IP Library › Granted Patent US 12,622,886
Granted Patent B2
US 12,622,886 · App. 17/792,249 · Granted May 12, 2026

Compositions comprising amino acids for prevention and/or treatment of cancer

Inventor: Paolo Luca Maria Giorgetti (Milan, IT)
Assignee: PROFESSIONAL DIETETICS S.P.A.
A61K31/198A61K31/194
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,622,886
App. No.
17/792,249
Granted
May 12, 2026
Kind
B2
Abstract

Composition for use in the prevention and/or treatment of cancer in a subject, the composition comprising an active agent, said active agent containing the amino acids leucine, isoleucine, valine, threonine, lysine and citric acid, 5succinic acid, malic acid.

Claims (20)

1 . A method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of an active agent, said active agent comprising leucine, isoleucine, valine, threonine, lysine, and citric acid, succinic acid, and malic acid, wherein the active agent is free of arginine, serine, proline, and alanine, and wherein said cancer is selected from the group consisting of adenocarcinoma, melanoma, colorectal carcinoma and breast cancer.

2 . The method according to claim 1 , wherein the weight ratio between (i) the sum of citric acid, malic acid, and succinic acid and (ii) the sum of leucine, isoleucine, valine, lysine, and threonine is comprised between 0.05 and 0.3.

3 . The method according to claim 1 , wherein the weight ratio between (i) the overall amount of citric acid, malic acid, and succinic acid and (ii) the overall amount of leucine, isoleucine, and valine is comprised between 0.1 and 0.4.

4 . The method according to claim 1 , wherein the weight ratio between (i) citric acid and (ii) the sum of malic acid and succinic acid is comprised between 1.0 and 4.0.

5 . The method according to claim 1 , wherein the citric acid: malic acid: succinic acid weight ratio is comprised between 10:1:1 and 2:1.5:1.5.

6 . The method according to claim 1 , wherein said active agent further comprises at least one amino acid selected from the group consisting of histidine, phenylalanine, methionine, tryptophan, tyrosine, and cysteine.

7 . The method according to claim 1 , wherein said active agent further comprises histidine, phenylalanine, methionine, tryptophan, and cysteine.

8 . The method according to claim 1 , wherein the ratio between (i) the overall molar amount of citric acid, malic acid, and succinic acid and (ii) the overall molar amount of methionine, phenylalanine, histidine and tryptophan is higher than 1.35.

9 . The method according to claim 1 , wherein the ratio between (i) the overall molar amount of citric acid, succinic acid, and malic acid and (ii) the overall molar amount of lysine and threonine is comprised between 0.10 and 0.70.

10 . The method according to claim 1 , wherein the weight or molar amount of citric acid is higher than the overall weight or molar amount of both malic acid and succinic acid.

11 . The method according to claim 1 , wherein the weight ratio between leucine and citric acid is comprised between 5 and 1.

12 . The method according to claim 1 , wherein said active agent further comprises histidine, phenylalanine, methionine, tryptophan, cysteine and tyrosine.

13 . The method according to claim 5 , wherein the citric acid: malic acid: succinic acid weight ratio is comprised between 7:1:1 and 1.5:1:1.

14 . The method according to claim 5 , wherein the citric acid: malic acid: succinic acid weight ratio is comprised between 5:1:1 and 3:1:1.

15 . The method according to claim 7 , wherein the ratio between 1 the overall molar amount of citric acid, succinic acid, and malic acid and (ii) the overall molar amount of lysine and threonine is comprised between 0.15 and 0.55.

16 . The method according to claim 11 , wherein the weight ratio between leucine and citric acid is comprised between 2.50 and 3.50.

17 . A method of treating breast cancer in a subject comprising administering to the subject

a) a therapeutically effective amount of an active agent, said active agent comprising leucine, isoleucine, valine, threonine, lysine, citric acid, succinic acid, and malic acid, and

