Granted Patent
B2
US 12,364,735 · App. 17/826,659 · Granted Jul 22, 2025
Lipoprotein complexes and manufacturing and uses thereof
Inventors:
Jean-Louis Dasseux (Toulouse, FR); Rose Ackermann (Northville, MI); Daniela Carmen Oniciu (Toulouse, FR)
Assignee:
ABIONYX PAHRMA SA
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present disclosure relates to lipoprotein complexes and lipoprotein populations and their use in the treatment and/or prevention of dyslipidemic diseases, disorders, and/or conditions. The disclosure further relates to recombinant expression of apolipoproteins, purification of apolipoproteins, and production of lipoprotein complexes using thermal cycling-based methods.
Claims (36)
1. A method for preparing lipoprotein complexes, comprising:
(a) cooling a starting suspension comprising a lipid component and a protein component from a temperature in a first temperature range to a temperature in a second temperature range, wherein:
(i) the lipid component comprises sphingomyelin;
(ii) the protein component comprises Apolipoprotein A-I (ApoA-I) and 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac (1-glycerol)] (“DPPG”);
(iii) the weight:weight (wt:wt) ratio of the sphingomyelin to the DPPG in the starting suspension is 97:3;
(iv) the protein:total lipid weight ratio in the starting suspension is 1:2.7; and
(v) the first temperature range is 55° C. to 60° C. and the second temperature range is between 35° C. and 40° C.;
(b) heating the cooled suspension of (a) from a temperature in the second temperature range to a temperature in the first temperature range;
(c) cooling the heated suspension of (b) from a temperature in the first temperature range to a temperature in the second temperature range; and
(d) repeating steps (b) and (c) until at least 80% of the protein component is incorporated into lipoprotein complexes,
thereby forming lipoprotein complexes.
2. The method of claim 1 , wherein the ApoA-I is a human ApoA-I protein.
3. The method of claim 1 , wherein the Apo A-I is a recombinant ApoA-I.
4. The method of claim 1 , wherein the ApoA-I has an amino acid sequence with at least 95% sequence identity to a protein corresponding to amino acids 25 to 267 of SEQ ID NO: 1.
5. The method of claim 4 , wherein the ApoA-I is expressed by a mammalian host cell engineered to express the ApoA-I.
6. The method of claim 5 , wherein the mammalian host cell is a Chinese hamster ovary (CHO), CHO-S, CHO-KI, VERO, BHK, BHK 570, HeLa, COS-I, COS-7, MDCK cells, 293, 3T3, myeloma, PC12 or W138 cell.
7. The method of claim 6 , wherein the mammalian host cell is a CHO cell.
8. The method of claim 7 , wherein the mammalian host cell is a CHO-S cell.
9. The method of claim 1 , wherein the temperature in the first temperature range is 57° C.
10. The method of claim 1 , wherein the temperature in the second temperature range is 37° C.
11. The method of claim 1 , in which steps (b) and (c) are repeated until at least 85% of the protein component is incorporated into lipoprotein complexes.
12. The method of claim 1 , in which steps (b) and (c) are repeated until at least 90% of the protein component is incorporated into lipoprotein complexes.
13. The method of claim 1 , in which steps (b) and (c) are repeated until at least 95% of the protein component is incorporated into lipoprotein complexes.
14. The method of claim 1 , wherein step (d) comprises repeating steps (b) and (c) at least three times.
15. The method of claim 1 , wherein step (d) comprises repeating steps (b) and (c) until lipoprotein complexes of 4 nm to 15 nm in diameter are obtained, as measured by gel filtration chromatography.
16. The method of claim 1 , further comprising, prior to step (a), the step of forming the starting suspension by a process comprising combining the lipid component and the protein component.
17. The method of claim 16 , wherein the lipid component and the protein component are each preheated at a temperature in the first range.
18. The method of claim 16 , which further comprises, prior to the step of forming the starting suspension, the step of subjecting the lipid component to high pressure homogenization.
19. The method of claim 1 , wherein the temperature in the first temperature range is 57° C. and the temperature in the second temperature range is 37° C.
20. The method of claim 1 , wherein the ApoA-I has an amino acid sequence comprising amino acids 25 to 267 of SEQ ID NO:1.
21. A method for making a pharmaceutical composition, comprising:
(a) preparing a population of lipoprotein complexes according to the method of claim 1 ; and
(b) combining the population of lipoprotein complexes with one or more pharmaceutically acceptable excipients.
