Granted Patent
B2
US 12,247,068 · App. 17/327,170 · Granted Mar 11, 2025
Anti-AP2 antibodies and antigen binding agents to treat metabolic disorders
Inventors:
Gökhan S. Hotamisligil (Wellesley, MA); Mehmet F. Burak (Brighton, MA); Feyza Engin (Madison, WI); Scott B. Widenmaier (Brighton, MA); Karen Inouye (Boston, MA); Elisabeth Helen Roberts (Slough, GB); Adrian Richard Moore (Slough, GB); Carl Brendan Doyle (Slough, GB); Ralph Adams (Slough, GB); Karine Jeannine Madeleine Hervé (Vancouver, CA); Shauna Mhairi Wales (Slough, GB); Kerry Louise Tyson (Slough, GB)
C07K16/18A61K39/00A61K2039/505A61K2039/507A61K2039/6018C07K2317/24C07K2317/55C07K2317/565C07K2317/70C07K2317/76C07K2317/92
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Abstract
This invention is in the area of improved anti-aP2 antibodies and antigen binding agents, and compositions thereof, which target the lipid chaperone aP2/FABP4 (referred to as “aP2”) for use in treating disorders such as diabetes, obesity, cardiovascular disease, fatty liver disease, and/or cancer, among others. In one aspect, improved treatments for aP2 mediated disorders are disclosed in which serum aP2 is targeted and the biological activity of aP2 is neutralized or modulated using low-binding affinity aP2 monoclonal antibodies, providing lower fasting blood glucose levels, improved systemic glucose metabolism, increased systemic insulin sensitivity, reduced fat mass, reduced liver steatosis, reduced cardiovascular disease and/or a reduced risk of developing cardiovascular disease.
Claims (29)
1. A method of reducing or attenuating the biological activity of secreted adipocyte protein 2 (aP2) in a human comprising administering an effective amount of a humanized anti-aP2 monoclonal antibody or antigen binding agent comprising:
(a) a light chain variable region comprising:
(i) a CDR-L1 complementarity determining region (CDR) comprising the amino acid sequence of Seq. ID No. 7;
(ii) a CDR-L2 CDR comprising the amino acid sequence of Seq. ID No. 8; and
(iii) a CDR-L3 CDR comprising an amino acid sequence selected from the group consisting of Seq. ID No. 9, Seq. ID No. 10, Seq. ID No. 11, and Seq. ID No. 12; and
(b) a heavy chain variable region comprising:
(i) a CDR-H1 CDR comprising the amino acid sequence of Seq. ID No. 14;
(ii) a CDR-H2 CDR comprising an amino acid sequence selected from the group consisting of Seq. ID No. 16 and Seq. ID No. 17; and
(iii) a CDR-H3 CDR comprising an amino acid sequence selected from the group consisting of Seq. ID No. 19 and Seq. ID No. 20.
2. The method of claim 1 , wherein reduction or attenuation of the biological activity of secreted aP2 results in lower fasting blood glucose levels.
3. The method of claim 1 , wherein reduction or attenuation of the biological activity of secreted aP2 results in increased insulin sensitivity.
4. The method of claim 1 , wherein reduction or attenuation of the biological activity of secreted aP2 results in reduced liver steatosis.
5. The method of claim 1 , wherein reduction or attenuation of the biological activity of secreted aP2 results in improved serum lipid profiles.
6. The method of claim 1 , wherein reduction or attenuation of the biological activity of secreted aP2 results in reduced atherogenic plaque formation.
7. The method of claim 1 , wherein the reduction or attenuation of the biological activity of secreted aP2 results in a decrease of liver glucose production.
8. The method of claim 1 , wherein the reduction or attenuation of the biological activity of secreted aP2 results in a decrease of triglyceride levels.
9. The method of claim 1 , wherein the reduction or attenuation of the biological activity of secreted aP2 results in a decrease of total cholesterol levels.
10. The method of claim 1 , wherein the reduction or attenuation of the biological activity of secreted aP2 results in a decrease of low-density lipoprotein (LDL).
11. The method of claim 1 , wherein the reduction or attenuation of the biological activity of secreted aP2 results in a decrease of very low-density lipoprotein (VLDL).
