IP Library › Granted Patent US 12,497,417
Granted Patent B2
US 12,497,417 · App. 17/831,710 · Granted Dec 16, 2025

Delivery systems for controlled drug release

Inventors: Felix Kratz (Ehrenkirchen, DE); Khalid Abu Ajaj (Berlin, DE); André Warnecke (Freiburg, DE); Stephan David Koester (Gundelfingen, DE); Friederike I. Nollmann (Freiburg, DE); Simon Waltzer (Freiburg, DE); Olga Fuchs (Herbolzheim, DE); Javier García Fernandez (Freiburg, DE)
Assignee: LADRX CORPORATION
C07F9/65586A61K47/6889C07H15/26C07H19/06C07K5/06052C07K5/06104C07K5/06191A61K45/06
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Quick Facts
Patent No.
US 12,497,417
App. No.
17/831,710
Granted
Dec 16, 2025
Kind
B2
Abstract

The present invention provides a compound having the structure of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof, for the controlled delivery and release of Agent.

Claims (13)

1 . A method of treating a cancer, wherein the cancer is selected from the group consisting of lung cancer, pancreatic cancer and ovarian cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound having the structure

or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof.

2 . The method according to claim 1 , wherein the compound is

3 . The method according to claim 1 , wherein the compound is a pharmaceutically acceptable salt of

4 . The method according to claim 1 , wherein the cancer is lung cancer.

5 . The method according to claim 2 , wherein the cancer is lung cancer.

6 . The method according to claim 3 , wherein the cancer is lung cancer.

7 . The method according to claim 1 , wherein the cancer is pancreatic cancer.

8 . The method according to claim 2 , wherein the cancer is pancreatic cancer.

9 . The method according to claim 3 , wherein the cancer is pancreatic cancer.

10 . The method according to claim 1 , wherein the cancer is ovarian cancer.

11 . The method according to claim 2 , wherein the cancer is ovarian cancer.

12 . The method according to claim 3 , wherein the cancer is ovarian cancer.

