IP Library › Granted Patent US 12,297,406
Granted Patent B2
US 12,297,406 · App. 17/613,886 · Granted May 13, 2025

Method for preparing a composition comprising cetylated fatty acids

Inventors: Andrea Lacorte (Pisa, IT); Germano Tarantino (Pisa, IT); Elisa Brilli (Pisa, IT)
Assignees: ALESCO S.R.L.; PHARMANUTRA S.P.A.
C11C3/003C07C67/08C11C1/08
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 12,297,406
App. No.
17/613,886
Granted
May 13, 2025
Kind
B2
Abstract

A composition is described comprising a mixture of at least one cetylated fatty acid or a mixture of cetylated fatty acids and an antioxidant in reduced percentages by weight, and related methods for treatment of arthritis and of inflammatory joint and musculoskeletal pain. Furthermore a composition is described comprising a mixture of at least one cetylated fatty acid or a mixture of cetylated fatty acids and, optionally, an antioxidant, and related treatment methods for protecting the gastric mucosa and for regulating the blood glucose levels. Additionally, a method is described for preparing the at least one cetylated fatty acid or mixture of cetylated fatty acids and for preparing compositions comprising the cetylated fatty acids and the antioxidant.

Claims (40)

1. A method for preparing at least one cetylated fatty acid or a mixture of cetylated fatty acids, the method comprising the steps of:

(I) placing in contact at least one fatty acid, cetyl alcohol and a metal catalyst in a chamber of a reactor in absence of solvent, to obtain a reaction mixture; followed by

(II) saturating the container using an inert gas bringing the container to a pressure P 1 of about 1 atmosphere, and applying a flow of said inert gas through said chamber; followed by

(III) applying a first heating ramp to said reaction mixture up to reaching a temperature T 1 from 120° C. to 200° C. at a pressure P 1 of about 1 atmosphere and in presence of the inert gas flow to initiate an esterification reaction with initial formation of said cetylated fatty acid or mixture of cetylated fatty acids and esterification water; followed by

(IV) keeping said reaction mixture under stirring at said temperature T 1 and pressure P 1 for a period of time comprised from 10 minutes to 2 hours; followed by

(V) applying a second heating ramp to said reaction mixture up to reaching a temperature T 2 comprised from 201° C. to 260° C. at a pressure P 1 of about 1 atmosphere and in the presence of the inert gas flow to continue the esterification reaction with further formation of said cetylated fatty acid or mixture of cetylated fatty acids and esterification water; followed by

(VI) keeping said reaction mixture under stirring at said temperature T 2 and pressure P 1 and in presence of the inert gas flow for a period of time from 4 hours to 12 hours;

(VII) applying a vacuum program in the chamber which reduces the reaction pressure up to reaching a reduced pressure P 2 comprised from 100 mbar to 10 mbar; and

(VIII) keeping said reaction mixture under stirring at said reduced pressure P 2 and in presence of the inert gas flow for a period of time from 30 minutes and 4 hours to obtain complete formation of said at least one unrefined cetylated fatty acid or mixture of unrefined cetylated fatty acids (MI).

2. The method according to claim 1 , wherein

said step (VI) of keeping said reaction mixture under stirring at said temperature T 2 and pressure P 1 and in presence of the inert gas flow for a period of time between 6 hours and 12 hours is carried out up to reaching an acidity value of the reaction mixture measured using the AOCS Official Method Cd 3d-63 stable over time and comprised between 5 mgKOH/g and 8 mgKOH/g; and

said step (VIII) of keeping said reaction mixture under stirring at said reduced pressure P 2 and in presence of the inert gas flow for a period of time comprised between 30 minutes and 4 hours up to obtaining an acidity value of the reaction mixture measured using the AOCS Official Method Cd 3d-63 between 4.5 mgKOH/g and 3.5 mgKOH/g to obtain complete formation of said at least one unrefined cetylated fatty acid or mixture of unrefined cetylated fatty acids (MI).

3. The method according to claim 1 , wherein said at least one fatty acid is selected from lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, eicosanoic acid, and mixtures thereof.

