Granted Patent
B2
US 12,534,727 · App. 17/274,907 · Granted Jan 27, 2026
Target to treat a metabolic disease in an individual
Inventors:
Patricia Aspichueta Celaá (Leioa-Vizcaya, ES); Xabier Buqué García (Leioa-Vizcaya, ES); Diego Sáenz de Urturi (Leioa-Vizcaya, ES)
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Abstract
Provided herein are methods, compounds, and compositions for reducing expression of MAT1a in a cell or individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a metabolic disease or disorder in an individual.
Claims (19)
1 . A method of treating or ameliorating a metabolic disease or disorder in an individual having a metabolic disease or disorder comprising administering a MAT1a specific inhibitor to the individual, thereby treating or ameliorating the metabolic disease or disorder in the individual, wherein the metabolic disease or disorder is obesity, diabetes, insulin resistance, or dyslipidemia, and wherein the MAT1a specific inhibitor is a nucleic acid comprising a modified oligonucleotide targeting MAT1a comprising:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides;
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is positioned immediately adjacent to and between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar; and wherein the modified oligonucleotide is selected from the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 159 and SEQ ID NO: 216.
2 . The method of claim 1 , wherein the treating or ameliorating of the metabolic disease or disorder includes at least one of a lowering of MAT1a specific inhibitor reduces or improves adiposity, an increase in adiponectin levels, an increase in insulin sensitivity, a reduction of body weight, a reduction of serum triglyceride levels, or improvement in fatty liver.
3 . The method of claim 1 , wherein the modified oligonucleotide comprises at least one modification selected from at least one modified internucleoside linkage and at least one modified nucleobase.
4 . The method of claim 3 , wherein the at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage and the at least one modified nucleobase is a 5-methylcytosine.
5 . The method of claim 1 , wherein at least one modified sugar comprises a 4′-CH(CH 3 )-O-2′ bridge or a 4′-(CH 2 ) n —O-2′ bridge, wherein n is 1 or 2.
6 . The method of claim 1 , wherein the MAT1a specific inhibitor is administered parenterally by subcutaneous or intravenous administration.
7 . The method of claim 1 , comprising co-administering the MAT1a specific inhibitor and at least one additional therapy.
8 . The method of claim 7 , wherein the MAT1a specific inhibitor and the additional therapy are administered concomitantly.
9 . The method of claim 7 , wherein the MAT1a specific inhibitor and the additional therapy are administered consecutively.
10 . The method of claim 1 , wherein the at least one modified sugar is a bicyclic sugar or 2′-O-methyoxyethyl.
11 . A method of inhibiting expression or activity of MAT1a in a cell comprising contacting the cell with a MAT1a specific inhibitor, thereby inhibiting expression or activity of MAT1a in the cell, wherein the cell is a hepatocyte from an individual having obesity, diabetes, insulin resistance, or dyslipidemia, and wherein the MAT1a specific inhibitor is a nucleic acid comprising a modified oligonucleotide targeting MAT1a comprising
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides;
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is positioned immediately adjacent to and between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar; and wherein the modified oligonucleotide is selected from the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 159 and SEQ ID NO: 216.
Priority Claims (1)
EP 18382648
· Sep 10, 2018
· regional
Continuity (1)
References Cited (155)
US 3687808A
· Merigan, Jr. et al.
· 1972
[cited by applicant]
US 4845205A
· Dinh et al.
· 1989
[cited by applicant]
US 5034506A
· Summerton et al.
· 1991
[cited by applicant]
US 5130302A
· Spielvogel et al.
· 1992
[cited by applicant]
US 5134066A
· Rogers et al.
· 1992
[cited by applicant]
US 5166315A
· Summerton et al.
· 1992
[cited by applicant]
US 5175273A
· Bischofberger et al.
· 1992
[cited by applicant]
US 5185444A
· Summerton et al.
· 1993
[cited by applicant]
US 5367066A
· Urdea et al.
· 1994
[cited by applicant]
US 5432272A
· Benner
· 1995
[cited by applicant]
US 5434257A
· Matteucci et al.
