SCIENCE & LEGAL: Book- Strategic Patenting & Drug Development

Thursday, December 10, 2009

Book- Strategic Patenting & Drug Development

Results from work done over the last three years by our group will be published in a book entitled "Patently Innovative: How Pharmaceutical Firms Use Emerging Patent Law to Extend Monopolies on Blockbuster Drugs."

Update : The book will be published by Biohealthcare Publishing (Oxford) Ltd. (Oxford, UK).

The manuscript was delivered in November 2010, and is set to be published in the summer of 2011. The book description is available at Amazon.com and other retailers.

About Me

Over the last 25 years I have trained and worked as a scientist, lawyer and professor.

In law I specialized in biomedical innovation, regulation, and intellectual property and how these contribute to global public health. More generally, my legal and academic career has focused on the science, law, policy, and commercialization of medical research, as well as strategic planning for commercialization of innovative biomedical technologies.

I started out as a scientist, obtaining a PhD and Post-Doctoral Fellowship in the field of excitation-contraction coupling. As shown in the composite data above, my work focused on the relationship between the flow of ionic current through various types of ion channels, ion exchangers and the shape of the cardiac action potential, the strength and duration of Ca-induced Ca release from internal SR stores, and the strength and duration of contraction of cardiac muscle and unloaded cell shortening in single cells.

The data in the figure show membrane current, membrane voltage, intracellular Ca, and cell shortening signals recorded simultaneously from either a single myocyte or a single single giant sarcolemmal patch. The cardiac myocyte has been subjected to a double voltage-clamp protocol.

After coming into contact with the biotechnology industry during my Post-Doctoral Fellowship, I shifted focus to obtain a law degree, specializing in pharmaceutical and biotechnology law. I have since been involved in the prosecution, acquisition, financing, distribution and litigation of intellectual property rights, and have appeared before the Federal Court of Canada and the Supreme Court of Canada. I have consulted with firms, universities, governments and international organizations on legal, regulatory and policy issues associated with medical inventions, including the Government of Canada and World Health Organization.

For the last several years I worked as a Professor cross-appointed in the Faculties of Law and Medicine at the University of Alberta and University of Manitoba. My work during this time was funded by federal and provincial funding agencies as well as private endowments.

My research group conducted theoretical and empirical research on existing and evolving drug approval models, domestic and global innovation policy, technology transfer, commercialization of publicly funded medical research, and intellectual property and regulatory rights associated with therapeutic products. Our primary focus was on the impact of government regulation and stimulus packages - particularly those involving patents- on biomedical innovation and access to affordable therapeutic products.

Our group had a strong interest in the governance and operational implications of emerging systems and network models, particularly for what we have termed a regulated Therapeutic Product Lifecycle (rTPL).

We were particularly interested in the implications of systems theory and practice for the exploration and explication of the concept of fitness in distributed biological, technological and social networks to distributive theories of law and democracy.

The goal of our work was to provide key decision-makers in public and private sectors with objective empirical evidence in order to understand and measure the efficiency and effectiveness of public policy as it operates in a "real-world" context.

As can be seen by a comparison of the data and figures from basic science experiments and empirical legal scholarship, our mandate was to extrapolate scientific experience in basic science to our empirical work in the legal scholarship arena.

A Lab Environment in Law

After spending 20 years doing basic scientific research my intent is to conduct empirical legal and public policy research in a manner that strongly mirrors the “lab” experience in the basic sciences.

Taking a scientific approach to law involves a focus on quantitative and qualitative research on complex legal problems involving medicine, basic science, and public policy. Considered important in this regard are: weekly journal clubs and lab meetings; attending and presenting at scholarly meetings and workshops; and maintaining a focus on publishing and grant funding. Most important is generally running an open-ended scholarly environment with a high degree of collaboration and respect among lab members.

We conduct qualitative and quantitative research. Students are encouraged to become familiar with, or ramp up, skills relating to numerical, statistical and other empirical methods for analyzing data.

As in science, both intellectual independence and collaboration are prized. Students and other researchers are expected to work together to independently carry and manage their own projects and meet deliverables. As importantly, vertical and horizontal mentoring between lab members is valued and expected. Students are encouraged to spend time helping one another, and to be open to change, adaptation and learning. Students are co-authors on published work, and may be lead author, if sufficient work and writing are done independently. The physical environment comprises a combination of group and personal space and is familiar to anyone with basic science experience.

