IP Library Granted Patent US 12,478,601
Granted Patent B2
US 12,478,601 · App. 18/174,706 · Granted Nov 25, 2025

Dietary product devoid of at least two non essential amino acids

Inventors: Oliver D. K. Maddocks (Glasgow, GB); Karen Vousden (Glasgow, GB)
Assignee: Cancer Research Technology Limited
A61K31/198A61K9/0056A61K9/0095A61K45/06A61P35/00
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 12,478,601
App. No.
18/174,706
Granted
Nov 25, 2025
Kind
B2
Abstract

The present invention relates to a dietary product comprising a plurality of amino acids, wherein the dietary product comprises all the essential amino acids and wherein the dietary product is substantially devoid of at least two non-essential amino acids; methods and uses thereof in the treatment of cancer; stratification methods and biomarkers for such applications.

Claims (27)

1 . A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject:

(a) a therapeutically effective amount of a dietary product,

wherein the dietary product comprises a plurality of amino acids or salts thereof, wherein the plurality of amino acids or salts thereof comprises methionine or a salt thereof, leucine or a salt thereof, phenylalanine or a salt thereof, isoleucine or a salt thereof, valine or a salt thereof, lysine or a salt thereof, threonine or a salt thereof, histidine or a salt thereof, and tryptophan or a salt thereof,

wherein the dietary product is substantially a sole source of exogenous amino acids consumed by the subject, and

wherein the dietary product is devoid of glycine, serine, and proline, and salts, prodrugs, homodimers, heterodimers, and esters of glycine, serine and proline; and

(b) a therapeutically effective amount of one or more therapeutic agents; wherein the cancer consumes exogenous serine and is characterized by phosphoglycerate dehydrogenase (PHGDH) expression reduced relative to non-cancerous tissue, wherein the cancer is colorectal cancer, pancreatic cancer, intestinal cancer, lymphoma, or breast cancer.

2 . The method of claim 1 , wherein the dietary product comprises at least 12 amino acids, salts of the at least 12 amino acids, or a combination of 12 amino acids or salts of the at least 12 amino acids.

3 . The method of claim 1 , wherein the dietary product further comprises alanine or a salt thereof, arginine or a salt thereof, aspartic acid or a salt thereof, asparagine or a salt thereof, cysteine or a salt thereof, glutamine or a salt thereof, glutamic acid or a salt thereof, or tyrosine or a salt thereof.

4 . The method of claim 1 , wherein the dietary product is formulated as a solid, a powder, a liquid, a beverage, or an enteral nutritional product.

5 . The method of claim 1 , wherein the one or more therapeutic agents comprise one or more chemotherapeutic agents.

6 . The method of claim 5 , wherein the one or more chemotherapeutic agents comprise gemcitabine.

7 . The method of claim 5 , wherein the one or more chemotherapeutic agents comprise bevacizumab.

8 . The method of claim 5 , wherein the one or more chemotherapeutic agents comprise oxaliplatin.

9 . The method of claim 5 , wherein the one or more chemotherapeutic agents comprise paclitaxel or nab-paclitaxel.

10 . The method of claim 5 , wherein the one or more chemotherapeutic agents comprise capecitabine.

11 . The method of claim 5 , wherein the one or more chemotherapeutic agents comprise 5-fluorouracil.

12 . The method of claim 5 , wherein the one or more chemotherapeutic agents comprise irinotecan.

13 . The method of claim 1 , wherein the one or more therapeutic agents comprise radiotherapy or a radiotherapeutic agent.

14 . The method of claim 1 , wherein the cancer has reduced expression or reduced activity of one or more of phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH).

15 . The method of claim 1 , wherein the cancer is a solid tumor.

16 . The method of claim 1 , wherein the cancer is lymphoma.

17 . The method of claim 1 , wherein the cancer is colorectal cancer.

18 . The method of claim 1 , wherein the cancer is pancreatic cancer.

19 . The method of claim 1 , wherein the method results in inhibition of cancer cell proliferation in the subject.

20 . The method of claim 1 , wherein the cancer is characterized by PHGDH expression reduced by at least about 30% relative to non-cancerous tissue.

