691 Burkitt lymphomas Diseases 0.000 claims 2
- 102000019034 Chemokines Human genes 0.000 claims 2
- 108010012236 Chemokines Proteins 0.000 claims 2
- 102000004127 Cytokines Human genes 0.000 claims 2
- 108090000695 Cytokines Proteins 0.000 claims 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims 2
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 239000003470 adrenal cortex hormone Substances 0.000 claims 2
- 229940100198 alkylating agent Drugs 0.000 claims 2
- 239000002168 alkylating agent Substances 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 229960004630 chlorambucil Drugs 0.000 claims 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims 2
- 229960000390 fludarabine Drugs 0.000 claims 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical group C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims 2
- 239000003102 growth factor Substances 0.000 claims 2
- 229940125721 immunosuppressive agent Drugs 0.000 claims 2
- 239000003018 immunosuppressive agent Substances 0.000 claims 2
- 102000040430 polynucleotide Human genes 0.000 claims 2
- 108091033319 polynucleotide Proteins 0.000 claims 2
- 239000002157 polynucleotide Substances 0.000 claims 2
- 150000003212 purines Chemical class 0.000 claims 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 1
- 206010002412 Angiocentric lymphomas Diseases 0.000 claims 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 1
- 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 claims 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims 1
- 208000023328 Basedow disease Diseases 0.000 claims 1
- 208000023611 Burkitt leukaemia Diseases 0.000 claims 1
- 208000015023 Graves' disease Diseases 0.000 claims 1
- 208000017604 Hodgkin disease Diseases 0.000 claims 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims 1
- 208000028622 Immune thrombocytopenia Diseases 0.000 claims 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 claims 1
- 201000003791 MALT lymphoma Diseases 0.000 claims 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims 1
- 201000002481 Myositis Diseases 0.000 claims 1
- 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 claims 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 1
- 241000721454 Pemphigus Species 0.000 claims 1
- 208000007452 Plasmacytoma Diseases 0.000 claims 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 1
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 claims 1
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 claims 1
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000012829 chemotherapy agent Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000012636 effector Substances 0.000 claims 1
- 201000006569 extramedullary plasmacytoma Diseases 0.000 claims 1
- 201000003444 follicular lymphoma Diseases 0.000 claims 1
- 201000009277 hairy cell leukemia Diseases 0.000 claims 1
- 208000013643 idiopathic inflammatory myopathy Diseases 0.000 claims 1
- 208000026876 intravascular large B-cell lymphoma Diseases 0.000 claims 1
- 210000004698 lymphocyte Anatomy 0.000 claims 1
- 208000006116 lymphomatoid granulomatosis Diseases 0.000 claims 1
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 claims 1
- 201000001268 lymphoproliferative syndrome Diseases 0.000 claims 1
- 230000003211 malignant effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 206010028417 myasthenia gravis Diseases 0.000 claims 1
- 208000025113 myeloid leukemia Diseases 0.000 claims 1
- 210000000653 nervous system Anatomy 0.000 claims 1
- 201000006039 nodal marginal zone lymphoma Diseases 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 150000003230 pyrimidines Chemical class 0.000 claims 1
- 230000003439 radiotherapeutic effect Effects 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 102220080600 rs797046116 Human genes 0.000 claims 1
- 201000006576 solitary osseous plasmacytoma Diseases 0.000 claims 1
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 claims 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
Classifications
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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
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- 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
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- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- 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
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- 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
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- 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
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- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
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- C—CHEMISTRY; METALLURGY
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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
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C—CHEMISTRY; METALLURGY
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- C07K2317/565—Complementarity determining region [CDR]
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- C—CHEMISTRY; METALLURGY
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- C07K2317/567—Framework region [FR]
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- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
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- C07K2317/622—Single chain antibody (scFv)
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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
- C07K2317/72—Increased effector function due to an Fc-modification
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
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Claims (27)
1. Humanizirani CD37-specifični vezni protein obuhvaća:
a. regije iz okvira ljudskog lakog lanca, CDR1 lakog lanca obuhvaća slijed aminokiselina identifikacijskog broja SEQ ID NO:61, CDR2 lakog lanca obuhvaća slijed aminokiselina identifikacijskog broja SEQ ID NO:64 i CDR3 lakog lanca obuhvaća slijed aminokiselina identifikacijskog broja SEQ ID NO:66; i
b. regije iz okvira ljudskog teškog lanca, CDR1 teškog lanca obuhvaća slijed aminokiselina identifikacijskog broja SEQ ID NO:63, CDR2 teškog lanca obuhvaća slijed aminokiselina identifikacijskog broja SEQ ID NO:65 i CDR3 teškog lanca obuhvaća slijed aminokiselina identifikacijskog broja SEQ ID NO:67 ili 68
pri čemu se humanizirani vezni protein natječe s monoklonskim protutijelom G28-1 za vezanje s ljudskim CD37.
