JPWO2020168271A5

JPWO2020168271A5 -

Info

Publication number: JPWO2020168271A5
Application number: JP2021547415A
Authority: JP
Publication date: 2023-02-22

Description

本明細書に記載される様々な実施形態の特性のうちの１つ、いくつか、またはすべてを組み合わせて、本開示の他の実施形態を形成することができることを、理解されたい。本開示のこれらおよび他の態様は、当業者には明らかであろう。本開示のこれらおよび他の実施形態は、以下の詳細な説明によってさらに説明される。
本発明は、例えば、以下の項目を提供する。
(項目１)
個体における胃炎、腸炎、十二指腸炎、または胃腸炎の１つまたは複数の症状を処置または予防するための方法であって、
（ａ）前記個体の胃、十二指腸、空腸、回腸、または結腸の粘膜から得られた第１の試料に由来するマスト細胞の数を検出するステップと、
（ｂ）前記個体の胃、十二指腸、空腸、回腸、または結腸の粘膜から得られた第２の試料に由来する好酸球の数を検出するステップと、
（ｃ）前記第１の試料が、マスト細胞の参照と比較して、マスト細胞の数の増加を有し、前記第２の試料が、好酸球の参照と比較して、好酸球の数の増加を有さない場合、前記個体に、有効量の、ヒトＳｉｇｌｅｃ－８に結合する抗体を含む組成物を投与するステップと
を含む、方法。
(項目２)
個体における胃炎、腸炎、十二指腸炎、または胃腸炎の１つまたは複数の症状を処置または予防するための方法であって、前記個体に、有効量の、ヒトＳｉｇｌｅｃ－８に結合する抗体を含む組成物を投与するステップを含み、前記個体が、マスト細胞の参照と比較して、前記胃、十二指腸、空腸、回腸、または結腸の粘膜の少なくとも一部分においてマスト細胞の数の増加を有し、前記個体が、好酸球の参照と比較して、前記胃、十二指腸、空腸、回腸、または結腸の粘膜の少なくとも一部分において好酸球の数の増加を有さない、方法。
(項目３)
前記個体の前記胃、十二指腸、空腸、回腸、または結腸の粘膜から得られた第１の試料が、前記マスト細胞の参照と比較して、マスト細胞の数の増加を有し、前記個体の前記胃、十二指腸、空腸、回腸、結腸の粘膜から得られた第２の試料が、前記好酸球の参照と比較して、好酸球の数の増加を有さない、項目２に記載の方法。
(項目４)
前記第１の試料と前記第２の試料が、同じである、項目１または項目３に記載の方法。
(項目５)
前記第１の試料と第２の試料の一方または両方が、胃または十二指腸の生検に由来する、項目１、３、および４のいずれか一項に記載の方法。
(項目６)
前記第１の試料と第２の試料の一方または両方が、生検による食道胃十二指腸内視鏡検査（ＥＧＤ）に由来する、項目１、３、および４のいずれか一項に記載の方法。
(項目７)
前記第１の試料が、強拡大視野（ＨＰＦ）当たり２０個またはそれを上回るマスト細胞のマスト細胞数を有する、少なくとも１つのＨＰＦを有する、項目１、３、および４から６のいずれか一項に記載の方法。
(項目８)
マスト細胞が、トリプターゼ、ＣＤ１１７、またはＩｇＥ受容体に関する免疫組織化学（ＩＨＣ）染色によって検出される、項目７に記載の方法。
(項目９)
前記第２の試料が、それぞれ、ＨＰＦ当たり３０個未満の好酸球の好酸球数を有する、１つまたは複数のＨＰＦを有する、項目１、３、および４から８のいずれか一項に記載の方法。
(項目１０)
前記第２の試料が、前記個体の前記胃粘膜から得られ、前記第２の試料が、それぞれ、ＨＰＦ当たり３０個またはそれを上回る好酸球の好酸球数を有する少なくとも５つのＨＰＦを有さない、項目１、３、および４から８のいずれか一項に記載の方法。
(項目１１)
前記第２の試料が、前記個体の前記十二指腸粘膜から得られ、前記第２の試料が、それぞれ、ＨＰＦ当たり３０個またはそれを上回る好酸球の好酸球数を有する少なくとも３つのＨＰＦを有さない、項目１、３、および４から８のいずれか一項に記載の方法。
(項目１２)
前記第１の試料における前記マスト細胞の数が、前記組成物の投与の４５日またはそれより前に検出される、項目１、３、および４から１１のいずれか一項に記載の方法。
(項目１３)
前記個体が、胃食道逆流性疾患（ＧＥＲＤ）を有するか、またはそれであると診断されている、項目１から１２のいずれか一項に記載の方法。
(項目１４)
前記個体が、制酸剤、Ｈ２ブロッカー、および／またはプロトンポンプ阻害剤による処置に対して不応性である、項目１３に記載の方法。
(項目１５)
前記個体が、過敏性腸症候群（ＩＢＳ）を有するか、またはそれであると診断されている、項目１から１２のいずれか一項に記載の方法。
(項目１６)
前記個体が、機能性消化不良を有するか、またはそれであると診断されている、項目１から１２のいずれか一項に記載の方法。
(項目１７)
前記個体が、好酸球性胃炎を有していたか、またはそれであると以前に診断されており、前記個体が、好酸球の上昇を有さない好酸球性胃炎の１つまたは複数の症状を有する、項目１から１２のいずれか一項に記載の方法。
(項目１８)
前記個体が、好酸球性胃腸炎を有していたか、またはそれであると以前に診断されており、前記個体が、好酸球の上昇を有さない好酸球性胃腸炎の１つまたは複数の症状を有する、項目１から１２のいずれか一項に記載の方法。
(項目１９)
前記個体の前記胃、十二指腸、空腸、回腸、または結腸の粘膜から得られた試料におけるマスト細胞の数または活性のうちの一方または両方が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に低減される、項目１から１８のいずれか一項に記載の方法。
(項目２０)
前記組成物の投与前に、前記個体が、胃炎または胃腸炎に対する１つまたは複数の標準的な治療処置に失敗しているかまたはそれで適切に制御されていない、項目１から１９のいずれか一項に記載の方法。
(項目２１)
胃炎または胃腸炎に対する前記１つまたは複数の標準的な治療処置が、プロトンポンプ阻害剤（ＰＰＩ）処置、コルチコステロイド処置、および食事処置からなる群から選択される、項目２０に記載の方法。
(項目２２)
前記個体における胃炎、十二指腸炎、腸炎、または胃腸炎の前記１つまたは複数の症状が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に低減される、項目１から２１のいずれか一項に記載の方法。
(項目２３)
前記個体における胃炎、十二指腸炎、腸炎、または胃腸炎の前記１つまたは複数の症状が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に、少なくとも６０％低減される、項目２２に記載の方法。
(項目２４)
前記個体における腹痛、悪心、嘔吐、食欲喪失、腹部けいれん、食事を終える前の満腹感、腹部膨満、下痢、および液状または水様便のうちの１つまたは複数が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に低減される、項目１から２１のいずれか一項に記載の方法。
(項目２５)
個体における食道炎の１つまたは複数の症状を処置または予防するための方法であって、
（ａ）前記個体の食道粘膜から得られた第１の試料に由来するマスト細胞の数を検出するステップと、
（ｂ）前記個体の前記食道粘膜から得られた第２の試料に由来する好酸球の数を検出するステップと、
（ｃ）前記第１の試料が、マスト細胞の参照と比較して、マスト細胞の数の増加を有し、前記第２の試料が、好酸球の参照と比較して、好酸球の数の増加を有さない場合、前記個体に、有効量の、ヒトＳｉｇｌｅｃ－８に結合する抗体を含む組成物を投与するステップと
を含む、方法。
(項目２６)
個体における食道炎の１つまたは複数の症状を処置または予防するための方法であって、前記個体に、有効量の、ヒトＳｉｇｌｅｃ－８に結合する抗体を含む組成物を投与するステップを含み、前記個体が、マスト細胞の参照と比較して、食道粘膜の少なくとも一部分においてマスト細胞の数の増加を有し、前記個体が、好酸球の参照と比較して、前記食道粘膜の少なくとも一部分において好酸球の数の増加を有さない、方法。
(項目２７)
前記個体の前記食道粘膜から得られた第１の試料が、前記マスト細胞の参照と比較して、マスト細胞の数の増加を有し、前記個体の前記食道粘膜から得られた第２の試料が、前記好酸球の参照と比較して、好酸球の数の増加を有さない、項目２６に記載の方法。
(項目２８)
前記第１の試料と前記第２の試料が、同じである、項目２５または項目２７に記載の方法。
(項目２９)
前記第１の試料と第２の試料の一方または両方が、食道生検試料に由来する、項目２５、２７、および２８のいずれか一項に記載の方法。
(項目３０)
前記第１の試料と第２の試料の一方または両方が、生検による食道胃十二指腸内視鏡検査（ＥＧＤ）に由来する、項目２５、２７、および２８のいずれか一項に記載の方法。
(項目３１)
前記第１の試料が、強拡大視野（ＨＰＦ）当たり１０個またはそれを上回るマスト細胞のマスト細胞数を有する、少なくとも１つのＨＰＦを有する、項目２５、２７、および２８から３０のいずれか一項に記載の方法。
(項目３２)
マスト細胞が、トリプターゼ、ＣＤ１１７、またはＩｇＥ受容体に関する免疫組織化学（ＩＨＣ）染色によって検出される、項目３１に記載の方法。
(項目３３)
前記第２の試料が、ＨＰＦ当たり１５個未満の好酸球の好酸球数を有する、１つまたは複数のＨＰＦを有する、項目２５、２７、および２８から３２のいずれか一項に記載の方法。
(項目３４)
前記第２の試料が、ＨＰＦ当たり１５個またはそれを上回る好酸球の好酸球数を有するＨＰＦを有さない、項目２５、２７、および２８から３２のいずれか一項に記載の方法。
(項目３５)
前記個体が、胃食道逆流性疾患（ＧＥＲＤ）を有するか、またはそれであると診断されている、項目２５から３４のいずれか一項に記載の方法。
(項目３６)
前記個体が、制酸剤、Ｈ２ブロッカー、および／またはプロトンポンプ阻害剤による処置に対して不応性である、項目３５に記載の方法。
(項目３７)
前記個体の前記食道粘膜から得られた試料におけるマスト細胞の数、活性、または位置のうちの１つまたは複数が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に低減される、項目２５から３６のいずれか一項に記載の方法。
(項目３８)
前記組成物の投与前に、前記個体が、食道炎に対する１つまたは複数の標準的な治療処置に失敗しているかまたはそれで適切に制御されていない、項目２５から３７のいずれか一項に記載の方法。
(項目３９)
前記個体における食道炎の前記１つまたは複数の症状が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に低減される、項目２５から３８のいずれか一項に記載の方法。
(項目４０)
前記個体における食道炎の前記１つまたは複数の症状が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に、少なくとも６０％低減される、項目３９に記載の方法。
(項目４１)
前記個体における胸やけ、悪心、嚥下障害／嚥下困難、嘔吐、腹痛、咳、食片圧入、早期満腹感、食欲喪失、胸部痛、哺乳不耐または哺乳拒否、および胃食道逆流のうちの１つまたは複数が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に低減される、項目２５から３８のいずれか一項に記載の方法。
(項目４２)
個体における大腸炎の１つまたは複数の症状を処置または予防するための方法であって、
（ａ）前記個体の結腸粘膜から得られた第１の試料に由来するマスト細胞の数を検出するステップと、
（ｂ）前記個体の結腸粘膜から得られた第２の試料に由来する好酸球の数を検出するステップと、
（ｃ）前記第１の試料が、マスト細胞の参照と比較して、マスト細胞の数の増加を有し、前記第２の試料が、好酸球の参照と比較して、好酸球の数の増加を有さない場合、前記個体に、有効量の、ヒトＳｉｇｌｅｃ－８に結合する抗体を含む組成物を投与するステップと
を含む、方法。
(項目４３)
個体における大腸炎の１つまたは複数の症状を処置または予防するための方法であって、前記個体に、有効量の、ヒトＳｉｇｌｅｃ－８に結合する抗体を含む組成物を投与するステップを含み、前記個体が、マスト細胞の参照と比較して、結腸粘膜の少なくとも一部分においてマスト細胞の数の増加を有し、前記個体が、好酸球の参照と比較して、前記結腸粘膜の少なくとも一部分において好酸球の数の増加を有さない、方法。
(項目４４)
前記個体の前記結腸粘膜から得られた第１の試料が、前記マスト細胞の参照と比較して、マスト細胞の数の増加を有し、前記個体の前記結腸粘膜から得られた第２の試料が、前記好酸球の参照と比較して、好酸球の数の増加を有さない、項目４３に記載の方法。
(項目４５)
前記第１の試料と前記第２の試料が、同じである、項目４２または項目４４に記載の方法。
(項目４６)
前記大腸炎が、潰瘍性大腸炎である、項目４２から４５のいずれか一項に記載の方法。
(項目４７)
前記第１の試料が、強拡大視野（ＨＰＦ）当たり３０個またはそれを上回るマスト細胞のマスト細胞数を有する、少なくとも１つのＨＰＦを有する、項目４２から４６のいずれか一項に記載の方法。
(項目４８)
マスト細胞が、トリプターゼ、ＣＤ１１７、またはＩｇＥ受容体に関する免疫組織化学（ＩＨＣ）染色によって検出される、項目４７に記載の方法。
(項目４９)
前記第２の試料が、ＨＰＦ当たり６０個未満の好酸球の好酸球数を有する、１つまたは複数のＨＰＦを有する、項目４２から４８のいずれか一項に記載の方法。
(項目５０)
前記第２の試料が、ＨＰＦ当たり６０個またはそれを上回る好酸球の好酸球数を有するＨＰＦを有さない、項目４２から４８のいずれか一項に記載の方法。
(項目５１)
前記第１の試料における前記マスト細胞の数が、前記組成物の投与の４５日またはそれより前に検出される、項目４２から５０のいずれか一項に記載の方法。
(項目５２)
前記個体が、好酸球性大腸炎を有していたか、またはそれであると以前に診断されており、前記個体が、好酸球の上昇を有さない好酸球性大腸炎の１つまたは複数の症状を有する、項目４２から５１のいずれか一項に記載の方法。
(項目５３)
前記個体の前記結腸粘膜から得られた試料におけるマスト細胞の数または活性のうちの一方または両方が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に低減される、項目４２から５２のいずれか一項に記載の方法。
(項目５４)
前記組成物の投与前に、前記個体が、大腸炎に対する１つまたは複数の標準的な治療処置に失敗しているかまたはそれで適切に制御されていない、項目４２から５３のいずれか一項に記載の方法。
(項目５５)
前記個体における大腸炎の前記１つまたは複数の症状が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に低減される、項目４２から５４のいずれか一項に記載の方法。
(項目５６)
前記個体における大腸炎の前記１つまたは複数の症状が、前記組成物の投与前のベースラインレベルと比較して、前記組成物の投与後に、少なくとも６０％低減される、項目５５に記載の方法。
(項目５７)
前記組成物が、静脈内注入によって投与される、項目１から５６のいずれか一項に記載の方法。
(項目５８)
前記組成物が、３ヶ月またはそれを上回る間、１ヶ月に１回、静脈内注入によって投与される、項目５７に記載の方法。
(項目５９)
前記組成物が、皮下注射によって投与される、項目１から５６のいずれか一項に記載の方法。
(項目６０)
