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KR-20260064755-A - Anti-ACVR2B Antibody and Uses thereof

KR20260064755AKR 20260064755 AKR20260064755 AKR 20260064755AKR-20260064755-A

Abstract

An anti-ACVR2B antibody or an antigen-binding fragment thereof, and a use thereof for inhibiting or antagonizing ACVR2B are provided. The antibody and the antigen-binding fragment may be used in a therapeutic method for treating ACVR2B or ACVR2B ligand-related diseases or disorders that are improved or aggravated by the inhibition of ACVR2B.

Inventors

  • 장, 루이펑
  • 양, 멍쉐
  • 루, 크리스 샹양
  • 구, 샹-주 저스틴
  • 후, 메이쥐안

Assignees

  • 레크나 테라퓨틱스 상하이 씨오., 엘티디.

Dates

Publication Date
20260507
Application Date
20240731
Priority Date
20230801

Claims (20)

  1. As an antibody that binds to ACVR2B or an antigen-binding fragment thereof, The affinity of the antibody or antigen-binding fragment for ACVR2B is greater than that of ACVR2A, and optionally, the antibody or antigen-binding fragment is (i) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 1, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 2; (ii) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 3, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 4; (iii) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 5, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 6; (iv) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 7, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 8; (v) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 9, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 10; (vi) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 11, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 12; (vii) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 13, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 14; (viii) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 15, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 16; (ix) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 17, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 18; (x) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 19, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 20; (xi) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 21, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 22; (xii) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 23, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 24; (xiii) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 25, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 26; (xiv) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 27, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 28; (xv) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 29, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 30; (xvi) HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 31, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 32; or (xvii) An antibody or its antigen-binding fragment that binds to ACVR2B, comprising HCDR1, HCDR2, and HCDR3 as presented in VH containing the amino acid sequence of SEQ No. 33, and LCDR1, LCDR2, and LCDR3 as presented in VL containing the amino acid sequence of SEQ No. 34.
  2. In paragraph 1, (i) HCDR1 comprises the amino acid sequence of SEQ ID NO. 35, HCDR2 comprises the amino acid sequence of SEQ ID NO. 36, HCDR3 comprises the amino acid sequence of SEQ ID NO. 37, LCDR1 comprises the amino acid sequence of SEQ ID NO. 38, LCDR2 comprises the amino acid sequence of SEQ ID NO. 39, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 40; (ii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 41, HCDR2 comprises the amino acid sequence of SEQ ID NO. 42, HCDR3 comprises the amino acid sequence of SEQ ID NO. 43, LCDR1 comprises the amino acid sequence of SEQ ID NO. 44, LCDR2 comprises the amino acid sequence of SEQ ID NO. 45, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 46; (iii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 47, HCDR2 comprises the amino acid sequence of SEQ ID NO. 48, HCDR3 