Anti-interleukin-11 antibodies and uses thereof

Abstract

Disclosed is an anti-interleukin 11 (IL-11) antibody or a fragment thereof that has high affinity for the antigen IL-11, blocks the formation of the IL-11 / IL-11Rα / GP130 ternary complex, and inhibits the activation of the STAT3 signal pathway. Thus, the anti-interleukin 11 antibody or a fragment thereof can effectively neutralize the activity of IL-11, and can be used to prevent, treat, and / or ameliorate diseases or conditions associated with IL-11 expression (including overexpression).

Description

[Technical field]

[0001] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims the benefit of priority from Chinese Patent Application No. 202210112310.7, filed on January 29, 2022, the entire contents of which are incorporated herein by reference for all purposes.

[0002] The present invention belongs to the field of biopharmaceuticals and relates to an antibody or an antigen-binding fragment thereof against interleukin-11 (IL-11), and applications of the antibody or the antigen-binding fragment thereof. [Background technology]

[0003] IL-11, discovered in 1990, is a member of the IL-6 family, consisting of 178 amino acids and with a molecular weight of approximately 19 kDa. IL-11 can be expressed by various cells, including leukocytes, fibroblasts, epithelial cells, etc., and its expression is regulated by various cytokines, such as TGF-β, IL-1β, IL-22, IL-17F, IFN-γ, TNF-α, COX-2, etc. IL-11 binds to the IL-11 receptor alpha subunit (IL-11Rα), and then activates downstream signaling pathways by forming a 2:2:2 (IL-11 / IL-11Rα / GP130) complex with the glycoprotein beta receptor subunit (GP130).

[0004] The most clearly studied physiological function of IL-11 is to promote the expansion of megakaryocytes and thus the production of platelets. In addition to hematopoietic function, another major physiological function of IL-11 is to promote bone formation (osteoblasts constitutively express IL-11 and IL-11Rα). IL-11 is a downstream response gene of TGF-β, and its expression is regulated by TGF-β. It has been reported that IL-11 can stimulate the production of red blood cells, promote the differentiation of macrophages and NK cells, regulate the release of Th1 / Th2-related cytokines, and in turn reduce tissue damage caused by inflammation.

[0005] Researchers have reported that IL-11 expression is upregulated in various tumors, including melanoma, breast cancer, colorectal cancer, non-small cell lung cancer, etc. In mouse models, in addition to tumor cells, tumor-infiltrating macrophages and T cells were found to express IL-11. In human colorectal cancer tissues, tumor-associated fibroblasts were the main source of IL-11 expression. IL-11 has been found to be involved in tumor-promoting processes at multiple levels by activating STAT3. Furthermore, IL-11 expression has been directly associated with the prognosis of various tumors. With regard to breast cancer, upregulation of IL-11 can further promote tumor bone metastasis. In mice with the IL-11Rα gene knocked out, the incidence of colorectal cancer was significantly reduced compared to that in wild-type mice.

[0006] IL-11 has also been found to be involved in renal and cardiac fibrosis, and in one study, IL-11 expression was found to be upregulated in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and correlated with the severity of lung disease. Multiple studies of IL-11 and its receptors in vitro and in animal models suggest that IL-11 can be considered as a drug target for various fibrosis-related diseases, including pulmonary fibrosis.

[0007] Although a number of studies on anti-IL-11 monoclonal antibodies have been conducted in the prior art, the signal transduction mechanism through which anti-IL-11 monoclonal antibodies function and the downstream therapeutic effects of anti-IL-11 monoclonal antibodies need to be further investigated. In particular, IL-11 has various biological activities and is involved in various physiological functions, and screening and obtaining new monoclonal antibodies that can specifically bind to the IL-11Rα and / or GP130 binding sites on IL-11 and inhibit the formation of IL-11 / IL-11Rα / GP130 complex and the activation of STAT3 is of great significance in treating diseases associated with the expression or overexpression of IL-11 and the abnormal activation of STAT3. Summary of the Invention

[0008] In consideration of the above problems, an object of the present disclosure is to provide a novel antibody or an antigen-binding fragment thereof against IL-11, particularly human IL-11. Compared with existing anti-IL-11 antibodies, the antibody provided by the present disclosure has a higher affinity for the antigen IL-11, and can block the formation of the IL-11 / IL-11Rα / GP130 complex with higher activity and inhibit the activation of the STAT3 signaling pathway, thereby making it possible to more effectively neutralize the activity of IL-11.

[0009] The present disclosure provides the following technical solutions:

[0010] In one aspect, the present disclosure provides antibodies or fragments thereof capable of binding with high affinity to the antigen IL-11, particularly human IL-11. According to certain embodiments of the present disclosure, the present disclosure provides the following antibodies: murine antibodies obtained by using human IL-11 or murine IL-11 as an immunogen; humanized antibodies obtained by humanizing murine antibodies, and antibodies obtained by sequence-optimizing the humanized antibodies by using yeast display technology.

[0011] Specifically, the present disclosure provides: A heavy chain variable region (VH) including complementary determining regions (CDRs), i.e., H-CDR1, H-CDR2, and H-CDR3; and a light chain variable region (VL) including CDRs, i.e., L-CDR1, L-CDR2, and L-CDR3; The present invention provides an antibody or fragment thereof comprising:

[0012] In some particular embodiments, the antibody or fragment thereof comprises: (1) The heavy chain variable region comprises: The amino acid sequence shown in SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32 or SEQ ID NO:33, The heavy chain variable region comprises a heavy chain CDR1 (H-CDR1), a heavy chain CDR2 (H-CDR2) and a heavy chain CDR3 (H-CDR3) derived from the heavy chain variable region comprising the amino acid sequence The light chain variable region comprises: The amino acid sequence shown in SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45 or SEQ ID NO:46, The light chain variable region comprises a light chain CDR1 (L-CDR1), a light chain CDR2 (L-CDR2) and a light chain CDR3 (L-CDR3) derived from the light chain variable region comprising the amino acid sequence Or, (2) The heavy chain variable region comprises: The amino acid sequence shown in SEQ ID NO:5, SEQ ID NO:9, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67 or SEQ ID NO:68, The heavy chain variable region comprises a heavy chain CDR1 (H-CDR1), a heavy chain CDR2 (H-CDR2) and a heavy chain CDR3 (H-CDR3) derived from the heavy chain variable region comprising the amino acid sequence The light chain variable region comprises: The amino acid sequence shown in SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86 or SEQ ID NO:87, The light chain variable region comprises a light chain CDR1 (L-CDR1), a light chain CDR2 (L-CDR2) and a light chain CDR3 (L-CDR3) derived from the light chain variable region comprising the amino acid sequence of:

[0013] The amino acid sequences in the above groups (1) and (2) are the amino acid sequences of the heavy chain variable region or the light chain variable region contained in the anti-IL-11 antibody provided by the present disclosure, respectively. By using schemes known in the art for defining the complementarity determining regions in the heavy chain variable region or the light chain variable region of an antibody (e.g., Chothia, Kabat, IMGT, Contact, etc.), one skilled in the art can easily determine the heavy and light chain CDRs contained in each sequence. According to certain embodiments of the present disclosure, the CDRs in the variable region sequences are defined using Kabat numbering.

