UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
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`COALITION FOR AFFORDABLE DRUGS VIII, LLC
`Petitioner,
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`v.
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`THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
`Patent Owner
`
`______________
`
`Case: IPR2015-01836
`Patent No. 7,932,268
`______________
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`DECLARATION OF FRANK SACKS, M.D., IN SUPPORT OF PATENT
`OWNER’S RESPONSE TO PETITION FOR INTER PARTES REVIEW
`AND IN SUPPORT OF MOTION TO AMEND
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`TABLE OF CONTENTS
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`Page
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`I. QUALIFICATIONS ............................................................................................ 4
`II.
`INFORMATION CONSIDERED .................................................................. 14
`III. SUMMARY OF OPINIONS .......................................................................... 14
`IV. LEGAL PRINCIPLES .................................................................................... 17
`V. RELEVANT DATE OF INVENTION, PERSON OF ORDINARY SKILL
`IN THE ART, AND CLAIM CONSTRUCTION ................................................... 20
`A. Date of Invention ......................................................................................... 20
`B.
`Person of Ordinary Skill in the Art ............................................................. 20
`C. Claim Construction ...................................................................................... 22
`VI. THE PATENTS AT ISSUE ........................................................................... 23
`VII. BACKGROUND AND STATE OF THE ART .......................................... 29
`A. Hypercholesterolemia .................................................................................. 29
`B.
`Therapeutic Drugs for Hypercholesterolemia ............................................. 29
`1. Statins .......................................................................................................... 30
`2. Bile Acid Sequestrants ................................................................................ 32
`3. Nicotinic Acid ............................................................................................. 33
`4. Fibrates ........................................................................................................ 35
`C. Differences Among the Statins ................................................................... 35
`D. Use of Drug Therapy to Achieve Treatment Goals .................................... 38
`E. Homozygous Familial Hypercholesterolemia ............................................. 39
`F. MTP Inhibitors ............................................................................................ 41
`VIII. NO CHALLENGED CLAIM OF THE ’135 OR ’268 PATENT IS
`OBVIOUS OVER ANY COMBINATION OF PRIOR ART CITED BY THE
`PETITIONER IN GROUNDS 1 OR 2 .................................................................... 44
`A. A POSA Would Not Have Been Motivated to Combine Chang With Either
`Pink Sheet 2004 or Stein 2004, and These Combinations Would Not Have Given
`a POSA a Reasonable Expectation of Success that Substituting Lomitapide Into
`Dr. Stein’s Protocol for Implitapide Would Have Resulted in a Means of
`Treating Patients in a Safe and Efficacious Manner ............................................. 45
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`1. A POSA would not have been motivated to select lomitapide for
`development ....................................................................................................... 45
`2. Chang does not suggest that implitapide and lomitapide would have similar
`effects at similar doses ....................................................................................... 48
`3. Titration to reduce side effects was not the norm for most cholesterol-
`lowering drugs, and a POSA would not have expected upward titration to
`reduce lomitapide’s side effects ........................................................................ 56
`4. Clinicians would not have used references like Pink Sheet or Stein to
`devise dosing regimens ...................................................................................... 64
`5. A POSA would not have understood Dr. Stein to be proposing a method of
`treating patients via upward titration to ameliorate side effects ........................ 66
`6. The results of Dr. Stein’s proposed experiment were unknown, so there
`was no indication that he was able to even find a therapeutic window for
`implitapide ......................................................................................................... 68
`B. Dependent Claims of the ’135 Patent .......................................................... 69
`C. Dependent Claims of the ’268 Patent .......................................................... 71
`D.
`Secondary Considerations ........................................................................... 73
`1. Long-Felt Need ............................................................................................ 73
`2. Praise ........................................................................................................... 76
`3. Unexpected Results ..................................................................................... 76
`4. Teaching Away ............................................................................................ 77
`5. Failure of Others .......................................................................................... 79
`IX. MOTION TO AMEND .................................................................................. 80
`A. The Proposed Substitute Claims Are Supported By the Written Description
`of the Provisional Application .............................................................................. 80
`B.
`The Proposed Substitute Claims Are Patentable Over All Prior Art of
`Record .................................................................................................................103
`X.
`PRIOR EXPERT TESTIMONY ..................................................................104
`XI. COMPENSATION .......................................................................................106
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`I, Frank Sacks, M.D., declare and state as follows:
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`I.
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`QUALIFICATIONS
`1.
