HRP20170016T1 - Neutralizirajuća antitijela prolaktin receptora i njihova terapeutska uporaba - Google Patents
Neutralizirajuća antitijela prolaktin receptora i njihova terapeutska uporaba Download PDFInfo
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- HRP20170016T1 HRP20170016T1 HRP20170016TT HRP20170016T HRP20170016T1 HR P20170016 T1 HRP20170016 T1 HR P20170016T1 HR P20170016T T HRP20170016T T HR P20170016TT HR P20170016 T HRP20170016 T HR P20170016T HR P20170016 T1 HRP20170016 T1 HR P20170016T1
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- 102100029000 Prolactin receptor Human genes 0.000 title claims 7
- 108010002519 Prolactin Receptors Proteins 0.000 title claims 4
- 230000003472 neutralizing effect Effects 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000007523 nucleic acids Chemical group 0.000 claims 96
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 86
- 239000000427 antigen Substances 0.000 claims 15
- 108091007433 antigens Proteins 0.000 claims 15
- 102000036639 antigens Human genes 0.000 claims 15
- 239000012634 fragment Substances 0.000 claims 14
- 108020004707 nucleic acids Proteins 0.000 claims 10
- 102000039446 nucleic acids Human genes 0.000 claims 10
- 210000004027 cell Anatomy 0.000 claims 7
- 239000003814 drug Substances 0.000 claims 7
- 101001123448 Homo sapiens Prolactin receptor Proteins 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 208000005641 Adenomyosis Diseases 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 201000009274 endometriosis of uterus Diseases 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 238000007911 parenteral administration Methods 0.000 claims 2
- 201000004384 Alopecia Diseases 0.000 claims 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims 1
- 206010006298 Breast pain Diseases 0.000 claims 1
- 201000009273 Endometriosis Diseases 0.000 claims 1
- 208000006662 Mastodynia Diseases 0.000 claims 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 208000011803 breast fibrocystic disease Diseases 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000013604 expression vector Substances 0.000 claims 1
- 208000024963 hair loss Diseases 0.000 claims 1
- 230000003676 hair loss Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 238000001361 intraarterial administration Methods 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 238000007914 intraventricular administration Methods 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 230000006651 lactation Effects 0.000 claims 1
- 210000004962 mammalian cell Anatomy 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 210000001236 prokaryotic cell Anatomy 0.000 claims 1
- 230000011664 signaling Effects 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 239000013598 vector Substances 0.000 claims 1
- 210000005253 yeast cell Anatomy 0.000 claims 1
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Claims (19)
1. Antitijelo 006-H08 ili njegove definirane sazrjele varijante u skladu s tablicom 5 ili njegovi fragmenti koji vežu antigen koji antagonizira signalizaciju posredovanu s prolaktinskim receptorom i koje se veže na epitope izvanstanične domene receptora prolaktina i njihove ljudske polimorfne varijante, naznačeno time da sekvenca amino kiseline izvanstanične domene prolaktin receptora odgovara SEQ ID NO: 70, te sekvenca nukleinske kiseline odgovara SEQ ID NO: 71, pri čemu SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 18 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 29 odgovara LCDR3, ili pri čemu
a. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 74 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ IDNO: 78 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 90 odgovara LCDR3; ili
b. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 75 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 82 varijabilnog lakog lanca odgovara LCDR 1. SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 91 odgovara LCDR3; ili
c. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ IDNO: 13 odgovara HCDR3, i SEQ ID NO: 82 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 29 odgovara LCDR3; ili
d. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ IDNO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 86 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 29 odgovara LCDR3; ili
e. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 74 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 87 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 100 odgovara LCDR3; ili
f. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 74 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 87 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 92 odgovara LCDR3; ili
g. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 74 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 89 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 93 odgovara LCDR3; ili
h. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 74 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 79 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 101 odgovara LCDR3, ili
i. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 76 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 89 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 90 odgovara LCDR3; ili
j. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 18 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 100 odgovara LCDR3: ili
k. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 18 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 97 odgovara LCDR3; ili
1. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 18 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 98 odgovara LCDR3; ili
m. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 74 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 83 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 99 odgovara LCDR3; ili
n. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 18 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 96 odgovara LCDR3; ili
o. SEQ IDNO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ IDNO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 18 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 94 odgovara LCDR3; ili
p. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 74 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 88 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 90 odgovara LCDR3; ili
q. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 74 odgovara HCDR2, SEQ IDNO: 13 odgovara HCDR3, i SEQ IDNO: 81 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 95 odgovara LCDR3; ili
r. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 75 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 18 varijabilnog lakog lanca odgovara LCDR 1. SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 29 odgovara LCDR3; ili
s. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 77 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 18 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 29 odgovara LCDR3; ili
t. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 80 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 29 odgovara LCDR3; ili
u. SEQ ID NO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ IDNO: 85 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i
SEQ ID NO: 29 odgovara LCDR3 9; ili
v. SEQIDNO: 1 varijabilnog teškog lanca odgovara HCDR1, SEQ ID NO: 7 odgovara HCDR2, SEQ ID NO: 13 odgovara HCDR3, i SEQ ID NO: 84 varijabilnog lakog lanca odgovara LCDR 1, SEQ ID NO: 24 odgovara LCDR2 i SEQ ID NO: 29 odgovara LCDR3.
