Production of functional antibodies in filamentous fungi
OwnerScott D. Power, Huaming Wang +1inventors
InventorsScott D. Power, Huaming Wang, Michael Ward
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Abstract
Described herein are methods for the production of monoclonal antibodies in filamentous fungi host cells. The monoclonal antibodies are expressed as full-length fusion proteins that retain functional antigen binding and antibody-dependent cellular cytotoxicity capabilities. Improvements in the cleavage of the glucoamylase-light chain fusion protein to yield a mature antibody are also provided. The antibodies produced in filamentous fungi show equivalent pharmacokinetic disposition to antibodies produced in mammalian cells.
Claims47
A monoclonal antibody comprising two heavy chains and two light chains wherein each of the chains comprising the monoclonal antibody has been expressed in a filamentous fungal host cell as a fusion protein, wherein the fusion protein comprises a secreted polypeptide or portion thereof normally secreted from a filamentous fungus and an immunoglobulin chain.
The monoclonal antibody of claim wherein the filamentous fungus is an Aspergillus niger.
A monoclonal antibody comprising two heavy chains and two light chains wherein at least one of the heavy chains and at least one of the light chains comprising the monoclonal antibody has been expressed in a filamentous fungal host cell as a fusion protein, wherein the fusion protein comprises a secreted polypeptide or portion thereof normally secreted from a filamentous fungus and an immunoglobulin chain.
A monoclonal antibody fragment selected from the group consisting of F(ab′)2, Fab′ and Fab, said fragment comprising at least one heavy chain and at least one light chain wherein each of the chains comprising the monoclonal antibody fragment has been expressed in a filamentous fungal host cell as a fusion protein, wherein the fusion protein comprises a secreted polypeptide or portion thereof normally secreted from a filamentous fungus and an immunoglobulin chain.
A fusion nucleic acid encoding a fusion polypeptide comprising, from a 5′ end of said fusion nucleic acid, first, second, third and fourth nucleic acids, wherein said first nucleic acid encodes a signal polypeptide functional as a secretory sequence in a first filamentous fungus, said second nucleic acid encodes a secreted polypeptide or functional portion thereof normally secreted from said first or a second filamentous fungus, said third nucleic acid encodes a cleavable linker and said fourth nucleic acid encodes an immunoglobulin light chain or fragment thereof.
A filamentous fungal host cell that has been transformed with a first and second fusion nucleic acid wherein
- a. the first fusion nucleic acid encodes at least the variable domain of either the immunoglobulin heavy or light chain one chain;
- and
- b. the second fusion nucleic acid encodes the other chain.
Dependencies are inferred from the claim text.