Polypeptide linker for preparing multispecific antibodies
AssigneeBiomunex Pharmaceuticals
InventorsEugene Zhukovsky, Olivier Leger
Life of this patent
Estimating the term…
Abstract
The present invention relates to a mutant polypeptide linker for preparing multispecific antibodies, multispecific antibodies, and methods for producing multispecific antibodies.
Claims12
A multispecific antigen-binding fragment comprising at least two Fab fragments, wherein each Fab fragment recognizes a different epitope of interest, and said Fab fragments are tandemly arranged in any order, the C-terminal end of the CH1 domain of a first Fab fragment being linked to the N-terminal end of the VH domain of the following Fab fragment through a polypeptide linker,
- characterized in that the polypeptide linker sequence comprises EPKX1CDKX2HX3X4PPX5PAPELLGGPX6X7PPX8PX9PX10GG (SEQ ID NO:
- 1),
- wherein:
- X1, X2 and X3, identical or different, are Threonine (T) or Serine (S);
- X4 and X5, identical or different, are any amino acid selected from the group consisting of Serine (S), Cysteine (C), Alanine (A), and Glycine (G);
- and
- X6, X7, X8, X9, X10, identical or different, are selected from the group consisting of Alanine (A), Glycine (G), Valine (V), Asparagine (N), Aspartic acid (D) and Isoleucine (I).
A multispecific antibody comprising two heavy chains and four light chains,
- wherein each heavy chain comprises:
- a) a Fc region of an immunoglobulin comprising Hinge-CH2-CH3 domains;
- b) wherein said Fc region is linked to Fab heavy chain CH1-VH of antibody 1 (Ab1) by said Hinge domain;
- and
- c) wherein said Fab heavy chain CH1-VH of Ab1 is linked to Fab heavy chain CH1-VH of antibody 2 (Ab2) by a polypeptide linker sequence, wherein the polypeptide linker sequence links the N-terminus of said Fab heavy chain VH domain of Ab1 with the C-terminus of said Fab heavy chain CH1 domain of Ab2,
- and the four light chains comprise light chains of Ab1 and light chains of Ab2 associated with their cognate heavy chain domains;
- wherein the polypeptide linker sequence comprises EPKX1CDKX2HX3X4PPX5PAPELLGGPX6X7PPX8PX9PX10GG (SEQ ID NO:
- 1),
- wherein:
- X1, X2 and X3, identical or different, are Threonine (T) or Serine (S);
- X4 and X5, identical or different, are any amino acid selected from the group consisting of Serine (S), Cysteine (C), Alanine (A), and Glycine (G);
- and
- X6, X7, X8, X9, X10, identical or different, are selected from the group consisting of Alanine (A), Glycine (G), Valine (V), Asparagine (N), Aspartic acid (D) and Isoleucine (I).
Dependencies are inferred from the claim text.