22. A method for making a pharmaceutical composition, comprising:
(a) preparing a population of lipoprotein complexes according to the method of claim 19 ; and
(b) combining the population of lipoprotein complexes with one or more pharmaceutically acceptable excipients.
Assignments (2)
CHANGE OF NAME
Recorded Jun 4, 2025
From: CERENIS THERAPEUTICS HOLDING S.A.
To: ABIONYX PHARMA S.A.
Reel/Frame 071495/0745 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 2, 2025
From: DASSEUX, JEAN-LOUIS; ONICIU, DANIELA CARMEN; ACKERMANN, ROSE
To: CERENIS THERAPEUTICS HOLDING S.A.
Reel/Frame 071289/0158 →
Continuity (8)
Provisional Application
61487263
· May 17, 2011
Provisional Application
61452630
· Mar 14, 2011
Provisional Application
61440371
· Feb 7, 2011
References Cited (148)
US 5116739A
· Teranishi et al.
· 1992
[cited by applicant]
US 5408038A
· Smith et al.
· 1995
[cited by applicant]
US 5874075A
· Collins et al.
· 1999
[cited by applicant]
US 5876968A
· Sirtori et al.
· 1999
[cited by applicant]
US 6090608A
· Oppenheim et al.
· 2000
[cited by applicant]
US 6090921A
· Winge et al.
· 2000
[cited by applicant]
US 6258596B1
· Benoit et al.
· 2001
[cited by applicant]
US 6287590B1
· Dasseux
· 2001
[cited by applicant]
US 6306433B1
· Andersson et al.
· 2001
[cited by applicant]
US 6413744B1
· Morris et al.
· 2002
[cited by applicant]
US 6455088B1
· Dasseux
· 2002
[cited by applicant]
US 6503498B1
· Gerard et al.
· 2003
[cited by applicant]
US 6617134B1
· Sirtori et al.
· 2003
[cited by applicant]
US 6844327B2
· Dasseux
· 2005
[cited by applicant]
US 6852510B2
· Bremel et al.
· 2005
[cited by applicant]
US 6953840B2
· Zhu et al.
· 2005
[cited by applicant]
US 7157557B2
· Sassenfeld et al.
· 2007
[cited by applicant]
US 7179484B2
· Singh
· 2007
[cited by applicant]
US 7189411B2
· Dasseux et al.
· 2007
[cited by applicant]
US 7223726B2
· Oda et al.
· 2007
[cited by applicant]
US 7332333B2
· Bremel et al.
· 2008
[cited by applicant]
US 7378273B2
· Bleck
· 2008
[cited by applicant]
US 7575763B2
· Sligar et al.
· 2009
[cited by applicant]
US 7994120B2
· Dasseux et al.
· 2011
[cited by applicant]
US 8206750B2
· Dasseux
· 2012
[cited by applicant]
US 8617615B2
· Dasseux
· 2013
[cited by applicant]
US 9187551B2
· Dasseux et al.
· 2015
[cited by applicant]
US 9567388B2
· Dasseux
· 2017
[cited by applicant]
US 20080293633A1
· Bisgaier et al.
· 2008
[cited by applicant]
US 20110293557A1
· Prieto Valtuena et al.
· 2011
[cited by applicant]
US 20120232005A1
· Dasseux et al.
· 2012
[cited by applicant]
WO 198604144A1
· 1986
[cited by applicant]
WO 198803166A1
· 1988
[cited by applicant]
WO 199012879A2
· 1990
[cited by applicant]
WO 199300443A1
· 1993
[cited by applicant]
WO 199312143A1
· 1993
[cited by applicant]
WO 199413819A1
· 1994
[cited by applicant]
WO 199525786A1
· 1995
[cited by applicant]
WO 199530762A1
· 1995
[cited by applicant]
WO 199627608A1
· 1996
[cited by applicant]
WO 200202738A2
· 2002
[cited by applicant]
WO 2003096983A2
· 2003
[cited by applicant]
WO 2004010939A2
· 2004
[cited by applicant]
WO 2005007803A2
· 2005
[cited by applicant]
WO 2005041866A2
· 2005
[cited by applicant]
WO 2005072129A2
· 2005
[cited by applicant]
WO 2006012632A2
· 2006
[cited by applicant]
WO 2006100567A1
· 2006
[cited by applicant]
WO 2007023476A2
· 2007
[cited by applicant]
WO 2008104890A2
· 2008
[cited by applicant]
WO 2008141230A1
· 2008
[cited by applicant]
WO 2009055538A1
· 2009
[cited by applicant]
WO 2010093918A1
· 2010
[cited by applicant]
WO 2012109162A1
· 2012
[cited by applicant]
Walsh et al., J. Lipid Res. 31:1051-1062 (1990) (Year: 1990).