21 . The method of claim 1 , wherein the cancer is intestinal cancer.

22 . The method of claim 1 , wherein the cancer is breast cancer.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 27, 2023
From: MADDOCKS, OLIVER; VOUSDEN, KAREN
To: CANCER RESEARCH TECHNOLOGY LIMITED
Reel/Frame 065051/0301 →
Priority Claims (2)
GB 1603098 · Feb 23, 2016 · national
GB 1609441 · May 27, 2016 · national
Continuity (2)
Continuation 15999666
Related Publication 20230277492A1 · Sep 7, 2023
References Cited (208)
US 3832465A · Ghadimi · 1974 [cited by applicant]
US 4734401A · Blouin · 1988 [cited by applicant]
US 4988724A · Ajani et al. · 1991 [cited by applicant]
US 6218420B1 · Dioguardi · 2001 [cited by applicant]
US 6713501B1 · Walser · 2004 [cited by applicant]
US 10973251B1 · Li et al. · 2021 [cited by applicant]
US 11241407B2 · Li et al. · 2022 [cited by applicant]
US 12042477B2 · Maddocks et al. · 2024 [cited by applicant]
US 12109184B2 · Maddocks · 2024 [cited by applicant]
US 12220402B2 · Maddocks · 2025 [cited by applicant]
US 20030129262A1 · Epner et al. · 2003 [cited by applicant]
US 20060280840A1 · Robertson · 2006 [cited by applicant]
US 20070270355A1 · Garcia et al. · 2007 [cited by applicant]
US 20070286909A1 · Smith et al. · 2007 [cited by applicant]
US 20080317886A1 · Sparkman · 2008 [cited by applicant]
US 20110118528A1 · Longo et al. · 2011 [cited by applicant]
US 20110153221A1 · Stefanon et al. · 2011 [cited by applicant]
US 20130123363A1 · Uesugi et al. · 2013 [cited by applicant]
US 20140087970A1 · Possemato · 2014 [cited by examiner]
US 20140100357A1 · Miao et al. · 2014 [cited by applicant]
US 20140170259A1 · Poels et al. · 2014 [cited by applicant]
US 20140363417A1 · Cheng et al. · 2014 [cited by applicant]
US 20150315561A1 · Schabbauer et al. · 2015 [cited by applicant]
US 20170143025A1 · Rason et al. · 2017 [cited by applicant]
US 20200230092A1 · Maddocks et al. · 2020 [cited by applicant]
US 20200281243A1 · Hannon et al. · 2020 [cited by applicant]
US 20220054444A1 · Maddocks · 2022 [cited by applicant]
US 20220117943A1 · Maddocks · 2022 [cited by applicant]
US 20220193447A1 · Maddocks et al. · 2022 [cited by applicant]
US 20220400730A1 · Li et al. · 2022 [cited by applicant]
US 20250020651A1 · Maddocks et al. · 2025 [cited by applicant]
JP 2005289938A · 2005 [cited by applicant]
JP 2009519942A · 2009 [cited by applicant]
JP 2014512803A · 2014 [cited by applicant]
WO WO9802441A2 · 1998 [cited by applicant]
WO WO0114387A1 · 2001 [cited by applicant]
WO WO2006043090A1 · 2006 [cited by applicant]
WO WO2009077766A1 · 2009 [cited by applicant]
WO WO2010075007A3 · 2010 [cited by applicant]
WO WO2011092469A1 · 2011 [cited by applicant]
WO WO2011143579A2 · 2011 [cited by applicant]
WO WO2012116229A2 · 2012 [cited by examiner]
WO WO2014049566A2 · 2014 [cited by applicant]
WO WO2015075483A1 · 2015 [cited by applicant]
WO WO2016130918A1 · 2016 [cited by applicant]
WO 2017053328A1 · 2017 [cited by applicant]
WO WO2017144877A1 · 2017 [cited by applicant]
WO WO2018071873A2 · 2018 [cited by applicant]
WO WO2019092455A1 · 2019 [cited by applicant]
WO WO2019118519A1 · 2019 [cited by applicant]
WO WO2019118549A1 · 2019 [cited by applicant]
WO WO2019211605A1 · 2019 [cited by applicant]
WO WO2021016132A1 · 2021 [cited by applicant]
WO WO2021247724A1 · 2021 [cited by applicant]
WO WO2021247923A1 · 2021 [cited by applicant]
WO WO2022015951A2 · 2022 [cited by applicant]
WO WO2022132981A1 · 2022 [cited by applicant]
WO WO2023023147A1 · 2023 [cited by applicant]
WO WO2023130140A2 · 2023 [cited by applicant]
WO WO2024105276A1 · 2024 [cited by applicant]