前記組成物が、約０．３ｍｇ／ｋｇから約３．０ｍｇ／ｋｇの間の前記抗体を含む１回または複数の用量で、静脈内注入によって投与される、項目１から５６のいずれか一項に記載の方法。
(項目６１)
前記個体に、約０．３ｍｇ／ｋｇの前記抗体を含む第１の用量、約１．０ｍｇ／ｋｇの前記抗体を含む第２の用量、および約３．０ｍｇ／ｋｇの前記抗体を含む第３の用量を投与するステップを含む、項目１から５６のいずれか一項に記載の方法。
(項目６２)
前記個体に、約０．３ｍｇ／ｋｇの前記抗体を含む第１の用量を１日目に、約１．０ｍｇ／ｋｇの前記抗体を含む第２の用量を２６日目から３２日目の間に、約３．０ｍｇ／ｋｇの前記抗体を含む第３の用量を５４日目から６０日目の間に、約３．０ｍｇ／ｋｇの前記抗体を含む第４の用量を８２日目から８８日目の間に、約３．０ｍｇ／ｋｇの前記抗体を含む第５の用量を１１０日目から１１６日目の間に、約３．０ｍｇ／ｋｇの前記抗体を含む第６の用量を１３８日目から１４４日目の間に投与するステップを含む、項目６１に記載の方法。
(項目６３)
前記抗体が、Ｆｃ領域と、前記Ｆｃ領域に連結されたＮ－グリコシド結合型炭水化物鎖とを含み、前記組成物中の前記抗体の前記Ｎ－グリコシド結合型炭水化物鎖のうちの５０％未満が、フコース残基を含む、項目１から６２のいずれか一項に記載の方法。
(項目６４)
前記組成物中の前記抗体の前記Ｎ－グリコシド結合型炭水化物鎖のうちの実質的にすべてが、フコース残基を含まない、項目６３に記載の方法。
(項目６５)
前記抗体が、重鎖可変領域および軽鎖可変領域を含み、前記重鎖可変領域が、（ｉ）配列番号６１のアミノ酸配列を含むＨＶＲ－Ｈ１、（ｉｉ）配列番号６２のアミノ酸配列を含むＨＶＲ－Ｈ２、および（ｉｉｉ）配列番号６３のアミノ酸配列を含むＨＶＲ－Ｈ３を含み、かつ／または前記軽鎖可変領域が、（ｉ）配列番号６４のアミノ酸配列を含むＨＶＲ－Ｌ１、（ｉｉ）配列番号６５のアミノ酸配列を含むＨＶＲ－Ｌ２、および（ｉｉｉ）配列番号６６のアミノ酸配列を含むＨＶＲ－Ｌ３を含む、項目１から６４のいずれか一項に記載の方法。
(項目６６)
前記抗体が、重鎖可変領域および軽鎖可変領域を含み、前記重鎖可変領域が、（ｉ）配列番号６１のアミノ酸配列を含むＨＶＲ－Ｈ１、（ｉｉ）配列番号６２のアミノ酸配列を含むＨＶＲ－Ｈ２、および（ｉｉｉ）配列番号６７～７０から選択されるアミノ酸配列を含むＨＶＲ－Ｈ３を含み、かつ／または前記軽鎖可変領域が、（ｉ）配列番号６４のアミノ酸配列を含むＨＶＲ－Ｌ１、（ｉｉ）配列番号６５のアミノ酸配列を含むＨＶＲ－Ｌ２、および（ｉｉｉ）配列番号７１のアミノ酸配列を含むＨＶＲ－Ｌ３を含む、項目１から６４のいずれか一項に記載の方法。
(項目６７)
前記抗体が、配列番号６のアミノ酸配列を含む重鎖可変領域、および／または配列番号１６もしくは２１から選択されるアミノ酸配列を含む軽鎖可変領域を含む、項目１から６４のいずれか一項に記載の方法。
(項目６８)
前記抗体が、配列番号１１～１４から選択されるアミノ酸配列を含む重鎖可変領域、および／または配列番号２３～２４から選択されるアミノ酸配列を含む軽鎖可変領域を含む、項目１から６４のいずれか一項に記載の方法。
(項目６９)
前記抗体が、配列番号２～１４から選択されるアミノ酸配列を含む重鎖可変領域、および／または配列番号１６～２４から選択されるアミノ酸配列を含む軽鎖可変領域を含む、項目１から６４のいずれか一項に記載の方法。
(項目７０)
前記抗体が、配列番号２～１０から選択されるアミノ酸配列を含む重鎖可変領域、および／または配列番号１６～２２から選択されるアミノ酸配列を含む軽鎖可変領域を含む、項目１から６４のいずれか一項に記載の方法。
(項目７１)
前記抗体が、
（ａ）（１）配列番号２６～２９から選択されるアミノ酸配列を含むＨＣ－ＦＲ１、
（２）配列番号６１のアミノ酸配列を含むＨＶＲ－Ｈ１、
（３）配列番号３１～３６から選択されるアミノ酸配列を含むＨＣ－ＦＲ２、
（４）配列番号６２のアミノ酸配列を含むＨＶＲ－Ｈ２、
（５）配列番号３８～４３から選択されるアミノ酸配列を含むＨＣ－ＦＲ３、
（６）配列番号６３のアミノ酸配列を含むＨＶＲ－Ｈ３、および
（７）配列番号４５～４６から選択されるアミノ酸配列を含むＨＣ－ＦＲ４を含む、重鎖可変領域、ならびに／または
（ｂ）（１）配列番号４８～４９から選択されるアミノ酸配列を含むＬＣ－ＦＲ１、
（２）配列番号６４のアミノ酸配列を含むＨＶＲ－Ｌ１、
（３）配列番号５１～５３から選択されるアミノ酸配列を含むＬＣ－ＦＲ２、
（４）配列番号６５のアミノ酸配列を含むＨＶＲ－Ｌ２、
（５）配列番号５５～５８から選択されるアミノ酸配列を含むＬＣ－ＦＲ３、
（６）配列番号６６のアミノ酸配列を含むＨＶＲ－Ｌ３、および
（７）配列番号６０のアミノ酸配列を含むＬＣ－ＦＲ４を含む、軽鎖可変領域
を含む、項目１から６４のいずれか一項に記載の方法。
(項目７２)
前記抗体が、
（ａ）（１）配列番号２６のアミノ酸配列を含むＨＣ－ＦＲ１、
（２）配列番号６１のアミノ酸配列を含むＨＶＲ－Ｈ１、
（３）配列番号３４のアミノ酸配列を含むＨＣ－ＦＲ２、
（４）配列番号６２のアミノ酸配列を含むＨＶＲ－Ｈ２、
（５）配列番号３８のアミノ酸配列を含むＨＣ－ＦＲ３、
（６）配列番号６３のアミノ酸配列を含むＨＶＲ－Ｈ３、および
（７）配列番号４５のアミノ酸配列を含むＨＣ－ＦＲ４を含む、重鎖可変領域、ならびに／または
（ｂ）（１）配列番号４８のアミノ酸配列を含むＬＣ－ＦＲ１、
（２）配列番号６４のアミノ酸配列を含むＨＶＲ－Ｌ１、
（３）配列番号５１のアミノ酸配列を含むＬＣ－ＦＲ２、
（４）配列番号６５のアミノ酸配列を含むＨＶＲ－Ｌ２、
（５）配列番号５５のアミノ酸配列を含むＬＣ－ＦＲ３、
（６）配列番号６６のアミノ酸配列を含むＨＶＲ－Ｌ３、および
（７）配列番号６０のアミノ酸配列を含むＬＣ－ＦＲ４を含む、軽鎖可変領域
を含む、項目１から６４のいずれか一項に記載の方法。
(項目７３)
前記抗体が、
（ａ）（１）配列番号２６のアミノ酸配列を含むＨＣ－ＦＲ１、
（２）配列番号６１のアミノ酸配列を含むＨＶＲ－Ｈ１、
（３）配列番号３４のアミノ酸配列を含むＨＣ－ＦＲ２、
（４）配列番号６２のアミノ酸配列を含むＨＶＲ－Ｈ２、
（５）配列番号３８のアミノ酸配列を含むＨＣ－ＦＲ３、
（６）配列番号６３のアミノ酸配列を含むＨＶＲ－Ｈ３、および
（７）配列番号４５のアミノ酸配列を含むＨＣ－ＦＲ４を含む、重鎖可変領域、ならびに／または
（ｂ）（１）配列番号４８のアミノ酸配列を含むＬＣ－ＦＲ１、
（２）配列番号６４のアミノ酸配列を含むＨＶＲ－Ｌ１、
（３）配列番号５１のアミノ酸配列を含むＬＣ－ＦＲ２、
（４）配列番号６５のアミノ酸配列を含むＨＶＲ－Ｌ２、
（５）配列番号５８のアミノ酸配列を含むＬＣ－ＦＲ３、
（６）配列番号６６のアミノ酸配列を含むＨＶＲ－Ｌ３、および
（７）配列番号６０のアミノ酸配列を含むＬＣ－ＦＲ４を含む、軽鎖可変領域
を含む、項目１から６４のいずれか一項に記載の方法。
(項目７４)
前記抗体が、
（ｉ）配列番号８８のアミノ酸配列を含むＨＶＲ－Ｈ１、（ｉｉ）配列番号９１のアミノ酸配列を含むＨＶＲ－Ｈ２、および（ｉｉｉ）配列番号９４のアミノ酸配列を含むＨＶＲ－Ｈ３を含む、重鎖可変領域、ならびに／もしくは（ｉ）配列番号９７のアミノ酸配列を含むＨＶＲ－Ｌ１、（ｉｉ）配列番号１００のアミノ酸配列を含むＨＶＲ－Ｌ２、および（ｉｉｉ）配列番号１０３のアミノ酸配列を含むＨＶＲ－Ｌ３を含む、軽鎖可変領域、
（ｉ）配列番号８９のアミノ酸配列を含むＨＶＲ－Ｈ１、（ｉｉ）配列番号９２のアミノ酸配列を含むＨＶＲ－Ｈ２、および（ｉｉｉ）配列番号９５のアミノ酸配列を含むＨＶＲ－Ｈ３を含む、重鎖可変領域、ならびに／もしくは（ｉ）配列番号９８のアミノ酸配列を含むＨＶＲ－Ｌ１、（ｉｉ）配列番号１０１のアミノ酸配列を含むＨＶＲ－Ｌ２、および（ｉｉｉ）配列番号１０４のアミノ酸配列を含むＨＶＲ－Ｌ３を含む、軽鎖可変領域、または
（ｉ）配列番号９０のアミノ酸配列を含むＨＶＲ－Ｈ１、（ｉｉ）配列番号９３のアミノ酸配列を含むＨＶＲ－Ｈ２、および（ｉｉｉ）配列番号９６のアミノ酸配列を含むＨＶＲ－Ｈ３を含む、重鎖可変領域、ならびに／もしくは（ｉ）配列番号９９のアミノ酸配列を含むＨＶＲ－Ｌ１、（ｉｉ）配列番号１０２のアミノ酸配列を含むＨＶＲ－Ｌ２、および（ｉｉｉ）配列番号１０５のアミノ酸配列を含むＨＶＲ－Ｌ３を含む、軽鎖可変領域
を含む、項目１から６４のいずれか一項に記載の方法。
(項目７５)
前記抗体が、
配列番号１０６のアミノ酸配列を含む重鎖可変領域、および／もしくは配列番号１０９のアミノ酸配列を含む軽鎖可変領域、
配列番号１０７のアミノ酸配列を含む重鎖可変領域、および／もしくは配列番号１１０のアミノ酸配列を含む軽鎖可変領域、または
配列番号１０８のアミノ酸配列を含む重鎖可変領域、および／もしくは配列番号１１１のアミノ酸配列を含む軽鎖可変領域
を含む、項目１から６４のいずれか一項に記載の方法。
(項目７６)
前記抗体が、ヒトＳｉｇｌｅｃ－８および非ヒト霊長類Ｓｉｇｌｅｃ－８に結合する、項目１から６４のいずれか一項に記載の方法。
(項目７７)
前記非ヒト霊長類が、ヒヒである、項目７６に記載の方法。
(項目７８)
前記抗体が、ヒトＳｉｇｌｅｃ－８のドメイン１内のエピトープに結合し、ドメイン１が、配列番号１１２のアミノ酸配列を含む、項目７６に記載の方法。
(項目７９)
前記抗体が、ヒトＳｉｇｌｅｃ－８のドメイン３内のエピトープに結合し、ドメイン３が、配列番号１１４のアミノ酸配列を含む、項目７６に記載の方法。
(項目８０)
前記抗体が、抗体４Ｆ１１と同じエピトープに結合する、項目７６に記載の方法。
(項目８１)
前記抗体が、ヒトＳｉｇｌｅｃ－８のドメイン２またはドメイン３内のエピトープに結合する、項目１から６４のいずれか一項に記載の方法。
(項目８２)
ドメイン２が、配列番号１１３のアミノ酸配列を含む、項目８１に記載の方法。
(項目８３)
前記抗体が、抗体１Ｃ３と同じエピトープに結合する、項目８１に記載の方法。
(項目８４)
ドメイン３が、配列番号１１４のアミノ酸配列を含む、項目８１に記載の方法。
(項目８５)
前記抗体が、抗体１Ｈ１０と同じエピトープに結合する、項目８１に記載の方法。
(項目８６)
前記抗体が、ヒトＳｉｇｌｅｃ－８のドメイン１内のエピトープに結合し、Ｓｉｇｌｅｃ－８への結合について、抗体４Ｆ１１と競合する、項目１から６４のいずれか一項に記載の方法。
(項目８７)
前記抗体が、Ｓｉｇｌｅｃ－８への結合について、抗体２Ｅ２と競合しない、項目８６に記載の方法。
(項目８８)
前記抗体が、抗体２Ｅ２ではない、項目８７に記載の方法。
(項目８９)
ドメイン１が、配列番号１１２のアミノ酸配列を含む、項目８６に記載の方法。
(項目９０)
前記抗体が、ヒト抗体、ヒト化抗体、またはキメラ抗体である、項目６５から８９のいずれか一項に記載の方法。
(項目９１)
前記抗体が、血中好酸球を枯渇させ、マスト細胞の活性化を阻害する、項目６５から９０のいずれか一項に記載の方法。
(項目９２)
前記抗体が、ヒトＩｇＧＦｃ領域を含む重鎖Ｆｃ領域を含む、項目６５から９１のいずれか一項に記載の方法。
(項目９３)
前記ヒトＩｇＧＦｃ領域が、ヒトＩｇＧ１Ｆｃ領域を含む、項目９２に記載の方法。
(項目９４)
前記ヒトＩｇＧ１Ｆｃ領域が、フコシル化されていない、項目９３に記載の方法。
(項目９５)
前記ヒトＩｇＧＦｃ領域が、ヒトＩｇＧ４Ｆｃ領域を含む、項目９２に記載の方法。
(項目９６)
前記ヒトＩｇＧ４Ｆｃ領域が、アミノ酸置換Ｓ２２８Ｐを含み、アミノ酸残基が、ＫａｂａｔにおけるようにＥＵインデックスに従って番号付けされている、項目９５に記載の方法。
(項目９７)
前記抗体が、抗体依存性細胞媒介性細胞傷害（ＡＤＣＣ）活性を向上させるように操作されている、項目６５から８９のいずれか一項に記載の方法。
(項目９８)
前記抗体が、前記Ｆｃ領域に、ＡＤＣＣ活性を向上させる少なくとも１つのアミノ酸置換を含む、項目９７に記載の方法。
(項目９９)
前記抗体の前記重鎖のうちの少なくとも１つまたは２つが、フコシル化されていない、項目６５から９１のいずれか一項に記載の方法。
(項目１００)
前記抗体が、配列番号７５のアミノ酸配列を含む重鎖、および／または配列番号７６もしくは７７から選択されるアミノ酸配列を含む軽鎖を含む、項目１から６４のいずれか一項に記載の方法。
(項目１０１)
前記抗体が、モノクローナル抗体である、項目１から１００のいずれか一項に記載の方法。
(項目１０２)
前記組成物が、胃炎、胃腸炎、または食道炎を処置または予防するための１つまたは複数の追加の治療剤と組み合わせて投与される、項目１から１０１のいずれか一項に記載の方法。
(項目１０３)
胃炎、胃腸炎、または食道炎を処置または予防するための前記１つまたは複数の追加の治療剤が、ＰＰＩ、全身的コルチコステロイド、局所的コルチコステロイド、抗ヒスタミン薬、マスト細胞安定剤、Ｈ－２ブロッカー、抗ＩｇＥ抗体、カルシニューリン阻害剤、免疫調節剤、および免疫抑制剤からなる群から選択される、項目１０２に記載の方法。
(項目１０４)
前記個体が、ヒトである、項目１から１０３のいずれか一項に記載の方法。
(項目１０５)
前記組成物が、前記抗体および薬学的に許容される担体を含む、医薬組成物である、項目１から１０４のいずれか一項に記載の方法。
(項目１０６)
ヒトＳｉｇｌｅｃ－８に結合する抗体を含む組成物を含む医薬と、項目１から１０５のいずれか一項に記載のそれを必要とする個体における前記医薬の投与のための説明を含む添付文書とを含む、製品。
It is to be understood that one, some, or all of the features of the various embodiments described herein can be combined to form other embodiments of the disclosure. These and other aspects of the disclosure will be apparent to those skilled in the art. These and other embodiments of the present disclosure are further described by the detailed description below.
The present invention provides, for example, the following items.
(Item 1)
A method for treating or preventing one or more symptoms of gastritis, enteritis, duodenitis, or gastroenteritis in an individual comprising:
(a) detecting the number of mast cells from a first sample obtained from the mucosa of the stomach, duodenum, jejunum, ileum, or colon of said individual;
(b) detecting the number of eosinophils from a second sample obtained from the mucosa of the stomach, duodenum, jejunum, ileum, or colon of said individual;