4. The method according to claim 1 , wherein said flow of inert gas is applied using blowing means positioned in the volume portion of the chamber overlying the reaction mixture.

5. The method according to claim 1 , wherein the esterification water, drawn out of the chamber during the esterification reaction is condensed in a horizontal condenser and collected in a container after flowing through the vertical condenser.

6. The method according to claim 1 , wherein said method further comprises the step of

(IX) filtering said at least one unrefined cetylated fatty acid (MI) obtained from step (VIII) on bleaching earth and/or filtering earth in a filter press, to obtain at least one filtered cetylated fatty acid (Mf) wherein the metal catalyst is absent or present at an amount smaller than 2% by weight with respect to the weight of said filtered cetylated fatty acid or mixture of filtered cetylated fatty acids (Mf).

7. The method according to claim 6 , wherein said method further comprises, subsequently to step (IX), the step of

(X) treating said at least one filtered cetylated fatty acid (Mf) in a reactor at a temperature T 3 comprised from 150° C. to 200° C. and a reduced pressure P 3 comprised from 1 mbar to 20 mbar in the presence of a water vapour flow for a period of time comprised from 1 hour to 5 hours to obtain at least one refined cetylated fatty acid (MF).

8. A method for preparing a composition comprising said at least one cetylated fatty acid, the method comprising the step of

obtaining at least one filtered cetylated fatty acid or mixture of filtered cetylated fatty acids (Mf) by performing the method of claim 6 , and

mixing said at least one filtered cetylated fatty acid (Mf) with at least one antioxidant, at a percentage by weight from 0.001% to 0.5% with respect to the total weight of the composition.

9. The method according to claim 8 , wherein said at least one filtered cetylated fatty acid (Mf) comprises a mixture of cetylated myristic acid and cetylated oleic acid, and wherein said at least one antioxidant is tert-butyl-hydroquinone (TBHQ).

10. The method according to claim 8 , wherein said at least one filtered cetylated fatty acid (Mf) obtained from step (IX) is subjected to a step of

(XII) of adding said at least one filtered cetylated fatty acid (Mf) with a vegetable oil, to form a mixture comprising a filtered cetylated fatty acid (Mf) and vegetable oil.

11. The method according to claim 1 , wherein said at least one fatty acid is selected from myristic acid, oleic acid and a mixture of myristic acid and oleic acid, and mixtures thereof.

12. The method according to claim 8 , wherein the mixing is performed with the at least one antioxidant at a percentage by weight from between 0.005% to 0.1%, with respect to the total weight of the composition.

13. The method according to claim 8 , wherein the mixing is performed with the at least one antioxidant at a percentage by weight from between 0.01% to 0.08%, with respect to the total weight of the composition.

14. The method according to claim 8 , wherein said at least one filtered cetylated fatty acid (Mf) obtained from step (IX), is a mixture of filtered cetylated myristic acid and cetylated oleic acid.

15. The method according to claim 10 , wherein the vegetable oil is olive oil.

16. A method for preparing a composition comprising said at least one cetylated fatty acid, the method comprising the steps of

obtaining at least one refined cetylated fatty acid (MF) by performing the method of claim 7 , and

mixing said at least one refined cetylated fatty acid (MF) with at least one antioxidant, at a percentage by weight from 0.001% to 0.5% with respect to the total weight of the composition.

17. The method according to claim 16 , wherein said at least one refined cetylated fatty acid (MF) comprises a mixture of cetylated myristic acid and cetylated oleic acid, and wherein said at least one antioxidant is tert-butyl-hydroquinone (TBHQ).

18. The method according to claim 16 , wherein before step (X), said at least one filtered cetylated fatty acid (Mf) obtained from step (IX), is subjected to a step of

(XII) of adding said at least one filtered cetylated fatty acid (Mf) with a vegetable oil, to form a mixture comprising a filtered cetylated fatty acid (Mf) and vegetable oil which is subsequently subjected to step (X).