comprises the amino acid sequence of SEQ ID NO. 49, LCDR1 comprises the amino acid sequence of SEQ ID NO. 50, LCDR2 comprises the amino acid sequence of SEQ ID NO. 51, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 52; (iv) HCDR1 comprises the amino acid sequence of SEQ ID NO. 53, HCDR2 comprises the amino acid sequence of SEQ ID NO. 54, HCDR3 comprises the amino acid sequence of SEQ ID NO. 55, LCDR1 comprises the amino acid sequence of SEQ ID NO. 56, LCDR2 comprises the amino acid sequence of SEQ ID NO. 57, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 58; (v) HCDR1 comprises the amino acid sequence of SEQ ID NO. 59, HCDR2 comprises the amino acid sequence of SEQ ID NO. 60, HCDR3 comprises the amino acid sequence of SEQ ID NO. 61, LCDR1 comprises the amino acid sequence of SEQ ID NO. 62, LCDR2 comprises the amino acid sequence of SEQ ID NO. 63, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 64; (vi) HCDR1 comprises the amino acid sequence of SEQ ID NO. 65, HCDR2 comprises the amino acid sequence of SEQ ID NO. 66, HCDR3 comprises the amino acid sequence of SEQ ID NO. 67, LCDR1 comprises the amino acid sequence of SEQ ID NO. 68, LCDR2 comprises the amino acid sequence of SEQ ID NO. 69, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 70; (vii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 71, HCDR2 comprises the amino acid sequence of SEQ ID NO. 72, HCDR3 comprises the amino acid sequence of SEQ ID NO. 73, LCDR1 comprises the amino acid sequence of SEQ ID NO. 74, LCDR2 comprises the amino acid sequence of SEQ ID NO. 75, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 76; (viii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 77, HCDR2 comprises the amino acid sequence of SEQ ID NO. 78, HCDR3 comprises the amino acid sequence of SEQ ID NO. 79, LCDR1 comprises the amino acid sequence of SEQ ID NO. 80, LCDR2 comprises the amino acid sequence of SEQ ID NO. 81, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 82; (ix) HCDR1 comprises the amino acid sequence of SEQ ID NO. 83, HCDR2 comprises the amino acid sequence of SEQ ID NO. 84, HCDR3 comprises the amino acid sequence of SEQ ID NO. 85, LCDR1 comprises the amino acid sequence of SEQ ID NO. 86, LCDR2 comprises the amino acid sequence of SEQ ID NO. 87, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 88; (x) HCDR1 comprises the amino acid sequence of SEQ ID NO. 89, HCDR2 comprises the amino acid sequence of SEQ ID NO. 90, HCDR3 comprises the amino acid sequence of SEQ ID NO. 91, LCDR1 comprises the amino acid sequence of SEQ ID NO. 92, LCDR2 comprises the amino acid sequence of SEQ ID NO. 93, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 94; (xi) HCDR1 comprises the amino acid sequence of SEQ ID NO. 95, HCDR2 comprises the amino acid sequence of SEQ ID NO. 96, HCDR3 comprises the amino acid sequence of SEQ ID NO. 97, LCDR1 comprises the amino acid sequence of SEQ ID NO. 98, LCDR2 comprises the amino acid sequence of SEQ ID NO. 99, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 100; (xii) HCDR1 comprises the amino acid sequence of SEQ NO. 101, HCDR2 comprises the amino acid sequence of SEQ NO. 102, HCDR3 comprises the amino acid sequence of SEQ NO. 103, LCDR1 comprises the amino acid sequence of SEQ NO. 104, LCDR2 comprises the amino acid sequence of SEQ NO. 105, and LCDR3 comprises the amino acid sequence of SEQ NO. 106; (xiii) HCDR1 comprises the amino acid sequence of SEQ NO. 107, HCDR2 comprises the amino acid sequence of SEQ NO. 108, HCDR3 comprises the amino acid sequence of SEQ NO. 109, LCDR1 comprises the amino acid sequence of SEQ NO. 110, LCDR2 comprises the amino acid sequence of SEQ NO. 111, and LCDR3 comprises the amino acid sequence of SEQ NO. 112; (xiv) HCDR1 comprises the amino acid sequence of SEQ NO. 113, HCDR2 comprises the amino acid sequence of SEQ NO. 114, HCDR3 comprises the amino acid sequence of SEQ NO. 115, LCDR1 comprises the amino acid sequence of SEQ NO. 116, LCDR2 comprises the amino acid sequence of SEQ NO. 117, and LCDR3 