Combined these elements form a reasonable template for conducting qualitative and quantitative legal research in a manner that mirrors the experience in the basic medical sciences, and which values intellectual independence and mentoring (1).

We have been fortunate as to date the lab has been comprised of students from several faculties and departments relevant to our research enterprise, including Law, Medicine, Science, Political Science and Management Studies. Most students have some background (BSc, MSc) or interest in basic science prior to joining the team. Students from the group have gone on to complete doctoral studies in law, management and social sciences, and to have successful careers in the practice of law and medicine, managing biotechnology and other technology firms, and in international diplomacy.

The ultimate goal is to have a multidisciplinary group able to speak with confidence and factual expertise on themes relating to medical product development and regulation, health policy, patent law, regulatory law, theories of justice and democracy, clinical trials, technology commercialization, and national science and technology policy.

Our objective is to conduct theoretical and empirical work on these themes that will have an impact on the rate and direction of innovative activity in the pharmaceutical and biotechnology industries, and thus the marketplace for life sciences products available to the public. The lab is currently focused on these themes as stand alone projects but also as they relate to other systems theories which place innovative medical research in broader legal, democratic and cultural contexts.

(1) Lefkowitz, R.J. The Spirit of Science. Presidential Address to the American Society for Clinical Investigation. Washington, DC. April 30, 1988. J. Clin. Invest. 82: 375-378. 1988.

Active Research Projects

Patent Litigation:

With competition between brand-name and generic drug manufacturers no where near peaking and debate over the value of strong patent protection in biomedical product development gaining momentum, this is a fruitful area for law and science scholarship.

My work on this topic derives from time spent in the legal trenches participating in the drug wars. In both Canada and the United States drug approval is linked to patent protection for drug products via “linkage regulations”. U.S. linkage regulations are referred to as Hatch Waxman while in Canada they are called the Patented Medicines (Notice of Compliance) Regulations. The Canadian regulations came into force when compulsory licensing was abolished in the early 1990s in order for the nation to be TRIPS-compliant.

One problem that frequently comes up in the obviousness analysis in life sciences litigation is whether or not experimental research or testing leading to crystallization of an invention constitutes an inventive step from the perspective of persons with ordinary skill in the art (PHOSITA) of the relevant field.

The issue of “testing” is thus shorthand for whatever scientific experimentation and research was conducted prior to crystallization of the invention. This issue is significant in the context of pharmaceutical inventions because like all biomedical inventions they typically come about as a result of cumulative incremental advances over the prior art. That is, they do not come into being in vacuo.

To date the lab has three papers on topic. All deal with the issue of testing during the lead-up to invention. The first deals with pharmaceutical litigation under the NOC Regulations. It addresses a body of jurisprudence where testing is per se obviated based on a line of cases approving a quote by Professor Harold Fox to the effect that no testing whatsoever can be carried out in the context of the obviousness analysis.

The second paper deals with a separate line of cases where the inherent creativity and inventiveness of the PHOSITA is put at issue. Contrary to appellate case law in the U.S. and U.K., the Canadian PHOSITA is said to possess not even a “mere scintilla” of inventiveness or creativity notwithstanding the pharmaceutical and biotechnology industries are amongst the most technologically and strategically advanced in the world.

The third deals with the applicability of the recent obviousness decision by the U.S. Supreme Court in KSR v. Teleflex. The court made specific pronouncements on the inherent creativity and inventiveness of the PHOSITA that are directly applicable to Canadian law on point. Indeed, the current Canadian test for obviousness is not dissimilar to the “rigid and narrow” test overturned in KSR.

Combined, the three papers challenge the Canadian “mythical” PHOSITA as being wrong as a matter of science and as a matter of law, drawing on broad constitutional arguments, STS studies and detailed domestic and comparative case law reviews. All three are published and available on ssrn.com (Canadian Journal of Law & Technology. 6(1): 1-27. 2007; University of Ottawa Law & Technology Journal. 4(1): 1-55. 2007; Health Law Journal. 15(1): 222-246. 2008).

Translational Research & Technology Commercialization:

The lab also pursues a line of research relating to the social benefits of publicly funded medical research and university technology transfer.

This work has been published in three related articles, including Nature Biotechnology. Together they review the complex and interrelated network of public and private actors and institutions embedded within the large legal-regulatory regime responsible for commercialization.

