US 12,098,400 B2Granted

Highly potent ISVD compounds capable of substituting for FVIII(A)

AssigneeNovo Nordisk A/S

InventorsAndreas Vegge, Daniele Granata, Jais Rose Bjelke, Jacob Lund, Philip Jonas Sassene, Per J. Greisen, Thomas Egebjerg, Evelyn De Tavernier, Soren Steffensen, Marie-Ange Buyse, Frantisek Hubalek, Simone Fulle, Mathias Norrman

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Abstract

The present invention provides ISVD polypeptide derivatives capable of binding coagulation Factor IX(a) and Factor X(a) which are highly potent and provide a sufficiently long half-life such to allow for effective subcutaneous—as well as peroral administration. The ISVD polypeptides derivatives disclosed herein are thus suitable for treatment of haemophilia A, haemophilia A with inhibitors and acquired haemophilia A by various routes of administration including subcutaneous and peroral administration.

Claims9

Dependent claims

A procoagulant VHH polypeptide derivative comprising a first VHH capable of binding to Factor IX (SEQ ID NO:1) or the activated form thereof, a second VHH capable of binding to Factor X (SEQ ID NO:2), a linker (L1-2) linking said first VHH and said second VHH, and a C-terminal extension (E) having SEQ ID NO:9,

having the formula (N- to C-terminal):
“second VHH”-L1-2-“first VHH”-E, further comprising a first and a second protraction moiety attached to E,
wherein
1)
said first VHH comprises
CDR1:
(SEQ ID NO:
172)
IYTMS,
CDR2:
(SEQ ID NO:
173)
GLRWTDSSTEYADSVKG,
and
CDR3:
(SEQ ID NO:
174)
DRSFLFAQALGATKNYEY;
and
said second VHH comprises
CDR1:
(SEQ ID NO:
152)
RYAMG,
CDR2:
(SEQ ID NO:
153)
AISRRGGSTNYADSVKG,
CDR3:
(SEQ ID NO:
154)
DDSVGDGYLDY;
or
2)
said first VHH comprises
CDR1:
(SEQ ID NO:
132)
IYTMS,
CDR2:
(SEQ ID NO:
133)
GLRWTDSSTEYADSVKG,
and
CDR3:
(SEQ ID NO:
134)
DRSFLFAQALGATKNYEY;
and
said second VHH comprises
CDR1:
(SEQ ID NO:
128)
RLAMG,
CDR2:
(SEQ ID NO:
129)
AISRRGGSTNYADSVKG,
CDR3:
(SEQ ID NO:
130)
DDSVGDGYLDY.

59 more elements

Dependencies are inferred from the claim text.