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CN-122029190-A - Anti-TSLP antibodies and uses thereof

CN122029190ACN 122029190 ACN122029190 ACN 122029190ACN-122029190-A

Abstract

Anti-TSLP antibodies or antigen-binding fragments thereof are provided. Also provided are polynucleotides encoding the antibodies or antigen binding protein constructs, and expression vectors and host cells comprising the same. Immunoconjugates, pharmaceutical compositions and medicaments, and their use in the treatment of diseases or disorders are also provided.

Inventors

  • LI LI

Assignees

  • 信达生物制药(苏州)有限公司

Dates

Publication Date
20260512
Application Date
20241011
Priority Date
20231012

Claims (20)

  1. 1. An antibody or antigen-binding fragment thereof that binds TSLP (thymic stromal lymphopoietin), comprising: A heavy chain variable region (VH) comprising Complementarity Determining Regions (CDRs) 1,2 and 3, wherein the VH CDR1 region comprises an amino acid sequence at least 80% identical to the selected VH CDR1 amino acid sequence, the VH CDR2 region comprises an amino acid sequence at least 80% identical to the selected VH CDR2 amino acid sequence, and the VH CDR3 region comprises an amino acid sequence at least 80% identical to the selected VH CDR3 amino acid sequence, and A light chain variable region (VL) comprising CDR1, CDR2, and CDR3, wherein the VL CDR1 region comprises an amino acid sequence that is at least 80% identical to the selected VL CDR1 amino acid sequence, the VL CDR2 region comprises an amino acid sequence that is at least 80% identical to the selected VL CDR2 amino acid sequence, and the VL CDR3 region comprises an amino acid sequence that is at least 80% identical to the selected VL CDR3 amino acid sequence; Wherein the selected VH CDR1, VH CDR2, and VH CDR3 amino acid sequences and the selected VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are one of: (1) Selected VH CDR1, VH CDR2, and VH CDR3 amino acid sequences are shown in SEQ ID NOs 37, 38, 39, respectively, and selected VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are shown in SEQ ID NOs 40, 41, 42, respectively; (2) Selected VH CDR1, VH CDR2, and VH CDR3 amino acid sequences are shown in SEQ ID NOs 86, 38, 39, respectively, and selected VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are shown in SEQ ID NOs 40, 41, 42, respectively; (3) The selected VH CDR1, VH CDR2 and VH CDR3 amino acid sequences are shown as SEQ ID NOS 117, 118, 119, respectively, and the selected VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are shown as SEQ ID NOS 120, 121, 122, respectively.
  2. 2. The antibody or antigen-binding fragment thereof of claim 1, wherein the VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 37, 38, 39, respectively, and the VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 40, 41, 42, respectively; wherein VH CDR1 is determined according to the AbM definition, Wherein VH CDR2, VH CDR3 and VL CDR1, VL CDR2, VL CDR3 are determined according to the Kabat definition.
  3. 3. The antibody or antigen-binding fragment thereof of claim 1, wherein the VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 86, 38, 39, respectively, and the VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 40, 41, 42, respectively, according to the Kabat definition.
  4. 4. The antibody or antigen-binding fragment thereof of claim 1, wherein the VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 117, 118, 119, respectively, and the VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 120, 121, 122, respectively, according to Chothia definition.
  5. 5. An antibody or antigen-binding fragment thereof that binds TSLP, comprising: A heavy chain variable region (VH) comprising an amino acid sequence at least 90% identical to a selected VH sequence and a light chain variable region (VL) comprising an amino acid sequence at least 90% identical to a selected VL sequence; wherein the selected VH sequence and the selected VL sequence are one of: (1) The selected VH sequence is SEQ ID NO. 43 and the selected VL sequence is SEQ ID NO. 44, and (2) The VH sequence selected is SEQ ID NO. 45 and the VL sequence selected is SEQ ID NO. 46.