[cited by examiner]
Suurkuusk et al., Eur. J. Biochem. 265:346-352 (1999) (Year: 1999).
[cited by examiner]
Arsov et al., Chem. Physics Lipids 213:102-110 (2018) (Year: 2018).
[cited by examiner]
NP_000030.1, apolipoprotein A-I isoform 1 preproprotein [
[cited by applicant]
GenBank: AAA62829.1, proapolipoprotein [
[cited by applicant]
Kopfler et al., 1994, “Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice icreases circulating high-density lipoprotein cholesterol,” Circulation 90(3):1319-1327.
[cited by applicant]
Makrides, 2004, “Chapter 2: Vectors for gene expression in mammalian cells,” New Comprehensive Biochemistry 38:9-26.
[cited by applicant]
Palomares et al., 2004, “Production of recombinant proteins: challenges and solutions,” Methods Mol Biol 267:15-52.
[cited by applicant]
Altamirano et al., 2006, “Specific nutrient supplementation of defined serum-free medium for the improvement of CHO cells growth and t-PA production,” Electronic Journal of Biotechnology, 9(1).
[cited by applicant]
Asztalos et al., 1997, “Role of Free Apolipoprotein A-I in Cholesterol Efflux,” Arterioscler Thromb Basc Biol, 17(9):1630-1637.
[cited by applicant]
Benjwal et al., 2006, “Monitoring protein aggregation during thermal unfolding in circular dichroism experiments,” Protein Science, 15:635-639.
[cited by applicant]
Bielicki et al., 1992, “Efflux of lipid from fibroblasts to apolipoproteins: dependence on elevated levels of cellular unesterified cholesterol,” Journal of Lipid Research, 33:1699-1709.
[cited by applicant]
Brewer et al., 1986, “Isolation and Characterization of Apolipoproteins A-I, A-II, and A-IV,” Methods in Enzymology, 128:223-246.
[cited by applicant]
Brissette et al., 1991, “Expression of Recombiant Human Apolipoprotein A-I in Chinese Hamster Ovary Cells and
[cited by applicant]
Cappuccio et al., 2008, “Cell-free Co-expression of Functional Membrane Proteins and Apolipoprotein, Forming Soluble Nanolipoprotein Particles,” Molecular & Cellular Proteomics 7.11:2246-2253.
[cited by applicant]
Chau et al., 2006, “Mechanism of Prebeta-HDL Formation and Activation,” Biochemistry, 45:3981-3987.
[cited by applicant]
Chau et al., 2007, “Bone Morphogenetic Protein-1 (BMP-1) Cleaves Human Proapolipoprotein A1 and Regulates Its Activation for Lipid Binding,” Biochemistry, 46:8445-8450.
[cited by applicant]
Chromy et al., 2007, “Different Apolipoproteins Impact Nanolipoprotein Particle Formation,” J. Am. Chem. Soc., Suppl. 129:S1-S8.
[cited by applicant]
Cuellar et al., 2014, “Aoikuoioriteub A-I configuration and cell cholesterol efflux activity of discoidal lipoproteins depend on the reconstitution process,” Biochimica et Biophysica Acta, 1841:180-189.
[cited by applicant]
Davidson et al., 1994, “The Molecular Basis for the Difference in Charge between Pre-beta and alpha-Migrating High Density Lipoproteins,” Journal of Biological Chemistry 269 (12):8959-8965.
[cited by applicant]
“Definition of Suspension”, available online at www.chemicool.com/definition/suspension.html, 1 page (2014).
[cited by applicant]
DeSilva et al., 1990, “Purification and characterization of apolipoprotein J.,” J. Biol. Chem., 265(24):14292-14297.
[cited by applicant]
Dixon et al., 1989, “Expression and secretion of chicken apolipoprotein AI in transfected COS cells,” Biochemica et Biophysica Acta, 1009(1):47-53.
