Treatment of asthma with anti-TSLP antibody
The present disclosure, relates, in general, to methods of treating asthma, including severe asthma and eosinophilic asthma, using an antibody specific for thymic stromal lymphopoietin (TSLP).
1. A method for treating asthma in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 70 mg to 280 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain comprising:
i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3;
ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4;
iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6;
ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and
iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.
2. The method of claim 1 wherein the antibody or antibody variant is administered every 4 weeks.
3. The method of claim 1 wherein the antibody or antibody variant is administered at a dose of 70 mg.
4. The method of claim 1 wherein the antibody or antibody variant is administered at a dose of 210 mg.
5. The method of claim 1 wherein the antibody or antibody variant is administered at a dose of 280 mg.
6. The method of claim 1 wherein the antibody or antibody variant is administered for a period of at least 4 months, 6 months, 9 months, 1 year or more.
7. The method of claim 1 , wherein said anti-TSLP antibody or antibody variant thereof is bivalent and selected from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a monoclonal antibody, a recombinant antibody, an antigen-binding antibody fragment, a single chain antibody, a monomeric antibody, a diabody, a triabody, a tetrabody, a Fab fragment, an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, and an IgG4 antibody.
8. The method of claim 1 , wherein the antibody is an IgG2 antibody.
9. The method of claim 1 , wherein the antibody or antibody variant is a human antibody.
10. The method of claim 1 wherein, the antibody or antibody variant further comprises a pharmaceutically acceptable carrier or excipient.
11. The method of claim 1 wherein, wherein the asthma is severe asthma.
12. The method of claim 1 , wherein the asthma is eosinophilic or non-eosinophilic asthma.
13. The method claim 1 , wherein the asthma is low eosinophil asthma.
14. The method of claim 1 , wherein the subject is an adult.
15. The method of claim 1 , wherein the subject is a child or adolescent.
16. The method of claim 1 , wherein the administration decreases eosinophils in blood, sputum, broncheoalveolar fluid, or lungs of the subject.
17. The method of claim 1 , wherein the administration shifts cell counts in the subject from a Th2 high population to a Th2 low population.
18. The method of claim 1 , wherein the administration improves one or more measures of asthma in a subject selected from the group consisting of forced expiratory volume (FEV), FEV 1 reversibility, forced vital capacity (FCV), FeNO, Asthma Control Questionnaire-6 score and AQLQ(S)+12 score.
19. The method of claim 1 , wherein the administration improves one or more symptoms of asthma as measured by an asthma symptom diary.
20. The method of claim 1 wherein the antibody is tezepelumab.
21. The method of claim 20 wherein the antibody is an IgG2 antibody, and has the full length heavy and light chain sequences set out in SEQ ID NOs: 105 and 106, respectively.
22. The method of claim 1 wherein the administration is subcutaneous or intravenous.
23. A method for treating asthma in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 70 mg to 280 mg at an interval of every two weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain selected from the group consisting of:
i. a sequence of amino acids at least 80% identical to SEQ ID NO:12;
ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11;
iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and
b. a heavy chain variable domain selected from the group consisting of:
i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10;
ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9;
iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.
24. A method for treating asthma in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain comprising:
i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3;
ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4;
iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6;
ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and
iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.
25. A method for treating asthma in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 210 mg at an interval of every 4 weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain selected from the group consisting of:
i. a sequence of amino acids at least 80% identical to SEQ ID NO:12;
ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11;
iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and
b. a heavy chain variable domain selected from the group consisting of:
i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10;
ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9;
iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b), wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.
26. The method of claim 25 , wherein said anti-TSLP antibody variant is selected from the group consisting of a diabody, a triabody, a tetrabody, a Fab fragment, single domain antibody, scFv, wherein the dose is adjusted such that the binding sites to be equimolar to the those dosed by bivalent antibodies.
27. A method for treating asthma in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 70 to 280 mg at an interval of every 2 weeks or every 4 weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain comprising:
i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3;
ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4;
iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6;
ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and
iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antibody specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2, wherein the antibody is an IgG2 antibody.
28. The method of claim 27 wherein the antibody is administered every 4 weeks.
29. The method of claim 27 wherein the antibody is administered at a dose of 70 mg, 210 mg or 280 mg.
30. A method of reducing the frequency of asthma exacerbation in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 70 mg to 280 mg at an interval of every 2 weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain comprising:
i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3;
ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4;
iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6;
ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and
iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.