(c) said first sample has an increased number of mast cells compared to a mast cell reference and said second sample has an increased number of eosinophils compared to a reference of eosinophils; If not, administering to said individual an effective amount of a composition comprising an antibody that binds to human Siglec-8;
A method, including
(Item 2)
A method for treating or preventing one or more symptoms of gastritis, enteritis, duodenitis, or gastroenteritis in an individual, said composition comprising an effective amount of an antibody that binds to human Siglec-8. administering an agent, wherein said individual has an increased number of mast cells in at least a portion of the mucosa of said stomach, duodenum, jejunum, ileum, or colon compared to a mast cell reference; does not have an increase in the number of eosinophils in at least a portion of the mucosal membrane of said stomach, duodenum, jejunum, ileum, or colon compared to a reference for eosinophils.
(Item 3)
wherein a first sample obtained from the mucosa of said stomach, duodenum, jejunum, ileum, or colon of said individual has an increased number of mast cells compared to a reference of said mast cells; 3. The method of item 2, wherein the second sample obtained from the mucosa of the stomach, duodenum, jejunum, ileum, colon does not have an increase in the number of eosinophils compared to said eosinophil reference. .
(Item 4)
The method of item 1 or item 3, wherein the first sample and the second sample are the same.
(Item 5)
5. The method of any one of items 1, 3, and 4, wherein one or both of the first and second samples are derived from a gastric or duodenal biopsy.
(Item 6)
5. The method of any one of items 1, 3, and 4, wherein one or both of the first and second samples are derived from biopsy esophagogastroduodenoscopy (EGD).
(Item 7)
Any one of items 1, 3, and 4-6, wherein the first sample has at least one HPF with a mast cell count of 20 or more mast cells per high power field (HPF) The method described in .
(Item 8)
8. The method of item 7, wherein the mast cells are detected by immunohistochemical (IHC) staining for tryptase, CD117, or IgE receptor.
(Item 9)
9. Any one of items 1, 3, and 4-8, wherein said second sample has one or more HPFs each having an eosinophil count of less than 30 eosinophils per HPF described method.
(Item 10)
said second sample is obtained from said gastric mucosa of said individual, said second sample having at least 5 HPFs each having an eosinophil count of 30 or more eosinophils per HPF; 9. The method of any one of items 1, 3, and 4-8.
(Item 11)
said second sample is obtained from said duodenal mucosa of said individual, said second sample having at least 3 HPFs each having an eosinophil count of 30 or more eosinophils per HPF; 9. The method of any one of items 1, 3, and 4-8.
(Item 12)
The method of any one of items 1, 3, and 4-11, wherein the number of mast cells in the first sample is detected at or before 45 days of administration of the composition.
(Item 13)
13. The method of any one of items 1-12, wherein the individual has or is diagnosed with gastroesophageal reflux disease (GERD).
(Item 14)
14. The method of item 13, wherein said individual is refractory to treatment with antacids, H2 blockers, and/or proton pump inhibitors.
(Item 15)
13. The method of any one of items 1-12, wherein the individual has or has been diagnosed with irritable bowel syndrome (IBS).
(Item 16)
13. The method of any one of items 1-12, wherein the individual has or has been diagnosed with functional dyspepsia.
(Item 17)
said individual had or was previously diagnosed with eosinophilic gastritis, and said individual has one or more of eosinophilic gastritis without elevated eosinophils 13. The method of any one of items 1-12, wherein the method is symptomatic.
(Item 18)
said individual had or was previously diagnosed with eosinophilic gastroenteritis, and said individual has one of eosinophilic gastroenteritis without elevated eosinophils or 13. The method of any one of items 1-12, having multiple symptoms.
(Item 19)
one or both of mast cell number or activity in a sample obtained from the mucosa of the stomach, duodenum, jejunum, ileum, or colon of the individual compared to baseline levels prior to administration of the composition , reduced after administration of said composition.
(Item 20)
20. Any one of items 1-19, wherein the individual has failed or is not adequately controlled with one or more standard therapeutic treatments for gastritis or gastroenteritis prior to administration of the composition. The method described in .
(Item 21)
21. The method of item 20, wherein said one or more standard therapeutic treatments for gastritis or gastroenteritis are selected from the group consisting of proton pump inhibitor (PPI) treatment, corticosteroid treatment, and dietary treatment.
(Item 22)
Item 1, wherein said one or more symptoms of gastritis, duodenitis, enteritis, or gastroenteritis in said individual are reduced after administration of said composition as compared to a baseline level prior to administration of said composition. 22. The method of any one of 21.
(Item 23)
said one or more symptoms of gastritis, duodenitis, enteritis, or gastroenteritis in said individual is reduced by at least 60% after administration of said composition as compared to a baseline level prior to administration of said composition; 23. The method of item 22.
(Item 24)
one or more of abdominal pain, nausea, vomiting, loss of appetite, abdominal cramps, feeling full before finishing a meal, abdominal bloating, diarrhea, and liquid or watery stools in said individual prior to administration of said composition; 22. The method of any one of items 1-21, wherein the level is reduced after administration of the composition as compared to baseline levels.
(Item 25)
A method for treating or preventing one or more symptoms of esophagitis in an individual comprising:
(a) detecting the number of mast cells from a first sample obtained from the esophageal mucosa of said individual;
(b) detecting the number of eosinophils from a second sample obtained from said esophageal mucosa of said individual;
(c) said first sample has an increased number of mast cells compared to a mast cell reference and said second sample has an increased number of eosinophils compared to a reference of eosinophils; If not, administering to said individual an effective amount of a composition comprising an antibody that binds to human Siglec-8;
A method, including
(Item 26)
1. A method for treating or preventing one or more symptoms of esophagitis in an individual comprising administering to said individual an effective amount of a composition comprising an antibody that binds to human Siglec-8, said individual has an increased number of mast cells in at least a portion of the esophageal mucosa compared to a mast cell reference, and said individual has an increased number of mast cells in at least a portion of said esophageal mucosa compared to an eosinophil reference A method that does not have an increase in the number of eosinophils.