  6. 6. The antibody or antigen-binding fragment thereof of any one of claims 1-5, wherein the antibody or antigen-binding fragment specifically binds human TSLP and/or monkey TSLP.
  7. 7. The antibody or antigen-binding fragment thereof of any one of claims 1-6, wherein the antibody or antigen-binding fragment is a human antibody or antigen-binding fragment thereof, or a humanized antibody or antigen-binding fragment thereof.
  8. 8. The antibody or antigen-binding fragment thereof of any one of claims 1-7, wherein the antigen-binding fragment is selected from the group consisting of a Fab fragment, a Fab 'fragment, a F (ab') 2 fragment, a Fd fragment, an Fv fragment, a dAb fragment, an isolated CDR region, an scFv, and a nanobody.
  9. 9. An antibody or antigen-binding fragment thereof that binds TSLP, comprising: A heavy chain variable region (VH) comprising VH CDR1, VH CDR2, and VH CDR3 identical to VH CDR1, VH CDR2, and VH CDR3 of the selected VH sequence, and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3 identical to VL CDR1, VL CDR2, and VL CDR3 of the selected VL sequence; wherein the selected VH sequence and the selected VL sequence are one of: (1) The selected VH sequence is SEQ ID NO. 43 and the selected VL sequence is SEQ ID NO. 44, and (2) The VH sequence selected is SEQ ID NO. 45 and the VL sequence selected is SEQ ID NO. 46.
  10. 10. An antibody or antigen-binding fragment thereof that cross-competes with the antibody or antigen-binding fragment thereof of any one of claims 1-9.
  11. 11. The antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the antibody or antigen-binding fragment thereof is a bispecific antibody or a multispecific antibody or antigen-binding fragment thereof.
  12. 12. A nucleic acid comprising a polynucleotide encoding a polypeptide comprising: (1) An immunoglobulin heavy chain or fragment thereof, said heavy chain or fragment thereof comprising a VH comprising CDR1, CDR2 and CDR3, said CDR comprising the amino acid sequences shown in SEQ ID NOs 37, 38, 39, respectively, 86, 38, 39, respectively, or 117, 118, 119, respectively, and wherein said VH binds to TSLP when paired with a light chain variable region (VL) comprising the amino acid sequences shown in SEQ ID NOs 44 or 46; (2) An immunoglobulin light chain or fragment thereof, the light chain or fragment thereof comprising a VL comprising CDR1, CDR2 and CDR3, the CDRs comprising the amino acid sequences shown in SEQ ID NOs 40, 41, 42, respectively, or the amino acid sequences shown in SEQ ID NOs 120, 121, 122, respectively, and wherein the VL binds to a TSLP when the VL is paired with a VH comprising the amino acid sequences shown in SEQ ID NOs 43 or 45.
  13. 13. The nucleic acid of claim 12, wherein the VH specifically binds human TSLP when paired with a VL.
  14. 14. The nucleic acid of claim 12 or 13, wherein the immunoglobulin heavy chain or fragment thereof is a heavy chain of a human immunoglobulin or fragment thereof, or a heavy chain of a humanized immunoglobulin or fragment thereof.
  15. 15. The nucleic acid of any one of claims 12-14, wherein the nucleic acid encodes a single chain variable fragment (scFv), a bispecific or multispecific antibody, or an antigen-binding fragment thereof.
  16. 16. The nucleic acid of any one of claims 12-15, wherein the nucleic acid is cDNA.
  17. 17. A vector comprising one or more nucleic acids of any one of claims 12-16, or a nucleic acid encoding the antibody or antigen-binding fragment thereof of any one of claims 1-11.
  18. 18. A cell comprising the vector of claim 17.
  19. 19. The cell of claim 18, wherein the cell is a CHO cell.
  20. 20. A cell comprising one or more nucleic acids of any one of claims 12-16, or a nucleic acid encoding the antibody or antigen-binding fragment thereof of any one of claims 1-11.

