Fc region-based heterodimer molecule and use thereof
OwnerSiyi HU, Zhaoyuan CHEN +1inventors
InventorsSiyi HU, Zhaoyuan CHEN, Mao HUANG
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Abstract
The present disclosure relates to heterodimeric Fc scaffolds based on the Fc region of an immunoglobulin, heteromultimeric proteins comprising said heterodimeric Fc scaffolds, in particular mono- or multi-specific binding proteins, and compositions comprising the same and uses thereof.
Claims21
A heterodimeric Fc scaffold comprising a first polypeptide and a second polypeptide,
- wherein the first polypeptide comprises a first Fc region and the second polypeptide comprises a second Fc region,
- wherein the first Fc region comprises a first CH3 domain and the second Fc region comprises a second CH3 domain,
- wherein, relative to a wild-type CH3 domain, the first Fc region and the second Fc region comprise, in their respective CH3 domains, a knob mutation and a hole mutation of knobs-into-holes (KIH) mutations, respectively;
- and wherein:
- (a) the Fc region comprising the hole mutation further comprises an L351Y mutation;
- or
- (b) the Fc region comprising the hole mutation further comprises L351Y and D399R mutations, and the Fc region comprising the knob mutation further comprises a K409D mutation;
- wherein the first polypeptide and the second polypeptide pair and heterodimerize via the first and second Fc regions to form the Fc scaffold;
- wherein amino acid residues are numbered according to Kabat EU numbering.
A CH3 heterodimer comprising a first immunoglobulin CH3 domain and a second immunoglobulin CH3 domain that are heterodimerized, wherein, relative to a wild-type CH3 domain, the first CH3 domain and the second CH3 domain comprise, respectively, a knob mutation and a hole mutation of knobs-into-holes (KIH) mutations;
- and wherein:
- (a) the CH3 domain comprising the hole mutation further comprises an L351Y mutation;
- or
- (b) the CH3 domain comprising the hole mutation further comprises L351Y and D399R mutations, and the CH3 domain comprising the knob mutation further comprises a K409D mutation;
- wherein amino acid residues are numbered according to Kabat EU numbering;
- preferably, the first and second CH3 domains are of IgG class, e.g., IgG1, IgG2, IgG3, or IgG4 subclass;
- preferably, the wild-type CH3 domain is a CH3 domain of a native human IgG1 immunoglobulin;
- and
- more preferably, relative to the wild-type CH3 domain, each of the first and second CH3 domains further comprises 0 to 3 amino acid residue changes.
Dependencies are inferred from the claim text.