comprises the amino acid sequence of SEQ NO. 118; (xv) HCDR1 comprises the amino acid sequence of SEQ ID NO. 119, HCDR2 comprises the amino acid sequence of SEQ ID NO. 120, HCDR3 comprises the amino acid sequence of SEQ ID NO. 121, LCDR1 comprises the amino acid sequence of SEQ ID NO. 122, LCDR2 comprises the amino acid sequence of SEQ ID NO. 123, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 124; (xvi) HCDR1 comprises the amino acid sequence of SEQ NO. 125, HCDR2 comprises the amino acid sequence of SEQ NO. 126, HCDR3 comprises the amino acid sequence of SEQ NO. 127, LCDR1 comprises the amino acid sequence of SEQ NO. 128, LCDR2 comprises the amino acid sequence of SEQ NO. 129, and LCDR3 comprises the amino acid sequence of SEQ NO. 130; or (xvii) An antibody or antigen-binding fragment, wherein HCDR1 comprises the amino acid sequence of SEQ NO. 131, HCDR2 comprises the amino acid sequence of SEQ NO. 132, HCDR3 comprises the amino acid sequence of SEQ NO. 133, LCDR1 comprises the amino acid sequence of SEQ NO. 134, LCDR2 comprises the amino acid sequence of SEQ NO. 135, and LCDR3 comprises the amino acid sequence of SEQ NO. 136.
  3. In paragraph 1, (i) HCDR1 comprises the amino acid sequence of SEQ ID NO. 137, HCDR2 comprises the amino acid sequence of SEQ ID NO. 138, HCDR3 comprises the amino acid sequence of SEQ ID NO. 139, LCDR1 comprises the amino acid sequence of SEQ ID NO. 140, LCDR2 comprises the amino acid sequence of SEQ ID NO. 141, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 142; (ii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 143, HCDR2 comprises the amino acid sequence of SEQ ID NO. 144, HCDR3 comprises the amino acid sequence of SEQ ID NO. 145, LCDR1 comprises the amino acid sequence of SEQ ID NO. 146, LCDR2 comprises the amino acid sequence of SEQ ID NO. 147, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 148; (iii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 149, HCDR2 comprises the amino acid sequence of SEQ ID NO. 150, HCDR3 comprises the amino acid sequence of SEQ ID NO. 151, LCDR1 comprises the amino acid sequence of SEQ ID NO. 152, LCDR2 comprises the amino acid sequence of SEQ ID NO. 153, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 154; (iv) HCDR1 comprises the amino acid sequence of SEQ ID NO. 155, HCDR2 comprises the amino acid sequence of SEQ ID NO. 156, HCDR3 comprises the amino acid sequence of SEQ ID NO. 157, LCDR1 comprises the amino acid sequence of SEQ ID NO. 158, LCDR2 comprises the amino acid sequence of SEQ ID NO. 159, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 160; (v) HCDR1 comprises the amino acid sequence of SEQ ID NO. 161, HCDR2 comprises the amino acid sequence of SEQ ID NO. 162, HCDR3 comprises the amino acid sequence of SEQ ID NO. 163, LCDR1 comprises the amino acid sequence of SEQ ID NO. 164, LCDR2 comprises the amino acid sequence of SEQ ID NO. 165, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 166; (vi) HCDR1 comprises the amino acid sequence of SEQ ID NO. 167, HCDR2 comprises the amino acid sequence of SEQ ID NO. 168, HCDR3 comprises the amino acid sequence of SEQ ID NO. 169, LCDR1 comprises the amino acid sequence of SEQ ID NO. 170, LCDR2 comprises the amino acid sequence of SEQ ID NO. 171, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 172; (vii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 173, HCDR2 comprises the amino acid sequence of SEQ ID NO. 174, HCDR3 comprises the amino acid sequence of SEQ ID NO. 175, LCDR1 comprises the amino acid sequence of SEQ ID NO. 176, LCDR2 comprises the amino acid sequence of SEQ ID NO. 177, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 178; (viii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 179, HCDR2 comprises the amino acid sequence of SEQ ID NO. 180, HCDR3 comprises the amino acid sequence of SEQ ID NO. 181, LCDR1 comprises the amino acid sequence of SEQ ID NO. 182, LCDR2 comprises the amino acid sequence of SEQ ID NO. 183, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 