# US 2025/0084183 A1 · Engineered compositions for bone-targeted therapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0084183 A1 - Document ID: US20250084183A1 - Status: Published application - Kind: A1 - Application number: 18/580,548 - Filed: 2022-07-20 - Published: 2025-03-13 - Earliest claimed: 2021-07-20 - Assignees: William Marsh Rice University - Applicants: William Marsh Rice University - Inventors: Han XIAO; Chenfei YU; Zeru TIAN - Web page: https://patentgrep.com/patent/US20250084183A1 ## CPC - C07K 16/32: against translation products of oncogenes - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) - A61K 47/68031: {the drug being an auristatin} - A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant} - A61K 47/6851: {the antibody targeting a determinant of a tumour cell} - A61K 47/6855: {the tumour determinant being from breast cancer cell} - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 19/10: for osteoporosis - A61P 35/04: specific for metastasis - C07K 14/5412: {IL-6} - C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere} - C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids} - A61K 2039/505: {comprising antibodies} - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - C07K 2318/10: Immunoglobulin or domain(s) thereof as scaffolds for inserted non-Ig peptide sequences, e.g. for vaccination purposes - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present disclosure provides methods for treating bone disease, such as bone cancers or bone metastasis of cancers, by administering an engineered bone-targeting compositions, such as an antibody or one or more polypeptides, such as an antibody or polypeptide engineered to comprise bone-homing peptide(s). Further provided herein are bone-targeting compositions, such as an antibody or one or more polypeptides, such as an antibody or polypeptide engineered to comprise bone-homing peptide(s). ## Claims ### Claim 1 A bone-targeting antibody engineered to comprise at least one bone-homing peptide which selectively binds to bone hydroxyapatite (HA). ### Claim 2 (depends on 1) The antibody of claim 1, wherein the at least one bone-homing peptide is inserted at a permissive internal site of the antibody. ### Claim 3 (depends on 1, 2) The antibody of claim 1 or 2, wherein the at least one bone-homing peptide is inserted at the light chain (LC), heavy chain (CH1), and/or C-terminus (CT) of the antibody. ### Claim 4 (depends on 1, 2, 3) The antibody of any of claims 1-3, wherein the antibody comprises two, three, or four bone-homing peptides. ### Claim 5 (depends on 1, 2, 3, 4) The antibody of any of claims 1-4, wherein the bone-homing peptide is L-Asp3, L-Asp4, L-Asp5, L-Asp6, L-Asp7, L-Asp8, L-Asp9, or L-Asp10. ### Claim 6 (depends on 1, 2, 3, 4) The antibody of any of claims 1-4, wherein the bone-homing peptide is L-Asp6. ### Claim 7 (depends on 1, 2, 3, 4, 5, 6) The antibody of any of claims 1-6, wherein the antibody is a monoclonal antibody, bispecific antibody, Fab′, a F(ab′)2, a F(ab′)3, a monovalent scFv, a bivalent scFv, a single domain antibody, or nanobody. ### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7) The antibody of any of claims 1-7, wherein the antibody is an immune checkpoint inhibitor. ### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8) The antibody of any of claims 1-8, wherein the antibody is an anti-HER2 antibody, anti-CD99 antibody, anti-IGF-IR antibody, anti-PD-L1, anti-PD-1, anti-CTLA4-antibody, anti-Siglec-2 antibody, anti-Siglec-3 antibody, anti-Siglec-5 antibody, anti-Siglec-6 antibody, anti-Siglec-7 antibody, anti-Siglec-8 antibody, anti-Siglec9 antibody, anti-Siglec-10 antibody, anti-Siglec-11 antibody, anti-Siglec-15 antibody, anti-RANKL antibody, anti-EGFR antibody, anti-VEGFR antibody, anti-CD20 antibody, anti-CD22 antibody, anti-CD52 antibody, anti-Trop-2 antibody, anti-CD30 antibody, anti-CD152 antibody, anti-IL-6R antibody, anti-GD2 antibody, or anti-TGFβ antibody. ### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8) The antibody of any of claims 1-8, wherein the antibody is an anti-CD99 antibody. ### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9) The antibody of any of claims 1-9, wherein the antibody is conjugated to a drug. ### Claim 12 (depends on 11) The antibody of claim 11, wherein the drug is monomethyl auristatin E (MMAE), ozogamicin, tiuxetan, vedotin, pasudotoxtdfx, vedotin, mafodotin, calicheamicin, maytansine, or