19. The method according to claim 16 , wherein the mixing is performed with the at least one antioxidant at a percentage by weight from between 0.005% to 0.1%, with respect to the total weight of the composition.

20. The method according to claim 16 , wherein the mixing is performed with the at least one antioxidant at a percentage by weight from between 0.01% to 0.08%, with respect to the total weight of the composition.

21. The method according to claim 16 , wherein said at least one filtered cetylated fatty acid (Mf) obtained from step (IX), is a mixture of filtered cetylated myristic acid and cetylated oleic acid.

22. The method according to claim 18 , wherein the vegetable oil is olive oil.

Assignments (2)
MERGER Recorded Jul 22, 2025
From: ALESCO S.R.L.; PHARMANUTRA S.P.A.
To: PHARMANUTRA S.P.A.
Reel/Frame 072168/0863 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 22, 2022
From: LACORTE, ANDREA; TARANTINO, GERMANO; BRILLI, ELISA
To: PHARMANUTRA S.P.A.; ALESCO S.R.L.
Reel/Frame 059070/0287 →
Priority Claims (1)
IT 102019000007311 · May 27, 2019 · national
Continuity (1)
Related Publication 20220220414A1 · Jul 14, 2022
References Cited (176)
US 4113881A · Diehl · 1978 [cited by applicant]
US 4393133A · Knowles et al. · 1983 [cited by applicant]
US 5888563A · Mehansho et al. · 1999 [cited by applicant]
US 6039978A · Bangs et al. · 2000 [cited by applicant]
US 6361800B1 · Cooper et al. · 2002 [cited by applicant]
US 6417227B1 · Lord et al. · 2002 [cited by applicant]
US 8404745B2 · Barathur · 2013 [cited by examiner]
US 9861670B2 · Clements · 2018 [cited by examiner]
US 20020058705A1 · Gonzales Bravo et al. · 2002 [cited by applicant]
US 20030181521A1 · Leonard et al. · 2003 [cited by applicant]
US 20050100636A1 · Botteri et al. · 2005 [cited by applicant]
US 20050261257A1 · Vermeer · 2005 [cited by applicant]
US 20070065521A1 · Venkataraman et al. · 2007 [cited by applicant]
US 20070148258A1 · O'Neill et al. · 2007 [cited by applicant]
US 20070148259A1 · Gupta · 2007 [cited by applicant]
US 20090186939A1 · Chan et al. · 2009 [cited by applicant]
US 20090326060A1 · Chan et al. · 2009 [cited by applicant]
US 20100021573A1 · Gonzalez et al. · 2010 [cited by applicant]
US 20110054030A1 · Petraglia et al. · 2011 [cited by applicant]
US 20110294665A1 · Makino · 2011 [cited by applicant]
US 20120265119A1 · Barathur et al. · 2012 [cited by applicant]
US 20130157974A1 · Ziegler et al. · 2013 [cited by applicant]
US 20140121156A1 · Hausman · 2014 [cited by applicant]
US 20140322314A1 · Fawzy et al. · 2014 [cited by applicant]
US 20150250885A1 · Lacorte et al. · 2015 [cited by applicant]
US 20160008415A1 · Clements et al. · 2016 [cited by applicant]
US 20160310445A1 · Vermeer · 2016 [cited by applicant]
US 20170056465A1 · Tobin · 2017 [cited by examiner]
US 20170080023A1 · Agam et al. · 2017 [cited by applicant]
US 20170112178A1 · Perrin et al. · 2017 [cited by applicant]
US 20170202802A1 · Fernandez et al. · 2017 [cited by applicant]
US 20200085710A1 · Denda et al. · 2020 [cited by applicant]
US 20200206157A1 · Lacorte et al. · 2020 [cited by applicant]
US 20200246377A1 · Lacorte et al. · 2020 [cited by applicant]
US 20220211655A1 · Lacorte et al. · 2022 [cited by applicant]
US 20220226274A1 · Lacorte et al. · 2022 [cited by applicant]
CN 106343566A · 2017 [cited by applicant]
CN 108137472A · 2018 [cited by applicant]
EP 0679394A2 · 1995 [cited by applicant]
EP 2380578A1 · 2011 [cited by applicant]
EP 2886129A1 · 2015 [cited by applicant]
GB 2552952A · 2018 [cited by applicant]
JP S5841813A · 1983 [cited by applicant]
JP H08253415A · 1996 [cited by applicant]
JP 2002515866A · 2002 [cited by applicant]
