JPWO2021055409A5

JPWO2021055409A5 -

Info

Publication number: JPWO2021055409A5
Application number: JP2022517173A
Authority: JP
Publication date: 2023-09-22

Description

本明細書で引用される刊行物、特許、及び特許出願は、具体的には、参照によりそれらの全体が組み込まれる。記載された本発明を、その特定の実施形態を参照して説明してきたが、当業者は、本発明の真の主旨及び範囲から逸脱することなく、様々な変更が行われてもよく、均等物が置き換えられてもよいことを理解されたい。加えて、記載された本発明の客観的精神及び範囲に対して特定の状況、材料、物質の組成、プロセス、プロセスステップ（複数可）を採用するために多くの変更が行われ得る。すべてのそのような修正は、特許請求の範囲内であることが意図される。
本発明は、例えば、以下の項目を提供する。
(項目１)
炎症性または線維性腎疾患の治療を必要とする対象における炎症性または線維性腎疾患を治療するための方法であって、前記対象に、幹細胞因子（ＳＣＦ）に特異的に結合する抗体またはその抗原結合断片を投与することを含み、前記抗体またはその抗原結合断片が、それぞれ、配列番号１、２、及び３を含む重鎖ＣＤＲ１、ＣＤＲ２、及びＣＤＲ３と、それぞれ、配列番号４、５、及び６による軽鎖ＣＤＲ１、ＣＤＲ２、及びＣＤＲ３と、を含む、前記方法。
(項目２)
前記抗体またはその断片が、配列番号７、８、９、１０、及び１１から選択される配列に対して少なくとも８０％の同一性を有する重鎖可変領域を含む、項目１に記載の方法。
(項目３)
前記抗体またはその断片が、配列番号７、８、９、１０、及び１１から選択される配列に対して少なくとも９０％の同一性を有する重鎖可変領域を含む、項目１または項目２に記載の方法。
(項目４)
前記抗体またはその断片が、配列番号１３、１４、１５、及び１６から選択される配列に対して少なくとも８０％の同一性を有する軽鎖可変領域を含む、項目１～３のいずれか一項に記載の方法。
(項目５)
前記抗体またはその断片が、配列番号１３、１４、１５、及び１６から選択される配列に対して少なくとも９０％の同一性を有する軽鎖可変領域を含む、項目１～４のいずれか一項に記載の方法。
(項目６)
前記抗体またはその断片が、配列番号７、８、９、１０、及び１１から選択される重鎖可変領域アミノ酸配列と、配列番号１３、１４、１５、及び１６から選択される軽鎖可変領域アミノ酸配列と、を含む、項目１～５のいずれか一項に記載の方法。
(項目７)
前記抗体またはその断片が、配列番号７に記載の重鎖可変領域アミノ酸配列と、配列番号１６に記載の軽鎖可変領域アミノ酸配列と、を含む、項目１～６のいずれか一項に記載の方法。
(項目８)
前記抗体またはその断片が、配列番号８に記載の重鎖可変領域アミノ酸配列と、配列番号１６に記載の軽鎖可変領域アミノ酸配列と、を含む、項目１～６のいずれか一項に記載の方法。
(項目９)
前記抗体またはその断片が、配列番号９に記載の重鎖可変領域アミノ酸配列と、配列番号１６に記載の軽鎖可変領域アミノ酸配列と、を含む、項目１～６のいずれか一項に記載の方法。
(項目１０)
前記抗体またはその断片が、配列番号１０に記載の重鎖可変領域アミノ酸配列と、配列番号１６に記載の軽鎖可変領域アミノ酸配列と、を含む、項目１～６のいずれか一項に記載の方法。
(項目１１)
前記抗体またはその断片が、配列番号１１に記載の重鎖可変領域アミノ酸配列と、配列番号１６に記載の軽鎖可変領域アミノ酸配列と、を含む、項目１～６のいずれか一項に記載の方法。
(項目１２)
前記抗体またはその断片が、ヒト化されている、項目１に記載の方法。
(項目１３)
前記抗体が、モノクローナル抗体である、項目１～１２のいずれか一項に記載の方法。
(項目１４)
前記抗体が、ヒトＩｇＧ４ドメインを含む、項目１３に記載の方法。
(項目１５)
前記ＩｇＧ４ドメインが、アミノ酸残基２４１におけるＳ２４１Ｐ変異及びアミノ酸残基２４８におけるＬ２４８Ｅ変異を含み、前記残基の番号付けが、Ｋａｂａｔ番号付けシステムのものである、項目１４に記載の方法。
(項目１６)
前記抗体が、配列番号４２に記載の重鎖と、配列番号４９に記載の軽鎖と、を含む、項目１３～１５のいずれか一項に記載の方法。
(項目１７)
前記抗体が、配列番号４３に記載の重鎖と、配列番号４９に記載の軽鎖と、を含む、項目１３～１５のいずれか一項に記載の方法。
(項目１８)
前記抗体またはその断片が、ＳＣＦ２４８に特異的に結合する、項目１～１７のいずれか一項に記載の方法。
(項目１９)
前記抗体が、ＳＣＦ２２０に結合しない、項目１～１８のいずれか一項に記載の方法。
(項目２０)
前記炎症性または線維性腎疾患が、慢性腎疾患（ＣＫＤ）、末期腎疾患（ＥＲＳＤ）、腎線維症、糸球体腎炎、及び腎症からなる群から選択される、項目１～１９のいずれか一項に記載の方法。
(項目２１)
前記腎症または糸球体腎炎が、ＩｇＡ腎症、糖尿病性腎症、巣状分節性糸球体硬化症、急速進行性糸球体腎症、半月体形成性糸球体腎炎、ループス腎炎、高血圧性腎症、または糖尿病性腎症である、項目２０に記載の方法。 The publications, patents, and patent applications cited herein are specifically incorporated by reference in their entirety. Although the described invention has been described with reference to particular embodiments thereof, those skilled in the art will appreciate that various changes may be made and equivalents may be made without departing from the true spirit and scope of the invention. It should be understood that things may be substituted. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process step(s) to the objective spirit and scope of the invention as described. All such modifications are intended to be within the scope of the claims.
The present invention provides, for example, the following items.
(Item 1)
A method for treating inflammatory or fibrotic kidney disease in a subject in need of treatment, the method comprising: administering to the subject an antibody that specifically binds to stem cell factor (SCF) or an antibody thereof that specifically binds to stem cell factor (SCF); administering an antigen-binding fragment, wherein the antibody or antigen-binding fragment thereof has heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NO: 1, 2, and 3, respectively, and SEQ ID NO: 4, 5, and CDR3, respectively. and light chain CDR1, CDR2, and CDR3 according to No. 6.
(Item 2)