2. Humanizirani CD37-specifični vezni protein u skladu s patentnim zahtjevom 1, pri čemu se CDR1, CDR2 i CDR3 lakog lanca sastoje od sljedova aminokiselina SEQ ID NOS: 61, 64 i 66, redom; i
pri čemu se CDR1, CDR2 i CDR3 teškog lanca sastoje od sljedova aminokiselina SEQ ID NOS: 63, 65 i 67, redom.
3. Humanizirani CD37-specifični vezni protein u skladu s patentnim zahtjevom 1, pri čemu se CDR1, CDR2 i CDR3 lakog lanca sastoje od sljedova aminokiselina SEQ ID NOS: 61, 64 i 66, redom; i
pri čemu se CDR1, CDR2 i CDR3 teškog lanca sastoje od sljedova aminokiselina SEQ ID NOS: 63, 65 i 68, redom.
4. Humanizirani CD37-specifični vezni protein u skladu s bilo kojim od prethodnih patentnih zahtjeva, obuhvaća:
regiju iz okvira ljudskog lakog lanca odabranu između SEQ ID NOS: 170-172, 175, 179, 182, 184-188, 191, 194-198, 203 i 205-209; ili
regiju iz okvira ljudskog teškog lanca odabranu između SEQ ID NOS: 140, 141, 143-147, 150, 151, 154-163, 168 i 169.
5. Humanizirani CD37-specifični vezni protein u skladu s bilo kojim od prethodnih patentnih zahtjeva, obuhvaća:
prvu regiju iz okvira ljudskog lakog lanca (FR1) odabranu između SEQ ID NOS: 170-172, 175 i 177-181; FR2 regiju iz okvira ljudskog lakog lanca odabranu između SEQ ID NOS: 182, 184-188 i 191; FR3 regiju iz okvira ljudskog lakog lanca odabranu između SEQ ID NOS: 194-198, 203 i 205; i FR4 regiju iz okvira ljudskog lakog lanca odabranu između SEQ ID NOS: 206-209; ili
prvu regiju iz okvira ljudskog teškog lanca (FR1) odabranu između SEQ ID NOS: 140, 141 i 143-146; FR2 regiju iz okvira ljudskog teškog lanca odabranu između SEQ ID NOS: 147, 150 i 151; FR3 regiju iz okvira ljudskog teškog lanca odabranu između SEQ ID NOS: 154-160; i FR4 regiju iz okvira ljudskog teškog lanca odabranu između SEQ ID NOS: 161-163, 168 i 169.
6. Humanizirani CD37-specifični vezni protein u skladu s bilo kojim od prethodnih patentnih zahtjeva,
pri čemu je vezni protein jednolančani Fv (scFv) polipeptid, protutijelo ili njegov vezni dio, ili protein udružen s imunoglobulinom koji obuhvaća, od amino do karboksilnog kraja, (i) veznu domenu koja ima varijabilne regije lakog i teškog lanca imunoglobulina razdvojene povezujućim peptidom, (ii) polipeptid zglobne regije imunoglobulina ili polipeptid mutirane zglobne regije IgG1 koji ima bilo nula, jedan ili dva cisteinska ostatka, i (iii) CH2 i CH3 domene imunoglobulina.
7. Humanizirani CD37-specifični vezni protein u skladu s patentnim zahtjevom 6, pri čemu polipeptid zglobne regije imunoglobulina može biti polipeptid zglobne regije IgG1, IgA ili IgE ili mutirani IgG1.
8. Humanizirani CD37-specifični vezni protein u skladu s patentnim zahtjevom 6, pri čemu:
vezni protein je udruženi protein imunoglobulina koji obuhvaća varijabilnu regiju lakog lanca pričvršćenu na varijabilnu regiju teškog lanca povezujućim peptidom koji obuhvaća (Gly4Ser)n, gdje je n 1, 2, 3, 4, 5, ili 6 kako je unaprijed postavljeno u SEQ ID NOS: 221, 222, 223, 224, 225, ili 226; i
povezane laka i teška varijabilne regije su spojene na efektorsku domenu IgG1 putem zgloba koji se sastoji od slijeda aminokiselina odabranog iz grupe koja se sastoji od SEQ ID NO: 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 115, 116, 118,120, 122, 124, 126, ili 127.
