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CN-122003439-A - Anti-IL-4 Rα antibodies and uses thereof

CN122003439ACN 122003439 ACN122003439 ACN 122003439ACN-122003439-A

Abstract

Provided herein are anti-IL-4 ra antibodies or antigen-binding fragments thereof, and to polynucleotides encoding the antibodies or antigen-binding protein constructs, as well as 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
  • ZHU MENGZHU

Assignees

  • 信达生物制药(苏州)有限公司

Dates

Publication Date
20260508
Application Date
20241011
Priority Date
20231012

Claims (20)

  1. 1. An antibody or antigen-binding fragment thereof that binds IL-4 ra (interleukin-4 receptor alpha subunit), 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%, 90% or 100% 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%, 90%, or 100% 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: (1) The selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as GFTFX 1 X 2 NAMN（SEQ ID NO:57）、RIRTKX 3 X 4 X 5 YATYHADSVKD（SEQ ID NO:59） and DVGRGFAY (SEQ ID NO: 3), respectively, wherein X 1 = N, E, K or D, X 2 = I or M, X 3 = S, G or T, X 4 = N, A or S, X 5 = N, K or D, wherein the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX 6 X 7 X 8 X 9 SYX 10 H（SEQ ID NO:60）、LX 11 X 12 X 13 LQS（SEQ ID NO:61） and QHSX 14 EX 15 PX 16 T (SEQ ID NO: 62), respectively, wherein X 6 =T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, t or R, X 13 = N, Y, F or H, X 14 = R or T, X 15 = L or I, X 16 = L or I; (2) The selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as GFTFX 1 MNAMN（SEQ ID NO:58）、RIRTKX 3 X 4 X 5 YATYHADSVKD (SEQ ID NO: 59) and DVGRGFAY (SEQ ID NO: 3), respectively, wherein X 1 = N, E, K or D, X 3 = S, G or T, X 4 = N, A or S, X 5 = N, K or D, wherein the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX 6 X 7 X 8 X 9 SYX 10 H（SEQ ID NO:60）、LX 11 X 12 X 13 LQS（SEQ ID NO:61） and QHSX 14 EX 15 PX 16 T (SEQ ID NO: 62), respectively, wherein X 6 =T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, t or R, X 13 = N, Y, F or H, X 14 = R or T, X 15 = L or I, X 16 = L or I; (3) Selected VH CDR1, VH CDR2, The VH CDR3 amino acid sequences are shown as X 2 NAMN（SEQ ID NO:123）、RIRTKX 3 X 4 X 5 YATYHADSVKD (SEQ ID NO: 59) and DVGRGFAY (SEQ ID NO: 3), respectively, where X 2 =I or M, X 3 =S, G or T, X 4 = N, A or S, X 5 = N, K or D, wherein the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX 6 X 7 X 8 X 9 SYX 10 H（SEQ ID NO:60）、LX 11 X 12 X 13 LQS（SEQ ID NO:61） and QHSX 14 EX 15 PX 16 T (SEQ ID NO: 62), respectively, wherein X 6 =T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, t or R, X 13 = N, Y, F or H, X 14 = R or T, X 15 = L or I, X 16 = L or I; (4) The selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as MNAMN (SEQ ID NO: 85), RIRTKX 3 X 4 X 5 YATYHADSVKD (SEQ ID NO: 59) and DVGRGFAY (SEQ ID NO: 3), respectively, wherein X 3 = S, G or T, X 4 = N, A or S, X 5 = N, K or D, wherein the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX 6 X 7 X 8 X 9 SYX 10 H（SEQ ID NO:60）、LX 11 X 12 X 13 LQS（SEQ ID NO:61） and QHSX 14 EX 15 PX 16 T (SEQ ID NO: 62), respectively, wherein X 6 =T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, t or R, X 13 = N, Y, F or H, X 14 = R or T, X 15 = L or I, X 16 = L or I; (5) The selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as GFTFX 1 X 2 N（SEQ ID NO:124）、RTKX 3 X 4 X 5 YA (SEQ ID NO: 125) and DVGRGFAY (SEQ ID NO: 3), respectively, wherein X 1 = N, E, K or D, X 2 = I or M, X 3 = S, G or T, X 4 = N, A or S, X 5 = N, K or D, wherein the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX 6 X 7 X 8 X 9 SYX 10 H（SEQ ID NO:60）、LX 11 X 12 X 13 LQS（SEQ ID NO:61） and QHSX 14 EX 15 PX 16 T (SEQ ID NO: 62), respectively, wherein X 6 =T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, T or R, X 13 = N, Y, F or H, X 14 = R or T, X 15 = L or I, X 16 = L or I, or (6) The selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as GFTFX 1 MN（SEQ ID NO:126）、RTKX 3 X 4 X 5 YA (SEQ ID NO: 125) and DVGRGFAY (SEQ ID NO: 3), respectively, wherein X 1 = N, E, K or D, X 3 = S, G or T, X 4 = N, A or S, X 5 = N, K or D, wherein the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX 6 X 7 X 8 X 9 SYX 10 H（SEQ ID NO:60）、LX 11 X 12 X 13 LQS（SEQ ID NO:61） and QHSX 14 EX 15 PX 16 T (SEQ ID NO: 62), respectively, wherein X 6 =T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, T or R, X 13 = N, Y, F or H, X 14 =r or T, X 15 =l or I, X 16 =l or I.