(Item 27)
wherein a first sample obtained from said esophageal mucosa of said individual has an increased number of mast cells compared to said mast cell reference, and a second sample obtained from said esophageal mucosa of said individual. does not have an increase in the number of eosinophils compared to said eosinophil reference.
(Item 28)
28. The method of item 25 or item 27, wherein the first sample and the second sample are the same.
(Item 29)
29. The method of any one of items 25, 27 and 28, wherein one or both of the first and second samples are derived from an esophageal biopsy sample.
(Item 30)
29. The method of any one of items 25, 27, and 28, wherein one or both of the first and second samples are from esophagogastroduodenoscopy (EGD) by biopsy.
(Item 31)
Any one of items 25, 27, and 28-30, wherein the first sample has at least one HPF with a mast cell count of 10 or more mast cells per high power field (HPF) The method described in .
(Item 32)
32. The method of item 31, wherein the mast cells are detected by immunohistochemical (IHC) staining for tryptase, CD117, or IgE receptor.
(Item 33)
33. Any one of items 25, 27, and 28-32, wherein the second sample has one or more HPFs with an eosinophil count of less than 15 eosinophils per HPF. Method.
(Item 34)
33. The method of any one of items 25, 27, and 28-32, wherein said second sample has no HPFs with an eosinophil count of 15 or more eosinophils per HPF.
(Item 35)
35. The method of any one of items 25-34, wherein the individual has or has been diagnosed with gastroesophageal reflux disease (GERD).
(Item 36)
36. The method of item 35, wherein said individual is refractory to treatment with antacids, H2 blockers, and/or proton pump inhibitors.
(Item 37)
one or more of mast cell number, activity, or location in a sample obtained from said esophageal mucosa of said individual compared to baseline levels prior to administration of said composition 37. A method according to any one of items 25-36, which is subsequently reduced.
(Item 38)
38. Any one of paragraphs 25-37, wherein the individual has failed or is not adequately controlled with one or more standard therapeutic treatments for esophagitis prior to administration of the composition. the method of.
(Item 39)
39. Any one of items 25-38, wherein said one or more symptoms of esophagitis in said individual are reduced after administration of said composition as compared to a baseline level prior to administration of said composition. described method.
(Item 40)
40. The method of item 39, wherein the one or more symptoms of esophagitis in the individual are reduced by at least 60% after administration of the composition as compared to baseline levels prior to administration of the composition. .
(Item 41)
one of heartburn, nausea, dysphagia/dysphagia, vomiting, abdominal pain, cough, food compression, early satiety, loss of appetite, chest pain, intolerance or refusal to feed, and gastroesophageal reflux in said individual 39. The method of any one of items 25-38, wherein or more are reduced after administration of said composition compared to baseline levels prior to administration of said composition.
(Item 42)
A method for treating or preventing one or more symptoms of colitis in an individual comprising:
(a) detecting the number of mast cells from a first sample obtained from the colonic mucosa of said individual;
(b) detecting the number of eosinophils from a second sample obtained from the colonic mucosa of said individual;
(c) said first sample has an increased number of mast cells compared to a mast cell reference and said second sample has an increased number of eosinophils compared to a reference of eosinophils; If not, administering to said individual an effective amount of a composition comprising an antibody that binds to human Siglec-8;
A method, including
(Item 43)
1. A method for treating or preventing one or more symptoms of colitis in an individual comprising administering to said individual an effective amount of a composition comprising an antibody that binds to human Siglec-8; said individual has an increased number of mast cells in at least a portion of the colonic mucosa compared to a mast cell reference, and said individual has an increased number of mast cells in at least a portion of said colonic mucosa compared to an eosinophil reference A method that does not have an increase in the number of eosinophils.
(Item 44)
wherein a first sample obtained from said colonic mucosa of said individual has an increased number of mast cells compared to said mast cell reference, and a second sample obtained from said colonic mucosa of said individual. does not have an increase in the number of eosinophils compared to said eosinophil reference.
(Item 45)
45. The method of item 42 or item 44, wherein the first sample and the second sample are the same.
(Item 46)
46. The method of any one of items 42-45, wherein the colitis is ulcerative colitis.
(Item 47)
47. The method of any one of items 42-46, wherein the first sample has at least one HPF with a mast cell count of 30 or more mast cells per high power field (HPF).
(Item 48)
48. The method of item 47, wherein the mast cells are detected by immunohistochemical (IHC) staining for tryptase, CD117, or IgE receptor.
(Item 49)
49. The method of any one of items 42-48, wherein the second sample has one or more HPFs with an eosinophil count of less than 60 eosinophils per HPF.
(Item 50)
49. The method of any one of items 42-48, wherein the second sample does not have HPFs with an eosinophil count of 60 or more eosinophils per HPF.
(Item 51)
51. The method of any one of items 42-50, wherein the number of mast cells in the first sample is detected at or before 45 days of administration of the composition.
(Item 52)
said individual had or was previously diagnosed with eosinophilic colitis, and said individual has one of eosinophilic colitis without elevated eosinophils or 52. The method of any one of items 42-51, having multiple symptoms.
(Item 53)
one or both of mast cell number or activity in a sample obtained from said colonic mucosa of said individual is reduced after administration of said composition compared to a baseline level prior to administration of said composition , items 42 to 52.
(Item 54)
54. Any one of paragraphs 42-53, wherein the individual has failed or is not adequately controlled with one or more standard therapeutic treatments for colitis prior to administration of the composition. the method of.
(Item 55)
55. Any one of items 42-54, wherein said one or more symptoms of colitis in said individual are reduced after administration of said composition as compared to a baseline level prior to administration of said composition described method.
(Item 56)