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`I am a Professor of Cardiovascular Disease Prevention in the
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`Department of Nutrition at the Harvard T.H. Chan School of Public Health, a
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`Professor of Medicine in the Channing Division of Network Medicine at
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`Harvard Medical School, and Senior Physician at Brigham & Women’s
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`Hospital. My responsibilities include research, teaching, and previously clinical
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`practice, all pertaining to hyperlipidemia, hypertension, and associated
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`conditions in the prevention and treatment of cardiovascular disease (CVD). I
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`also participate as a member, chair, or fellow in numerous professional societies,
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`committees, and editorial boards.
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`2. My clinical field of expertise is lipidology, the diagnosis and
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`treatment of lipid disorders including hypercholesterolemia (high blood
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`cholesterol), hypertriglyceridemia (high blood triglycerides), and low high-
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`density lipoprotein (HDL) cholesterol.
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`3.
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`I am a fully licensed physician in the State of Massachusetts.
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`4. My professional interests include research and public policy in
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`nutrition, cholesterol disorders, hypertension, and cardiovascular disease. I have
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`240 peer-reviewed publications of original research in peer-reviewed journals,
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`including in journals such as the New England Journal of Medicine (NEJM) and
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`the Journal of the American Medical Association (JAMA), and over 90 reviews,
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`editorials and chapters relating to my interests. In addition, I am the editor or
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`co-editor of three books relating to cardiovascular disease, cholesterol disorders,
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`and nutrition.
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`5.
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`In 1970, I received a Bachelor of Science degree in Biology with an
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`emphasis in Biochemistry from Brown University. From 1972 to 1973, I was a
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`research assistant at the Channing Laboratory, Harvard Medical School, at
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`which time I began research in nutrition and cardiovascular disease. In 1977, I
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`received a Doctor of Medicine degree from Columbia University College of
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`Physicians and Surgeons. From 1977 to 1978, I was a Resident in Surgery at
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`University Hospital in Madison, Wisconsin. In 1978, I received a license to
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`practice medicine in Wisconsin.
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`6.
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`From 1978 to 1980, I was an emergency room physician at several
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`hospitals in Wisconsin. From 1980 to 1982, I served as a Postdoctoral Research
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`Fellow in the Department of Medicine at Harvard Medical School and Brigham
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`and Women’s Hospital concentrating on nutrition in the prevention and
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`treatment of cardiovascular disease (CVD) and stroke. From 1982 to 1993, I
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`had faculty appointments at Harvard Medical School, was employed at Brigham
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`and Women’s Hospital, and also had hospital appointments at Children’s
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`Hospital and Beth Israel Hospital, all in Boston and pertaining to diagnosis and
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`treatment of lipid disorders and research in lipid disorders and cardiovascular
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`disease.
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`7.
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`Since 1993, I have been employed by the Harvard School of Public
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`Health and Brigham and Women’s Hospital. From 1993 to 2000, I was an
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`Associate Professor in the Department of Nutrition at the Harvard School of
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`Public Health. In 2000, I assumed my present position as Professor with tenure
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`at the Harvard School of Public Health. From 1993 to 2004, I was also an
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`Associate Professor of Medicine at Harvard Medical School. In 2004, I
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`assumed my present position as Professor of Medicine at Harvard Medical
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`School. From 2006-2009, I consulted for Aegerion Pharmaceuticals, Inc., for 1-
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`2 days a year, for a total of $13,400 in compensation.
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`8. My clinical field of expertise is lipidology. Clinical lipidology is
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`the diagnosis and treatment of lipid disorders including hypercholesterolemia
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`(high blood cholesterol), hypertriglyceridemia (high blood triglycerides), and
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`low high-density lipoprotein (HDL) cholesterol. Before statins were available,
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`lipidology was a very difficult field to work in because of the absence of
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`effective and safe medications, and it had little interest to most physicians.
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`After lovastatin was approved for clinical use, lipidology attracted many
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`physicians across a range of medical specialties including internal medicine and
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`its subspecialties, especially endocrinology, gastroenterology, and cardiology, as
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`well as family practice and pediatrics. The National Lipid Association (NLA)
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`developed a certification examination and credentials, based on a rigorous
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`teaching program and examination. Last year, I was invited to serve on the
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`Board of Directors of the National Board of Lipidology which designs the
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`examinations and approves the criteria for board certification. The NLA has
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`national and regional educational conferences and established the Journal of
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`Clinical Lipidology, a professional, peer-reviewed journal that publishes articles
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`on research and clinical practice in lipidology. I was an Associate Editor of this
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`journal.