[0014] In the antibodies or fragments thereof provided by the present disclosure, the heavy chain variable region and the light chain variable region preferably comprise the heavy chain CDR1, heavy chain CDR2 and heavy chain CDR3, and the light chain CDR1, light chain CDR2 and light chain CDR3 from the heavy chain variable region and light chain variable region shown in the following combination of amino acid sequences, respectively: (1) (1-1) SEQ ID NO:7 + SEQ ID NO:8; (1-2) SEQ ID NO:11 + SEQ ID NO:12; (1-3) SEQ ID NO:15+SEQ ID NO:12; (1-4) SEQ ID NO:16 + SEQ ID NO:12; (1-5) SEQ ID NO:17 + SEQ ID NO:12; (1-6) SEQ ID NO:18 + SEQ ID NO:12; (1-7) SEQ ID NO:15 + SEQ ID NO:34; (1-8) SEQ ID NO:15 + SEQ ID NO:35; (1-9) SEQ ID NO:15 + SEQ ID NO:36; (1-10) SEQ ID NO:15 + SEQ ID NO:37; (1-11) SEQ ID NO:15 + SEQ ID NO:38; (1-12) SEQ ID NO:15 + SEQ ID NO:39; (1-13) SEQ ID NO:15 + SEQ ID NO:40; (1-14) SEQ ID NO:15 + SEQ ID NO:41; (1-15) SEQ ID NO:15 + SEQ ID NO:42; (1-16) SEQ ID NO:19 + SEQ ID NO:40; (1-17) SEQ ID NO:20 + SEQ ID NO:40; (1-18) SEQ ID NO:21 + SEQ ID NO:40; (1-19) SEQ ID NO:22 + SEQ ID NO:40; (1-20) SEQ ID NO:23 + SEQ ID NO:40; (1-21) SEQ ID NO:15 + SEQ ID NO:43; (1-22) SEQ ID NO:15 + SEQ ID NO:44; (1-23) SEQ ID NO:15 + SEQ ID NO:45; (1-24) SEQ ID NO:15 + SEQ ID NO:46; (1-25) SEQ ID NO:23 + SEQ ID NO:43; (1-26) SEQ ID NO:23 + SEQ ID NO:44; (1-27) SEQ ID NO:23 + SEQ ID NO:45; (1-28) SEQ ID NO:23 + SEQ ID NO:46; (1-29) SEQ ID NO:24 + SEQ ID NO:44; (1-30) SEQ ID NO:25 + SEQ ID NO:44; (1-31) SEQ ID NO:26 + SEQ ID NO:44; (1-32) SEQ ID NO:27 + SEQ ID NO:44; (1-33) SEQ ID NO:28 + SEQ ID NO:44; (1-34) SEQ ID NO:29 + SEQ ID NO:44; (1-35) SEQ ID NO:30 + SEQ ID NO:44; (1-36) SEQ ID NO:31 + SEQ ID NO:44; (1-37) SEQ ID NO:32 + SEQ ID NO:44; (1-38) SEQ ID NO:33 + SEQ ID NO:44; Or, (2) (2-1) SEQ ID NO:5 + SEQ ID NO:6; (2-2) SEQ ID NO: 9 + SEQ ID NO: 10; (2-3) SEQ ID NO: 9 + SEQ ID NO: 69; (2-4) SEQ ID NO: 9 + SEQ ID NO: 70; (2-5) SEQ ID NO: 9 + SEQ ID NO: 71; (2-6) SEQ ID NO: 9 + SEQ ID NO: 72; (2-7) SEQ ID NO: 9 + SEQ ID NO: 73; (2-8) SEQ ID NO:9 + SEQ ID NO:74; (2-9) SEQ ID NO:9 + SEQ ID NO:76; (2-10) SEQ ID NO:9 + SEQ ID NO:77; (2-11) SEQ ID NO:9 + SEQ ID NO:78; (2-12) SEQ ID NO:9 + SEQ ID NO:79; (2-13) SEQ ID NO:9 + SEQ ID NO:80; (2-14) SEQ ID NO:9 + SEQ ID NO:81; (2-15) SEQ ID NO:49 + SEQ ID NO:10; (2-16) SEQ ID NO:50 + SEQ ID NO:10; (2-17) SEQ ID NO:49 + SEQ ID NO:75; (2-18) SEQ ID NO:49 + SEQ ID NO:82; (2-19) SEQ ID NO:49 + SEQ ID NO:83; (2-20) SEQ ID NO:49 + SEQ ID NO:77; (2-21) SEQ ID NO:49 + SEQ ID NO:79; (2-22) SEQ ID NO:50 + SEQ ID NO:77; (2-23) SEQ ID NO:50 + SEQ ID NO:79; (2-24) SEQ ID NO:53 + SEQ ID NO:77; (2-25) SEQ ID NO:9 + SEQ ID NO:84; (2-26) SEQ ID NO:9 + SEQ ID NO:85; (2-27) SEQ ID NO:51 + SEQ ID NO:77; (2-28) SEQ ID NO:52 + SEQ ID NO:77; (2-29) SEQ ID NO:54 + SEQ ID NO:77; (2-30) SEQ ID NO:9 + SEQ ID NO:86; (2-31) SEQ ID NO:52 + SEQ ID NO:86; (2-32) SEQ ID NO:55 + SEQ ID NO:87; (2-33) SEQ ID NO:56 + SEQ ID NO:87; (2-34) SEQ ID NO:57 + SEQ ID NO:87; (2-35) SEQ ID NO:51 + SEQ ID NO:87; (2-36) SEQ ID NO:54 + SEQ ID NO:87; (2-37) SEQ ID NO:58 + SEQ ID NO:87; (2-38) SEQ ID NO:59 + SEQ ID NO:87; (2-39) SEQ ID NO:60 + SEQ ID NO:87; (2-40) SEQ ID NO:61 + SEQ ID NO:87; (2-41) SEQ ID NO:62 + SEQ ID NO:87; (2-42) SEQ ID NO:63 + SEQ ID NO:87; (2-43) SEQ ID NO:64 + SEQ ID NO:87; (2-44) SEQ ID NO:65 + SEQ ID NO:87; (2-45) SEQ ID NO:66 + SEQ ID NO:87; (2-46) SEQ ID NO:67 + SEQ ID NO:87; (2-47) SEQ ID NO: 68 + SEQ ID NO: 87.

[0015] As mentioned above, the CDRs in each sequence of the variable regions of the above combinations can be defined using Kabat numbering. See the examples of the present disclosure (especially Tables 3 and 6). In addition, in the above combinations, the combinations of CDRs in the heavy chain variable region and the light chain variable region are contained in the antibody or fragment thereof provided by the present disclosure.

[0016] Thus, in the antibodies or fragments thereof provided by the present disclosure, the heavy and light chain variable regions comprise a combination of heavy and light chain CDRs (H-CDR1, H-CDR2, and H-CDR3, and L-CDR1, L-CDR2, and L-CDR3) selected from the group consisting of: (1) (1-1) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 95, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 97, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-2) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 100, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 97, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-3) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 97, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-4) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 102, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 97, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-5) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 103, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 97, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-6) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 104, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 97, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-7) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 115, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-8) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 116, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-9) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 117, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-10) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 118, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-11) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 119, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-12) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 120, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-13) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-14) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 122, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-15) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 123, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-16) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 105, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-17) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 106, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-18) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 107, SEQ ID NO: 101, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-19) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 108, and SEQ ID NO: 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-20) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 98, and SEQ ID NO: 99, respectively; (1-21) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO:94, SEQ ID NO:101, and SEQ ID NO:96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO:121, SEQ ID NO:124, and SEQ ID NO:99, respectively; (1-22) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO:94, SEQ ID NO:101, and SEQ ID NO:96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO:121, SEQ ID NO:125, and SEQ ID NO:99, respectively; (1-23) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO:94, SEQ ID NO:101, and SEQ ID NO:96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO:121, SEQ ID NO:126, and SEQ ID NO:99, respectively; (1-24) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO:94, SEQ ID NO:101, and SEQ ID NO:96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO:121, SEQ ID NO:127, and SEQ ID NO:99, respectively; (1-25) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 124, and SEQ ID NO: 99, respectively; (1-26) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO:94, SEQ ID NO:101, and SEQ ID NO:109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO:121, SEQ ID NO:125, and SEQ ID NO:99, respectively; (1-27) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO:94, SEQ ID NO:101, and SEQ ID NO:109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO:121, SEQ ID NO:126, and SEQ ID NO:99, respectively; (1-28) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO:94, SEQ ID NO:101, and SEQ ID NO:109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO:121, SEQ ID NO:127, and SEQ ID NO:99, respectively; (1-29) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO:94, SEQ ID NO:110, and SEQ ID NO:96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO:121, SEQ ID NO:125, and SEQ ID NO:99, respectively; (1-30) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 111, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 125, and SEQ ID NO: 99, respectively; (1-31) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 112, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 125, and SEQ ID NO: 99, respectively; (1-32) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 113, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 125, and SEQ ID NO: 99, respectively; and (1-33) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 114, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 125, and SEQ ID NO: 99, respectively; Or, (2) (2-1) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-2) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 146, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-3) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 147, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-4) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 148, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-5) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 149, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-6) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 150, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-7) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 151, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-8) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 153, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-9) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 154, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-10) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 155, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-11) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 156, and SEQ ID NO: 93, respectively; (2-12) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 157, and SEQ ID NO: 93, respectively; (2-13) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 158, and SEQ ID NO: 93, respectively; (2-14) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-15) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 131, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-16) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 152, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-17) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 159, and SEQ ID NO: 93, respectively; (2-18) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 160, and SEQ ID NO: 93, respectively; (2-19) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 154, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-20) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 156, and SEQ ID NO: 93, respectively; (2-21) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 131, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 154, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-22) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 131, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 156, and SEQ ID NO: 93, respectively; (2-23) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in the order of SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 134, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in the order of SEQ ID NO: 154, SEQ ID NO: 92, and SEQ ID NO: 93; (2-24) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 91, SEQ ID NO: 161, and SEQ ID NO: 93, respectively; (2-25) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 156, and SEQ ID NO: 93, respectively; (2-26) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 132, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 154, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-27) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 133, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 154, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-28) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 135, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 154, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-29) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 88, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 160, and SEQ ID NO: 93, respectively; (2-30) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 133, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 160, and SEQ ID NO: 93, respectively; (2-31) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 136, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-32) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 137, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-33) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 138, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-34) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 132, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-35) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 135, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-36) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 139, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-37) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 140, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-38) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 141, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-39) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 142, SEQ ID NO: 89, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-40) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 135, SEQ ID NO: 143, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-41) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 135, SEQ ID NO: 144, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-42) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 139, SEQ ID NO: 144, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; (2-43) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 139, SEQ ID NO: 143, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively; and (2-44) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 139, SEQ ID NO: 145, and SEQ ID NO: 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 162, SEQ ID NO: 92, and SEQ ID NO: 93, respectively.

[0017] The antibody or fragment thereof provided by the present disclosure is preferably an anti-interleukin-11 (IL-11) antibody or fragment thereof. The IL-11 is preferably human IL-11 (hIL-11). An exemplary amino acid sequence of human IL-11 is set forth in GenBank Accession No. AAH12506.1.

[0018] The anti-IL-11 antibodies or fragments thereof of the present disclosure comprise at least a heavy chain variable region and a light chain variable region, both of which comprise the above-mentioned CDRs and interspersed framework regions (FRs), preferably arranged as follows: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4.