56. The method of item 55, wherein the one or more symptoms of colitis in the individual are reduced by at least 60% after administration of the composition as compared to baseline levels prior to administration of the composition. .
(Item 57)
57. The method of any one of items 1-56, wherein the composition is administered by intravenous infusion.
(Item 58)
58. The method of item 57, wherein the composition is administered by intravenous infusion once a month for 3 months or more.
(Item 59)
57. The method of any one of items 1-56, wherein the composition is administered by subcutaneous injection.
(Item 60)
57. Any one of items 1-56, wherein said composition is administered by intravenous infusion in one or more doses comprising between about 0.3 mg/kg and about 3.0 mg/kg of said antibody. The method described in .
(Item 61)
administering to said individual a first dose comprising about 0.3 mg/kg of said antibody, a second dose comprising about 1.0 mg/kg of said antibody, and a third dose comprising about 3.0 mg/kg of said antibody; 57. The method of any one of items 1-56, comprising administering a dose of
(Item 62)
The individual receives a first dose comprising about 0.3 mg/kg of the antibody on day 1 and a second dose comprising about 1.0 mg/kg of the antibody between days 26 and 32. a third dose comprising about 3.0 mg/kg of said antibody on days 54-60, and a fourth dose comprising about 3.0 mg/kg of said antibody on days 82-88. Between days 110 and 116, a fifth dose containing about 3.0 mg/kg of said antibody, and a sixth dose containing about 3.0 mg/kg of said antibody between days 138 and 138 62. The method of item 61, comprising administering between days 1 and 144.
(Item 63)
said antibody comprises an Fc region and N-glycoside carbohydrate chains linked to said Fc region, wherein less than 50% of said N-glycoside carbohydrate chains of said antibody in said composition are 63. A method according to any one of items 1 to 62, comprising a fucose residue.
(Item 64)
64. The method of item 63, wherein substantially all of said N-glycoside-linked carbohydrate chains of said antibody in said composition are free of fucose residues.
(Item 65)
said antibody comprising a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region comprises (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:61, (ii) HVR comprising the amino acid sequence of SEQ ID NO:62 -H2, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:63, and/or HVR-L1, wherein said light chain variable region (i) comprises the amino acid sequence of SEQ ID NO:64, (ii) the sequence 65. A method according to any one of items 1 to 64, comprising HVR-L2 comprising the amino acid sequence of number 65 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:66.
(Item 66)
said antibody comprising a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region comprises (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:61, (ii) HVR comprising the amino acid sequence of SEQ ID NO:62 -H2, and (iii) HVR-H3 comprising an amino acid sequence selected from SEQ ID NOs:67-70, and/or HVR-L1 wherein said light chain variable region (i) comprises the amino acid sequence of SEQ ID NO:64 , (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:65, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:71.
(Item 67)
65. The antibody according to any one of items 1 to 64, wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 6 and/or a light chain variable region comprising an amino acid sequence selected from SEQ ID NO: 16 or 21. described method.
(Item 68)
of items 1 to 64, wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 11-14 and/or a light chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 23-24 A method according to any one of paragraphs.
(Item 69)
of items 1 to 64, wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 2-14 and/or a light chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 16-24 A method according to any one of paragraphs.
(Item 70)
of items 1 to 64, wherein said antibody comprises a heavy chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 2-10 and/or a light chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 16-22 A method according to any one of paragraphs.
(Item 71)
the antibody
(a) (1) HC-FR1 comprising an amino acid sequence selected from SEQ ID NOS: 26-29;
(2) HVR-H1 comprising the amino acid sequence of SEQ ID NO:61;
(3) HC-FR2 comprising an amino acid sequence selected from SEQ ID NOS: 31-36;
(4) HVR-H2 comprising the amino acid sequence of SEQ ID NO:62;
(5) HC-FR3 comprising an amino acid sequence selected from SEQ ID NOS: 38-43;
(6) HVR-H3 comprising the amino acid sequence of SEQ ID NO:63, and
(7) a heavy chain variable region comprising HC-FR4 comprising an amino acid sequence selected from SEQ ID NOS: 45-46, and/or
(b) (1) LC-FR1 comprising an amino acid sequence selected from SEQ ID NOS: 48-49;
(2) HVR-L1 comprising the amino acid sequence of SEQ ID NO:64;
(3) LC-FR2 comprising an amino acid sequence selected from SEQ ID NOS:51-53;
(4) HVR-L2 comprising the amino acid sequence of SEQ ID NO:65;
(5) LC-FR3 comprising an amino acid sequence selected from SEQ ID NOS:55-58;
(6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:66, and
(7) a light chain variable region comprising LC-FR4 comprising the amino acid sequence of SEQ ID NO:60
65. The method of any one of items 1-64, comprising
(Item 72)
the antibody
(a) (1) HC-FR1 comprising the amino acid sequence of SEQ ID NO:26;
(2) HVR-H1 comprising the amino acid sequence of SEQ ID NO:61;
(3) HC-FR2 comprising the amino acid sequence of SEQ ID NO:34;
(4) HVR-H2 comprising the amino acid sequence of SEQ ID NO:62;
(5) HC-FR3 comprising the amino acid sequence of SEQ ID NO:38;
(6) HVR-H3 comprising the amino acid sequence of SEQ ID NO:63, and
(7) a heavy chain variable region comprising HC-FR4 comprising the amino acid sequence of SEQ ID NO:45, and/or
(b) (1) LC-FR1 comprising the amino acid sequence of SEQ ID NO:48;
(2) HVR-L1 comprising the amino acid sequence of SEQ ID NO:64;
(3) LC-FR2 comprising the amino acid sequence of SEQ ID NO:51;
(4) HVR-L2 comprising the amino acid sequence of SEQ ID NO:65;
(5) LC-FR3 comprising the amino acid sequence of SEQ ID NO:55;
(6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:66, and
(7) a light chain variable region comprising LC-FR4 comprising the amino acid sequence of SEQ ID NO:60
65. The method of any one of items 1-64, comprising
(Item 73)
the antibody
(a) (1) HC-FR1 comprising the amino acid sequence of SEQ ID NO:26;
(2) HVR-H1 comprising the amino acid sequence of SEQ ID NO:61;
(3) HC-FR2 comprising the amino acid sequence of SEQ ID NO:34;
(4) HVR-H2 comprising the amino acid sequence of SEQ ID NO:62;
(5) HC-FR3 comprising the amino acid sequence of SEQ ID NO:38;
(6) HVR-H3 comprising the amino acid sequence of SEQ ID NO:63, and
(7) a heavy chain variable region comprising HC-FR4 comprising the amino acid sequence of SEQ ID NO:45, and/or
(b) (1) LC-FR1 comprising the amino acid sequence of SEQ ID NO:48;
