HRP20240213T1 - Bispecifična antitijela protiv ceacam5 i cd47 - Google Patents

Bispecifična antitijela protiv ceacam5 i cd47 Download PDF

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HRP20240213T1
HRP20240213T1 HRP20240213TT HRP20240213T HRP20240213T1 HR P20240213 T1 HRP20240213 T1 HR P20240213T1 HR P20240213T T HRP20240213T T HR P20240213TT HR P20240213 T HRP20240213 T HR P20240213T HR P20240213 T1 HRP20240213 T1 HR P20240213T1
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seq
bispecific antibody
variable region
light chain
binding part
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HRP20240213TT
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Vanessa BUATOIS
Anja SECKINGER
Dirk HOSE
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Lamkap Bio Beta Ag
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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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • C07K16/3007Carcino-embryonic Antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • 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
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • 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
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    • 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
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/40Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41Glycosylation, sialylation, or fucosylation
    • 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)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Claims (27)

1. Bispecifično antitijelo koje sadrži prvi vezujući dio koji se specifično veže za humani CEACAM5 i drugi vezujući dio koji se specifično veže za humani CD47 naznačen time što: a) prvi vezujući dio kao varijabilna regija teškog lanca sadrži varijabilnu regiju teškog lanca koji sadrži CDRH1 prema SEQ ID NO:1, CDRH2 prema SEQ ID NO:2 i CDRH3 prema SEQ ID NO:3, b) prvi vezujući dio kao varijabilna regija lakog lanca sadrži varijabilnu regiju lakog lanca koji sadrži CDRL set izabran iz grupe koja se sastoji od CDRL1 prema SEQ ID NO:17, CDRL2 prema SEQ ID NO:18 i CDRL3 prema SEQ ID NO:19, ili CDRL1 prema SEQ ID NO:23, CDRL2 prema SEQ ID NO:24 i CDRL3 prema SEQ ID NO:25, i c) drugi vezujući dio kao varijabilna regija teškog lanca sadrži varijabilnu regiju teškog lanca koji sadrži CDRH1 prema SEQ ID NO:1, CDRH2 prema SEQ ID NO:2 i CDRH3 prema SEQ ID NO:3, i kao varijabilna regija lakog lanca sadrži varijabilnu regiju lakog lanca koji sadrži CDRL1 prema SEQ ID NO:7, CDRL2 prema SEQ ID NO:8 i CDRL3 prema SEQ ID NO:9.
2. Bispecifično antitijelo prema patentnom zahtjevu 1, naznačeno time što sadrži prvi vezujući dio koji se specifično veže za humani CEACAM5 i drugi vezujući dio koji se specifično veže za humani CD47, naznačen time što u prvom vezujućem dijelu kao varijabilna regija teškog lanca sadrži varijabilnu regiju teškog lanca SEQ ID NO: 4 i kao varijabilna regija lakog lanca sadrži varijabilnu regiju lakog lanca SEQ ID NO: 33 ili SEQ ID NO: 35 i koji u drugom vezujućem dijelu kao varijabilna regija teškog lanca sadrži varijabilnu regiju teškog lanca SEQ ID NO:4 i kao varijabilna regija lakog lanca sadrži varijabilnu regiju lakog lanca koji ima SEQ ID NO:10.
3. Bispecifično antitijelo koje sadrži prvi vezujući dio koji se specifično veže za humani CEACAM5 i drugi vezujući dio koji se specifično veže za humani CD47, naznačen time što u prvom vezujućem dijelu kao varijabilna regija teškog lanca sadrži varijabilnu regiju teškog lanca SEQ ID NO:4 i kao varijabilna regija lakog lanca sadrži varijabilnu regiju lakog lanca izabran iz grupe koja se sastoji od SEQ ID NO:32, SEQ ID NO:34 i SEQ ID NO:36 i u drugom vezujućem dijelu kao varijabilna regija teškog lanca sadrži varijabilnu regiju teškog lanca SEQ ID NO:4 i kao varijabilna regija lakog lanca sadrži varijabilnu regiju lakog lanca koji ima SEQ ID NO:10.
4. Bispecifično antitijelo prema patentnom zahtjevu 2, naznačeno time što u prvom vezujućem dijelu sadrži teški lanac koji sadrži SEQ ID NO: 5 i laki lanac izabran iz grupe koja se sastoji od SEQ ID NO: 38 ili SEQ ID NO: 40 i u drugom vezujućem dijelu sadrži regiju teškog lanca SEQ ID NO:5 i laki lanac koji ima SEQ ID NO:11.