The work reviews whether public and private actors need necessarily be at odds with one another in the commercialization process as is often claimed and explores distributive remedies to correct imbalances in benefit distribution, including a compulsory royalty to government for inventions commercialized using substantial public funds.

The path to balancing public and private interests in technology commercialization in a global political environment where both legal and democratic norms are rapidly changing is referred to as “the third way”, following a long line of philosophical writings on the issue of balancing.

Given the evolving human rights and economic landscapes in developed and developing nations, the notion of balance has direct relevance to the availability on reasonable terms of essential medical products and services in health care system that are wholly or even partially publicly funded.

The papers have been published and are also available on ssrn.com. (Nature Biotechnology. 26(1): 31-36. 2008; Boston University Journal of Science and Technology Law. 13(2): 120-192. 2007; Munk Centre for International Studies Briefings. CPHS 5: 190-216. 2007).

Drug Regulation & Clinical Trials:

We are interested in how drugs and biologics are approved by national food and drug agencies, the manner in which approval regimes are converging over time, and the evolution of drug approval from a more linear “front-loaded” policy and procedural mechanism to a more “back-loaded” adaptive mechanism.

Drug regulation presents a fertile target for network theories owing to the diverse yet vital range of public and private actors interested in the character and outcome(s) of the system e.g., intellectual property and regulatory rights, benefit distribution, regulatory harmony, and the perceived economic efficiency of drug development.

Indeed, this is an excellent time to be interested in the scientific, economic and political complexities underpinning drug regulation. Canada, the E.U. and, the U.S., are all moving in the direction of “real world" frameworks for drug approval. Canada is in the process of completely revamping its drug regulation regime and the methods by which scientific evidence is used in the approval process. Significant concerns have been expressed over what is perceived to be a lowering of the standard of approval in the new progressive licensing regime relating to the use of risk management and benefit:risk decision-making tools.

We have papers published on these topics in top-tier legal journals and well regarded yearly reports- all of which are available on ssrn.com. (Canadian Health Law & Policy, 3rd ed. Toronto. 2007; The Global Forum Update on Research for Health. 4th ed. London, Pro-Brook Publishing Ltd. 2007).

More recently, we developed an novel empirical methodology to investigate innovation in the pharmaceutical industry, and the manner in which innovative product development is related to emerging lifecycle models of regulation. The papers are available at ssrn.com (McGill Journal of Law & Health 3: 51-86, 2009; McGill Journal of Law & Health 3: 87-138, 2009).

Local and Global Complex Systems and Innovation Ecologies:

The forth pillar of the lab is looking at innovative medical research and product development through the lens of systems frameworks. This includes complex adaptive systems, systems dynamics, actor network theory, ecological systems and other network theories.

As local innovation ecologies converge into a global ecology, firms, government and the public will, and indeed are, being challenged to continue growing and improving in this new larger scale system. The same is true of the larger public health systems in which domestic innovation ecologies are embedded.

We have referred to the systems nature of drug development and regulation in our work as a regulated Therapeutic Product Lifecycle (rTPL) model.

The challenge is to understand how an increasing network of nations, corporations, organizations and individuals (along with their relative strengths and weaknesses) operates and how this operation impacts nations with differentially constrained political and legal systems.

We are actively engaged in research on a number of themes relating to medical product development, regulation and litigation. This includes application of actor network theory (ANT) to and other theories of knowledge creation and uptake; the application of systems dynamics and complex adaptive systems theories to drug regulation and national science and technology policy; and application of distributed networks and theoretical and empirical work in complexity to distributive theories of justice, democracy and public health.

Our initial foray into the theoretical application of network and systems theories to patent litigation, drug regulation and science policy have been published and is available on ssrn.com. (University of Ottawa Law & Technology Journal. 4(1): 1-53. 2007; Health Law Journal. 15(1): 247-293. 2008; Health Law Review. 17(1): 28-43. 2008).

We have completed two empirical studies on the relationship between drug approval, drug patenting and innovation in the pharmaceutical sector. The projects are the first to empirically link innovation patterns to the basket of legal incentives claimed to underpin innovation, in particular patents.

Data from the work has been recently published. The pilot study on the relationship between patent protection under the linkage regime for 16 drugs and 772 patents was published by the Berkeley Technology Law Journal (24(4): 1461-1522. 2009) and the follow up study on 95 drugs and 4,000 patents was published by the Northwestern Journal of Technology and Intellectual Property (8(2): 174-227. 2010).