(2) HVR-L1 comprising the amino acid sequence of SEQ ID NO:64;
(3) LC-FR2 comprising the amino acid sequence of SEQ ID NO:51;
(4) HVR-L2 comprising the amino acid sequence of SEQ ID NO:65;
(5) LC-FR3 comprising the amino acid sequence of SEQ ID NO:58;
(6) HVR-L3 comprising the amino acid sequence of SEQ ID NO:66, and
(7) a light chain variable region comprising LC-FR4 comprising the amino acid sequence of SEQ ID NO:60
65. The method of any one of items 1-64, comprising
(Item 74)
the antibody
A heavy chain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:88, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:91, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:94. variable region and/or (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:97, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:100, and (iii) HVR- comprising the amino acid sequence of SEQ ID NO:103 a light chain variable region comprising L3;
A heavy chain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:89, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:92, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:95 variable region and/or (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:98, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:101, and (iii) HVR- comprising the amino acid sequence of SEQ ID NO:104 a light chain variable region comprising L3, or
A heavy chain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:90, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:93, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:96 variable region and/or (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:99, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:102, and (iii) HVR- comprising the amino acid sequence of SEQ ID NO:105 light chain variable region, including L3
65. The method of any one of items 1-64, comprising
(Item 75)
the antibody
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 106 and/or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 109;
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 107 and/or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 110, or
A heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 108 and/or a light chain variable region comprising the amino acid sequence of SEQ ID NO: 111
65. The method of any one of items 1-64, comprising
(Item 76)
65. The method of any one of items 1-64, wherein said antibody binds to human Siglec-8 and non-human primate Siglec-8.
(Item 77)
77. The method of item 76, wherein said non-human primate is a baboon.
(Item 78)
77. The method of item 76, wherein said antibody binds to an epitope within domain 1 of human Siglec-8, and domain 1 comprises the amino acid sequence of SEQ ID NO:112.
(Item 79)
77. The method of item 76, wherein said antibody binds to an epitope within domain 3 of human Siglec-8, and domain 3 comprises the amino acid sequence of SEQ ID NO:114.
(Item 80)
77. The method of item 76, wherein said antibody binds to the same epitope as antibody 4F11.
(Item 81)
65. The method of any one of items 1-64, wherein said antibody binds to an epitope within domain 2 or domain 3 of human Siglec-8.
(Item 82)
82. The method of item 81, wherein domain 2 comprises the amino acid sequence of SEQ ID NO:113.
(Item 83)
82. The method of item 81, wherein said antibody binds to the same epitope as antibody 1C3.
(Item 84)
82. The method of item 81, wherein domain 3 comprises the amino acid sequence of SEQ ID NO:114.
(Item 85)
82. The method of item 81, wherein said antibody binds to the same epitope as antibody 1H10.
(Item 86)
65. The method of any one of items 1-64, wherein said antibody binds to an epitope within domain 1 of human Siglec-8 and competes with antibody 4F11 for binding to Siglec-8.
(Item 87)
87. The method of item 86, wherein said antibody does not compete with antibody 2E2 for binding to Siglec-8.
(Item 88)
88. The method of item 87, wherein said antibody is not antibody 2E2.
(Item 89)
87. The method of item 86, wherein Domain 1 comprises the amino acid sequence of SEQ ID NO:112.
(Item 90)
90. The method of any one of items 65-89, wherein said antibody is a human antibody, a humanized antibody, or a chimeric antibody.
(Item 91)
91. The method of any one of items 65-90, wherein said antibody depletes blood eosinophils and inhibits mast cell activation.
(Item 92)
92. The method of any one of items 65-91, wherein said antibody comprises a heavy chain Fc region comprising a human IgG Fc region.
(Item 93)
93. The method of item 92, wherein said human IgG Fc region comprises a human IgG1 Fc region.
(Item 94)
94. The method of item 93, wherein said human IgG1 Fc region is non-fucosylated.
(Item 95)
93. The method of item 92, wherein said human IgG Fc region comprises a human IgG4 Fc region.
(Item 96)
96. The method of item 95, wherein said human IgG4 Fc region comprises the amino acid substitution S228P and amino acid residues are numbered according to the EU index as in Kabat.
(Item 97)
90. The method of any one of items 65-89, wherein said antibody is engineered to enhance antibody-dependent cell-mediated cytotoxicity (ADCC) activity.
(Item 98)
98. The method of item 97, wherein said antibody comprises at least one amino acid substitution in said Fc region that enhances ADCC activity.
(Item 99)
92. The method of any one of items 65-91, wherein at least one or two of said heavy chains of said antibody are not fucosylated.
(Item 100)
65. The method of any one of items 1-64, wherein said antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:75 and/or a light chain comprising an amino acid sequence selected from SEQ ID NO:76 or 77.
(Item 101)
101. The method of any one of items 1-100, wherein said antibody is a monoclonal antibody.
(Item 102)
102. The method of any one of items 1-101, wherein the composition is administered in combination with one or more additional therapeutic agents for treating or preventing gastritis, gastroenteritis, or esophagitis.
(Item 103)
The one or more additional therapeutic agents for treating or preventing gastritis, gastroenteritis, or esophagitis are PPIs, systemic corticosteroids, topical corticosteroids, antihistamines, mast cell stabilizers, 103. The method of item 102, selected from the group consisting of H-2 blockers, anti-IgE antibodies, calcineurin inhibitors, immunomodulatory agents, and immunosuppressive agents.
(Item 104)
104. The method of any one of items 1-103, wherein the individual is a human.
(Item 105)
105. The method of any one of items 1-104, wherein said composition is a pharmaceutical composition comprising said antibody and a pharmaceutically acceptable carrier.
(Item 106)
a medicament comprising a composition comprising an antibody that binds to human Siglec-8 and an package insert containing instructions for administration of said medicament in an individual in need thereof according to any one of items 1 to 105 including, products.