31. The method of claim 30 wherein the antibody or antibody variant is administered every 4 weeks.
32. The method of claim 30 wherein the antibody or antibody variant is administered at a dose of 70 mg, 210 mg or 280 mg.
33. The method of claim 30 wherein the administration delays the time to an asthma exacerbation compared to a subject not receiving the anti-TSLP antibody.
34. The method claim 30 wherein the administration reduces frequency of or levels of co-administered therapy in the subject.
35. The method of claim 34 wherein the co-administered therapy is inhaled corticosteroids (ICS), long-acting β2 agonist (LABA), leukotriene receptor antagonists (LTRA), long-acting anti-muscarinics (LAMA), cromones, short-acting β2 agonist (SABA), and theophylline or oral corticosteroids.
36. The method of claim 34 , wherein the administration eliminates the need for corticosteroid therapy.
37. The method of claim 30 wherein the anti-TSLP antibody is tezepelumab.
38. A method of reducing the frequency of asthma exacerbation in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 70 mg to 280 mg at an interval of every 2 weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain selected from the group consisting of:
i. a sequence of amino acids at least 80% identical to SEQ ID NO:12;
ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11;
iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and
b. a heavy chain variable domain selected from the group consisting of:
i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10;
ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9;
iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).
39. A method for reducing ACQ-6 score in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 70 mg to 280 mg at an interval of every 2 weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain comprising:
i. a light chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:3;
ii. a light chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:4;
iii. a light chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:5; and
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence comprising the amino acid sequence set forth in SEQ ID NO:6;
ii. a heavy chain CDR2 sequence comprising the amino acid sequence set forth in SEQ ID NO:7, and
iii. a heavy chain CDR3 sequence comprising the amino acid sequence set forth in SEQ ID NO:8, wherein the antigen binding protein specifically binds to a TSLP polypeptide as set forth in amino acids 29-159 of SEQ ID NO:2.
40. A method for reducing ACQ-6 score in a subject comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant in a dose of 70 mg to 280 mg at an interval of every 2 weeks, wherein both binding sites of the antibody have identical binding to TSLP, and the antibody comprises
a. a light chain variable domain selected from the group consisting of:
i. a sequence of amino acids at least 80% identical to SEQ ID NO:12;
ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:11;
iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:11; and
b. a heavy chain variable domain selected from the group consisting of:
i. a sequence of amino acids that is at least 80% identical to SEQ ID NO:10;
ii. a sequence of amino acids encoded by a polynucleotide sequence that is at least 80% identical to SEQ ID NO:9;
iii. a sequence of amino acids encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of SEQ ID NO:9; or c. a light chain variable domain of (a) and a heavy chain variable domain of (b).
41. The method of claim 40 wherein the administration is subcutaneous or intravenous.