· 1995
[cited by applicant]
US 5457187A
· Gmeiner et al.
· 1995
[cited by applicant]
US 5457191A
· Cook et al.
· 1995
[cited by applicant]
US 5459255A
· Cook et al.
· 1995
[cited by applicant]
US 5484908A
· Froehler et al.
· 1996
[cited by applicant]
US 5502177A
· Matteucci et al.
· 1996
[cited by applicant]
US 5525711A
· Hawkins et al.
· 1996
[cited by applicant]
US 5552540A
· Haralambidis
· 1996
[cited by applicant]
US 5587469A
· Cook et al.
· 1996
[cited by applicant]
US 5587470A
· Cook et al.
· 1996
[cited by applicant]
US 5594121A
· Froehler et al.
· 1997
[cited by applicant]
US 5596091A
· Switzer
· 1997
[cited by applicant]
US 5614617A
· Cook et al.
· 1997
[cited by applicant]
US 5645985A
· Froehler et al.
· 1997
[cited by applicant]
US 5681941A
· Cook et al.
· 1997
[cited by applicant]
US 5698685A
· Summerton et al.
· 1997
[cited by applicant]
US 5750692A
· Cook et al.
· 1998
[cited by applicant]
US 5763588A
· Matteucci et al.
· 1998
[cited by applicant]
US 5808027A
· Cook et al.
· 1998
[cited by applicant]
US 5811534A
· Cook et al.
· 1998
[cited by applicant]
US 5830653A
· Froehler et al.
· 1998
[cited by applicant]
US 5859221A
· Cook et al.
· 1999
[cited by applicant]
US 5948903A
· Cook et al.
· 1999
[cited by applicant]
US 6005087A
· Cook et al.
· 1999
[cited by applicant]
US 6005096A
· Matteucci et al.
· 1999
[cited by applicant]
US 6166199A
· Cook et al.
· 2000
[cited by applicant]
US 6268490B1
· Imanishi et al.
· 2001
[cited by applicant]
US 6525191B1
· Ramasamy
· 2003
[cited by applicant]
US 6531584B1
· Cook et al.
· 2003
[cited by applicant]
US 6670461B1
· Wengel et al.
· 2003
[cited by applicant]
US 6673661B1
· Liu et al.
· 2004
[cited by applicant]
US 6770748B2
· Imanishi et al.
· 2004
[cited by applicant]
US 6794499B2
· Wengel et al.
· 2004
[cited by applicant]
US 7034133B2
· Wengel et al.
· 2006
[cited by applicant]
US 7053207B2
· Wengel et al.
· 2006
[cited by applicant]
US 7399845B2
· Seth et al.
· 2008
[cited by applicant]
US 7427672B2
· Imanishi et al.
· 2008
[cited by applicant]
US 7547684B2
· Seth et al.
· 2009
[cited by applicant]
US 7569686B1
· Bhat et al.
· 2009
[cited by applicant]
US 7572582B2
· Wengel et al.
· 2009
[cited by applicant]
US 7666854B2
· Seth et al.
· 2010
[cited by applicant]
US 7696345B2
· Allerson et al.
· 2010
[cited by applicant]
US 7741457B2
· Seth et al.
· 2010
[cited by applicant]
US 7750131B2
· Seth et al.
· 2010
[cited by applicant]
US 7875733B2
· Bhat et al.
· 2011
[cited by applicant]
US 7939677B2
· Bhat et al.
· 2011
[cited by applicant]
US 8022193B2
· Seth et al.
· 2011
[cited by applicant]
US 8030467B2
· Seth et al.
· 2011
[cited by applicant]
US 8034909B2
· Wengel et al.
· 2011
[cited by applicant]
US 8080644B2
· Wengel et al.
· 2011
[cited by applicant]
US 8088746B2
· Seth et al.
· 2012
[cited by applicant]
US 8088904B2
· Swayze et al.
· 2012
[cited by applicant]
US 8124745B2
· Allerson et al.
· 2012
[cited by applicant]
US 8153365B2
· Wengel et al.
· 2012
[cited by applicant]
US 8268980B2
· Seth et al.
