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US 2023/0235013 A1Published application
Modified immunoglubin fc regions
AssigneeMabsolve Limited
InventorsGeoffrey HALE, Ian Wilkinson
Life of this patent
Estimating the term…
Abstract
Provided are proteins comprising a variant IgG Fc region, wherein the proteins exhibit significantly reduced binding to human FcγRI when compared with a reference protein comprising the amino acid substitutions L234A/L235A/P329G. Also provided are compositions, methods of treatment and methods to reduce Fc-induced effector functions in a parent protein.
Claims27
A protein comprising a variant Fc region, wherein the variant Fc region comprises:
- (a) amino acid substitutions at both positions 234 and 235;
- and (b) an amino acid alteration to arginine (R) at position 236;
- wherein:
- (i) the amino acid substituted at position 234 is selected from the list D, E, G, H, K, N, Q, R, S, T;
- (ii) the amino acid substituted at position 235 is selected from the list A, D, E, G, H, I, K, L, M, N, Q, R, S, T, V;
- (iii) the amino acid numbering is according to the EU index as in Kabat;
- and (iv) the binding of the protein to human FcγRI is less than 50% of the binding of a LALAPG reference protein, optionally when measured by surface plasmon resonance.
4 more elements
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:
- (a) a variant Fc region or variant Cγ2 domain which comprises a combination of amino acid substitutions selected from:
- L234A/L235A/G236R, L234A/L235S/G236R, L234A/L235T/G236R, L234D/L235H/G236R, L234D/L235K/G236R, L234D/L235Q/G236R, L234D/L235S/G236R, L234D/L235T/G236R, L234E/L235D/G236R, L234E/L235H/G236R, L234E/L235I/G236R, L234E/L235V/G236R, L234G/L235H/G236R, L234G/L235Q/G236R, L234G/L235S/G236R, L234H/L235I/G236R, L234H/L235S/G236R, L234K/L235Q/G236R, L234K/L235R/G236R, L234K/L235S/G236R, L234K/L235T/G236R, L234K/L235V/G236R, L234Q/L235A/G236R, L234Q/L235D/G236R, L234Q/L235H/G236R, L234Q/L235Q/G236R, L234Q/L235R/G236R, L234Q/L235S/G236R, L234Q/L235T/G236R, L234Q/L235V/G236R, L234R/L235D/G236R, L234R/L235E/G236R, L234R/L235H/G236R, L234R/L235I/G236R, L234R/L235K/G236R, L234R/L235Q/G236R, L234R/L235R/G236R, L234R/L235T/G236R, L234S/L235D/G236R, L234S/L235E/G236R, L234S/L235G/G236R, L234S/L235H/G236R, L234S/L235I/G236R, L234S/L235R/G236R, L234S/L235T/G236R, L234S/L235V/G236R, L234T/L235A/G236R, L234T/L235I/G236R, L234T/L235K/G236R, L234T/L235Q/G236R, L234T/L235R/G236R, L234T/L235S/G236R, L234T/L235T/G236R, L234T/L235V/G236R;
- (b) a variant human IgG2 Fc region or variant IgG2 Cγ2 domain which comprises a combination of amino acid alterations selected from:
- V234A/A235S/Δ236R, V234A/A235T/Δ236R, V234D/A235H/Δ236R, V234D/A235K/Δ236R, V234D/A235Q/Δ236R, V234D/A235S/Δ236R, V234D/A235T/Δ236R, V234E/A235D/Δ236R, V234E/A235H/Δ236R, V234E/A235I/Δ236R, V234E/A235V/Δ236R, V234G/A235H/Δ236R, V234G/A235Q/Δ236R, V234G/A235S/Δ236R, V234H/A235I/Δ236R, V234H/A235S/Δ236R, V234K/A235Q/Δ236R, V234K/A235R/Δ236R, V234K/A235S/Δ236R, V234K/A235T/Δ236R, V234K/A235V/Δ236R, V234Q/A235D/Δ236R, V234Q/A235H/Δ236R, V234Q/A235Q/Δ236R, V234Q/A235R/Δ236R, V234Q/A235S/Δ236R, V234Q/A235T/Δ236R, V234Q/A235V/Δ236R, V234R/A235D/Δ236R, V234R/A235E/Δ236R, V234R/A235H/Δ236R, V234R/A235I/Δ236R, V234R/A235K/Δ236R, V234R/A235L/Δ236R, V234R/A235Q/Δ236R, V234R/A235R/Δ236R, V234R/A235T/Δ236R, V234S/A235D/Δ236R, V234S/A235E/Δ236R, V234S/A235G/Δ236R, V234S/A235H/Δ236R, V234S/A235I/Δ236R, V234S/A235L/Δ236R, V234S/A235R/Δ236R, V234S/A235T/Δ236R, V234S/A235V/Δ236R, V234T/A235I/Δ236R, V234T/A235K/Δ236R, V234T/A235Q/Δ236R, V234T/A235R/Δ236R, V234T/A235S/Δ236R, V234T/A235T/Δ236R, V234T/A235V/Δ236R;
- or (c) a variant human IgG4 Fc region or variant IgG4 Cγ2 domain which comprises a combination of amino acid substitutions selected from:
- F234A/L235A/G236R, F234A/L235S/G236R, F234A/L235T/G236R, F234D/L235H/G236R, F234D/L235K/G236R, F234D/L235Q/G236R, F234D/L235S/G236R, F234D/L235T/G236R, F234E/L235D/G236R, F234E/L235H/G236R, F234E/L235I/G236R, F234E/L235V/G236R, F234G/L235H/G236R, F234G/L235Q/G236R, F234G/L235S/G236R, F234H/L235I/G236R, F234H/L235S/G236R, F234K/L235Q/G236R, F234K/L235R/G236R, F234K/L235S/G236R, F234K/L235T/G236R, F234K/L235V/G236R, F234Q/L235A/G236R, F234Q/L235D/G236R, F234Q/L235H/G236R, F234Q/L235Q/G236R, F234Q/L235R/G236R, F234Q/L235S/G236R, F234Q/L235T/G236R, F234Q/L235V/G236R, F234R/L235D/G236R, F234R/L235E/G236R, F234R/L235H/G236R, F234R/L235I/G236R, F234R/L235K/G236R, F234R/L235Q/G236R, F234R/L235R/G236R, F234R/L235T/G236R, F234S/L235D/G236R, F234S/L235E/G236R, F234S/L235G/G236R, F234S/L235H/G236R, F234S/L235I/G236R, F234S/L235R/G236R, F234S/L235T/G236R, F234S/L235V/G236R, F234T/L235A/G236R, F234T/L235I/G236R, F234T/L235K/G236R, F234T/L235Q/G236R, F234T/L235R/G236R, F234T/L235S/G236R, F234T/L235T/G236R, F234T/L235V/G236R;
- wherein:
- (i) the amino acid numbering is according to the EU index as in Kabat;
- and (ii) the binding of the protein to human FcγRI is less than 50% of the binding of a LALAPG reference protein, optionally when measured by surface plasmon resonance.
6 more elements
Dependencies are inferred from the claim text.