42. A method for treating asthma in a subject having a non-eosinophilic profile or a low eosinophil profile comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant, wherein the antibody or antibody variant binding to TSLP inhibits TSLP activity.
43. The method of claim 42 wherein the anti-TSLP antibody or anti-TSLP antibody variant is selected from an antibody described in Table A:
TABLE A
WO2017/042701
An anti-TSLP antibody comprising a heavy chain (HC) CDR1
comprising the sequence of SEQ ID NO: 13, a HC CDR2
comprising the sequence of SEQ ID NO: 14, and a HC CDR3
comprising the sequence of SEQ ID NO: 15;
An anti-TSLP antibody comprising a light chain (LC) CDR1
comprising the sequence of SEQ ID NO: 16, a LC CDR2
comprising the sequence of SEQ ID NO: 17, a LC CDR3
comprising the sequence of SEQ ID NO: 18;
An anti-TSLP antibody comprising a heavy chain (HC) CDR1
comprising the sequence of SEQ ID NO: 19, a HC CDR2
comprising the sequence of SEQ ID NO: 20, a HC CDR3
comprising the sequence of SEQ ID NO: 15;
An anti-TSLP antibody comprising a light chain (LC) CDR1
comprising the sequence of SEQ ID NO: 21, a LC CDR2
comprising the sequence of SEQ ID NO: 22, a LC CDR3
comprising the sequence of SEQ ID NO: 23;
An anti-TSLP antibody comprising a HC variable region comprising
the sequence of SEQ ID NO: 26 and/or a LC variable region
comprising the sequence of SEQ ID NO: 27;
An anti-TSLP antibody comprising a HC variable region comprising
the sequence of SEQ ID NO: 28 and/or a LC variable region
comprising the sequence of SEQ ID NO: 29;
An anti-TSLP antibody that comprises a paratope comprising at
least one of the following residues: Thr28, Asp31, Tyr32, Trp33,
Asp56, Glu101, Ile102, Tyr103, Tyr104, Tyr105 of a heavy chain
sequence of SEQ ID NO: 26 or Gly28, Ser29, Lys30, Tyr31, Tyr48,
Asp50, Asn51, Glu52, Asn65, and Trp92 of a light chain sequence
of SEQ ID NO: 27;
An anti-TSLP antibody that specifically binds an epitope in human
TSLP, wherein the epitope comprises at least one of the following
residues: Lys38, Ala41, Leu44, Ser45, Thr46, Ser48, Lys49, Ile52,
Thr53, Ser56, Gly57, Thr58, Lys59, Lys101, Gln145, and Arg149 of
SEQ ID NO: 30;
WO2016/142426
An anti-TSLP antibody comprising the amino acid sequence of SEQ
ID NO: 31;
An anti-TSLP antibody comprising a CDR1 comprising the
sequence of SEQ ID NO: 32; a CDR2 comprising the sequence of
SEQ ID NO: 33, and a CDR3 comprising the sequence of SEQ ID
NO: 34;
An anti-TSLP antibody comprising a CDR1 comprising the
sequence of SEQ ID NO: 32; a CDR2 comprising the sequence of
SEQ ID NO: 35, and a CDR3 comprising the sequence of SEQ ID
NO: 34;
An anti-TSLP antibody comprising a variant of the CDR1 of SEQ ID
NO: 31 wherein the residue corresponding to residue 28 in SEQ ID
NO: 31 is Pro, the residue corresponding to residue 30 in SEQ ID
NO: 31 is Arg, the residue corresponding to residue 31 in SEQ ID
NO: 31 is Asn, the residue corresponding to residue 32 in SEQ ID
NO: 31 is Trp and the residue corresponding to residue 34 in SEQ
ID NO: 31 is Asp;
An anti-TSLP antibody comprising a variant of the CDR2 of SEQ ID
NO: 31 wherein the residue corresponding to residue 50 in SEQ ID
NO: 31 is Gly, the residue corresponding to residue 53 in SEQ ID
NO: 31 is His and the residue corresponding to residue 55 in SEQ
ID NO: 31 is Gln;
An anti-TSLP antibody comprising a variant of the CDR3 of SEQ ID
NO: 31 wherein the residue corresponding to residue 91 in SEQ ID
NO: 31 is He, Leu, Val or Phe, the residue corresponding to residue
92 in SEQ ID NO: 31 is Gly or Ala, the residue corresponding to
residue 93 in SEQ ID NO: 31 is Glu, Phe, Asp or Ser and the
residue corresponding to residue 94 in SEQ ID NO: 31 is Asp.