[cited by applicant]
Dufourcq et al., 1986, “Morphological changes of phosphatidylcholine bilayers induced by melittin: vesicularization, fusion, discoidal particles,” Biochimica et Biophysica Acta, 859:33-48.
[cited by applicant]
Duong et al., 2008, “Characterization and properties of preβ-HDL particles formed by ABCA1-mediated cellular lipid efflux to apoA-I,” Journal of Lipid Research, 49(5):1006-1014.
[cited by applicant]
Edelstein et al., 1980, “Effect of Guanidine Hydrochloride on the Hydrodynamic and Thermodynamic Properties of Human Apolipoprotein A-I in Solution,” Journal of Biological Chemistry, 255(12):5747-5754.
[cited by applicant]
“Effect of CER-001 on Atherosclerosis in Acute Coronary Syndrome (ACS) Patients—Efficacy and Safety: The Chi Square Trial,” www.clinicaltrials.gov, 2011.
[cited by applicant]
Feng et al., 2006, “High yield and secretion of recombinant human apolipoprotein AI in Pichia pastoris,” Protein Expression and Purification, 46:337-342.
[cited by applicant]
Fennewald et al., 1988, “Expression of Human PreproapoAI and Pre (Δpro)apoAI in a Murine Pituitary Cell Line (AtT-20),” Journal of Biological Chemistry, 263(3):15568-15577.
[cited by applicant]
Fielding et al., 1995, “Molecular physiology of reverse cholesterol transport,” Journal of Lipid Research, 36(2):221-228.
[cited by applicant]
Formisano et al., 1978, “Effect of Pressure and Ionic Strength on the Self-association of Apo-A-I from the Human High Density Lipoprotein Complex,” Journal of Biological Chemistry, 253(2):354-360.
[cited by applicant]
Forte et al., 1987, “Lipid-poor apolipoprotein A-I in Hep G2 cells: formation of lipid-rich particles by incubation with dimyristoylphosphatidylcholine,” Biochimica et Biophysica Acta, 920:185-194.
[cited by applicant]
Forte et al., 1990, “Physical and chemical characteristics of apolipoprotein A-I-lipid complexes produced by Chinese hamster ovary cells transfected with human apolipoprotein A-I gene,” Biochimica et Biophysica Acta, 10…
[cited by applicant]
Forte et al., 1993, “Apolipoprotein A-I-cell membrane interaction: extracellular assembly of heterogeneous nascent HDL particles,” Journal of Lipid Research, 34(2):317-324.
[cited by applicant]
Forte et al., 1995, “Recruitment of cell phospholipids and cholesterol by apolipoproteins A-II and A-I: formation of nascent apolipoprotein-specific HDL that differ in size, phospholipid composition, and reactivity with…
[cited by applicant]
Forte et al., 1996, “Structural relationships between nascent apoA-I-containing particles that are extracellularly assembled in cell culture,” Journal of Lipid Research, 37:1076-1085.
[cited by applicant]
Frank et al., 2000, “Apolipoprotein A-I: structure-function relationships,” Journal of Lipid Research, 41(6):853-872.
[cited by applicant]
Germershausen et al., 1981, “Preparative High Speed Gel Permeation Chromatography of Proteins on Toyopearl HW55F,” Biochemical and Biophysical Research Communications, 99(3):1020-1027.
[cited by applicant]
Gursky et al., 1996, “Thermal unfolding of human high-density apolipoprotein A-1: Implications for a lipid-free molten globular state,” Proc. Natl. Acad. Sci. USA, 93(7):2991-2995.
[cited by applicant]
He et al., 2013, “Controlling the diameter, monodispersity, and solubility of ApoA1 nanolipoprotein particles using telodendrimer chemistry,” Protein Science, 22:1078-1086.
[cited by applicant]
Jayaraman et al., 2005, “Kinetic Stabilization and Fusion of Apolipoprotein A-2:DMPC Disks: Comparison with apoA-1 and apoC-1,” Biophysical Journal, 88:2907-2918.
[cited by applicant]
Jonas, 1986, “Reconstitution of High-Density Lipoproteins,” Methods in Enzymology, 128:553-582.
[cited by applicant]
Kim et al., 2013, “Single Step Reconstitution of Multifunctional High-Density Lipoprotein-Derived Nanomaterials Using Microfluidics,” ACS Nano, 7(11):9975-9983.
