JPWO2019121906A5 - FC binding fragment with PD-LI antigen binding site - Google Patents

FC binding fragment with PD-LI antigen binding site Download PDF

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JPWO2019121906A5
JPWO2019121906A5 JP2020533846A JP2020533846A JPWO2019121906A5 JP WO2019121906 A5 JPWO2019121906 A5 JP WO2019121906A5 JP 2020533846 A JP2020533846 A JP 2020533846A JP 2020533846 A JP2020533846 A JP 2020533846A JP WO2019121906 A5 JPWO2019121906 A5 JP WO2019121906A5
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好ましくは、第１の配列は、ＣＨ３ドメインの残基１４から１８において局在し、第２の配列は、ＣＨ３ドメインの４５．１から７８位において局在し、及び／又は第３の配列は、ＣＨ３ドメインの９２から１００位、又は９２から１０１位において局在し、アミノ酸残基ナンバリングは、ImMunoGeneTics（ＩＭＧＴ）ナンバリングスキームに従う。
 Preferably, the first sequence is located at residues 14 to 18 of the CH3 domain, the second sequence is located at positions 45.1 to 78 of the CH3 domain, and/or the third sequence is located at positions 45.1 to 78 of the CH3 domain. , located at positions 92 to 100 , or 92 to 101 of the CH3 domain, and amino acid residue numbering follows the ImMunoGeneTics (IMGT) numbering scheme.

Claims (59)

プログラム細胞死リガンド１（ＰＤ－Ｌ１）に結合する特異的結合メンバーであって、
当該特異的結合メンバーは、ＣＨ３ドメインを含み、かつ、当該特異的結合メンバーは、前記ＣＨ３ドメイン中に局在するＰＤ－Ｌ１抗原結合部位を含み、
前記ＣＨ３ドメインが、当該ＣＨ３ドメインの１１から１８位に局在するＡＢ構造ループと、当該ＣＨ３ドメインの４３から７８位に局在するＣＤ構造ループと、当該ＣＨ３ドメインの９２から１０１位に局在するＥＦ構造ループと、を含み、
前記ＰＤ－Ｌ１抗原結合部位が、
（ｉ）前記ＣＨ３ドメインの１４から１８位におけるＡＢ構造ループ中に局在する第１の配列であって、前記特異的結合メンバーが、前記ＣＨ３ドメインの１４、１５又は１６位におけるアミノ酸欠失を含み、当該第１の配列が、
（ａ）アミノ酸配列ＳＧＹＷ（配列番号２３）、又は
（ｂ）配列番号２３のバリアントからなり、
前記セリン（Ｓ）が、アミノ酸Ａ、Ｅ、Ｆ、Ｇ、Ｈ、Ｉ、Ｌ、Ｐ、Ｒ、Ｔ、Ｖ、又はＹにより置換されており、及び／又は
前記グリシン（Ｇ）が、アミノ酸Ａ、Ｄ、Ｅ、Ｆ、Ｈ、Ｋ、Ｌ、Ｎ、Ｐ、Ｒ、Ｔ、Ｖ、又はＹにより置換されている、
第１の配列；
（ｉｉ）前記ＣＨ３ドメインの４５．１から７８位におけるＣＤ構造ループ中に局在する第２の配列であって、当該第２の配列が、
（ａ）アミノ酸配列ＥＰＱＹＷＡ（配列番号１１）、又は
（ｂ）配列番号１１のバリアントからなり、
前記グルタミン酸（Ｅ）が、アミノ酸Ａ、Ｇ、Ｈ、Ｉ、Ｌ、Ｎ、Ｑ、Ｒ、Ｓ、又はＷにより置換されており、及び／又は
前記プロリン（Ｐ）が、アミノ酸Ａ、Ｄ、Ｅ、Ｇ、Ｈ、Ｎ、Ｑ、Ｗ、又はＹにより置換されており、及び／又は
前記グルタミン（Ｑ）が、アミノ酸Ｈ、又はＮにより置換されており、及び／又は
前記チロシン（Ｙ）が、アミノ酸Ａ、Ｄ、Ｈ、Ｔ、又はＶにより置換されており、及び／又は
前記アラニン（Ａ）が、アミノ酸Ｄ、Ｅ、Ｇ、Ｌ、Ｒ、Ｓ、又はＷにより置換されている、
第２の配列；及び
（ｉｉｉ）前記ＣＨ３ドメインの９２から１００位又は９２から１０１位におけるＥＦ構造ループ中に局在する第３の配列であって、当該第３の配列が、
（ａ）アミノ酸配列ＳＮＷＲＷＱＭＤＤ（配列番号１９）、又は
（ｂ）配列番号１９のバリアントからなり、
９２位における前記セリン（Ｓ）が、アミノ酸Ａ、又はＧにより置換されており、及び／又は