JP 2003342159A · 2003 [cited by applicant]
JP 2007523056A · 2007 [cited by applicant]
JP 2009525277A · 2009 [cited by applicant]
JP 2015523409A · 2015 [cited by applicant]
NZ 332959A · 2001 [cited by applicant]
WO 1997031620A2 · 1997 [cited by applicant]
WO 0064436A1 · 2000 [cited by applicant]
WO 03018731A1 · 2003 [cited by applicant]
WO 2004019923A1 · 2004 [cited by applicant]
WO 2004084829A2 · 2004 [cited by applicant]
WO 2004084829A3 · 2005 [cited by applicant]
WO 2005044189A2 · 2005 [cited by applicant]
WO 2007089577A2 · 2007 [cited by applicant]
WO 2010079514A1 · 2010 [cited by applicant]
WO 2010117194A2 · 2010 [cited by applicant]
WO 2012161572A1 · 2012 [cited by applicant]
WO 2014009806A1 · 2014 [cited by applicant]
WO 2014160279A1 · 2014 [cited by applicant]
WO 2016131993A2 · 2016 [cited by applicant]
WO WO2017029580A1 · 2017 [cited by examiner]
WO 2018034797A1 · 2018 [cited by applicant]
WO 2018221534A1 · 2018 [cited by applicant]
WO 2019021232A1 · 2019 [cited by applicant]
WO 2019025922A1 · 2019 [cited by applicant]
WO 2020240438A1 · 2020 [cited by applicant]
WO 2020240441A1 · 2020 [cited by applicant]
WO 2020240443A1 · 2020 [cited by applicant]
Barot, B.S. et al. Physiochemical and structural characterization of iron-sucrose formulations: a comparative study. Pharmaceutical Development and Technology. (Published online May 23, 2013) 19 (5): 513-520. 9 pages. [cited by applicant]
Barpanda P et al. “Sodium iron pyrophosphate: a novel 3.0V iron-based cathode for sodium-ion batteries”, Electrochemistry Communications, vol. 24, Oct. 2012, pp. 116-119. 11 pages. [cited by applicant]
Breymann, Prof. Dr. Christian. Preventing and Treating Iron Deficiency Anaemia in Pregnant Women. Are we doing our best? Presentation in Zurich, Switzerland, May 15, 2017. 27 pages. [cited by applicant]
Commission Regulation (EU) No. 231/2012 of Mar. 9, 2012. Laying down Specifications for food additives listed on Annexes II and III to Regulation (EC) No. 1333/2008 of the European Parliament and of the Council. Officia… [cited by applicant]
Regulation (EC) No. 1333/2008 of the European Parliament and of the Council of Dec. 16, 2008 on food additives. Dated: Mar. 22, 2023. pp. 346. [cited by applicant]
“E number” from European Food Safety Authority, Downloaded Jul. 21, 2023. 1 page. Website: www.efsa.europa.eu/en/glossary/e-number#:˜:text=A%20number%20used%20in%20the,has%20been%20apprvoed%20for%20use. [cited by applicant]
Eur-Lex, Access to European Union Law, Document 51977PC0304. Proposal for a Council Directive amending for the first time Directive 74/329/EEC on the approximation of the laws of the Member States relating to emulsifier… [cited by applicant]
Final Office Action for U.S. Appl. No. 16/631,426, filed Jan. 15, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Nov. 16, 2023. 17 Pages. [cited by applicant]
Firdaus S et al. “Green synthesis of silver nanoparticles using Carica Papaya fruit extract under sunlight irradiation and their colorimetric detection of mercury ions”, 2nd International Symposium on Frontier of Applie… [cited by applicant]
“Food additives” from European Food Safety Authority, Downloaded Jul. 21, 2023. 9 pages. Website: www.efsa.europa.eu/en/topics/topic/food-additives. [cited by applicant]
“Food additives” from European Food Safety Authority (EFSA), Downloaded though The Wayback Machine for Jul. 17, 2017. 2 pages. Website: www.efsa.europa.eu/en/topics/topic/food-additives. [cited by applicant]
Geisser, P. et al. Review: The Pharmacokinetics and Pharmacodynamics of Iron Preparations. Pharmaceutics, (Jan. 2011) 3, pp. 12-33. Doi.org/10.3390/pharmaceutics3010012. Website: mdpi.com/journal/pharmaceutics. [cited by applicant]
