Granted Patent
B2
US 12,377,175 · App. 17/016,189 · Granted Aug 5, 2025
Trifunctional constructs with tunable pharmacokinetics useful in imaging and anti-tumor therapies
Inventors:
John W. Babich (New York, NY); James M. Kelly (New York, NY); Alejandro Amor-Coarasa (New York, NY); Shashikanth Ponnala (New York, NY)
Assignee:
Cornell University
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Abstract
The present technology provides compounds, as well as compositions including such compounds, useful for imaging and/or treatment of a glioma, a breast cancer, an adrenal cortical cancer, a cervical carcinoma, a vulvar carcinoma, an endometrial carcinoma, a primary ovarian carcinoma, a metastatic ovarian carcinoma, a non-small cell lung cancer, a small cell lung cancer, a bladder cancer, a colon cancer, a primary, gastric adenocarcinoma, a primary colorectal adenocarcinoma, a renal cell carcinoma, and/or a prostate cancer.
Claims (1)
1. A compound that is
Continuity (7)
Continuation In Part
PCTUS2018026340
· Apr 5, 2018
Provisional Application
62574720
· Oct 19, 2017
Provisional Application
62482038
· Apr 5, 2017
Provisional Application
62353735
· Jun 23, 2016
References Cited (143)
US 8211401B2
· Babich et al.
· 2012
[cited by applicant]
US 8778305B2
· Pomper et al.
· 2014
[cited by applicant]
US 8921528B2
· Holt et al.
· 2014
[cited by applicant]
US 8926944B2
· Babich et al.
· 2015
[cited by applicant]
US 9226981B2
· Pomper et al.
· 2016
[cited by applicant]
US 9295739B2
· Schibli et al.
· 2016
[cited by applicant]
US 20060252107A1
· Kubota et al.
· 2006
[cited by applicant]
US 20150064185A1
· Holt et al.
· 2015
[cited by applicant]
US 20160228587A1
· Eder et al.
· 2016
[cited by applicant]
US 20170326261A1
· Oukhatar et al.
· 2017
[cited by applicant]
US 20210121584A1
· Babich et al.
· 2021
[cited by applicant]
US 20220143231A1
· Salter et al.
· 2022
[cited by applicant]
US 20220184217A1
· White et al.
· 2022
[cited by applicant]
US 20230011134A1
· Salter et al.
· 2023
[cited by applicant]
US 20230044430A1
· Krantz et al.
· 2023
[cited by applicant]
US 20230122503A1
· Goldberg et al.
· 2023
[cited by applicant]
AU 2018249559AA
· 2019
[cited by applicant]
CA 3058663A1
· 2018
[cited by applicant]
CA 3070610A1
· 2021
[cited by applicant]
CN 110612126A
· 2019
[cited by applicant]
EP 3609541A1
· 2020
[cited by applicant]
JP 2010509358A
· 2010
[cited by applicant]
JP 2011529919A
· 2011
[cited by applicant]
JP 2012511023A
· 2012
[cited by applicant]
JP 2014524419A
· 2014
[cited by applicant]
JP 2014531407A
· 2014
[cited by applicant]
JP 2015078168A
· 2015
[cited by applicant]
JP 2016535013A
· 2016
[cited by applicant]
JP 2020516611A
· 2020
[cited by applicant]
KR 20190129931A
· 2019
[cited by applicant]
WO WO2008053360A2
· 2008
[cited by applicant]
WO WO2008058192A2
· 2008
[cited by applicant]
WO WO2010014933A2
· 2010
[cited by applicant]
WO WO2010032248A2
· 2010
[cited by applicant]
WO WO2015055318A1
· 2015
[cited by applicant]
WO WO2017070482A2
· 2017
[cited by applicant]
WO WO2018187631A1
· 2018
[cited by applicant]
WO WO2022162210A1
· 2022
[cited by applicant]
WO WO2022162549A2
· 2022
[cited by applicant]
WO WO2023026235A1
· 2023
[cited by applicant]
WO WO2023049963A1
· 2023
[cited by applicant]
WO WO2023084396A1
· 2023
[cited by applicant]
WO WO2023084397A1
· 2023
[cited by applicant]
Guo, et al. AAPS Pharmsci, 1999; 1 (4) pp. 1-7.
