Granted Patent
B2
US 12,357,684 · App. 17/818,887 · Granted Jul 15, 2025
Modified RSV F proteins and methods of their use
Inventors:
Peter M. Pushko (Frederick, MD); Yingyun Wu (Clarksburg, MD); Michael J. Massare (Mt. Airy, MD); Ye Liu (Clarksville, MD); Gale Smith (Germantown, MD); Bin Zhou (Clarksburg, MD)
A61K39/155A61K9/0019A61K9/1075A61K39/12A61K39/39C07K14/005C12N7/00A61K39/00A61K2039/5258A61K2039/54A61K2039/545A61K2039/55A61K2039/55505A61K2039/57A61K2039/575C07K2319/00C12N2760/18522C12N2760/18523C12N2760/18534C12N2760/18562C12N2760/18571
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Abstract
The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.
Claims (22)
1. An immunogenic formulation comprising a pharmaceutically acceptable carrier and a respiratory syncytial virus (RSV) F glycoprotein comprising:
(i) an inactivated primary furin cleavage site; wherein the primary furin cleavage site is inactivated by amino acid substitution of one or more amino acids of arginine 133, arginine 135, and arginine 136;
(ii) a wild-type secondary furin cleavage site having an amino acid sequence of RARR (SEQ ID NO: 23),
(iii) a p27 protein; and
(iv) a transmembrane domain;
wherein the RSV F glycoprotein lacks an N-terminal signal peptide;
wherein the RSV F glycoprotein is cleaved into F1 and F2 subunits which are disulfide linked;
wherein the p27 protein is connected to the F1 subunit via an amide bond; and
wherein the amino acids of the RSV F glycoprotein are numbered according to the RSV F glycoprotein of SEQ ID NO: 2.
2. The immunogenic formulation of claim 1 , wherein one amino acid of arginine 133, arginine 135, and arginine 136 is substituted.
3. The immunogenic formulation of claim 1 , wherein two amino acids of arginine 133, arginine 135, and arginine 136 are substituted.
4. The immunogenic formulation of claim 1 , wherein each of arginine 133, arginine 135, and arginine 136 are substituted.
5. The immunogenic formulation of claim 2 , wherein the one amino acid is substituted with glutamine.
6. The immunogenic formulation of claim 3 , wherein the two amino acids are substituted with glutamine.
7. The immunogenic formulation of claim 4 , wherein each of arginine 133, arginine 135, and arginine 136 are substituted with glutamine.
8. The immunogenic formulation of claim 1 , wherein the RSV F glycoprotein comprises a deletion of the fusion domain corresponding to amino acids 137-146 of SEQ ID NO: 2.
9. The immunogenic formulation of claim 7 , wherein the RSV F glycoprotein comprises a deletion of the fusion domain corresponding to amino acids 137-146 of SEQ ID NO: 2.
10. The immunogenic formulation of claim 1 , comprising an adjuvant.
11. A method of eliciting an immune response to an RSV infection in a human comprising administering the immunogenic formulation of claim 1 .
12. The method of claim 11 , wherein the human is an infant.
13. The method of claim 11 , wherein the administering is intramuscular.
14. The immunogenic formulation of claim 1 , wherein the RSV F glycoprotein comprises up to four mutations relative to the RSV F glycoprotein of SEQ ID NO: 2.
Assignments (2)
SECURITY INTEREST
Recorded Feb 25, 2026
From: NOVAVAX, INC.
To: MIDCAP FINANCIAL TRUST
Reel/Frame 074976/0089 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 11, 2022
From: PUSHKO, PETER; WU, YINGYUN; MASSARE, MICHAEL; LIU, YE; SMITH, GALE; ZHOU, BIN
To: NOVAVAX, INC.
Reel/Frame 060787/0836 →
Continuity (9)
Provisional Application
61224787
· Jul 10, 2009
Provisional Application
61169077
· Apr 14, 2009
Provisional Application
61121126
· Dec 9, 2008
References Cited (162)
US 5149650A
· Wertz et al.
· 1992
[cited by applicant]
US 6245532B1
· Smith et al.
· 2001
[cited by applicant]
US 6352697B1
· Cox et al.
