Nucleic acids encoding modified immunoglobulin Fc regions

A nucleic acid comprising a nucleotide sequence encoding a protein comprising a variant IgG Fc region or a variant Cγ2 domain, wherein the variant IgG Fc region or variant Cγ2 domain is either:

• (i) a variant Fc region or variant Cγ2 domain which comprises a combination of amino acids selected from the group consisting of:
• 234A/235T/236R, 234D/235H/236R, 234D/235K/236R, 234D/235Q/236R, 234D/235S/236R, 234D/235T/236R, 234E/235D/236R, 234E/235H/236R, 234E/235I/236R, 234E/235V/236R, 234G/235Q/236R, 234G/235S/236R, 234H/235I/236R, 234H/235S/236R, 234K/235Q/236R, 234K/235R/236R, 234K/235S/236R, 234K/235T/236R, 234K/235V/236R, 234Q/235A/236R, 234Q/235D/236R, 234Q/235H/236R, 234Q/235Q/236R, 234Q/235R/236R, 234Q/235S/236R, 234Q/235T/236R, 234Q/235V/236R, 234R/235D/236R, 234R/235E/236R, 234R/235H/236R, 234R/235I/236R, 234R/235K/236R, 234R/235Q/236R, 234R/235R/236R, 234R/235T/236R, 234S/235D/236R, 234S/235E/236R, 234S/235G/236R, 234S/235H/236R, 234S/23511236R, 234S/235R/236R, 234S/235T/236R, 234S/235V/236R, 234T/235A/236R, 234T/235I/236R, 234T/235K/236R, 234T/235Q/236R, 234T/235R/236R, 234T/235S/236R, 234T/235T/236R, and 234T/235V/236R;
• (ii) a variant human IgG2 Fc region or variant IgG2 Cγ2 domain which comprises a combination of amino acids selected from:
• 234A/235T/236R, 234D/235H/236R, 234D/235K/236R, 234D/235Q/236R, 234D/235S/236R, 234D/235T/236R, 234E/235D/236R, 234E/235H/236R, 234E/235I/236R, 234E/235V/236R, 234G/235Q/236R, 234G/235S/236R, 234H/235I/236R, 234H/235S/236R, 234K/235Q/236R, 234K/235R/236R, 234K/235S/236R, 234K/235T/236R, 234K/235V/236R, 234Q/235D/236R, 234Q/235H/236R, 234Q/235Q/236R, 234Q/235R/236R, 234Q/235S/236R, 234Q/235T/236R, 234Q/235V/236R, 234R/235D/236R, 234R/235E/236R, 234R/235H/236R, 234R/235I/236R, 234R/235K/236R, 234R/235L/236R, 234R/235Q/236R, 234R/235R/236R, 234R/235T/236R, 234S/235D/236R, 234S/235E/236R, 234S/235G/236R, 234S/235H/236R, 234S/235I/236R, 234S/235L/236R, 234S/235R/236R, 234S/235T/236R, 234S/235V/236R, 234T/235I/236R, 234T/235K/236R, 234T/235Q/236R, 234T/235R/236R, 234T/235S/236R, 234T/235T/236R, and 234T/235V/236R;
• or
• (iii) a variant human IgG4 Fc region or variant IgG4 Cγ2 domain which comprises a combination of amino acids selected from:
• 234A/235T/236R, 234D/235H/236R, 234D/235K/236R, 234D/235Q/236R, 234D/235S/236R, 234D/235T/236R, 234E/235D/236R, 234E/235H/236R, 234E/235I/236R, 234E/235V/236R, 234G/235Q/236R, 234G/235S/236R, 234H/235I/236R, 234H/235S/236R, 234K/235Q/236R, 234K/235R/236R, 234K/235S/236R, 234K/235T/236R, 234K/235V/236R, 234Q/235A/236R, 234Q/235D/236R, 234Q/235H/236R, 234Q/235Q/236R, 234Q/235R/236R, 234Q/235S/236R, 234Q/235T/236R, 234Q/235V/236R, 234R/235D/236R, 234R/235E/236R, 234R/235H/236R, 234R/235I/236R, 234R/235K/236R, 234R/235Q/236R, 234R/235R/236R, 234R/235T/236R, 234S/235D/236R, 234S/235E/236R, 234S/235G/236R, 234S/235H/236R, 234S/235I/236R, 234S/235R/236R, 234S/235T/236R, 234S/235V/236R, 234T/235A/236R, 234T/235I/236R, 234T/235K/236R, 234T/235Q/236R, 234T/235R/236R, 234T/235S/236R, 234T/235T/236R, and 234T/235V/236R;
• wherein the amino acid numbering for (i), (ii) and (iii) is according to the EU index as in Kabat, and
• wherein the binding of the protein to human FcγRI, when measured by surface plasmon resonance, is less than 50% of the binding of a reference protein comprising an Fc region comprising the amino acid sequence of SEQ ID NO:
• 2.