2. Antitijelo ili fragment koji veže antigen prema zahtjevu 1, naznačeno time da antitijelo
a. 006-H08 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 46, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 34, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 52, te sekvencu nukleinske kiseline u skladusaSEQ ID NO:40,
b. 006-H08-12-2 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 331, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 143, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 353, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 165,
c. 006-H08-13-2 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 332,,i sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 144, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 354, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 166.
d. 006-H08-13-6-1 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 333, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 145, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 355, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 167,
e. 006-H08-14-6-0 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 334, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 146, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 356, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 168,
f. 006-H08-15-5 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 335. te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 147, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 357, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 169,
g. 006-H08-19-1 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 336, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 148, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 358, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 170,
h. 006-H08-29-1 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 337, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 149, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 359, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 171,
i. 006-H08-32-2 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 338, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 150, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 360, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 172,
j. 006-H08-33-0 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 339, te sekvencu nukleinske kiseline u skladu sa SEQ IDNO: 151, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 361, te sekvencu nukleinske kiseline u skladu sa SEQ IDNO: 173,
k. 006-H08-33-16-0 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 340, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 152, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 362. te sekvencu nukleinske kiseline u skladu sa SEQ IDNO: 174,
1. 006-H08-35-17-1 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 341, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 153, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 363. te sekvencu nukleinske kiseline u skladu sa SEQ IDNO: 175,
m. 006-H08-35-17-4 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 342, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 154, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 364, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 176,
n. 006-H08-35-1 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 343, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 155, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 365, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 177,
o. 006-H08-36-17-0 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 344, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 156, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 366, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 178,
p. 006-H08-37-19-0 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 345, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 157, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 367, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 179,
q. 006-H08-39-7 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 346, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 158, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 368, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 180,
r. 006-H08-48-5 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 347, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 159. i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 369, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 181,
s. 006-H08-53-27-0 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 348, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 160, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 370, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 182,
t. 006-H08-59-30-0 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 349, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 161, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 371, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 183,
u. 006-H08-63-32-4 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 350, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 162, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 372, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 184,
v. 006-H08-65-33-2 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 351, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 163, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 373, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 185,
w. 006-H08-68-35-2 sadrži promjenjivu domenu teškog lanca koja odgovara sekvenci nukleinske kiseline u skladu sa SEQ ID NO: 352, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 164, i promjenjivu domenu lakog lanca sa sekvencom nukleinske kiseline u skladu sa SEQ ID NO: 374, te sekvencu nukleinske kiseline u skladu sa SEQ ID NO: 186.
3. Antitijelo prema zahtjevu 1 do 2, naznačeno time da se antitijelo sastoji od regije koja veže antigen koja se specifično veže na ili ima visoki afinitet za jednu ili više regija od PRLR, čija je sekvenca amino kiseline prikazana sa SEQ ID NO: 70 i ljudskim polimorfnim varijantama iz SEQ ID NO: 70, položajem amino kiseline 1 do 210, pri čemu je afinitet barem 100 nM, poželjnije s afinitetom od manje od oko 100 nM, poželjnije s afinitetom od manje od oko 30 nM, čak još poželjnije s afinitetom od manje od oko 10 nM, ili čak još poželjnije s afinitetom od manje od 1 nM.
4. Antitijelo prema zahtjevu 1 do 3 naznačeno time da teški konstantni lanac je modificirani ili nemodificirani IgG1, IgG2, IgG3 ili IgG4.
5. Izolirana sekvenca nukleinske kiseline naznačena time da kodira antitijelo ili fragment koji veže antigen prema bilo kojem od zahtjeva 1 do 4.
6. Ekspresijski vektor naznačen time da sadrži sekvencu nukleinske kiseline prema zahtjevu 5.
7. Stanica domaćin naznačena time da sadrži vektor prema zahtjevu 6 ili molekulu nukleinske kiseline prema zahtjevu 5, pri čemu stanica domaćin može biti viša eukariotska stanica domaćin, kao što je stanica sisavca, niža eukariotska stanica domaćin, kao što je stanica kvasca, te može biti prokariotska stanica, kao što je bakterijska stanica.
8. Postupak korištenja stanice domaćina prema zahtjevu 7 za proizvodnju antitijela ili fragmenta koji veže antigen, naznačen time da sadrži kultiviranje stanice domaćina prema zahtjevu 7 pod pogodnim uvjetima i izdvajanje navedenog antitijela.
9. Antitijelo ili fragment koji veže antigen prema bilo kojem od zahtjeva 1 do 4 naznačeno time da se pročišćava do barem 95% homogenosti po težini.
