Targeting the TGF-β signaling pathway: an updated patent review (2021–present)

References

• Massagué J, Sheppard D. TGF-β signaling in health and disease. Cell. 2023 Sep 14;186(19):4007–4037. English. doi: 10.1016/j.cell.2023.07.036.
   PubMed Web of Science ®Google Scholar
• Morikawa M, Derynck R, Miyazono K. TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology. Cold Spring Harbor Perspect Biol. 2016 May 1;8(5):a021873. en. doi: 10.1101/cshperspect.a021873.
   PubMed Web of Science ®Google Scholar
• Derynck R, Budi EH. Specificity, versatility, and control of TGF-β family signaling. Sci Signaling. 2019 Feb 26;12(570):eaav5183. doi: 10.1126/scisignal.aav5183
   PubMed Web of Science ®Google Scholar
• Wrana JL. TGF-β receptors and signalling mechanisms. Mineral And Electrolyte Metabolism. 1998 Feb 23;24(2–3):120–130. doi: 10.1159/000057359
   PubMedGoogle Scholar
• Massagué J, Weis-Garcia F. Serine/Threonine kinase receptors: mediators of transforming growth factor beta family signals. Cancer Surveys. 1996 Jan 01;27:41–64. eng.
   PubMedGoogle Scholar
• Massagué J, Attisano L, Wrana JL. The TGF-β family and its composite receptors. Trends Cell Biol. 1994 May 01;4(5):172–178. English. doi: 10.1016/0962-8924(94)90202-X.
   PubMedGoogle Scholar
• Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFβ activation. J Cell Sci. 2003 Jan 15;116(2):217–224. doi: 10.1242/jcs.00229
   PubMed Web of Science ®Google Scholar
• Robertson IB, Horiguchi M, Zilberberg L, et al. Latent TGF-β-binding proteins. Matrix Biol. 2015;47:44–53. doi: 10.1016/j.matbio.2015.05.005.
   PubMed Web of Science ®Google Scholar
• Li X, Ding Z, Wu Z, et al. Targeting the TGF-β signaling pathway for fibrosis therapy: a patent review (2015–2020). Expert Opin Ther Patents. 2021 Aug 03;31(8):723–743. doi: 10.1080/13543776.2021.1896705
   PubMed Web of Science ®Google Scholar
• Sheppard D. Integrin-mediated activation of latent transforming growth factor β. Cancer Metast Rev. 2005 Sep 01;24(3):395–402. en. doi: 10.1007/s10555-005-5131-6.
   PubMed Web of Science ®Google Scholar
• Pang X, He X, Qiu Z, et al. Targeting integrin pathways: mechanisms and advances in therapy. Signal Transduct Target Ther. 2023 Jan 02;8(1):1. en. doi: 10.1038/s41392-022-01259-6.
   PubMed Web of Science ®Google Scholar
• Stockis J, Dedobbeleer O, Lucas S. Role of GARP in the activation of latent TGF-β1. Mol Biosyst. 2017 Sep 26;13(10):1925–1935. eng. doi: 10.1039/c7mb00251c.
   PubMedGoogle Scholar
• Peng D, Fu M, Wang M, et al. Targeting TGF-β signal transduction for fibrosis and cancer therapy. Mol cancer. 2022;21(1):104. en. doi: 10.1186/s12943-022-01569-x.
   PubMed Web of Science ®Google Scholar
• Malla RR, Vempati RK. Talin: a potential drug target for cancer therapy. Curr Drug Metab. 2020 Jan 01;21(1):25–32. doi: 10.2174/1389200221666200214114018
   PubMed Web of Science ®Google Scholar
• Craft CS, Broekelmann TJ, Mecham RP. Microfibril-associated glycoproteins MAGP-1 and MAGP-2 in disease. Matrix Biol. 2018 Oct 01;71-72:100–111. DOI:10.1016/j.matbio.2018.03.006.
   PubMed Web of Science ®Google Scholar
• Lin HY, Moustakas A. TGF-beta receptors: structure and function. Cell Mol Biol (Noisy-le-grand). 1994 May 01;40(3):337–349. eng
   PubMed Web of Science ®Google Scholar
• Derynck R, Zhang YE. Smad-dependent and smad-independent pathways in TGF-β family signalling. Nature. 2003;425(6958):577–584. doi: 10.1038/nature02006
   PubMed Web of Science ®Google Scholar
• Zhang YE. Non-smad pathways in TGF-β signaling. Cell Res. 2009;19(1):128–139. en. doi: 10.1038/cr.2008.328
   PubMed Web of Science ®Google Scholar
• Prud’homme GJ. Pathobiology of transforming growth factor β in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab Invest. 2007 Nov 01;87(11):1077–1091. doi: 10.1038/labinvest.3700669
   PubMed Web of Science ®Google Scholar
• Meulmeester E, ten Dijke P. The dynamic roles of TGF-β in cancer. J Pathol. 2011;223(2):206–219. en. doi: 10.1002/path.2785
   Web of Science ®Google Scholar
• Gorelik L, Flavell RA. Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity. 2000 Feb 01;12(2):171–181. English. doi: 10.1016/S1074-7613(00)80170-3.