[0019] In the anti-IL-11 antibody or fragment thereof provided by the present disclosure, (1) The heavy chain variable region is An amino acid sequence as set forth in SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, or SEQ ID NO:33, or an amino acid sequence having at least 75% identity to said amino acid sequence, and / or comprising an amino acid sequence selected from the group consisting of: The light chain variable region is An amino acid sequence as set forth in SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, or SEQ ID NO:46, or an amino acid sequence having at least 75% identity to said amino acid sequence; The amino acid sequence is selected from the group consisting of Or, (2) The heavy chain variable region is An amino acid sequence as set forth in SEQ ID NO:5, SEQ ID NO:9, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, or SEQ ID NO:68, or an amino acid sequence having at least 75% identity to said amino acid sequence, and / or comprising an amino acid sequence selected from the group consisting of: The light chain variable region is An amino acid sequence as set forth in SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, or SEQ ID NO:87, or an amino acid sequence having at least 75% identity to said amino acid sequence, It is further preferred that the amino acid sequence is selected from the group consisting of:

[0020] By "at least 75% identity", up to 25% differences in amino acid sequence may be present in any framework region within the heavy or light chain variable region, or in any domain or sequence other than the heavy and light chain variable regions of the antibody or fragment thereof according to the present disclosure. Differences may be due to deletion, addition or substitution of amino acids at any position, and the substitutions may be conservative or non-conservative. "At least 75% identity" encompasses any percent identity between 75% identity and 100% identity, for example, 75%, 80%, 85%, 90%, or even 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or even 100% identity.

[0021] According to certain embodiments of the present disclosure, in the anti-IL-11 antibody or fragment thereof provided by the present disclosure, the heavy chain variable region and the light chain variable region comprise the following: (1) (1-1) an amino acid sequence shown in SEQ ID NO: 7 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 8 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-2) an amino acid sequence shown in SEQ ID NO: 11 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-3) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-4) an amino acid sequence shown in SEQ ID NO: 16 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-5) an amino acid sequence shown in SEQ ID NO: 17 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-6) an amino acid sequence shown in SEQ ID NO: 18 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity thereto; (1-7) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 34 or an amino acid sequence having at least 75% identity thereto; (1-8) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 35 or an amino acid sequence having at least 75% identity thereto; (1-9) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 36 or an amino acid sequence having at least 75% identity thereto; (1-10) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 37 or an amino acid sequence having at least 75% identity thereto; (1-11) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 38 or an amino acid sequence having at least 75% identity thereto; (1-12) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 39 or an amino acid sequence having at least 75% identity thereto; (1-13) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity thereto; (1-14) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 41 or an amino acid sequence having at least 75% identity thereto; (1-15) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 42 or an amino acid sequence having at least 75% identity thereto; (1-16) an amino acid sequence shown in SEQ ID NO: 19 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity thereto; (1-17) the amino acid sequence shown in SEQ ID NO: 20 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity thereto; (1-18) an amino acid sequence shown in SEQ ID NO: 21 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity thereto; (1-19) an amino acid sequence shown in SEQ ID NO: 22 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity thereto; (1-20) an amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity thereto; (1-21) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 43 or an amino acid sequence having at least 75% identity thereto; (1-22) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-23) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 45 or an amino acid sequence having at least 75% identity thereto; (1-24) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 46 or an amino acid sequence having at least 75% identity thereto; (1-25) the amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 43 or an amino acid sequence having at least 75% identity thereto; (1-26) an amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-27) the amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 45 or an amino acid sequence having at least 75% identity thereto; (1-28) the amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 46 or an amino acid sequence having at least 75% identity thereto; (1-29) the amino acid sequence shown in SEQ ID NO: 24 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-30) the amino acid sequence shown in SEQ ID NO: 25 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-31) the amino acid sequence shown in SEQ ID NO: 26 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-32) an amino acid sequence shown in SEQ ID NO: 27 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-33) the amino acid sequence shown in SEQ ID NO: 28 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-34) the amino acid sequence shown in SEQ ID NO: 29 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-35) the amino acid sequence shown in SEQ ID NO: 30 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-36) the amino acid sequence shown in SEQ ID NO: 31 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; (1-37) the amino acid sequence shown in SEQ ID NO: 32 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; and (1-38) the amino acid sequence shown in SEQ ID NO: 33 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity thereto; Or, (2) (2-1) an amino acid sequence shown in SEQ ID NO:5 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO:6 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-2) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 10 or an amino acid sequence having at least 75% identity thereto; (2-3) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 69 or an amino acid sequence having at least 75% identity thereto; (2-4) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 70 or an amino acid sequence having at least 75% identity thereto; (2-5) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 71 or an amino acid sequence having at least 75% identity thereto; (2-6) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 72 or an amino acid sequence having at least 75% identity thereto; (2-7) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 73 or an amino acid sequence having at least 75% identity thereto; (2-8) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 74 or an amino acid sequence having at least 75% identity thereto; (2-9) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 76 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-10) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity thereto; (2-11) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 78 or an amino acid sequence having at least 75% identity thereto; (2-12) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 79 or an amino acid sequence having at least 75% identity thereto; (2-13) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 80 or an amino acid sequence having at least 75% identity thereto; (2-14) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 81 or an amino acid sequence having at least 75% identity thereto; (2-15) an amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 10 or an amino acid sequence having at least 75% identity thereto; (2-16) an amino acid sequence shown in SEQ ID NO: 50 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 10 or an amino acid sequence having at least 75% identity thereto; (2-17) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 75 or an amino acid sequence having at least 75% identity thereto; (2-18) an amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 82 or an amino acid sequence having at least 75% identity thereto; (2-19) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 83 or an amino acid sequence having at least 75% identity thereto; (2-20) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity thereto; (2-21) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 79 or an amino acid sequence having at least 75% identity thereto; (2-22) an amino acid sequence shown in SEQ ID NO: 50 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity thereto; (2-23) an amino acid sequence shown in SEQ ID NO: 50 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 79 or an amino acid sequence having at least 75% identity thereto; (2-24) the amino acid sequence shown in SEQ ID NO: 53 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity thereto; (2-25) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 84 or an amino acid sequence having at least 75% identity thereto; (2-26) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 85 or an amino acid sequence having at least 75% identity thereto; (2-27) the amino acid sequence shown in SEQ ID NO: 51 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity thereto; (2-28) the amino acid sequence shown in SEQ ID NO: 52 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity thereto; (2-29) the amino acid sequence shown in SEQ ID NO: 54 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity thereto; (2-30) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 86 or an amino acid sequence having at least 75% identity thereto; (2-31) the amino acid sequence shown in SEQ ID NO: 52 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 86 or an amino acid sequence having at least 75% identity thereto; (2-32) an amino acid sequence shown in SEQ ID NO: 55 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-33) an amino acid sequence shown in SEQ ID NO: 56 or an amino acid sequence having at least 75% identity thereto, and an amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-34) the amino acid sequence shown in SEQ ID NO: 57 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-35) the amino acid sequence shown in SEQ ID NO: 51 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-36) the amino acid sequence shown in SEQ ID NO: 54 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-37) the amino acid sequence shown in SEQ ID NO: 58 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-38) the amino acid sequence shown in SEQ ID NO: 59 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-39) the amino acid sequence shown in SEQ ID NO: 60 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-40) the amino acid sequence shown in SEQ ID NO: 61 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-41) the amino acid sequence shown in SEQ ID NO: 62 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-42) the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-43) the amino acid sequence shown in SEQ ID NO: 64 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-44) the amino acid sequence shown in SEQ ID NO: 65 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-45) the amino acid sequence shown in SEQ ID NO: 66 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; (2-46) the amino acid sequence shown in SEQ ID NO: 67 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; and (2-47) the amino acid sequence shown in SEQ ID NO: 68 or an amino acid sequence having at least 75% identity thereto, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity thereto; The amino acid sequence of the present invention is selected from the group consisting of:

[0022] With respect to the antigen, the antibody or fragment thereof provided by the present disclosure is an anti-IL-11 antibody or an antigen-binding fragment thereof. The antibody is preferably a mouse antibody, a rabbit antibody, a human antibody, a chimeric antibody, or a fully or partially humanized antibody. The antibody may also be a derivatized antibody, for example, an antibody obtained by CDR grafting, affinity maturation, point mutation engineering, chemical modification, etc., performed on the original mouse monoclonal antibody, where the chemical modification includes glycosylation, acetylation, pegylation, phosphorylation, amidation, cleavage by a protease, attachment to a cellular ligand or effector molecule, protection and / or blocking of active reactive groups, etc. The antigen-binding fragment of the anti-IL-11 antibody may be any form of fragment of the antibody, for example, a single chain variable fragment (scFv), a bivalent single chain variable fragment (BsFv), a disulfide stabilized variable fragment (dsFv), a (disulfide stabilized variable fragment) 2 ((dsFv) 2 ), antigen-binding fragment (Fab), Fab' fragment (Fab'), F(ab') 2 Fragment(F(ab') 2 ), or a variable fragment (Fv).

[0023] The antibodies or fragments thereof provided by the present disclosure further comprise, in addition to the variable regions, a heavy chain constant region (CH) and / or a light chain constant region (CL), preferably a human or mouse heavy chain constant region and / or a light chain constant region. Preferably, the antibodies or fragments thereof comprise an IgG, IgA, IgM, IgD or IgE heavy chain constant region, and / or a kappa or lambda type light chain constant region.

[0024] According to certain embodiments of the present disclosure, the antibody is a monoclonal antibody, preferably a murine, chimeric or humanized monoclonal antibody. According to certain embodiments of the present disclosure, the monoclonal antibody comprises a sequence of a murine IgG1 heavy chain constant region, for example the sequence of the murine IgG1 heavy chain constant region shown in SEQ ID NO: 3, and / or comprises a sequence of a murine light chain constant region, for example the sequence of the murine light chain constant region shown in SEQ ID NO: 4. According to certain embodiments of the present disclosure, the monoclonal antibody comprises a human heavy chain constant region and a human light chain constant region, for example the human heavy chain constant region and the human light chain constant region shown in SEQ ID NO: 13 and SEQ ID NO: 14, respectively.

[0025] According to certain embodiments of the present disclosure, the anti-IL-11 antibody provided by the present disclosure is a monoclonal antibody. The anti-IL-11 antibody provided by the present disclosure is preferably an immunoglobulin. For example, the immunoglobulin is of human IgA, IgD, IgE, IgG, or IgM subtype, more preferably human IgG1, IgG2, IgG3, or IgG4 subtype.