Description

Anti-TSLP antibodies and uses thereof Priority claim The present application claims priority from chinese application No. 202311318859.2 filed 10/12 in 2023. The entire contents of the foregoing application are incorporated herein by reference. Technical Field The present disclosure relates to the field of immunopharmaceuticals, and in particular to antibodies or antigen-binding fragments thereof capable of specifically binding TSLP. The disclosure also relates to pharmaceutical compositions comprising them and their use. Background Autoimmune diseases are conditions caused by an abnormal immune response to a normal body part. There are at least 80 autoimmune diseases. The etiology of autoimmune diseases is often less clear. Some autoimmune diseases (e.g., lupus) are familial, while some other autoimmune diseases may be triggered by infection or other environmental factors. Some common autoimmune diseases include, for example, celiac disease, type 1 diabetes, graves' disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. Recent clinical and commercial success of therapeutic antibodies has led to great interest in using antibodies to treat various immune-related disorders. There is a need to develop antibodies for use in various antibody-based therapies to treat immune disorders. Disclosure of Invention The present disclosure relates to anti-TSLP antibodies, or antigen-binding fragments thereof, that can specifically bind to TSLP. The antibodies or antigen-binding fragments thereof are useful in the treatment of diseases or disorders (e.g., cancer or immune disorders). In one aspect, the disclosure relates to an antibody or antigen-binding fragment thereof that binds TSLP (thymic stromal lymphopoietin), comprising a heavy chain variable region (VH) comprising Complementarity Determining Regions (CDRs) 1,2, and 3, in some embodiments, the VH CDR1 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR1 amino acid sequence, the VH CDR2 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR2 amino acid sequence, and the VH CDR3 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR3 amino acid sequence; the light chain variable region comprises CDR1, CDR2 and CDR3, in some embodiments, the VL CDR1 region comprises an amino acid sequence at least 80% identical to the selected VL CDR1 amino acid sequence, the VL CDR2 region comprises an amino acid sequence at least 80% identical to the selected VL CDR2 amino acid sequence, and the VL CDR3 region comprises an amino acid sequence at least 80% identical to the selected VL CDR3 amino acid sequence, in some embodiments, the selected VH CDR1, VH CDR2 and VH CDR3 amino acid sequence and the selected VL CDR1, VL CDR2 and VL CDR3 amino acid sequence are one of (1) the selected VH CDR1, VH CDR2 and VH CDR3 amino acid sequence shown as SEQ ID NO:37, 38, 39, respectively, and the selected VL CDR1, VL 2 and VL CDR3 amino acid sequences shown as SEQ ID NO:40, 41, 42, respectively, (2) the selected VH CDR1, VH CDR2 and VH CDR3 amino acid sequence shown as SEQ ID NO:86, 38, 39, respectively, and the selected VL CDR3 amino acid sequence shown as SEQ ID NO:40, 39, respectively, the VL CDR2 and VL CDR3 amino acid sequences are shown as SEQ ID NOS: 40, 41, 42, respectively, (3) the selected VH CDR1, VH CDR2, and VH CDR3 amino acid sequences are shown as SEQ ID NOS: 117, 118, 119, respectively, and the selected VL CDR1, VL CDR2, and VL CDR3 amino acid sequences are shown as SEQ ID NOS: 120, 121, 122, respectively. In some embodiments, the VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 37, 38, 39, respectively, and the VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 40, 41, 42, respectively, in some embodiments, the VH CDR1 is determined according to the AbM definition, in some embodiments, the VH CDR2, VH CDR3 and VL CDR1, VL CDR2, VL CDR3 are determined according to the Kabat definition. In some embodiments, according to the Kabat definition, the VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS: 86, 38, 39, respectively, and the VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS: 40, 41, 42, respectively. In some embodiments, according to the Chothia definition, the VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 117, 118, 119, respectively, and the VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 120, 121, 122, respectively. In one aspect, the disclosure relates to an antibody or antigen-binding fragment thereof that binds TSLP, comprising a heavy chain variable region (VH) comprising an amino acid sequence that is at least 90% identical to a selected VH sequence and a light chain variable region (VL) comp