[cited by applicant]
Kunitake et al., 1990, “Pre-Beta High Denisty Lipoprotein—Unique Disposition of Apolipoprotein A-I Increases Susceptibility to Proteolysis,” Arteriosclerosis, 10:25-30.
[cited by applicant]
Kunitake et al., 1992, “Interconversion between apolipoprotein A-I-containing lipoproteins of pre-beta and alpha electrophoretic mobilities,” Journal of Lipid Research, 33(12):1807-1816.
[cited by applicant]
Lamon-Fava et al., 1987, “Secretion of Apolipoprotein A-I in Lipoprotein Particles Following Transfection of the Human Apolipoprotein A-I Gene into 3T3 Cells,” Journal of Biological Chemistry, 262(19):8944-8947.
[cited by applicant]
Law et al., 1984, “Nucleotide sequence and the encoded amino acids of human apolipoprotein A-I mRNA,” Proc. Natl. Acad. Sci USA, 81:66-70.
[cited by applicant]
Li et al., 2004, “Double Belt Structure of Discoidal High Density Lipoproteins: Molecular Basis for Size Heterogeneity,” J. Mol. Biol., 343(5):1293-1311.
[cited by applicant]
Lorenzetti et al., 1986, “Expression of the human apolipoprotein AI gene fused to the
[cited by applicant]
Lu et al., 2000, “Conformational Reorganization of the Four-helix Bundle of Human Apolipoprotein E in Binding to Phospholipid,” Journal of Biological Chemistry, 275(27):20775-20781.
[cited by applicant]
Mallory et al., 1987, “Expression and Characterization of Human Apolipoprotein A-I in Chinese Hamster Ovary Cells,” Journal of Biological Chemistry, 262(9):4241-4247.
[cited by applicant]
Marcel et al., 2003, “Structure-function relationships of apolipoprotein A-I: a flexible protein with dynamic lipid associations,” Curr Opin Lipidol, 14(2):151-157.
[cited by applicant]
McGuire et al., 1996, “High yield overexpression and characterization of human recombant proapolipoprotein A-I,” Journal of Lipid Research, 37:1519-1528.
[cited by applicant]
Nanjee et al., 1999, “Acute Effects of Intravenous Infusion of ApoA1/Phosphatidylcholine Discs on Plasma Lipoproteins in Humans,” Arterioscler Thromb Basc Biol, 19:979-989.
[cited by applicant]
Nanjee et al., 2001, “Intravenous apoA-I/Lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans,” Journal of Lipid Research, 42:1586-1593.
[cited by applicant]
Nykiforuk et al., 2011, “Expression and recovery of biologically active recombinant Apolipoprotein AIMilano from transgenic safflower (
[cited by applicant]
PCT International Search Report and Written Opinion of the International Searching Authority from PCT/US2012/024020, dated May 9, 2012.
[cited by applicant]
Persson et al., 1999, “Thermoseparating water/polymer system: a novel one-polymer aqueous two-phase system for protein purification,”
[cited by applicant]
Pyle et al., 1997, “Production of Mature Human Apolipoprotein A-I in a Baculovirus-Insect Cell System: Propeptide Is Not Essential for Intracellular Processing but May Assist Rapid Secretion,” Analytical Biochemistry, 2…
[cited by applicant]
Roberts et al., 1997, “Structural Analysis of Apolipoprotein A-I: Limited Proteolysis of Methionine-Reduced and -Oxidized Lipid-Free and Lipid-Bound Human Apo A-I,” Biochemistry, 36:7615-7624.
[cited by applicant]
Ryan et al., 2003, “Optimized bacterial expression of human apolipoprotein A-I,” Protein Expression and Purification, 27:98-103.
[cited by applicant]
Schmidt et al., 1997, “Expression and Purification of Recombinant Human Apolipoprotein A-I in Chinese Hamster Ovary Cells,” Protein Expression and Purification, 10:226-236.
[cited by applicant]
Schmidt et al., 1997, “In vivo kinetics as sensitive method for testing physiologically intact human recombinant apolipoprotein A-I: comparison of three different expression systems,” Clinica Chimica Acta, 268:41-60.