· 2012
[cited by applicant]
US 8278283B2
· Seth et al.
· 2012
[cited by applicant]
US 8278425B2
· Prakash et al.
· 2012
[cited by applicant]
US 8278426B2
· Seth et al.
· 2012
[cited by applicant]
US 8440803B2
· Swayze et al.
· 2013
[cited by applicant]
US 8501805B2
· Seth et al.
· 2013
[cited by applicant]
US 8530640B2
· Seth et al.
· 2013
[cited by applicant]
US 8546556B2
· Seth et al.
· 2013
[cited by applicant]
US RE44779E
· Imanishi et al.
· 2014
[cited by applicant]
US 9005906B2
· Swayze et al.
· 2015
[cited by applicant]
US 9012421B2
· Migawa et al.
· 2015
[cited by applicant]
US 20030158403A1
· Manoharan et al.
· 2003
[cited by applicant]
US 20030175906A1
· Manoharan et al.
· 2003
[cited by applicant]
US 20080039618A1
· Allerson et al.
· 2008
[cited by applicant]
US 20100190837A1
· Migawa et al.
· 2010
[cited by applicant]
US 20150191727A1
· Migawa et al.
· 2015
[cited by applicant]
US 20160208261A1
· Satishchandran et al.
· 2016
[cited by applicant]
WO 1999014226A2
· 1999
[cited by applicant]
WO 0063364A2
· 2000
[cited by applicant]
WO 2004106356A1
· 2004
[cited by applicant]
WO 2007134181A2
· 2007
[cited by applicant]
WO 2008101157A1
· 2008
[cited by applicant]
WO 2011133876A2
· 2011
[cited by applicant]
WO 2015106128A2
· 2015
[cited by applicant]
WO 2017161168A1
· 2017
[cited by applicant]
Komal Ramani, et al, “Methionine adenosyltransferases in liver health and diseases”, Liver Research 1, pp. 103-111 (Year: 2017).
[cited by examiner]
Shelly C. Lu, et al, Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation:, PNAS vol. 98, pp. 5560-5565 (Year: 2001).
[cited by examiner]
Standards of medical care in diabetes—2021 Abridged for primary care providers, Clinical Diabetes Journal, vol. 29, pp. 14-43, 2021, doi.org/10.2337/cd21-as01, retrieved on-line on Oct. 12, 2023) (Year: 2021).
[cited by examiner]
Devaraj, et al. “Laboratory Investigation of Dyslipidemia”, Laboratory Medicine, vol. 29, pp. 432-436, 1998 (Year: 1998).
[cited by examiner]
Hagedorn et al., “Managing the sequence-specificity of antisense oligonucleotides in drug discovery”, Nucleic Acids Research vol. 45, No. 5, Published Jan. 30, 2017. (Year: 2017).
[cited by examiner]
Woolf et al., “Specificity of antisense oligonucleotides in vivo,” Proc. Natl. Acad. Sci., Aug. 1992, 7305-7309, 89, National Academy of Sciences, Washington, D.C. (5 pages).
[cited by applicant]
Gautschi et al., “Activity of a Novel bcl-2/bcl-xL-Bispecific Antisense Oligonucleotide Against Tumors of Diverse Histologic Origins,” J. Natl. Cancer Inst., Mar. 2001, 463-471, 93(6), Oxford University Press, New York.…
[cited by applicant]
Maher, L.J. et al., “Comparative hybrid arrest by tandem antisense oligodeoxyribonucleotides or oligodeoxy-ribonucleoside methylphosphonates in a cell-free system,” Nuc. Acid. Res., 1988, 3341-3358, 16(8), Oxford Univer…
[cited by applicant]
Seth et al., “Short Antisense Oligonucleotides with Novel 2′-4′ Conformationaly Restricted Nucleoside Analogues Show Improved Potency without Increased Toxicity in Animals,” J. Med. Chem., 2009, 10-13, 52, American Chem…
[cited by applicant]
Egli et al., “Synthesis, Improved Antisense Activity and Structural Rationale for the Divergent RNA Affinities of 3′-Fluoro Hexitol Nucleic Acid (FHNA and Ara-FHNA) Modified Oligonucleotides,” J. Am. Chem. Soc., 2011, 1…
[cited by applicant]
Altschul et al., “Basic Local Alignment Search Tool,” J. Mol. Biol., 1990, 403-410, 215, Elsevier, Amsterdam. (8 pages).