[0026] In another aspect, the present disclosure provides a nucleic acid molecule comprising a nucleotide sequence encoding a heavy chain CDR, a light chain CDR, a heavy chain variable region, a light chain variable region, a heavy chain or a light chain contained in an antibody or fragment thereof provided by the present disclosure.

[0027] The nucleic acid molecules provided by the present disclosure can be cloned into a vector, which in turn can be used to transfect or transform a host cell. Thus, in yet another aspect, the present disclosure provides a vector comprising the nucleic acid molecules provided by the present disclosure. The vector can be a eukaryotic expression vector, a prokaryotic expression vector, an artificial chromosome, a phage vector, etc. The vector or nucleic acid molecules provided by the present disclosure can be used to transform or transfect a host cell, such as for protection or expression of an antibody. Thus, in a further aspect, the present disclosure provides a host cell comprising the nucleic acid molecules and / or vectors provided by the present disclosure, or transformed or transfected with the nucleic acid molecules and / or vectors provided by the present disclosure. The host cell can be any prokaryotic or eukaryotic cell, such as a bacterial cell, or an insect cell, a fungal cell, a plant cell, or an animal cell.

[0028] The antibodies or fragments thereof provided by the present disclosure can be obtained using any conventional technique known in the art. For example, a host cell provided by the present disclosure is cultured under conditions that allow the host cell to express the heavy and light chains of the antibody. Optionally, the method further comprises a step of recovering the produced antibody.

[0029] The antibodies or fragments thereof, nucleic acid molecules, vectors, and / or host cells provided by the present disclosure can be contained in compositions, more particularly pharmaceutical compositions, e.g., pharmaceutical preparations, for use for various purposes as actually required.

[0030] Thus, in yet a further aspect, the present disclosure also provides compositions comprising the antibodies or fragments thereof, nucleic acid molecules, vectors, and / or host cells provided by the present disclosure, and optionally pharma- ceutically acceptable auxiliary materials. The compositions provided by the present disclosure can be formulated into a variety of dosage forms known in the medical or pharmaceutical arts and administered in an appropriate manner.

[0031] In yet another aspect, the present disclosure also provides for the use of the antibody or fragment thereof, nucleic acid molecule, vector, host cell and / or composition in the manufacture of a medicament for preventing, treating and / or ameliorating a disease or disorder associated with expression (including overexpression) of IL-11. The antibody or fragment thereof, nucleic acid molecule, vector, host cell and / or composition may function, inter alia, by binding to IL-11, blocking the formation of the IL-11 / IL-11Rα / GP130 complex and inhibiting activation of the STAT3 signaling pathway. According to certain embodiments of the present disclosure, the disease or disorder is an inflammatory disease or tumor, such as liver injury, pulmonary fibrosis and colon cancer.

[0032] Thus, the present disclosure also provides a method of preventing, treating and / or ameliorating a disease or disorder associated with expression (including overexpression) of IL-11, comprising administering to a subject in need thereof an antibody or fragment thereof, a nucleic acid molecule, a vector, a host cell and / or a composition provided by the present disclosure. Preferably, the disease or disorder is an inflammatory disease or tumor, such as liver injury, pulmonary fibrosis and colon cancer. Preferably, the subject is a mammal, and more preferably, the subject is a human.

[0033] The methods of preventing, treating, and / or ameliorating a disease or disorder provided by the present disclosure are used depending on a variety of factors, including the particular active ingredient of the pharmaceutical composition being administered, the age, weight, sex, or physical and medical condition of the patient, the severity of the condition being treated, the route of administration, etc.

[0034] In yet a further aspect, the present disclosure also provides the use of an antibody or fragment thereof, nucleic acid molecule, vector, host cell and / or composition provided by the present disclosure in the manufacture of a medicament for diagnosing a disease or disorder associated with expression (including overexpression) of IL-11. Preferably, the disease or disorder is an inflammatory disease or tumor, such as liver injury, pulmonary fibrosis and colon cancer.

[0035] In yet another aspect, the present disclosure provides a kit comprising the antibody or fragment thereof, nucleic acid molecule, vector, host cell and / or composition provided by the present disclosure. The kit can be used for the above-mentioned treatment or diagnosis, or for antigen detection. For example, the kit is a kit for detecting the expression of IL-11 in any biological sample using ELISA.

[0036] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of the present invention will now be described in detail with reference to the accompanying drawings. [Brief description of the drawings]

[0037] [Figure 1] FIG. 1 shows the binding activity of hybridoma supernatants to human IL-11 and mouse IL-11. [Diagram 2] Figure 1 shows the inhibitory activity of anti-IL-11 antibodies against the formation of IL-11 / IL-11Rα / GP130. 2a: mu8C8; 2b: mu18A10; 2c: 3C6-mFc. [Diagram 3] FIG. 1 shows the results of an analysis of reporter gene expression in STAT3 / IL-11Rα / GP130-HEK293 cells stimulated with IL-11. [Figure 4A] 4A and 4B show the in vivo activity of anti-IL-11 antibodies in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. 4a: Results of H&E and Masson staining of lung tissue sections. [Figure 4B] Figure 4 shows the in vivo activity of anti-IL-11 antibodies in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. 4b: Fibrosis and lung function analysis. [Diagram 5] Figure 5: Efficacy of anti-IL-11 antibodies in a mouse tumor model bearing MC38 tumor cells. 5a: tumor volume; 5b: tumor weight. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038] The present invention will now be described with reference to specific examples. It will be appreciated by those skilled in the art that these examples are merely illustrative of the present invention and do not limit the scope of the present invention in any way.

[0039] The experimental procedures in the following examples are all conventional unless otherwise specified. Raw materials and reagents used in the following examples are all commercially available unless otherwise specified. EXAMPLES

[0040] Example 1 Preparation and analysis of hybridoma-derived mouse anti-IL-11 antibodies Mouse anti-IL-11 hybridoma monoclonals 5C2, 8C8, 16B5, 18A10, 18H10, 23G6 and 29C11 were obtained by mouse hybridoma technology. The binding activity of the supernatants of these clones to human IL-11 (AAH12506.1, Pro22-Leu199; SEQ ID NO: 128) and mouse IL-11 (NP_032376.1, Pro22-Leu199; SEQ ID NO: 129) immobilized on the surface of an ELISA plate was detected by direct ELISA. The results are shown in Figure 1.

[0041] When hybridoma cells were cultured to a certain number, the culture supernatant was collected and purified using protein G affinity chromatography to obtain mouse hybridoma antibodies (Hy5C2, Hy8C8, Hy16B5, Hy18A10, Hy18H10, Hy23G6 and Hy29C11). The affinity of the mouse antibodies purified from the hybridoma supernatant was determined using an anti-mouse IgG Fc capture biosensor to capture the Fc fragment of the antibody using an Octet QKe System instrument from Fortebio Inc. As a positive control, a recombinantly expressed anti-IL-11 antibody named "3C6-mFc" was used at the same concentration. Specifically, the hybridoma supernatant was diluted with HBS-EP+ buffer (GE) and passed over the surface of an AMC probe (catalog number: 18-5088, PALL), so that the antibodies in the hybridoma supernatant were captured on the surface of the probe. Human IL-11 diluted in HBS-EP+ buffer (300 nM) was then used as the mobile phase to react with the antibody captured on the surface of the probe. Both binding and dissociation were performed for 300 seconds. Upon completion of the experiment, the data, minus the response value of the blank control, was fitted by the software using a 1:1 Langmuir binding model, and the rate constant of antigen-antibody binding was then calculated. The binding signal was detected using Hy5C2, Hy8C8, Hy16B5, Hy18A10, and Hy18H10 on an Octet QKe System instrument. The final results of the measurement are shown in Table 1 below.

[0042] The sequence of the positive control anti-IL-11 antibody 3C6-mFc is disclosed in WO 2019 / 238882. The sequence of the heavy chain variable region of 3C6-mFc is designated "3C6-VH" and is as set forth in SEQ ID NO: 1, the sequence of the light chain variable region of 3C6-mFc is designated "3C6-VL" and is as set forth in SEQ ID NO: 2, and 3C6-mFc has a murine IgG1 constant region, i.e., the heavy chain constant region of the murine antibody set forth in SEQ ID NO: 3 and the light chain constant region of the murine antibody set forth in SEQ ID NO: 4.

[0043] [Table 1]

[0044] SEQ ID NO: 1 3C6-VH EVQLVQSGAEVKKPGASVKISCKASGYTFTDYNMDWVKQAPGQRLEWIGDINPHNGGPIYNQKFTGRATLTVDKSASTAYMELSSLRSEDTAVYYCARGELGHWYFDVWGQGTTVTVSS

[0045] SEQ ID NO:2 3C6-VL DIVLTQSPASLALSPGERATLSCRASKSVSTSGYSYIHWYQQKPGQAPRLLIYLASNLDSGVPARFSGSGSGTDFTLTISSLEEEDFATYYCQHSRDLPPTFGQGTKLEIK

[0046] SEQ ID NO: 3: Heavy chain constant region of mouse antibody AKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVPSSTWPSETVTCNVAHPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVH TAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK

[0047] SEQ ID NO: 4 Mouse antibody light chain constant region RTVAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC

[0048] Example 2 Gene cloning and recombinant expression of mouse anti-IL11 antibodies When the hybridoma cells were cultured to a certain number, the cells were harvested and total RNA was extracted from the cells. The obtained RNA was subjected to reverse transcription PCR to obtain and sequence the genes encoding the light and heavy chain variable regions of the mouse antibody. The sequence of the heavy chain variable region of Hy18A10 is called "mu18A10 VH" and is shown in SEQ ID NO: 5, and the sequence of the light chain variable region of Hy18A10 is called "mu18A10 VL" and is shown in SEQ ID NO: 6. The sequence of the heavy chain variable region of Hy8C8 is called "mu8C8 VH" and is shown in SEQ ID NO: 7, and the sequence of the light chain variable region of Hy8C8 is called "mu8C8 VL" and is shown in SEQ ID NO: 8. The CDRs are defined according to Kabat numbering and are underlined. The same applies below.