· 2002
[cited by applicant]
US 8563002B2
· Baudoux et al.
· 2013
[cited by applicant]
US 8715692B2
· Pushko
· 2014
[cited by examiner]
US 9675685B2
· Pushko
· 2017
[cited by examiner]
US 20040028698A1
· Colau et al.
· 2004
[cited by applicant]
US 20050142148A1
· Fouchier et al.
· 2005
[cited by applicant]
US 20080233150A1
· Smith et al.
· 2008
[cited by applicant]
US 20100239671A1
· Edelman et al.
· 2010
[cited by applicant]
US 20130122032A1
· Smith et al.
· 2013
[cited by applicant]
US 20140227309A1
· Smith et al.
· 2014
[cited by applicant]
US 20150306207A1
· Smith et al.
· 2015
[cited by applicant]
US 20150335730A1
· Smith et al.
· 2015
[cited by applicant]
AU 2003245220B2
· 2004
[cited by applicant]
AU 2014100888A4
· 2014
[cited by applicant]
CN 101090711A
· 2007
[cited by applicant]
CN 102107003A
· 2011
[cited by applicant]
EP 0109942A2
· 1984
[cited by applicant]
EP 0180564B1
· 1986
[cited by applicant]
EP 0242380B1
· 1987
[cited by applicant]
EP 0362279B1
· 1990
[cited by applicant]
EP 0436620B1
· 1991
[cited by applicant]
EP 0889736B1
· 1999
[cited by applicant]
EP 1539231B1
· 2005
[cited by applicant]
EP 3718566A1
· 2020
[cited by applicant]
JP H10508301A
· 1998
[cited by applicant]
RU 2531235C2
· 2014
[cited by applicant]
WO 8809336A1
· 1988
[cited by applicant]
WO 9003184A1
· 1990
[cited by applicant]
WO WO9100104A1
· 1991
[cited by applicant]
WO 9611711A1
· 1996
[cited by applicant]
WO 9730728A1
· 1997
[cited by applicant]
WO 9836772A1
· 1998
[cited by applicant]
WO 0035481A2
· 2000
[cited by applicant]
WO WO20010066137A1
· 2001
[cited by applicant]
WO 2004004762A1
· 2004
[cited by applicant]
WO WO2005021713A2
· 2005
[cited by applicant]
WO WO2005080417A2
· 2005
[cited by applicant]
WO WO2007149490A1
· 2007
[cited by applicant]
WO WO2008114149A2
· 2008
[cited by applicant]
WO WO2008133663A2
· 2008
[cited by applicant]
WO WO2009012487A2
· 2009
[cited by applicant]
WO WO2009108689A1
· 2009
[cited by applicant]
WO WO2010077717A1
· 2010
[cited by applicant]
WO WO2010138193A2
· 2010
[cited by applicant]
WO WO2011008974A2
· 2011
[cited by applicant]
WO WO2012061815A2
· 2012
[cited by applicant]
WO WO2013006842A2
· 2013
[cited by applicant]
WO WO2013049342A1
· 2013
[cited by applicant]
WO WO2014024024A1
· 2014
[cited by applicant]
WO WO2014124423A1
· 2014
[cited by applicant]
WO WO2014174018A1
· 2014
[cited by applicant]
Begona et al. J Gen Virol. 2004, vol. 85, pp. 3677-3687 (Year: 2004).
[cited by examiner]
Amorij et al., “Development of Stable Influenza Vaccine Powder Formulations: Challenges and Possibilities,” Pharmaceutical Research 25(6):1256-1273 (2008).
[cited by applicant]
Anderson et al., “Intracellular processing of the human respiratory syncytial virus fusion glycoprotein: amino acid substitutions affecting folding, transport and cleavage,” J. Gen. Virol. 73:1177-118 (1992).
[cited by applicant]
Brandenburg et al., Respiratory Syncytial Virus Specific Serum Antibodies in Infants Under Six Months of Age: Limited Serological Response Upon Infection, J. Med. Virol. 52:97-104 (1997).
[cited by applicant]
Calder et al., “Electron Microscopy of the Human Respiratory Syncytial Virus Fusion Protein and Complexes That It Forms with Monoclonal Antibodies,” Virol. 271:122-131 (2000).