b) a therapeutically effective amount of doxorubicin,

wherein the active agent and doxorubicin are administered simultaneously, separately or sequentially.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 12, 2022
From: GIORGETTI, PAOLO LUCA MARIA
To: PROFESSIONAL DIETETICS S.P.A.
Reel/Frame 060483/0777 →
Priority Claims (1)
IT 102020000000454 · Jan 13, 2020 · national
Continuity (1)
Related Publication 20230079527A1 · Mar 16, 2023
References Cited (110)
US 6537969B1 · Blass · 2003 [cited by applicant]
US 7982066B2 · Scheele · 2011 [cited by applicant]
US 9597367B2 · Wolfe et al. · 2017 [cited by applicant]
US 10226441B2 · Higashi et al. · 2019 [cited by applicant]
US 11337946B2 · Giorgetti · 2022 [cited by applicant]
US 11452702B2 · Giorgetti · 2022 [cited by applicant]
US 11957651B2 · Giorgetti · 2024 [cited by applicant]
US 12239622B2 · Giorgetti · 2025 [cited by applicant]
US 20030013761A1 · Joshi · 2003 [cited by applicant]
US 20030055099A1 · Martynyuk et al. · 2003 [cited by applicant]
US 20130084378A1 · Jun et al. · 2013 [cited by applicant]
US 20130237605A1 · Zemel · 2013 [cited by applicant]
US 20140243400A1 · Mcgill · 2014 [cited by applicant]
US 20140315788A1 · Wolfe · 2014 [cited by applicant]
US 20150335627A1 · Yue et al. · 2015 [cited by applicant]
US 20160038565A1 · Khan · 2016 [cited by applicant]
US 20180000764A1 · Hernández Miramontes · 2018 [cited by applicant]
US 20200230093A1 · Giorgetti · 2020 [cited by applicant]
US 20200253906A1 · Giorgetti · 2020 [cited by applicant]
US 20210260011A1 · Giorgetti · 2021 [cited by applicant]
US 20220110899A1 · Giorgetti · 2022 [cited by applicant]
US 20220249418A1 · Giorgetti · 2022 [cited by applicant]
US 20230067642A1 · Giorgetti · 2023 [cited by applicant]
US 20230079527A1 · Giorgetti · 2023 [cited by applicant]
CA 2972889A1 · 2016 [cited by applicant]
CN 105982914A · 2016 [cited by applicant]
EP 2196203A2 · 2010 [cited by applicant]
EP 2676664A1 · 2013 [cited by applicant]
EP 2881112A1 · 2015 [cited by applicant]
GB 2029220A · 1980 [cited by applicant]
JP H0873351A · 1996 [cited by applicant]
JP 2007161642A · 2007 [cited by applicant]
JP 6023813B2 · 2016 [cited by applicant]
WO 2001051047A · 2001 [cited by applicant]
WO 2003013487A1 · 2003 [cited by applicant]
WO 2005034932A2 · 2005 [cited by applicant]
WO 2006046746A1 · 2006 [cited by applicant]
WO 2007049818A1 · 2007 [cited by applicant]
WO 2012040707A2 · 2012 [cited by applicant]
WO 2012147901A1 · 2012 [cited by applicant]
WO 2016093104A1 · 2016 [cited by applicant]
WO 2016116580A1 · 2016 [cited by applicant]
WO 2016179657A1 · 2016 [cited by applicant]
WO 2016181335A1 · 2016 [cited by applicant]
WO 2017020121A1 · 2017 [cited by applicant]
WO 2017089612A1 · 2017 [cited by applicant]
WO 2018201024A1 · 2018 [cited by applicant]
WO 2019021135 · 2019 [cited by applicant]
WO 2019021137A1 · 2019 [cited by applicant]
WO 2019070750A1 · 2019 [cited by applicant]
WO 2019165321A1 · 2019 [cited by applicant]
WO 2020003013 · 2020 [cited by applicant]
WO 2022023932A1 · 2022 [cited by applicant]
WO 2022266480A1 · 2022 [cited by applicant]
Schafer et al. Drug Discovery Today 2008, 13 (21/22), 913-916 (Year: 2008). [cited by examiner]
Horig et al. Journal of Translational Medicine 2004, 2(44) (Year: 2004). [cited by examiner]
Bianchi et al. (Current Opinion in Cell Biology. 2020; 63:135-143) (Year: 2020). [cited by examiner]
Boshuizen et al. (Molecular Cell. 2020;78:1002-1018) (Year: 2020). [cited by examiner]
MedlinePlus. Types of Chemotherapy. https://medlineplus.gov/ency/patientinstructions/000910.htm#:˜: text=There%20are%20more%20than%20100,from%20typical%20chemotherapy%20side%20effects) (Year: 2023). [cited by examiner]
Pantuck et al. (Anesth Analg. 1989; 69: 727-731) (Year: 1989). [cited by examiner]
Bonfili et al. (The FEBS Journal. 2017; 284: 1726-1737) (Year: 2017). [cited by examiner]
Fakouri et al. (Biology. 2019;8(2): 3). (Year: 2019). [cited by examiner]
Demarco, C. MDAndersonCancerCenter.2021. 'https://www.mdanderson.org/cancerwise/adenocarcinomas--6-things-to-know-about-the--cancer-of-the-cavities.h00-159465579.html#:˜: text=That%20being%20said%2C%20chemotherapy%20is,… [cited by examiner]