  2. 2. An antibody or antigen-binding fragment thereof that binds IL-4 ra (interleukin-4 receptor alpha subunit), 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, VH CDR3 amino acid sequence and the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequence are one of the following: (1) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 1, 2, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 4, 5,6, respectively; (2) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 11, 12, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 13, 14, 15, respectively; (3) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 18, 19, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 20, 21, 22, respectively; (4) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 25, 26, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 27, 28, 29, respectively; (5) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 32, 19, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 33, 34, 6, respectively; (6) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 84, 2, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 4, 5, 6, respectively; (7) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 85, 12, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 13, 14, 15, respectively; (8) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 85, 19, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 20, 21, 22, respectively; (9) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 85, 26, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 27, 28, 29, respectively; (10) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 85, 19, 3, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 33, 34, 6, respectively; (11) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown in SEQ ID NOs 87, 88, 89, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown in SEQ ID NOs 90, 91, 92, respectively; (12) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as SEQ ID NOs 93, 94, 95, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as SEQ ID NOs 96, 97, 98, respectively; (13) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as SEQ ID NOs 99, 100, 101, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as SEQ ID NOs 102, 103, 104, respectively; (14) Selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as SEQ ID NOS 105, 106, 107, respectively, and selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as SEQ ID NOS 108, 109, 110, respectively, and (15) The selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as SEQ ID NOS 111, 112, 113, respectively, and the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as SEQ ID NOS 114, 115, 116, respectively.
  3. 3. The antibody or antigen-binding fragment thereof of claim 2, wherein: (1) VH comprising CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 1, 2, 3, respectively, and VL comprising CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 4, 5, 6, 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; (2) VH comprising CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID nos. 11, 12, 3, respectively, and VL comprising CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID nos. 13, 14, 15, 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) VH comprising CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID nos. 18, 19, 3, respectively, and VL comprising CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID nos. 20, 21, 22, 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; (4) VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 25, 26, 3, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOs 27, 28, 29, 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, or (5) VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID nos. 32, 19, 3, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID nos. 33, 34, 6, 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.
  4. 4. The antibody or antigen-binding fragment thereof of claim 2, wherein: (1) According to the Kabat definition, VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NO 84, 2, 3, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NO 4, 5, 6, respectively; (2) According to the Kabat definition, VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 85, 12, 3, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 13, 14, 15, respectively; (3) According to the Kabat definition, VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 85, 19, 3, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 20, 21, 22, respectively; (4) According to the Kabat definition, the VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS: 85, 26, 3, respectively, and the VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS: 27, 28, 29, respectively, or (5) According to the Kabat definition, VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS: 85, 19, 3, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS: 33, 34, 6, respectively.