184; (ix) HCDR1 comprises the amino acid sequence of SEQ ID NO. 185, HCDR2 comprises the amino acid sequence of SEQ ID NO. 186, HCDR3 comprises the amino acid sequence of SEQ ID NO. 187, LCDR1 comprises the amino acid sequence of SEQ ID NO. 188, LCDR2 comprises the amino acid sequence of SEQ ID NO. 189, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 190; (x) HCDR1 comprises the amino acid sequence of SEQ ID NO. 191, HCDR2 comprises the amino acid sequence of SEQ ID NO. 192, HCDR3 comprises the amino acid sequence of SEQ ID NO. 193, LCDR1 comprises the amino acid sequence of SEQ ID NO. 194, LCDR2 comprises the amino acid sequence of SEQ ID NO. 195, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 196; (xi) HCDR1 comprises the amino acid sequence of SEQ ID NO. 197, HCDR2 comprises the amino acid sequence of SEQ ID NO. 198, HCDR3 comprises the amino acid sequence of SEQ ID NO. 199, LCDR1 comprises the amino acid sequence of SEQ ID NO. 200, LCDR2 comprises the amino acid sequence of SEQ ID NO. 201, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 202; (xii) HCDR1 comprises the amino acid sequence of SEQ ID NO. 203, HCDR2 comprises the amino acid sequence of SEQ ID NO. 204, HCDR3 comprises the amino acid sequence of SEQ ID NO. 205, LCDR1 comprises the amino acid sequence of SEQ ID NO. 206, LCDR2 comprises the amino acid sequence of SEQ ID NO. 207, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 208; (xiii) HCDR1 comprises the amino acid sequence of SEQ NO. 209, HCDR2 comprises the amino acid sequence of SEQ NO. 210, HCDR3 comprises the amino acid sequence of SEQ NO. 211, LCDR1 comprises the amino acid sequence of SEQ NO. 212, LCDR2 comprises the amino acid sequence of SEQ NO. 213, and LCDR3 comprises the amino acid sequence of SEQ NO. 214; (xiv) HCDR1 comprises the amino acid sequence of SEQ NO. 215, HCDR2 comprises the amino acid sequence of SEQ NO. 216, HCDR3 comprises the amino acid sequence of SEQ NO. 217, LCDR1 comprises the amino acid sequence of SEQ NO. 218, LCDR2 comprises the amino acid sequence of SEQ NO. 219, and LCDR3 comprises the amino acid sequence of SEQ NO. 220; (xv) HCDR1 comprises the amino acid sequence of SEQ ID NO. 221, HCDR2 comprises the amino acid sequence of SEQ ID NO. 222, HCDR3 comprises the amino acid sequence of SEQ ID NO. 223, LCDR1 comprises the amino acid sequence of SEQ ID NO. 224, LCDR2 comprises the amino acid sequence of SEQ ID NO. 225, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 226; (xvi) HCDR1 comprises the amino acid sequence of SEQ ID NO. 227, HCDR2 comprises the amino acid sequence of SEQ ID NO. 228, HCDR3 comprises the amino acid sequence of SEQ ID NO. 229, LCDR1 comprises the amino acid sequence of SEQ ID NO. 230, LCDR2 comprises the amino acid sequence of SEQ ID NO. 231, and LCDR3 comprises the amino acid sequence of SEQ ID NO. 232; (xvii) An antibody or antigen-binding fragment, wherein HCDR1 comprises the amino acid sequence of SEQ NO. 233, HCDR2 comprises the amino acid sequence of SEQ NO. 234, HCDR3 comprises the amino acid sequence of SEQ NO. 235, LCDR1 comprises the amino acid sequence of SEQ NO. 236, LCDR2 comprises the amino acid sequence of SEQ NO. 237, and LCDR3 comprises the amino acid sequence of SEQ NO. 238.
  4. In any one of paragraphs 1 to 3, the antibody or antigen-binding fragment is (i) VH comprising the amino acid sequence of SEQ ID NO. 1, and VL comprising the amino acid sequence of SEQ ID NO. 2; (ii) VH comprising the amino acid sequence of SEQ ID NO. 3, and VL comprising the amino acid sequence of SEQ ID NO. 4; (iii) VH comprising the amino acid sequence of SEQ ID NO. 5, and VL comprising the amino acid sequence of SEQ ID NO. 6; (iv) VH containing the amino acid sequence of SEQ ID NO. 7, and VL containing the amino acid sequence of SEQ ID NO. 8; (v) VH containing the amino acid sequence of SEQ ID NO. 9, and VL containing the amino acid sequence of SEQ ID NO. 10; (vi) VH comprising the amino acid sequence of SEQ ID NO. 11, and VL comprising the amino acid sequence of