   PubMed Web of Science ®Google Scholar
• Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-β signaling in fibrosis. Growth Factors. 2011 Oct 01;29(5):196–202. doi: 10.3109/08977194.2011.595714
   PubMed Web of Science ®Google Scholar
• Yingling JM, Blanchard KL, Sawyer JS. Development of TGF-β signalling inhibitors for cancer therapy. Nat Rev Drug Discov. 2004;3(12):1011–1022. en. doi: 10.1038/nrd1580
   PubMed Web of Science ®Google Scholar
• Akhurst RJ, Hata A. Targeting the TGFβ signalling pathway in disease. Nat Rev Drug Discov. 2012;11(10):790–811. doi: 10.1038/nrd3810
   PubMed Web of Science ®Google Scholar
• Hyytiäinen M, Penttinen C, Keski-Oja J. Latent TGF-β binding proteins: extracellular matrix association and roles in TGF-β activation. Crit Rev Clin Lab Sci. 2004 Jan 01;41(3):233–264. doi: 10.1080/10408360490460933
   PubMed Web of Science ®Google Scholar
• Hao W, Meiling C, Xiaohong S, et al. Development of small molecule inhibitors targeting TGF-β ligand and receptor: structures, mechanism, preclinical studies and clinical usage. Eur J Med Chem. 2020 Apr 01;191:112154. en-US. 10.1016/j.ejmech.2020.112154
   PubMed Web of Science ®Google Scholar
• Yousefi F, Shabaninejad Z, Vakili S, et al. TGF-β and WNT signaling pathways in cardiac fibrosis: non-coding RNAs come into focus. Cell Commun Signaling. 2020 Jun 09;18(1):87. doi: 10.1186/s12964-020-00555-4
   PubMed Web of Science ®Google Scholar
• Gulley JL, Schlom J, Barcellos-Hoff MH, et al. Dual inhibition of TGF-β and PD-L1: a novel approach to cancer treatment. Mol Oncol. 2022;16(11):2117–2134. en. doi: 10.1002/1878-0261.13146.
   PubMed Web of Science ®Google Scholar
• Ken-Ichi K, Haruka Y, Hayato S, et al., inventors 1, 4, 5, 6-Tetrahydropyrimidine-2-Amine derivative patent WO2021230325. 2021 Nov 18.
   Google Scholar
• Baker D, James HS, Claire HM, et al., inventorsANTI-αVβ8 integrin antibodies for use in treating kidney disease patent WO2021151889. 2021-Aug-5.
   Google Scholar
• Liang S, Liang B, Yu J-C, et al. Inventors anti-integrin antibody or antigen-binding fragment, and use thereof patent WO2022057862. 2022-Mar-24
   Google Scholar
• Li X, Pei T, PHAN S, et al. Arrowhead Pharmaceuticals, Inc., assignee. Integrin targeting ligands and uses thereof patent WO2022056286A1. 2022 Mar 17. inventors.
   Google Scholar
• McNally E, Heydemann A. Ceco E, Inventors; mitigating tissue damage and fibrosis via latent transforming growth factor beta binding protein (LTBP4) patent US2022089717; 2022 Mar 24.
   Google Scholar
• McNally E, Heydemann A, Ceco E. Inventors; Ikaika Therapeutics Inc, assignee. Mitigating tissue damage and fibrosis via latent transforming growth factor beta binding protein (ltbp4) patent US20230235044A1. 2023 Jun 27.
   Google Scholar
• Wawersik S, Schurpf T, Chapron C, et al. inventors TGFβ inhibitors and use thereoF patent WO2021142427. 2021-Aug-19
   Google Scholar
• Cheng G, Ge H, Cao Z, et al. inventors GARP/TGFβ1 antibody and use thereof patent WO2022206753. 2022 Oct 06.
   Google Scholar
• Zhang J, Pan Z, Yang X, et al., Inventors; Jiangxi Jemincare Group Co Ltd, Shanghai Jemincare Pharmaceuticals Co Ltd, assignee. GARP protein antibody and application thereof patent WO2022152285A1. 2022 Jun 21.
   Google Scholar
• WANG J-T, Tseng C-L, Jiang W-D, et al., Inventors; Shanghai Henlius Biotech, Inc., assignee. Anti-GARP/TGFβ antibodies and methods of use patent WO2022116877A1. 2022 Jun 09.
   Google Scholar
• Xu W, Fang X, Xu D, et al. Inventors; Betta Pharmaceuticals Co Ltd, assignee. Bispecific antibody and application thereof patent WO2023051656A1. 2023 Apr 06.