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`9. My clinical practice in lipidology was in the Cardiology Division at
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`Brigham and Women’s Hospital from 1984 to 2010. I have treated over one
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`thousand patients for hyperlipidemia, and often also for additional conditions
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`associated with cardiovascular disease, including hypertension and type 2
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`diabetes. In the late 1980’s, I helped Boston Children’s Hospital establish a
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`pediatric lipidology clinic, which included training pediatric endocrinologists
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`and cardiologists. In the Cardiology Clinic at Brigham and Women’s Hospital, I
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`taught residents in internal medicine and clinical fellows in subspecialty training
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`in cardiology or endocrinology the management of lipid disorders by diet and
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`drug treatments. All cardiology trainees and endocrinology trainees who had a
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`particular interest in lipidology rotated through this clinic. I taught these
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`residents and fellows risk assessment for cardiovascular disease and treatment of
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`hyperlipidemia by diet and drugs. I also treated patients who had a wide range
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`of clinical problems in lipids at this clinic. These included severe
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`hyperlipidemia caused by rare genetic defects; hyperlipidemia in patients with
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`diabetes or other endocrine diseases; hyperlipidemia treatment complicated by
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`adverse drug interactions such as with anti-hypertensive drugs; patients who
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`wanted an opinion on starting statin treatment; and patients who were suspected
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`of having a complication of treatment with statins or other lipid drugs such as
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`nicotinic acid or gemfibrozil.
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`10.
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`I am one of the very few clinicians who has clinical experience
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`with lomitapide prior to 2004. In 1999, I undertook compassionate use of
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`lomitapide to treat a patient suffering from near-fatal pancreatitis secondary to
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`severe hypertriglyceridemia. This treatment lasted more than a decade and was
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`presented as a case study in JAMA-Internal Medicine. Ex. 2043 (Frank M.
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`Sacks et al., Severe Hypertriglyceridemia with Pancreatitis[:] Thirteen Years’
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`Treatment with Lomitapide, 174(3) JAMA INTERN. MED. 443-447 (2014)).
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`11. My research has been on how very-low-density lipoprotein
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`(VLDL), low-density lipoprotein (LDL), and HDL are produced, interconverted,
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`and removed from the blood circulation, and the effects on these processes of
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`various diets, estrogens, and drugs. My laboratory has and is also learning about
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`different types of these lipoproteins that have more or less harmful or beneficial
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`effects on CVD.
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`12. My lipoprotein research, nearly all in humans, has been funded
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`continuously by major grants from the National Heart, Lung, and Blood Institute
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`(NHLBI) of the National Institutes of Health (NIH) since the 1980’s. My
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`laboratory also has had smaller grants from biotechnology and pharmaceutical
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`companies to study how drugs affect the lipoprotein system.
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`13.
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`I have been studying dietary patterns and conducting dietary trials
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`for my entire career, related to hypertension, lipoproteins, and obesity. I have
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`participated in and led many clinical trials and other studies relating to heart
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`disease and hyperlipidemia, including:
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` (2008-10) Effect on apolipoprotein C-III, of mipomersen, a novel
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`antisense oligonucleotide drug that suppresses the production in the
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`liver of apolipoprotein B and its associated lipoproteins, VLDL and
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`LDL, in hypercholesterolemia. (Grant from ISIS Pharmaceuticals to
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`Harvard University: F. Sacks, Principal Investigator);
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` (2009-10) Establishing a platform for evaluating the effects of diet
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`and drugs on the function of human HDL. (Harvard Catalyst Grant for
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`innovative research with translational potential: F. Sacks, Principal
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`Investigator);
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` (2010-15) Diet and human HDL metabolism. (Grant from National
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`Heart, Lung, and Blood Institute to determine how dietary fat and
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`carbohydrate affect the principal function of HDL in removing
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`cholesterol from the body: F. Sacks, Principal Investigator);
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` (1996-2002) Dietary Approaches to Stop Hypertension (“DASH”) and
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`Sodium Trial - a multicenter trial on blood pressure and lipids of
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`dietary patterns and sodium reduction (Grant from National Heart,
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`Lung, and Blood Institute: F. Sacks Principal Investigator);
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` (2003-07) VLDL and LDL particle types as CHD risk factors (NIH:
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`R01 HL070159) (Grant from National Heart, Lung, and Blood
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`Institute: F. Sacks Principal Investigator);
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` (2002-06) Apo A2, Cl and C2 and diet in human apoB metabolism
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`(NIH: 1R01 HL69376) (Grant from National Heart, Lung, and Blood
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`Institute: F. Sacks, Principal Investigator);
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` (1997-2002) “Kinetics of human postprandial lipoprotein metabolism”
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`(NIH RO1HL56210) (Grant from National Heart, Lung, and Blood
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`Institute: F. Sacks, Principal Investigator);
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` (1997-2001) “Lipoprotein ancillary project in the CARE trial,” study
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`of lipoprotein subtractions to predict cardiovascular events, and
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`differential response to treatment (Grant from Bristol Myers Squibb
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`Company (“BMS”) to Brigham & Women’s Hospital: F. Sacks,
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`Principal Investigator);
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` (1988-96) “Cholesterol and Recurrent Events (CARE) trial”. (Grant
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`from BMS to Brigham & Women’s Hospital: F. Sacks, Principal
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`Investigator); and
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` (1986-97) “Postmenopausal estrogens and atherosclerosis”; study of
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`effect of sex hormones on lipoprotein metabolism (NIH: RO1
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`HL34980) (Grant from National Heart, Lung, and Blood Institute: F.