2. The method of item 1, wherein said antibody or fragment thereof comprises a heavy chain variable region having at least 80% identity to a sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11.
(Item 3)
According to item 1 or item 2, the antibody or fragment thereof comprises a heavy chain variable region having at least 90% identity to a sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11. Method.
(Item 4)
According to any one of items 1 to 3, said antibody or fragment thereof comprises a light chain variable region having at least 80% identity to a sequence selected from SEQ ID NOs: 13, 14, 15, and 16. Method described.
(Item 5)
According to any one of items 1 to 4, the antibody or fragment thereof comprises a light chain variable region having at least 90% identity to a sequence selected from SEQ ID NOs: 13, 14, 15, and 16. Method described.
(Item 6)
The antibody or fragment thereof has a heavy chain variable region amino acid sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11 and a light chain variable region amino acid sequence selected from SEQ ID NOs: 13, 14, 15, and 16. The method according to any one of items 1 to 5, comprising:
(Item 7)
The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 7 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16, according to any one of items 1 to 6. Method.
(Item 8)
The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 8 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16, according to any one of items 1 to 6. Method.
(Item 9)
The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 9 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16, according to any one of items 1 to 6. Method.
(Item 10)
The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 10 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16, according to any one of items 1 to 6. Method.
(Item 11)
The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 11 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16, according to any one of items 1 to 6. Method.
(Item 12)
2. The method of item 1, wherein the antibody or fragment thereof is humanized.
(Item 13)
The method according to any one of items 1 to 12, wherein the antibody is a monoclonal antibody.
(Item 14)
14. The method of item 13, wherein the antibody comprises a human IgG4 domain.
(Item 15)
15. The method of item 14, wherein the IgG4 domain comprises a S241P mutation at amino acid residue 241 and a L248E mutation at amino acid residue 248, and the numbering of the residues is of the Kabat numbering system.
(Item 16)
16. The method according to any one of items 13 to 15, wherein the antibody comprises a heavy chain as set forth in SEQ ID NO: 42 and a light chain as set forth in SEQ ID NO: 49.
(Item 17)
16. The method according to any one of items 13 to 15, wherein the antibody comprises a heavy chain set forth in SEQ ID NO: 43 and a light chain set forth in SEQ ID NO: 49.
(Item 18)
18. The method of any one of items 1-17, wherein the antibody or fragment thereof specifically binds to SCF248.
(Item 19)
19. The method of any one of items 1-18, wherein said antibody does not bind to SCF220.
(Item 20)
Any of items 1 to 19, wherein the inflammatory or fibrotic kidney disease is selected from the group consisting of chronic kidney disease (CKD), end stage renal disease (ERSD), renal fibrosis, glomerulonephritis, and nephropathy. The method described in paragraph 1.
(Item 21)
The nephropathy or glomerulonephritis is IgA nephropathy, diabetic nephropathy, focal segmental glomerulosclerosis, rapidly progressive glomerulonephropathy, crescentic glomerulonephritis, lupus nephritis, hypertensive nephropathy , or diabetic nephropathy, the method according to item 20.