   Google Scholar
• Satoh K, Kobayashi Y, Fujimaki K, et al. Abstract 1847: anti-GARP antibody DS-1055a augments antitumor immunity by depleting highly suppressive GARP+ regulatory T cells. Cancer Res. 2021 Jun 01;81(13_Supplement):1847. doi: 10.1158/1538-7445.AM2021-1847
   Web of Science ®Google Scholar
• Woning SVD, Borgions F, Dreier T, et al., inventors; Universite Catholique de Louvain UCL, ArgenX BVBA, assignee. Garp-tgf-beta antibodies patent US20210324061A1. 2021 Oct 21.
   Google Scholar
• Lykke Sørensen G, Schlosser A, Holmskov U, inventors;MFAP4 and treatment of fibrosis patent WO2022218908. 2022-Oct-20.
   Google Scholar
• Hayashi M, Takeuchi T, Nomura Y, et al., inventors;Polypeptide having MMP2-inhibitory effect patent WO2021090959. 2021 May 14.
   Google Scholar
• Masakazu K, Koo XC, Hideki S. inventors;Use of cross-species anti-latent TGF-β1 antibodies and methods of use patent JP2023061346. 2023-May-1.
   Google Scholar
• Shimada H, Kanamori M, Koo XC, inventors;Cross-species anti-latent TGF-BETA 1 antibodies and methods of use patent WO2021039945. 2021-Mar-04.
   Google Scholar
• Shimada H, Kanamori M, Koo X, et al., inventors;Uses of cross-species anti-latent TGF-Beta 1 antibodies patent WO2022180764. 2022-Sep-01.
   Google Scholar
• Bai Y, Inventoranti-LAP monoclonal antibody, antigen binding fragment thereof and application thereof patent CN113402607A. 2021 Sep 17.
   Google Scholar
• Genentech I. A phase Ib, open-label, multicenter dose-expansion study evaluating the safety, pharmacokinetics, and activity of RO7496353 in combination with a checkpoint inhibitor with or without standard-of-care chemotherapy in patients with locally advanced or metastatic solid tumors. clinicaltrials.gov. 2024.
   Google Scholar
• Campbell ID, Humphries MJ. Integrin structure, activation, and interactions. Cold Spring Harbor Perspect Biol. 2011 Mar 1;3(3):a004994. en. doi: 10.1101/cshperspect.a004994.
   PubMed Web of Science ®Google Scholar
• Giancotti FG, Ruoslahti E. Integrin signaling. Science. 1999 Aug 13;285(5430):1028–1033. doi: 10.1126/science.285.5430.1028
   PubMed Web of Science ®Google Scholar
• Danhier F, Le Breton A, Préat V. RGD-based strategies To target alpha(v) beta(3) integrin in cancer therapy and diagnosis. Mol Pharmaceut. 2012 Nov 05;9(11):2961–2973. doi: 10.1021/mp3002733
   PubMed Web of Science ®Google Scholar
• Öklü R, Hesketh R. The latent transforming growth factor β binding protein (LTBP) family. Biochem J. 2000 Dec 08;352(3):601–610. doi: 10.1042/bj3520601
   PubMedGoogle Scholar
• Metelli A, Salem M, Wallace CH, et al. Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer. J Hematol Oncol. 2018 Feb 20;11(1):24. doi: 10.1186/s13045-018-0570-z
   PubMedGoogle Scholar
• Hubbell J, White M, inventors; The university of chicago, assignee. methods and compositions for treating fibrosis patent WO2022256824A1. 2022 Dec 08.
   Google Scholar
• Farhat YM, Al-Maliki AA, Easa A, et al. TGF-β1 suppresses plasmin and MMP activity in flexor tendon cells via PAI-1: Implications for scarless flexor tendon repair. J Cell Physiol. 2015;230(2):318–326. en. doi: 10.1002/jcp.24707.
   PubMed Web of Science ®Google Scholar
• de Streel G, Lucas S. Targeting immunosuppression by TGF-β1 for cancer immunotherapy. Biochem Pharmacol. 2021 Oct 01;192:114697. DOI:10.1016/j.bcp.2021.114697.
   PubMed Web of Science ®Google Scholar
• Mariën L, De Boeck G, Lucas S, et al., inventorsTGF-β ANTIBODIES patent WO2023170241. 2023 Sep 14.
   Google Scholar
• Gan L, Schurpf T, Coricor G, et al., inventors; Scholar Rock, Inc., assignee. Tgf-beta inhibitors and therapeutic use thereof patent WO2022256723A2. 2022 Dec 08.
   Google Scholar
• Liang W-C, Tyagi T, Wu J, et al., inventors; Isoform-selective anti-TGF-beta antibodies and methods of use patent WO2021188749. 2021-Sep-23.
   Google Scholar
• Zhang H, Wang Q, inventors; Beijing Xinsong Biotechnology Co ltd, assignee. Monoclonal antibody targeting TGF-beta 1 and combined application of monoclonal antibody and mesenchymal stem cell exosome patent CN112961240A. 2021 Jun 15.
   Google Scholar
• Liang W-C, Arron JR, Depianto D, et al., inventors; Genentech, Inc., assignee. Isoform-selective anti-tgf-beta antibodies and methods of use patent WO2021188749A1. 2021 Sep 23.