Geisser, Peter. Safety and Efficacy of Iron(III)-hydroxide Polymaltose Complex. Arzneimittel-Forschung (Drug Research) 2007: 57 (6a): 439-452. [cited by applicant]
Gomez-Ramirez, Susana et al. Sucrosomial® Iron: A New Generation Iron for Improving Oral Supplementation. Pharmaceuticals. (2018). 11, 97. 23 pages. DOI:10.3390/ph11040097. Website: mdpi.com/journal/pharmaceutical. [cited by applicant]
Gupta A., et al. “Dialysate iron therapy: Infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis” Kidney International (1999); 55(5):1891-1898. [cited by applicant]
“Iron polymaltose” from Wikipedia, Downloaded: Jul. 23, 2023. 5 pages. Website: en.wikipedia.org/wiki/Iron_polymaltose. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/635,516, filed Jan. 30, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Oct. 4, 2023. 25 pages. [cited by applicant]
Search of Search Food Additives Database for “E473” from European Food Safety Authority, Downloaded Jul. 21, 2023. 3 pages. Website: food.ec.europa.eu/safety/food-improvement-agents/additives/database_en. [cited by applicant]
Shah, R.B. et al., “Pharmaceutical characterization and thermodynamic stability assessment of a colloidal iron drug product: Iron sucrose”, International Journal of Pharmaceutics, 464 (Jan. 17, 2014), pp. 46-52. [cited by applicant]
SiderAL product page on Pharmanutra website. 2 pages. Printed Jul. 21, 2023. Website: www.pharmanutra.it/en/brand/pharmanutra/sideral/. [cited by applicant]
Sideral.it website. Printed May 19, 2023. 11 pages. [cited by applicant]
Toblli, J.E. et al., Iron(III)-hydroxide Polymaltose Complex in Iron Deficiency Anemia. Review and Meta-analysis. Arzneimittel-Forschung (Drug Research) 2007: 57 (6a): 431-438. [cited by applicant]
Fragala M.S. et al: “Influences of a dietary supplement in combination with an exercise and diet regimen on adipocytokines and adiposity in women who are overweight”, European Journal Of Applied Physiology, vol. 105, No… [cited by applicant]
International Search Report for International Application No. PCT/IB2020/055028 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Sep. 9, 2020 4 pages. [cited by applicant]
International Search Report for International Application No. PCT/IB2020/055031 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Aug. 28, 2020 5 pages. [cited by applicant]
International Search Report for International Application No. PCT/IB2020/055037 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Sep. 10, 2020 4 pages. [cited by applicant]
Written Opinion for International Application No. PCT/IB2020/055028 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Sep. 9, 2020 6 pages. [cited by applicant]
Written Opinion for International Application No. PCT/IB2020/055031 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Aug. 28, 2020 8 pages. [cited by applicant]
Written Opinion for International Application No. PCT/IB2020/055037 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Sep. 10, 2020 5 pages. [cited by applicant]
Advisory Action for U.S. Appl. No. 16/631,426, filed Jan. 15, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Dec. 20, 2022. 4 Pages. [cited by applicant]
Aoun, M. et al. “High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K2, A pre-post intervention clinical trial”, BMC Nephrology, Jun. 2017, vol. 18, 191. 10 pages. [cited by applicant]
Barisani et al. “Iron overload and gene expression in HepG2 cells: analysis by differential display” [cited by applicant]
Chung, B. et al. “Oncostatin M is a potent inducer of hepcidin, the iron regulatory hormone”, [cited by applicant]
Commission Directive 96/77/EC of Dec. 2, 1996; last amendment M7 Commission Directive 2006/129/EC of Dec. 8, 2006. 165 pages. [cited by applicant]