The constitutional and policy implications of our empirical work as it relates to the successes and failures of government stimulus packages intended to promote innovation in the United States and Canada is in press with the Marquette Intellectual Property Review (15(1): 1-52.2011).

Finally, the lab has broadened its perspective from North American pharmaceutical linkage to global linkage.

In conjunction with a recently formed Global Consortium for the Study of Pharmaceutical Linkage, we have put forward a "structure-function" model for the analysis of global linkage law and policy based on analytical frameworks of this nature in the life sciences. Our first paper has just been published by the Minnesota Journal of Law, Science & Technology (12(2): 391-457. 2011).

Pharmaceutical Innovation Practice & Policy:

Connected with our group's empirical work on drug regulation, is our new work on constructing a novel innovation index to qualify the value of pharmaceutical products.

Qualifying the value of pharmaceutical patents in particular has been a highly sought method, given the complexities and difficulties involved using solely quantitative, or 'counting,' models of patent value. The work has just been published in the form of two companion papers.

The first Article entails the description of a harmonized method to quantify pharmaceutical products, patents and associated chemical components (Boston University Journal of Science and Technology Law. 18(1): 1-63. In Press. July 2011.).

The second Article provides the method to transform raw data into innovation index data, justifies the use of this model in terms of formal objective and subjective considerations, lays out the results of the analysis, and provides an interpretation of the data in relation to existing pharmaceutical law and policy (Santa Clara Computer and High Technology Law Journal. 29(1): 78 pp. In. Press. July 2011).

Along with two economist colleagues, Paul Grootendorst and Aidan Hollis, the policy implications of the need to qualify pharmaceutical patents in relation to drug costs and expenditures has also been assessed. This work has just been accepted for publication (Canadian Medical Association Journal. 1-10. 2011.).

Sample Publications

A. LAW

Full-Length Papers:

Bouchard, R.A. Qualifying Intellectual Property II: A Novel Innovation Index for Pharmaceutical Patents and Products. Santa Clara Computer and High Technology Law Journal. 29(1): 287-402. 2012.

Bouchard, R.A. Qualifying Intellectual Property I: Harmonized Measurement of New and Follow-On Drug Approvals, Patents and Chemical Components. Boston University Journal of Science and Technology Law. 18(1): 38-97. 2012.

Grootendorst, P., Bouchard, R.A., Hollis, A. Canada's Pharmaceutical Intellectual Property Laws: The Case for Fundamental Reform. Canadian Medical Association Journal. 184(17): 1-7. 2011.

Bouchard, R.A. Cahoy, D., Domeij, B., Dutfield, G., Faunce, T., Hollis, A., Jones, P., Ali Khader, F., Lexchin, J., Nam, H., & Serrano, J.L. Structure-Function Analysis of Global Pharmaceutical Linkage Regulations. Minnesota Journal of Law, Science & Technology. 12(2): 391-457. 2011.

Bouchard, R.A. I’m Still Your Baby: Canada’s Continuing Support of U.S. Linkage Regulations for Pharmaceuticals. Marquette Intellectual Property Law Review. 15(1): 79-147. 2011.

Bouchard, R.A., Hawkins, R.W. Clark, R., Hagtvedt, R., Sawani, J. Empirical Analysis of Drug Approval-Patenting Linkage for High Value Pharmaceuticals. Northwestern Journal of Technology & Intellectual Property. 8(2): 1-86. 2010.

Bouchard, R.A., Sawani, J., McLelland, C. Sawicka, M. & Hawkins, R. The Pas de Deux of Pharmaceutical Regulation and Innovation: Who’s Leading Whom? Berkeley Technology Law Journal. 24(3): 1-66. 2009.

Bouchard, R.A. & Sawicka, M. The Mud and the Blood and the Beer: Canada’s new Progressive Licensing Framework for drug approval. McGill Journal of Law & Health. 3: 51-86. 2009.

Sawicka, M. & Bouchard, R.A. Empirical analysis of Canadian drug approval data 2001-2008: Are Canadian pharmaceutical players “doing more with less?” McGill Journal of Law & Health. 3: 87-151. 2009.