[cited by applicant]
Citovsky et al., “Fusion of Sendai Virions or Reconstituted Sendai Virus Envelopes with Liposomes or Erythrocyte Membranes Lacking Virus Receptors,” The Journal of Biological Chemistry 260(22)12072-12077 (1985).
[cited by applicant]
Creemers et al., “Endoproteolytic Cleavage of Its Propeptide Is a Prerequisite for Efficient Transport of Furin Out of the Endoplasmic Reticulum,” J. Biol. Chem. 270(6):2695-2702 (1995).
[cited by applicant]
Crowe, Jr. et al. “Passively Acquired Antibodies Suppress Humoral But Not Cell-Mediated Immunity in Mice Immunized with Live Attenuated Respiratory Syncytial Virus Vaccines,” J. Immunol. 167:3910-3918 (2001).
[cited by applicant]
Crowe, Jr., “Influence of Maternal Antibodies on Neonatal Immunization against Respiratory Viruses,” Clin. Infect. Dis. 33:1720-1727 (2001).
[cited by applicant]
Demirjian and Levy, “Safety and Efficacy of Neonatal Vaccination,” Eur. J. Immunol. 39(1):36-46 (2009).
[cited by applicant]
Eckert et al., “Mechanisms of Viral Membrane Fusion and Its Inhibition,” Annual Review of Biochemistry 70:770-810 (2001).
[cited by applicant]
European Search Report, EP Appl. No. 16166033.7, 8 pages (Aug. 10, 2016).
[cited by applicant]
European Search Report, EP Appl. No. 16843191.4, 13 pages, dated Mar. 14, 2019.
[cited by applicant]
Extended European Search Report issued by the European Patent Office for Application No. 19770704.5, dated Jan. 3, 2022, 10 pages.
[cited by applicant]
Extended European Search Report issued by the European Patent Office for Application No. 20171841.8, dated Aug. 5, 2020, 11 pages.
[cited by applicant]
Genbank Accession No. AAC55970.1, “fusion glycoprotein precursor [Human respiratory syncytial virus]” (1996), 1 page.
[cited by applicant]
Glenn et al., “Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine,” Vaccine. Jan. 7, 2013;31(3):524-532.
[cited by applicant]
Glenn, “Recombinant, Insect Cell-Derived RSV Nanoparticle Vaccine,” Novavax.com, 34 pages (Jul. 4, 2012) https://www.novavax.com/download/file/RSV nanoparticle Vaccine-MVADsJuly4(2).pdf.
[cited by applicant]
Gonzalez-Reyes et al., “Cleavage of the human respiratory syncytial virus fusion protein at two distinct sites is required for activation of membrane fusion,” Proc. Natl. Acad. Sci. USA 98(17):9859-9864 (2001).
[cited by applicant]
Gruenke et al., “New Insights into the Spring-Loaded Conformational Change of Influenza Virus Hemagglutinin,” Journal of Virology, May 2002, 76:(9) 4456-4466 (2002).
[cited by applicant]
Halsey and Galazka, “The efficacy of DPT and oral poliomyelitis immunization schedules initiated from birth to 12 weeks of age,” Bull. World Health Org. 63(6):1151-1169 (1985).
[cited by applicant]
Hancock et al., “Adjuvants Recognized by Toll-Like Receptors Inhibit the Induction of Polarized Type 2 T Cell Responses by Natural Attachment (G) Protein of Respiratory Syncytial Virus,” Vaccine 21(27-30):4348-4358 (200…
[cited by applicant]
Higgins et al., “Advances in RSV vaccine research and development—A global agenda,” Vaccine 34:2870-2875 (2016).
[cited by applicant]
Idrus, “Novavax Announces Initiation of Ebola Vaccine Phase 1 Clinical Trial Supported by Non-Human Primate Challenge Data and Documented Rapid Manufacturing Capabilities,” Fierce Pharma, dated Feb. 17, 2015, 4 pages, r…
[cited by applicant]
International Search Report, 4 pages, PCT appl. No. PCT/US09/67269 (mailed Mar. 4, 2010).
[cited by applicant]
International Search Report, 5 pages, PCT appl. No. PCT/US2012/057546 (mailed Jan. 22, 2013).
