HRP20211582T1 - Protutijela specifična za tgf-beta - Google Patents
Protutijela specifična za tgf-beta Download PDFInfo
- Publication number
- HRP20211582T1 HRP20211582T1 HRP20211582TT HRP20211582T HRP20211582T1 HR P20211582 T1 HRP20211582 T1 HR P20211582T1 HR P20211582T T HRP20211582T T HR P20211582TT HR P20211582 T HRP20211582 T HR P20211582T HR P20211582 T1 HRP20211582 T1 HR P20211582T1
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- Croatia
- Prior art keywords
- antibody
- cancer
- light chain
- heavy chain
- nucleic acid
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- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 title claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 13
- 102000039446 nucleic acids Human genes 0.000 claims 13
- 108020004707 nucleic acids Proteins 0.000 claims 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims 11
- 206010028980 Neoplasm Diseases 0.000 claims 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims 9
- 239000002773 nucleotide Substances 0.000 claims 6
- 125000003729 nucleotide group Chemical group 0.000 claims 6
- 210000004027 cell Anatomy 0.000 claims 5
- 201000011510 cancer Diseases 0.000 claims 4
- 150000001413 amino acids Chemical class 0.000 claims 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims 3
- 210000004443 dendritic cell Anatomy 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 claims 3
- 206010016654 Fibrosis Diseases 0.000 claims 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 230000004761 fibrosis Effects 0.000 claims 2
- 210000003289 regulatory T cell Anatomy 0.000 claims 2
- 239000013598 vector Substances 0.000 claims 2
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 208000032612 Glial tumor Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000001461 cytolytic effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 230000003176 fibrotic effect Effects 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 230000016784 immunoglobulin production Effects 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 238000012004 kinetic exclusion assay Methods 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 210000000822 natural killer cell Anatomy 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims 1
- 230000003614 tolerogenic effect Effects 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
Classifications
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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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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- C07K2317/55—Fab or Fab'
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- C07K2317/565—Complementarity determining region [CDR]
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- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Hospice & Palliative Care (AREA)
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- Urology & Nephrology (AREA)
- Gynecology & Obstetrics (AREA)
- Pulmonology (AREA)
Claims (21)
1. Protutijelo koje se veže na transformirajući faktor rasta beta (TGFβ)1, TGFβ2 i TGFβ3, naznačeno time, da sadrži:
(a) CDR1 teškog lanca kako je prikazano aminokiselinskim slijedom SEQ ID NO: 19;
(b) CDR2 teškog lanca kako je prikazano aminokiselinskim slijedom SEQ ID NO: 20; i
(c) CDR3 teškog lanca kako je prikazano aminokiselinskim slijedom SEQ ID NO: 21;
(d) CDR1 lakog lanca kako je prikazano aminokiselinskim slijedom SEQ ID NO: 22;
(e) CDR2 lakog lanca kako je prikazano aminokiselinskim slijedom SEQ ID NO: 23; i
(f) CDR3 lakog lanca kako je prikazano aminokiselinskim slijedom SEQ ID NO: 24;
pri čemu se protutijelo veže na TGFβ1 i TGFβ2 s većim afinitetom nego na TGFβ3 i veže se na TGFβ1 i TGFβ2 s afinitetom Kd od 10-9 M ili manje prema mjerenju putem površinske plazmonske rezonancije ili kinetičkog ispitivanja ekskluzije.
2. Protutijelo prema bilo kojem od prethodnih patentnih zahtjeva, naznačeno time, da nadalje sadrži konstantnu regiju teškog lanca, pri čemu je konstantna regija teškog lanca modificirani ili nemodificirani IgG, IgM, IgA, IgD, IgE, njihov fragment, ili njihove kombinacije.
3. Protutijelo prema bilo kojem od prethodnih patentnih zahtjeva, naznačeno time, da se u njemu jedan ili više okvirnih aminokiselina lakog lanca nadomještava s odgovarajućom aminokiselinom ili odgovarajućim aminokiselinama iz nekog drugog aminokiselinskog slijeda ljudskog protutijela.
4. Protutijelo prema bilo kojem od prethodnih patentnih zahtjeva, naznačeno time, da protutijelo posjeduje varijabilnu regiju teškog lanca kako je prikazano aminokiselinskim slijedom SEQ ID NO: 6 i varijabilnu regiju lakog lanca kako je prikazano aminokiselinskim slijedom SEQ ID NO: 8.
5. Protutijelo prema bilo kojem od prethodnih patentnih zahtjeva, naznačeno time, da nadalje sadrži ljudsku konstantnu regiju lakog lanca vezanu sa spomenutom varijabilnom regijom lakog lanca.
6. Protutijelo prema bilo kojem od prethodnih patentnih zahtjeva, naznačeno time, da protutijelo neutralizira djelovanje TGFβ1 i TGFβ2 u većoj mjeri nego isto od TGFβ3.