Claims

A composition for use in a method for treating or preventing one or more symptoms of gastritis, enteritis, duodenitis, or gastroenteritis in an individual, said composition comprising an antibody that binds to human Siglec-8, said the method is
(a) detecting the number of mast cells from a first sample obtained from the mucosa of the stomach, duodenum, jejunum, ileum, or colon of said individual;
(b) detecting the number of eosinophils from a second sample obtained from the mucosa of the stomach, duodenum, jejunum, ileum, or colon of said individual;
(c) said first sample has an increased number of mast cells compared to a mast cell reference and said second sample has an increased number of eosinophils compared to a reference of eosinophils; If not having an increase in number , administering to said individual an effective amount of said composition.

A composition for use in a method for treating or preventing one or more symptoms of gastritis, enteritis, duodenitis, or gastroenteritis in an individual, said composition comprising an antibody that binds to human Siglec-8, said The method comprises administering an effective amount of the composition to the individual, wherein the individual has at least a portion of the mucosa of the stomach, duodenum, jejunum, ileum, or colon as compared to a mast cell reference. and said individual has an increased number of eosinophils in at least a portion of the mucosa of said stomach, duodenum, jejunum, ileum, or colon compared to a reference eosinophil No composition .

wherein a first sample obtained from the mucosa of said stomach, duodenum, jejunum, ileum, or colon of said individual has an increased number of mast cells compared to a reference of said mast cells; 3. The method of claim 2, wherein a second sample obtained from the mucosa of the stomach, duodenum, jejunum, ileum, colon does not have an increase in the number of eosinophils compared to the eosinophil reference. Composition for use .

4. The composition for use according to claim 1 or claim 3, wherein said first sample and said second sample are the same.

Claim 1, 3, wherein one or both of said first and second samples are derived from a gastric or duodenal biopsy or from biopsy esophagogastroduodenoscopy (EGD). and 5. A composition for use according to any one of claims 4 and 5.

wherein said first sample has at least one HPF having a mast cell number of 20 or more mast cells per high power field (HPF) ; , or as detected by immunohistochemical ( IHC ) staining for IgE receptors .

(a) said second sample has one or more HPFs, each having an eosinophil count of less than 30 eosinophils per HPF;
(b) said second sample is obtained from said gastric mucosa of said individual, said second sample each having an eosinophil count of 30 or more eosinophils per HPF; do not have HPF, or
(c) said second sample is obtained from said duodenal mucosa of said individual, said second sample each having an eosinophil count of 30 or more eosinophils per HPF; having no HPF;
7. A composition for use according to any one of claims 1, 3 and 4-6 .

8. The use of any one of claims 1, 3, and 4-7 , wherein the number of mast cells in the first sample is detected 45 days or more prior to administration of the composition. composition for .

said individual is
(a) has or has been diagnosed as having gastroesophageal reflux disease (GERD), and optionally said individual has been treated with an antacid, an H2 blocker, and/or a proton pump inhibitor; refractory to
(b) has or has been diagnosed with irritable bowel syndrome (IBS);
(c) has or is diagnosed as having functional dyspepsia;
(d) had or was previously diagnosed as having eosinophilic gastritis, and said individual has one or more symptoms of eosinophilic gastritis without elevated eosinophils; or
(e) had or was previously diagnosed with eosinophilic gastroenteritis, and said individual has one or more of eosinophilic gastroenteritis without elevated eosinophils; have symptoms of
A composition for use according to any one of claims 1 to 8 .

one or both of mast cell number or activity in a sample obtained from the mucosa of the stomach, duodenum, jejunum, ileum, or colon of the individual compared to baseline levels prior to administration of the composition , is reduced after administration of said composition.

Prior to administration of the composition, the individual has failed or is not adequately controlled with one or more standard therapeutic treatments for gastritis or gastroenteritis and, optionally, gastritis or gastroenteritis. 11. Any one of claims 1-10 , wherein the one or more standard therapeutic treatments for inflammation are selected from the group consisting of proton pump inhibitor (PPI) treatments, corticosteroid treatments, and dietary treatments. A composition for use as described in .

(a) said one or more symptoms of gastritis, duodenitis, enteritis, or gastroenteritis in said individual are reduced after administration of said composition as compared to a baseline level prior to administration of said composition; optionally, the one or more symptoms of gastritis, duodenitis, enteritis, or gastroenteritis in said individual are reduced after administration of said composition compared to baseline levels prior to administration of said composition , is reduced by at least 60%, or
(b) one or more of abdominal pain, nausea, vomiting, loss of appetite, abdominal cramps, feeling full before finishing a meal, bloating, diarrhea, and liquid or watery stools in said individual is associated with said composition; reduced after administration of the composition compared to baseline levels prior to administration;
A composition for use according to any one of claims 1 to 11 .

1. A composition for use in a method for treating or preventing one or more symptoms of esophagitis in an individual, comprising an antibody that binds to human Siglec-8, said method comprising:
(a) detecting the number of mast cells from a first sample obtained from the esophageal mucosa of said individual;
(b) detecting the number of eosinophils from a second sample obtained from said esophageal mucosa of said individual;
(c) said first sample has an increased number of mast cells compared to a mast cell reference and said second sample has an increased number of eosinophils compared to a reference of eosinophils; If not having an increase in number , administering to said individual an effective amount of said composition.

A composition for use in a method for treating or preventing one or more symptoms of esophagitis in an individual, said method comprising an antibody that binds to human Siglec-8, said method comprising: amount of the composition, wherein the individual has an increased number of mast cells in at least a portion of the esophageal mucosa compared to a mast cell reference, and the individual has eosinophils A composition that does not have an increased number of eosinophils in at least a portion of said esophageal mucosa compared to a reference.

wherein a first sample obtained from said esophageal mucosa of said individual has an increased number of mast cells compared to said mast cell reference, and a second sample obtained from said esophageal mucosa of said individual. does not have an increase in the number of eosinophils compared to said eosinophil reference.

16. The composition for use according to claim 13 or claim 15 , wherein said first sample and said second sample are the same.

17. One or both of said first and second samples are derived from an esophageal biopsy sample or from esophagogastroduodenoscopy (EGD) with biopsy . A composition for use according to any one of

The first sample has at least one HPF with a mast cell count of 10 or more mast cells per high power field (HPF), and optionally the mast cells are characterized by tryptase, CD117, 18. A composition for use according to any one of claims 13, 15 and 16-17 , as detected by immunohistochemical (IHC) staining for IgE receptors .

said second sample has an eosinophil count of less than 15 eosinophils per HPF; has one or more HPFs; 19. The composition for use according to any one of claims 13, 15 and 16 to 18 , having no HPF with an eosinophil count of acid globules .

said individual has or has been diagnosed with gastroesophageal reflux disease (GERD) , and optionally said individual is treated with an antacid, an H2 blocker, and/or a proton pump inhibitor 20. A composition for use according to any one of claims 13 to 19 , which is refractory to

one or more of mast cell number, activity, or location in a sample obtained from said esophageal mucosa of said individual compared to baseline levels prior to administration of said composition 14. reduced after and/or prior to administration of said composition said individual has failed or is not adequately controlled with one or more standard therapeutic treatments for esophagitis. 21. A composition for use according to any one of claims 20 to 20 .

(a) said one or more symptoms of esophagitis in said individual are reduced after administration of said composition compared to a baseline level prior to administration of said composition; the one or more symptoms of esophagitis in the individual are reduced by at least 60% after administration of the composition as compared to baseline levels prior to administration of the composition;
(b) of heartburn, nausea, dysphagia/dysphagia, vomiting, abdominal pain, cough, food compression, early satiety, loss of appetite, chest pain, intolerance or refusal to feed, and gastroesophageal reflux in said individual is reduced after administration of the composition compared to baseline levels prior to administration of the composition;
A composition for use according to any one of claims 13-21 .

1. A composition for use in a method for treating or preventing one or more symptoms of colitis in an individual, comprising an antibody that binds to human Siglec-8, said method comprising:
(a) detecting the number of mast cells from a first sample obtained from the colonic mucosa of said individual;
(b) detecting the number of eosinophils from a second sample obtained from the colonic mucosa of said individual;
(c) said first sample has an increased number of mast cells compared to a mast cell reference and said second sample has an increased number of eosinophils compared to a reference of eosinophils; If not having an increase in number , administering to said individual an effective amount of said composition.

A composition for use in a method for treating or preventing one or more symptoms of colitis in an individual, said method comprising an antibody that binds to human Siglec-8, said method comprising: amount of the composition, wherein the individual has an increased number of mast cells in at least a portion of the colonic mucosa compared to a mast cell reference, and the individual has eosinophils A composition that does not have an increased number of eosinophils in at least a portion of said colonic mucosa compared to a reference.

wherein a first sample obtained from said colonic mucosa of said individual has an increased number of mast cells compared to said mast cell reference, and a second sample obtained from said colonic mucosa of said individual. does not have an increase in the number of eosinophils compared to said eosinophil reference.

26. The composition for use according to claim 23 or claim 25 , wherein said first sample and said second sample are the same.

27. A composition for use according to any one of claims 23 to 26 , wherein said colitis is ulcerative colitis.

The first sample has at least one HPF with a mast cell count of 30 or more mast cells per high power field (HPF), and optionally the mast cells are characterized by tryptase, CD117, or as detected by immunohistochemical (IHC) staining for IgE receptors .

said second sample has an eosinophil count of less than 60 eosinophils per HPF; has one or more HPFs; 29. The composition for use according to any one of claims 23 to 28 , having no HPF with an eosinophil count of acid globules .

(a) the number of mast cells in the first sample is detected 45 days or more prior to administration of the composition;
(b) said individual had or was previously diagnosed with eosinophilic colitis and said individual has eosinophilic colitis without elevated eosinophils; have one or more symptoms;
(c) one or both of mast cell number or activity in a sample obtained from said colonic mucosa of said individual is compared to a baseline level prior to administration of said composition after administration of said composition; reduced,
(d) prior to administration of the composition, the individual has failed or is not adequately controlled with one or more standard therapeutic treatments for colitis, and/or
(e) said one or more symptoms of colitis in said individual are reduced after administration of said composition compared to a baseline level prior to administration of said composition; said one or more symptoms of colitis are reduced by at least 60% after administration of said composition as compared to baseline levels prior to administration of said composition;
30. A composition for use according to any one of claims 23-29 .