“Coordination Complex” from Wikipedia, through the Wayback Machine dated Nov. 18, 2016. 10 pages. [cited by applicant]
Cutcliffe T et al., “Vitamin K2 may reverse calcification of blood vessels in people with kidney disease” [cited by applicant]
Decision of Rejection for Japanese Application No. 2020-502672 filed on Jul. 26, 2018 on behalf of Pharmanutra S.P.A. Dated Jan. 4, 2023. 9 pages. [cited by applicant]
E322-Lechitins: on the web site of INCHEM (Internationally Peer Reviewed Chemical Safety Information), World Health Organization, the following Summary of Evaluations Performed by the Joint FAO/WHO Expert Committee on F… [cited by applicant]
Erni, I. Oswald N. et al. “Chemical characterization of iron (III)-hydroxide-dextrin complexes. A comparative study of commercial preparations with alleged reproductions used in the examination of bioavailability”, Arzn… [cited by applicant]
Final Office Action for U.S. Appl. No. 16/631,426, filed Jan. 15, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Aug. 11, 2022. 18 Pages. [cited by applicant]
Final Office Action for U.S. Appl. No. 16/635,516, filed Jan. 30, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Dec. 1, 2021. 15 pages. [cited by applicant]
Final Office Action for U.S. Appl. No. 16/635,516, filed Jan. 30, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Feb. 22, 2023. 18 pages. [cited by applicant]
Garrelds, I. M. et al. “Time dependent production of cytokines and eicosanoids by human monocytic leukaemia U937 cells; effects of glucocorticosteroids” [cited by applicant]
Huang, Z.B. et al. “HMGB1 release by human liver L02 and HepG2 cells induced by lipopolysaccharide” [cited by applicant]
Ilbert, Marianne et al., “Review: Insight into the evolution of the iron oxidation pathways”, Biochimica et Biophysica Acta, 1827 (2013), pp. 161-175. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/IB2018/055586 filed on Jul. 26, 2018 on behalf of Pharmanutra S.P.A. Mail Date: Jan. 28, 2020. 7 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/IB2018/055634 filed on Jul. 27, 2018 on behalf of Pharmanutra S.P.A. Mail Date: Feb. 4, 2020. 8 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/IB2020/055028 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Nov. 16, 2021. 7 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/IB2020/055031 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Nov. 16, 2021. 9 pages. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/IB2020/055037 filed on May 27, 2020 on behalf of Alesco S.R.L. Mail Date: Nov. 16, 2021. 6 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/IB2018/055586 filed on Jul. 26, 2018 on behalf Pharmanutra S.P.A. Mail Date: Oct. 25, 2018. 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/IB2018/055634 filed on Jul. 27, 2018 on behalf Pharmanutra S.P.A. Mail Date: Dec. 4, 2018. 12 pages. [cited by applicant]
“Iron Dextran” from DrugBank, DrugBank Accession No. DB00893, dated Nov. 26, 2022, 14 pages. [cited by applicant]
“Iron Sucrose” from Wikipedia, through the Wayback Machine dated Oct. 22, 2016. 1 page. [cited by applicant]
Kidney disease—Wikipedia, Dated: May 6, 2017, 7 pages. [cited by applicant]
Liu, H.Z. et al. “The U937 cell line induced to express CD14 protein by 1,25-dihydroxyvitamin D3 and be sensitive to endotoxin stimulation” [cited by applicant]
McCarty, M.F. et al. “Bioavailable dietary phosphate, a mediator of cardiovascular disease, may be decreased with plant-based diets, phosphate binder, niacin, and avoidance of phosphate additives”, Nutrition, (Jul.-Aug.… [cited by applicant]