[cited by examiner]
Othman et al. Nuclear Medicine and Biology 2017, 46, 12-18 (Year: 2017).
[cited by examiner]
Capello et al. J. Nucl. Med. 2003, 44, 98-104 (Year: 2003).
[cited by examiner]
Dumelin et al. Angew. Chem. Int. Ed. 2008, 47, 3196-3201 (Year: 2008).
[cited by examiner]
Janckson et al. Neoplasia 2015, 17, 43-54 (Year: 2015).
[cited by examiner]
Jansen et al. ACS Med. Chem. Lett. 2013, 4, 491-496 (Year: 2013).
[cited by examiner]
Cho et al. Scientific Reports 2020, 10, 21280, pp. 1-16 (Year: 2020).
[cited by examiner]
Chen et al. J. Med. Chem. 2008, 51, 7933-7943 (Year: 2008).
[cited by examiner]
Dörwald, F. Zaragoza. Side Reactions in Organic Synthesis: A Guide to Successful Synthesis Design, Weinheim: Wiley-VCH Verlag GmbH & Co. KgaA, 2005, Preface (Year: 2005).
[cited by examiner]
Tian et al. Theranostics 2018, 8, 735-745 (Year: 2018).
[cited by examiner]
O'Dorislo et al. Cell Growth % Differentiation 1994, 5, 1-8 (Year: 1994).
[cited by examiner]
Kelly et al. Eur. J. Nucl. Med. Mol. Imaging 2018, 45, 1841-1851 (Year: 2018).
[cited by examiner]
Kelly, et al., “Dual-Target Binding Ligands with Modulated Pharmacokinetics for Endoradiotherapy of Prostate Cancer,”
[cited by applicant]
Office Action issued in Chinese Patent Application No. 201780046339.7, dated Apr. 23, 2021.
[cited by applicant]
C. Muller et al., “DOTA Conjugate with an Albumin-Binding Entity Enables the First Folic Acid-Targeted 177Lu-Radionuclide Tumor Therapy in Mice”, The J0urnal 0f Nuclear Medicine, vol. 54, No. 1, pp. 124-131 (Jan. 1, 201…
[cited by applicant]
Renata Farkas, et al. “64 Cu- and 68 Ga-Based PET Imaging of Folate Receptor-Positive Tumors: Development and Evaluation of an Albumin-Binding NODAGA-Folate”, Molecular Pharmaceutics, vol. 13, No. 6, pp. 1979-1987 (Jun.…
[cited by applicant]
Foreign Search Report on EP 18780348.1 dated Dec. 7, 2020.
[cited by applicant]
Baccala, et al., “Expression of Prostate-Specific Membrane Antigen in Tumor-Associated Neovasculature of Renal Neoplasms,” Urology, 70 (2), 2007, pp. 385-390.
[cited by applicant]
Cancer [online], [retrieved on Jul. 6, 2007], Retrieved from the Internet,URL: http://www.nlm.nih.gov/medlineplus/cancer.html, 10 pages.
[cited by applicant]
Chang, et al., “Five Different Anti-Prostate-specific Membrane Antigen (PSMA) Antibodies Confirm PSMA Expression in Tumor-associated Neovasculature,” Cancer Research 59, Jul. 1, 1999, pp. 3192-3198.
[cited by applicant]
Chen, et al., “Quantitative Studies of Allosteric Effects by Biointeraction Chromatography: Analysis of Protein Binding for Low-Solubility Drugs,” Analytical Chemistry, vol. 78, No. 8, Apr. 15, 2006, pp. 2672-2683.
[cited by applicant]
Chen, et al., “Radiohalogenated Prostate-Specific Membrane Antigen (PSMA)-Based Ureas as Imagine Agents for Prostate Cancer,” J. Med. Chern., 51, 2008, pp. 7933-7943.