[0049] SEQ ID NO:5 (CDR: SEQ ID NO:88 / 89 / 90) mu18A10-VH QVQLQQPGAELVKPGASVKMSCKASGYKFI TYNMD WVKQTPGQGLEWIG TIYPGNGDTSYNQKFKG KATLTADKSSSTAYMQLSSLTSEDSAVYYCAR GDLYALDY WGQGTSVTVSS

[0050] SEQ ID NO:6 (CDR: SEQ ID NO:91 / 92 / 93) mu18A10-VL SIVMTQTPKFLLVSAGDRVTITC KASQSVSNDVA WYQQKPGQSPKLLIY SASNRYT GVPDRFTGSGYGTDFTFTINTVQAEDLAVYFC QHDYSSPYT FGGGTKLEIKR

[0051] SEQ ID NO:7 (CDR: SEQ ID NO:94 / 100 / 96) mu8C8-VH DVQLVESGGGLVQPGGSRKLSCAASGFTFS SFGMH WVRQSPERGLEWVA YITSGSNTIYYADTVKG RFTISRDNPENTLFLQMTSLRSEDTAMYYCAR EYYSYDEGFAY WGQGTLVTVSA

[0052] SEQ ID NO:8 (CDR: SEQ ID NO:97 / 98 / 99) mu8C8-VL EIVLTQSPTTMAASPGEKITITC SVSSSISSNYLH WYQQKPGFSPKLLIY RTSNLAS GVPARFSGSGSGTSHSLTIDTMEAEDVATYYC QQGVDVPFT FGSGTKLEIKR

[0053] According to the amino acid sequence of the mouse antibody obtained by gene cloning, the antibody-encoding gene was optimized and synthesized. Restriction enzyme cleavage sites were designed and introduced into both ends of the gene, and the gene encoding the variable region of the antibody was linked to the gene encoding the heavy chain constant region and light chain constant region of the mouse antibody (the amino acid sequences are as shown in SEQ ID NO: 3 and SEQ ID NO: 4) by enzymatic digestion. The obtained genes were cloned into eukaryotic cell transient expression vectors, respectively, to obtain recombinant mouse antibody expression vectors. Then, the antibody light chain and heavy chain expression vectors were introduced into Escherichia coli (E. coli) for plasmid propagation and transformed, and a large number of plasmids were isolated. The heavy and light chain plasmids of the candidate antibodies were co-transfected into HEK293 cells according to the instructions of 293fectin Transfection Reagent to recombinantly express the antibody. Five to six days after the transfection of the cells, the culture supernatant was collected and purified using a protein G affinity chromatography column to obtain recombinant mouse antibodies mu8C8 and mu18A10.

[0054] Example 3 Analysis of the activity of recombinant mouse anti-IL-11 antibodies to block the formation of the IL-11 / IL-11Rα / GP130 complex The activity of recombinant mouse anti-IL-11 antibodies to block the formation of the IL-11 / IL-11Rα / GP130 complex was analyzed by competitive ELISA. First, IL-11Rα-His (NP_004503.1, Met1-Val363, C-terminal 6×His tag) was added to ELISA plates to coat the plates overnight. The next day, samples were prepared as follows: first, IL-11 (catalog number: 12225-HNCE, Sino Biological Inc.) at a constant concentration of 0.4 μg / ml was mixed with serially diluted (working concentrations: 75 μg / ml, 25 μg / ml, 8.33 μg / ml, 2.78 μg / ml, 0.926 μg / ml, 0.309 μg / ml, and 0.103 μg / ml) mouse anti-IL-11 antibody, co-incubated, and then mixed with gp130-hFc (NP_034690.3, Met1-Glu617, C-terminus-mFc) at a final concentration of 1 μg / ml, and then the resulting mixture was added to an ELISA plate. After co-incubation and washing, anti-human Fc secondary antibody conjugated with HRP was added to develop the color, which was then detected. Finally, the results showed that the murine antibodies mu8C8 and mu18A10 had fairly good blocking effects, as shown by their IC50 values ​​of 1.610 μg / ml and 1.402 μg / ml, respectively (Figures 2a and 2b), which were comparable to the IC50 value of the control antibody 3C6-mFc (2.104 μg / ml, Figure 2c).

[0055] Example 4 Humanization of antibodies The murine antibodies mu8C8 and mu18A10 were engineered for humanization and the humanized antibodies were recombinantly expressed.

[0056] The heavy and light chain CDRs of the murine antibodies mu8C8 and mu18A10 were grafted into human templates with high homology to the murine antibodies, backmutations were performed if necessary, and the humanized antibodies designated "hz18A10" and "hz8C8" were obtained. The sequence of the heavy chain variable region of hz18A10 is designated "hz18A10-VH" and is as set forth in SEQ ID NO: 9, and the sequence of the light chain variable region of hz18A10 is designated "hz18A10-VL" and is as set forth in SEQ ID NO: 10. The sequence of the heavy chain variable region of "hz8C8" is designated "hz8C8-VH" and is as set forth in SEQ ID NO: 11, and the sequence of the light chain variable region of "hz8C8" is designated "hz8C8-VL" and is as set forth in SEQ ID NO: 12.

[0057] SEQ ID NO: 9 (CDR: SEQ ID NO: 88 / 89 / 90): hz18A10-VH EVQLVQSGAEVKKPGASVKVSCKASGYTFT TYNMD WVRQAPGQGLEWMG TIYPGNGDTSYNQKFKG RVTTMTRDTTSTSTVYMELSSLRSEDTAVYYCAR GDLYALDY WGQGTLVTVSS

[0058] SEQ ID NO: 10 (CDR: SEQ ID NO: 91 / 92 / 93): hz18A10-VL DIQMTQSPSSLSASVGDRVTITC KASQSVSNDVA WYQQKPGKAPKLLIY SASNRYT GVPSRFSGSGSGTTDFTFTISSLQPEDIATYYC QHDYSSPYT FGQGTKLEIK

[0059] SEQ ID NO: 11 (CDR: SEQ ID NO: 94 / 100 / 96): hz8C8-VH EVQLVESGGGLVQPGGSLRLSCAASGFTFS SFGMH WVRQAPGKGLEWVA YITSGSNTIYYADTVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR EYYSYDEGFAY WGQGTLVTVSS

[0060] SEQ ID NO: 12 (CDR: SEQ ID NO: 97 / 98 / 99): hz8C8-VL EIVLTQSPATLSLSPGERATLSC SVSSSISSNYLH WYQQKPGQAPRLLIY RTSNLAS GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC QQGVDVPFT FGQGTKLEIK

[0061] According to the amino acid sequence of the obtained humanized antibody, the antibody-encoding gene was optimized and synthesized. Restriction enzyme cleavage sites were designed and introduced at both ends of the gene, and the gene encoding the variable region of the antibody was linked to the gene encoding the heavy chain constant region and the light chain constant region of the human antibody (the amino acid sequences are as shown in SEQ ID NO: 13 and SEQ ID NO: 14) by enzyme digestion. The obtained genes were respectively cloned into eukaryotic transient expression vectors to obtain expression vectors of recombinant humanized antibodies. Then, according to the method presented in Example 2, recombinant humanized antibody hz18A10 derived from clone 18A10 and recombinant humanized antibody hz8C8 derived from clone 8C8 were prepared.

[0062] The affinity of hz18A10 and hz8C8 was determined according to the method presented in Example 1, using instead the AHC bioprobe for capturing the human Fc fragment, with other conditions unchanged. As a positive control, recombinantly expressed anti-IL-11 antibody 3C6-hFc was used at the same concentration. The final results of the affinity measurements are shown in Tables 4 and 7.

[0063] The sequence of the positive control anti-IL-11 antibody 3C6-hFc is disclosed in WO 2019 / 238882. The sequence of the heavy chain variable region of 3C6-hFc is designated "3C6-VH" and is as set forth in SEQ ID NO: 1, the sequence of the light chain variable region of 3C6-hFc is designated "3C6-VL" and is as set forth in SEQ ID NO: 2, and 3C6-hFc has a human IgG1 constant region, i.e., the heavy chain constant region of the human antibody set forth in SEQ ID NO: 13 and the light chain constant region of the human antibody set forth in SEQ ID NO: 14.

[0064] SEQ ID NO: 13: Heavy chain constant region of human antibody ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0065] SEQ ID NO: 14 Human antibody light chain constant region RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[0066] Example 5 Sequence optimization of hz8C8 Random mutations were performed on all or certain amino acid residues in six CDRs contained in the heavy chain variable region (SEQ ID NO: 11) and light chain variable region (SEQ ID NO: 12) of the humanized antibody hz8C8 by yeast display technology to construct a yeast display single chain antibody (scFv) library (Table 2). Then, 4 to 5 rounds of selection were performed by magnetic bead selection technology and flow cytometry selection technology to obtain mutants with affinities equivalent to or better than those of the parent antibody. Information on "hot spot" amino acids was obtained by comprehensively analyzing the mutation sites of the mutants. Then, the mutation sequences of the light chain variable region and the heavy chain variable region were recombined and designed with consideration to avoid sites that may cause immunogenicity risks, such as T cell epitopes and B cell epitopes, and PTM sites (Table 3).