   Google Scholar
• Johnson D, Scott AA, Shultz MR, et al. inventors Bispecific antigen binding proteins targeting PD-L1 and TGF-N2 and methods of use patent WO2022006555. 2022 Jan 06.
   Google Scholar
• Vanasse KGJ, Sun H, Dostalek M, et al., inventors; Novartis Ag, assignee. Combination of anti tim-3 antibody mbg453 and anti tgf-beta antibody nis793, with or without decitabine or the anti pd-1 antibody spartalizumab, for treating myelofibrosis and myelodysplastic syndrome patent WO2021123902A1. 2021 Jun 24.
   Google Scholar
• Kim B-G, Malek E, Choi SH, et al. Novel therapies emerging in oncology to target the TGF-β pathway. J Hematol Oncol. 2021 Apr 06;14(1):55. en. doi: 10.1186/s13045-021-01053-x.
   PubMed Web of Science ®Google Scholar
• O’Connor M, Tremblay G, Denis J-F, et al., inventors transforming growth factor beta (TGFN2) binding agents and uses thereof patent WO2021248247. 2021 Dec 16.
   Google Scholar
• Romo A, Dewey RA. Consejo Nacional De Investigaciones Cientificas Y Tecnicas, Radbio USA, Inc., assignee. Method of treatment of fibrosis and wound healing patent WO2022076272A1. 2022 Apr 14. inventors.
   Google Scholar
• Lavrovsky Y, Chestukhin A, Repik A, et al., inventors; R-Pharm Overseas, Inc., assignee. TGF-β inhibitor composition and use thereof patent WO2023043473A1. 2023 Mar 23.
   Google Scholar
• Kumar R, Grinberg A, Sako DS, et al. Acceleron Pharma Inc, assignee. Tgf-beta receptor type ii variants and uses thereof patent US20210230252A1. 2021 Jun 29. inventors.
   Google Scholar
• Zhang C, Yao C, Zhang H, et al., inventors;Fusion protein of ETA antibody and TGF-N2 trap and pharmaceutical composition and application thereof patent WO2021008519. 2021-01-21.
   Google Scholar
• Qian X, Li H, Teng F, et al., inventors; Suzhou Transcenta Therapeutics Co., Ltd., assignee. Bi-functional molecules patent WO2022105817A1. 2022 May 27.
   Google Scholar
• Sun D, Wu Z, Sun J, et al., inventors; Elpiscience (Suzhou) Biopharma, Ltd., Elpiscience Biopharma, Ltd., assignee. Novel conjugate molecules targeting cd39 and tgfβeta patent WO2022111576A1. 2022 Jun 02.
   Google Scholar
• Cheng H, inventor; Shenzhen Maijiarui Biotechnology Co ltd, assignee. Bispecific antibody for specifically neutralizing helper T cell TGF-beta signal, pharmaceutical composition and application thereof patent CN112500491A. 2021 Jun 16.
   Google Scholar
• Tang N, Sui J, Liu X, et al., inventors; Pulmongene (Hong Kong) Co., Limited, assignee. Bi-functional fusion protein and uses thereof patent WO2023030511A1. 2023 Mar 09.
   Google Scholar
• Diaz CAP, inventor; Cura Therapeutics, Inc., assignee. Anti-pathogen interleukin-tgf-beta receptor fusion polypeptides patent WO2022178033A1. 2022 Aug 25.
   Google Scholar
• Wang Z, Zhang H, Zhu Z, et al., inventors; BJ Bioscience Inc assignee. Bifunctional molecule binding to human TGFbeta and PD-L1, and use thereof patent WO2022188865A1. 2022 Sep 15.
   Google Scholar
• Li X, Zhang X, Wang X, et al., inventors; Chia Tai Tianqing Pharmaceutical Group Co Ltd, assignee. Combined drug for treating tumors patent WO2023072043A1. 2023 May 04.
   Google Scholar
• Zhang X, Yang L, Wang X, et al., inventors; Chia Tai Tianqing Pharmaceutical Group Co Ltd, assignee. Combined medicine for treating tumour patent CN114984204A. 2022 Sep 02.
   Google Scholar
• Cheng Y, Yang K, Xiao S, et al., inventors; Chia Tai Tianqing Pharmaceutical Group Co Ltd, assignee. Pharmaceutical composition comprising fusion protein targeting PD-L1 and TGF-beta patent CN114984203A. 2022 Sep 02.
   Google Scholar
• Zhao W, Li Y, Lv H, et al., inventors; Chia Tai Tianqing Pharmaceutical Group Co Ltd, Nanjing Shunxin Pharmaceutical Co Ltd, assignee. Bifunctional protein for PD-1 and TGF-beta patent CN115322259A. 2022 Nov 11.