WO2010/017468
An anti-TSLP antibody (9B7) comprising a HC CDR3 comprising
the sequence of SEQ ID NO: 38, wherein the other CDRs of the HC
and LC comprise the sequences of SEQ ID NOs: 36, 37, and 39-41;
An anti-TSLP antibody (6C5) comprising a HC CDR3 comprising
the sequence of SEQ ID NO: 44, wherein the other CDRs of the HC
and LC comprise the sequences of SEQ ID NOs: 42, 43, and 45-47;
An anti-TSLP antibody (6A3) comprising a HC CDR3 comprising
the sequence of SEQ ID NO: 50, wherein the other CDRs of the HC
and LC comprise the sequences of SEQ ID NOs: 48, 49, and 51-53;
An anti-TSLP antibody (1A11) comprising a HC CDR3 comprising
the sequence of SEQ ID NO: 56, wherein the other CDRs of the HC
and LC comprise the sequences of SEQ ID NOs: 54, 55, and 57-59;
An anti-TSLP antibody comprising (i) heavy chain variable region of
SEQ ID NO: 60 and/or the light chain variable region of SEQ ID
NO: 61;
An anti-TSLP antibody comprising (i) heavy chain variable region of
SEQ ID NO: 62 and/or the light chain variable region of SEQ ID
NO: 63;
An anti-TSLP antibody comprising (i) heavy chain variable region of
SEQ ID NO: 64 and/or the light chain variable region of SEQ ID
NO: 65;
An anti-TSLP antibody comprising (i) heavy chain variable region of
SEQ ID NO: 66 and/or the light chain variable region of SEQ ID NO:
67;
An anti-TSLP antibody comprising (i) heavy chain variable region of
SEQ ID NO: 68 and/or the light chain variable region of SEQ ID NO:
69;
An anti-TSLP antibody comprising a HC CDR selected from the
group consisting of SEQ ID NO: 38, SEQ ID NO: 44, SEQ ID NO: 50
and SEQ ID NO: 56, and analogs thereof;
An anti-TSLP antibody comprising a heavy chain comprising the
following CDRs or analogs thereof CDRH1: RYNVH (SEQ ID
NO: 36), CDRH2: MIWDGGSTDYNSALKS (SEQ ID NO: 37),
CDRH3: NRYESG (SEQ ID NO: 38), and a light chain comprising
the following CDRs or analogs thereof CDRL1:
KSSQSLLNSGNRKNYLT (SEQ ID NO: 39), CDRL2: WASTRES
(SEQ ID NO: 40), and CDRL3: QNDYTYPFTFGS (SEQ ID NO: 41);
or
An anti-TSLP antibody comprising a heavy chain comprising the
following CDRs or analogs thereof CRDH1: AYWMS (SEQ ID
NO: 42), CDRH2: EINPDSSTINCTPSLKD (SEQ ID NO: 43), CDRH3:
RLRPFWYFDVW (SEQ ID NO: 44), and a light chain comprising the
following CDRs or analogs thereof CDRL1:
RSSQSIVQSNGNTYLE (SEQ ID NO: 45), CDRL2: KVSNRFS (SEQ
ID NO: 46), and CDRL3: FQGSHVPRT (SEQ ID NO: 47);
An anti-TSLP antibody comprising a heavy chain comprising the
following CDRs or analogs thereof CRDH1: TDYAWN (SEQ ID
NO: 48), CDRH2: YIFYSGSTTYTPSLKS (SEQ ID NO: 49), CDRH3:
GGYDVNYF (SEQ ID NO: 50), and a light chain comprising the
following CDRs or analogs thereof CDRL1: LASQTIGAWLA (SEQ
ID NO: 51), CDRL2: AATRLAD (SEQ ID NO: 52), and CDRL3:
QQFFSTPWT (SEQ ID NO: 53);
An anti-TSLP antibody comprising a heavy chain comprising the
following CDRs or analogs thereof CDRH1: GYTMN (SEQ ID
NO: 54), CDRH2: LINPYNGVTSYNQKFK (SEQ ID NO: 55), CDRH3:
GDGNYWYF (SEQ ID NO: 56), and a light chain comprising the
following CDRs or analogs thereof CDRL1: SASSSVTYMHW (SEQ
ID NO: 57), CDRL2: EISKLAS (SEQ ID NO: 58), and CDRL3:
QEWNYPYTF (SEQ ID NO: 59);
An anti-TSLP antibody comprising a HC CDR1 comprising the
sequence of SEQ ID NO: 70; a CDR2 comprising the sequence of
SEQ ID NO: 71 , and a CDR3 comprising the sequence of SEQ ID
NO: 72;
An anti-TSLP antibody comprising a LC CDR1 comprising the
sequence of SEQ ID NO: 73; a CDR2 comprising the sequence of
SEQ ID NO: 74, and a CDRS comprising the sequence of SEQ ID
NO: 75;
US2012/0020988
An anti-TSLP antibody comprising a heavy chain variable domain
comprising a CDR1 region of SEQ ID NO: 76, a CDR2 region of
SEQ ID NO: 77, and CDR3 region of SEQ ID NO: 78, and a light
chain variable domain comprising a CDR1 region of SEQ ID NO:
79, a CDR2 region of SEQ ID NO: 80, and a CDR3 region of SEQ
ID NO: 81.