[0067] Then, light and heavy chain expression vectors for preparing the mutated antibodies were constructed using the mutated sequences shown in Table 3, appropriately linked with human IgG1 constant region (SEQ ID NO: 13 and SEQ ID NO: 14), according to the method for preparing recombinant antibodies presented in Example 4. The light and heavy chains were then rationally matched and co-transfected into eukaryotic cells for transient expression, and then recombinant protein samples of the mutated antibodies were obtained by affinity purification. The obtained samples were tested for affinity on Fortebio's Octet, according to the method for measuring affinity presented in Example 1. The final results of the measurement are shown in Table 4 below. Furthermore, hz8C8 and its affinity matured variants were analyzed for their activity in blocking the formation of the IL-11 / IL-11Rα / GP130 complex, using the protocol presented in Example 3. The results are shown in Table 4 below.

[0068] SEQ ID NO: 94: hz8C8 H-CDR1 SFGMH

[0069] SEQ ID NO: 100: hz8C8 H-CDR2 YITSGSNTIYYADTVKG

[0070] SEQ ID NO: 96: hz8C8 H-CDR3 EYYSYDEGFAY

[0071] SEQ ID NO: 97: hz8C8 L-CDR1 SVSSSISSNYLH

[0072] SEQ ID NO: 98: hz8C8 L-CDR2 RTSNLAS

[0073] SEQ ID NO: 99: hz8C8 L-CDR3 QQGVDVPFT

[0074] [Table 2]

[0075] [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5]

[0076] [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4]

[0077] Example 6 Optimization of the sequence of hz18A10 Following the protocol for carrying out affinity maturation of hz8C8 described above, a mutation library (Table 5) was constructed by yeast display technology and used to carry out affinity maturation and sequence optimization of humanized anti-IL-11 antibody hz18A10. The designed mutant sequences of the light chain variable region and heavy chain variable region are shown in Table 6. The mutant antibodies were recombinantly expressed and their affinities were measured. The results are shown in Table 7 below.

[0078] SEQ ID NO: 88: hz18A10 H-CDR1 TYNMD

[0079] SEQ ID NO: 89: hz18A10 H-CDR2 TIYPGNGDTSYNQKFKG

[0080] SEQ ID NO: 90: hz18A10 H-CDR3 GDLYALDY

[0081] SEQ ID NO: 91: hz18A10 L-CDR1 KASQSVSNDVA

[0082] SEQ ID NO: 92: hz18A10 L-CDR2 SASNRYT

[0083] SEQ ID NO: 93: hz18A10 L-CDR3 QHDYSSPYT

[0084] [Table 5]

[0085] [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4] [Table 6-5] [Table 6-6]

[0086] [Table 7-1] [Table 7-2] [Table 7-3]

[0087] Example 7 Analysis of the effects of hz8C8 and its mutants on the STAT3 signaling pathway using a reporter gene system (1) Construction of IL-11Rα / GP130 / STAT3-luc HEK293 reporter gene system To analyze the cytological activity of the antibody, an IL-11Rα / STAT3-luc HEK293 reporter system was constructed. A vector containing the STAT3-Luciference reporter gene system (Cobioer Inc.) was transfected into HEK293 cells, and a stable cell line called STAT3-Luc / HEK293, in which the STAT3-Luciference gene was integrated, was obtained by pressure screening. Next, based on this cell line, a vector containing the full-length gene of human IL-11Rα (Sino Biological Inc.) was transfected into the cells, and a pool capable of stably expressing human IL-11Rα (IL-11Rα / STAT3-luc HEK293 pool) was obtained by pressure screening. Finally, the pool was subjected to isolation and screening of single clones to obtain IL-11Rα / STAT3-luc HEK293 monoclonal cells. Monoclonal cells that could be stably passaged were selected and stored as cell strains. HEK293 cells constitutively express GP130 and were therefore stably transfected with IL-11Rα / STAT3-luc to construct the IL-11Rα / GP130 / STAT3-luc HEK293 reporter gene system.

[0088] To detect the stimulatory activity, cells were seeded in 96-well plates. IL-11 was also diluted to an appropriate concentration and then subjected to serial dilution. The diluted IL-11 was then added to the cells in the 96-well plates. Blank wells were also included in the 96-well plates. During data processing, the fluorescence measurements from the blank wells were subtracted from the fluorescence measurements of all other wells, and the resulting data were used to generate a dose-effect curve. The results (Figure 3) showed that IL-11 could stimulate the transcriptional expression of the reporter gene, with a clearly defined dose effect. The EC50 of IL-11 for stimulating the transcriptional expression of the STAT3-luc reporter gene was 0.11 ng / ml.

[0089] (2) The effects of hz8C8, hz18A10 and their mutants on the STAT3 signaling pathway, as determined using a reporter gene system. The activity of the antibodies in inhibiting the stimulation of cell reporter genes by IL-11 was determined using the IL-11Rα / GP130 / STAT3-luc HEK293 reporter gene system. Cells were seeded in 96-well plates. IL-11 was also diluted to 0.3ng / ml and co-incubated with serially diluted antibodies (10μg / ml, then diluted 3-fold to obtain 10 concentrations) for 30 minutes, and then the mixture was added to the cells and incubated for 6 hours. After that, the detection reagent of Luciferase Assay kit (Vazyme Biotech Co., Ltd, D1201-02 bio-lite) was added, and the signal value was read (RLUsample). In this experiment on inhibitory activity, 3C6-hFc was used as a positive control antibody, irrelevant human IgG (NC-hIgG) was used as a negative control antibody, PBS with IL-11 was used as a positive blank control (RLUhigh), and PBS was used as a negative blank control (RLUlow).

[0090] The % inhibition for each well was calculated using the readings from wells with different concentrations of antibody added. The formula for calculating % inhibition is as follows: Inhibition % = (RLUhigh-RLUsample) / (RLUhigh-RLUlow) x 100%

[0091] Using GraphPad Prism software, dose-effect curves were plotted by fitting to a four parameter equation by plotting the concentration of antibody on the X-axis against the mean % inhibition on the Y-axis, and then the IC50 value for each antibody was determined.

[0092] According to the above method, hz8C8, hz18A10 and their mutants were analyzed for their inhibitory activity on the transcriptional expression of cellular reporter genes stimulated by IL-11. The results (Table 8) show that the majority of the mutants maintain substantially the same inhibitory activity as that of the parent antibody.

[0093] [Table 8-1] [Table 8-2] [Table 8-3] [Table 8-4] [Table 8-5]

[0094] Example 8 Pharmacodynamic evaluation of anti-IL-11 antibodies in a ConA-induced acute liver injury model (1) Establishment of a model of ConA-induced acute liver injury A mouse model of acute liver injury was established using ConA induction, and the correlation between IL-11 and liver injury was analyzed.

[0095] Twelve Balb / c mice were randomly divided into two groups of six mice each, namely, the blank group and the model group. Mice in the model group were injected with ConA (Sigma) via the tail vein to induce acute liver injury and establish the model. 24 hours after the establishment of the model, blood was collected from the suborbital vein, serum was separated, and the activities of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase were detected according to the instructions of the Glutamic-Pyruvic Transaminase Activity Assay kit and the Glutamic-Oxaloacetic Transaminase Activity Assay kit, respectively. After blood collection, the mice were euthanized and the left hepatic lobe tissue was obtained. The tissues obtained were fixed in 10% formaldehyde, embedded in paraffin, sectioned, and stained with HE for histopathological examination and pathological lesion scoring, as well as for detection of IL-11 in the tissues by IHC using an anti-mouse IL-11 antibody (Invitrogen).

[0096] According to the above protocol, a mouse model of ConA-induced acute liver injury was established. The experimental results show that the activities of glutamic pyruvate transaminase and glutamic oxaloacetate transaminase in serum from the mouse model with ConA were significantly increased (P<0.01) (Table 9). Histopathological examination showed that the established liver injury model was mainly characterized by inflammatory cell infiltration and hepatocyte necrosis. The infiltrated inflammatory cells were mainly located in the portal vein area, then around the central vein and within the hepatic lobule, mainly neutrophilic granulocytes or lymphocytes, etc. The necrosis was coagulation necrosis, distributed as plaques, and in severe areas, the necrotic lesions were connected to each other and bridge-like (Table 10). These results demonstrate that ConA can cause acute liver injury in mice. The results of IHC staining detection showed that the expression of IL-11 was significantly increased in the mouse model of ConA-induced acute liver injury, suggesting that there is a correlation between acute liver injury and increased IL-11 expression (Table 10).

[0097] [Table 9]

[0098] [Table 10]

[0099] (2) Pharmacodynamic evaluation of anti-IL-11 antibodies in a ConA-induced acute liver injury model Seventy Balb / c mice were randomly divided into seven groups of 10 mice each: normal group, and six model groups G1, G2, G3, G4, G5, and G6. Except for the normal group mice, the other groups were injected with ConA at 10 mg / kg via the tail vein. All mice were fasted but had free access to water. The normal group mice did not receive antibodies, the G1 group mice received isotype-IgG and this group was used as the model group, the G2 group mice received antibodies 1 hour before challenge with ConA and this group was used as the prophylactic group, and all other groups mice received antibodies via the tail vein 2 hours after challenge with ConA (0.2 ml per 20 g body weight, Table 11). After administration, all animals were fasted but had free access to water. 24 hours after the last administration, the mice were weighed and blood samples were taken from the orbit. Serum was separated, and the activities of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase were detected according to the instructions of the Glutamic-Pyruvic Transaminase Activity Assay kit and the Glutamic-Oxaloacetic Transaminase Activity Assay kit, respectively. Left hepatic lobe tissue was obtained, and the tissue was fixed in 10% formaldehyde, embedded in paraffin, sectioned, and stained with HE for histopathological examination and pathological lesion scoring. All data were processed, and the rank sum test was performed for the data of pathological lesion scoring, and the t-test was performed for the other data, and the results were statistically analyzed.