９３位における前記アスパラギン（Ｎ）が、アミノ酸Ａ、Ｅ、Ｆ、Ｇ、Ｈ、Ｉ、Ｋ、Ｌ、Ｑ、Ｒ、Ｓ、Ｔ、又はＹにより置換されており、及び／又は
９７位における前記グルタミン（Ｑ）が、アミノ酸Ａ、Ｄ、Ｅ、Ｆ、Ｇ、Ｈ、Ｋ、Ｌ、Ｎ、Ｒ、Ｓ、又はＶにより置換されており、及び／又は
９８位における前記メチオニン（Ｍ）が、アミノ酸Ｆ、Ｉ、Ｌ、Ｖ、Ｗ、又はＹにより置換されており、及び／又は
９９位における前記アスパラギン酸（Ｄ）が、アミノ酸Ａ、Ｉ、Ｌ、Ｒ、Ｓ、Ｔ、Ｖ、Ｗ、Ｙ、又はＧにより置換されており、及び／又は
１００位における前記アスパラギン酸（Ｄ）が、アミノ酸Ａ、Ｅ、Ｆ、Ｉ、Ｋ、Ｌ、Ｎ、Ｒ、Ｖ、Ｗ、又はＹにより置換されている、
第３の配列；
を含み、
前記ＣＨ３ドメインの１０１位におけるアミノ酸が、バリン（Ｖ）、アラニン（Ａ）であり、又は不存在であり；
前記アミノ酸残基ナンバリングが、ImMunoGeneTics（ＩＭＧＴ）ナンバリングスキームに従う、
特異的結合メンバー。 A specific binding member that binds to programmed cell death ligand 1 (PD-L1),
the specific binding member comprises a CH3 domain, and the specific binding member comprises a PD-L1 antigen binding site located in the CH3 domain;
The CH3 domain has an AB structural loop located at positions 11 to 18 of the CH3 domain, a CD structural loop located at positions 43 to 78 of the CH3 domain, and a CD structural loop located at positions 92 to 101 of the CH3 domain. an EF structure loop,
The PD-L1 antigen binding site is
(i) a first sequence located in an AB structural loop at positions 14 to 18 of said CH3 domain, wherein said specific binding member has an amino acid deletion at positions 14, 15 or 16 of said CH3 domain; and the first array comprises:
(a) consisting of the amino acid sequence SGYW (SEQ ID NO: 23), or (b) a variant of SEQ ID NO: 23,
the serine (S) is substituted with the amino acid A, E, F, G, H, I, L, P, R, T, V, or Y, and/or the glycine (G) is substituted with the amino acid A , D, E, F, H, K, L, N, P, R, T, V, or Y.
first array;
(ii) a second sequence localized in the CD structural loop at positions 45.1 to 78 of the CH3 domain, the second sequence comprising:
(a) consisting of the amino acid sequence EPQYWA (SEQ ID NO: 11), or (b) a variant of SEQ ID NO: 11,
the glutamic acid (E) is replaced by the amino acid A, G, H, I, L, N, Q, R, S, or W, and/or the proline (P) is replaced by the amino acid A, D, E , G, H, N, Q, W, or Y, and/or the glutamine (Q) is replaced by the amino acid H, or N, and/or the tyrosine (Y) is is substituted with the amino acid A, D, H, T, or V, and/or the alanine (A) is substituted with the amino acid D, E, G, L, R, S, or W.