[cited by applicant]
Zhang et al., “PowerBLAST: A New Network BLAST Application for Interactive or Automated Sequence Analysis and Annotation,” Genome Res., 1997, 649-656, 7, Cold Spring Harbor Laboratory Press, Cold Spring Harbor. (8 pages…
[cited by applicant]
Smith, T.F. et al., “Comparison of Biosequences,” Adv. Appl. Math., 1981, 482-489, 2, Elsevier, Amsterdam. (8 pages).
[cited by applicant]
Zhou et al., “Fine Tuning of Electrostatics around the Internucleotidic Phosphate through Incorporation of Modified 2′,4′-Carbocyclic-LNAs and -ENAs Leads to Significant Modulation of Antisense Properties,” J. Org. Chem…
[cited by applicant]
Freier et al., “The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA:RNA duplexes”, Nucleic Acids Research, 1997, 4429-4443, 25(22), Oxford University Press, New Yor…
[cited by applicant]
Albaek et al., “Analogues of a Locked Nucleic Acid with Three-Carbon 2′,4′-Linkages: Synthesis by Ring-Closing Metathesis and Influence on Nucleic Acid Duplex Stability and Structure”, J. Org. Chem., 2006, 7731-7740, 71…
[cited by applicant]
Singh et al., “LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition,” Chem. Commun., 1998, 455-456, 4, Royal Society of Chemistry, London, United Kingdom. (2 pages).
[cited by applicant]
Koshkin, A.A. et al., “LNA (Locked Nucleic Acids): Synthesis of the Adenine, Cytosine, Guanine, 5-Methylcytosine, Thymine and Uracil Bicyclonucleoside Monomers, Oligomerisation, and Unprecedented Nucleic Acid Recognitio…
[cited by applicant]
Wahlestedt, C. et al., “Potent and nontoxic antisense oligonucleotides containing locked nucleic acids”, Proc. Natl. Acad. Sci., May 2000, 5633-5638, 97(10), National Academy of Sciences, Washington, D.C. (6 pages).
[cited by applicant]
Kumar et al., “The First Analogues of LNA (Locked Nucleic Acids): Phosphorothioate-LNA and 2′-Thio-LNA”, Bioorg. Med. Chem. Lett., 1998, 2219-2222, 8, Elsevier, Amsterdam. (4 pages).
[cited by applicant]
Singh et al., “Synthesis of 2′-Amino-LNA: A Novel Conformationally Restricted High-Affinity Oligonucleotide Analogue with a Handle”, J. Org. Chem., 1998, 10035-10039, 63, American Chemical Society, Washington, D.C. (5 p…
[cited by applicant]
Srivastava, P. et al., “Five- and Six-Membered Conformationally Locked 2′,4′-Carbocyclic ribo-Thymidines: Synthesis, Structure, and Biochemical Studies”, J. Am. Chem. Soc., 2007, 8362-8379, 129, American Chemical Societ…
[cited by applicant]
Elayadi et al., “Application of PNA and LNA oligomers to chemotherapy”, Curr. Opinion Inves. Drugs, 2001, 558-561, 2, PharmaPress Ltd, London, United Kingdom. (4 pages).
[cited by applicant]
Braasch et al., “Locked nucleic acid (LNA): fine-tuning the recognition of DNA and RNA”, Chem. Biol., 2001, 1-7, 8, Elsevier, Amsterdam. (7 pages).
[cited by applicant]
Frieden et al., “Expanding the design horizon of antisense oligonucleotides with alpha-L-LNA”, Nucleic Acids Research, 2003, 6365-6372, 31(21), Oxford University Press, New York. (8 pages).