deruxtecan. ### Claim 13 (depends on 11) The antibody of claim 11, wherein the drug is an anti-mitotic drug. ### Claim 14 (depends on 13) The antibody of claim 13, wherein the anti-mitotic drug is monomethyl auristatin E (MMAE). ### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9) The antibody of any of claims 1-9, wherein the antibody is an anti-HER2 antibody. ### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15) The antibody of any of claims 1-15, wherein the antibody is trastuzumab (Herceptin), pertuzumab (Perjeta), or atezolizumab. ### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The antibody of any of claims 1-16, wherein the antibody is trastuzumab. ### Claim 18 (depends on 17) The antibody of claim 17, wherein the trastuzumab is conjugated to MMAE. ### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17) The antibody of any of claims 1-17, wherein the bone-homing peptide is inserted at residue A153, A165, and/or G449 of trastuzumab. ### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19) The antibody of any of claims 1-19, wherein the antibody has an amino acid sequence having at least 90% sequence identity to Tras-LC (SEQ ID NOs: 3-4), Tras-CH1 (SEQ ID NOs: 5-6), Tras-CT (SEQ ID NOs: 7-8), Tras-LC/CH1 (SEQ ID NOs: 9-10), Tras-LC/CT (SEQ ID NOs: 11-12), Tras-CH1/CT (SEQ ID NOs: 13-14), or Tras-LC/CH1/CT (SEQ ID NOs: 15-16). ### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The antibody of any of claims 1-20, wherein the antibody has an amino acid sequence having at least 95% sequence identity to Tras-LC (SEQ ID NOs: 3-4), Tras-CH1 (SEQ ID NOs: 5-6), Tras-CT (SEQ ID NOs: 7-8), Tras-LC/CH1 (SEQ ID NOs: 9-10), Tras-LC/CT (SEQ ID NOs: 11-12), Tras-CH1/CT (SEQ ID NOs: 13-14), or Tras-LC/CH1/CT (SEQ ID NOs: 15-16). ### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21) The antibody of any of claims 1-21, wherein the antibody comprises Tras-LC (SEQ ID NOs: 3-4), Tras-CH1 (SEQ ID NOs: 5-6), Tras-CT (SEQ ID NOs: 7-8), Tras-LC/CH1 (SEQ ID NOs: 9-10), Tras-LC/CT (SEQ ID NOs: 11-12), Tras-CH1/CT (SEQ ID NOs: 13-14), or Tras-LC/CH1/CT (SEQ ID NOs: 15-16). ### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22) The antibody of any of claims 1-22, wherein the bone-targeting antibody has increased binding affinity to HA as compared to an antibody that does not comprise the bone-homing peptide. ### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) The antibody of any of claims 1-23, wherein the bone-targeting antibody has two-fold to three-fold higher binding affinity to HA as compared to an antibody that does not comprise the bone-homing peptide. ### Claim 25 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) A method of treating or preventing bone disease in a subject comprising administering to the subject an effective amount of a bone-targeting antibody of any of claims 1-23. ### Claim 26 (depends on 25) The method of claim 25, wherein the subject has bone cancer or bone metastasis. ### Claim 27 (depends on 26) The method of claim 26, wherein the bone cancer is Ewing sarcoma, osteosarcoma, or chondrosarcoma. ### Claim 28 (depends on 26) The method of claim 26, wherein the bone metastasis is from breast cancer, myeloma, renal cancer, lung cancer, prostate cancer, thyroid cancer, or bladder cancer. ### Claim 29 (depends on 25, 26, 27, 28) The method of any of claims 25-28, wherein the breast cancer is triple-negative breast cancer. ### Claim 30 (depends on 28, 29) The method of any of claims 28-29, wherein the breast cancer is HER2-negative breast cancer. ### Claim 31 (depends on 28, 29, 30) The method of any of claims 28-30, wherein the breast cancer is HER2-positive breast cancer. ### Claim 32 (depends on 25, 26, 27, 28, 29, 30, 31, 32, 33, 34) The method of any of claims 25-34, wherein the bone-targeting antibody results in increased concentration of therapeutic antibody at the bone tumor niche, inhibits cancer development in the bone, and/or limits secondary metastases to other organs. ### Claim 33 (depends on 25, 26, 27, 28, 29, 30, 31, 32) The method of any of claims 25-32, wherein the bone-targeting antibody results in decreased micrometastasis-induced osteolyic lesions. ### Claim 34 (depends on 25, 26, 27, 28, 29, 30, 31, 32, 33) The method of any of claims 25-33, wherein the method comprises further administering an additional anti-cancer therapy. ### Claim 35 (depends on 34) The method