a second sequence; and (iii) a third sequence located in the EF structural loop at positions 92 to 100 or 92 to 101 of the CH3 domain, the third sequence comprising:
(a) consisting of the amino acid sequence SNWRWQMDD (SEQ ID NO: 19), or (b) a variant of SEQ ID NO: 19,
The serine (S) at position 92 is replaced by the amino acid A or G, and/or the asparagine (N) at position 93 is replaced by the amino acid A, E, F, G, H, I, K, L. , Q, R, S, T, or Y, and/or said glutamine (Q) at position 97 is substituted with amino acids A, D, E, F, G, H, K, L, N, R , S, or V, and/or said methionine (M) at position 98 is replaced by an amino acid F, I, L, V, W, or Y, and/or said methionine (M) at position 99 aspartic acid (D) is substituted by amino acid A, I, L, R, S, T, V, W, Y, or G, and/or said aspartic acid (D) at position 100 is replaced by amino acid A , E, F, I, K, L, N, R, V, W, or Y.
Third array;
including;
the amino acid at position 101 of the CH3 domain is valine (V), alanine (A), or absent;
the amino acid residue numbering follows the ImMunoGeneTics (IMGT) numbering scheme;
Specific binding member. 請求項１に記載のアミノ酸置換基から選択される前記第１、第２及び第３の配列中の合計５つまでのアミノ酸置換を含む、請求項１に記載の特異的結合メンバー。 2. A specific binding member according to claim 1, comprising a total of up to five amino acid substitutions in said first, second and third sequences selected from the amino acid substitutions according to claim 1. ９８位における前記メチオニン（Ｍ）が、アミノ酸Ｌにより置換されている、請求項１又は２に記載の特異的結合メンバー。 3. Specific binding member according to claim 1 or 2, wherein the methionine (M) at position 98 is replaced by the amino acid L. 請求項１に記載のアミノ酸置換基から選択される前記第１の配列中の２つまでのアミノ酸置換及び／又は請求項１に記載のアミノ酸置換基から選択される前記第３の配列中の３つまでのアミノ酸置換を含む、請求項１から３のいずれか１項に記載の特異的結合メンバー。 up to two amino acid substitutions in the first sequence selected from the amino acid substitutions according to claim 1 and/or three in the third sequence selected from the amino acid substitutions according to claim 1. 4. A specific binding member according to any one of claims 1 to 3, comprising up to three amino acid substitutions. 前記第１の配列が、
（ａ）アミノ酸配列ＳＧＹＷ（配列番号２３）、又は
（ｂ）配列番号２３のバリアントであって、前記セリン（Ｓ）が、アミノ酸Ｅ、又はＴにより置換されているバリアント
からなり；
前記第２の配列が、アミノ酸配列ＥＰＱＹＷＡ（配列番号１１）からなり；
前記第３の配列が、
（ａ）アミノ酸配列ＳＮＷＲＷＱＭＤ１Ｄ２（配列番号１９）、又は
（ｂ）配列番号１９のバリアントであって、前記メチオニン（Ｍ）が、アミノ酸Ｉ、Ｌ、又はＶにより置換されており、前記アスパラギン酸（Ｄ１）が、任意でグリシン（Ｇ）により置換されているバリアント
からなり；
前記ＣＨ３ドメインの１０１位におけるアミノ酸が、バリン（Ｖ）、アラニン（Ａ）であり、又は不存在である、
請求項１から４のいずれか１項に記載の特異的結合メンバー。 The first array is
(a) the amino acid sequence SGYW (SEQ ID NO: 23), or (b) a variant of SEQ ID NO: 23, in which the serine (S) is replaced by the amino acid E or T;
the second sequence consists of the amino acid sequence EPQYWA (SEQ ID NO: 11);
The third array is
(a) the amino acid sequence SNWRWQMD 1 D 2 (SEQ ID NO: 19), or (b) a variant of SEQ ID NO: 19, in which the methionine (M) is replaced by the amino acid I, L, or V, and the asparagine a variant in which the acid (D 1 ) is optionally replaced by glycine (G);
the amino acid at position 101 of the CH3 domain is valine (V), alanine (A), or absent;