12. The method of claim 1 , wherein the humanized anti-aP2 monoclonal antibody or antigen binding agent comprises:
(a) a light chain variable region comprising an amino acid sequence selected from the group consisting of Seq. ID No. 446, Seq. ID No. 448, Seq. ID No. 487, Seq. ID No. 488, Seq. ID No. 450, and Seq. ID No. 452; and
(b) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of Seq. ID No. 455, Seq. ID No. 457, Seq. ID No. 459, Seq. ID No. 461, and Seq. ID No. 463.
13. The method of claim 12 , wherein the light chain variable region comprises the amino acid sequence of Seq. ID No. 446.
14. The method of claim 12 , wherein the heavy chain variable region comprises the amino acid sequence of Seq. ID No. 455.
15. The method of claim 13 , wherein the heavy chain variable region comprises the amino acid sequence of Seq. ID No. 455.
16. The method of claim 12 , wherein the heavy chain variable region comprises the amino acid sequence of Seq. ID No. 461.
17. The method of claim 13 , wherein the heavy chain variable region comprises the amino acid sequence of Seq. ID No. 461.
18. The method of claim 12 , wherein the heavy chain variable region comprises the amino acid sequence of Seq. ID No. 463.
19. The method of claim 13 , wherein the heavy chain variable region comprises the amino acid sequence of Seq. ID No. 463.
Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 3, 2025
From: BURAK, MEHMET F.; HOTAMISLIGIL, GÖKHAN S.; WIDENMAIER, SCOTT B.; ENGIN, FEYZA
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 070092/0048 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 3, 2025
From: INOUYE, KAREN
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 070092/0063 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 3, 2025
From: MOORE, ADRIAN RICHARD; DOYLE, CARL BRENDAN; ADAMS, RALPH; ROBERTS, ELISABETH HELEN; WALES, SHAUNA MHAIRI; HERVÉ, KARINE JEANNINE MADELEINE; TYSON, KERRY LOUISE
To: UCB BIOPHARMA SPRL
Reel/Frame 070092/0092 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 3, 2025
From: UCB BIOPHARMA SPRL
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 070092/0105 →
Continuity (6)
Provisional Application
62268257
· Dec 16, 2015
Provisional Application
62232148
· Sep 24, 2015
Provisional Application
62155217
· Apr 30, 2015
References Cited (120)
US 5858366A
· Sodroski et al.
· 1999
[cited by applicant]
US 5889167A
· Cascieri et al.
· 1999
[cited by applicant]
US 6548529B1
· Robl et al.
· 2003
[cited by applicant]
US 7390824B1
· Robl et al.
· 2008
[cited by applicant]
US 7906117B2
· Smith et al.
· 2011
[cited by applicant]
US 8846413B2
· Ruzicka
· 2014
[cited by applicant]
US 9062104B2
· Garcia-Martinez et al.
· 2015
[cited by applicant]
US 20020035064A1
· Robl et al.
· 2002
[cited by applicant]
US 20040010119A1
· Guo et al.
· 2004
[cited by applicant]
US 20040110226A1
· Lazar et al.
· 2004
[cited by applicant]
US 20120134998A1
· Hotamisligil et al.
· 2012
[cited by applicant]
US 20150093769A1
· Ruzicka
· 2015
[cited by applicant]
CN 103665139A
· 2014
[cited by applicant]
DE 102006034607A
· 2007
[cited by applicant]
WO WO2000015229
· 2000
[cited by applicant]
WO WO2000015230
· 2000
[cited by applicant]
WO WO2000047734
· 2000
[cited by applicant]
WO WO2003043624
· 2003
[cited by applicant]
WO WO2010057260
· 2010
[cited by applicant]
WO WO2010102171
· 2010
[cited by applicant]
WO WO2014093189
· 2014
[cited by applicant]
WO WO2016044337
· 2016
[cited by applicant]
U.S. Pat. No. 9,879,078, U.S. Appl. No. 15/093,508, Hotamisligil et al., Jan. 30, 2018.
[cited by applicant]
U.S. Pat. No. 10,160,798, U.S. Appl. No. 15/143,162, Hotamisligil et al., Dec. 25, 2018.
[cited by applicant]
U.S. Pat. No. 10,882,901, U.S. Appl. No. 15/851,040, Hotamisligil et al., Jan. 5, 2021.
[cited by applicant]
U.S. Pat. No. 11,014,979, U.S. Appl. No. 16/197,066, Hotamisligil et al., May 25, 2021.
[cited by applicant]
U.S. Pat. No. 11,345,748, U.S. Appl. No. 16/708,015, Hotamisligil et al., May 31, 2022.