(a) said composition is administered by intravenous infusion, optionally said composition is administered by intravenous infusion once a month for 3 months or more;
(b) the composition is administered by subcutaneous injection;
(c) said composition is administered by intravenous infusion in one or more doses comprising between about 0.3 mg/kg and about 3.0 mg/kg of said antibody, or
(d) said method administering to said individual a first dose comprising about 0.3 mg/kg of said antibody, a second dose comprising about 1.0 mg/kg of said antibody, and about 3.0 mg/kg; optionally wherein said method administers to said individual a first dose comprising about 0.3 mg/kg of said antibody on day 1 for about A second dose comprising 1.0 mg/kg of said antibody between days 26 and 32 and a third dose comprising about 3.0 mg/kg of said antibody between days 54 and 60. a fourth dose comprising about 3.0 mg/kg of said antibody between days 82 and 88, and a fifth dose comprising about 3.0 mg/kg of said antibody from day 110. administering a sixth dose comprising about 3.0 mg/kg of said antibody during day 116 between days 138 and 144;
31. A composition for use according to any one of claims 1-30 .

said antibody comprises an Fc region and N-glycoside carbohydrate chains linked to said Fc region, wherein less than 50% of said N-glycoside carbohydrate chains of said antibody in said composition are of claims 1-31 , comprising fucose residues, and optionally substantially all of said N-glycoside-linked carbohydrate chains of said antibody in said composition being free of fucose residues. A composition for use according to any one of the claims.

said antibody comprises a heavy chain variable region and a light chain variable region;
(a) said heavy chain variable region comprises (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:61, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:62, and (iii) the amino acid sequence of SEQ ID NO:63. and wherein said light chain variable region comprises (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:64, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:65, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 66;
(b) said heavy chain variable region comprises (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:61, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:62, and (iii) from SEQ ID NOS:67-70 HVR-H3 comprising a selected amino acid sequence, wherein said light chain variable region comprises (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:64, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:65 and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:71.
(c) said heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 6 and said light chain variable region comprises an amino acid sequence selected from SEQ ID NO: 16 or 21;
(d) said heavy chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 11-14, and said light chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 23-24;
(e) said heavy chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 2-14, and said light chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 16-24;
(f) said heavy chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 2-10, and said light chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 16-22;
(g) the heavy chain variable region is selected from (1) HC-FR1 comprising an amino acid sequence selected from SEQ ID NOS:26-29, HVR-H1 comprising the amino acid sequence of SEQ ID NO:61, and SEQ ID NOS:31-36; HC-FR2 containing the amino acid sequence of SEQ ID NO: 62, HVR-H2 containing the amino acid sequence of SEQ ID NO: 62, HC-FR3 containing the amino acid sequence selected from SEQ ID NOS: 38-43, HVR-H3 containing the amino acid sequence of SEQ ID NO: 63, and HC-FR4 comprising an amino acid sequence selected from SEQ ID NOS: 45-46, wherein said light chain variable region comprises an amino acid sequence selected from SEQ ID NOS: 48-49, LC-FR1 comprising an amino acid sequence of SEQ ID NO: 64; LC-FR2 comprising an amino acid sequence selected from SEQ ID NOS: 51-53; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 65; LC-FR3 comprising an amino acid sequence selected from SEQ ID NOS: 55-58 , HVR-L3 comprising the amino acid sequence of SEQ ID NO:66, and LC-FR4 comprising the amino acid sequence of SEQ ID NO:60,
(h) the heavy chain variable region comprises HC-FR1 comprising the amino acid sequence of SEQ ID NO: 26, HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HC-FR2 comprising the amino acid sequence of SEQ ID NO: 34, SEQ ID NO: 62 HVR-H2 comprising the amino acid sequence, HC-FR3 comprising the amino acid sequence of SEQ ID NO:38, HVR-H3 comprising the amino acid sequence of SEQ ID NO:63, and HC-FR4 comprising the amino acid sequence of SEQ ID NO:45, said light chain LC-FR1 whose variable region contains the amino acid sequence of SEQ ID NO: 48, HVR-L1 whose variable region contains the amino acid sequence of SEQ ID NO: 64, LC-FR2 whose variable region contains the amino acid sequence of SEQ ID NO: 51, and HVR-L2 whose variable region contains the amino acid sequence of SEQ ID NO: 65 , LC-FR3 comprising the amino acid sequence of SEQ ID NO:55, HVR-L3 comprising the amino acid sequence of SEQ ID NO:66, and LC-FR4 comprising the amino acid sequence of SEQ ID NO:60.
(i) the heavy chain variable region comprises HC-FR1 comprising the amino acid sequence of SEQ ID NO:26, HVR-H1 comprising the amino acid sequence of SEQ ID NO:61, HC-FR2 comprising the amino acid sequence of SEQ ID NO:34, SEQ ID NO:62 HVR-H2 comprising the amino acid sequence, HC-FR3 comprising the amino acid sequence of SEQ ID NO:38, HVR-H3 comprising the amino acid sequence of SEQ ID NO:63, and HC-FR4 comprising the amino acid sequence of SEQ ID NO:45, said light chain LC-FR1 whose variable region contains the amino acid sequence of SEQ ID NO: 48, HVR-L1 whose variable region contains the amino acid sequence of SEQ ID NO: 64, LC-FR2 whose variable region contains the amino acid sequence of SEQ ID NO: 51, and HVR-L2 whose variable region contains the amino acid sequence of SEQ ID NO: 65 , LC-FR3 comprising the amino acid sequence of SEQ ID NO:58, HVR-L3 comprising the amino acid sequence of SEQ ID NO:66, and LC-FR4 comprising the amino acid sequence of SEQ ID NO:60.
(j) the heavy chain variable region comprises (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:88, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:91, and (iii) the amino acid sequence of SEQ ID NO:94. and wherein said light chain variable region comprises (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 97, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 100, and (iii) SEQ ID NO: including HVR-L3, which comprises a 103 amino acid sequence;
(k) the heavy chain variable region comprises (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:89, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:92, and (iii) the amino acid sequence of SEQ ID NO:95. and wherein said light chain variable region comprises (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 98, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 101, and (iii) SEQ ID NO: HVR-L3 comprising a 104 amino acid sequence;
(l) the heavy chain variable region comprises (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:90, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:93, and (iii) the amino acid sequence of SEQ ID NO:96. and wherein said light chain variable region comprises (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 99, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 102, and (iii) SEQ ID NO: including HVR-L3, which comprises a 105 amino acid sequence;
(m) said heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 106 and said light chain variable region comprises the amino acid sequence of SEQ ID NO: 109;
(n) said heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 107 and said light chain variable region comprises the amino acid sequence of SEQ ID NO: 110, or
(o) said heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 108 and said light chain variable region comprises the amino acid sequence of SEQ ID NO: 111;
33. A composition for use according to any one of claims 1-32 .

Composition for use according to any one of claims 1 to 32 , wherein said antibody binds to human Siglec-8 and non-human primate Siglec-8.

Composition for use according to any one of claims 1 to 32 , wherein said antibody binds to an epitope within domain 2 or domain 3 of human Siglec-8.

Composition for use according to any one of claims 1 to 32 , wherein said antibody binds to an epitope within domain 1 of human Siglec-8 and competes with antibody 4F11 for binding to Siglec-8. things .

37. The composition for use according to any one of claims 33-36 , wherein said antibody is a human, humanized or chimeric antibody.

38. The composition for use according to any one of claims 33 to 37 , wherein said antibody depletes blood eosinophils and inhibits mast cell activation.

39. The composition for use according to any one of claims 33-38 , wherein said antibody comprises a heavy chain Fc region comprising a human IgG Fc region.

(a) said human IgG Fc region comprises a human IgG1 Fc region, optionally said human IgG1 Fc region is not fucosylated, or
(b) said human IgG Fc region comprises a human IgG4 Fc region, optionally said human IgG4 Fc region comprises the amino acid substitution S228P, wherein amino acid residues are numbered according to the EU index as in Kabat; ing,
A composition for use according to claim 39 .

wherein said antibody has been engineered to enhance antibody-dependent cell-mediated cytotoxicity (ADCC) activity , and optionally said antibody comprises in said Fc region at least one amino acid substitution that enhances ADCC activity 37. A composition for use according to any one of claims 33 to 36 , comprising

39. The composition for use according to any one of claims 33-38 , wherein at least one or two of said heavy chains of said antibody are non-fucosylated.

33. Use according to any one of claims 1 to 32 , wherein said antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 75 and/or a light chain comprising an amino acid sequence selected from SEQ ID NO: 76 or 77. composition for .

44. Composition for use according to any one of claims 1 to 43 , wherein said antibody is a monoclonal antibody.

The composition is administered in combination with one or more additional therapeutic agents for treating or preventing gastritis, gastroenteritis, or esophagitis, and optionally gastritis, gastroenteritis, or esophagitis. said one or more additional therapeutic agents for treatment or prevention are PPIs, systemic corticosteroids, topical corticosteroids, antihistamines, mast cell stabilizers, H-2 blockers, anti-IgE antibodies, 45. A composition for use according to any one of claims 1 to 44 , selected from the group consisting of calcineurin inhibitors, immunomodulatory agents and immunosuppressive agents .

46. The composition for use according to any one of claims 1-45 , wherein said individual is a human.

47. Composition for use according to any one of claims 1 to 46 , wherein said composition is a pharmaceutical composition comprising said antibody and a pharmaceutically acceptable carrier.

a medicament comprising a composition comprising an antibody that binds to human Siglec-8 and an insert containing instructions for the administration of said medicament in an individual in need thereof according to any one of claims 1 to 47 Products, including.