N-terminal scFv multispecific binding molecules
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsYang Shen, Ann-Hwee Lee, Yan Yang, Chia-Yang Lin
Life of this patent
Estimating the term…
Abstract
Multispecific binding molecules (MBMs) comprising an N-terminal scFv, a first Fab and a second Fab, MBM conjugates comprising the MBMs and cytotoxic or cytostatic agents, pharmaceutical compositions containing the MBMs and MBM conjugates, methods of using the MBMs, MBM conjugates and pharmaceutical compositions for treating cancer, nucleic acids encoding the MBMs, cells engineered to express the MBMs, and methods of producing MBMs.
Claims26
A trivalent multispecific binding molecule (MBM), comprising:
- (a) a first polypeptide chain comprising in an N-to C-terminal orientation:
- (i) an scFv comprising means for binding to human klotho beta (KLB);
- (ii) a linker;
- (iii) a first heavy chain region of a first Fab comprising means for binding to human fibroblast growth factor receptor 1c (FGFR1c);
- and
- (iv) a first Fc domain;
- and
- (b) a second polypeptide chain comprising, in an N-to C-terminal orientation:
- (i) a second heavy chain region of a second Fab comprising means for binding to human KLB;
- and
- (ii) a second Fc domain, wherein the second Fc domain forms a heterodimer with the first Fc domain;
- (c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form the first Fab;
- and
- (d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form the second Fab.
A method, comprising contacting a cell expressing KLB and FGFR1c with a trivalent MBM comprising:
- (a) a first polypeptide chain comprising in an N-to C-terminal orientation:
- (i) an scFv comprising means for binding to KLB;
- (ii) a linker;
- (iii) a first heavy chain region of a first Fab comprising means for binding to human FGFR1c;
- and
- (iv) a first Fc domain;
- and
- (b) a second polypeptide chain comprising, in an N-to C-terminal orientation:
- (i) a second heavy chain region of a second Fab comprising means for binding to human KLB;
- and
- (ii) a second Fc domain, wherein the second Fc domain forms a heterodimer with the first Fc domain;
- (c) a third polypeptide chain comprising a first light chain that pairs with the first heavy chain region to form the first Fab;
- and
- (d) a fourth polypeptide chain comprising a second light chain that pairs with the second heavy chain region to form the second Fab.
Dependencies are inferred from the claim text.