9. Humanizirani CD37-specifični vezni protein u skladu s patentnim zahtjevom 1, obuhvaća slijed aminokiselina odabran iz grupe koja se sastoji od SEQ ID NO: 48 i 52.
10. Sastav koji obuhvaća vezni protein iz bilo kojeg od prethodnih patentnih zahtjeva i farmaceutski prihvatljiv nosač.
11. Izolirani polinukleotid koji kodira vezni protein iz bilo kojeg od prethodnih patentnih zahtjeva.
12. Vektor koji obuhvaća polinukleotid iz patentnog zahtjeva 11.
13. Stanica domaćin koja koji obuhvaća vektor iz patentnog zahtjeva 12.
14. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u liječenju.
15. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u metodi liječenja neoplazme B-stanica ili autoimune bolesti.
16. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u liječenju neoplazme B-stanica, gdje je neoplazma B-stanica Hodgkinova bolest, non-Hodgkinov linfom, limfom središnjeg živčanog sustava, akutna limfoblastična leukemija, kronična limfocitna leukemija, leukemija vlasastih stanica, kronična mijeloblastična leukemija, multipli mijelom, limfom malih limfocita, B-stanična prolimfocitna leukemija, limfoplazmacitni limfom, limfom marginalne zone slezene, plazmastanični mijelom, solitarni plazmacitom kostiju, ekstramedularni plazmacitom, B-stanični ekstranodalni limfom marginalne zone limfoidnog tkiva povezanog s mukozom, B-stanični nodalni limfom marginalne zone, folikularni limfom, limfom plaštenih stanica, difuzni limfom velikih B-stanica, medijastinalni (timusni) limfom velikih B-stanica, intravaskularni limfom velikih B-stanica, primarni limfom izljeva, Burkittov limfom/leukemija, B-stanična proliferacija neutvrđenog malignog potencijala, limfomatoidna granulomatoze, ili posttransplantacijski limfoproliferativni poremećaj.
17. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u liječenju autoimune bolesti, pri čemu je autoimuna bolest reumatoidni artritis, multipla skleroza, sustavni eritemski lupus, Chronova bolest, Sjogrenov sindrom, Gravesova bolest, šećerna bolest tipa I, psorijaza, imuna trombocitopenična purpura, pemfigus, idiopatska upalna miopatija, miastenija gravis, ili Waldenstromova makroglobulinemija.
18. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u bilo kojem od patentnih zahtjeva 14-17, karakteriziranu na način da se humanizirani CD37-specifični vezni protein koristi u kombinaciji s drugim agensom.
19. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u patentnom zahtjevu 18, pri čemu je drugi agens kemoterapijski agens, modifikator biološkog odgovora, specifično protutijelo na ljudski CD37 ili njegov dio koji se veže za CD37, citokin, kemokin, čimbenik rasta, radioterapijski agens, adrenokortikosteroid/agonist ili imunosupresijski agens.
20. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u patentnom zahtjevu 19, pri čemu je drugi agens kemoterapijski agens, i pri čemu je kemoterapijski agens alkilirajući agens, analog pirimidina, ili analog purina.
21. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u patentnom zahtjevu 19, pri čemu je drugi agens kemoterapijski agens, i pri čemu je kemoterapijski agens fludarabin ili klorambucil.
22. Humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1 do 8, ili sastav iz patentnog zahtjeva 10, za uporabu u patentnom zahtjevu 19, pri čemu je drugi agens modifikator biološkog odgovora, pri čemu je modifikator biološkog odgovora G-CSF ili GM-CSF.
23. Proizvodni artikl obuhvaća humanizirani CD37-specifični vezni protein iz bilo kojeg od patentnih zahtjeva 1-8 i drugi agens.
24. Proizvodni artikl iz patentnog zahtjeva 23, pri čemu je drugi agens CD20-specifični vezni protein ljudskog imunoglobulina, kemoterapijski agens, modifikator biološkog odgovora, specifično protutijelo na ljudski CD37 ili njegov vezni dio, citokin, kemokin, čimbenik rasta, radioterapijski agens, adrenokortikosteroid/antagonist, ili imunosupresijski agens.
25. Proizvodni artikl iz patentnog zahtjeva 24, pri čemu je drugi agens kemoterapijski agens, i gdje je kemoterapijski agens aliklirajući agens, analog pirimidina, ili analog purina.
26. Proizvodni artikl iz patentnog zahtjeva 24, pri čemu je drugi agens kemoterapijski agens, i gdje je kemoterapijski agens fludarabin ili klorambucil.
27. Proizvodni artikl iz patentnog zahtjeva 24, pri čemu je drugi agens modifikator biološkog odgovora, gdje je modifikator biološkog odgovora G-CSF ili GM-CSF.
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