[cited by applicant]
Iyer et al., Purified, Proteolytically Mature HIV Type 1 SOSIP gp140 Envelope Trimers, AIDS Research and Human Retroviruses 23(6):817-828 (2007).
[cited by applicant]
Kim et al., “Respiratory Syncytial Virus Disease in Infants Despite Prioir Administration of Antigenic Inactivated Vaccine,” Am. J. Epidemil. 89(4):422-434 (1969).
[cited by applicant]
Lee et al., “Recent Advances of Vaccine Adjuvants for Infectious Diseases ,” Immune Network, 51-57 (2015).
[cited by applicant]
Lichtenberg et al., “The Mechanism of Detergent Solubilization of Lipid Bilayers,” Biophysical Journal, vol. 105:289-299 (2013).
[cited by applicant]
Lieberman et al., “Preparation and immunogenic properties of a recombinant West Nile subunit vaccine,” Vaccine 25:414-423 (2007).
[cited by applicant]
Martin et al., “Sequence elements of the fusion peptide of human respiratory syncytial virus fusion protein required for activity,” J. Gen. Virol. 87:1649-1658 (2006).
[cited by applicant]
Martinez et al., “Combining DNA and protein vaccines for early life immunization against respiratory syncytial virus in mice,” Eur. J. Immunol. 29:3390-3400 (1999).
[cited by applicant]
Murphy et al., “An update on approaches to the development of respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) vaccines,” Virus Res. 32:13-26 (1994).
[cited by applicant]
Murphy et al., “Effect of Age and Preexisting Antibody on Serum Antibody Response of Infants and Children to the F and G Glycoproteins during Respiratory Syncytial Virus Infection,” J. Clin. Microbiol. 24(5):894-898 (19…
[cited by applicant]
Murphy et al., “Effect of passive antibody on the immune repspone of cotton rats to purified F and G glycoproteins of repiratory suncytial virus (RSV),” Vaccine 9:185-189 (1991).
[cited by applicant]
Murphy et al., “Passive Transfer of Respiratory Syncytial Virus (RSV) Antiserum Suppresses the Immune Response to the RSV Fusion (F) and Large (G) Glycoproteins Expressed by Recombinant Vacccinia Viruses,” J. Virol. 62(…
[cited by applicant]
“Novavax NanoFlu Achieves All Primary Endpoints In Phase 3 Clinical Trial,” Press Release dated Mar. 24, 2020, 3 pages.
[cited by applicant]
Nussbaum et al., “Fusion of influenza Virus particles with liposomes: requirement for cholesterol and virus receptors to allow fusion with and lysis of neutral but not of negatively charged liposomes”,. Journal of Gener…
[cited by applicant]
Parrington et al., “Baculovirus expression of the respiratory syncytial virus fusion protein using Trichoplusia ni insect cells,” Virus Genes 14:63-72 (1997).
[cited by applicant]
Rama et al., “An insect cell derived respiratory syncytial virus (RSV) F nanoparticle vaccine induces antigenic site II antibodies and protects against RSV challenge in cotton rats by active and passive immunization”, V…
[cited by applicant]
Roder, et al., “Purification of respiratory syncytial virus F and G-proteins,” Journal of Chromatography B: Biomedical Sciences and Applications 737:97-106 (2000).
[cited by applicant]
Ruiz-Arguello et al., “Effect of Proterlytic Processing at Two Distinct Sites on Shape and Aggregation of an Anchorless Fusion Protein of Human Respiratory Syncytial Virus and Fate of the Intervening Segment,” Virol. 29…
[cited by applicant]
Ruiz-Arguello et al., “Thermostability of the human respiratory syncytial virus fusion protein before and after activation: implications for the membrane-fusion mechanism,” J. Gen. Virol. 85:3677-3687 (2004).
[cited by applicant]
Sales and Wang, “Respiratory syncytial virus vaccine: Is it coming?” Paediatr. Child Health 8(10):605-608 (2003).
[cited by applicant]
Shi et al., “Stabilization of Human Papillomavirus Virus-Like Particles by Non-Ionic Surfactants,” Journal of Pharmaceutical Sciences, 2005, p. 1538-1551.