[cited by applicant]
Leumann, C.J., “DNA Analogues: From Supramolecular Principles to Biological Properties”, Bioorg. & Med. Chem., 2002, 841-854, 10, Elsevier, Amsterdam. (14 pages).
[cited by applicant]
Braash, D.A. et al., “Novel Antisense and Peptide Nucleic Acid Strategies for Controlling Gene Expression,” Biochemistry, 2002, 4503-4510, 41(14), American Chemical Society, Washington, D.C. (8 pages).
[cited by applicant]
Kumar et al., “Design, synthesis, biophysical and primer extension studies of novel acyclic butyl nucleic acid (BuNA)”, Org. Biomol. Chem., 2013, 5853-5865, 11, Royal Society of Chemistry, London, United Kingdom. (13 pa…
[cited by applicant]
Englisch et al., “Chemically Modified Oligonucleotides as Probes and Inhibitors”, Angewandte Chemie, International Edition, Jun. 1991, 613-722, 30(6), VCH Verlagsgesellschaft mbH, Weinheim. (17 pages).
[cited by applicant]
Sanghvi, Y.S., Chapter 15, Antisense Research and Applications, Crooke, S.T. and Lebleu, B., Eds., CRC Press, 1993, 273-288. (19 pages).
[cited by applicant]
Agrawal, S. et al., “Antisense Research and Application”, 1998, 273-290, Springer-Verlag, New York. (21 pages).
[cited by applicant]
Crooke, S.T. et al., “Second Edition Antisense Drug Technology: Principles, Strategies, and Applications,” CRC Press, 2008, Chapters 6 and 15, 163-166 and 442-443, Boca Raton. (14 pages).
[cited by applicant]
Sanghvi, Y.S. et al., “Carbohydrate Modifications in Antisense Research,” ACS Symposium Series 580, 1994, Chapters 3 and 4, 40-65, American Chemical Society, Washington, DC. (28 pages).
[cited by applicant]
Genbank, “Mus musculus methionine adenosyltransferase I, alpha (Mat1a), mRNA,” Database accession No. NM_133653.3, Apr. 2021, National Library of Medicine, Betheseda. (4 pages).
[cited by applicant]
Genbank, “
[cited by applicant]
Genbank, “Mus musculus strain C57BL/6J chromosome 14, GRCm38.p6 C57BL/6J,” Database accession No. NC_000080.6, Jun. 2020, National Library of Medicine, Betheseda. (2 pages).
[cited by applicant]
Li et al., “The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis,” Cell Metab, 2006; 321-31, 3, Elsevier, Amsterdam. (11 pages).
[cited by applicant]
Fu et al., “Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity”, Nature, 2011, 528-31, 473, Macmillan Publishers Limited, New York City. (4 pages).
[cited by applicant]
Mato, JM et al., “S-Adenosylmethionine: a control switch that regulates liver function”, 2002, 15-26, 16(1), FASEB, Rockville. (12 pages).
[cited by applicant]
Martinez-Chantar, et al., “Loss of the Glycine N-Methyltransferase Gene Leads to Steatosis and Hepatocellular Carcinoma in Mice,” Hepatology, 2008, 1191-9, 47(4), Wiley, Hoboken, New Jersey. (9 pages).
[cited by applicant]
Martinez-Una, et al., “Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis,” Hepatology, 2013, 1296-1305, 58(4), Wiley, Hoboken, New Jersey. (19 pages).
[cited by applicant]
Martinez-Una, et al., “S-Adenosylmethionine increases circulating very-low density lipoprotein clearance in non-alcoholic fatty liver disease,” Journal of Hepatology, 2015, 673-81,62, Elsevier, Amsterdam. (9 pages).
[cited by applicant]
Gao, X. et al., “Decreased lipogenesis in white adipose tissue contributes to the resistance to high fat diet-induced obesity in phosphatidylethanolamine N-methyltransferase-deficient mice,” Biochim Biophys Acta, 2015, …
[cited by applicant]
Kraus, D. et al., “Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity,” Nature, 2014, 258-62, 508(7495), Macmillan Publishers Limited, New York City. (7 pages).