  5. 5. The antibody or antigen-binding fragment thereof of claim 2, wherein: (1) According to the Chothia definition, VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS 87, 88, 89, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS 90, 91, 92, respectively; (2) According to the Chothia definition, VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 93, 94, 95, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 96, 97, 98, respectively; (3) According to the Chothia definition, VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 99, 100, 101, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 102, 103, 104, respectively; (4) According to the Chothia definition, the VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS 105, 106, 107, respectively, and the VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown in SEQ ID NOS 108, 109, 110, respectively, or (5) According to the Chothia definition, VH comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 111, 112, 113, respectively, and VL comprises CDR1, CDR2, CDR3 having the amino acid sequences shown as SEQ ID NOS: 114, 115, 116, respectively.
  6. 6. An antibody or antigen-binding fragment thereof that binds IL-4 ra, 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 VH sequence selected is SEQ ID NO. 7 and the VL sequence selected is SEQ ID NO. 8; (2) The VH sequence selected is SEQ ID NO. 9 and the VL sequence selected is SEQ ID NO. 10; (3) The VH sequence selected is SEQ ID NO. 16 and the VL sequence selected is SEQ ID NO. 17; (4) The VH sequence selected is SEQ ID NO. 23 and the VL sequence selected is SEQ ID NO. 24; (5) The VH sequence selected is SEQ ID NO. 30 and the VL sequence selected is SEQ ID NO. 31; (6) The VH sequence selected is SEQ ID NO. 35 and the VL sequence selected is SEQ ID NO. 36, and (7) The VH sequence selected is selected from the group consisting of SEQ ID NOs 7,9, 16, 23, 30 and 35, and the VL sequence selected is selected from the group consisting of SEQ ID NOs 8, 10, 17, 24, 31 and 36.
  7. 7. The antibody or antigen-binding fragment thereof of any one of claims 1-6, wherein the antibody or antigen-binding fragment specifically binds human IL-4 ra.
  8. 8. The antibody or antigen-binding fragment thereof of any one of claims 1-7, 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.
  9. 9. The antibody or antigen-binding fragment thereof of any one of claims 1-8, 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.
  10. 10. An antibody or antigen-binding fragment thereof that binds IL-4 ra, 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 a 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 a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of: (1) The VH sequence selected is SEQ ID NO. 7 and the VL sequence selected is SEQ ID NO. 8; (2) The VH sequence selected is SEQ ID NO. 9 and the VL sequence selected is SEQ ID NO. 10; (3) The VH sequence selected is SEQ ID NO. 16 and the VL sequence selected is SEQ ID NO. 17; (4) The VH sequence selected is SEQ ID NO. 23 and the VL sequence selected is SEQ ID NO. 24; (5) The VH sequence selected is SEQ ID NO. 30 and the VL sequence selected is SEQ ID NO. 31; (6) The VH sequence selected is SEQ ID NO. 35 and the VL sequence selected is SEQ ID NO. 36, and (7) The VH sequence selected is selected from the group consisting of SEQ ID NOs 7,9, 16, 23, 30 and 35, and the VL sequence selected is selected from the group consisting of SEQ ID NOs 8, 10, 17, 24, 31 and 36.
  11. 11. An antibody or antigen-binding fragment thereof that cross-competes with the antibody or antigen-binding fragment thereof of any one of claims 1-10.
  12. 12. The antibody or antigen-binding fragment thereof of any one of claims 1-11, wherein the antibody or antigen-binding fragment thereof is a bispecific antibody or a multispecific antibody or antigen-binding fragment thereof.
