Antibody constant domain regions and uses thereof
OwnerGenevieve HANSENinventor
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Abstract
The invention provides recombinant protein (e.g., a recombinant antibody or soluble receptor) having (i) a binding domain capable of specific binding to an epitope (for example an antibody variable domains, a receptor, a growth factor, a cytokine, or a fragment of any of the foregoing which is capable of specifically binding the desired epitope) and (ii) an effector domain comprising a constant domain region which is derived from immunoglobulin of a first species which is a companion mammal, e.g. dog, cat, or horse, having engineered substitutions at one or more positions and having an altered interaction with one or more FcRs or other ligands, and optionally enhanced effector function, relative to the parent constant domain region.
Claims38
A recombinant protein comprising
- a. a binding domain, or a fragment thereof, that specifically binds to an epitope;
- and
- b. an effector domain comprising a constant domain region;
- wherein the constant domain region is derived from immunoglobulin of a companion mammal, selected from dogs, cats and horses, comprising a deletion, addition, or substitution for at least one amino acid position and has an altered enhanced biophysical property or effector function interaction with at least one ligand.
A recombinant protein comprising any of the sequences of SEQ ID NOS 1-9.
A recombinant protein comprising any of the sequences of SEQ ID NOS 10-21.
A method of engineering an antibody for use in treating a dog, cat or horse, comprising:
- a. Isolating spleen cells or peripheral blood mononuclear cells from the species to be treated;
- b. Making cDNA in said cells and amplifying the cDNA encoding the antibody constant domains from said cells;
- c. Transforming a host cell with an expression vector comprising cDNA for the constant domain together with DNA encoding a variable region having affinity for an epitope;
- d. Expressing and retrieving antibody from the host cell thus transformed, and
- e. Assessing the effector function of the constant regions of antibodies thus obtained,
- i. by directly assessing the binding of the antibody to Fc;
- and/or
- ii. by assessing the ability of the antibody to kill a target cell, wherein the variable region of the antibody recognizes an epitope on the target cell, in the absence of complement (ADCC) and/or presence of complement (CDC);
- f. Selecting a constant region having the desired effector function;
- g. Making an antibody comprising the selected constant region and a variable region having affinity for the desired target.
A recombinant protein comprising
- a. a binding domain, or a fragment thereof, that specifically binds to an epitope;
- the binding domain comprising (i) a non-canine antibody hypervariable region or an epitope-binding fragment thereof, or (ii) a soluble receptor binding domain or an epitope-binding fragment thereof;
- and
- b. an effector domain that provides ADCC and/or CDC effector function to the recombinant protein;
- the effector domain comprising a constant domain region;
- wherein the constant domain exhibits at least 80% amino acid sequence identity to any of SEQ ID NO:
- 1-7.
Dependencies are inferred from the claim text.