Locasale (Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 13, 572-583 (2013). https://doi.org/10.1038/nrc3557) (Year: 2013). [cited by examiner]
“Anonymous. ClinicalTrials.gov Archive. NCT02337894 on Jan. 13, 2015”, Retrieved from the Internet: https://clinicaltrials.gov/archive/NCT. Retrieved on Apr. 2, 2017. 5 pages. [cited by applicant]
“Institute of Medicine, Food and Nutrition Board. (Dietary reference intakes for water, potassium, sodium, chloride, and sulfate”, Washington, DC: National Academy Press, 2005. [cited by applicant]
“International Search Report and Written Opinion, PCT/GB2017/050458, mailed Jul. 18, 2017, 20 pages.” [cited by applicant]
“Search Report, Intellectual Property Office, United Kingdom Application No. GB1609441.9, Mar. 1, 2017, 5 pages.” [cited by applicant]
Bartlett, David L., et al., “Effect of growth hormone and protein intake on tumor growth and host cachexia”, Surgery, 1995, vol. 117, No. 3, pp. 260-267. [cited by applicant]
Bunz F , et al., “Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. Nov. 1998; 282: 1497-1501.” [cited by applicant]
Kshattry, Sabin , et al., “Abstract 367: Assessing the therapeutic efficacy of Cyst(e)inase to induce oxidative stress mediated cytotoxicity in pancreatic cancer cells”, Experimental and Molecular Therapeutics, 4 pages,… [cited by applicant]
Labuschagne CF , et al., “Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Reports 7, 1248-1258, May 22, 2014.” [cited by applicant]
Lancha, Jr., A.H. , “Effect of Aspartate, Asparagine, and Carnitine Supplementation in the Diet on Metabolism of Skeletal Muscle During a Moderate Exercise”, Physiol Behav. Feb. 1995;57(2, 1995, 367-371. [cited by applicant]
Lopez-Lazaro, M. , “Selective amino acid restriction therapy (SAART): a non-pharmacological strategy against all types of cancer cells.”, Oncoscience, 2015, 857-866. [cited by applicant]
Maddocks Odk , et al., “Serine metabolism supports the methionine cycle and DNR/RNA methylation through de novo ATP synthesis in cancer cells.”, Molecular Cell, 2016, 210-221. [cited by applicant]
Maddocks Odk , et al., “Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. Dec. 2013; 493(7433): 542-546.” [cited by applicant]
McCormack, William P., et al., “Oral nutritional supplement fortified with beta-alanine improves physical working capacity in older adufts: A randomized, placebo-controlled study”, Expiremental Gerontology 48.9, 2013, 9… [cited by applicant]
Okada, Kenzo , et al., “Tumor glutamine level is negatively correlated with tumor weight in tumor-bearing rats administered a glutamine antagonist and a new imbalanced amino acid solution”, Journal of Clinical Biochemis… [cited by applicant]
Paddon-Jones, Douglas , et al., “Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein”, Expiremental Gerontology, 2006. [cited by applicant]
Polet F , et al., “Reducing the serine availability complements the inhibition of the glutamine metabolism to block leukemia cell growth. Oncotarget. Jan. 2016; 7(2): 1765-1776.” [cited by applicant]
Rose WC , et al., “Growth on diets devoid of glycine, serine, and cystine, and low in choline”, J Biol Chem. 1952, 1952, 194: 321-328. [cited by applicant]
Mgneron AM , et al., “Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP. Genes & Development. 2010; 24: 2430-2439.” [cited by applicant]
Wernerman, Jan , “Clinical Use of Glutamine Supplementation”, Nutr. 2008, 2008, 2040S-2044S. [cited by applicant]
Zhang, Wan , et al., “Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia”, Nature Cell Biology, 14(3), 2012, 276-286. [cited by applicant]