[cited by applicant]
U.S. Pat. No. 11,685,774, U.S. Appl. No. 17/102,329, Hotamisligil et al., Jun. 27, 2023.
[cited by applicant]
2021/0171599, U.S. Appl. No. 16/937,316, Hotamisligil et al., Jun. 10, 2021.
[cited by applicant]
2022/0411490, U.S. Appl. No. 17/825,697, Hotamisligil et al., Dec. 29, 2022.
[cited by applicant]
2023/0203142, U.S. Appl. No. 17/983,098, Hotamisligil et al., Jun. 29, 2023.
[cited by applicant]
2024/0209072, U.S. Appl. No. 18/341,404, Hotamisligil et al., Jun. 27, 2024.
[cited by applicant]
Almagro & Fransson Frontiers in Bioscience. 13:1619-1633, 2008.
[cited by applicant]
Barf et al. N-Benzyl-indolo carboxylic acids: Design and synthesis of potent and selective adipocyte fatty-acid binding protein (A-FABP) inhibitors. Bioorganic and Medicinal Chemistry Letters. 19(6):1745-1748, Mar. 15, …
[cited by applicant]
Banaszak et al. Lipid-binding proteins: a family of fatty acid and retinoid transport proteins. Adv. Protein Chem. 45:89-151, 1994.
[cited by applicant]
Baxa et al. Human adipocyte lipid-binding protein: purification of the protein and cloning of its complementary DNA. Biochemistry. 28:8683-8690, 1989.
[cited by applicant]
Blanc et al. Exosome release by reticulocytes—An integral part of the red blood cell differentiation system. Blood Cells, Molecules and Diseases. 35:21-26, 2005.
[cited by applicant]
Boord et al. Adipocyte Fatty Acid-Binding protein, aP2, Alters Late Atherosclerotic Lesion Formation in Severe Hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 22(10):1686-1691, Oct. 2002.
[cited by applicant]
Brand, C.L. et al. Immunoneutralization of endogenous glucagon with monoclonal glucagon antibody normalizes hyperglycaemia in moderately streptozotocin-diabetic rats. Diabetologia. 34(10):985-993, 1994.
[cited by applicant]
Burak, M.F. et al. Development of a therapeutic monoclonal antibody targeting secreted aP2 to treat type 2 diabetes. PDB:5D8J deposited on Aug. 17, 2015 and available at: www.rcsb.org/pdb/explore/explore do?structureId=…
[cited by applicant]
Burak, M.F. et al. Chain L, Development of a Therapeutic Monoclonal Antibody Targeting Secreted Ap2 To Treat Type 2 Diabetes. PDB:5D8J_L deposited on Aug. 17, 2015 and available at: www.ncbi.nlm.nih.gov/protein/5D8J_L, …
[cited by applicant]
Burak, M.F. et al. Chain D, Development of a Monoclonal Antibody Targeting Secreted Ap2 to Treat Diabetes and Fatty Liver Disease. PDB:5CON_D deposited on Jun. 12, 2015 and available at: www.ncbi.nlm.nih.gov/protein/5C0…
[cited by applicant]
Burak, M.F. et al. Development of a monoclonal antibody targeting secreted aP2 to treat diabetes and fatty liver disease. PDB:5CON deposited on Jun. 12, 2015 and available at: www.rcsb.org/pdb/explore/explore.do?structu…
[cited by applicant]
Cabre et al. Fatty acid binding protein 4 is increased in metabolic syndrome and with thiazolidinedione treatment in diabetic patients. Atherosclerosis. 195(1):e150-e158, Nov. 2007.
[cited by applicant]
Cai et al. Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein 4 in vitro and lowers the blood glucose level in db/db mice. Acta Pharmacologica Sinica. 34:1397-1402, 2013.
[cited by applicant]
Cao et al. Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism. Cell. 134:933-944, Sep. 19, 2008.
[cited by applicant]
Cao et al. Adipocyte lipid chaperone aP2 is a secreted adipokine regulating hepatic glucose production. Cell Metabolism. 17(5):768-778, May 2013.
[cited by applicant]
Cao et al. Regulation of Metabolic Responses by Adipocyte/Macrophage Fatty Acid-Binding Proteins in Leptin-Deficient Mice. Diabetes. 55:1915-1922, Jul. 2006.