5. Bispecifično antitijelo prema patentnom zahtjevu 3, naznačeno time što u prvom vezujućem dijelu sadrži teški lanac koji sadrži SEQ ID NO: 5 i laki lanac izabran iz grupe koja se sastoji od SEQ ID NO: 37, SEQ ID NO: 39 i SEQ ID NO: 41 i u drugom vezujućem dijelu sadrži regiju teškog lanca SEQ ID NO:5 i laki lanac koji ima SEQ ID NO:11.
6. Bispecifično antitijelo prema bilo kojem od patentnih zahtjeva 1 do 5, naznačeno time što je navedeno antitijelo monovalentno za prvi vezujući dio i monovalentno za drugi vezujući dio.
7. Bispecifično antitijelo prema bilo kojem od patentnih zahtjeva 1 do 6, naznačeno time što navedeno antitijelo sadrži Fc regiju koja je konstruiran glikoinženjeringom tako da ima smanjen broj ostataka fukoze u usporedbi sa istim bispecifičnim antitijelom koje nije konstruirano glikoinženjeringom.
8. Bispecifično antitijelo prema patentnom zahtjevu 1, naznačeno odnosom KD vrijednosti za vezivanje za rekombinantni CEACAM3 i rekombinantni CEACAM5 faktora od 100 ili više.
9. Bispecifično antitijelo prema patentnom zahtjevu 1, naznačeno povećanjem od najmanje 8% maksimalnog indeksa fagocitoze LoVo tumorskih stanica u usporedbi sa indeksom fagocitoze bispecifičnog antitijela K2AC22, koje sadrži uobičajeni teški lanac SEQ ID NO:6, vezujući dio lakog lanca koji se veže za CD47 SEQ ID NO: 42, i laki lanac koji se veže za CEACAM5 prema SEQ ID NO:11.
10. Bispecifično antitijelo prema patentnom zahtjevu 9, naznačeno povećanjem maksimalnog indeksa fagocitoze između 8% i 20% za LoVo tumorske stanice.
11. Bispecifično antitijelo prema patentnom zahtjevu 1, naznačeno inhibiranjem interakcije između CD47 i SIRPα na MKN-45 stanicama sa IC50 od 0.1 nM ili niže.
12. Bispecifično antitijelo prema patentnom zahtjevu 11, naznačeno inhibiranjem interakcije između CD47 i SIRPα na MKN-45 stanicama sa IC50 od 0.1 nM do 0.04 nM.
13. Bispecifično antitijelo prema patentnom zahtjevu 1, pri čemu je navedeno bispecifično antitijelo naznačeno time što cibisatamab u koncentraciji od 300 nM, ne pomiče EC50 krive vezivanja navedenog bispecifičnog antitijela za stanice MKN-45 ili za LS174T stanice za više od faktora 3 ka višim koncentracijama.
14. Izolirani polinukleotid ili set polinukleotida koji kodira bispecifično antitijelo prema bilo kojem od patentnih zahtjeva 1 do 13.
15. Ekspresijski vektor koji sadrži polinukleotid ili polinukleotide prema patentnom zahtjevu 14.
16. Stanica domaćin koja sadrži ekspresijski vektor prema patentnom zahtjevu 15.
17. Postupak za proizvodnju bispecifičnog antitijela prema bilo kojem od patentnih zahtjeva 1-13, koji sadrži a) kultiviranje stanice domaćina prema patentnom zahtjevu 16 pod uvjetima koji dozvoljavaju proizvodnju navedenog bispecifičnog antitijela, i b) izoliranje navedenog antitijela.
18. Bispecifično antitijelo prema bilo kojem od patentnih zahtjeva 1-13, za uporabu u terapiji humanog raka.
19. Bispecifično antitijelo za uporabu prema patentnom zahtjevu 18, naznačeno time što rak je solidni rak.
20. Bispecifično antitijelo za uporabu prema patentnom zahtjevu 19, naznačeno time što rak je kolorektalni rak, NSCLC (nesitnostanični rak pluća), rak želuca, rak gušterače, rak dojke ili drugi rak koji eksprimira CEACAM5.
21. Bispecifično antitijelo prema bilo kojem od patentnih zahtjeva 1-13 za uporabu u istovremenoj, odvojenoj ili uzastopnoj kombinaciji sa drugim bispecifičnim antitijelom koje sadrži treći vezujući dio koji se specifično veže za humani CEACAM5, i četvrti vezujući dio koji se specifično veže za humani CD3ε u liječenju subjekta koji ima rak koji eksprimira CEACAM5.
22. Bispecifično antitijelo prema patentnom zahtjevu 21, naznačeno time što drugo bispecifično antitijelo je cibisatamab.
23. Bispecifično antitijelo za uporabu prema patentnom zahtjevu 21 ili 22 naznačeno time što bispecifično antitijelo prema pronalasku i drugo bispecifično antitijelo se primjenjuju na navedenog subjekta istovremeno u intervalima od 6 do 15 dana.
24. Farmaceutska kompozicija koja sadrži bispecifično antitijelo prema bilo kojem od patentnih zahtjeva 1 do 13 i farmaceutski prihvatljiv ekscipijens ili nosač.
25. Farmaceutski pripravak prema patentnom zahtjevu 24, za uporabu kao lijek.
26. Farmaceutski pripravak prema zahtjevu 24, za uporabu kao lijek u liječenju solidnog raka.
27. Farmaceutski pripravak prema patentnom zahtjevu 24, za uporabu kao lijek u liječenju kolorektalnog raka, NSCLC (nesitnostaničnog raka pluća), raka želuca, raka gušterače ili raka dojke.
HRP20240213TT 2020-12-18 2021-12-17 Bispecifična antitijela protiv ceacam5 i cd47 HRP20240213T1 (hr)