Miyo, Masaaki, et al., “Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer”, Scientific Reports 6:38415, 2016 (13 pages). [cited by applicant]
Solerte, Sebastiano B., et al., “Metabolic Effects of Orally Administered Amino Acid Mixture in Elderly Subjects with Poorly Controlled Type 2 Diabetes Mellitus”, American Journal of Cardiology. 93:23A-29A, 2004. [cited by applicant]
Adams et al., “The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice” Nature (1985) 318:533-538. [cited by applicant]
Amelio et al., “Serine and glycine metabolism in cancer” Trends Biochem Sci. (2014) Apr. 39(4):191-198. [cited by applicant]
Badgley et al., “Absract A41: Leveraging metabolic dependencies in cancer: Cystein addiction in pancreatic cancer cells” Mol Cancer Research (2016) 14(1_Supp): A41, 4 pages. [cited by applicant]
Barker et al., “Crypt stem cells as the cells-of-origin of intestinal cancer” Nature (2009) 457:608-611. [cited by applicant]
Bertino et al., “Targeting tumors that lack methylthioadenosine phosphorylase (MTAP) activity: current strategies” Cancer Biol Ther. Apr. 1, 2011; 11(7):627-632. [cited by applicant]
Commisso et al., “Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells” Nature (2013) 497:633-637. [cited by applicant]
Corsetti et al., “Protect and Counter-attack: Nutritional Supplementation with Essential Amino acid Ratios Reduces Doxorubicin-induced Cardiotoxicity in vivo and promote Cancer Cell Death in vitro” J. Cytol. Histol. (20… [cited by applicant]
Donehower, et al. “Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours”, Nature, Mar. 19, 1992, pp. 215-221, vol. 356. [cited by applicant]
Dredge, K et al., “The polyamine analog PG11047 potentiates the antitumor activity of cisplatin and bevacizumab in preclinical models of lung and prostate cancer” Cancer Chemother Pharmacol. 65, 191-195 (2009). [cited by applicant]
Fiatarone et al., “Exercise training and nutritional supplementation for physical frailty in very elderly people” N. Engl. J. Med. Jun. 23, 1994; 330(25):1769-75. [cited by applicant]
Fiatarone Singh et al., “The effect of oral nutritional supplements on habitual dietary quality and quantity in frail elders” J. Nutr. Health Aging (2000) 4(1):5-12. [cited by applicant]
Final Office Action mailed on Aug. 10, 2023, for U.S. Appl. No. 17/338,283, filed Jun. 3, 2021, 14 pages. [cited by applicant]
Final Office Action mailed on Sep. 22, 2021, for U.S. Appl. No. 15/999,666, filed Aug. 20, 2018, 11 pages. [cited by applicant]
Final Office Action mailed on Sep. 2, 2022, for U.S. Appl. No. 15/999,666, filed Aug. 20, 2018, 13 pages. [cited by applicant]
Finkelstein et al., “Methionine metabolism in mammals. The methionine-sparing effect of cystine” J Biol Chem. 263(24):11750-11754 (1998). [cited by applicant]
Geck et al., “Nonessential amino acid metabolism in breast cancer” Advances in Biological Regulation (2016) 62:11-17. [cited by applicant]
Gravel et al., “Serine deprivation enhances antineoplastic activity of biguanides” Cancer Res. Dec. 15, 2014; 74(24):7521-7533. [cited by applicant]
Hingorani et al., “Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice” Cancer Cell (2005) 7:469-483. [cited by applicant]
Hirakawa et al., “Comparative utilization of a crystalline amino acid diet and a methionine-fortified casein diet by young rats and mice” Nutr Res (1984) 4(5):891-895. [cited by applicant]
Institute of Medicine, “Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids” Chapters 6, 7, and 8, Sep. 2002, 323 pages. [cited by applicant]