   Google Scholar
• Liu H, Liu P, He L, et al., inventors; Shanghai Junshi Biosciences Co Ltd, Suzhou Junmeng Biosciences Co Ltd, assignee. Bifunctional protein pharmaceutical composition targeting PD-1 and TGF beta and application thereof patent CN116803420A. 2023 Sep 26.
   Google Scholar
• Zhou Z, Zhang J, inventors; Chimagen Biosciences, Ltd, assignee. Heterodimeric antibodies and antigen-binding fragment thereof patent WO2022223016A1. 2022 Oct 27.
   Google Scholar
• Zhang J, Wang S, Jiao S, et al., inventors; Mabwell (Shanghai) Bioscience Co Ltd assignee. TGF-beta rii mutant and fusion protein thereof patent WO2022017487A1. 2022 Jan 27.
   Google Scholar
• Wei X, Zhu X, Pan X, et al., inventors; Huabo Biopharm Co Ltd,Shanghai Huaota Biopharmaceutical Co Ltd, assignee. Anti-PD-L1/TGF-beta bifunctional antibody and use thereof patent WO2022117003A1. 2022 Jun 09.
   Google Scholar
• Qu X, inventor; Qurebio Ltd, assignee. Trifunctional fusion protein containing tumor-associated antigen (TAA) antibody and application thereof patent WO2022116480A1. 2022 Jun 09.
   Google Scholar
• Qu X, inventor; Qurebio Ltd assignee. Anti-PD-L1 nanobody and trifunctional fusion protein patent WO2022105832A1. 2022 May 27.
   Google Scholar
• Zhang X, Li Q, Huang H, et al., inventors; Sunshine Guojian Pharmaceutical Shanghai Co Ltd, assignee. A bifunctional fusion protein targeting human CD73 and human TGFbeta, preparation method and use thereof patent CN116265489A. 2023 Jun 20.
   Google Scholar
• Geuijen CAW, Mayes P, Stewart SM, et al., inventors; Merus N.V., Incyte Corporation, assignee. Multispecific binding moieties comprising pd-1 and tgf-brii binding domains patent WO2023089083A1. 2023 May 25.
   Google Scholar
• Zhang Z, Jia Y, Li Z, inventors; Biotheus Inc, assignee. Fusion protein targeting CD73 protein patent CN116135885A. 2023 May 19.
   Google Scholar
• Jung BH, Lee JW, Park DW, et al., inventors; Theranotics Co Ltd assignee. Bispecific molecule specifically binding to B7-H3 and TGFbeta and uses thereof patent WO2023027561A1. 2023 Mar 02.
   Google Scholar
• Lo K-M, inventor; Merck Patent GmbH, assignee. Targeted TGFß Inhibition patent US20230056881A1. 2023 Feb 23.
   Google Scholar
• Wang Z, Zhang P, Li B, et al., inventors; Akeso Biopharma Inc assignee. Fusion protein containing anti-tigit antibody and TGF-beta, and pharmaceutical composition and use thereof patent WO2023020625A1. 2023 Feb 23.
   Google Scholar
• Huang H, Deng L, Zhu Z, et al., inventors; HanBio Therapeutics Inc assignee. TGF-beta/VEGF bi-functional antibody fusion protein patent WO2023020592A1. 2023 Feb 23.
   Google Scholar
• Shi J, Fang L, Yan Y, et al., inventors; Wuhan YZY Biopharma Co Ltd, assignee. Anti-TGFbeta antibody and preparation method and application thereof patent WO2023019505A1. 2023 Feb 23.
   Google Scholar
• Huang Y, Inventor, Zhejiang Doer Biologics Corp, assignee, assignee. Multi-domain fusion protein and use thereof patent WO2022174781A1. 2022 Aug 25.
   Google Scholar
• Huang Y, inventor; Zhejiang Doer Biologics Corp, assignee. Multi-domain fusion protein having anti-cancer activity patent WO2022174451A1. 2022 Aug 25.
   Google Scholar
• Fang L, Zhang J, Wang X, et al., inventors; Wuhan Youzhiyou Biopharmaceutical Co ltd, assignee. A modification of anti-PD-1 antibody, preparation and application thereof patent CN115707714A. 2023 Feb 21.
   Google Scholar
• Ling E, Lee W-C. TGF-Beta Type I Receptor (Alk5) Kinase Inhibitors in Oncology. Curr Pharm Biotechnol. 2011 Dev 01;12(12):2190–2202. doi: 10.2174/138920111798808257
   PubMed Web of Science ®Google Scholar
• Bullough DA, Foulkes JG, Beeley NRA, et al., inventors; Thirona Bio, Inc., assignee. Methods for treating a pulmonary disease with an alk-5 (tgf beta r1) inhibitor patent WO2022235621A1. 2022 Nov 10.
   Google Scholar
• Cheng C, Du S, Zhao L, et al., inventors; Nanjing Shenghe Pharmaceutical Research And Development Co ltd, assignee. Crystal forms of quinoline TGF-beta 1 inhibitor patent CN113527306A. 2021 Oct 22.
