SI2753646T1 - Protitelesa anti-CD40, uporabe in metode - Google Patents

Protitelesa anti-CD40, uporabe in metode Download PDF

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SI2753646T1
SI2753646T1 SI201231140T SI201231140T SI2753646T1 SI 2753646 T1 SI2753646 T1 SI 2753646T1 SI 201231140 T SI201231140 T SI 201231140T SI 201231140 T SI201231140 T SI 201231140T SI 2753646 T1 SI2753646 T1 SI 2753646T1
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seq
antibody
antigen
binding
fragment
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Peter Bo Joakim Ellmark
Eva Maria Dahlen
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Alligator Bioscience Ab
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    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
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    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Claims (13)

  1. Protitelesa anti-CD40, uporabe in metode Patentni zahtevki
    1. Protitelo ali njegov delec, ki veže antigen z multivalentno vezavno specifičnostjo za CD40, kjer protitelo ali delec vsebuje variabilno lahko verigo (VL) v kateri CDR1 vsebuje ali sestoji iz zaporedja amino kislin: CTGSXiSNIGAGYX2VY [SEQ ID NO:l] kjer Xi predstavlja S ali T; in X2 je K ali H ali D ali G ali N kjer protitelo ali delec vsebuje variabilno lahko verigo (VL) v kateri CDR2 vsebuje ali sestoji iz zaporedja amino kislin: X3NINRPS [SEQ ID NO:2] kjer: X3 predstavlja G ali R kjer protitelo ali delec vsebuje variabilno lahko verigo (VL) v kateri CDR3 vsebuje ali sestoji iz zaporedja amino kislin: CAAWDX4X5X6X7GLX8 [SEQ ID 0:3] kjer: Χ4 predstavlja D ali S ali E ali G ali K; in Χ5 je S ali T ali G; in Χβ je L ali S ali T ali L ali I; in Χ7 je S ali T ali L; in Xs je V ali L kjer protitelo ali delec vsebuje variabilno težko verigo (VH) v kateri CDR1 vsebuje ali sestoji iz zaporedja amino kislin: GFTFSTYGMH [SEQ ID NO:28] kjer protitelo ali delec vsebuje variabilno težko verigo (VH) v kateri CDR2 vsebuje ali sestoji iz zaporedja amino kislin: GKGLEWLSYISGGSSYIFYADSVRGR [SEQ ID NO:29] kjer protitelo ali delec vsebuje variabilno težko verigo (VH) v kateri CDR3 vsebuje ali sestoji iz zaporedja amino kislin: CARILRGGSGMDL [SEQ ID NO:30] kjer je učinkovitost protitelesa ali delca, ki veže antigen za aktivacijo dendritskih celic višja ali enaka njegovi učinkovitosti za aktivacijo B celic in, kjer ima protitelo ali delec, ki veže antigen afiniteto (KD) za CD40 manj kot lxlO’10 M, kjer je protitelo ali delec, ki veže antigen zmožen vezave na domeno 1 CD40 in kjer je afiniteta (KD) za CD40 merjena s površinsko plazmonsko resonanco.
  2. 2. Protitelo ali delec, ki veže antigen po zahtevku 1, kjer ima protitelo ali delec, ki veže antigen višjo učinkovitost za aktivacijo dendritskih celic kot protitelo B44, ki vsebuje zaporedje amino kislin SEQ ID NO: 58 variabilne lahke verige in zaporedje amino kislin SEQ ID NO: 60 variabilne težke verige.