SEQ ID NO. 12; (vii) VH comprising the amino acid sequence of SEQ ID NO. 13, and VL comprising the amino acid sequence of SEQ ID NO. 14; (viii) VH comprising the amino acid sequence of SEQ ID NO. 15, and VL comprising the amino acid sequence of SEQ ID NO. 16; (ix) VH comprising the amino acid sequence of SEQ ID NO. 17, and VL comprising the amino acid sequence of SEQ ID NO. 18; (x) VH comprising the amino acid sequence of SEQ ID NO. 19, and VL comprising the amino acid sequence of SEQ ID NO. 20; (xi) VH containing the amino acid sequence of SEQ ID NO. 21, and VL containing the amino acid sequence of SEQ ID NO. 22; (xii) VH containing the amino acid sequence of SEQ ID NO. 23, and VL containing the amino acid sequence of SEQ ID NO. 24; (xiii) VH containing the amino acid sequence of SEQ ID NO. 25, and VL containing the amino acid sequence of SEQ ID NO. 26; (xiv) VH containing the amino acid sequence of SEQ ID NO. 27, and VL containing the amino acid sequence of SEQ ID NO. 28; (xv) VH containing the amino acid sequence of SEQ ID NO. 29, and VL containing the amino acid sequence of SEQ ID NO. 30; (xvi) VH comprising the amino acid sequence of SEQ ID NO. 31, and VL comprising the amino acid sequence of SEQ ID NO. 32; or (xvii) An antibody or antigen-binding fragment comprising VH having the amino acid sequence of SEQ No. 33, and VL having the amino acid sequence of SEQ No. 34.
  5. An antibody or antigen-binding fragment according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment is IgG.
  6. In any one of claims 1 to 5, the antibody or antigen-binding fragment is a human antibody.
  7. In any one of paragraphs 1 through 6, The antibody or antigen-binding fragment comprises one or more mutations within the Fc region to reduce or eliminate antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC) effects.
  8. In any one of claims 1 to 7, the antibody or antigen-binding fragment is (1) One or two mutations of L239A and L240A; or (2) An antibody or antigen-binding fragment containing one or two mutations of L234A and L235A.
  9. In any one of claims 1 to 8, the antibody or its antigen-binding fragment is an antibody or antigen-binding fragment that is genetically fused or chemically conjugated to an agent.
  10. A nucleic acid molecule encoding an antibody or antigen-binding fragment of any one of claims 1 to 9.
  11. A vector containing the nucleic acid molecule of claim 10.
  12. Host cells transformed with the vector of claim 11.
  13. A composition comprising a therapeutically effective amount of an antibody or antigen-binding fragment of any one of claims 1 to 9, a nucleic acid molecule of claim 10, or a vector of claim 11, and a pharmaceutically acceptable excipient.
  14. As a method of treating a disease or disorder in a subject, A method comprising the step of administering the composition of claim 13 to the subject.
  15. In paragraph 14, the above disease or disorder is related to ACVR2B, method.
  16. In paragraph 14, the above disease or disorder is related to the ACVR2B ligand, method.
  17. In paragraph 14, the above disease or disorder is related to Activin A, Activin B, Activin AB, GDF8, or GDF11.
  18. In any one of paragraphs 14 to 17, the disease or disability is a musculoskeletal disease or a disability, method.
  19. In paragraph 18, the above musculoskeletal disease or disorder is selected from the group consisting of muscular atrophy, spinal muscular atrophy, and cancer cachexia.
  20. A method according to any one of claims 14 to 17, wherein the disease or disorder is an age-related disease selected from the group consisting of sarcopenia, cutaneous atrophy, muscle wasting, cerebral atrophy, atherosclerosis, arteriosclerosis, emphysema, osteoporosis, osteoarthritis, immunodeficiency, hypertension, dementia, Huntington's disease, Alzheimer's disease, cataract, age-related macular degeneration, prostate cancer, stroke, reduced life expectancy, senility, memory loss, wrinkles, impaired renal function, and age-related hearing loss.