of claim 34, wherein the additional anti-cancer therapy comprises surgery, chemotherapy, radiation therapy, hormonal therapy, immunotherapy or cytokine therapy. ### Claim 36 (depends on 34) The method of claim 34, wherein the additional anti-cancer therapy comprises immunotherapy or chemotherapy. ### Claim 37 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) Use of a bone-targeting antibody of any of claims 1-23 for the treatment or prevention of bone tumors in a subject with cancer. ### Claim 38 (depends on 37) The use of claim 37, wherein the subject has bone cancer or bone metastasis. ### Claim 39 (depends on 38) The use of claim 38, wherein the bone cancer is Ewing sarcoma, osteosarcoma, or chondrosarcoma. ### Claim 40 (depends on 38) The use of claim 38, wherein the bone metastasis is from breast cancer, myeloma, renal cancer, lung cancer, prostate cancer, thyroid cancer, or bladder cancer. ### Claim 41 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) A method for engineering a bone-targeting antibody of any of claims 1-23 comprising inserting at least one bone-homing peptide at a permissive internal site of said antibody. ### Claim 42 (depends on 41) The method of claim 41, wherein the antibody comprises two, three, or four bone-homing peptides. ### Claim 43 (depends on 41, 43) The method of claim 41 or 43, wherein the bone-homing peptide is L-Asp6. ### Claim 44 A bone-targeting composition comprising one or more polypeptides engineered to comprise at least one bone-homing peptide which selectively binds to bone hydroxyapatite (HA). ### Claim 45 (depends on 44) The antibody of claim 44, wherein the at least one bone-homing peptide is inserted at a permissive internal site of the polypeptide. ### Claim 46 (depends on 44, 45) The antibody of claim 44 or 45, wherein the at least one bone-homing peptide is inserted at the C-terminus or N-terminus of the polypeptide. ### Claim 47 (depends on 44, 45, 46) The antibody of any of claims 44-46, wherein the polypeptide comprises two, three, or four bone-homing peptides. ### Claim 48 (depends on 44, 45, 46, 47) The antibody of any of claims 44-47, wherein the bone-homing peptide is L-Asp3, L-Asp4, L-Asp5, L-Asp6, L-Asp7, L-Asp8, L-Asp9, or L-Asp10. ### Claim 49 (depends on 44, 45, 46, 47) The antibody of any of claims 44-47, wherein the bone-homing peptide is L-Asp6. ### Claim 50 (depends on 44, 45, 46, 47, 48, 49) The antibody of any of claims 44-49, wherein the one or more polypeptides comprise an adrenergic agonist, an anti-apoptosis factor, an apoptosis inhibitor, a cytokine receptor, a cytokine, a cytotoxin, an erythropoietic agent, a glutamic acid decarboxylase, a glycoprotein, a growth factor, a growth factor receptor, a hormone, a hormone receptor, an interferon, an interleukin, an interleukin receptor, a kinase, a kinase inhibitor, a nerve growth factor, a netrin, a neuroactive peptide, a neuroactive peptide receptor, a neurogenic factor, a neurogenic factor receptor, a neuropilin, a neurotrophic factor, a neurotrophin, a neurotrophin receptor, an N-methyl-D-aspartate antagonist, a plexin, a protease, a protease inhibitor, a protein decarboxylase, a protein kinase, a protein kinase inhibitor, a proteolytic protein, a proteolytic protein inhibitor, a semaphorin, a semaphorin receptor, a serotonin transport protein, a serotonin uptake inhibitor, a serotonin receptor, a serpin, a serpin receptor, or a tumor suppressor. ### Claim 51 (depends on 44, 45, 46, 47, 48, 49, 50) The antibody of any of claims 44-50, wherein the one or more polypeptides comprise a cytokine. ### Claim 52 (depends on 51) The antibody of claim 51, wherein the cytokine is IL-6. ### Claim 53 (depends on 44, 45, 46, 47, 48, 49, 50, 51, 52) The antibody of any of claims 44-52, wherein the one or more polypeptides are conjugated to a drug. ### Claim 54 (depends on 53) The antibody of claim 53, wherein the drug is monomethyl auristatin E (MMAE), ozogamicin, tiuxetan, vedotin, pasudotoxtdfx, vedotin, mafodotin, calicheamicin, maytansine, or deruxtecan. ### Claim 55 (depends on 53) The antibody of claim 53, wherein the drug is an anti-mitotic drug. ### Claim 56 (depends on 55) The antibody of claim 55, wherein the anti-mitotic drug is monomethyl auristatin E (MMAE). ### Claim 57 (depends on 22, 44) The antibody of any of claims 44-22, wherein the bone-targeting composition has increased binding affinity to HA as compared to a