[0100] According to the above protocol, the preventive effect of anti-IL-11 antibody on ConA-induced acute liver injury in a mouse model of ConA-induced acute liver injury was evaluated. The results are as follows:

[0101] As can be seen from Table 11, the activity of glutamic pyruvate transaminase, glutamic oxaloacetate transaminase and tumor necrosis factor-α in serum from mice model using ConA was significantly increased (P<0.01), thereby indicating that ConA can cause acute liver injury in mice.Compared with the model group, the administration of G2, G4, G5 and G6 groups significantly reduced the levels of glutamic pyruvate transaminase, glutamic oxaloacetate transaminase and tumor necrosis factor-α in serum from mice with acute experimental lung injury, showing obvious statistical differences (P<0.05 or P<0.01).In G3 group, administration reduced the levels of glutamic pyruvate transaminase, glutamic oxaloacetate transaminase and tumor necrosis factor-α in mice with acute experimental lung injury.

[0102] Histopathological examination showed that the established liver injury model was mainly characterized by inflammatory cell infiltration and hepatocyte necrosis (Table 12). The inflammatory cells were mainly located in the portal vein area, then around the central vein and in the hepatic lobule, mainly neutrophilic granulocytes or lymphocytes, etc. The necrosis was coagulation necrosis, distributed as plaques, and in severe areas, the necrotic lesions were connected to each other and bridge-like. After administration of anti-IL-11 antibody, the degree of inflammation and necrosis of liver tissue was obviously reduced, and the effect of anti-IL-11 antibody was in the order from high to low: group G5, group G4, group G2, group G6, and group G3.

[0103] The above results indicate that the anti-IL-11 antibodies hz8C8m7 (variable region is hz8C8-VHm1+hz8C8-VLm7) and hz18A10m19 (variable region is hz18A10-VHm19+hz18A10-VLm19) have prophylactic or preventive effects against ConA-induced acute liver injury in mice.

[0104] [Table 11]

[0105] [Table 12]

[0106] Example 9 Pharmacodynamic evaluation of anti-IL-11 antibodies in a BLM-induced pulmonary fibrosis model The pharmacodynamic activity of anti-IL-11 antibodies was evaluated in a BLM-induced pulmonary fibrosis model. Mice were randomly divided into six groups. The blank control group consisted of five mice and was administered saline via the trachea. The other five groups consisted of 10 mice each and were administered bleomycin (2 U / kg) via the trachea to establish the pulmonary fibrosis model. The five groups administered bleomycin were as follows:

[0107] Bleomycin model group (BLM): Normal saline was administered; Positive drug nintedanib group (nintedanib): nintedanib was administered at 100 mg / kg; 3C6-hFc group (hz3C6): 3C6-hFc (variable regions are 3C6-VH and 3C6-VL, and constant regions are as shown in SEQ ID NO:13 and SEQ ID NO:14) was administered at 20 mg / kg; hz8C8m7 group: hz8C8m7 (variable regions are hz8C8-VHm1 and hz8C8-VLm7, constant regions are as shown in SEQ ID NO:13 and SEQ ID NO:14) was administered at 20 mg / kg; hz18A10m19 group: hz18A10m19 (variable regions are hz18A10-VHm19 and hz18A10-VLm19, and constant regions are as shown in SEQ ID NO: 13 and SEQ ID NO: 14) was administered at 20 mg / kg.

[0108] Starting 2 days after the establishment of the model, antibody was intraperitoneally injected 8 times, once every 2 days.The weight of mice was continuously detected during the administration process.18 days after the establishment of the model, lung tissue was sampled to determine the lung function of mice, detect pathological indicators including H&E and Masson staining of lung tissue sections, and analyze the area of ​​pulmonary fibrosis.

[0109] The experimental results showed that no changes in fibrosis-related indicators and lung function impairment were observed in the blank control group administered with saline (Figure 4). In the bleomycin model group, obvious pulmonary fibrosis was observed, hydroxyproline (HYP) in the lung tissue was obviously increased, and lung function was severely damaged. The treatment groups administered with 20 mg / kg of antibodies 3C6-hFc, hz8C8m7, and hz18A10m19 showed different degrees of preventive effects, which were reflected in the reduction of fibrosis-related indicators and the improvement of lung function.

[0110] Example 10 Pharmacodynamic evaluation of anti-IL-11 antibodies in mouse tumor models Six-week-old female C57BL / 6 mice were inoculated with 3 × 10 mouse MC38 colon cancer cells. 6 The tumor was approximately 70 mm 3 When the mice grew to 100 mm, they were randomly divided into groups of 6 mice per group. The grouping and the dose and frequency of administration for each group are shown in Table 13. Each group was intravenously injected twice a week for three times. At the same time, the tumor volume and body weight of each mouse were measured. If any mouse showed a weight loss of more than 15% or the tumor volume exceeded 3000 mm, the mouse was eliminated. 3 If any animal was found to have a tumor volume greater than 2000 mm or if the mean tumor volume for the entire group of animals was greater than 2000 mm 3 If the serum concentration exceeded this limit, the experiment was stopped and the mouse / group of mice was euthanized.

[0111] [Table 13]

[0112] WBP336C-VH (SEQ ID NO: 47) QVQLVQSGAEVKKPGSSVKVSCKASGFTFTTYYISWVRQAPGQGLEYLGYINMGSGGTNYNEKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCAIIGYFDYWGQGTMVTVSS

[0113] WBP336C-VL (SEQ ID NO: 48) DVVMTQSPLSLPVTLGQPASISCRSSQSLLDSDGGTYLYWFQQRPGQSPRRLIYLVSTLGSGVPDRFSGSGSGTDFTLKISRVEAEEDVGVYYCMQLTHWPYTFGQGTKLEIK

[0114] As can be seen from Figure 5, in the MC38 tumor subcutaneous xenograft C57BL / 6 mouse model, the combination of hz8C8m7 and anti-mPD1 antibody significantly inhibited tumor growth compared with the control group of mice treated with isotype antibody NC-mIgG1, and the difference was statistically significant. The results suggest that hz8C8m7 can enhance the therapeutic effect of anti-PD-1 antibody, thus demonstrating the synergistic anti-tumor effect of hz8C8m7 and therapeutic antibodies against the PD-1 / PD-L1 pathway.

[0115] The above description of the embodiments of the present disclosure is not intended to limit the present disclosure, and those skilled in the art may make various changes and modifications to the present disclosure without departing from the spirit of the present disclosure, which should be included in the scope of the appended claims.

Claims

1. An antibody or fragment thereof comprising a heavy chain variable region (VH) and a light chain variable region (VL) comprising a combination of heavy chain and light chain CDRs (H-CDR1, H-CDR2, and H-CDR3, and L-CDR1, L-CDR2, and L-CDR3) selected from the group consisting of: （１） (1-13) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 98, and 99, respectively; (1-1) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 95, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 97, 98, and 99, respectively; (1-2) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 100, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 97, 98, and 99, respectively; (1-3) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 97, 98, and 99, respectively; (1-4) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 102, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 97, 98, and 99, respectively; (1-5) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 103, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 97, 98, and 99, respectively; (1-6) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 104, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 97, 98, and 99, respectively; (1-7) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 115, 98, and 99, respectively; (1-8) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 116, 98, and 99, respectively; (1-9) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 117, 98, and 99, respectively; (1-10) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 118, 98, and 99, respectively; (1-11) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 119, 98, and 99, respectively; (1-12) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 120, 98, and 99, respectively; (1-14) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 122, 98, and 99, respectively; (1-15) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 123, 98, and 99, respectively; (1-16) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 105, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 98, and 99, respectively; (1-17) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 106, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 98, and 99, respectively; (1-18) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 107, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 98, and 99, respectively; (1-19) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 108, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 98, and 99, respectively; (1-20) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 98, and 99, respectively; (1-21) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 124, and 99, respectively; (1-22) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 125, and 99, respectively; (1-23) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 126, and 99, respectively; (1-24) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 127, and 99, respectively; (1-25) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 124, and 99, respectively; (1-26) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 125, and 99, respectively; (1-27) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 126, and 99, respectively; (1-28) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 94, 101, and 109, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 121, 127, and 99, respectively; (1-29) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 110, and 96, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 125, and 99, respectively; (1-30) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 111, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 125, and 99, respectively; (1-31) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 112, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 125, and 99, respectively; (1-32) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 94, SEQ ID NO: 101, and SEQ ID NO: 113, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NO: 121, SEQ ID NO: 125, and SEQ ID NO: 99, respectively; and (1-33) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 94, 101, and 114, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 121, 125, and 99, respectively; Or, （２） (2-1) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 92, and 93, respectively; (2-2) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 146, 92, and 93, respectively; (2-3) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 147, 92, and 93, respectively; (2-4) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 148, 92, and 93, respectively; (2-5) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 149, 92, and 93, respectively; (2-6) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 150, 92, and 93, respectively; (2-7) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 151, 92, and 93, respectively; (2-8) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 153, 92, and 93, respectively; (2-9) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 154, 92, and 93, respectively; (2-10) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 155, 92, and 93, respectively; (2-11) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 156, and 93, respectively; (2-12) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 157, and 93, respectively; (2-13) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 158, and 93, respectively; (2-14) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 92, and 93, respectively; (2-15) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 131, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 92, and 93, respectively; (2-16) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 152, 92, and 93, respectively; (2-17) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 159, and 93, respectively; (2-18) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 160, and 93, respectively; (2-19) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 154, 92, and 93, respectively; (2-20) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 130, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 156, and 93, respectively; (2-21) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 131, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 154, 92, and 93, respectively; (2-22) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 131, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 156, and 93, respectively; (2-23) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in the order of SEQ ID NOs: 88, 89, and 134, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in the order of SEQ ID NOs: 154, 92, and 93; (2-24) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 91, 161, and 93, respectively; (2-25) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 156, and 93, respectively; (2-26) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 132, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 154, 92, and 93, respectively; (2-27) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 133, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 154, 92, and 93, respectively; (2-28) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 135, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 154, 92, and 93, respectively; (2-29) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 88, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 160, and 93, respectively; (2-30) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 133, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 160, and 93, respectively; (2-31) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 136, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-32) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 137, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-33) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 138, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-34) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 132, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-35) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 135, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-36) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 139, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-37) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 140, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-38) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 141, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-39) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 142, 89, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 162, 92, and 93, respectively; (2-40) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 135, 143, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-41) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 135, 144, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-42) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 139, 144, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; (2-43) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 139, 143, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences shown in SEQ ID NOs: 162, 92, and 93, respectively; and (2-44) H-CDR1, H-CDR2, and H-CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 139, 145, and 90, respectively, and L-CDR1, L-CDR2, and L-CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 162, 92, and 93, respectively.