International Search Report and Written Opinion issued in PCT/2021/35780 on Oct. 1, 2021. 11 pages. [cited by applicant]
International Search Report and Written Opinion mailed on Apr. 11, 2022, for PCT/US2021/063639, filed on Dec. 15, 2021, 8 pages. [cited by applicant]
International Search Report and Written Opinion mailed on Jun. 26, 2023, for PCT/US2023/60025, filed on Jan. 3, 2023, 9 pages. [cited by applicant]
International Search Report and Written Opinion issued in PCT/US2021/035476 on Oct. 12, 2021. 10 pages. [cited by applicant]
Labadie et al., “Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan-Kynurenine-Aryl Hydrocarbon Axis” Clin Cancer Res. Mar. 1, 2019; 25(5):1462-1471. [cited by applicant]
Morton et al., “Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer” PNAS USA (2010) 107:246-251. [cited by applicant]
Moser et al., “A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse” Science (1990) 322-324. [cited by applicant]
Nas. IOM. Food and Nutrition Board, “Dietary Reference Intakes: RDA and AI for Vitamins and Elements” (2017) 3 pages. [cited by applicant]
Non-Final Office Action mailed on Mar. 18, 2021, for U.S. Appl. No. 15/999,666, filed Aug. 20, 2018, 8 pages. [cited by applicant]
Non-Final Office Action mailed on May 10, 2023, for U.S. Appl. No. 15/999,666, filed Aug. 20, 2018, 12 pages. [cited by applicant]
Non-Final Office Action mailed on Jan. 5, 2023, for U.S. Appl. No. 17/338,283, filed Jun. 3, 2021, 14 pages. [cited by applicant]
Paddon-Jones et al., “Amino acid ingestion improves muscle protein synthesis in the young and elderly” Am J Physiol Endocrinol Metab. Mar. 2004; 286(3):E321-E328. [cited by applicant]
Partial European Search Report mailed on Sep. 20, 2023, for EP Application No. EP 23151551.1, 23 pages. [cited by applicant]
PCT/US2021/035780 International Preliminary Report on Patentability (Chapter I) dated Dec. 6, 2022. 9 Pages. [cited by applicant]
Possemato et al., “Functional genomics reveal that the serine synthesis pathway is essential in breast cancer” Nature Aug. 18, 2011; 476(7360):346-350. [cited by applicant]
Ran et al., “Genome engineering using the CRISPR-Cas9 system” Nat Protoc. Nov. 2013; 8(11):2281-2308. [cited by applicant]
Sahu et al., “Proline Starvation Induces Unresolved ER Stress and Hinders mTORC1-Dependent Tumorigenesis” Cell Metabolism (2016) 24:753-761. [cited by applicant]
Snezhkina, A.V. et al., “The Dysregulation of Polyamine Metabolism in Colorectal Canceris Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection” Oxid Med Cell Long… [cited by applicant]
Su et al., “Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene” Science (1992) 256:668-670. [cited by applicant]
Tang et al., “Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas” Cancer Res. Apr. 1, 2016; 76(7):1892-1903. [cited by applicant]
Trumbo et al., “Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids” J Am Diet Assoc. Nov. 2002;102(11):1621-1630. [cited by applicant]
Walpole et al., “The weight of nations: an estimation of adult human biomass” BMC Public Health. Jun. 18, 2012; 12:439. [cited by applicant]
Ying et al., “Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism” Cell (2012) 149:656-670. [cited by applicant]
Zhang et al., “Application of Holistic Liquid Chromatography-High Resolution Mass Spectrometry Based Urinary Metabolomics for Prostate Cancer Detection and Biomarker Discovery” PLoS One (2013) 8(6):e65880, 10 pages. [cited by applicant]
Zhang et al., “Polyamine pathway activity promotes cysteine essentiality in cancer cells” Nature Metabolism (2020) 2:1062-1076, 27 pages. [cited by applicant]