Assignments (4)
CHANGE OF NAME Recorded Feb 23, 2023
From: CYTRX CORPORATION
To: LADRX CORPORATION
Reel/Frame 062850/0019 →
MERGER Recorded Sep 7, 2022
From: CENTURION BIOPHARMA CORPORATION
To: CYTRX CORPORATION
Reel/Frame 061014/0553 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2022
From: KRATZ, FELIX; ABU AJAJ, KHALID; WARNECKE, ANDRÉ; KOESTER, STEPHAN DAVID; NOLLMANN, FRIEDERIKE I.; WALTZER, SIMON; FUCHS, OLGA; GARCÍA FERNANDEZ, JAVIER
To: CYTRX CORPORATION
Reel/Frame 060098/0858 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2022
From: CYTRX CORPORATION
To: CENTURION BIOPHARMA CORPORATION
Reel/Frame 060098/0935 →
Continuity (5)
Division 15735885
Provisional Application 62261563 · Dec 1, 2015
Provisional Application 62261213 · Nov 30, 2015
Provisional Application 62182219 · Jun 19, 2015
Related Publication 20230023537A1 · Jan 26, 2023
References Cited (90)
US 4125704A · Henry · 1978 [cited by applicant]
US 4699880A · Goldstein · 1987 [cited by applicant]
US 4816397A · Boss et al. · 1989 [cited by applicant]
US 4816567A · Cabilly et al. · 1989 [cited by applicant]
US 4946778A · Ladner et al. · 1990 [cited by applicant]
US 4966999A · Coughlin et al. · 1990 [cited by applicant]
US 5225539A · Winter · 1993 [cited by applicant]
US 5476786A · Huston et al. · 1995 [cited by applicant]
US 5514548A · Krebber et al. · 1996 [cited by applicant]
US 6884869B2 · Senter et al. · 2005 [cited by applicant]
US 7098308B2 · Senter et al. · 2006 [cited by applicant]
US 7387771B1 · Kratz · 2008 [cited by applicant]
US 8703724B2 · Kratz · 2014 [cited by applicant]
US 20060233707A1 · Kratz · 2006 [cited by applicant]
US 20120165296A1 · Kratz et al. · 2012 [cited by applicant]
US 20120195832A1 · Kratz · 2012 [cited by applicant]
US 20130129753A1 · Doroski et al. · 2013 [cited by applicant]
US 20150250896A1 · Zhao · 2015 [cited by applicant]
US 20200385421A1 · Kratz et al. · 2020 [cited by applicant]
US 20230391794A1 · Kratz et al. · 2023 [cited by applicant]
CA 3130994A1 · 2014 [cited by applicant]
CN 101490087A · 2009 [cited by applicant]
EP 0120694A2 · 1984 [cited by applicant]
EP 0194276A1 · 1986 [cited by applicant]
EP 0345723A2 · 1989 [cited by applicant]
EP 0239400B1 · 1994 [cited by applicant]
EP 0451216B1 · 1996 [cited by applicant]
EP 0125023B2 · 2002 [cited by applicant]
EP 0519596B1 · 2005 [cited by applicant]
EP 2289558A1 · 2011 [cited by applicant]
WO 8601533A1 · 1986 [cited by applicant]
WO 9306213A1 · 1993 [cited by applicant]
WO 0162726A2 · 2001 [cited by applicant]
WO 2002088172A2 · 2002 [cited by applicant]
WO 2005055939A2 · 2005 [cited by applicant]
WO 2013072813A2 · 2013 [cited by applicant]
WO 2013124068A1 · 2013 [cited by applicant]
WO 2014080251A1 · 2014 [cited by applicant]
WO 2014094353A1 · 2014 [cited by applicant]
WO 2015118497A1 · 2015 [cited by applicant]
WO 2016160615A1 · 2016 [cited by applicant]
RN2055867-93-9 (Year: 2017). [cited by examiner]
U.S. Appl. No. 15/735,885, filed Dec. 12, 2017, Felix Kratz, et al., Issued. [cited by applicant]
U.S. Appl. No. 16/768,418, filed May 29, 2020, Felix Kratz, et al., Issued. [cited by applicant]
U.S. Appl. No. 16/768,436, filed May 29, 2020, Felix Kratz, et al., Issued. [cited by applicant]
U.S. Appl. No. 18/086,076, filed Dec. 21, 2022, Felix Kratz, et al., Pending. [cited by applicant]
Berge, et al., “Pharmaceutical salts,” Journal of Pharmaceutical Sciences, 66:1-19 (1977). [cited by applicant]
Bird, et al., “Single-Chain Antigen-Binding Proteins”, Science 242: 423-426 (1988). [cited by applicant]
Boothroyd, et al., “Why Do Some Molecules Form Hydrates or Solvates?,” Crystal Growth and Design 18:1903-1908 (2018). [cited by applicant]
Carter et al., “Structure of serum albumin,” Advances in Protein Chemistry, 45:153-203 (1994). [cited by applicant]
Chari, et al., “Antibody-Drug Conjugates: An Emerging Concept in Cancer Therapy”, Angewandte Reviews 53: 3796-3827 (2014). [cited by applicant]
Chen, et al., “Tubulin Inhibitor-Based Antibody-Drug Conjugates for Cancer Therapy,” Molecules, 22(8):1281-1309 (2017). [cited by applicant]
Cross, et al., “Rules for the Nomenclature of Organic Chemistry-Section E: Stereochemistry”, Pure and Applied Chemistry 45: 11-30 (1976). [cited by applicant]
Dao, et al., “Design, synthesis, and initial biological evaluation of a steroidal anti-estrogen-doxorubicin bioconjugate for targeting estrogen receptor-positive breast cancer cells,” Bioconjugate Chemistry, 23:785-795 … [cited by applicant]
Daugherty, et al., “Polymerase chain reaction facilitates the cloning, CDR-grafting, and rapid expression of a murine monoclonal antibody directed against the CD18 component of leukocyte integrins,” Nucleic Acids Resear… [cited by applicant]
Doronina et al., “Development of potent monoclonal antibody auristatin conjugates for cancer therapy,” Nature Biotechnology, 21(7):778-784 (2003). [cited by applicant]
Era et al., “Further studies on the resolution of human mercapt- and nonmercaptalbumin and on human serum albumin in the elderly by high-performance liquid chromatography,” International Journal of Peptide and Protein R… [cited by applicant]
Etoh et al., “Rapid analysis of human serum albumin by high-performance liquid chromatography,” Journal of Chromatography A, 578:292-296 (1992). [cited by applicant]
Hagenfeldt et al., “Glutathione and gamma-glutamylcysteine in whole blood, plasma and erythrocytes,” Clinica Chimica Acta, 85:167-173 (1978). [cited by applicant]
Hartung, et al., “Phase I trial of methotrexate-albumin in a weekly intravenous bolus regimen in cancer patients. Phase I Study Group of the Association for Medical Oncology of the German Cancer Society,” Clinical Cance… [cited by applicant]
