Antibodies comprising chimeric constant domains
First Claim
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1. A recombinant polypeptide comprising a heavy chain constant (CH) region comprising, from N-terminus to C-terminus, a CH1 domain, a chimeric hinge, a CH2 domain, and a CH3 domain wherein:
- (a) the CH1 domain comprises the amino acid sequence DKKV or DKRV from positions 212 to 215 (EU numbering),(b) the chimeric hinge comprises a human IgG1 or a human IgG4 upper hinge amino acid sequence from positions 216 to 227 (EU numbering) and a human IgG2 lower hinge amino acid sequence PCPAPPVA (SEQ ID NO;
3) from positions 228 to 236 (EU numbering),(c) the CH2 domain comprises a human IgG4 CH2 domain amino acid sequence from positions 237 to 340 (EU numbering) comprising the amino acid sequence of SEQ ID NO;
10, and(d) the CH3 domain comprises a human IgG1 or a human IgG4 CH3 domain sequence from positions 341 to 447 (EU numbering).
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Abstract
Antibodies, antigen-binding proteins and Fc-fusion proteins that comprise recombinant polypeptides containing a chimeric heavy chain constant region sequence are provided that bind to certain Fc receptors however have reduced effector functions. Methods of making constructs for expression of such chimeric Fc-containing antibodies, antigen-binding proteins and Fc-fusion proteins in cell systems, and methods of producing and isolating the chimeric Fc-containing proteins are provided.
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21 Claims
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1. A recombinant polypeptide comprising a heavy chain constant (CH) region comprising, from N-terminus to C-terminus, a CH1 domain, a chimeric hinge, a CH2 domain, and a CH3 domain wherein:
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(a) the CH1 domain comprises the amino acid sequence DKKV or DKRV from positions 212 to 215 (EU numbering), (b) the chimeric hinge comprises a human IgG1 or a human IgG4 upper hinge amino acid sequence from positions 216 to 227 (EU numbering) and a human IgG2 lower hinge amino acid sequence PCPAPPVA (SEQ ID NO;
3) from positions 228 to 236 (EU numbering),(c) the CH2 domain comprises a human IgG4 CH2 domain amino acid sequence from positions 237 to 340 (EU numbering) comprising the amino acid sequence of SEQ ID NO;
10, and(d) the CH3 domain comprises a human IgG1 or a human IgG4 CH3 domain sequence from positions 341 to 447 (EU numbering). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 21)
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11. A recombinant polypeptide, wherein the polypeptide comprises N′
- -VD1-X1-Y1-Y2-X2-X3-C′
, wherein;(a) N′
is the N-terminus and C′
is the C-terminus of the polypeptide,(b) VD1 is an amino acid sequence comprising an antigen-binding domain, (c) X1 is an amino acid sequence comprising a domain selected from the group consisting of an IgG1 CH1 domain, an IgG4 CH1 domain, and at least positions 212-215 (EU numbering) of an IgG1 or IgG4 CH1 domain, (d) Y1 comprises an amino acid sequence from positions 216-227 (EU numbering) of an IgG1 or IgG4 hinge region, (e) Y2 comprises the human IgG2 lower hinge region amino acid sequence PCPAPPVA (SEQ ID NO;
3) from positions 228 to 236 (EU numbering),(f) X2 is an amino acid sequence comprising an IgG4 CH2 domain comprising the amino acid sequence of SEQ ID NO. 10, and (g) X3 is an amino acid sequence comprising an IgG1 CH3 domain or an IgG4CH3 domain. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20)
- -VD1-X1-Y1-Y2-X2-X3-C′
Specification