International Search Report and Written Opinion of the ISA for PCT/IB2020/062301 dated Mar. 1, 2021 (12 pages). [cited by applicant]
Wang, X. et al., “Increases in mitochondrial biogenesis impair carcinogenesis at multiple levels” Molecular Oncology, Elsevier. Jul. 27, 2011., vol. 5, No. 5, pp. 399-409 (11 pages). [cited by applicant]
Abdullah, Chowdhury S. et al., “Doxorubicin-induced cardiomyopathy associated with inhibition of autophagic degradation process and defects in mitochondrial respiration”, Scientific Reports, vol. 9, No. 1, Feb. 14, 2019… [cited by applicant]
Anonymous: “Amino acid-derived therapy for Inflammatory bowel disease: L-Leucine, the branched chain amino acid, promotes NFKB-p50/p65 dimer formation, induces inflammatory gene expression downstream of RelA/p65, inhibi… [cited by applicant]
Ashida, Toshifumi et al., “Effect of Oral Administration of Isoleucine, Stimulant of Innate Immunity, in IBD Patients”, Gastroenterology, vol. 26, No. 4, Suppl 2, Apr. 1, 2004, 1 page, XP093023803, retrieved from the In… [cited by applicant]
Balaraman Kalyanaraman, “Teaching the basics of the mechanism of doxorubicin-induced cardiotoxicity: Have we been barking up the wrong tree?” Redox Biology, 29: 101394 (2020). [cited by applicant]
Beale et al., A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease No Evidence of Benefit, JAMA Neurol., 71(5), pp. 543-552, 2014. [cited by applicant]
Bournat, J.C., et al., Mitochondrial Dysfunction in Obesity Current Opinion Endocrinol Obesity, October, 17(5): 446-452, 2010. [cited by applicant]
Brocca et al., “Proteomic analysis of plasma after branched chain enriched mixture supplementation in mice”, Journal of the International Society of Sports Nutrition, vol. 10, No. 1, Apr. 3, 2013, 5 pages. [cited by applicant]
Brown et al., Mitochondrial function as a therapeutic target in heart failure, Nat Rev Cardiol., 14(4), pp. 238-250, 2017. [cited by applicant]
Chiechio, et al., “L-Acetylcarnitine: A Proposed Therapeutic Agent for Painful Peripheral Neuropathies”, Current Neuropharmacology, vol. 4, No. 3, Jul. 1, 2006, pp. 233-237 (5 pages). [cited by applicant]
Choudhury, Aaheli Roy et al., “Mitochondrial determinants of cancer health disparities”, Seminars in Cancer Biology, 47, 2017, pp. 125-146. [cited by applicant]
Daher et al., J Clin Transl Hepatol. Mar. 28, 2018;6(1 ):69-78 (Year: 2018). [cited by applicant]
Damiani, Roberto Marques et al., “Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone”, Archives of Toxicology, vol. 90, No. 9, Jun. 25, 2016, pp. 2063-2076. [cited by applicant]
Database WPI Week Apr. 4, 2007, May 3, 2007, Thomson Scientific, London, GB, XP002788927, 3 pages. [cited by applicant]
Fernández-Vizarra, et al., Tissue-specific differences in mitochondrial activity and biogenesis, Mitochondrion, vol. 11, pp. 207-213, 2011. [cited by applicant]
Gilliam, Laura A.A. et al., “The anticancer agent doxorubicin disrupts mitochondrial energy metabolism and redox balance in skeletal muscle”, Free Radical Biology and Medicine, vol. 65, Sep. 7, 2013, pp. 988-996. [cited by applicant]
Gorshinova et al., “Mitochondrial dysfunction as one of the mechanisms of impaired reproductive function in obesity.” Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2014; 7: 9-13. in Russian with English Abstract. [cited by applicant]
Green et al. (Biochmica et Biophysica Acta 1588 (2002) 94-101 (Year: 2002). [cited by applicant]
Hall et al., “Lipid Peroxidation in Brain or Spinal Cord Mitochondria After Injury” J Bioenerg. Biomembr. Apr. 2016; 48(2): 169-174 (2017). [cited by applicant]
Hiensch, Anouk E. et al., “Doxorubicin-induced skeletal muscle atrophy: Elucidating the underlying molecular pathways”, Acta Physiologica, vol. 229, No. 2, Oct. 10, 2019, 18 pp. [cited by applicant]
Keenan et al.,, “Effects of carboxylic acids on the uptake of non-transferrin-bound iron by astrocytes, Neurochemistry International”, 2010, 56: 843-849. [cited by applicant]