Miki, K. et al. “Extracellular activation of arginase-1 decreases enterocyte inducible nitric oxide synthase activity during systemic inflammation” [cited by applicant]
Muriuki J.M. et al., “Malaria is a cause of iron deficiency in African children” [cited by applicant]
Neven E. et al., “Iron and vascular calcification. Is there a link” [cited by applicant]
Nicoll, R. et al. “A Review of the Effect of Diet on Cardiovascular Calcification”, Int. J. Mol. Sci., (2015), vol. 16, pp. 8861-8883. ISSN 0004771926. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/631,426, filed Jan. 15, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Feb. 2, 2023. 17 Pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/631,426, filed Jan. 15, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Nov. 10, 2021. 17 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/635,516, filed Jan. 30, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Jul. 26, 2022. 18 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 16/635,516, filed Jan. 30, 2020 on behalf of Pharmanutra S.P.A. Mail Date: May 12, 2021. 30 pages. [cited by applicant]
O'Neill, W.C. et al. “Plasma pyrophosphate and vascular calcification in chronic kidney disease”, Nephrol Dial Transplant (2010), 25: 187-191. Doi: 10.1093/ndt/gfp362. [cited by applicant]
O'Neill, W.C. et al. “Treatment with pyrophosphate inhibits uremic vascular calcification”, Kidney Int, Mar. 2011, 76(5): 512-517. 15 pages. Doi: 10.1038/ki.2010.461. [cited by applicant]
Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Material in Contact with Food on Sucrose esters of fatty acids, e 473 and sucroglycerides, E 474 based on a request from the Commission… [cited by applicant]
Ozcelik, Berrin. “Fungi/Bactericidal and Static Effect of Ultraviolet Light in 254 and 354 nm wavelengths” [cited by applicant]
Pepys, M. et al., C-reactive protein: a critical update [cited by applicant]
Restriction Requirement for U.S. Appl. No. 16/631,426, filed Jan. 15, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Aug. 20, 2021. 10 pages. [cited by applicant]
Rincon, M. “Interleukin-6: from an inflammatory marker to a target for inflammatory diseases” [cited by applicant]
Saliou, C. et al. “Selective inhibition of NF-KB activation by the flavonoid hepatoprotector silymarin in HepG2, Evidence for different activating pathways” [cited by applicant]
“Salt (chemistry)” from Wikipedia, through the Wayback Machine dated Feb. 11, 2016. 4 pages. [cited by applicant]
Shelley, C. S. et al. “During Differentiation of the Monocytic Cell Line U937, PurAlpha Mediates Induction of the CD11c Beta2 Integrin Gene Promoter” [cited by applicant]
Smith, E. M.; Tangpricha, V. “Vitamin D and Anemia: Insights into an Emerging Association”. Curr Opin Endocrinol Diabetes Obes, Dec. 2015, 22(6), 432-438. 14 pages. [cited by applicant]
Sonou, T. et al., “Magnesium prevents phosphate-induced vascular calcification via TRPM7 and Pit-1 in an aortic tissue culture model”. Hypertension Research, (2017), vol. 40, pp. 562-567. ISSN 0004771924. [cited by applicant]
Spiegel D.M. et al., “Long-term effects of magnesium carbonate on coronary artery calcification and bone mineral density in hemodialysis patients: a pilot study” [cited by applicant]
Strober W. “Trypan blue exclusion test of cell viability” [cited by applicant]
Villarroel P. et al. “Interleukin 6 and lipopolysaccharide modulate hepcidin mRNA expression by HepG2 cells” [cited by applicant]
Wikipedia page for “International Numbering System for Food Additives” dated Dec. 22, 2016 (16 pp). [cited by applicant]
Wikipedia page for “E number” dated Jul. 17, 2017. (29 pp). [cited by applicant]
Zughaier, S.M. et al. “The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes” [cited by applicant]