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EP20215766 2020-12-18
US202163135996P 2021-01-11 2021-01-11
EP21834934.8A EP4055055B1 (en) 2020-12-18 2021-12-17 Bispecific antibodies against ceacam5 and cd47
PCT/IB2021/061983 WO2022130348A1 (en) 2020-12-18 2021-12-17 Bispecific antibodies against ceacam5 and cd47

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EP (1) EP4055055B1 (hr)
JP (1) JP2024501809A (hr)
KR (1) KR20230121772A (hr)
AU (1) AU2021400227A1 (hr)
CA (1) CA3193210A1 (hr)
CL (1) CL2023001797A1 (hr)
CO (1) CO2023009100A2 (hr)
ES (1) ES2967381T3 (hr)
HR (1) HRP20240213T1 (hr)
HU (1) HUE065728T2 (hr)
IL (1) IL301701A (hr)
MX (1) MX2023007220A (hr)
PE (1) PE20231386A1 (hr)
PL (1) PL4055055T3 (hr)
RS (1) RS65211B1 (hr)
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CA3193210A1 (en) 2020-12-18 2022-06-23 Vanessa BUATOIS Bispecific antibodies against ceacam5 and cd47
WO2023170474A1 (en) * 2022-03-07 2023-09-14 Novimmune Sa Cd28 bispecific antibodies for targeted t cell activation
WO2023242351A1 (en) 2022-06-16 2023-12-21 Lamkap Bio Beta Ag Combination therapy of bispecific antibodies against ceacam5 and cd47 and bispecific antibodies against ceacam5 and cd3

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