Horstmann, et al., “Synthesis of azobenzenealkylmaleimide probes to photocontrol the enzyme activity of a bacterial histone deacetylase-like amidohydrolase,” Bioorganic Chemistry, 57:155-161 (2014). [cited by applicant]
Kamman, et al., “Rapid insertional mutagenesis of DNA by polymerase chain reaction (PCR)”, Nucleic Acids Research, 17(13): 5404 (1989). [cited by applicant]
Kratz et al., “Probing the cysteine-34 position of endogenous serum albumin with thiol-binding doxorubicin derivatives. Improved efficacy of an acid-sensitive doxorubicin derivative with specific albumin-binding propert… [cited by applicant]
Kratz, “DOXO-EMCH (INNO-206): the first albumin-binding prodrug of doxorubicin to enter clinical trials,” Expert Opinion on Investigational Drugs, 16:855-866 (2007). [cited by applicant]
Kratz, “Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles,” Journal of Controlled Release, 132:171-183 (2008). [cited by applicant]
Kratz, et al. “Serum Proteins as Drug Carriers of Anticancer Agents: A Review,” Drug Delivery, 5:281-299 (1998). [cited by applicant]
Kratz, et al., “Transferrin conjugates of doxorubicin: Synthesis, characterization, cellular uptake, and in vitro efficacy,” Journal of Pharmaceutical Sciences, 87(3):338-346 (1998). [cited by applicant]
Kratz, et al., “Preparation, characterization and in vitro efficacy of albumin conjugates of doxorubicin”, Biological & Pharmaceutical Bulletin 21(1): 56-61 (1998). [cited by applicant]
Kratz, et al., “Prodrug strategies in anticancer chemotherapy”, ChemMedChem, 3(1):20-53 (2008). [cited by applicant]
Lau, et al., “Novel doxorubincon-monoclonal anti-carcinoembryonic antigen antibody immunoconjugate activity in vitro”, Bioorganic & Medicinal Chemistry, 3(10): 1305-1312 (1995). [cited by applicant]
Lewis, et al., “Immunoglobulin complementarity-determining region grafting by recombinant polymerase chain reaction to generate humanized monoclonal antibodies”, Gene 101:297-302 (1991). [cited by applicant]
Mansoor, et al., “Determination of the in vivo redox status of cysteine, cysteinylglycine, homocysteine, and glutathione in human plasma,” Analytical Biochemistry, 200:218-229 (1992). [cited by applicant]
Marks, et al., “A Phase II Study of the Dolastatin 15 Analogue LU103793 in the Treatment of Advanced Non-Small-Cell Lung Cancer,” American Journal of Clinical Oncology, 26:336-337 (2003). [cited by applicant]
Mita, et al., “Pharmacokinetic study of aldoxorubicin in patients with solid tumors,” Investigational New Drugs, 33:341-348 (2015). [cited by applicant]
Newman, et al., “Primatization” of Recombinant Antibodies for Immunotherapy of Human Diseases: A Macaque/Human Chimeric Antibody Against Human CD4, Biotechnology 10:1455-1460 (1992). [cited by applicant]
Nollman, et al., “Abstract 2661: Novel albumin-binding maytansinoids inducing long-term partial and complete tumor regressions in several human cancer xenograft models in nude mice,” Cancer Research, 78(13) (2018) (4pag… [cited by applicant]
Nollmann et al., 11 Structure-activity relationship studies and biological evaluation of novel maytansinoids, a class of highly selective tubulin inhibitors 11, Cancer Research, 78(13)(Supplement) (2019). [cited by applicant]
Panowski, et al., “Site-specific antibody drug conjugates for cancer therapy”, mAbs, 6(1): 34-45 (2014). [cited by applicant]
Pedersen, et al, “Reactivity of the thiol group in human and bovine albumin at pH 3-9, as measured by exchange with 2,2′-dithiodipyridine,” European Journal of Biochemistry, 106(1(:291-295 (1980). [cited by applicant]
Perez, et al., “Phase II trial of dolastatin-10 in patients with advanced breast cancer,” Investigational New Drugs, 23:257-261 (2005). [cited by applicant]
Peters, “Serum albumin,” Advances in Protein Chemistry, 37:161-245 (1985). [cited by applicant]
Ponta, et al., “Tumor-preferential sustained drug release enhances antitumor activity of block copolymer micelles”, Journal of Drug Targeting, 22(7):619-628 (2014). [cited by applicant]
Pyataev, et al., “Targeted Delivery of Antitumor Chemotherapeutics: Advanced Technologies and Development Prospects,” Povolzhskiy Onkologicheskiy Vestnik, 2:60-71 (2012). [cited by applicant]
Rea, et al., “Site-specifically radioiodinated antibody for targeting tumors”, Cancer Research (Suppl.), 50:857s-861s (1990). [cited by applicant]
Rodrigues, et al., “Correlation of the acid-sensitivity of polyethylene glycol daunorubicin conjugates with their invitro antiproliferative activity”, Bioorganic & Medicinal Chemistry, 14(12):4110-4117 (2006). [cited by applicant]
Sato, et al., “Reshaping a Human Antibody to Inhibit the Interleukin 6-dependent Tumor Cell Growth”, Cancer Research 53: 851-856 (1993). [cited by applicant]
Seetharam, et al., “Aldoxorubicin therapy for the treatment of patients with advanced soft tissue sarcoma,” Future Oncology, 14(23) (12 pages) (2018). [cited by applicant]
Sogami, et al., “High-performance liquid chromatographic studies on non-mercapt in equilibrium with mercapt conversion of human serum albumin. II,” Journal of Chromatography A, 332:19-27 (1985). [cited by applicant]
Temming, et al., “Evaluation of RGD-targeted albumin earners for specific delivery of auristatin E to tumor blood vessels,” Bioconjugate Chemistry, 17(6):1385-1394 (2006). [cited by applicant]
Von Merren, et al., “Phase II trial of dolastatin-10, a novel anti-tubulin agent, in metastatic soft tissue sarcomas,” Sarcoma, 8(4):107-111 (2004). [cited by applicant]