   Google Scholar
• Owens C, Kulyk S, Sullivan SDE, et al., inventors; Theravance Biopharma R&D Ip, Llc, assignee. Substituted 1,5-naphthyridines or quinolines as alk5 inhibitors patent WO2021102468A1. 2021 May 27.
   Google Scholar
• Owens C, Kulyk S, Sullivan SDE, et al., inventors; Theravance Biopharma R&D IP LLC, assignee. Substituted pyridines and methods of use patent US20230218597A1. 2023 Jul 13.
   Google Scholar
• Seo J, Han C, Yoon C, et al., inventors; Bisichem Co., Ltd., assignee. Fused ring heteroaryl compounds and use thereof patent WO2023018313A1. 2023 Feb-16.
   Google Scholar
• Nishida N, Kim D-K, inventors; Ewha Drugdesignhouse Co., Ltd., assignee. Composition or method containing an alk5 inhibitor, ew-7197 patent WO2023013993A1. 2023 Feb 09.
   Google Scholar
• Mai H-Q, Guo Y, Yang M-H, et al. A phase Ib/II study of GFH018 in combination with toripalimab in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC). J Clin Oncol. 2023;41(16_suppl):6026–6026. doi: 10.1200/JCO.2023.41.16_suppl.6026
   Web of Science ®Google Scholar
• AS SL. A Phase 2a, randomized, placebo-controlled, double-blind study to assess the safety, pharmacokinetics, and pharmacodynamics of AGMB-129 in patients with fibrostenotic crohn’s disease. clinicaltrials.gov. 2023.
   Google Scholar
• Jung M, Lee C-K, Kim HS, et al. 1453P safety and efficacy of vactosertib, a TGF-βR1 kinase inhibitor, in combination with paclitaxel in patients with metastatic gastric adenocarcinoma. Ann Oncol. 2020 Sep 01;31:S912. English. 10.1016/j.annonc.2020.08.1959.
   PubMed Web of Science ®Google Scholar
• Owens C, Sullivan SDE, Allegretti P, et al., inventors; Theravance Biopharma R&D Ip, Llc, assignee. Bicyclic inhibitors of alk5 and methods of use patent WO2022251359A1. 2022 Dec-01.
   Google Scholar
• Jin G, Wu Q, Zhang K, et al., inventors; Jiangsu Simcere Pharmaceutical Co Ltd, assignee. Quinoline compound patent CN114437082A. 2022 May 06.
   Google Scholar
• Tian Q, Zhang Y, Miao Y, et al., inventors; Sichuan Kelun Biotech Biopharmaceutical Co Ltd, assignee. Pyrazolo pyridine compound, and pharmaceutical composition, preparation method and application thereof patent CN114380818A. 2022 Apr 22.
   Google Scholar
• Tian Q, Zhang Y, Jiang X, et al., inventors; Sichuan Kelun-Biotech Biopharmaceutical Co Ltd, assignee. Pyrazole compound and preparation method therefor and use thereof patent WO2022063050A1. 2022 Mar-31.
   Google Scholar
• Wen X, Wu G, Sun H, et al., inventors; China Pharmaceutical University, assignee. Imidazole-2-methylamine derivative and medical application thereof patent CN114380823A. 2022 Apr 22.
   Google Scholar
• Smith SW, Hunt KW, inventors; Silverback Therapeutics, Inc., assignee. Alk5 inhibitors, conjugates, and uses thereof patent WO2022076905A1. 2022 Apr 14.
   Google Scholar
• Brozell A, Dabros M, Fu J, et al., inventors; Theravance Biopharma R&D Ip, Llc, assignee. Naphthyridine derivatives useful as alk5 inhibitors patent WO2021253041A1. 2021 Dec 16.
   Google Scholar
• Loo M, Kulyk S, Bailey C, et al., inventors; Theravance Biopharma R&D Ip, Llc, assignee. Substituted pyrimidines and methods of use patent WO2021203131A1. 2021 Oct 07.
   Google Scholar
• Kim MS, inventor; Institute of Zoology of CAS, assignee. Use of PPD in preparing medicine for preventing or treating TGF beta pathway related diseases patent CN113318117A. 2021 Aug-31.
   Google Scholar
• Artal RB, Casal BP, Laria JCP, inventors; Origo Biopharma, S.L., assignee. Benzylamide derivatives as inhibitors of transforming growth factor-beta receptor i/alk5 patent WO2021105317A1. 2021 Jun 03.
   Google Scholar
• Artal RB, Casal BP, Laria JCP, inventors; Origo Biopharma, S.L., assignee. 2-(3-pyridin-2-yl-4-quinolin-4-yl-pyrazol-1-yl)-acetamide derivatives as inhibitors of transforming growth factor-beta receptor i/alk5 patent WO2022069509A1. 2022 Apr 07.
   Google Scholar
• Smith SW, inventor; Silverback Therapeutics, Inc., assignee. Galnac-tgfbr1 inhibitor conjugates for the treatment of liver diseases patent WO2021072330A1. 2021 Apr 15.