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`Sacks, Principal Investigator).
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`14.
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`I have given several named lectureships at major academic
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`institutions in the U.S., Canada, and the U.K. I was the 2011 recipient of the
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`American Heart Association (AHA)’s Research Achievement Award for
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`lifetime research in cardiovascular disease. This is the top annual award of the
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`AHA for research.
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`15.
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`I have held editorial positions with numerous publications in my
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`fields of study. From 2007-2010, I was Associate Editor of The American
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`Journal of Clinical Nutrition, the leading journal publishing research and
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`commentary on nutrition and human disease. This position involved evaluating
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`the quality and determining the acceptability of over 200 research manuscripts
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`each year. I was also an Associate Editor of the Journal of Clinical Lipidology.
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`16. Over the past ten years, I have peer-reviewed hundreds of papers
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`submitted for publication to scientific journals. Many involved randomized,
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`double-blind, and placebo-controlled clinical studies or other less well-designed
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`clinical studies. Nearly all involved the study of CVD or coronary heart disease
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`(CHD) or related matters, such as surrogate endpoints, side effects,
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`complications, or causes thereof. In reviewing these papers, among other things,
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`I assessed the adequacy of the design and conduct of the clinical research, and
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`appropriateness and accuracy of the statistical test methodology used, and I
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`evaluated whether the analysis was sound.
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`17. At the Harvard School of Public Health, I have taught Nutritional
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`Epidemiology (1986-1998); Nutritional Aspects of Human Disease (1986-
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`1992); Cardiovascular Disease Epidemiology (1988-2014); Nutrition and
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`Cardiovascular Disease (Course Director, 1997-2002); The Science of Human
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`Nutrition – Nutritional Biochemistry (Course Director, 1998-2015); and
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`Scientific Writing (Course director, 2004-2015). At Harvard Medical School, I
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`have taught Principles of Pharmacology, including cholesterol disorders (1990-
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`2006); Clinical Epidemiology, including cardiovascular disease epidemiology
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`and clinical trials (2000-2005); and Preventive Medicine and Nutrition (2000-
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`2003).
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`18.
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`I have given many lectures to medical residents at Brigham &
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`Women’s Hospital and Massachusetts General Hospital on the identification and
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`management of lipid disorders. I have also lectured on lipid treatment many
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`times in Harvard Medical School continuing medical education courses and in
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`other courses throughout the U.S.
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`19.
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`I recently was elected to the Board of Directors of the National
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`Board of Lipidology, the organization that teaches and certifies competence in
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`lipidology.
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`20.
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`I have been active in national and international committees and
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`conferences in dietary and drug treatments of dyslipidemia and nutrition and
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`health guidelines. The National Cholesterol Education Program (NCEP) Adult
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`Treatment Panel (ATP) III appointed me as a peer reviewer of the national
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`guidelines for cholesterol treatment. In 2008, I was appointed a member of the
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`NCEP ATP IV and served on this Panel through 2011. From 2008 to 2013, I
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`was a member of the NHLBI Lifestyle Working Group that wrote guidelines for
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`diet and exercise to prevent cardiovascular disease that were released in 2013 by
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`the AHA and American College of Cardiology (ACC). I was a member of the
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`Hypertriglyceridemia Guidelines Committee of the Endocrine Society that
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`developed guidelines for diagnosis and treatment of elevated triglyceride levels.
