HRP20191010T1 - Protutijelo protiv adrenomedulina (adm) ili fragment protutijela protiv adm ili ne-ig okosnica protutijela protiv adm, namijenjeno sprječavanju ili smanjivanju disfunkcije organa ili insuficijencije organa kod pacijenta s kroničnom ili akutnom bolešću ili akutnim stanjem - Google Patents
Protutijelo protiv adrenomedulina (adm) ili fragment protutijela protiv adm ili ne-ig okosnica protutijela protiv adm, namijenjeno sprječavanju ili smanjivanju disfunkcije organa ili insuficijencije organa kod pacijenta s kroničnom ili akutnom bolešću ili akutnim stanjem Download PDFInfo
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- HRP20191010T1 HRP20191010T1 HRP20191010TT HRP20191010T HRP20191010T1 HR P20191010 T1 HRP20191010 T1 HR P20191010T1 HR P20191010T T HRP20191010T T HR P20191010TT HR P20191010 T HRP20191010 T HR P20191010T HR P20191010 T1 HRP20191010 T1 HR P20191010T1
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- Prior art keywords
- adm
- adrenomedullin
- acute
- antibody against
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- 208000030090 Acute Disease Diseases 0.000 title claims 38
- 230000001154 acute effect Effects 0.000 title claims 38
- 208000017667 Chronic Disease Diseases 0.000 title claims 22
- 230000001684 chronic effect Effects 0.000 title claims 21
- 230000004768 organ dysfunction Effects 0.000 title claims 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 title claims 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 title claims 3
- 206010053159 Organ failure Diseases 0.000 title claims 2
- 230000002265 prevention Effects 0.000 title 1
- 102000004379 Adrenomedullin Human genes 0.000 claims 95
- 101800004616 Adrenomedullin Proteins 0.000 claims 95
- ULCUCJFASIJEOE-NPECTJMMSA-N adrenomedullin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H]1C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)[C@@H](C)O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 ULCUCJFASIJEOE-NPECTJMMSA-N 0.000 claims 95
- 239000012634 fragment Substances 0.000 claims 27
- 238000002560 therapeutic procedure Methods 0.000 claims 17
- 239000008194 pharmaceutical composition Substances 0.000 claims 15
- 206010040047 Sepsis Diseases 0.000 claims 3
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims 3
- 210000000056 organ Anatomy 0.000 claims 3
- 102100021243 G-protein coupled receptor 182 Human genes 0.000 claims 2
- 206010019280 Heart failures Diseases 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 206010040070 Septic Shock Diseases 0.000 claims 2
- 108010063640 adrenomedullin receptors Proteins 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 238000011990 functional testing Methods 0.000 claims 2
- 238000001802 infusion Methods 0.000 claims 2
- 230000036303 septic shock Effects 0.000 claims 2
- 210000002966 serum Anatomy 0.000 claims 2
- 230000035939 shock Effects 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 102000016550 Complement Factor H Human genes 0.000 claims 1
- 108010053085 Complement Factor H Proteins 0.000 claims 1
- 101000690940 Homo sapiens Pro-adrenomedullin Proteins 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 210000004204 blood vessel Anatomy 0.000 claims 1
- 150000003943 catecholamines Chemical class 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 210000002216 heart Anatomy 0.000 claims 1
- 102000046663 human ADM Human genes 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 208000019423 liver disease Diseases 0.000 claims 1
- 230000005976 liver dysfunction Effects 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 210000000496 pancreas Anatomy 0.000 claims 1
- 231100000572 poisoning Toxicity 0.000 claims 1
- 230000000607 poisoning effect Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 210000000813 small intestine Anatomy 0.000 claims 1
- 210000000952 spleen Anatomy 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- 230000008733 trauma Effects 0.000 claims 1
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- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
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Claims (22)
1. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin, namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja radi sprječavanja ili smanjivanja disfunkcije organa ili sprječavanja insuficijencije organa kod navedenog pacijenta, naznačeni time što se navedeno protutijelo ili protutijelo fragment ili ne-Ig okosnica veže na područje od najmanje 4 aminokiselina u slijedu od aa 1-21 zrelog ljudskog ADM: YRQSMNNFQGLRSFGCRFGTC (SEQ ID NO: 23),
što se navedeni organ bira iz skupine koju čine srce, bubreg, jetra, pluća, gušterača, tanko crijevo i slezena,
te što se navedena kronična ili akutna bolest odnosno akutno stanje bira iz skupine koju čine teške infekcije, sindrom sistemnog upalnog odgovora (SIRS), sepsa, dijabetes, rak, akutne i kronične bolesti krvnih žila, poput primjerice srčane insuficijencije, infarkta miokarda, inzulta, ateroskleroze, šoka, poput primjerice septičnog šoka, i disfunkcija organa, disfunkcija jetre, opekline, kirurški zahvat, traume, otrovanje, oštećenja uzrokovana kemoterapijom.
2. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s patentnim zahtjevom 1, naznačeni time što su navedeno protutijelo ili protutijelo fragment ili ne-Ig okosnica monospecifični.
3. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, naznačeni time što navedeno protutijelo ili fragment ili okosnica pokazuje afinitet vezanja na ADM od najmanje 10–7 M, naznačeni time što se navedeni afinitet vezanja određuje kao u Primjeru 1.
4. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačeni time što navedeno protutijelo ili fragment ili okosnica nije ADM-vežući-Protein-1, komplementni čimbenik H.
5. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačeni time što navedeno protutijelo ili fragment ili okosnica prepoznaje i veže se na N-terminalni kraj, aa 1, zrelog adrenomedulina.
6. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačeni time što su navedeno protutijelo ili navedeni fragment ili navedena okosnica protutijelo ili fragment ili okosnica koje stabiliziraju ADM te mu produljuju poluvijek, t1/2 poluretencijsko vrijeme, adrenomedulina u serumu, krvi, plazmi najmanje 10%, po mogućnosti najmanje 50%, poželjnije > 50%, najpoželjnije > 100%.
7. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačeni time što navedeno protutijelo ili fragment ili okosnica blokira bioaktivnost ADM najviše 80%, po mogućnosti najviše 50%, prilikom određivanja bioaktivnosti ADM u funkcionalnom ispitivanju na cAMP na ljudskom rekombinantnom adrenomedulinskom receptoru kao u Primjeru 2.
8. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačeni time što navedeni pacijent boluje od bolesti koju se bira iz skupine koju čine sepsa, dijabetes, rak, srčana insuficijencija, te šok.
9. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačeni time što navedena bolest nije SIRS, sepsa ili septični šok.
10. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 9, naznačeni time što je navedeno protutijelo ili fragment ljudsko monoklonsko protutijelo ili fragment koji se veže na ADM ili njegov fragment gdje teški lanac sadrži slijed kojeg se bira iz skupine koju čine:
SEQ ID NO: 1
GYTFSRYW
SEQ ID NO: 2
ILPGSGST
SEQ ID NO: 3
TEGYEYDGFDY
te gdje laki lanac sadrži sljedove
SEQ ID NO: 4
QSIVISNGNTY
SEQ ID NO: 5
RVS
SEQ ID NO: 6
FQGSHIPYT.
11. Ljudsko monospecifično protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s patentnim zahtjevom 10, naznačeni time što navedeno protutijelo ili fragment sadrži slijed kojeg se bira iz skupine koju čine:
SEQ ID NO: 7 (AM-VH-C)
QVQLQQSGAELMKPGASVKISCKATGYTFSRYWIEWVKQRPGHGLEWIGEILP
GSGSTNYNEKFKGKATITADTSSNTAYMQLSSLTSEDSAVYYCTEGYEYDGFD
YWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLISLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR
VEPKHHHHHH
SEQ ID NO: 8 (AM-VH1)
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSRYWISWVRQAPGQGLEWMGRIL
PGSGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTEGYEYDGFD
YWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLISLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR
VEPKHHHHHH
SEQ ID NO: 9 (AM-VH2-E40)
QVQLVQSGAEVKKPGSSVKVSCKASGYTFSRYWIEWVRQAPGQGLEWMGRIL
PGSGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTEGYEYDGFD
YWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLISLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR
VEPKHHHHHH
SEQ ID NO: 10 (AM-VH3-T26-E55)
QVQLVQSGAEVKKPGSSVKVSCKATGYTFSRYWISWVRQAPGQGLEWMGEIL
PGSGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTEGYEYDGFD
YWGQGTTVTVSSASTKGPSVFPLAPSSK8TSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLISLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR
VEPKHHHHHH
SEQ ID NO: 11 (AM-VH4-T26-E40-E55)
QVQLVQSGAEVKKPGSSVKVSCKATGYTFSRYWIEWVRQAPGQGLEWMGEIL
PGSGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCTEGYEYDGFD
YWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN
SGALTSGVHTFPAVLQSSGLISLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKR
VEPKHHHHHH
SEQ ID NO: 12 (AM-VL-C)
DVLLSQTPLSLPVSLGDQATISCRSSQSIVISNGNTYLEWYLQKPGQSPKLLIYR
VSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHIPYTFGGGTKLE
IKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS
QESVTEQDSKDSTISLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGE
C
SEQ ID NO: 13 (AM-VL1)
DVVMTQSPLSLPVTLGQPASISCRSSQSIVISNGNTYLNWFQQRPGQSPRRLIYR
VSNRDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHIPYTFGQGTKL
EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN
SQESVTEQDSKDSTISLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG
EC
SEQ ID NO: 14 (AM-VL2-E40)
DVVMTQSPLSLPVTLGQPASISCRSSQSIVISNGNTYLEWFQQRPGQSPRRLIYRVSNRD
SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHIPYTFGQGTKLEIKRTVAAPSV
FIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTIS
LSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC.
12. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačeni time što je navedeno protutijelo ili fragment ili okosnica modulirajuće protutijelo ili fragment ili okosnica koji produljuju poluvijek, t1/2 poluretencijsko vrijeme, adrenomedulina u serumu, krvi, plazmi najmanje 10%, po mogućnosti najmanje 50%, poželjnije > 50%, najpoželjnije > 100%, te što blokiraju Bioaktivnost ADM najviše 80%, po mogućnosti najviše 50%, prilikom određivanja bioaktivnosti ADM u funkcionalnom ispitivanju na cAMP na ljudskom rekombinantnom adrenomedulinskom receptoru kao u Primjeru 2.
13. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 12, naznačeni time što ih treba upotrijebiti u kombinaciji s vazopresorima, primjerice s katekolaminom i/ili s tekućinama koje se primijenjuje intravenski.
14. Protutijelo protiv adrenomedulina (ADM) ili fragment protutijela protiv ADM koje se veže na adrenomedulin ili ne-Ig okosnica protutijela protiv ADM koje se veže na adrenomedulin namijenjeni upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 13, naznačeni time što ih treba upotrijebiti u kombinaciji s proteinom koji se veže na ADM i/ili dodatni aktivnim sastojcima.
15. Farmaceutska formulacija, naznačena time što sadrži protutijelo protiv ADM ili fragment protutijela protiv ADM ili ne-Ig okosnicu protutijela protiv ADM u skladu s bilo kojim od patentnih zahtjeva 1 do 14 namijenjen upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s bilo kojim od patentnih zahtjeva 1 do 14.
16. Farmaceutska formulacija namijenjena upotrebi u terapiji pacijenta koji boluje od kronične ili akutne bolesti ili akutnog stanja pacijenta u skladu s patentnim zahtjevom 15, naznačena time što je navedena farmaceutska formulacija otopina, po mogućnosti otopina spremna za upotrebu.
17. Farmaceutska formulacija namijenjena upotrebi u terapiji akutne bolesti ili akutnog stanja pacijenta koji boluje od kronične i/ili akutne bolesti ili akutnog stanja u skladu s patentnim zahtjevom 16, naznačeni time što je navedena farmaceutska formulacija u stanju osušenom smrzavanjem.
18. Farmaceutska formulacija namijenjena upotrebi u skladu s bilo kojim od patentnih zahtjeva 15 do 17, naznačena time što se navedenu farmaceutsku formulaciju primijenjuje intramuskularno.
19. Farmaceutska formulacija namijenjena upotrebi u skladu s bilo kojim od patentnih zahtjeva 15 do 17, naznačena time što se navedenu farmaceutsku formulaciju primijenjuje intravaskularno.
20. Farmaceutska formulacija namijenjena upotrebi u skladu s patentnih zahtjeva 15 do 17, naznačena time što se navedenu farmaceutsku formulaciju primijenjuje infuzijom.
21. Farmaceutska formulacija namijenjena upotrebi u skladu s patentnih zahtjeva 15 do 17, naznačena time što navedenu farmaceutsku formulaciju treba primijeniti sistemno na pacijentu radi sprječavanja ili smanjivanja disfunkcije organa ili insuficijencije organa kod navedenog pacijenta koji boluje od kronične ili akutne bolesti ili akutnog stanja.
22. Farmaceutska formulacija namijenjena upotrebi u skladu s patentnih zahtjeva 15 do 17, naznačena time što navedenu farmaceutsku formulaciju treba primijeniti sistemno infuzijom na pacijentu radi sprječavanja ili smanjivanja disfunkcije organa ili insuficijencije organa kod navedenog pacijenta koji boluje od kronične ili akutne bolesti ili akutnog stanja.
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| EP12784631.9A EP2780369B1 (en) | 2011-11-16 | 2012-11-16 | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or anti-adm non-ig scaffold for prevention or reduction of organ dysfunction or organ failure in a patient having a chronic or acute disease or acute condition |
| PCT/EP2012/072930 WO2013072511A1 (en) | 2011-11-16 | 2012-11-16 | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or anti-adm non-ig scaffold for prevention or reduction of organ dysfunction or organ failure in a patient having a chronic or acute disease or acute condition |
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| HRP20191010TT HRP20191010T1 (hr) | 2011-11-16 | 2019-06-04 | Protutijelo protiv adrenomedulina (adm) ili fragment protutijela protiv adm ili ne-ig okosnica protutijela protiv adm, namijenjeno sprječavanju ili smanjivanju disfunkcije organa ili insuficijencije organa kod pacijenta s kroničnom ili akutnom bolešću ili akutnim stanjem |
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| CN105949301B (zh) | 2010-06-08 | 2020-03-27 | 皮里斯制药有限公司 | 结合IL-4受体α的泪脂质运载蛋白突变蛋白 |
| FR2964103B1 (fr) | 2010-08-30 | 2018-11-23 | Universite D'aix-Marseille | Anticorps se liant a l'adrenomedulline et aux recepteurs de l'adrenomedulline et leurs utilisations comme medicament |
| MY178654A (en) | 2011-11-16 | 2020-10-20 | Adrenomed Ag | Anti-adrenomedullin (adm) antibody or anti-adm antibody fragment or an anti-adm non-ig protein scaffold for use in therapy |
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