[cited by applicant]
Cayman Chemical FABP4 Polyclonal Antibody product sheet (5 pages) downloaded on Sep. 30, 2015.
[cited by applicant]
Chen et al. Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations. The EMBO Journal. 14(12):2784-2794, 1995.
[cited by applicant]
Colman, P.M. Effects of amino acid sequence changes on antibody-antigen interactions. Research in Immunology. Editions Scientifiques et Medicales Elsevier FR. 145(1):33-36, 1994.
[cited by applicant]
Defronzo. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Brenard Lecture 2009. Diabetologia. 53:1270-1287, 2010.
[cited by applicant]
De Genst, E. et al. Antibody repertoire development in camelids. Dev Comp Immunol. 30(1-2):187-198, 2006.
[cited by applicant]
Distel et al. Fatty Acid Regulation of Gene Expression: Transcriptional and Post-Transcriptional Mechanism. The Journal of Biological Chemistry. 267(9):5937-5941, Mar. 25, 1992.
[cited by applicant]
Erbay et al. Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nature Medicine. 15(12):1383-1391, Dec. 2009.
[cited by applicant]
Ertunc et al. Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity. Journal of Lipid Research. 56:423-434, 2015.
[cited by applicant]
European Search Report for PCT/US2016/030303 mailed on Apr. 20, 2020.
[cited by applicant]
European Search Report for PCT/US2017/039585 mailed on Feb. 18, 2020.
[cited by applicant]
Fu et al. Oxidized LDL induces the expression of ALBP/aP2 mRNA and protein in human THP-1 macrophages. Journal of Lipid Research. 41(12):2017-2023, Dec. 2000.
[cited by applicant]
Furuhashi et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 447(21):959-965, 2007.
[cited by applicant]
Furuhashi et al. Adipocyte/Macrophage Fatty Acid-Binding Proteins Contribute to Metabolic Deterioration Through Actions in Both Macrophages and Adipocytes in Mice. J Clin Invest. 118(7):2640-2650, Jul. 2008.
[cited by applicant]
Furuhashi et al. Serum Fatty Acid-Binding Protein 4 is a Predictor of Cardiovascular Events in End-Stage Renal Disease. PLOS ONE. 6(11):e27356, Nov. 2011.
[cited by applicant]
Gillilan et al. Structural Basis for Activation of Fatty Acid-binding Protein 4. J Mol Biol. 372:1246-1260, 2007.
[cited by applicant]
Girona et al. FABP4 Induces Vascular Smooth Muscle Cell Proliferation and Migration through a MAPK-Dependent Pathway. PLoS ONE. 8(11):e81914, Nov. 2013.
[cited by applicant]
Gorbenko et al. Generation and Characterization of Monoclonal Antibodies against FABP4. Hybridoma. 25(2):86-90, 2006.
[cited by applicant]
Hall et al. USP7 Attenuates Hepatic Gluconoegenesis Through Modulation of FoxO1 Gene Promoter Occupancy. Mol Endocrinol. 28(6):912-924, Jun. 2014.
[cited by applicant]
Hecker et al. Heat Shock proteins as biomarkers for the rapid detection of brain and spinal cord ischemia: a review and comparison to other methods of detection in thoracic aneurysm repair. Cell Stress and Chaperones. 1…
[cited by applicant]
Hellberg et al. X-ray crystallographic analysis of adipocyte fatty acid binding protein (aP2) modified with 4-hydroxy-2-nonenal. Protein Science. 19:1480-1489, 2010.
[cited by applicant]
Hertzel et al. Identification and characterization of a small molecule inhibitor of Fatty Acid binding proteins. Journal of Medicinal Chemistry. 52(19):6024-6031, Oct. 8, 2009.
[cited by applicant]
Hoo et al. Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice. Journal of Hepatology, 58: 358-364, 2013.
[cited by applicant]
Hotamisligil et al. Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in aP2, the Adipocyte Fatty Acid Binding Protein. Science. 274(5291):1377-1379, Nov. 22, 1996.
[cited by applicant]
Hunt et al. Adipocyte P2 gene: Developmental expression and homology of 5′—flanking sequences among fat cell-specific genes. PNAS. 83:3786-3790, Jun. 1986.
[cited by applicant]
Hunter-Lavin et al. Hsp70 release from peripheral blood mononuclear cells. Biochemical and Biophysical Research Communications. 324(2):511-517, Nov. 12, 2004.
