HRP20120870T1 - Protutijela protiv hepcidina i njihova upotreba - Google Patents

Protutijela protiv hepcidina i njihova upotreba Download PDF

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Publication number
HRP20120870T1
HRP20120870T1 HRP20120870AT HRP20120870T HRP20120870T1 HR P20120870 T1 HRP20120870 T1 HR P20120870T1 HR P20120870A T HRP20120870A T HR P20120870AT HR P20120870 T HRP20120870 T HR P20120870T HR P20120870 T1 HRP20120870 T1 HR P20120870T1
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Croatia
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seq
amino acid
acid sequences
antibody
given
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HRP20120870AT
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English (en)
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Yuping Anthony Cai
Dennis Patrick Gately
Luhong He
Donmienne Doen Leung
Peng Luan
Barbara Anne Swanson
Ying Tang
Derrick Ryan Witcher
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Eli Lilly And Company
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Application filed by Eli Lilly And Company filed Critical Eli Lilly And Company
Publication of HRP20120870T1 publication Critical patent/HRP20120870T1/hr

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/26Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06Antianaemics
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (20)

1. Izolirano protutijelo, naznačeno time što se veže na ljudski hepcidin-25 s KD od 800 pM ili manje, što je određeno površinskom plazmonskom rezonancijom (SPR) na 25 °C i sadrži šest CDR, koje se bira iz skupine koju čine: (i) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, te HCDR3, koji imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 52, 60, 62, 65, 71, odnosno 75; (ii) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, te HCDR3, koji imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 42, 76, 62, 79, 87, odnosno 46; (iii) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, te HCDR3, koji imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 41, 53, 31, 63, 84, odnosno 46; (iv) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, te HCDR3, koji imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 43, 30, 31, 32, 44, odnosno 46; (v) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, te HCDR3, koji imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 43, 53, 61, 63, 85, odnosno 46; i (vi) LCDR1, LCDR2, LCDR3, HCDR1, HCDR2, te HCDR3, koji imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 43, 57, 61, 63, 84, odnosno 46.
2. Protutijelo u skladu s patentnim zahtjevom 1, naznačeno time što protutijelo ima KD za ljudski hepcidin-25 između 400 pM i 30 pM, što je određeno uz pomoć SPR na 25 °C.
3. Protutijelo u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačeno time što protutijelo ima KD za ljudski hepcidin-25 između 200 pM i 30 pM, što je određeno uz pomoć SPR na 25 °C.
4. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-3, naznačeno time što protutijelo ima IC50 između 100 nM i 50 nM u ispitivanju bioaktivnosti hepcidina-25 in vitro, gdje se u navedenom ispitivanju mjeri internaliziranje i/ili razgradnju feroportina induciranu hepcidinom.
5. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačeno time što protutijelo ima IC50 između 100 nM i 25 nM u ispitivanju bioaktivnosti hepcidina-25 in vivo, gdje se u navedenom ispitivanju mjeri smanjivanje razina željeza u serumu inducirano s IL-6.
6. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-5, naznačeno time što je protutijelo ljudsko modificirano protutijelo.
7. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-6, naznačeno time što se kostur varijabilnog područja lakog lanca bira između 02, 018 ili L12.
8. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-7, naznačeno time što se kostur varijabilnog područja teškog lanca bira između VH1-69, VH1-18 ili VH1-46.
9. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-8, naznačeno time što sadrži varijabilno područje teškog lanca (HCVR) i varijabilno područje lakog lanca (LCVR), gdje (i) HCVR i LCVR imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 148 odnosno 126; (ii) HCVR i LCVR imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 128 odnosno 127; (iii) HCVR i LCVR imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 150 odnosno 124; ili (iv) HCVR i LCVR imaju aminokiselinske sljedove kao što su dani u SEQ ID NO: 151 odnosno 125.
10. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-9, naznačeno time što sadrži teški lanac i laki lanac, koji imaju (i) aminokiselinske sljedove kao što su dani u SEQ ID NO: 6 odnosno 14; (ii) aminokiselinske sljedove kao što su dani u SEQ ID NO: 7 odnosno 15; (iii) aminokiselinske sljedove kao što su dani u SEQ ID NO: 9 odnosno 17; ili (iv) aminokiselinske sljedove kao što su dani u SEQ ID NO: 8 odnosno 16.
11. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-10, naznačeno time što sadrži dva polipeptida teškog lanca i dva polipeptida lakog lanca, te što svaki od polipeptida teškog lanca ima aminokiselinski slijed kao što je dan u SEQ ID NO: 8, a svaki od polipeptida lakog lanca ima aminokiselinski slijed kao što je dan u SEQ ID NO: 16.
12. Polinukleotid, naznačen time što sadrži nukleotidni slijed koji kodira protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-11.
13. Polinukleotid u skladu s patentnim zahtjevom 12, naznačen time što sadrži nukleotidni slijed koji kodira polipeptid lakog lanca, koji ima aminokiselinski slijed kao što je dan u SEQ ID NO: 14, 15, 16, ili 17.
14. Polinukleotid u skladu s patentnim zahtjevom 12, naznačen time što sadrži nukleotidni slijed kao što je dan u SEQ ID NO: 12 ili 13.
15. Farmaceutski pripravak, naznačen time što sadrži protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-11, kao i farmaceutski prihvatljivu podlogu, razrjeđivač ili pomoćnu tvar.
16. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-11, naznačeno time što je namijenjeno upotrebi u terapiji.
17. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-11, naznačeno time što je namijenjeno upotrebi u liječenju i/ili sprječavanju anemije.
18. Protutijelo u skladu s bilo kojim od patentnih zahtjeva 1-11, naznačeno time što je namijenjeno upotrebi u povećavanju razina željeza u serumu, broja retikulocita, broja eritrocita, hemoglobina ili hematokrita kod subjekta.
19. Imunoispitivanje, naznačeno time što se sastoji u a) dobivanju uzorka kojeg treba ispitati za zreli ljudski hepcidin; b) stavljanju u kontakt uzorka s protutijelom u skladu s bilo kojim od patentnih zahtjeva 1-11 u uvjetima pogodnim za vezanje protutijela i koji omogućuju da sav prisutan zreli ljudski hepcidin tvori kompleks s protutijelom; i c) detektiranju prisutnosti ili odsutnosti kompleksa; i/ili određivanju količine kompleksa u uzorku postupkom imunodetekcije.
20. Imunoispitivanje u skladu s patentnim zahtjevom 18, naznačeno time što je postupak imunodetekcije enzimoimunosno ispitivanje (ELISA), radioimunosno ispitivanje (RIA), imunohistokemijsko (IHC) ispitivanje, imunofluorescentno (IF) ispitivanje, ispitivanje aglutinacije, western blot ispitivanje (zapadno bugačenje), dot blot ispitivanje (točkasto bugačenje), slot blot ispitivanje ili postupak detekcije uz pomoć površinske plazmonske rezonancije.
HRP20120870AT 2007-11-02 2012-10-29 Protutijela protiv hepcidina i njihova upotreba HRP20120870T1 (hr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US98491007P 2007-11-02 2007-11-02
PCT/US2008/081493 WO2009058797A1 (en) 2007-11-02 2008-10-29 Anti-hepcidin antibodies and uses thereof