Kim, Yun-Gi et al., “Neonatal acquisition of [cited by applicant]
Liu, Yulan et al., “Roles of amino acids in preventing and treating intestinal diseases: recent studies with pig models”, Amino Acids, vol. 49, No. 8, Jun. 14, 2017, pp. 1277-1291. [cited by applicant]
Ma et al., Inhibition of AMP-Activated Protein Kinase Signaling Alleviates Impairments in Hippocampal Synaptic Plasticity Induced by Amyloid, The Journal of Neuroscience, 34(36), 12230-12238, Sep. 3, 2014. [cited by applicant]
Mao, Xiangbing et al., “I-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats”, Frontiers in Immunology, vol. 12, Article 817583, Jan. 11, 2022, 12 pages. [cited by applicant]
MP Biomedical—Technical Information—AIN-93-Diet,pp. 1-3 (Year: 2023). [cited by applicant]
Nakagaichi, M., et al., “Effects of Exercise Training Plus Vespa Amino Acid Mixture (VAAM) Ingestion in Obese Women,” Japanese Journal of Health Promotion, 3, Nov. 16, 2001 with English Abstract. [cited by applicant]
Nakamura, E., et al., “Assessment of Biological Age by Principal Component Analysis,” Mechanisms of Ageing and Development, vol. 46. Issues1-3, pp. 1-18, 1988, with English Translation of Office Action for JP Applicatio… [cited by applicant]
Nergiz et al.; “Organic acid content and composition of the olive fruits during ripening and its relationship with oil and sugar”; 2009; Scientia Horticulturae; 122: 216-220 (Year: 2009). [cited by applicant]
Rao et al., Mitochondrial permeability transition pore is a potential drug target for neurodegeneration, Biochimica et Biophysica Acta, 1267-1272, 2014. [cited by applicant]
Sbodio et al., Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities, Antioxidants & Redox Signaling, vol. 30, No. 11, pp. 1450-1499, 2019. [cited by applicant]
Scholpa & Schnellmann, “Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target.” J Pharmacol Exp Ther 363:303-313, Dec. 2017. [cited by applicant]
Short et al., Decline in skeletal muscle mitochondrial function with aging in humans, PNAS, vol. 102, No. 15, pp. 5618-5623, Apr. 12, 2005. [cited by applicant]
Sprong et al., “Dietary cheese whey protein protects rats against mild dextran sulfate sodium-induced colitis: Role of mucin and microbiota”, Journal of Dairy Science, vol. 93, No. 4, Apr. 1, 2010, pp. 1364-1371. [cited by applicant]
Sullivan et al., “Mitochondrial Permeability Transition in CNS Trauma: Cause or Effect of Neuronal Cell Death?” Journal of Neuroscience Research, 2005, 79:231-239. [cited by applicant]
Sun et al., The Mitochondrial Basis of Aging, Mol Cell., 61(5), pp. 654-666, Mar. 3, 2016. [cited by applicant]
Tapper et al., JAMA. 2023;329(18):1589-1602 (Year: 2023). [cited by applicant]
Tedesco et al., A specific amino acid formula prevents alcoholic liver disease in rodents, Am J Physiol Gastrointest Liver Physiol ., Epub Jan. 25, 2018, 314(5):G566-G582. [cited by applicant]
Vingtdeux et al., AMPK is abnormally activated in tangle- and pre-tangle-bearing neurons in Alzheimer's disease and other tauopathies, Acta Neuropathol, vol. 121, pp. 337-349, 2010. [cited by applicant]
Wang et al., “Mitochondrial dysfunction in neurodegenerative diseases and the potential countermeasure,” CNS Neurosci Ther. 25: 816-824 (2019). [cited by applicant]
Westermann et al., Mitochondrial fusion and fission in cell life and death, Molecular Cell Biology, vol. 11, 13 pages, Dec. 2010. [cited by applicant]
Youle et al., Mitochondrial Fission, Fusion, and Stress, Science, 337(6098), pp. 1062-1065, Aug. 31, 2012. [cited by applicant]
Xu et al., “mTOR signaling in tumorigenesis” Biochim Biophys Acta. Dec. 2014 ; 1846(2): 638-654. [cited by applicant]
Moberg et al., “Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise,” Am J Physiol Cell Physiol 310: C874-C884, 2016. [cited by applicant]
Lee et al., “Mitochondrial DNA plasticity is an essential inducer of tumorigenesis,” Cell Death Discovery (2016) 2, 16016; 11 pages. [cited by applicant]
U.S. Appl. No. 18/878,129; first inventor: Giorgetti, 371(c) date Dec. 23, 2024. [cited by applicant]