Polypeptide Heterodimers and Uses Thereof
AssigneeEmergent Product Development Seattle, LLC
InventorsJohn W. Blankenship, Philip Tan
Life of this patent
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Abstract
The present disclosure provides polypeptide heterodimers formed between two different single chain fusion polypeptides via natural heterodimerization of an immunoglobulin CH1 region and an immunoglobulin light chain constant region (CL). One chain of a heterodimer comprises a binding domain that specifically binds a target (e.g., a receptor). In addition, both chains of a heterodimer further comprise an Fc region portion. The present disclosure also provides nucleic acids, vectors, host cells and methods for making polypeptide heterodimers as well as methods for using such polypeptide heterodimers, such as in reducing T cell activation, inhibiting solid malignancy growth, and treating autoimmune or inflammatory conditions.
Claims53
A polypeptide heterodimer, comprising:
- (a) a first single chain polypeptide comprising a binding domain that specifically binds a target, a hinge, a first immunoglobulin heterodimerization domain, and an Fc region portion;
- and
- (b) a second single chain polypeptide comprising a hinge, a second immunoglobulin heterodimerization domain that is not the same as the first immunoglobulin heterodimerization domain of the first single chain polypeptide, and an Fc region portion;
- wherein the first and second immunoglobulin heterodimerization domains associate with each other to form a polypeptide heterodimer comprised of the first and the second single chain polypeptides, and wherein
- (i) the first immunoglobulin heterodimerization domain comprises a first immunoglobulin CH1 region and the second immunoglobulin heterodimerization domain comprises a first immunoglobulin CL region, or,
- (ii) the first immunoglobulin heterodimerization domain comprises a first immunoglobulin CL region and the second immunoglobulin heterodimerization domain comprises a first immunoglobulin CH1 region, and
- wherein the Fc region portion comprises an immunoglobulin CH2 domain of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, or any combination thereof;
- an immunoglobulin CH2 domain and CH3 domain of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, or any combination thereof;
- an immunoglobulin CH3 domain of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgD, IgE, IgM, or any combination thereof;
- or an immunoglobulin CH3CH4 domain of IgE, IgM, or a combination thereof.
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Dependencies are inferred from the claim text.