[cited by applicant]
Shinde et al., “Improved Titers Against Influenza Drift Variants with a Nanoparticle Vaccine,” N Engl Med 378:24 (2018), 3 pages.
[cited by applicant]
Shinde et al., Induction of Broadly Cross-Reactive Immune Responses Against A(H3N2) Viruses: Results of a Phase 2 Trial of a Novel Recombinant Hemagglutinin Saponin-Adjvanted nanoparticle Influenza Vaccine (“NanoFlu”), …
[cited by applicant]
Siegrist et al., “Protective Efficacy against Respiratory Syncytial Virus following Murine Neonatal Immunization with BBG2Na Vaccine: Influence of Adjuvants and Maternal Antibodies,” J. Infect. Dis. 179:1326-1333 (1999).
[cited by applicant]
Siegrist, “Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants,” Vaccine 21:3406-3412 (2003).
[cited by applicant]
Smith et al., “Respiratory Syncytial Virus Fusion Glycoprotein Expressed in Insect Cells Form Protein Nanoparticles That Induce Protective Immunity in Cotton Rats,” PLOS ONE 7(11):e50852, 12 pages (2012).
[cited by applicant]
Supplementary European Search Report, EP Appl. No. 09836751.9, 9 pages (Apr. 29, 2013).
[cited by applicant]
Supplementary European Search Report, EP Appl. No.12835033.7, 7 pages (Feb. 17, 2015).
[cited by applicant]
Tekewe et al., A rapid and simple screening method to identify conditions for enhanced stability of modular vaccine candidates, Biochemical Engineering Journal 100:50-58 (2015).
[cited by applicant]
Vaarala et al., “Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix Associated Narcolepsy Risk ,” PLOS One, 1-23 (2014).
[cited by applicant]
Wang et al., “Expression and purification of an influenza hemagglutinin-one step closer to a recombinant protein-based influenza vaccine,” Vaccine vol. 24, Issue 12, pp. 2176-2185 (2006).
[cited by applicant]
Wang, “Protein aggregation and its inhibition in biopharmaceutics,” International Journal of Pharmaceutics 289 (2005) 1-30.
[cited by applicant]
Wathen et al., Immunization of Cotton Rats with the Human Respiratory Syncytial Virus F Glycoprotein produced usinga Baculovirus Vector, The Journal of Infectious Diseases 159(2):255-264 (1989).
[cited by applicant]
Weisshaar et al., “Blocking Respiratory Syncytial Virus Entry: A Story with Twists,” DNA Cell Biol. 34:505-510 (2015).
[cited by applicant]
Whitehead et al., “Recombinant Respiratory Syncytial Virus (RSV) Bearing a Set of Mutations from Cold-Passaged RSV is Attenuated in Chimpanzees,” J. Virol. 72(5):4467-4471 (1998).
[cited by applicant]
Widjaja et al., “Recombinant Soluble Respiratory Syncytial Virus F Protein That Lacks Heptad Repeat B, Contains a GCN4 Trimerization Motif and Is Not Cleaved Displays Prefusion-Like Characteristics,” PLoS One 10(6):e013…
[cited by applicant]
Written Opinion of the International Searching Authority, 4 pages, PCT appl. No. PCT/US09/67269 (mailed Mar. 4, 2010).
[cited by applicant]
Written Opinion of the International Searching Authority, 5 pages, PCT appl. No. PCT/US2012/057546 (mailed Jan. 22, 2013).
[cited by applicant]
European Search Report, EP Appl. No. 16166033.7, 10 pages (Aug. 10, 2016).
[cited by applicant]
Bangham et al., Human and Murin Cytotoxic T Cells, J. Immunol 137, pp. 3973-3977 (1986).
[cited by applicant]
Barr, et al., ISCOMS . . . , Advanced Drug Delivery Reviews vol. 32, pp. 247-271 (1998).
[cited by applicant]
Barr, et al., ISCOMS . . . , Immunol. and Cell Biology vol. 74, 19 pgs (1996).
[cited by applicant]
Behboudi et al., Quaillaja Saponin Formulations that Stimulate . . . Scand. J. Immunol. 50, pp. 371-377 (1999).