A specific binding member according to any one of claims 1 to 4. 前記第１の配列が、配列番号４２に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号４３に記載の配列を有する、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 42, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 43. 6. A specific binding member according to any one of claims 1 to 5, having the following: 前記第１の配列が、配列番号４７に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号４３に記載の配列を有する、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 47, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 43. 6. A specific binding member according to any one of claims 1 to 5, having the following: 前記第１の配列が、配列番号４７に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号７８に記載の配列を有する、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 47, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 78. 6. A specific binding member according to any one of claims 1 to 5, having the following: 前記第１の配列が、配列番号４２に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号７４に記載の配列を有し、前記特異的結合メンバーの前記ＣＨ３ドメインの１１３位における残基が、アルギニン（Ｒ）である、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 42, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 74. 6. A specific binding member according to any one of claims 1 to 5, wherein the residue at position 113 of the CH3 domain of the specific binding member is arginine (R). 前記第１の配列が、配列番号４７に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号７０に記載の配列を有し、前記特異的結合メンバーの前記ＣＨ３ドメインの８４．１、８５．３、１０１及び１１３位における残基が、それぞれプロリン（Ｐ）、トレオニン（Ｔ）、アラニン（Ａ）及びアルギニン（Ｒ）である、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 47, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 70. and the residues at positions 84.1, 85.3, 101 and 113 of the CH3 domain of the specific binding member are proline (P), threonine (T), alanine (A) and arginine (R), respectively. ).) A specific binding member according to any one of claims 1 to 5. 前記第１の配列が、配列番号２３に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号３１に記載の配列を有する、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 23, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 31. 6. A specific binding member according to any one of claims 1 to 5, having the following: 前記第１の配列が、配列番号２３に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号１９に記載の配列を有する、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 23, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 19. 6. A specific binding member according to any one of claims 1 to 5, having the following: 前記第１の配列が、配列番号２３に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号２７に記載の配列を有する、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 23, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 27. 6. A specific binding member according to any one of claims 1 to 5, having the following: 前記第１の配列が、配列番号２３に記載の配列を有し、前記第２の配列が、配列番号１１に記載の配列を有し、前記第３の配列が、配列番号３５に記載の配列を有する、請求項１から５のいずれか１項に記載の特異的結合メンバー。 The first sequence has the sequence set forth in SEQ ID NO: 23, the second sequence has the sequence set forth in SEQ ID NO: 11, and the third sequence has the sequence set forth in SEQ ID NO: 35. 6. A specific binding member according to any one of claims 1 to 5, having the following: 前記ＣＨ３ドメインの１０１位におけるアミノ酸が、バリン（Ｖ）である、請求項６から９のいずれか１項に記載の特異的結合メンバー。 10. A specific binding member according to any one of claims 6 to 9, wherein the amino acid at position 101 of the CH3 domain is valine (V). 前記ＣＨ３ドメインが、ヒトＩｇＧ１ ＣＨ３ドメインである、請求項１から１５のいずれか１項に記載の特異的結合メンバー。 16. A specific binding member according to any one of claims 1 to 15, wherein the CH3 domain is a human IgG1 CH3 domain. 