Non-Final Office Action mailed on Feb. 23, 2024, for U.S. Appl. No. 17/338,283, filed Jun. 3, 2021, 13 pages. [cited by applicant]
Non-Final Office Action mailed on Mar. 29, 2024, for U.S. Appl. No. 17/337,077, filed Jun. 2, 2021, 14 pages. [cited by applicant]
Notice of Allowance mailed on Apr. 12, 2024, for U.S. Appl. No. 15/999,666, filed Aug. 20, 2018, 11 pages. [cited by applicant]
Notice of Allowance mailed on Jan. 4, 2024, for U.S. Appl. No. 15/999,666, filed Aug. 20, 2018, 12 pages. [cited by applicant]
Notice of Allowance mailed on May 9, 2024, for U.S. Appl. No. 15/999,666, filed Aug. 20, 2018, 9 pages. [cited by applicant]
Bassiri et al., “Translational development of difluoromethylornithine (DFMO) for the treatment of neuroblastoma” Transl Pediatr. Jul. 2015; 4(3):226-238. [cited by applicant]
Blau et al., eds., “Laboratory Guide to the Methods in Biochemical Genetics” (2008) Berlin Heidelberg, Germany: Springer Verlag. p. 74. 59 pages. [cited by applicant]
Butler et al., “Amino Acid Depletion Therapies: Starving Cancer Cells to Death,” Trends in Endocrinology and Metabolism Jun. 2021;32(6):367-381. [cited by applicant]
CAS Registry No. 1036730-42-3, STN entry date: Jul. 28, 2008, Pidilizumab, 1 page. [cited by applicant]
CAS Registry No. 1374853-91-4, STN entry date: May 31, 2012, Pembrolizumab, 1 page. [cited by applicant]
CAS Registry No. 1380723-44-3, STN entry date: Jul. 3, 2012, Atezolizumab, 1 page. [cited by applicant]
CAS Registry No. 1428935-60-7, STN entry date: Apr. 23, 2013, Durvalumab, 1 page. [cited by applicant]
CAS Registry No. 1537032-82-8, STN entry date: Feb. 4, 2014, Avelumab, 1 page. [cited by applicant]
CAS Registry No. 1801342-60-8, STN entry date: Aug. 4, 2015, Cemiplimab, 1 page. [cited by applicant]
CAS Registry No. 477202-00-9, dated Dec. 19, 2002, 1 page. [cited by applicant]
CAS Registry No. 70052-12-9, STN entry date: Nov. 16, 1984, Eflornithine, 2 pages. [cited by applicant]
CAS Registry No. 946414-94-4, STN entry date: Sep. 7, 2007, Nivolumab, 1 page. [cited by applicant]
CAS Registry No. 96020-91-6, STN entry date: Apr. 21, 1985, Ornithine, 1 page. [cited by applicant]
Casero Jr. et al., “Polyamine metabolism and cancer: treatments, challenges and opportunities,” Nature Reviews Cancer. Nov. 2018; 18(11):681-695. [cited by applicant]
Cavuoto et al., “A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension” Cancer Treatment Reviews Oct. 2012; 38(6):726-736. [cited by applicant]
Doxsee et al., “Sulfasalazine-Induced Cystine Starvation: Potential Use for Prostate Cancer Therapy” Prostate Feb. 1, 2007; 67(2):162-171. [cited by applicant]
Extended European Search Report for EP Application No. 21907754.2 mailed on Oct. 16, 2024, 13 pages. [cited by applicant]
Extended European Search Report mailed on Feb. 1, 2024, for EP Application No. 23151551.1, 27 pages. [cited by applicant]
Extended European Search Report mailed on Sep. 18, 2023, for EP Application No. 23166882.3, 11 pages. [cited by applicant]
Faubert et al., “Stable isotope tracing to assess tumor metabolism in vivo” Nat Protoc. Nov. 2021; 16(11):5123-5145. [cited by applicant]
Fu et al., “Specific amino acid dependency regulates invasiveness and viability of androgen-independent prostate cancer cells” Nutr Cancer. (2003) 45(1):60-73. [cited by applicant]
Ge et al., “Activation of caspases and cleavage of Bid are required for tyrosine and phenylalanine deficiency-induced apoptosis of human A375 melanoma cells” Arch Biochem Biophys. Jul. 1, 2002; 403(1):50-58. [cited by applicant]