Bouchard, R.A. & Lemmens, T. Privatizing biomedical research- A ‘third way’. Nature Biotechnology. 26(1): 31-36. 2008.

Bouchard, R.A. Balancing Public and Private Interests in the Commercialization of Publicly Funded Medical Research: Is There a Role for Compulsory Government Royalty Fees? Boston University Journal of Science and Technology Law. 13(2): 120-192. 2007.

Bouchard, R.A. Reflections on the value of systems models for regulation of medical research and product development. Health Law Review. 17(1): 28-43. 2008.

Bouchard, R.A. KSR v. Teleflex Part 2: Impact of U.S. Supreme Court patent law on Canadian and global systems-based innovation ecologies. Health Law Journal. 15(1): 247-293. 2008.

Bouchard, R.A. KSR v. Teleflex Part 1: Impact of U.S. Supreme Court patent law on Canadian intellectual property and regulatory rights landscape. Health Law Journal. 15(1): 222-246. 2008.

Bouchard, R.A. Living separate and apart is never easy: Inventive capacity of the PHOSITA as the tie that binds obviousness and inventiveness. University of Ottawa Law & Technology Journal. 4(1): 1-57. 2007.

Bouchard, R.A. Should scientific research in the lead-up to invention vitiate obviousness under the Patented Medicines (Notice of Compliance) Regulations: To test or not to test? Canadian Journal of Law & Technology. 6(1): 1-27. 2007.

Bouchard, R.A. Benefit sharing and the privatization of medical research. Munk Centre for International Studies Briefings. CPHS 5: 190-216. 2007.

Bouchard, R.A. Book Review: Law Reform & Medical Injury Litigation. S. McLean. Queen’s Law Journal. 21(2): 541-548, 1996.

Books:

Bouchard, R.A. Patently Innovative. How Pharmaceutical Firms Use Emerging Patent Law to Extend Monopolies on Blockbuster Drugs. Biohealthcare Publishing Limited (Oxford UK). 2011.

Book Chapters:

Bouchard, R.A. Legal, Regulatory and Ethical Dimensions of Mandatory Clinical Trial Regulation. Clinical Trials: Law and Regulation. A. Sabitha, ed. (Amicus Books, Icfai University Press). 1-30. 2008.

Lemmens, T. & Bouchard, R.A. Regulation of Pharmaceuticals in Canada. J. Downie, T. Caulfield & C. Flood, eds., Canadian Health Law & Policy, 3rd ed. Toronto. Butterworths. 318-387. 2007.

Lemmens, T. & Bouchard, R.A. Mandatory clinical trial registration: Rebuilding public trust in medical research. The Global Forum Update on Research for Health. 4th ed. London, Pro-Brook Publishing Ltd. 40-46. 2007.

Law Blogs:

Bouchard, R.A. Jurisdynamics. Innovation Incentives Part 3: Combining Innovation Index and Product Cluster Models of Drug Development. Innovation Ecology. December 6, 2011. Available at: http://jurisdynamics.blogspot.com. Also published at BioLaw.com.

Bouchard, R.A. Jurisdynamics. Innovation Incentives Part 2: Patent Valuation. December 6, 2011. Available at: http://jurisdynamics.blogspot.com. Also published at BioLaw.com.

Bouchard, R.A. Jurisdynamics. Innovation Incentives Part 1: regulated Therapeutic Product Lifecycle. November 30, 2011. Available at: http://jurisdynamics.blogspot.com. Also published at BioLaw.com.

Bouchard, R.A. IP Osgoode. Patent Valuation Part 2: Combining Innovation Index and Product-Patent Clusters. November 5, 2011. Available at: http://www.iposgoode.ca.

Bouchard, R.A. IP Osgoode Featured Post. Patent Valuation Part 1: A Novel Innovation Index for Valuation of Life Sciences Inventions. November 14, 2011. Available at:

Bouchard, R.A. IP Osgoode. Global Pharmaceutical Linkage Regulations: A Consortium Framework. November 23, 2010. Available at: http://www.iposgoode.ca/2010/11/global-pharmaceutical-linkage-regulations-a-consortium-framework/

Bouchard, R.A. IP Osgoode. Living Separate and Apart is Never Easy: Obviousness and Inventiveness in Pharmaceutical Litigation. March 26, 2010. Available at: http://www.iposgoode.ca/2010/04/living-separate-and-apart-is-never-easy-obviousness-and-inventiveness-in-pharmaceutical-litigation/

