Immunoglobulin variants
AssigneeGenentech, Inc.
InventorsPaula M. Jardieu, Leonard G. Presta
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Abstract
Two classes of polypeptides derived from human IgE are described. One class binds selectively to the high affinity IgE receptor on mast cells and basophils, but not to the low affinity IgE receptor on B-cells, monocytes, eosinophils and platelets. The other class binds to the low affinity receptor, but not the high affinity receptor. The differential binding polypeptides of this invention are useful in diagnostic procedures for IgE receptors or in the therapy of IgE-mediated disorders such as allergies. They also are useful in preparing antibodies capable of binding regions of IgE that participate in receptor binding.
Claims26
A differential binding Fc.epsilon.RI antagonist IgE polypeptide comprising from 30 to 250 residues from native heavy chain Fc IgE, comprising:
- a. an intact .beta.-strand D-domain of native IgE;
- and
- b. a non-functional loop AB and/or .beta.-strand B domain of native IgE;
- and wherein:
- (1) said polypeptide retains sufficient conformational integrity of native IgE to bind Fc.epsilon.RI with at least about 75% of the affinity with which native IgE binds Fc.epsilon.RI, but will not bind Fc.epsilon.RII with more than about 20% of the affinity which native IgE binds;
- and
- (2) said conformational integrity is conferred to the polyeptide by:
- (A) the presence of a human IgE Fc4 or IgG Fc3 sequence;
- or
- (B) cyclizing.
Dependencies are inferred from the claim text.