JP-2022533096-A5 -

Dates

Publication Date

20230522

Application Date

20200513

Description

[Invention 1001]An isolated polypeptide comprising a variant protein A (SpA) having (i) a lysine substitution of a glutamine residue in each of domains A to E corresponding to positions 9 and 10 in domain D, and (ii) a glutamate substitution in each of domains A to E corresponding to position 33 in domain D, wherein the isolated polypeptide does not crosslink with IgG and IgE in the blood, or activates basophils or mast cells, compared to a negative control.[Invention 1002] The isolated polypeptide of the present invention 1001, wherein the K A binding affinity to human IgG-derived VH3 is reduced compared to the SpA variant (SpA KKAA ), which consists of lysine substitutions of glutamine residues in domains A to E corresponding to positions 9 and 10 in domain D, and alanine substitutions of aspartic acid in domains A to E corresponding to positions 36 and 37 in domain D. [Invention 1003] Isolated polypeptides of the present invention 1001 or 1002, having a K A binding affinity to human IgG-derived VH3 that is at least twice as low as SpA KKAA . [Invention 1004] An isolated polypeptide according to any of invention 1001 to 1003, having a K A binding affinity to human IgG-derived VH3 of less than 1 × 10⁵ M - 1 . [Invention 1005] An isolated polypeptide according to any of invention 1001 to 1004, wherein the SpA variant has no substitutions in any of domains A to E corresponding to positions 36 and 37 in domain D. [Invention 1006] An isolated polypeptide of any of the inventions 1001 to 1005, wherein the only substitutions in the SpA variant are (i) and (ii). [Invention 1007] An isolated polypeptide comprising an SpA variant, according to any of invention 1001 to 1006. [Invention 1008] A composition comprising an isolated polypeptide according to any of the present invention 1001 to 1007, wherein, in addition to the isolated polypeptide, the composition contains less than 1% by weight of protein from the total protein amount. [Invention 1009] A composition according to the present invention 1008, further comprising an adjuvant. [Invention 1010] A composition of the present invention 1009, wherein an isolated polypeptide is coupled to an adjuvant. [Invention 1011] A composition according to Invention 1009 or 1010, wherein the adjuvant contains alum. [Invention 1012] A composition according to any one of the present invention 1008 to 1011, further comprising a pharmaceutically acceptable excipient. [Invention 1013] An isolated polypeptide comprising a variant protein A (SpA) having (i) a lysine substitution of a glutamine residue in each of domains A to E corresponding to positions 9 and 10 in domain D, and (ii) a threonine substitution in each of domains A to E corresponding to position 33 in domain D, wherein the isolated polypeptide does not crosslink with IgG and IgE in the blood, or activates basophils or mast cells, compared to a negative control. [Invention 1014] The isolated polypeptide of the present invention 1013, wherein the K A binding affinity to human IgG-derived VH3 is reduced compared to the SpA variant (SpA KKAA ), which consists of lysine substitutions of glutamine residues in domains A to E corresponding to positions 9 and 10 in domain D, and alanine substitutions of aspartic acid in domains A to E corresponding to positions 36 and 37 in domain D. [Invention 1015] Isolated polypeptides of the present invention 1013 or 1014, having a K A binding affinity to human IgG-derived VH3 that is at least twice as low as SpA KKAA . [Invention 1016] An isolated polypeptide according to any of invention 1013 to 1015, having a K A binding affinity to human IgG-derived VH3 of less than 1 × 10⁵ M - 1 . [Invention 1017] An isolated polypeptide according to any of invention 1013 to 1016, wherein the SpA variant has no substitutions in any of domains A to E corresponding to positions 36 and 37 in domain D. [Invention 1018] An isolated polypeptide of any of the inventions 1013 to 1017, wherein the only substitutions in the SpA variant are (i) and (ii). [Invention 1019] An isolated polypeptide comprising the SpA variant, according to any of invention 1013 to 1018. [Invention 1020] A composition comprising an isolated polypeptide according to any of the inventions 1013 to 1019, wherein, in addition to the isolated polypeptide, the composition contains less than 1% by weight of protein from the total protein amount. [Invention 1021] A composition of the present invention 1020, further comprising an adjuvant. [Invention 1022] A composition of the present invention 1021, wherein an isolated polypeptide is coupled to an adjuvant. [Invention 1023] A composition according to invention 1021 or 1022, wherein the adjuvant contains alum. [Invention 1024] A composition according to any one of the present invention 1020 to 1023, further comprising a pharmaceutically acceptable excipient. [Invention 1025] A method for inducing a safe immune response against Staphylococcus in a human patient, comprising the step of administerin