[cited by applicant]
Dennis et al., “Imaging Tumors with an Albumin-Binding Fab, a Novel Tumor-Targeting Agent,” Cancer Research, vol. 67, Jan. 1, 2007, pp. 254-261.
[cited by applicant]
Extended European Search Report on EP Patent Application No. 17816235.0 dated Jan. 24, 2020 (6 pages).
[cited by applicant]
Fendler, et al., “Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for metastatic castration-resistant prostate cancer,” Oncotarget, vol. 8, No. 2, 2017, pp. 3581…
[cited by applicant]
International Preliminary Report on Patentability issued on PCT/US2017/038832, dated Jan. 3, 2019.
[cited by applicant]
Golub, et al., “Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring”, Science 286: 531-537 (1999).
[cited by applicant]
Haffner, et al., “Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers,” Human Pathology, 40, 2009, pp. 1754-1761.
[cited by applicant]
Hillier et al., “Preclinical Evaluation of Novel Glutamate-Urea-Lysine Analogues That Target Prostate-Specific Membrane Antigen as Molecular Imaging Pharmaceuticals for Prostate Cancer,” Cancer Research, vol. 69, pp. 69…
[cited by applicant]
International Search Report and Written Opinion issued on PCT/US2017/038832, dated Sep. 21, 2017.
[cited by applicant]
International Search Report and Written Opinion on PCT/US2018/026340 (dated Jul. 27, 2018).
[cited by applicant]
Joseph, et al., “The effects of glycation on the binding of human serum albumin to warfarin and L-tryptophan,” Journal of Pharmaceutical and Biomedical Analysis, 53, 2010, pp. 811-818.
[cited by applicant]
Kelly et al., “Double Targeting Ligands with Modulated Pharmacokinetics for Endoradiotherapy of Prostate Cancer,” J. Nucl. Med, Apr. 27, 2017, 36 pages.
[cited by applicant]
Kelly, et al., “Synthesis and pre-clinical evaluation of a new class of high-affinity 18F-labeled PSMA ligands for detection of prostate cancer by PET imaging,” Eur J Nucl Med Mol Imaging, 44, 2017, pp. 647-661.
[cited by applicant]
Kiess et al. “(2S)-2-(3-1Carboxy-5-(4-211AT-Astatobenzamido)Pentyl)Ureido)-Pentanedioc Acid for PSMA-Targeted alpha-Particle Radiopharmaceutical Therapy,” J Nucl Med., 2016, vol. 57, pp. 1569-1575.
[cited by applicant]
Kratochwil, et al., “225Ac-PSMA-617 for PSMA-Targeted FFD3B1 -Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer,” The Journal of Nuclear Medicine, vol. 57, No. 12, Dec. 2016, pp. 1941-1944.
[cited by applicant]
Kratochwil, et al., “PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617,” The Journal of Nuclear Medicine, vol. 57, No. 8, Aug. 2016, pp. 1170-1176.
[cited by applicant]
Lala, et al., “Role of nitric oxide in tumor progression: Lessons from experimental tumors,” Cancer and Metastasis Reviews, (1998), 17(1):91-106.
[cited by applicant]
Maresca, et al., “A Series of Halogenated Heterodimeric Inhibitors of Prostate Specific Membrane Antigen (PSMA) as Radiolabeled Probes forTargeting Prostate Cancer,” J. Med. Chern., 52, 2009, pp. 347-367.
[cited by applicant]
Matsuda, “Analysis of Drug-Protein Interactions by High-Performance Affinity Chromatography: Interactions of Sulfonylurea Drugs with Normal and Glycated Human Serum Albumin,” Methods in Molecular Biology, vol. 1286, 201…
[cited by applicant]
Non-Final Office Action on U.S. Appl. No. 16/246,422 dated Jul. 11, 2019.
[cited by applicant]
Notice or Allowance in U.S. Appl. No. 16/240,422 dated Mar. 5, 2020.
[cited by applicant]
Notice of Allowance on U.S. Appl. No. 15/630,808 dated Sep. 6, 2018.
[cited by applicant]
O'Keefe, et al., “Comparative Analysis of Prostate-Specific Membrane Antigen (PSMA) Versus a Prostate-Specific Membrane Antigen-Like Gene,” The Prostate 58, 2004, pp. 200-210.