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`I was also chair of the Nutrition Committee of the AHA from 2010 to 2012.
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`The Nutrition Committee advises the AHA on matters of science and public
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`policy, and constructs guidelines and advisory statements to the government,
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`health professionals, and the public on nutrition.
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`21. My curriculum vitae, which lists my professional experience and
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`qualifications in greater detail, is set forth as Exhibit 2027.
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`II.
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`INFORMATION CONSIDERED
`22.
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`In forming the opinions set forth herein, I have relied on my own
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`experiences and knowledge, and have considered the prior art from the
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`viewpoint of a person of ordinary skill in the art as of March 2004 and March
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`2005. I have also considered the documents discussed in this declaration, as well
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`as the documents listed in Exhibit 2031.
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`III. SUMMARY OF OPINIONS
`23.
`I understand that in IPR2015-01835, the Petitioner is challenging
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`claims 1-10 of U.S. Patent 8,618,135 (the “’135 patent”), and that in IPR2015-
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`01836, the Petitioner is challenging claims 1-8 of U.S. Patent 7,932,268 (the
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`“’268 patent”). I was asked to consider whether the challenged claims would
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`have been obvious to a person of ordinary skill in the art (“POSA”) as of the
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`date of the invention, which I have been asked to assume is March 4, 2004.
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`24. Based on my analysis of the prior art as a whole, as well as the
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`specific references relied upon by the Petitioner, it is my opinion that the
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`challenged claims would not have been obvious to a POSA as of March 4, 2004.
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`25.
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`I was also asked whether my opinions would change if the date of
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`the invention were March 7, 2005. My opinions would not change using this
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`date. That is, it is also my opinion that the challenged claims would not have
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`been obvious to a POSA as of March 7, 2005. I summarize my opinions below.
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`26. Dr. Zusman opines that a POSA would have been motivated to
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`combine Chang (which discloses lomitapide) with Pink Sheet 2004 or Stein
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`2004 (which purportedly disclose a titration regimen for implitapide). I disagree
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`that a POSA would have been motivated to combine Chang with either the Pink
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`Sheet 2004 or Stein 2004, including for the following reasons:
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`a. As between other classes of drugs and MTP inhibitors, a POSA
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`would not have considered a titration regimen for statins or niacins
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`to inform a dosing treatment regimen with MTP inhibitors;
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`b. As between MTP inhibitors (i.e., implitapide and lomitapide), a
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`POSA would not have assumed that a dose for one drug in a class is
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`the same for other drugs in the same class;
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`c. Clinicians would not use references like Pink Sheet or Stein to
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`devise dosing regimens;
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`d. A POSA would not have understood Dr. Stein to be proposing a
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`method of treating patients via upward titration to ameliorate side
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`effects. Rather, a POSA would have understood Dr. Stein to be
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`proposing a dose-finding protocol to identify a dose that lowers
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`LDL-C by a modest amount and that is tolerated by the patient,
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`with the goal of establishing a low dose that produces 20%
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`lowering of LDL-C without treatment-limiting side effects. In
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`contrast, the procedure described in the claims of the ’135 and ’268
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`patents is to induce tolerance to a specific dose, i.e., 10 mg daily,
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`by starting with a lower dose, i.e., 5 mg, proceeding to 7.5 mg and
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`finally to 10 mg. Dr. Sasiela shows that this procedure can create
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`tolerance to much larger doses of lomitapide, even up to 60 mg,
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`that are needed to treat homozygous familial hypercholesterolemia
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`(“HoFH”);
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`e. A POSA would not have been motivated to select lomitapide for
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`development, as it had been reported to have serious adverse effects
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`at unknown doses; and
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`f. Contrary to the opinions expressed in Dr. Zusman and Dr.
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`Mayersohn’s declarations, Chang does not suggest that implitapide
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`and lomitapide would have similar effects at similar doses.
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`27.
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`I also disagree that the Chang + Pink Sheet 2004 and Chang + Stein
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`2004 combinations would have given a POSA a reasonable expectation of
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`success that substituting lomitapide into Dr. Stein’s dosing regimen for
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`implitapide would have resulted in a means of treating patients in a safe and
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`efficacious manner, including for the following reasons:
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`a. The prior art reported that development of lomitapide had been
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`discontinued due to adverse events, but did not report the doses of
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`lomitapide at which these adverse events were experienced; and
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`b. The results of Dr. Stein’s proposed experiment were unknown, so
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`there was no indication that he was able to even find a therapeutic
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`window for implitapide. In fact, Dr. Stein’s company PPD
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`discontinued its study of implitapide shortly thereafter without
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`indication of any solution to efficacy vs. adverse effects.