polypeptide that does not comprise the bone-homing peptide. ### Claim 58 (depends on 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57) The antibody of any of claims 44-57, wherein the bone-targeting composition has two-fold to three-fold higher binding affinity to HA as compared to a polypeptide that does not comprise the bone-homing peptide. ### Claim 59 (depends on 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57) A method of treating or preventing bone disease in a subject comprising administering to the subject an effective amount of a bone-targeting composition of any of claims 44-57. ### Claim 60 (depends on 59) The method of claim 59, wherein the subject has bone cancer or bone metastasis. ### Claim 61 (depends on 60) The method of claim 60, wherein the bone cancer is Ewing sarcoma, osteosarcoma, or chondrosarcoma. ### Claim 62 (depends on 60) The method of claim 60, wherein the bone metastasis is from breast cancer, myeloma, renal cancer, lung cancer, prostate cancer, thyroid cancer, or bladder cancer. ### Claim 63 (depends on 59, 60, 61, 62) The method of any of claims 59-62, wherein the breast cancer is triple-negative breast cancer. ### Claim 64 (depends on 62, 63) The method of any of claims 62-63, wherein the breast cancer is HER2-negative breast cancer. ### Claim 65 (depends on 62, 63, 64) The method of any of claims 62-64, wherein the breast cancer is HER2-positive breast cancer. ### Claim 66 (depends on 59, 60, 61, 62, 63, 64, 65, 66, 67, 68) The method of any of claims 59-68, wherein the bone-targeting composition results in increased concentration of therapeutic polypeptide at the bone tumor niche, inhibits cancer development in the bone, and/or limits secondary metastases to other organs. ### Claim 67 (depends on 59, 60, 61, 62, 63, 64, 65, 66) The method of any of claims 59-66, wherein the bone-targeting composition results in decreased micrometastasis-induced osteolyic lesions. ### Claim 68 (depends on 59, 60, 61, 62, 63, 64, 65, 66, 67) The method of any of claims 59-67, wherein the method comprises further administering an additional anti-cancer therapy. ### Claim 69 (depends on 68) The method of claim 68, wherein the additional anti-cancer therapy comprises surgery, chemotherapy, radiation therapy, hormonal therapy, immunotherapy or cytokine therapy. ### Claim 70 (depends on 68) The method of claim 68, wherein the additional anti-cancer therapy comprises immunotherapy or chemotherapy. ### Claim 71 (depends on 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57) Use of a bone-targeting composition of any of claims 44-57 for the treatment or prevention of bone tumors in a subject with cancer. ### Claim 72 (depends on 71) The use of claim 71, wherein the subject has bone cancer or bone metastasis. ### Claim 73 (depends on 72) The use of claim 72, wherein the bone cancer is Ewing sarcoma, osteosarcoma, or chondrosarcoma. ### Claim 74 (depends on 72) The use of claim 72, wherein the bone metastasis is from breast cancer, myeloma, renal cancer, lung cancer, prostate cancer, thyroid cancer, or bladder cancer. ### Claim 75 (depends on 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57) A method for engineering a bone-targeting composition of any of claims 44-57 comprising inserting at least one bone-homing peptide at a permissive internal site of the polypeptide. ### Claim 76 (depends on 75) The method of claim 75, wherein the polypeptide comprises two, three, or four bone-homing peptides. ### Claim 77 (depends on 75, 77) The method of claim 75 or 77, wherein the bone-homing peptide is L-Asp6. ### Claim at position 78 (depends on 25, 26, 27, 28, 29, 30, 31) 1 The method of any of claims 25-31, wherein the bone disease is wherein the bone disease is osteoporosis, osteomalacia, periodontitis, rheumatoid arthritis, metabolic bone disease, a parathyroid disorder, steroid-induced osteoporosis, chemotherapy-induced bone loss, pre-menopausal bone loss, fragility and recurrent fractures, renal osteodystrophy, bone infections, or Paget's disease. ### Claim at position 79 (depends on 60) 1 The method of claim 60, wherein the bone disease is osteoporosis, osteomalacia, periodontitis, rheumatoid arthritis, metabolic bone disease, a parathyroid disorder, steroid-induced osteoporosis, chemotherapy-induced bone loss, pre-menopausal bone loss, fragility and recurrent fractures, renal osteodystrophy, bone infections, or Paget's disease.