Harenza et al., “Transcriptomic profiling of 39 commonly-used neuroblastoma cell lines” Sci Data. Mar. 28, 2017: 4:170033. 8 pages. [cited by applicant]
Hogarty et al., “ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma” Cancer Res. Dec. 1, 2008; 68(23):9735-9745. [cited by applicant]
Holbert et al., “Polyamines in cancer: integrating organismal metabolism and antitumour immunity” Nat Rev Cancer Aug. 22, 2022; (8):467-480. [cited by applicant]
Hui et al., “Glucose feeds the TCA cycle via circulating lactate” Nature. Nov. 2, 2017; 551(7678):115-118. [cited by applicant]
Hui et al., “Quantitative Fluxomics of Circulating Metabolites” Cell Metab. Oct. 6, 2020; 32(4):676-688. e4. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/040588, mailed on Jan. 4, 2023, 14 pages. [cited by applicant]
Klement, “Fasting, Fats, and Physics: Combining Ketogenic and Radiation Therapy against Cancer” Complement Med Res. (2018) 25(2):102-113. [cited by applicant]
Kocak et al., “Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma” Cell Death Dis. Apr. 11, 2013; 4(4):e586. 11 pages. [cited by applicant]
Lewis et al., “A subset analysis of a phase II trial evaluating the use of DFMO as maintenance therapy for high-risk neuroblastoma” Int J Cancer. Dec. 1, 2020; 147(11):3152-3159. [cited by applicant]
Liberzon et al., “Molecular signatures database (MSigDB) 3.0” Bioinformatics. Jun. 15, 2011; 27(12):1739-1740. [cited by applicant]
Logiudice et al., “Alpha-Difluoromethylornithine, an Irreversible Inhibitor of Polyamine Biosynthesis, as a Therapeutic Strategy against Hyperproliferative and Infectious Diseases” Med Sci (Basel). Feb. 8, 2018; 6(1):12… [cited by applicant]
Mustafa J., et al., “Dietary Protein and Preservation of Physical Functioning Among Middle-Aged and Older Adults in the Framingham Offspring Study,” American Journal of Epidemiology (2018) 187(7):1411-1419. 37 pages. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 17/337,077 mailed Sep. 30, 2024, 10 pages. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 17/338,283 mailed Aug. 13, 2024, 6 pages. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 17/338,283 mailed Jul. 17, 2024, 9 pages. [cited by applicant]
Rounbehler et al., “Targeting ornithine decarboxylase impairs development of MYCN-amplified neuroblastoma” Cancer Res. Jan. 15, 2009; 69(2):547-553. [cited by applicant]
Sanchez-Castillo et al., “Linking Serine/Glycine Metabolism to Radiotherapy Resistance” Cancers Mar. 10, 2021; 13(6):1191, 25 pages. [cited by applicant]
Sholler et al., “A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma” PLoS One. May 27, 2015;10(5):e0127246. 20 pages. [cited by applicant]
Sholler et al., “Maintenance DFMO Increases Survival in High Risk Neuroblastoma” Sci Rep. Sep. 27, 2018; 8(1):14445. 9 pages. [cited by applicant]
Soldin et al., “Pediatric reference ranges” 3rd ed., Washington: AACC Press, (1999) pp. 11-20. [cited by applicant]
Su et al., “Metabolite Spectral Accuracy on Orbitraps” Anal Chem. Jun. 6, 2017; 89(11):5940-5948. [cited by applicant]
Tajan et al., “Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy” Nat Commun. Jan. 14, 2021; 12(1):366. 16 pages. [cited by applicant]
Uniprot P01137, Sep. 13, 2023, 14 pages. [cited by applicant]
Uniprot P14784, Sep. 13, 2023, 7 pages. [cited by applicant]
Uniprot P16410, Sep. 13, 2023, 11 pages. [cited by applicant]
Uniprot P25942, Sep. 13, 2023, 8 pages. [cited by applicant]
Uniprot P43489, Sep. 13, 2023, 6 pages. [cited by applicant]
Uniprot Q07011, Sep. 13, 2023, 6 pages. [cited by applicant]
Uniprot Q15116, Sep. 13, 2023, 9 pages. [cited by applicant]