   Google Scholar
• Kulyk S, Owens C, Sullivan SDE, et al., inventors; Theravance Biopharma R&D IP LLC, assignee. Alk5 inhibitors patent US20210154178A1. 2021 May 27.
   Google Scholar
• Park CH, Kim TH, Choi SW, et al., inventors; Autotelic Bio Inc assignee. Thiazole derivative compound and uses thereof patent WO2023182780A1. 2023 Sep-28.
   Google Scholar
• Pala D, Pizzirani D, Bruno P, et al., inventors; Chiesi Farmaceutici S.P.A., assignee. Pyrido oxazine derivatives as alk5 inhibitors patent WO2022136221A1. 2022 Jun 30.
   Google Scholar
• Franz B, Siddiqui-Jain A, Warner SL, et al., inventors; Sumitomo Pharma Oncology,Inc., assignee. Alk-5 inhibitors and uses thereof patent WO2022126133A1. 2022 Jun 16.
   Google Scholar
• Chen S, Song S, Liu C, et al., inventors; Sichuan Kelun Biotech Biopharmaceutical Co Ltd, assignee. Imidazopyrimidines containing a ring-like group, process for their preparation and their use patent CN116789681A. 2023 Sep 22.
   Google Scholar
• Pizzirani D, Ronchi P, Rescigno D. Pyridazinyl amino derivatives as alk5 inhibitors patent WO2023135107A1. 2023 Jul 20. inventors; Chiesi Farmaceutici S.P.A., assignee.
   Google Scholar
• Pizzirani D, Ronchi P, Guariento S, et al., inventors; Chiesi Farmaceutici S.P.A., assignee. Pyridazinyl amino derivatives as alk5 inhibitors patent WO2023046698A1. 2023 Mar-30.
   Google Scholar
• Deng P, Meng D, Jiang J, et al., inventors; Chongqing Medical University, assignee. 1, 3, 5-triazine compound and preparation method and application thereof patent CN114773320A. 2022 Jul 22.
   Google Scholar
• Liu M, Meng X, Li T, et al., inventors; Anhui Medical University, assignee. A diaryl pyrimidine amide compound or pharmaceutically acceptable salt thereof, pharmaceutical composition and application thereof patent CN115340497A. 2022 Nov 15.
   Google Scholar
• Franz B, Siddiqui-Jain A, Warner SL, inventors; Sumitomo Pharma Oncology, Inc., assignee. Alk-5 inhibitors and uses thereof patent WO2022204721A1. 2022 Sep 29.
   Google Scholar
• Zou Q, Zhang J, Chen Y, et al., inventors; 广州市恒诺康医药科技有限公司, assignee. Imidazole compound, pharmaceutical composition thereof, and use thereof patent WO2022184000A1. 2022 Sep 09.
   Google Scholar
• Smith SW, Baum PR, Dubose R, et al., inventors; Silverback Therapeutics, Inc., assignee. Alk5 inhibitors, conjugates, and uses thereof patent WO2022006340A1. 2022 Jan 06.
   Google Scholar
• Thomas-Karyat DA, inventor; Synthis Therapeutics Inc, assignee. Antibody-alk5 inhibitor conjugates and their uses patent US20230132568A1. 2023 May-04.
   Google Scholar
• Jang M-H, Yuk C-M, GO G-Y, et al., inventors;Novel peptide capable of inhibiting TGF-β signaling and use thereof patent WO2022139493A1. 2022 Jun 30.
   Google Scholar
• Wu Q, Li F, Chen H, et al., inventors; Xiamen University, assignee. Flavonol-like compound and application thereof in inhibiting pulmonary fibrosis caused by viruses patent CN116217533A. 2023 Jun 06.
   Google Scholar
• Burgstaller G, Gerckens M, Plettenburg O, et al., inventors; Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), assignee. Novel anti-fibrotic drugs patent WO2022258792A1. 2022 Dec 15.
   Google Scholar
• Tang F, Jin G, Wu Q, et al., inventors; Jiangsu Simcere Pharmaceutical R&D Co., Ltd., assignee. Pyrazole compounds patent WO2021129621A1. 2021 Jul 01.
   Google Scholar
• Kretzschmar M, Doody J, Timokhina I, et al. A mechanism of repression of TGFβ/Smad signaling by oncogenic Ras. Genes Dev. 1999 Apr 01;13(7):804–816. en. doi:10.1101/gad.13.7.804.
   PubMed Web of Science ®Google Scholar
• Yan Z, Winawer S, Friedman E. Two different signal transduction pathways can be activated by transforming growth factor beta 1 in epithelial cells. J Biol Chem. 1994 May 06;269(18):13231–13237. doi: 10.1016/S0021-9258(17)36823-0
   PubMed Web of Science ®Google Scholar
• Zavoronkovs A, Aliper A, Aladinskiy V, et al., inventors; Insilico Medicine Ip Limited, assignee. Analogs for the treatment of disease patent WO2022179528A1. 2022 Sep 01.