[cited by applicant]
Ishimura et al. Circulating Levels of Fatty Acid-Binding Protein Family and Metabolic Phenotype in the General Population. PLUS ONE. 8(11):e81318, Nov. 2013.
[cited by applicant]
Jack et al. C-terminal binding protein: A metabolic sensor implicated in regulating adipogenesis. The International Journal of Biochemistry & Cell Biology. 43:693-696, 2011.
[cited by applicant]
Joyner, C.J. et al. Development of a monoclonal antibody to the aP2 protein to identify adipocyte precursors in tumors of adipose differentiation. Pathology of Research and Practice. 195(7):461-466, 1999.
[cited by applicant]
Kaess et al. Cardiometabolic Correlates and Heritability of Fetuin-A, Retinol-Binding Protein 4, and Fatty-Acid Binding Protein 4 in the Framingham Heart Study. J Clin Endocrinol Metab. 97(10):e1943-e1947, Oct. 2012.
[cited by applicant]
Kajimura et al. Regulation of the brown and white fat gene programs through a PRDM16/ctBp transcriptional complex. Genes & Development. 22:1397-1409, 2008.
[cited by applicant]
Karakas et al. Serum fatty acid binding protein 4, free fatty acids, and metabolic risk markers. Metabolism Clinical and Experimental. 58:1002-1007, 2009.
[cited by applicant]
Kashima et al. Diagnostic utility of aP2/FABP4 expression in soft tissue tumors. Virchows Archiv., 462(4): 465-472, Apr. 2013.
[cited by applicant]
Kussie, P.H. et al. A single engineered amino acid substitution changes antibody fine specificity. J Immunol. 152(1):146-152, Jan. 1, 1994.
[cited by applicant]
Lalonde et al. X-ray Crystallographic Structures of Adipocyte Lipid-Binding Protein Complexed with Palmitate and Hexadecanesulfonic Acid. Properties of Cavity Binding Sites. Biochemistry. 33:4885-4895, 1994.
[cited by applicant]
Lan et al. Small-molecule inhibitors of FABP4/5 ameliorate dyslipidemia but not insulin resistance in mice with diet-induced obesity. Journal of Lipid Research. 52(4):646-656, Apr. 2011.
[cited by applicant]
Layne et al. Role of macrophage-expressed adipocyte fatty acid binding protein in the development of accelerated atherosclerosis in hypercholesterolemic mice. The FASEB Journal. 15:2733-2735, Dec. 2001.
[cited by applicant]
Lehmann et al. Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target. Bioorganic and Medicinal Chemistry Letters. 14(17):4445-4448, Sep. 6, 2004.
[cited by applicant]
Lin et al. Hormonal Regulation of Hepatic Glucose Production in Health and Disease. Cell Metabolism, 14:9-19, Jul. 6, 2011.
[cited by applicant]
Maeda et al. Adipocyte/Macrophage Fatty-Acid Bonding Proteins Control Integrated Metabolic Responses in Obesity and Diabetes. Cell Metab. 1:107-119, Feb. 2005.
[cited by applicant]
Makowski et al. Lack of Macrophage Fatty-Acid-Binding Protein aP2 Protects Mice Deficient in Apolipoprotein E Against Atherosclerosis. Nat. Med. 7(6):699-705, Jun. 2001.
[cited by applicant]
Makowski et al. The Fatty Acid-binding Protein, aP2, Coordinates Macrophage Cholesterol Trafficking and Inflammatory Activity. The Journal of Biological Chemistry. 280(13):12888-12895, Apr. 1, 2005.
[cited by applicant]
Melki et al. Expression of the adipocyte fatty acid-binding protein streptozotocin-diabetes: effects of insulin deficiency and supplementation. Journal of Lipid Research. 34:1527-1534, 1993.
[cited by applicant]
Miao et al. The mAb against adipocyte fatty acid-binding protein 2E4 attenuates the inflammation in the mouse model of high-fat diet-induced obesity via toll-like recetor 4 pathway. Molecular and Cellular Endocrinology.…
[cited by applicant]
Muniyappa et al. Am J Physiol Endocrinol Metab. 294:E15-E26, 2009.
[cited by applicant]
Nardini et al. CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission. The EMBO Journal. 22(12):3122-3130, 2003.
[cited by applicant]
Ozcan et al. Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes. Science. 313(5790):1137-1140, Aug. 25, 2006.