An anti-TSLP antibody comprising a heavy chain variable domain
comprising SEQ ID NO: 82 and a light chain variable domain
comprising SEQ ID NO: 83;
An anti-TSLP antibody comprising a heavy chain variable domain
comprising a CDR1 region of SEQ ID NO: 76 or 84, a CDR2 region
of SEQ ID NO: 77 or 85, and CDR3 region of SEQ ID NO: 78, and a
light chain variable domain comprising a CDR1 region of SEQ ID
NO: 79 or 86, a CDR2 region of SEQ ID NO: 80, 87, or 88, and a
CDR3 region of SEQ ID NO: 81.
An anti-TSLP antibody comprising a heavy chain variable domain
comprising a CDR1 region of SEQ ID NO: 76, a CDR2 region of
SEQ ID NO: 85, and CDR3 region of SEQ ID NO: 78, and a light
chain variable domain comprising a CDR1 region of SEQ ID NO:
86, a CDR2 region of SEQ ID NO: 87 and a CDR3 region of SEQ ID
NO: 81;
An anti-TSLP antibody comprising a heavy chain variable domain
comprising a CDR1 region of SEQ ID NO: 76, a CDR2 region of
SEQ ID NO: 85, and CDR3 region of SEQ ID NO: 78, and a light
chain variable domain comprising a CDR1 region of SEQ ID NO:
86, a CDR2 region of SEQ ID NO: 88 and a CDR3 region of SEQ ID
NO: 81;
An anti-TSLP antibody comprising a heavy chain variable domain
comprising a CDR1 region of SEQ ID NO: 84, a CDR2 region of
SEQ ID NO: 85, and CDR3 region of SEQ ID NO: 78, and a light
chain variable domain comprising a CDR1 region of SEQ ID NO:
86, a CDR2 region of SEQ ID NO: 88 and a CDR3 region of SEQ ID
NO: 81; or
An anti-TSLP antibody comprising a heavy chain variable domain
comprising a CDR1 region of SEQ ID NO: 76, a CDR2 region of
SEQ ID NO: 85, and CDR3 region of SEQ ID NO: 78, and a light
chain variable domain comprising a CDR1 region of SEQ ID NO:
86, a CDR2 region of SEQ ID NO: 80 and a CDR3 region of SEQ
ID NO: 81.
An anti-TSLP antibody comprising a heavy chain variable domain
comprises SEQ ID NO: 89 and a light chain variable domain
comprises SEQ ID NO: 90;
An anti-TSLP antibody comprising a heavy chain variable domain
comprises SEQ ID NO: 89 and a light chain variable domain
comprises SEQ ID NO: 91;
An anti-TSLP antibody comprising a heavy chain variable domain
comprises SEQ ID NO: 92 and a light chain variable domain
comprises SEQ ID NO: 93;
An anti-TSLP antibody comprising a heavy chain variable domain
comprises SEQ ID NO: 89 and a light chain variable domain
comprises SEQ ID NO: 94,
U.S. Pat. No.
An anti-TSLP antibody comprising heavy chain variable region
8,637,019
comprising: a CDR-H1 sequence comprising SEQ ID NO: 95, a
CDR-H2 sequence comprising SEQ ID NO: 96, and a CDR-H3
sequence comprising SEQ ID NO: 97; and/or an antibody light chain
variable region or a TSLP-binding fragment thereof, said light chain
variable region comprising: a CDR-L1 sequence comprising SEQ ID
NO: 98, a CDR-L2 sequence comprising SEQ ID NO: 99, and a
CDR-L3 sequence comprising SEQ ID NO: 100.
An anti-TSLP antibody comprising a heavy chain variable region
comprises the amino acid sequence of SEQ ID NO: 101 and the
light chain variable region comprises the amino acid sequence of
SEQ ID NO: 102.
An anti-TSLP antibody comprising SEQ ID NO: 103 and SEQ ID
NO: 104.
44. The method of claim 42 wherein the subject has an eosinophil count less than 250 cells/μL at start of treatment.
45. The method of claim 42 wherein the administration is subcutaneous or intravenous.
46. A method for treating asthma in a subject having a Th2 low profile comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant, wherein the antibody or antibody variant binding to TSLP inhibits TSLP activity.
47. The method of claim 46 wherein the subject has a Th2 profile of IgE less than or equal to 100 IU/ml or eosinophil count of less than 140 cells/μL at the time of diagnosis.
48. A method for reducing ACQ-6 score in a subject having a low eosinophil profile comprising administering a therapeutically effective amount of an anti-TSLP antibody or antibody variant, wherein the antibody or antibody variant binding to TSLP inhibits TSLP activity.