[cited by applicant]
Scorci-Thomas et al., 1996, “High level secretion of wild-type and mutant forms of human proapoA-I using baculovirus-mediated Sf-9 cell expression,” Journal of Lipid Research, 37(3):673-683.
[cited by applicant]
Scott R., 2007, “Quantitative Chromatography Analysis,” Part of the Chrom-Ed Series, available online at http://www.chromatography-online.org/quant/Chromatographic%20Data/Data%20Processing/Peak%20Area%20Measurements.htm…
[cited by applicant]
Sigalov et al., 2001, “Oxidation of methionine residues affects the structure and stability of apolipoprotein A-1 in reconstituted high density lipoprotein particles,” Chem. and Phys. Lipids, 113:133-146.
[cited by applicant]
Silva et al., 2005, “A Mass Spectrometric Determination of the Conformation of Dimeric Apolipoprotein A-I in Discoidal High Density Lipoproteins,” Biochemistry, 44:8600-8607.
[cited by applicant]
“Solution”, available online at www.thefreedictionary.com/p/Solution%20(chemistry), 5 pages (2014).
[cited by applicant]
Spieker et al., 2002, “High-Density Lipoprotein Restores Endothelial Function in Hypercholesterolemic Men,” Circulation, 105:1399-1402.
[cited by applicant]
Suprapaneni et al. 2012 “Designing Paclitaxel Drug Delivery Systems Aimed at Improved Patient Outcomes: Current Status and Challenges” ISRN Pharmacology 2012:15.
[cited by applicant]
Suurkuusk, et al., 2000 “Formation of HDL-like complexes from apolipoprotein A-IM and DMPC,” Intl. J. Pharmaceutics, 194:21-38.
[cited by applicant]
Sviridov et al., 1999, “Effectivity of Expression of Mature Forms of Mutant Human Apolipoprotein A-I,” Protein Expression and Purification, 17:231-238.
[cited by applicant]
Sviridov et al., 2000, “Deletion of the propeptide of apolipoprotein A-I reduces protein expression but stimulates effective conversion of preβ-high density lipoprotein to α-high density lipoprotein,” Journal of Lipid R…
[cited by applicant]
Swaney, JB., 1983, “Reconstitution of apolipoprotein A-I from human high density lipoprotein with bovine brain sphingomyelin.” J. Biol. Chem., 258(2): 1254-1259.
[cited by applicant]
Tardif et al., 2007, “Effects of Reconstituted High-Density Lipoprotein Infusions on Coronary Atherosclerosis—A Randomized Controlled Trial,” JAMA, 297(15)1675-1682.
[cited by applicant]
Thompson et al., 2006, “Physical Stability of Liposomes Prepared from Milk Fat Globule Membrane and Soya Phospholipids,” J. Agric. Food Chem., 54:6390-6397.
[cited by applicant]
UniProt Database, 1986, Accession No. P02647, 20 pages.
[cited by applicant]
Vitello et al., 1976, “Studies on Human Serum High Density Lipoproteins—Self-association of apolipoprotein A-I in aqueous solutions,” Journal of Biological Chemistry, 251(4):1131-1136.
[cited by applicant]
Weers et al., 2011, “Novel N-terminal mutation of human apolipoprotein A-I reduces self-assocation and impairs LCAT activation,” Journal of Lipid Research, 52:35-44.
[cited by applicant]
Weinberg et al., 1988, “Analytic and preparative separation of apolipoproteins A-I, A-II and A-IV by reverse phase liquid chromatography,” Journal of Lipid Research, 29(6):819-824.
[cited by applicant]
Weiss et al., 2006, “Flexible Methodology for Developing Mammalian Cell Lines,” BioPharm International, available online at http://www.biopharminternational.com/flexible-methodology-developing-mammalian-cell-lines.
[cited by applicant]
Yetukuri, 2010, “Compositions and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol,” Journal of Lipid Research, 51:2341-2351.
[cited by applicant]
Zhang X, et al., 2010, “Recombinant high density lipoprotein reconstituted with apolipoprotein A1 cysteine mutants as delivery vehicles for 10-hydroxycamptothecin,” Cancer Letters, 298:26-33.
[cited by applicant]
Zheng et al., 2004, “Chap. 23: Bioseparation Techniques and Their Applications,” Handbook of Molecular and Cellular Methods in Biology and Medicine, 2nd Ed., Cseke et al., eds., CRC Press, 329-353.
[cited by applicant]