Bouchard, R.A. IP Osgoode Featured Post. I‟m Still Your Baby: Canada‟s Continuing Support of U.S. Linkage Regulations for Pharmaceuticals. March 8, 2010. Available at: http://www.iposgoode.ca/2010/03/im-still-your-baby-canadas-continuing-support-of-u-s-linkage-regulations-for-pharmaceuticals/

Bouchard, R.A. Jurisdynamics. Complexity, IPR Rights and Innovation Ecologies. Part 1: Intellectual Property and Regulatory Rights Considerations. Mar. 14, 2008. Available at: http://jurisdynamics.blogspot.com/2008/03/complexity-ipr-rights-and-innovation.html

Bouchard, R.A. Jurisdynamics. Complexity, IPR Rights and Innovation Ecologies. Part 2: Distributive Considerations. March 16, 2008. Available at: http://jurisdynamics.blogspot.com/2008/03/complexity-ipr-rights-and-innovation_16.html

Bouchard, R.A. First Movers. Complexity and the PHOSITA. Feb. 21, 2007. Available at: http://firstmovers.blogspot.com/2007/02/complexity-and-phosita.html

Public Submissions, Articles & Book Reviews:

Lemmens, T & Bouchard, R.A. Comments on the Legal, Regulatory and Ethical Aspects of the WHO Clinical Trial Registry Platform. Submitted to the World Health Organization as part of its Formal Consultation on Disclosure Timing Policy. Geneva, April 2006. 1-8. http://www.who.int/ictrp/011_Lemmens_Bouchard_5April06.pdf

Bouchard, R.A. & Lemmens, T. Intellectual Property and Regulatory Implications of the WHO Clinical Trial Registration Platform. Invited Submission to WHO Directorate. 1-11. March 2006.

Bouchard, R.A. You and the pharmaceutical industry: David v. Goliath? New Queens Counsel. 7(1): 18-19, 1995.

Bouchard, R.A. Private health care: Coming soon to a hospital near you? New Queens Counsel. 6(4):11-12, 1995.

Bouchard, R.A. The right to die: Whose right is it anyway? New Queens Counsel. 6(2):11-12, 1994.

B. SCIENCE

Full-Length Peer-Reviewed Papers:

Omelchenko, A., Bouchard, R.A., Shurraw, S., Trac, M., Hnatowich, M., Hryshko, L.V. Frequency-dependent regulation of the cardiac NCX1.1 Na+-Ca2+ exchanger. American Journal of Physiology, Oct; 289(4):H1594-603. 2005.

Bouchard, R.A., Clark, R.B., Juhasz, A., Giles, W., R. Changes in extracellular K+ concentration modulate contractility in rat and rabbit cardiac myocytes via the inward rectifier K+ current IK1. Journal of Physiology, 556(3): 773-190. 2004.

Bouchard, R.A., Omelchenko, O., Le, H.L., Choptiany, P., Matsuoka, T,. Baba, A., Nicoll, D.A., Phillipson, K., Hnatowich, M., Hryshko, L.V. Effects of SEA0400 on mutant NCX1.1 Na+-Ca2+ exchangers with altered ionic regulation. Molecular Pharmacology, 65(3): 802-810. 2004.

Omelchenko, A., Bouchard, R.A., Le, H.L., Choptiany, P., Hnatowich, M., Hryshko, L.V. Inhibition of canine (NCX1.1) and Drosophila (CALX1.1) sarcolemmal Na+-Ca2+ exchangers by CGP-37157. Journal of Pharmacology & Experimental Therapeutics, 306: 1050-1057, 2003.

Bouchard, R.A., Pattarini, R., & Geiger, J.D. Review: Presence and functional significance of presynaptic ryanodine receptors. Progress in Neurobiology. 69(6): 391-418. 2003.

Bouchard, R.A., Weber, A.R., Geiger, J.D. Review: Informed decision making on sympathomimetic use in sport and health. Clinical Journal of Sports Medicine. 12:209-224. 2002.

Orta, G., Bouchard, R.A., Morales, F., Salinas, E. Inhibition of cardiac Na+ current by primaquine. British Journal of Pharmacology. 135: 751-763. 2002.