[cited by applicant]
PCT/US2016/030303, Invitation to pay additional fees and, where applicable, protest fee, mailed Sep. 12, 2016.
[cited by applicant]
PK Office Action for Pakistan application No. 246/2016, Sep. 26, 2017.
[cited by applicant]
Ringom et al. Substituted benzylamino-6-(trufluoromethyl)pyramidin-4(1H)-ones: a novel class of selective human A-FABP inhibitors. Bioorganic and Medicinal Chemistry Letters. 14:4449-4452, 2004.
[cited by applicant]
Rosen et al. Adipocytes as Regulators of Energy Balance and Glucose Homeostasis. Nature. 444:847-853, Dec. 14, 2006.
[cited by applicant]
Rudikoff, et al. Single amino acid substitution altering antigen-binding specificity. Proc Natl Acad Sci U S A. 79(6):1979-1983, 1982.
[cited by applicant]
Saksi et al. Low-Expression Variant of Fatty Acid-Binding Protein 4 Flavors Reduced Manifestations of Altherosclerotic Disease and Increased Plaque Stability. Circ. Cardiovasc. Genet., 7: 588-598, 2014.
[cited by applicant]
Storch et al. Structural and functional analysis of fatty acid-binding proteins. Journal of Lipid Research. 50:S126-S131, 2009.
[cited by applicant]
Suh et al. Serum AFBP levels are elevated in patients with nonalcoholic fatty liver disease. Scandinavian Journal of Gastroenterology, 49(8): 979-985, 2014.
[cited by applicant]
Sulsky et al. Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP). Bioorganic and Medicinal Chemistry Letters. 17(12):351-3515, Jun. 15, 2007.
[cited by applicant]
Tuncman et al. A genetic variant at the fattyacid-binding protein aP2 locus reduces the risk for hypertriglceridemia, type 2 diabetes, and cardiovascular disease. PNAS, 103(18): 6970-6975, May 2, 2006.
[cited by applicant]
Uysal, K.T. et al. Improved Glucose and Lipid Metabolism in Genetically Obese Mice Lacking aP2. Endocrinology. 141:3388-3396, 2000.
[cited by applicant]
Van Dongen et al. Structure-based screening as applied to human FABP4: a highly efficient alternative to HTS for hit generation. Journal of the American Chemical Society. 124(40): 11874-11880, Oct. 9, 2002.
[cited by applicant]
Vernochet et al. C/EBPalpha and the Corepressors CtBP2 Regulate Repression of Select Visceral White Adipose Genes during Induction of the Brown Phenotype in White Adipocytes by Peroxisome Proliferator-Activated Receptor…
[cited by applicant]
Von Eynatten et al. Circulating Adipocyte Fatty Acid-Binding Protein Levels and Cardiovascular Morbidity and Mortality in Patients with Coronary Heart Disease—A 10-year Prospective Study. Arteriscler Thromb Vasc Biol. 3…
[cited by applicant]
Won et al. Oligopeptide complex for targeted non-viral gene delivery to adipocytes. Nature Materials, 1157-1164, Dec. 13, 2014.
[cited by applicant]
Xu et al. The adipocyte lipid-binding protein at 1.6-A resolution. Crystal structures of the apoprotein and with bound saturated and unsaturated fatty acids. Journal of Biological Chemistry. 268:7874-7884, 1993.
[cited by applicant]
Xu et al. Adipocyte Fatty-Acid-Binding Protein is a Plasma Biomarker Closely Associated with Obesity and Metabolic Syndrome. Clinical Chemistry. 52(3):405-413, 2006.
[cited by applicant]
Xu et al. Circulating Adipocyte-Fatty Acid Binding Protein Levels Predict the Development of the Metabolic Syndrome—A 5-year Prospective Study. Circulation. 115:1537-1543, 2007.
[cited by applicant]
Yoo et al. Serum Adipocyte Fatty Acid-Binding Protein Is Associated Independently with Vascular Imflammation: Analysis with 18F-Fluorodeoxyglucose Positron Emission Tomography. J Clin Endocrinol Metab. 96(3):E488-E492, …
[cited by applicant]
Zhang et al. Exosomes a novel pathway to local and distant intercellular communication that facilitates the growth and metastasis of neoplastic lesions. American Journal of Pathology. 184(1):28-41, Jan. 2014.
[cited by applicant]
Cited By (1)