[cited by applicant]
Samplaski, et al., “Folate hydrolase (prostate-specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature,” Modern Pathology, 2011, pp. 1521-1529.
[cited by applicant]
U.S. Office Action on U.S. Appl. No. 15/630,808 dated Dec. 1, 2017.
[cited by applicant]
Wang, et al., “Expression of Prostate-Specific Membrane Antigen in Lung Cancer Cells and Tumor Neovasculature Endothelial Cells and Its Clinical Significance,” PLOS ONE, May 15, 2015, pp. 1-8.
[cited by applicant]
Wernicke, et al., “Prostate-specific Membrane Antigen (PSMA) Expression in the Neovasculature of Gynecological Malignancies: Implications for PSMA-targeted Therapy,” Appl Immunohistochem Mol Morphol, vol. 25, No. 4, Apr…
[cited by applicant]
Wustemann, et al., “Protecting salivary glands: Displacement of off-target bound prostate-specific membrane antigen ligands,” 2016, page S15.
[cited by applicant]
Zechmann, et al., “Radiation dosimetry and first therapy results with a 1241/131 l-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy,” Eur J Nucl Med Mol Imaging, 41, 2014, pp. 1280-1292.
[cited by applicant]
Zheng, et al., “Development of enhanced capacity affinity microcolumns by using a hybrid of protein cross-linking/modification and immobilization,” Journal of Chromatography A, 1400, 2015, pp. 82-90.
[cited by applicant]
Notice of Reasons for Rejection issued in co-pending Japanese Patent Application No. 2018-567684, dated May 18, 2021.
[cited by applicant]
Non-Final Office Action issued in co-pending U.S. Appl. No. 16/906,956, dated Jun. 9, 2021.
[cited by applicant]
Fischer, et al., “Radioimmunotherapy of Fibroblast Activation Protein Positive Tumors by Rapidly Internalizing Antibodies,” Clinical Cancer Research, 18(22):6208-6218 (2012) (12 pages).
[cited by applicant]
Third-Party Submission Under 37 CFR 1.290 issued in U.S. Appl. No. 17/132,552 dated Sep. 29, 2021 (19 pages).
[cited by applicant]
Office Action issued in co-pending U.S. Appl. No. 17/132,552, dated Dec. 13, 2021.
[cited by applicant]
Office Action issued in co-pending U.S. Appl. No. 16/906,956, dated Mar. 16, 2022.
[cited by applicant]
Siwowska, et al., “Preclinical Comparison of Albumin-Binding Radiofolates: Impact of Linker Entities on the In Vitro and In Vivo Properties,”
[cited by applicant]
Notice of Reasons for Rejection issued in co-pending Japanese Patent Application No. 2019-554886, dated Mar. 29, 2022.
[cited by applicant]
Notice of Reasons for Rejection issued in co-pending Japanese Patent Application No. 2018-567684, dated Mar. 29, 2022.
[cited by applicant]
Wang, H. et al., “Bioisosterism of urea-based GCPII inhibitors: Synthesis and structure-activity relationship studies,”
[cited by applicant]
Kumar, A. et al., Design of a Small-Molecule Drug Conjugate for Prostate Cancer Targeted Theranostics, Bioconjugate Chemistry, vol. 27(7), pp. 1681-1689 (2016).
[cited by applicant]
Office Action issued in co-pending U.S. Appl. No. 17/132,552, dated Aug. 29, 2022.
[cited by applicant]
Chen et al., “Novel molecular “add-on” based on Evans Blue confers superior pharmacokinetics and transforms drugs to theranostic agents,”
[cited by applicant]
Thiele, “An Eighteen-Membered Macrocycficligand for Actinium-225Targeted AlphaTherapy,” Angewandte Chemie International Edition, vol. 56, pp. 14712-14717 (2017).
[cited by applicant]
Abou, et al., “Towards the stable chelation of radium for biomedical applications with an 18-membered macrocyclic ligand,” Chemical Science, vol. 12, 3733-3742 (2021).