Tushima, R.G., Wickendon, A.D., Bouchard, R.A., Oudit, G.Y., Lui, P.P., Backx, P.H. Modulation of iron uptake in heart by L-type calcium channels: Possible implications in iron overload. Circulation Research. 84: 1302-1309. 1999.

Fedida, D., Bouchard, R.A., Chen, F.S.P. Slow gating charge immobilization in the human potassium channel Kv1.5 and its prevention by 4-Aminopyridine. Journal of Physiology. 494.2: 377-387. 1996.

Clark, R.B., Bouchard, R.A., Giles, W.R. Action potential duration modulates calcium influx, Na+-Ca2+ exchange and intracellular calcium release in rat ventricular myocytes. Annuls of the New York Academy of Sciences. 779: 417-428, 1996.

Bouchard, R.A., & Fedida, D. Closed and open state binding by 4-aminopyridine to the cloned human K+ channel Kv1.5. Journal of Pharmacology and Experimental Therapeutics. 275(2): 864-876. 1995.

Bouchard, R.A., Clark, R.B., Giles, W.R. Effects of action potential duration on excitation-contraction coupling in rat ventricular myocytes: Action potential voltage clamp measurements. Circulation Research. 76: 790-801. 1995 .

Bouchard, R.A., Clark, R.B., Giles, W.R. Role of sodium calcium exchange in activation of contraction in rat ventricle. Journal of Physiology. 472: 391 413. 1993.

Clark, R.B., Bouchard, R.A., Salinas, E., Sanchez, J., Giles, W.R. Heterogeneity of action potential waveforms and repolarizing potassium currents in rat ventricular myocytes. Cardiovascular Research. 27: 1795 1799. 1993 .

Bouchard, R.A., Clark, R.B., Giles, W.R. Regulation of unloaded cell shortening in isolated rat ventricular myocytes by sarcolemmal sodium calcium exchange. Journal of Physiology. 469: 583 599. 1993.

Fedida, D. & Bouchard, R.A. Mechanisms for the positive inotropic effect of alpha-1 adrenoceptor stimulation in isolated rat ventricular myocytes. Circulation Research. 71: 673 688. 1992.

Bouchard, R.A., & Bose, D. Contribution of sarcolemmal sodium calcium exchange and intracellular calcium release to force development in isolated canine ventricular muscle. Journal of General Physiology. 99: 931 960. 1992.

Bouchard, R.A. & Bose, D. Influence of experimental diabetes on sarcoplasmic reticulum function in rat ventricular muscle. American Journal of Physiology. 260 (Heart Circulation Physiology. 29) H341 H354. 1991.

Bouchard, R.A. & Bose, D. Analysis of the interval force relationship in rat and canine ventricular myocardium. American Journal of Physiology. (Heart Circulation Physiology. 26) 257:H2036 H2047, 1989.

Bouchard, R.A., Hryshko, L.V., Saha, J.K., Bose, D. Effect of caffeine and ryanodine on depression of post rest tension development produced by BAY K 8644 in canine ventricular myocardium. British Journal of Pharmacology. 97: 1279 1291. 1989.

Saha, J.K, Hryshko, L.V., Bouchard, R.A., Chau, T., Bose, D. Analysis of the effects of ( ) and (+) isomers of the 1,4 dihydropyridine calcium channel antagonist BAY K 8644 on post rest potentiation in the canine ventricular muscle. Canadian Journal of Physiology and Pharmacology. 67: 788 794. 1989.

Hryshko, L.V., Bouchard, R.A., Chau, T., Bose, D. Inhibition of rest potentiation in canine ventricular muscle by the calcium channel agonist BAY K 8644: Comparison with caffeine. American Journal of Physiology (Heart Circulation Physiology. 26) 257: H399 H406. 1989.

Bose, D., Kobayashi, T., Bouchard, R.A., Hryshko, L.V., and Bose, D. Scattered light intensity fluctuation in the canine ventricular myocardium: correlation with inotropic drug effect. Canadian Journal of Physiology and Pharmacology. 66: 1232-1238. 1988.

Book Chapters:

Bose, D., Bouchard, R.A., Saha, J.K., Hryshko, L.V., Chau, T. Inhibition of sarcoplasmic reticular Ca2+ release by the Ca2+ channel agonist, BAY K 8644: Are sarcolemmal Ca2+ channels involved? In Calcium channel modulators in ischemic heart disease and other cardiovascular disorders: Basic & therapeutic approaches. Ed. S. Abrahm, Pub. Alan R. Liss, Inc. N.Y. 1990.