Bagirova, V.L. et al. (1998) No. 6. C. 34-36. Russian original + English extract. 8 pages. (D6). [cited by applicant]
First Notification of Office Action for Chinese Application No. 202080039453.9 on behalf of Alesco S.R.L Pharmanutra S.P.A. Issued on Feb. 3, 2024. 3 pages. English translation only. [cited by applicant]
First Notification of Office Action for Chinese Application No. 202080039535.3 on behalf of Alesco S.R.L Pharmanutra S.P.A. Issued on Feb. 2, 2024. 9 pages. Original + English translation. [cited by applicant]
First Notification of Office Action for Chinese Application No. 202080039600.2 on behalf of Alesco S.R.L Pharmanutra S.P.A. Issued on Feb. 2, 2024. 10 pages. Original and English translation. [cited by applicant]
Search Report from The Intellectual Property Office of Singapore for Application No. 11202112774X filed on May 27, 2020. Mailed on Aug. 17, 2023. 2 pages. Issued in English. [cited by applicant]
Search Report from The Intellectual Property Office of Singapore for Application No. 11202112779Y filed on May 27, 2020. Mailed on Aug. 17, 2023. 2 pages. Issued in English. [cited by applicant]
The Eurasian Patent Office Application No. 202193083/28, Conclusion on patentability of the invention. Mailed on Dec. 19, 2022. 11 pages. Russian and partial English translation. [cited by applicant]
The Eurasian Patent Office Application No. 202193083/28, Conclusion on patentability of the invention. Mailed on Jul. 19, 2023. 18 pages. Russian and partial English translation. [cited by applicant]
Wikipedia, The Free Encyclopedia, “Pourbaix diagram”, (Dec. 11, 2017). Downloaded on Mar. 29, 2024. 8 pages. [cited by applicant]
Wikipedia, The Free Encyclopedia, “Sucrose”, (Dec. 31, 2017). Downloaded on Mar. 29, 2024. 24 pages. [cited by applicant]
Wikipedia, The Free Encyclopedia, “Sucrose esters”, (Nov. 16, 2017). Downloaded on Mar. 29, 2024. 7 pages. [cited by applicant]
Written Opinion from The Intellectual Property Office of Singapore for Application No. 11202112774X filed on May 27, 2020. Mailed on Aug. 21, 2023. 7 pages. Issued in English. [cited by applicant]
Written Opinion from The Intellectual Property Office of Singapore for Application No. 11202112779Y filed on May 27, 2020. Issued on Aug. 21, 2023. 7 pages. Issued in English. [cited by applicant]
“Converting Units of Measure for Folate, Niacin, and Vitamins A, D, and E on the Nutrition and Supplement Facts Labels: Guidance for Industry”, U.S. Dept of Health and Human Services, Food and Drug Administration, Cente… [cited by applicant]
European Food Safety Authority (EFSA), Scientific Opinion on the Safety of ‘Cetyl Myristoleate Complex’ as a food ingredient. 8 (7), 1686 (2010). 14 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 17/614,294, filed Nov. 24, 2021 on behalf of Alesco S.R.L. et al. Mailed on Aug. 28, 2024. 23 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 17/613,719, filed Nov. 23, 2021 on behalf of Alesco S.R.L. et al. Mailed on Sep. 18, 2024. 28 pages. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 16/635,516, filed Jan. 30, 2020 on behalf of Pharmanutra S.P.A. Mail Date: Jul. 31, 2024. 15 pages. [cited by applicant]
Notice of Reasons for Refusal for Japanese Application No. 2021-570463 filed May 27, 2020. Mailed on May 7, 2024. Original and Machine translation. 13 pages. [cited by applicant]
Shimoyama, Challenges to Unravel Mechanisms of GERD. Gastroesophageal Reflux Disease. Theory and Research. (Nov. 2018). [cited by applicant]
Ulatowski, L.M. et al., Vitamin E and neurodegeneration. Neurobiology of Disease, 84 (Dec. 2015), 78-83. [cited by applicant]
Cited By (1)
US 12,691,091