[cited by applicant]
Aluicio-Sardu, et al., “Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicone Applications,” Chemistry A European Journal Communication, vol. 26, pp. 1238-1242 92020).
[cited by applicant]
Bobba, et al., “Influence of short PEG linkers on biodistribution of 225AC-Macropa-YS5, an immunoconjugate for treating CD46 expressing cancer,” Abstract/Nuclear Medicine and Biology, pp. 108-109 (2022).
[cited by applicant]
Macropa-NCS Cat. No. HY-111605, Master of Bioactive Molcules, Aug. 2023, 3 pages.
[cited by applicant]
Randhawa, et al., “Development of novel sulfur-rich ligands for incorporation into mercury-197m/g radiopharmaceuticals,” Abstracts/Nuclear Medicine and Biology, pp. 108-109 (2022).
[cited by applicant]
Reissig, et al., “Modulating the pharmacokinetic profile of Actinium-225-labeled macropa-derived radioconjugates by dual targeting of PSMA and albumin,” Theranostics, vol. 12, No. 17, pp. 7203-7215 (2002).
[cited by applicant]
Shalgunov, et al., “Radiolabeling of a polypeptide polymer for intratumoral delivery of alpha-particle emitter, 225AC, and beta-particle emitter, 177Lu,” Nuclear Medicine and Biology, vol. 104-105, pp. 11-21 (2022).
[cited by applicant]
Thiele, et al., “An Eighteen-Membered Macrocyclic Ligand for Actinium-225 Targeted Alpha Therapy,” Angew Chem. Int. Ed. Eng., vol. 56, No. 46, pp. 14712-14717 (2017). [Abstract].
[cited by applicant]
Office Action issued in co-pending U.S. Appl. No. 16/906,956, dated May 9, 2023.
[cited by applicant]
Office Action issued in co-pending U.S. Appl. No. 17/132,552, dated Mar. 9, 2023.
[cited by applicant]
Shetty et al., “Ga-Labeled Radiopharmaceuticals for Position Emission Tomography”, Nucl. Med. Mol. Imaging, vol. 44, 2010, pp. 223-240.
[cited by applicant]
Benesova, et al., “Albumin-Binding PSMA Ligands: Optimization of the Tissue Distribution Profile,” Mol. Pharmaceuticals, vol. 15, pp. 934-946 (2018).
[cited by applicant]
Foreign Action issued in Korean Patent Application No. 10-2023-7009535, dated Nov. 27, 2024.
[cited by applicant]
Non-Final Office Action issued in U.S. Appl. No. 17/963,823, dated May 8, 2024.
[cited by applicant]
Notice of Allowance issued in U.S. Appl. No. 17/863,823, dated Nov. 26, 2024.
[cited by applicant]
Office Action issued in co-pending U.S. Appl. No. 16/906,956, dated Nov. 22, 2023.
[cited by applicant]
Liao, Z. et al., “Luminescent Metal-Organic Framework Thin Films: From Preparation to Biomedical Sensing Applications,” Crystals, Aug. 23, 2018, vol. 8, pp. 1-32.
[cited by applicant]
Notice of Reasons for Rejection issued in Japanese Patent Application No. 2023-202428, Dec. 17, 2024.
[cited by applicant]
Rubio-Martinez, et al., “New synthetic routes towards MOF production at scale,” Chem. Soc. Rev., The Royal Society of Chemistry, May 22, 2017, vol. 46, pp. 3453-3480.
[cited by applicant]
Huang, S., et al. Evaluation of the tumor targeting of a FAPalpha-based doxorubicin prodrug, J Drug Targeting, 19(7): 487-496 (2011).
[cited by third party]
Dvorakova, P., et al., Inhibitor-Decorated Polymer Conjugates Targeting Fibroblast Activation Protein, J Med Chem, 60(20): 8385-8393 (2017).
[cited by third party]
Müller, C., et al., DOTA conjugate with an albumin-binding entity enables the first folic acid-targeted 177Lu-radionuclide tumor therapy in mice, J Nucl Med, 54(1): 124-131 (2013).
[cited by third party]