Bose, D., Hryshko, L.V., Bouchard, R.A., Kobayashi, T., Saha, J., Chau, T. Unusual effects of calcium channel agonists. In Advances in Heart Diseases, ed. Anand. Pub. Kluwer Pub. Co. 1989.

Public Submissions, Articles & Book Reviews:

Geiger, J.D & Bouchard, R.A. Drug is not a “four letter word”. The Enhancer: Sport Medicine Council of Manitoba Journal. November: 1-2. 2002.

Abstracts:

Orta, G., Bouchard, R.A., Salinas E. Inhibition of INa by primaquine. Biophysical Journal. 80:224(a). 2001.

Tushima, R.G., Wickendon, A., Bouchard, R.A.., Lui, P.P., Backx, P. Fe2+ permeation through L-type Ca2+ channels: Mechanism of iron uptake by the heart. Circulation. 96(8) Supp. A1995. 1997.

Bouchard, R.A., Chen, F.S.P., Fedida, D. 4-Aminopyridine prevents gating charge immobilization and C-type inactivation in the cloned human potassium channel Kv1.5. Biophysical Journal. 1996.

Bouchard, R.A., Clark, R.B., Giles, W.R. E-C coupling and [Ca2+]i homeostasis in rat ventricular myocytes studied using the action potential clamp technique. Biophysical Journal. 66(2), M371, 1994.

Bouchard, R.A., Clark, R.B., Giles, W.R. Effects of action potential prolongation on Ca2+ current, [Ca2+]i and contraction studied using the action potential clamp technique. Biophysical Journal. 66(2): M372, 1994.

Bouchard, R.A., Clark, R.B., Giles, W.R. Voltage dependence of contraction in isolated rat ventricular myocytes. Biophysical. Journal. 64(2): M92, 1993.

Bouchard, R.A., Clark, R.B., Giles, W.R. Regulation of unloaded cell shortening by sarcolemmal Na+/Ca2+ exchange in isolated rat ventricular cells. Biophysical Journal. 64(2): M91, 1993.

Giles, W.R., Clark, R.B., Braun, A., Fedida, D., Bouchard, R.A. Ionic mechanisms of repolarization in mammalian ventricle. Journal of Molecular and Cellular Cardiology. 24(S4):S12, 1992.

Bouchard, R.A., & Fedida, D. The positive inotropic effect of 1 adrenoceptor activation is dependent upon action potential prolongation in rat cardiac myocytes. Journal of Physiology. 446:143P, 1991.

Fedida, D. & Bouchard, R.A. Relationship between action potential duration and unloaded cell shortening revealed by 1 adrenoceptor stimulation in rat ventricular cells. Canadian Journal of Cardiology. 7(SA):112A, 1991.

Bouchard, R.A., & Bose, D. Direct contribution of the Na+ Ca2+ exchange process toward developed tension in mammalian ventricular muscle. Biophysical Journal. 57(2): 455. 1990.

Bose, D., Hryshko, L.V., Bouchard, R.A., Saha, J.K., Chau, T., Unusual alteration of cardiac sarcoplasmic reticulum calcium stores by calcium agonists. 33rd Oholo Conference on Calcium Channel Modulators. Israel. 33: 18. 1989.

Bouchard, R.A., & Bose, D. Mechanism of the negative tension staircase in rat ventricular myocardium. The Physiologist. 31: 7-8. 1988.

Bouchard, R.A., Hryshko, L.V., Saha, J.K., Bose, D. The calcium channel agonist BAY K 8644 reveals differences in the mode of action of ryanodine and caffeine on mammalian cardiac sarcoplasmic reticular function. Federation Proceedings. 2: 4867. 1988.

Saha, J.K., Bouchard, R.A., Hryshko, L.V., Chau, T., Bose, D. Is inhibition of calcium release from the canine ventricular SR by BAY K 8644 due to an action on the calcium channel? Federation Proceedings. 2: 1819. 1988.

Bose, D., Bouchard, R.A., Hryshko, L.V., Kobayashi, T., Chau, T. Assessment of the contribution of sarcoplasmic reticular calcium in mammalian excitation-contraction coupling by laser light scattering. International Symposium on Heart Disease, International Society of Heart Research Meeting. India, 1988.

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