前記ＣＨ３ドメインの３８位におけるアミノ酸が、バリン又はアラニン残基である、請求項１から１６のいずれか１項に記載の特異的結合メンバー。 17. A specific binding member according to any one of claims 1 to 16, wherein the amino acid at position 38 of the CH3 domain is a valine or alanine residue. 前記ＣＨ３ドメインの３８位におけるアミノ酸が、アラニン残基である、請求項１から１７のいずれか１項に記載の特異的結合メンバー。 18. A specific binding member according to any one of claims 1 to 17, wherein the amino acid at position 38 of the CH3 domain is an alanine residue. 配列番号４４、４８、７１、７５、７９、３２、２４、２８、３６、又は３９に記載のＣＨ３ドメインを含む、請求項１から１８のいずれか１項に記載の特異的結合メンバー。 19. A specific binding member according to any one of claims 1 to 18, comprising a CH3 domain according to SEQ ID NO: 44, 48, 71, 75, 79, 32, 24, 28, 36 or 39. 配列番号４４、４８、７１、７５、７９、又は３２に記載のＣＨ３ドメインを含む、請求項１から１９のいずれか１項に記載の特異的結合メンバー。 20. A specific binding member according to any one of claims 1 to 19, comprising a CH3 domain according to SEQ ID NO: 44, 48, 71, 75, 79 or 32. 配列番号４４、４８、７１、７５、７９、又は３２に示される配列の直近のＣ末端のリジン残基（Ｋ）が欠失されている、請求項２０に記載の特異的結合メンバー。 21. Specific binding member according to claim 20, wherein the immediate C-terminal lysine residue (K) of the sequence shown in SEQ ID NO: 44, 48, 71, 75, 79 or 32 is deleted. ＣＨ２ドメインをさらに含む、請求項１から２１のいずれか１項に記載の特異的結合メンバー。 22. A specific binding member according to any one of claims 1 to 21, further comprising a CH2 domain. ヒトＩｇＧ１、ＩｇＧ２、ＩｇＧ３、又はＩｇＧ４のＣＨ２ドメインを含む、請求項１から２２のいずれか１項に記載の特異的結合メンバー。 23. A specific binding member according to any one of claims 1 to 22, comprising a CH2 domain of human IgG1, IgG2, IgG3, or IgG4. ヒトＩｇＧ１のＣＨ２ドメインを含む、請求項１から２３のいずれか１項に記載の特異的結合メンバー。 24. A specific binding member according to any one of claims 1 to 23, comprising the CH2 domain of human IgG1. 前記ＣＨ２ドメインが、配列番号５、６、又は８２に記載の配列を有する、請求項２２から２４のいずれか１項に記載の特異的結合メンバー。 25. Specific binding member according to any one of claims 22 to 24, wherein the CH2 domain has a sequence according to SEQ ID NO: 5, 6 or 82. 前記ＣＨ２ドメインのＮ末端における免疫グロブリンヒンジ領域、又はその一部をさらに含む、請求項２２から２５のいずれか１項に記載の特異的結合メンバー。 26. A specific binding member according to any one of claims 22 to 25, further comprising an immunoglobulin hinge region at the N-terminus of the CH2 domain, or a part thereof. 前記ヒンジ領域、又はその一部が、ヒトＩｇＧ１、ＩｇＧ２、ＩｇＧ３又はＩｇＧ４ヒンジ領域、又はその一部である、請求項２６に記載の特異的結合メンバー。 27. A specific binding member according to claim 26, wherein the hinge region, or a portion thereof, is a human IgG1, IgG2, IgG3 or IgG4 hinge region, or a portion thereof. 前記ヒンジ領域、又はその一部が、ヒトＩｇＧ１ヒンジ領域、又はその一部である、請求項２７に記載の特異的結合メンバー。 28. A specific binding member according to claim 27, wherein the hinge region, or a portion thereof, is a human IgG1 hinge region, or a portion thereof. 前記ヒンジ領域が、配列番号７に記載の配列を含むか、又はそれからなる、請求項２６から２８のいずれか１項に記載の特異的結合メンバー。 29. A specific binding member according to any one of claims 26 to 28, wherein the hinge region comprises or consists of the sequence set forth in SEQ ID NO:7. 配列番号４５、４６、４９、５０、７２、７３、７６、７７、８０、８１、３３、３４、２５、２６、２９、３０、３７、３８、４０、又は４１に記載の配列を含むか、又はそれからなる、請求項１から２９のいずれか１項に記載の特異的結合メンバー。 Contains the sequence set forth in SEQ ID NO: 45, 46, 49, 50, 72, 73, 76, 77, 80, 81, 33, 34, 25, 26, 29, 30, 37, 38, 40, or 41, or a specific binding member according to any one of claims 1 to 29 consisting of. 配列番号４５、４６、４９、５０、７２、７３、７６、７７、８０、８１、３３、又は３４に記載の配列を含むか、又はそれからなる、請求項１から２９のいずれか１項に記載の特異的結合メンバー。 