  13. 13. A nucleic acid comprising a polynucleotide encoding a polypeptide comprising: (1) An immunoglobulin heavy chain or fragment thereof comprising a VH, said VH comprising CDR1, CDR2 and CDR3, said CDR1, CDR2 and CDR3 comprising the amino acid sequences shown as SEQ ID nos. 1, 2, 3, respectively, the amino acid sequences shown as SEQ ID nos. 84, 2, 3, respectively, or the amino acid sequences shown as SEQ ID nos. 87, 88, 89, respectively, and wherein said VH binds to IL-4rα when paired with a light chain variable region (VL) comprising the amino acid sequences shown as SEQ ID nos. 8 or 10; (2) An immunoglobulin light chain or fragment thereof comprising a VL comprising CDR1, CDR2 and CDR3, said CDR1, CDR2 and CDR3 comprising the amino acid sequences shown in SEQ ID NOS 4, 5, 6, respectively, or the amino acid sequences shown in SEQ ID NOS 90, 91, 92, respectively, and wherein said VL binds to IL-4Rα when said VL is paired with a VH comprising the amino acid sequence shown in SEQ ID NOS 7 or 9; (3) An immunoglobulin heavy chain comprising a VH, or fragment thereof, the VH comprising CDR1, CDR2, and CDR3, the CDR1, CDR2, and CDR3 comprising the amino acid sequences shown in SEQ ID nos. 11, 12, 3, respectively, 85, 12, 3, respectively, or 93, 94, 95, respectively, and wherein the VH binds to IL-4rα when paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID No. 17; (4) An immunoglobulin light chain or fragment thereof comprising a VL comprising CDR1, CDR2 and CDR3, said CDR1, CDR2 and CDR3 comprising the amino acid sequences shown in SEQ ID NO. 13, 14, 15, respectively, or 96, 97, 98, respectively, and wherein said VL binds to IL-4Rα when said VL is paired with a VH comprising the amino acid sequence shown in SEQ ID NO. 16; (5) An immunoglobulin heavy chain or fragment thereof comprising a VH, said VH comprising CDR1, CDR2 and CDR3, said CDR1, CDR2 and CDR3 comprising the amino acid sequences shown as SEQ ID NOs 18, 19, 3, respectively, the amino acid sequences shown as SEQ ID NOs 85, 19, 3, respectively, or the amino acid sequences shown as SEQ ID NOs 99, 100, 101, respectively, and wherein said VH binds to IL-4 ra when paired with a light chain variable region (VL) comprising the amino acid sequences shown as SEQ ID NO 24; (6) An immunoglobulin light chain or fragment thereof comprising a VL comprising CDR1, CDR2 and CDR3, said CDR1, CDR2 and CDR3 comprising the amino acid sequences shown as SEQ ID NOS 20, 21, 22, respectively, or as SEQ ID NOS 102, 103, 104, respectively, and wherein said VL binds to IL-4Rα when said VL is paired with a VH comprising the amino acid sequence shown as SEQ ID NO 23; (7) An immunoglobulin heavy chain comprising a VH, or fragment thereof, the VH comprising CDR1, CDR2, and CDR3, the CDR1, CDR2, and CDR3 comprising the amino acid sequences shown in SEQ ID NOs 25, 26, 3, respectively, 85, 26, 3, respectively, or 105, 106, 107, respectively, and wherein the VH binds to IL-4 ra when paired with a light chain variable region (VL) comprising the amino acid sequence shown in SEQ ID NO 31; (8) An immunoglobulin light chain or fragment thereof comprising a VL comprising CDR1, CDR2 and CDR3, said CDR1, CDR2 and CDR3 comprising the amino acid sequences shown as SEQ ID NOS 27, 28, 29, respectively, or as SEQ ID NOS 108, 109, 110, respectively, and wherein said VL binds to IL-4Rα when said VL is paired with a VH comprising the amino acid sequence shown as SEQ ID NO 30; (9) An immunoglobulin heavy chain comprising a VH or fragment thereof, said VH comprising CDR1, CDR2 and CDR3, said CDR1, CDR2 and CDR3 comprising the amino acid sequences shown as SEQ ID NO. 32, 19, 3, respectively, the amino acid sequences shown as SEQ ID NO. 85, 19, 3, respectively, or the amino acid sequences shown as SEQ ID NO. 111, 112, 113, respectively, and wherein said VH binds to IL-4Rα when paired with a light chain variable region (VL) comprising the amino acid sequence shown as SEQ ID NO. 36, or (10) An immunoglobulin light chain or fragment thereof comprising a VL, said VL comprising CDR1, CDR2, and CDR3, said CDR1, CDR2, and CDR3 comprising the amino acid sequences shown in SEQ ID NOs 33, 34, 6, respectively, or the amino acid sequences shown in SEQ ID NOs 114, 115, 116, respectively, and wherein said VL binds to IL-4rα when said VL is paired with a VH comprising the amino acid sequence shown in SEQ ID NO 35.
  14. 14. The nucleic acid of claim 13, wherein the VH specifically binds human IL-4 ra when paired with VL.
  15. 15. The nucleic acid of claim 13 or 14, 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.
  16. 16. The nucleic acid of any one of claims 13-15, wherein the nucleic acid encodes a single chain variable fragment (scFv), a bispecific antibody, or a multispecific antibody, or an antigen-binding fragment thereof.
  17. 17. The nucleic acid of any one of claims 13-16, wherein the nucleic acid is cDNA.
  18. 18. A vector comprising one or more nucleic acids of any one of claims 13-17, or a nucleic acid encoding the antibody or antigen-binding fragment thereof of any one of claims 1-12.
  19. 19. A cell comprising the vector of claim 18.
  20. 20. The cell of claim 19, wherein the cell is a CHO cell.

