Anti-human TSLP receptor antibody
An anti-human TSLP receptor antibody that specifically binds to human TSLP receptor and inhibits an action of human TSLP through human TSLP receptor. A method for preventing or treating asthma by administering the anti-human TSLP receptor antibody or an antigen-binding fragment thereof. An anti-human TSLP receptor antibody had been studied by the present inventors, and an anti-human TSLP receptor antibody including a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3 was provided. It was revealed that the anti-human TSLP receptor antibody inhibits expression of TARC mRNA induced by TSLP and production of MDC proteins, and suppressed an allergic reaction in a monkey Ascaris antigen sensitization model.
1. A method for treating asthma, which comprises administering a therapeutically effective amount of an anti-human thymic stromal lymphopoietin (TSLP) receptor antibody or an antigen-binding fragment thereof, wherein the anti-human TSLP receptor antibody or the antigen-binding fragment thereof comprises a heavy chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 31 to 35 of SEQ ID NO: 1, CDR2 consisting of the amino acid sequence of amino acid numbers 50 to 66 of SEQ ID NO: 1, and CDR3 consisting of the amino acid sequence of amino acid numbers 99 to 107 of SEQ ID NO: 1, and a light chain variable region comprising CDR1 consisting of the amino acid sequence of amino acid numbers 24 to 34 of SEQ ID NO: 3, CDR2 consisting of the amino acid sequence of amino acid numbers 50 to 56 of SEQ ID NO: 3, and CDR3 consisting of the amino acid sequence of amino acid numbers 89 to 97 of SEQ ID NO: 3.
2. The method for treating asthma according to claim 1 , wherein the anti-human TSLP receptor antibody or the antigen-binding fragment thereof is selected from the group consisting of the following (1) and (2):
(1) an anti-human TSLP receptor antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3;
(2) an anti-human TSLP receptor antibody or an antigen-binding fragment thereof, wherein glutamic acid of the N-terminal of the heavy chain of the antibody or the antigen-binding fragment thereof of ( 1 ) is modified to pyroglutamic acid.
3. The method for treating asthma according to claim 2 , wherein the anti-human TSLP receptor antibody or the antigen-binding fragment thereof comprises a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3.
4. The method for treating asthma according to claim 2 , wherein the anti-human TSLP receptor antibody or the antigen-binding fragment thereof is the anti-human TSLP receptor antibody or the antigen-binding fragment thereof comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1, and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3, wherein glutamic acid of the N-terminal of the heavy chain is modified to pyroglutamic acid.
5. The method for treating asthma according to claim 2 , wherein the anti-human TSLP receptor antibody or the antigen-binding fragment thereof comprises a heavy chain constant region which is a human Igγ1 constant region.
6. The method for treating asthma according to claim 2 , wherein the anti-human TSLP receptor antibody or the antigen-binding fragment thereof comprises a light chain constant region which is a human Igκ constant region.
7. The method for treating asthma according to claim 2 , wherein the anti-human TSLP receptor antibody or the antigen-binding fragment thereof comprises a heavy chain constant region which is a human Igγ1 constant region and a light chain constant region which is a human Igκ constant region.
8. The method for treating asthma according to claim 3 , wherein the anti-human TSLP receptor antibody comprises a heavy chain consisting of the amino acid sequence shown by SEQ ID NO: 1 and a light chain consisting of the amino acid sequence shown by SEQ ID NO: 3.
9. The method for treating asthma according to claim 2 , wherein the antigen-binding fragment is a single-chain variable region fragment, Fab, Fab′, or F(ab′) 2 .
10. The method for treating asthma according to claim 2 , wherein the anti-human TSLP receptor antibody is an antibody comprising a heavy chain consisting of the amino acid sequence shown by SEQ ID NO: 1, wherein glutamic acid of the amino acid number 1 of SEQ ID NO: 1 is modified to pyroglutamic acid and/or lysine of the amino acid number 448 of SEQ ID NO: 1 is deleted, and a light chain consisting of the amino acid sequence shown by SEQ ID NO: 3.
11. The method for treating asthma according to claim 10 , wherein the anti-human TSLP receptor antibody comprises a heavy chain consisting of the amino acid sequence of amino acid numbers 1 to 447 of SEQ ID NO: 1, and a light chain consisting of the amino acid sequence shown by SEQ ID NO. 3.
12. The method for treating asthma according to claim 1 , wherein the anti-human TSLP receptor antibody or the antigen-binding fragment thereof is produced by a method comprising culturing a host cell to express an anti-human TSLP receptor antibody or an antigen-binding fragment thereof, wherein the host cell is selected from the group consisting of the following (a) and (b):
(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1 and a polynucleotide comprising a base sequence encoding a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3;
(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1 and an expression vector comprising a polynucleotide comprising a base sequence encoding a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3.
13. The method for treating asthma according to claim 1 , wherein the anti-human TSLP receptor antibody is produced by a method comprising culturing a host cell to express an anti-human TSLP receptor antibody, wherein the host cell is selected from the group consisting of the following (a) and (b):
(a) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding a heavy chain consisting of the amino acid sequence shown by SEQ ID NO: 1 and a polynucleotide comprising a base sequence encoding a light chain consisting of the amino acid sequence shown by SEQ ID NO: 3;
(b) a host cell transformed with an expression vector comprising a polynucleotide comprising a base sequence encoding a heavy chain consisting of the amino acid sequence shown by SEQ ID NO: 1 and an expression vector comprising a polynucleotide comprising a base sequence encoding a light chain consisting of the amino acid sequence shown by SEQ ID NO: 3.