30. According to any one of claims 1 to 29, comprising or consisting of the sequence according to SEQ ID NO: 45, 46, 49, 50, 72, 73, 76, 77, 80, 81, 33, or 34. specific binding member of. 第２の抗原結合部位をさらに含む、請求項１から３１のいずれか１項に記載の特異的結合メンバー。 32. A specific binding member according to any one of claims 1 to 31, further comprising a second antigen binding site. 前記第２の抗原結合部位が、ＣＤＲベース抗原結合部位である、請求項３２に記載の特異的結合メンバー。 33. A specific binding member according to claim 32, wherein the second antigen binding site is a CDR-based antigen binding site. 前記ＣＤＲベース抗原結合部位が、チェックポイントインヒビター、共刺激分子、又は腫瘍関連抗原に結合する、請求項３３に記載の特異的結合メンバー。 34. The specific binding member of claim 33, wherein the CDR-based antigen binding site binds a checkpoint inhibitor, costimulatory molecule, or tumor-associated antigen. 前記ＣＤＲベース抗原結合部位が、ＯＸ４０にも、誘導性Ｔ細胞共刺激因子（ＩＣＯＳ）にも、ＣＤ１３７にも結合しない、請求項３３又は３４に記載の特異的結合メンバー。 35. A specific binding member according to claim 33 or 34, wherein the CDR-based antigen binding site does not bind to OX40, inducible T cell co-stimulatory factor (ICOS) or CD137. 前記ＣＤＲベース抗原結合部位が、ＣＤ２７にも、グルココルチコイド誘導性ＴＮＦＲ関連タンパク質（ＧＩＴＲ）にも結合しない、請求項３３から３５のいずれか１項に記載の特異的結合メンバー。 36. A specific binding member according to any one of claims 33 to 35, wherein the CDR-based antigen binding site binds neither CD27 nor glucocorticoid-inducible TNFR-related protein (GITR). 前記ＣＤＲベース抗原結合部位が、リンパ球活性化遺伝子３（ＬＡＧ－３）に結合しない、請求項３３から３６のいずれか１項に記載の特異的結合メンバー。 37. A specific binding member according to any one of claims 33 to 36, wherein the CDR-based antigen binding site does not bind lymphocyte activation gene 3 (LAG-3). 前記特異的結合メンバーが、抗体分子である、請求項１から３７のいずれか１項に記載の特異的結合メンバー。 38. A specific binding member according to any one of claims 1 to 37, wherein said specific binding member is an antibody molecule. 前記抗体分子が、ヒトＩｇＧ１、ＩｇＧ２、ＩｇＧ３又はＩｇＧ４分子である、請求項３８に記載の特異的結合メンバー。 39. A specific binding member according to claim 38, wherein the antibody molecule is a human IgG1, IgG2, IgG3 or IgG4 molecule. 前記抗体分子が、ヒトＩｇＧ１である、請求項３９に記載の特異的結合メンバー。 40. A specific binding member according to claim 39, wherein said antibody molecule is human IgG1. 前記特異的結合メンバーが、免疫系モジュレーター、細胞傷害性分子、放射性同位体、又は検出可能な標識にコンジュゲートしている、請求項１から４０のいずれか１項に記載の特異的結合メンバー。 41. The specific binding member of any one of claims 1 to 40, wherein the specific binding member is conjugated to an immune system modulator, a cytotoxic molecule, a radioactive isotope, or a detectable label. 前記免疫系モジュレーター又は細胞傷害性分子が、サイトカインである、請求項４１に記載の特異的結合メンバー。 42. A specific binding member according to claim 41, wherein the immune system modulator or cytotoxic molecule is a cytokine. 前記免疫系モジュレーターが、細胞表面受容体、若しくは生物学的に活性なその断片；又は細胞表面受容体のリガンド、若しくは生物学的に活性な前記リガンドの断片である、請求項４１に記載の特異的結合メンバー。 42. The specific immune system of claim 41, wherein the immune system modulator is a cell surface receptor, or a biologically active fragment thereof; or a ligand of a cell surface receptor, or a biologically active fragment of said ligand. join member. 請求項１から４３のいずれか１項に記載の特異的結合メンバーをコードする核酸。 44. A nucleic acid encoding a specific binding member according to any one of claims 1 to 43. 請求項４４に記載の核酸を含むベクター。 A vector comprising the nucleic acid according to claim 44. 請求項４４に記載の核酸、又は請求項４５に記載のベクターを含む組換え宿主細胞。 A recombinant host cell comprising a nucleic acid according to claim 44 or a vector according to claim 45. 請求項１から４３のいずれか１項に記載の特異的結合メンバーを産生する方法であって、前記特異的結合メンバーの産生のための条件下で請求項４６に記載の組換え宿主細胞を培養することを含む方法。 