7. Izolirana molekula nukleinske kiseline, naznačena time, da sadrži nukleotidni slijed koji kodira teški lanac i nukleotidni slijed koji kodira laki lanac protutijela, pri čemu ista molekula nukleinske kiseline kodira teški lanac i laki lanac; ili time, da izolirana molekula nukleinske kiseline sadrži nukleotidni slijed koji kodira teški lanac i nukleotidni slijed koji kodira laki lanac protutijela, pri čemu različite molekule nukleinske kiseline kodiraju teški lanac i laki lanac;
pri čemu je protutijelo u skladu s bilo kojim od prethodnih patentnih zahtjeva.
8. Ekspresijski vektor ili ekspresijski vektori, naznačen/i time, da sadrže molekulu nukleinske kiseline ili molekule nukleinske kiseline prema patentnom zahtjevu 7, pri čemu je svaki od nukleotidnog slijeda koji kodira teški lanac i nukleotidnog slijeda koji kodira laki lanac, odvojivo vezan na slijed za kontrolu ekspresije.
9. Stanica domaćina, naznačena time, da sadrži vektor ili vektore prema patentnom zahtjevu 8, ili molekulu nukleinske kiseline ili molekule nukleinske kiseline prema patentnom zahtjevu 7.
10. Stanica domaćina prema patentnom zahtjevu 9, naznačena time, da sadrži molekulu nukleinske kiseline ili molekule nukleinske kiseline koja/koje kodira/kodiraju varijabilnu regiju lakog lanca, pri čemu se nukleinske kiseline teškog lanca i lakog lanca eksprimiraju pomoću različitih nukleinskih kiselina ili na istoj nukleinskoj kiselini.
11. Postupak uporabe stanice domaćina prema patentnom zahtjevu 9 ili 10 u svrhu proizvodnje protutijela, naznačen time, da obuhvaća kultiviranje stanice domaćina prema patentnom zahtjevu 9 ili 10 pod prikladnim uvjetima i dobivanje navedenog protutijela.
12. Sterilni farmaceutski pripravak, naznačen time, da sadrži protutijelo prema bilo kojem od patentnih zahtjeva 1 do 6, i farmaceutski prihvatljiv nosač.
13. Protutijelo prema bilo kojem od patentnih zahtjeva 1 do 6 ili farmaceutski pripravak prema patentnom zahtjevu 12, naznačeni time, da su za uporabu u postupku liječenja raka ili fibroze, pri čemu postupak obuhvaća korak davanja terapijski učinkovite količine protutijela ili farmaceutskog pripravka pojedincu kojemu je to potrebno.
14. Protutijelo prema bilo kojem od patentnih zahtjeva 1 do 6 ili farmaceutski pripravak prema patentnom zahtjevu 12, naznačeni time, da su za uporabu u postupku liječenja raka kod pojedinca kojemu je to potrebno.
15. Protutijelo ili farmaceutski pripravak za uporabu prema patentnom zahtjevu 14, naznačeni time, da protutijelo ili pripravak povećavaju broj prirodnih stanica ubojica (NK - engl. natural killer) u tumoru i/ili poboljšavaju citolitičko djelovanje NK stanice.
16. Protutijelo ili farmaceutski pripravak za uporabu prema patentnom zahtjevu 14, naznačeni time, da protutijelo ili pripravak smanjuju broj regulatornih T stanica u tumoru i/ili inhibiraju djelovanje regulatorne T stanice.
17. Protutijelo ili farmaceutski pripravak za uporabu prema patentnom zahtjevu 14, naznačeni time, da protutijelo ili pripravak povećavaju broj citotoksičnih T stanica (CTL) u tumoru i/ili pospješuju djelovanje CTL.
18. Protutijelo ili farmaceutski pripravak za uporabu prema patentnom zahtjevu 14, naznačeni time, da protutijelo smanjuje broj mijeloično izvedenih supresorskih stanica (MDSC) u tumoru i/ili inhibira djelovanje MDSC.
19. Protutijelo ili farmaceutski pripravak za uporabu prema patentnom zahtjevu 14, naznačeni time, da protutijelo smanjuje broj dendritičkih stanica (DC) u tumoru i/ili inhibira tolerogensko djelovanje dendritičkih stanica.
20. Protutijelo ili farmaceutski pripravak za uporabu prema bilo kojem od patentnih zahtjeva 14 do 19, naznačeni time, da se rak bira iz skupine koju čine rak pluća, rak prostate, rak dojke, hepatocelularni rak, rak jednjaka, kolorektalni rak, rak gušterače, rak mokraćnog mjehura, rak bubrega, rak jajnika, rak želuca, fibrotički rak, gliom i melanom.
21. Protutijelo prema bilo kojem od patentnih zahtjeva 1 do 6 ili farmaceutski pripravak prema patentnom zahtjevu 12, naznačeni time, da su za uporabu u postupku liječenja fibroze kod pojedinca kojemu je to potrebno.
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