2. The antibody or fragment thereof is an anti-interleukin-11 antibody or fragment thereof, and the IL-11 is preferably human IL-11; Preferably, the anti-IL-11 antibody or fragment thereof comprises at least a heavy chain variable region and a light chain variable region, each of which comprises a combination of CDRs as set forth in claim 1 and interspersed framework regions (FRs), and these regions are arranged as follows: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. The antibody or fragment thereof described in claim 1.

3. the heavy chain variable region and the light chain variable region are: （１） (1-13) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-1) an amino acid sequence shown in SEQ ID NO: 7 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 8 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-2) an amino acid sequence shown in SEQ ID NO: 11 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-3) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-4) an amino acid sequence shown in SEQ ID NO: 16 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-5) an amino acid sequence shown in SEQ ID NO: 17 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-6) an amino acid sequence shown in SEQ ID NO: 18 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 12 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-7) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 34 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-8) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 35 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-9) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 36 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-10) an amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 37 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-11) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 38 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-12) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 39 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-14) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 41 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-15) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 42 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-16) an amino acid sequence shown in SEQ ID NO: 19 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-17) an amino acid sequence shown in SEQ ID NO: 20 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-18) the amino acid sequence shown in SEQ ID NO: 21 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-19) the amino acid sequence shown in SEQ ID NO: 22 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-20) the amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-21) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 43 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-22) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-23) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 45 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-24) the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 46 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-25) the amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 43 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-26) the amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-27) the amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 45 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-28) the amino acid sequence shown in SEQ ID NO: 23 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 46 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-29) the amino acid sequence shown in SEQ ID NO: 24 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-30) the amino acid sequence shown in SEQ ID NO: 25 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-31) the amino acid sequence shown in SEQ ID NO: 26 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-32) the amino acid sequence shown in SEQ ID NO: 27 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-33) the amino acid sequence shown in SEQ ID NO: 28 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-34) the amino acid sequence shown in SEQ ID NO: 29 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-35) the amino acid sequence shown in SEQ ID NO: 30 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-36) the amino acid sequence shown in SEQ ID NO: 31 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; (1-37) an amino acid sequence set forth in SEQ ID NO: 32 or an amino acid sequence having at least 75% identity to that amino acid sequence, and an amino acid sequence set forth in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to that amino acid sequence; and (1-38) the amino acid sequence set forth in SEQ ID NO: 33 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence set forth in SEQ ID NO: 44 or an amino acid sequence having at least 75% identity to said amino acid sequence; Or, （２） (2-1) an amino acid sequence shown in SEQ ID NO: 5 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 6 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-2) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 10 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-3) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 69 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-4) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 70 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-5) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 71 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-6) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 72 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-7) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 73 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-8) an amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and an amino acid sequence shown in SEQ ID NO: 74 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-9) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to that amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 76 or an amino acid sequence having at least 75% identity to that amino acid sequence; (2-10) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-11) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 78 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-12) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 79 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-13) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 80 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-14) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 81 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-15) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 10 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-16) the amino acid sequence shown in SEQ ID NO: 50 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 10 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-17) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity to that amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 75 or an amino acid sequence having at least 75% identity to that amino acid sequence; (2-18) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 82 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-19) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 83 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-20) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-21) the amino acid sequence shown in SEQ ID NO: 49 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 79 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-22) the amino acid sequence shown in SEQ ID NO: 50 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-23) the amino acid sequence shown in SEQ ID NO: 50 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 79 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-24) the amino acid sequence shown in SEQ ID NO: 53 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-25) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 84 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-26) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 85 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-27) the amino acid sequence shown in SEQ ID NO: 51 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-28) the amino acid sequence shown in SEQ ID NO: 52 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-29) the amino acid sequence shown in SEQ ID NO: 54 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 77 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-30) the amino acid sequence shown in SEQ ID NO: 9 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 86 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-31) the amino acid sequence shown in SEQ ID NO: 52 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 86 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-32) the amino acid sequence shown in SEQ ID NO: 55 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-33) the amino acid sequence shown in SEQ ID NO: 56 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-34) the amino acid sequence shown in SEQ ID NO: 57 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-35) the amino acid sequence shown in SEQ ID NO: 51 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-36) the amino acid sequence shown in SEQ ID NO: 54 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-37) the amino acid sequence shown in SEQ ID NO: 58 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-38) the amino acid sequence shown in SEQ ID NO: 59 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-39) the amino acid sequence shown in SEQ ID NO: 60 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-40) the amino acid sequence shown in SEQ ID NO: 61 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-41) the amino acid sequence shown in SEQ ID NO: 62 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-42) the amino acid sequence shown in SEQ ID NO: 63 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-43) the amino acid sequence shown in SEQ ID NO: 64 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-44) the amino acid sequence shown in SEQ ID NO: 65 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-45) the amino acid sequence shown in SEQ ID NO: 66 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; (2-46) an amino acid sequence set forth in SEQ ID NO: 67 or an amino acid sequence having at least 75% identity to that amino acid sequence, and an amino acid sequence set forth in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to that amino acid sequence; and (2-47) the amino acid sequence shown in SEQ ID NO: 68 or an amino acid sequence having at least 75% identity to said amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 87 or an amino acid sequence having at least 75% identity to said amino acid sequence; 3. The antibody or fragment thereof according to claim 1 or 2, characterized in that it comprises a combination of amino acid sequences selected from the group consisting of:

4. An antibody or fragment thereof described in claim 1 or 2, characterized in that the heavy chain variable region and the light chain variable region comprise the amino acid sequence shown in SEQ ID NO: 15 or an amino acid sequence having at least 90% identity to that amino acid sequence, and the amino acid sequence shown in SEQ ID NO: 40 or an amino acid sequence having at least 90% identity to that amino acid sequence, and the difference in identity exists in any framework region of the heavy chain variable region or the light chain variable region.

5. An antibody or fragment thereof described in claim 1 or 2, characterized in that the heavy chain variable region and the light chain variable region comprise the amino acid sequences shown in SEQ ID NO: 15 and SEQ ID NO:

40.

6. 3. An antibody or fragment thereof according to claim 1 or 2, characterized in that it is a mouse antibody, a rabbit antibody, a human antibody, a chimeric antibody or a fully or partially humanized antibody, or a derivatized antibody.

7. The antigen-binding fragment may be any form of antibody fragment, such as scFv, BsFv, dsFv, (dsFv) ２ , Fab, Fab', F(ab') ２ 3. The antibody or fragment thereof according to claim 1 or 2, characterized in that it is an Fv or Fv.

8. An antibody or fragment thereof described in claim 1 or 2, characterized in that the antibody is a monoclonal antibody.

9. The antibody or fragment thereof described in claim 8, wherein the antibody comprises a heavy chain constant region of IgG, IgA, IgM, IgD or IgE, and optionally the constant region is a human constant region.

10. The antibody or fragment thereof of claim 9, wherein the antibody comprises an IgG1, IgG2, IgG3 or IgG4 region, and optionally the IgG1, IgG2, IgG3 or IgG4 region is a human region.

11. A nucleic acid molecule comprising a nucleotide sequence encoding the heavy chain CDR, light chain CDR, heavy chain variable region, light chain variable region, heavy chain and / or light chain contained in the antibody or fragment thereof according to claim 1 or 2.

12. A vector comprising the nucleic acid molecule of claim 11.

13. A host cell comprising the nucleic acid molecule of claim 11.

14. A composition comprising the antibody or fragment thereof of claim 1 or 2, and optionally pharmaceutically acceptable auxiliary materials.

15. 3. Use of the antibody or fragment thereof according to claim 1 or 2 in the manufacture of a medicament for preventing, treating and / or ameliorating a disease or disorder associated with expression (including overexpression) of IL-11.

16. 16. The use according to claim 15, wherein the disease or disorder is an inflammatory disease or a tumor.

17. The use described in claim 16, characterized in that the disease or disorder is pulmonary fibrosis.

18. The use described in claim 16, characterized in that the disease or disorder is liver damage.

19. The use described in claim 16, characterized in that the disease or disorder is colon cancer.

20. A pharmaceutical composition for preventing, treating, and / or ameliorating a disease or disorder associated with expression of IL-11 in a subject in need thereof, comprising an antibody or fragment thereof described in claim 1 or 2.

21. 21. The pharmaceutical composition of claim 20, wherein the disease or disorder is an inflammatory disease or a tumor, optionally wherein the disease or disorder is liver injury, pulmonary fibrosis or colon cancer.

22. 21. The pharmaceutical composition of claim 20, wherein the subject is a mammal.

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