44. A method of producing a specific binding member according to any one of claims 1 to 43, comprising culturing a recombinant host cell according to claim 46 under conditions for the production of said specific binding member. A method that includes doing. 前記特異的結合メンバーを単離し、及び／又は精製することをさらに含む、請求項４７に記載の方法。 48. The method of claim 47, further comprising isolating and/or purifying the specific binding member. 請求項１から４３のいずれか１項に記載の特異的結合メンバー及び薬学的に許容可能な賦形剤を含む医薬組成物。 44. A pharmaceutical composition comprising a specific binding member according to any one of claims 1 to 43 and a pharmaceutically acceptable excipient. 患者における癌を治療する方法における使用のための、請求項１から４３のいずれか１項に記載の特異的結合メンバー。 44. A specific binding member according to any one of claims 1 to 43 for use in a method of treating cancer in a patient. 患者における癌を治療するための医薬組成物であって、治療有効量の請求項１から４３のいずれか１項に記載の特異的結合メンバーを含む医薬組成物。 44. A pharmaceutical composition for treating cancer in a patient, the composition comprising a therapeutically effective amount of a specific binding member according to any one of claims 1 to 43. 前記方法が、第２の抗癌治療剤を前記患者に投与することをさらに含む、請求項５０に記載の使用のための特異的結合メンバー。 51. A specific binding member for use according to claim 50, wherein the method further comprises administering to the patient a second anti-cancer therapeutic agent. 前記医薬組成物が、第２の抗癌治療剤をさらに含む、請求項５１に記載の医薬組成物。 52. The pharmaceutical composition of claim 51, wherein the pharmaceutical composition further comprises a second anti-cancer therapeutic agent. 感染性疾患を治療する方法における使用のための、請求項１から４３のいずれか１項に記載の特異的結合メンバー。 44. A specific binding member according to any one of claims 1 to 43 for use in a method of treating an infectious disease. 患者における感染性疾患を治療するための医薬組成物であって、治療有効量の請求項１から４３のいずれか１項に記載の特異的結合メンバーを含む医薬組成物。 44. A pharmaceutical composition for treating an infectious disease in a patient, the composition comprising a therapeutically effective amount of a specific binding member according to any one of claims 1 to 43. 前記感染性疾患が、慢性感染性疾患である、請求項５４又は５５に記載の使用のための特異的結合メンバー、又は医薬組成物。 56. A specific binding member for use, or a pharmaceutical composition, according to claim 54 or 55, wherein the infectious disease is a chronic infectious disease. 炎症、炎症と関連する疾患若しくは病態、又は炎症性疾患を治療する方法における使用のための、請求項１から４３のいずれか１項に記載の特異的結合メンバー。 44. A specific binding member according to any one of claims 1 to 43 for use in inflammation, a disease or condition associated with inflammation, or a method of treating an inflammatory disease. 患者における炎症、炎症と関連する疾患若しくは病態、又は炎症性疾患を治療するための医薬組成物であって、治療有効量の請求項１から４３のいずれか１項に記載の特異的結合メンバーを含む医薬組成物。 44. A pharmaceutical composition for treating inflammation, a disease or condition associated with inflammation, or an inflammatory disease in a patient, comprising a therapeutically effective amount of a specific binding member according to any one of claims 1 to 43. A pharmaceutical composition comprising. 前記炎症、炎症と関連する疾患若しくは病態、又は炎症性疾患が、脳卒中、脳卒中関連炎症、又は血管炎症である、請求項５７又は５８に記載の使用のための特異的結合メンバー、又は医薬組成物。
 A specific binding member for use or a pharmaceutical composition for use according to claim 57 or 58, wherein the inflammation, disease or condition associated with inflammation, or inflammatory disease is stroke, stroke-related inflammation, or vascular inflammation. .
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