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US (3) US7820163B2 (hr)
EP (2) EP2527368B1 (hr)
JP (1) JP5469076B2 (hr)
KR (2) KR101335059B1 (hr)
CN (1) CN103492414B (hr)
AR (1) AR069062A1 (hr)
AU (1) AU2008318850B2 (hr)
BR (1) BRPI0819211A2 (hr)
CA (1) CA2704527C (hr)
CL (2) CL2008003190A1 (hr)
CO (1) CO6231037A2 (hr)
CR (1) CR11414A (hr)
CY (1) CY1113630T1 (hr)
DK (1) DK2209806T3 (hr)
DO (2) DOP2010000123A (hr)
EA (1) EA023406B1 (hr)
ES (1) ES2392123T3 (hr)
HK (1) HK1142341A1 (hr)
HR (1) HRP20120870T1 (hr)
IL (1) IL205355A (hr)
JO (1) JO2828B1 (hr)
MA (1) MA31886B1 (hr)
MX (1) MX2010004841A (hr)
MY (1) MY155708A (hr)
NZ (2) NZ598391A (hr)
PE (1) PE20091261A1 (hr)
PL (1) PL2209806T3 (hr)
PT (1) PT2209806E (hr)
RS (1) RS52592B (hr)
SI (1) SI2209806T1 (hr)
TN (1) TN2010000201A1 (hr)
TW (1) TWI409276B (hr)
UA (1) UA98983C2 (hr)
WO (1) WO2009058797A1 (hr)
ZA (1) ZA201003025B (hr)

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US20130164304A1 (en) 2013-06-27
KR101335059B1 (ko) 2013-12-11
CR11414A (es) 2010-08-05
US20110027261A1 (en) 2011-02-03
DOP2013000205A (es) 2013-12-15
CN103492414B (zh) 2016-04-13
PE20091261A1 (es) 2009-08-17
TWI409276B (zh) 2013-09-21
BRPI0819211A2 (pt) 2015-06-16
JP5469076B2 (ja) 2014-04-09
DOP2010000123A (es) 2010-08-15
US8765129B2 (en) 2014-07-01
MY155708A (en) 2015-11-13
EP2209806A1 (en) 2010-07-28
IL205355A0 (en) 2010-12-30
HK1142341A1 (en) 2010-12-03
WO2009058797A1 (en) 2009-05-07
US8329174B2 (en) 2012-12-11
KR20120107145A (ko) 2012-09-28
AU2008318850A1 (en) 2009-05-07
NZ584997A (en) 2012-06-29
US20090136495A1 (en) 2009-05-28
ZA201003025B (en) 2011-11-30
US7820163B2 (en) 2010-10-26
TW200927759A (en) 2009-07-01
KR20100067682A (ko) 2010-06-21
CY1113630T1 (el) 2016-06-22
EP2209806B1 (en) 2012-08-22
EP2527368A1 (en) 2012-11-28
CA2704527A1 (en) 2009-05-07
NZ598391A (en) 2013-07-26
JP2011502482A (ja) 2011-01-27
CL2008003190A1 (es) 2009-09-04
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