10. Uporaba antitijela ili fragmenta koji veže antigen prema bilo kojem od zahtjeva 1 do 4 naznačena time da je za uporabu kao lijek.
11. Farmaceutski pripravak naznačen time da sadrži antitijelo ili fragment koji veže antigen prema bilo kojem od zahtjeva 1 do 4 i farmaceutski prihvatljiv nosač koji sadrži pomoćna sredstva i pomoćne tvari.
12. Kompleti naznačeni time da sadrže antitijelo prema bilo kojem od zahtjeva 1 do 4 koji sadrže terapeutski učinkovitu količinu antitijela 006-H08 ili njegove zrele varijante, pakirano u spremnik, te navedeni komplet proizvoljno sadrži drugo terapeutsko sredstvo.
13. Antitijelo ili fragment koji veže antigen prema bilo kojem od zahtjeva 1 do 4 naznačeno time da je za uporabu kao lijek za liječenje i/ili prevenciju endometrioze i adenomioze (endometriosis interna).
14. Antitijelo ili fragment koji veže antigen prema bilo kojem od zahtjeva 1 do 4 naznačeno time da je za uporabu kao lijek za liječenje benigne bolesti dojke i mastalgije.
15. Antitijelo ili fragment koji veže antigen prema bilo kojem od zahtjeva 1 do 4 naznačeno time da je za uporabu kao lijek za inhibiciju laktacije.
16. Antitijelo ili fragment koji veže antigen prema bilo kojem od zahtjeva 1 do 4 naznačeno time da je za uporabu kao lijek za liječenje benigne hiperplazije prostate.
17. Antitijelo ili fragment koji veže antigen prema bilo kojem od zahtjeva 1 do 4 naznačeno time da je za uporabu kao lijek za liječenje od hiper i normoprolaktinemijskog gubitka kose.
18. Uporaba antitijela prema bilo kojem od zahtjeva 1 do 4 ili u obliku farmaceutskog pripravka u skladu sa zahtjevom 11 naznačena time da sadrži PRLR antitijela ili fragment koji veže antigene prema bilo kojem od zahtjeva 1 do 4 naznačen time daje za pripremu farmaceutske formulacije za parenteralnu primjenu, pri čemu postupci parenteralne primjene uključuju lokalnu, intraarterijsku, intramuskularnu, potkožnu, intramedularnu, intratekalnu, intraventrikularnu, intravenoznu, intraperitonealnu, intrauterinu, vaginalnu, ili intranazalnu primjenu.
19. Farmaceutski pripravak prema zahtjevu 11 naznačen time da sadrži PRLR antitijela ili fragment koji veže antigene prema bilo kojem od zahtjeva 1 do 4, u kombinaciji s barem jednim drugim sredstvom.
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| Application Number | Priority Date | Filing Date | Title |
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| EP09075546A EP2332995A1 (en) | 2009-12-10 | 2009-12-10 | Neutralizing prolactin receptor antibodies and their therapeutic use |
| EP10782255.3A EP2510006B1 (en) | 2009-12-10 | 2010-11-18 | Neutralizing prolactin receptor antibodies and their therapeutic use |
| PCT/EP2010/067742 WO2011069795A1 (en) | 2009-12-10 | 2010-11-18 | Neutralizing prolactin receptor antibodies and their therapeutic use |
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| HRP20161401TT HRP20161401T1 (hr) | 2009-12-10 | 2016-10-26 | Neutralizirajuća antitijela prolaktin receptora i njihova terapeutska uporaba |
| HRP20170016TT HRP20170016T1 (hr) | 2009-12-10 | 2017-01-05 | Neutralizirajuća antitijela prolaktin receptora i njihova terapeutska uporaba |
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| US7422899B2 (en) | 2005-10-05 | 2008-09-09 | Biogen Idec Ma Inc. | Antibodies to the human prolactin receptor |
| EA201201533A1 (ru) | 2006-08-18 | 2014-11-28 | Новартис Аг | Prlr-специфическое антитело и его применения |
| EP2167101A2 (en) | 2007-05-30 | 2010-03-31 | Auckland Uniservices Limited | Antibodies and sirna against growth hormone, prolactin and proliferin for use in the treatment of tumors and endometriosis |
| EP2025683A1 (en) * | 2007-08-13 | 2009-02-18 | INSERM (Institut National de la Santé et de la Recherche Medicale) | Variants of prolactin as antagonists of its receptor |
| EP2332995A1 (en) * | 2009-12-10 | 2011-06-15 | Bayer Schering Pharma Aktiengesellschaft | Neutralizing prolactin receptor antibodies and their therapeutic use |
| WO2011139375A1 (en) * | 2010-05-06 | 2011-11-10 | Ludwig Institute For Cancer Research Ltd | Antibodies directed against carbonic anhydrase ix and methods and uses thereof |
| GB201020995D0 (en) * | 2010-12-10 | 2011-01-26 | Bioinvent Int Ab | Biological materials and uses thereof |
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