[cited by applicant]
Stone, K.P. et al., “Mechanisms of Increased In Vivo Insulin Sensitivity by Dietary Methionine Restriction in Mice,” Diabetes, Nov. 2014, 3721-3733, 63, American Diabetes Association, Arlington. (13 pages).
[cited by applicant]
Taylor, J.C. et al., “Discovery of Novel Types of Inhibitors of S-Adenosylmethionine Synthesis by Virtual Screening,” J Med Chem, 2009, 5967-5973, 52(19), American Chemical Society, Washington, DC. (7 pages).
[cited by applicant]
Genbank, “
[cited by applicant]
Genbank, “
[cited by applicant]
Henkel, A.S et al., “Homocysteine Supplementation Attenuates the Unfolded Protein Response in a Murine Nutritional Model of Steatohepatitis,” Journal of Biological Chemistry, 2009, 31807-31816, 284(46), ASBMB, Rockville…
[cited by applicant]
Finamor, I. et al., “Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice,” Redox Biology, 2017, 701-707, 11, Elsevier, Amsterdam. (7 pages).
[cited by applicant]
Cano, A. et al., “Methionine Adenosyltransferase 1A Gene Deletion Disrupts Hepatic Very Low-Density Lipoprotein Assembly in Mice,” Hepatology, Dec. 2011, 1975-1986, 54(6), American Association for the Study of Liver Dis…
[cited by applicant]
Mato, J.M. et al., “S-adenosylmethionine metabolism and liver disease,” Ann Hepatol., 2013, 183-189, 12(2), Elsevier, Amsterdam. (11 pages).
[cited by applicant]
Yang, H. et al., “MicroRNAs regulate methionine adenosyltransferase 1A expression in hepatocellular carcinoma,” Journal of Clinical Investigation, 2012, 285-298, 123(1), American Society for Clinical Investigation, Ann …
[cited by applicant]
Wu, S. et al., “Thyroid hormone receptor-mediated regulation of the methionine adenosyltransferase 1 gene is associated with cell invasion in hepatoma cell lines,” Cellular and Molecular Life Sciences, 2010, 1831-1843, …
[cited by applicant]
Michelotti, G.A. et al, “NAFLD, NASH and liver cancer,” Nat Rev Gastroenterol Hepatol, 2013, 656-65, 10(11), Macmillan Publishers Limited, New York. (10 pages).
[cited by applicant]
Albhaisi, S. et al., “Non-alcoholic fatty liver disease in lean individuals,” JHEP Reports, 2019, 329-341, 1, EASL, Geneva, Switzerland. (13 pages).
[cited by applicant]
Denkmayr L. et al., “Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients,” J. Clin. Med. 2018, 562, 7, MDPI, Basel, Switzerland. (12 pages).
[cited by applicant]
Kauppinen, S. et al., “Locked nucleic acid (LNA): High affinity targeting of RNA for diagnostics and therapeutics,” Drug Discov Today Technol., 2005, 287-90, 2(3), Elsevier, Amsterdam. (4 pages).
[cited by applicant]
Zhao, Y. et al., “Lack of Phosphatidylethanolamine N-Methyltransferase Alters Plasma VLDL Phospholipids and Attenuates Atherosclerosis in Mice,” Arterioscler Thromb Vasc Biol, 2009, 1349-1355, 29, American Heart Associa…
[cited by applicant]
Orum, et al., “Locked nucleic acids: a promising molecular familyfor gene-function analysis and antisense drugdevelopment,” Curr. Opinion Mol. Ther., 2001, 239-243, 3(3), National Library of Medicine, Bethesda. (1 page)…
[cited by applicant]
Kroschwitz, J.I., Concise Encyclopedia Of Polymer Science And Engineering, 1990, 858-859, John Wiley & Sons, Hoboken. (2 pages); Cannot Locate Reference. Book Review Only.
[cited by applicant]
Zhao, Y. et al., “Role of phosphatidylethanolamine N-methyltransferase (PEMT) in hepatic VLDL production,” FASEB J, 2006, A1346-A1346, 20(5), FASEB, Rockville. (2 pages).
[cited by applicant]