Description

Anti-IL-4 Rα 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 anti-IL-4 ra antibodies or antigen-binding fragments thereof that are capable of specifically binding IL-4 ra. 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-IL-4 Rα antibodies or antigen-binding fragments thereof that can specifically bind IL-4Rα. 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 IL-4 ra (interleukin-4 receptor alpha subunit) 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%, 90%, or 100% 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, and the light chain variable region comprises CDR1, CDR2, and CDR3, in some embodiments, the VL CDR1 region comprises an amino acid sequence that is at least 80%, 90%, or 100% identical to a selected VL CDR1 amino acid sequence, the VL CDR2 region comprises an amino acid sequence that is at least 80% identical to a selected VL CDR2 amino acid sequence, and the VL CDR3 region comprises an amino acid sequence that is at least 80% identical to a selected VL 3 amino acid sequence. In some embodiments, the selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as GFTFX1X2NAMN（SEQ ID NO:57）、RIRTKX3X4X5YATYHADSVKD（SEQ ID NO:59） and DVGRGFAY (SEQ ID NO: 3), respectively, in some embodiments, X 1 = N, E, K or D, X 2 =i or M, X 3 =s, G or T, X 4 = N, A or S, X 5 = N, K or D, in some embodiments, the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX6X7X8X9SYX10H（SEQ ID NO:60）、LX11X12X13LQS（SEQ ID NO:61） and QHSX 14EX15PX16 T (SEQ ID NO: 62), respectively, in some embodiments, X 6 =T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, T or R, X 13 = N, Y, F or H, X 14 =r or T, X 15 =l or I, X 16 =l or I. In some embodiments, the selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown at GFTFX 1MNAMN（SEQ ID NO:58）、RIRTKX3X4X5 YATYHADSVKD (SEQ ID NO: 59) and DVGRGFAY (SEQ ID NO: 3), respectively, in some embodiments, X 1 = N, E, K or D, X 3 = S, G or T, X 4 = N, A or S, X 5 = N, K or D, in some embodiments selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX6X7X8X9SYX10H（SEQ ID NO:60）、LX11X12X13LQS（SEQ ID NO:61） and QHSX 14EX15PX16 T (SEQ ID NO: 62), respectively, in some embodiments, X 6 = T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, T or R, X 13 = N, Y, F or H, X 14 =r or T, X 15 =l or I, X 16 =l or I. In some embodiments, the selected VH CDR1, VH CDR2, VH CDR3 amino acid sequences are shown as X 2NAMN（SEQ ID NO:123）、RIRTKX3X4X5 YATYHADSVKD (SEQ ID NO: 59) and DVGRGFAY (SEQ ID NO: 3), respectively, in some embodiments, X 2 =i or M, X 3 =s, G or T, X 4 = N, A or S, X 5 = N, K or D, in some embodiments, the selected VL CDR1, VL CDR2, VL CDR3 amino acid sequences are shown as RASKSVSX6X7X8X9SYX10H（SEQ ID NO:60）、LX11X12X13LQS（SEQ ID NO:61） and QHSX 14EX15PX16 T (SEQ ID NO: 62), respectively, in some embodiments, X 6 =T, F. h or Y, X 7 = S, G, R or H, X 8 = G or E, X 9 = Y or F, X 10 = M or L, X 11 = a or G, X 12 = S, T or R, X 13 = N, Y, F or H, X 14 =r or T, X 15 =l or I, X 16 =l or I. In some embod