[cited by applicant]
Boulter, et al., Evaluation of Recombinant Sporozoite . . . , Tropical Medicine and Intl Health vol. 4, pp. A71-A77 (1999).
[cited by applicant]
Claassen, et al., The Iscom Structure . . . , Characteristics and Use of New-Generation Adjuvants, pp. 531-541 (1992).
[cited by applicant]
Copland, et al., Hydration of Lipid Films with an Aqueous Solution of Quil A . . . , Intl J. Pharma. vol. 196, pp. 135-139 (2000).
[cited by applicant]
Coulter, et al., Studies on Experimental Adjuvanted Influenza Vaccines . . . , Vaccine vol. 16, No. 11/12 pp. 1243-1253 (1997).
[cited by applicant]
Cox, et al., Adjuvants—a Classification and Review . . . Vaccine vol. 15, pp. 248-256 (1997).
[cited by applicant]
Cox, et al., Development of an Influenza—ISCOM Vaccine, Vaccine Design, pp. 33-49 (1997).
[cited by applicant]
Cox, et al., Prospects for the Development of New Vaccine Adjuvants, BioDrugs vol. 12, pp. 439-453 (1999).
[cited by applicant]
Demana, et al., A Comparison of Pseudo-Ternary Diagrams . . . , J. of Pharm. and Pharmacology vol. 56, pp. 573-580 (2004).
[cited by applicant]
Dermana, et al., Pseudo-Ternary Phase Diagrams of Aqueous Mixtures of Quil A . . . , Intl J. Pharma. vol. 270, pp. 229-239 (2004).
[cited by applicant]
Ekstrom et al., Iscom and Iscom-Matrix Enhance by Intranasal Route . . . Vaccine 17, pp. 2690-2701 (1999).
[cited by applicant]
Falsey et al., Comparison of the Safety, JID 198, pp. 1317-1326, 2008.
[cited by applicant]
Hu, et al., Immunostimulating Complexes, Advanced Drug Delivery Reviews vol. 51, p. 149-159 (2001).
[cited by applicant]
Johansson et al., Iscoms with Different Quaillaja Saponin Components . . . Vaccine 17, pp. 2894-2900 (1999).
[cited by applicant]
Kensil, et al., Saponins as Vaccine Adjuvants, Critical Reviews in Therapeutic Drug Carrier Systems, pp. 1-55 (1996).
[cited by applicant]
Kersten, et al., On the Structure of Immune-Stimulating Saponin . . . , Biochimica et Biophysica vol. 1062, pp. 165-171 (1991).
[cited by applicant]
Lovgren, et al., The Requirement of Lipids . . . , Biotechnology and Applied Biochemistry vol. 10, pp. 161-172 (1988).
[cited by applicant]
Lovgren-Bengtsson, et al., 4.5 Preparation and Use of Adjuvants, Methods in Microbiology vol. 32, pp. 551-588 (2002).
[cited by applicant]
Lovgren-Bengtsson, et al., 6 Preparation and Use of Adjuvants, Methods in Microbiology vol. 25, pp. 471-502 (1998).
[cited by applicant]
Morein, et al., Iscom, a novel structure for antigenic presentation . . . , Nature vol. 308, pp. 457-460 (1984).
[cited by applicant]
O'Hagan, et al., Microparticles as Vaccine Adjuvants and Delivery Systems, Expert Rev. Vaccines vol. 2, pp. 269-283 (2003).
[cited by applicant]
Ozel, et al., Quaternary Structure of the Immunostimulating Complex (Iscom), J. Ultrastructure and Molecular Structure Research vol. 102,240-248 (1989).
[cited by applicant]
Ronnberg, et al., Adjuvant Activity of Non-Toxic Quillaja Saponaria . . . , Vaccine vol. 13, No. 14, pp. 1375-1382 (1995).
[cited by applicant]
Sjolander, et al., ISCOMS: An Adjuvant with Multiple Functions, J. Leukocyte Biology vol. 64, pp. 713-723 (1998).
[cited by applicant]
Sjolander, et al., Uptake and Adjuvant Activity . . . Advanced Drug Delivery Reviews vol. 34, pp. 321-338 (1998).
[cited by applicant]
Cited By (1)