Claims

A composition for treating inflammatory or fibrotic kidney disease in a subject in need of treatment , the composition comprising an antibody that specifically binds to stem cell factor (SCF) or its antigen binding. wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NO: 1, 2, and 3, respectively, and light chain CDR1 according to SEQ ID NO: 4, 5, and 6, respectively. , CDR2, and CDR3 .

The composition of claim 1, wherein the antibody or fragment thereof comprises a heavy chain variable region having at least 80% identity to a sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11. .

3. The antibody or fragment thereof comprises a heavy chain variable region having at least 90% identity to a sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11. Compositions as described.

Any one of claims 1 to 3, wherein the antibody or fragment thereof comprises a light chain variable region having at least 80% identity to a sequence selected from SEQ ID NOs: 13, 14, 15, and 16. The composition described in .

Any one of claims 1 to 4, wherein the antibody or fragment thereof comprises a light chain variable region having at least 90% identity to a sequence selected from SEQ ID NOs: 13, 14, 15, and 16. The composition described in.

The antibody or fragment thereof has a heavy chain variable region amino acid sequence selected from SEQ ID NOs: 7, 8, 9, 10, and 11 and a light chain variable region amino acid sequence selected from SEQ ID NOs: 13, 14, 15, and 16. A composition according to any one of claims 1 to 5, comprising the sequence.

7. The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 7 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16. Composition of .

The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 8 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16, according to any one of claims 1 to 6. Composition of .

7. The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 9 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16. Composition of .

7. The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 10 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16. Composition of .

7. The antibody or fragment thereof comprises the heavy chain variable region amino acid sequence set forth in SEQ ID NO: 11 and the light chain variable region amino acid sequence set forth in SEQ ID NO: 16. Composition of .

2. The composition of claim 1, wherein the antibody or fragment thereof is humanized.

The composition according to any one of claims 1 to 12, wherein the antibody is a monoclonal antibody.

14. The composition of claim 13, wherein the antibody comprises a human IgG4 domain.

15. The composition of claim 14, wherein the IgG4 domain comprises a S241P mutation at amino acid residue 241 and a L248E mutation at amino acid residue 248, and the numbering of the residues is of the Kabat numbering system.

The composition according to any one of claims 13 to 15, wherein the antibody comprises a heavy chain according to SEQ ID NO: 42 and a light chain according to SEQ ID NO: 49.

The composition according to any one of claims 13 to 15, wherein the antibody comprises a heavy chain according to SEQ ID NO: 43 and a light chain according to SEQ ID NO: 49.

18. The composition according to any one of claims 1 to 17, wherein the antibody or fragment thereof specifically binds to SCF248.

The composition according to any one of claims 1 to 18, wherein the antibody does not bind to SCF220.

Any of claims 1 to 19, wherein the inflammatory or fibrotic kidney disease is selected from the group consisting of chronic kidney disease (CKD), end stage renal disease (ERSD), renal fibrosis, glomerulonephritis, and nephropathy. The composition according to item 1.

The nephropathy or glomerulonephritis is IgA nephropathy, diabetic nephropathy, focal segmental glomerulosclerosis, rapidly progressive glomerulonephropathy, crescentic glomerulonephritis, lupus nephritis, hypertensive nephropathy , or diabetic nephropathy .