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AssigneeGlenmark Pharmaceuticals S.A.
InventorsChristel AEBISCHER-GUMY, Pierre MORETTI, Martin BERTSCHINGER
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The invention relates to an expression construct for the soluble expression of polypeptides in host cells and for the expression of polypeptides on the surface of host cells, using alternative splicing. The amount of cell membrane expression of polypeptides such as antibodies, antibody fragments and bispecific antibodies can be correlated directly to the amount of soluble polypeptide expressed. In the case of bispecific antibodies, cell membrane expression of heterodimer and homodimer products can be correlated directly to the soluble expression of these products, thereby aiding selection of a desired producer clone.
An expression construct comprising in a 5′ to 3′ direction:
An expression construct according to any one of the preceding claims, wherein said intron comprises a poly(A) site.
An expression construct according to any one of the preceding claims, wherein the splice acceptor site of said intron comprises a poly(Y) tract and wherein the Y content of the poly(Y) tract is modified by altering the number of pyrimidine bases therein.
An expression construct according to any one of the preceding claims comprising at least one branch point region, wherein the sequence of said at least one branch point region is modified with respect to the branch point region consensus sequence CTRAYY (SEQ ID NO:
An expression construct according to any one of the preceding claims, wherein the consensus sequence of the splice donor site of the intron is modified.
An expression construct according to any one of the preceding claims, wherein the polypeptide of interest comprises an antibody heavy chain or fragment thereof.
A polynucleotide encoding an expression construct according to any one of the preceding claims.
Dependencies are inferred from the claim text.