   Google Scholar
• Ramadass V, Lee SY, Tergaonkar V, et al., inventors; Agency For Science, Technology And Research, assignee. Nf қb inducing kinase inhibitors and methods thereof patent WO2023177351A1. 2023 Sep 21.
   Google Scholar
• Frey RS, Mulder KM. Involvement of extracellular signal-regulated kinase 2 and stress-activated protein kinase/Jun N-terminal kinase activation by transforming growth factor β in the negative growth control of breast cancer cells1. Cancer res. 1997 Feb 01;57(4):628–633.
   PubMed Web of Science ®Google Scholar
• Burzyn D, Kamerkar S, Boutin AT, et al., inventors; Codiak Biosciences, Inc., assignee. Extracellular vesicle-aso constructs targeting stat6 patent WO2021030776A1. 2021 Feb 18.
   Google Scholar
• Chaum E, Bhattacharya S, Pfeffer L, inventors; Vanderbilt University, University of Tennessee Research Foundation, assignee. Combined targeting of stat3 and ulk1 to treat glioblastoma patent WO2023086927A1. 2023 May 19.
   Google Scholar
• Kang SS, Park ES, Park EH, et al., inventors; Ewha Womans University, Korea Pharma Co Ltd assignee. Novel JAK-specific inhibitor compound and method for preparing same patent WO2022114905A1. 2022 Jul 02.
   Google Scholar
• Bhowmick NA, Ghiassi M, Bakin A, et al. Transforming growth factor-β1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. ?Mol Biol Cell. 2001;12(1):27–36. doi: 10.1091/mbc.12.1.27
   Web of Science ®Google Scholar
• Ashraf M, inventor; Ips Heart, assignee. Cpc exosomes mirna373 combination therapies patent US20210054344A1. 2021 Feb 25.
   Google Scholar
• Ashraf M, inventor; Ips Heart Inc, assignee. Microvesicle and stem cell compositions for therapeutic applications patent JP2023145686A. 2023-Oct 11.
   Google Scholar
• Larsen SD, Neubig R, Kahl D, inventors; Regents of The University of Michigan, Board of Trustees of Michigan State University, assignee. Meta anilide compounds and methods for use of the same to treat diseases and disorders patent WO2023122325A2. 2023 Jun 29.
   Google Scholar
• Wilkes MC, Mitchell H, Penheiter SG, et al. Transforming Growth Factor-β Activation of Phosphatidylinositol 3-Kinase Is Independent of Smad2 and Smad3 and Regulates Fibroblast Responses via p21-Activated Kinase-2. Cancer res. 2005 Nov 15;65(22):10431–10440. doi: 10.1158/0008-5472.CAN-05-1522
   PubMed Web of Science ®Google Scholar
• Lv R, Chen Z, inventors; Tongrun Biomedical Shanghai Co ltd, assignee. PI3K delta/gamma medicine composition and method for treating tumor by using same patent CN115105600A. 2022-Sep 27.
   Google Scholar
• Xu J, Wang Z, Wang D, et al., inventors; Sirnaomics, Inc., assignee. Composition and use of siRNAs against vegfr2 and tgf-beta 1 in combination therapy for cancer patent WO2023288141A1. 2023 Jan 19.
   Google Scholar
• Sun T, Zhang W, Chen P, inventors; Naptide Qingdao Biomedical Co ltd, assignee. SiRNA for treating diseases associated with TGF beta 1 expression patent CN114854738A. 2022 Aug 05.
   Google Scholar
• Trieu V, inventor; Oncotelic Inc., assignee. Tgf-beta inhibition, agents and composition therefor patent WO2021186396A2. 2021 Sep 23.
   Google Scholar
• Park CH, Koo JH, Kim JH, et al., inventors; Autotelic Bio Inc, assignee. Antisense oligonucleotides patent WO2022060208A1. 2022 Mar 24.
   Google Scholar
• Nakamura Y, Takahashi M, Hashimoto Y, inventors; Ribomic Inc, assignee. Aptamer for TGF-beta1 and use of same patent WO2021006305A1. 2021 Jan 14.
   Google Scholar
• Xie L, Lin Y, inventors; Chongqing Medical University, assignee. A load s58 nucleic acid aptamer hydrogel solution, hydrogel and application thereof patent CN116350576A. 2023 Jun 30.
   Google Scholar
• Gao P, Wu J, Liu C, inventors; Beijing Yuyang Technology Co ltd, assignee. Chimeric antigen receptor (CAR) and application in treating tumour patent CN116063575A. 2023 May 05.
   Google Scholar
• Molyneaux M, Lu P, inventors; Sirnaomics, Inc., assignee. siRNA-copolymer compositions and methods of use for treatment of liver cancer patent WO2023288128A1. 2023 Jan 19.
   Google Scholar
• Sirnaomics. A randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of intralesional injection of STP705 in adult patients with cutaneous squamous cell carcinoma in situ (isSCC). clinicaltrials.gov. 2023.
   Google Scholar