Description

Anti-ACVR2B Antibody and Uses thereof Cross-reference of related applications This application claims priority to international patent application PCT/CN2023/110569 filed on August 1, 2023, the disclosure of which is incorporated herein by reference in its entirety. Sequence list The present application includes a list of electronic sequences submitted in XML file format together with the present application, the entire contents of which are incorporated herein by reference in their entirety. The XML file of the sequence list submitted together with the present application has the filename "14668-031-228_SEQ_LISTING.xml", was created on July 29, 2024, and has a size of 242,113 bytes. Technology field A molecule capable of binding to ACVR2B, a pharmaceutical composition comprising the same, and uses thereof are provided in this specification. Activin receptor type 2B (ACVR2B) is a receptor that mediates the function of activin among other biological activities. Activin is a dimeric growth and differentiation factor belonging to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins, playing a crucial role in numerous processes during embryonic development, organogenesis, and adult homeostasis. Activin signals via a dimeric complex of receptor serine kinases containing type I and type II receptors; these receptors consist of a ligand-binding extracellular domain with a cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with serine/threonine specificity. The type I receptor is essential for signal transduction; the type II receptor is required for ligand binding and the phosphorylation of the type I receptor. It has been revealed that type II receptors, including ACVR2A and ACVR2B, are involved in various disease states, and although the inventors have developed an ACVR2A-specific antibody (see International Patent Application Publication WO 2023/030503), there is a need in the industry for an improved antibody therapy that targets ACVR2B. In one embodiment, an antibody or an antigen-binding fragment thereof that selectively binds to ACVR2B is provided herein. In some embodiments, the antibody provided herein binds to ACVR2B compared to ACVR2A. In some embodiments, the antibody or antigen-binding fragment provided herein binds to ACVR2B with a higher affinity than ACVR2A. The present invention provides a method using an ACVR2B-binding protein. In some embodiments, the anti-ACVR2B antibody or antigen-binding fragment provided herein may inhibit or block the binding of ACVR2B to ACVR2B ligands, such as Activin A, Activin B, Activin AB, GDF8, and GDF11. In some embodiments, the antibody or antigen-binding fragment provided herein does not inhibit or block the binding of ACVR2A to ACVR2A ligands, such as Activin A, Activin B, Activin AB, GDF8, and GDF11. In some embodiments, the antibody or antigen-binding fragment provided herein has a greater inhibitory or blocking effect on the binding of ACVR2B to the ACVR2B ligand than on the binding of ACVR2A to the ACVR2A ligand. In some embodiments, the antibody or antigen-binding fragment provided herein is (i) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 1, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 2; (ii) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 3, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 4; (iii) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 5, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 6; (iv) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 7, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 8; (v) HCDR1, HCDR2, and HCDR3 as presented in SEQ No. 9, and LCDR1, LCDR2, and LCDR3 as presented in SEQ No. 10; (vi) HCDR1, HCDR2, and HCDR3 as presented in SEQ No. 11, and LCDR1, LCDR2, and LCDR3 as presented in SEQ No. 12; (vii) HCDR1, HCDR2, and HCDR3 as presented in SEQ No. 13, and LCDR1, LCDR2, and LCDR3 as presented in SEQ No. 14; (viii) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 15, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 16; (ix) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 17, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 18; (x) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 19, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 20; (xi) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 21, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 22; (xii) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 23, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 24; (xiii) HCDR1, HCDR2, and HCDR3 as presented in sequence no. 25, and LCDR1, LCDR2, and LCDR3 as presented in sequence no. 26; (xiv) HCDR1, HCDR2, and HCDR3 as presented in sequence no. 27, and LCDR1, LCDR2, and LCDR3 as presented in sequence no. 28; (xv) HCDR1, HCDR2, and HCDR3 as presented in Sequence No. 29, and LCDR1, LCDR2, and LCDR3 as presented in Sequence No. 30; (xvi) HCDR1, HCDR2, and