  3. 3. Protitelo ali delec, ki veže antigen po zahtevku 1 ali 2, kjer ima protitelo ali delec, kjer protitelo ali delec vsebuje naslednje CDR: (i) SEQ ID NO:4 in SEQ ID NO:10 in SEQ ID N0:12 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30; ali (ii) SEQ ID N0:5 in SEQ ID NO:10 in SEQ ID N0:13 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30; ali (iii) SEQ ID N0:4 in SEQ ID NO: 10 in SEQ ID NO: 12 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30; ali (iv) SEQ ID NO:6 in SEQ ID NO: 10 in SEQ ID NO: 14 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30; ali (v) SEQ ID NO:7 in SEQ ID NO: 11 in SEQ ID NO: 15 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30; ali (vi) SEQ ID NO:8 in SEQ ID NO: 10 in SEQ ID NO: 16 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30; ali (vii) SEQ ID NO:9 in SEQ ID NO:10 in SEQ ID NO:17 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30; ali (viii) SEQ ID NO:9 in SEQ ID NO:10 in SEQ ID NO:12 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30; ali (ix) SEQ ID NO:9 in SEQ ID NO:10 in SEQ ID NO:18 in SEQ ID NO:28 in SEQ ID NO:29 in SEQ ID NO:30.
  4. 4. Protitelo ali delec, ki veže antigen po kateremkoli predhodnem zahtevku, ki vsebuje regijo Fc iz protitelesa IgGl.
  5. 5. Protitelo ali delec, ki veže antigen po zahtevku 4, kjer regija Fc vsebuje ali sestoji iz zaporedja amino kislin SEQ ID NO: 62.
  6. 6. Protitelo ali delec, ki veže antigen po kateremkoli predhodnem zahtevku, ki nadalje vsebuje citotoksični del.
  7. 7. Protitelo ali delec, ki veže antigen po zahtevku 6, kjer je citotoksični del zmožen pretvoriti ne-citotoksično predzdravilo v citotoksično zdravilo ali kjer je citotoksični del radiosenzibilizator.
  8. 8. Molekula nukleinske kisline, ki kodira protitelo ali delec, ki veže antigen po kateremkoli zahtevku od 1 do 7.
  9. 9. Vektor, ki vsebuje molekulo nukleinske kisline po zahtevku 8.
  10. 10. Rekombinantna gostiteljska celica, ki vsebuje molekulo nukleinske kisline po zahtevku 8 ali vektor po zahtevku 9.
  11. 11. Farmacevtski sestavek, ki vsebuje učinkovito količino protitelesa ali delca, ki veže antigen po kateremkoli zahtevku od 1 do 7 in farmacevtsko sprejemljiv pufer, ekscipient, redčilo ali nosilec, neobvezno, kjer je farmacevtski sestavek primeren za parenteralno administracijo in/ali lokalno administracijo na ali blizu mesta tumorja.
  12. 12. Protitelo ali delec, ki veže antigen po kateremkoli zahtevku od 1 do 7 ali molekula nukleinske kisline po zahtevku 8 ali vektor po zahtevku 9 ali gostiteljska celica po zahtevku 10 ali farmacevtski sestavek po zahtevku 11, za uporabo v zdravljenju raka.
  13. 13. Protitelo ali delec, ki veže antigen ali molekula nukleinske kisline ali vektor ali gostiteljska celica ali farmacevtski sestavek za uporabo po zahtevku 12, kjer je rak izbran iz skupine, ki vsebuje: rak prostate; rak dojke; kolorektalni rak; rak trebušne slinavke; rak jajčnikov; pljučni rak; rak materničnega vratu; rabdomiosarkom; nevroblastom; multipli mielom; levkemijo; akutno limfoblastno levkemijo, melanom; rak mehurja in glioblastom.
SI201231140T 2011-09-05 2012-09-05 Protitelesa anti-CD40, uporabe in metode SI2753646T1 (sl)

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GBGB1115280.8A GB201115280D0 (en) 2011-09-05 2011-09-05 Antibodies, uses and methods
EP12761786.8A EP2753646B1 (en) 2011-09-05 2012-09-05 Anti-cd40 antibodies, uses and methods
PCT/GB2012/052179 WO2013034904A1 (en) 2011-09-05 2012-09-05 Anti-cd40 antibodies, uses and methods

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