Uniprot Q495A1, Sep. 13, 2023, 5 pages. [cited by applicant]
Uniprot Q5ZPR3, Sep. 13, 2023, 9 pages. [cited by applicant]
Uniprot Q8TDQ0, Sep. 13, 2023, 9 pages. [cited by applicant]
Uniprot Q9H7M9, Sep. 13, 2023, 7 pages. [cited by applicant]
Uniprot Q9NZQ7, Sep. 13, 2023, 9 pages. [cited by applicant]
Uniprot Q9Y6W8, Sep. 13, 2023, 4 pages. [cited by applicant]
Wang et al., “Peak Annotation and Verification Engine for Untargeted LC-MS Metabolomics” Anal Chem. Feb. 5, 2019; 91(3):1838-1846. [cited by applicant]
Weiss et al. “Targeted Expression of MYCN Causes Neuroblastoma in Transgenic Mice”, The EMBO Journal (1997), 16(11):2985-2995. [cited by applicant]
Wu et al., “Dietary protein intake and human health” Food Funct. Mar. 2016; 7(3):1251-1265. [cited by applicant]
Yan et al., “Effects of complex unbalanced amino acids on tumors in mice bearing liver cancer H22” Chinese Journal of Clinical Oncology (2011) 38(3):134-137. [cited by applicant]
Yan et al., “Effects of complex unbalanced amino acids on tumors in mice bearing liver cancer H22” Chinese Journal of Clinical Oncology (2011) 38(3):134-137 (with full English Translation). 8 total pages. [cited by applicant]
ClinicalTrials.gov ID NCT05078775 “Medical Food for the Dietary Management of Advanced/Metastatic Pancreatic Cancer” Sponsor: Faeth Therapeutics, Version 1 (Jan. 10, 2021) 17 pages. [cited by applicant]
ClinicalTrials.gov ID NCT05078775 “Medical Food for the Dietary Management of Advanced/Metastatic Pancreatic Cancer” Sponsor: Faeth Therapeutics, Version 11 (Jul. 17, 2025) 8 pages. [cited by applicant]
ClinicalTrials.gov ID NCT05183295 “Medical Food for the Dietary Management of Metastatic Colorectal Cancer” Sponsor: Faeth Therapeutics, Version 1 (Dec. 21, 2021) 18 pages. [cited by applicant]
ClinicalTrials.gov ID NCT05183295 “Medical Food for the Dietary Management of Metastatic Colorectal Cancer” Sponsor: Faeth Therapeutics, Version 6 (Mar. 30, 2023) 8 pages. [cited by applicant]
ClinicalTrials.gov ID NCT06380101 “Evaluating a Nonessential Amino Acid Restriction (NEAAR) Medical Food With Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer (LARC) (NEAAR-LARC)” Sponsor: University of Sout… [cited by applicant]
Extended European Search Report for European Application No. 22859101.2 mailed May 14, 2025, 11 pages. [cited by applicant]
Falcone et al., “Sensitisation of cancer cells to radiotherapy by serine and glycine starvation” Br J Cancer. Nov. 2022; 127(10):1773-1786. [cited by applicant]
International Search Report and Written Opinion for PCT Application No. PCT/US2025/022127 mailed Jun. 12, 2025, 11 pages. [cited by applicant]
Javle et al., “Bevacizumab combined with gemcitabine and capecitabine for advanced pancreatic cancer: a phase II study” Br J Cancer. Jun. 16, 2009; 100(12):1842-1845. [cited by applicant]
Lito et al., “Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism” Science. Feb. 5, 2016; 351(6273):604-608. [cited by applicant]
Loree, J.M., et al., “Survival Impact of CAPOX Versus FOLFOX in the Adjuvant Treatment of Stage III Colon Cancer” Clinical Colorectal Cancer (2018) vol. 17(2):156-163. [cited by applicant]
Onivyde™ (irinotecan liposome injection), accessdata.fda.gov, Oct. 2015, prescribing information drug label for intravenous use, Injection: 43 mg/10 mL single dose vial, Initial U.S. Approval: 1996, Reference ID: 383676… [cited by applicant]
Safran et al., “Folfox+Nab-Paclitaxel (Folfox-A) for Advanced Pancreatic Cancer: A Brown University Oncology Research Group Phase I Study” Am J Clin Oncol. Dec. 2016; 39(6):619-622. [cited by applicant]