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`28. Secondary considerations of nonobviousness, including long-felt
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`need, praise, unexpected results, teaching away, and failure of others,
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`demonstrate that the claims would not have been obvious.
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`IV. LEGAL PRINCIPLES
`29.
`I have been informed by counsel that an issued patent claim is
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`unpatentable as obvious if it can be shown that the differences between the
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`claimed subject matter and the prior art are such that the subject matter as a
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`whole would have been obvious, at the time the invention was made, to a person
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`having ordinary skill in the art. Relevant considerations include the level of
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`ordinary skill in the art, the scope and content of the prior art, any differences
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`between the prior art and the asserted claims, and the so-called objective
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`secondary considerations of nonobviousness.
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`30.
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`I have been informed by counsel that obviousness in this inter
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`partes proceeding must be established by a preponderance of the evidence. I
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`understand this to mean that, for a claim to be found invalid as obvious, it must
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`be found more probable than not to be obvious.
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`31.
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`I have been informed by counsel that the obviousness inquiry
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`requires that the prior art be considered in its entirety. I am further informed and
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`I understand that an invention cannot be obvious to try where the breadth of the
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`choices and the numerous combinations indicate that the disclosures would not
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`have rendered the claimed invention obvious to try.
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`32.
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`I have been informed by counsel that there must be some showing
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`that a person of ordinary skill in the art would have been motivated to combine
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`the asserted combination of prior art references and that there would have been a
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`reasonable expectation of successfully achieving the claimed invention from
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`such combination in order to support an obviousness determination.
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`33.
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`I have been informed and understand that a patent claim composed
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`of several limitations is not obvious merely because each limitation was
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`independently known in the prior art. I have been informed by counsel that, in
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`considering the obviousness of a claimed invention, one should not view the
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`invention and the prior art with the benefit of hindsight. I understand that for
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`this reason, obviousness is assessed by the person of ordinary skill in the art at
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`the time the invention was made in light of the prior art as a whole. In this
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`regard, I have been informed that the invention cannot be used as a guide to
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`selecting and understanding the prior art.
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`34.
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`I have been informed that a reference may be said to teach away
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`when a person of ordinary skill, upon reading the reference, would be
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`discouraged from following the path set out in the reference, or would be led in
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`a direction divergent from the path that was taken by the inventor.
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`35.
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`I have been informed that in determining the obviousness or
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`nonobviousness of a claimed invention, one must examine any secondary
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`considerations of nonobviousness such as whether the invention was
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`commercially successful as a result of the merits of the claimed invention (rather
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`than the result of design needs, market-pressure, advertising, or similar
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`activities); whether the invention satisfied a long-felt need; whether others had
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`tried and failed to make the invention; whether the invention achieved
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`unexpected results; whether others in the field praised the invention; and
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`whether persons having ordinary skill in the art of the invention expressed
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`surprise or disbelief regarding the invention. I understand that there must be a
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`“nexus” between the secondary considerations and the claimed subject matter.
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`V. RELEVANT DATE OF INVENTION, PERSON OF ORDINARY
`SKILL IN THE ART, AND CLAIM CONSTRUCTION
`A. Date of Invention
`36.
`I was asked to consider whether the challenged claims would have
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`been obvious to a POSA as of the date of the invention, which I have been asked
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`to assume is March 4, 2004. I understand that this is the filing date of the
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`earliest patent application in the chain that led to the ’135 and ’268 patents.
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`37.
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`I understand, however, that the parties dispute whether the Patent
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`Owner is entitled to the benefit of the March 4, 2004 date. I understand that the
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`Petitioner contends that the earliest filing date to which Patent Owner is entitled
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`to claim benefit is March 7, 2005. Accordingly I was asked whether my
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`opinions would change if the date of the invention were March 7, 2005. My
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`opinions would not change using this date.
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`B.
`38.
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`Person of Ordinary Skill in the Art
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`I have been informed that the claims of a patent must be analyzed
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`from the perspective of a POSA at the time of the invention. I understand that a
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`POSA is a hypothetical person who is presumed to know all of the relevant prior
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`art, has ordinary creativity, is not an automaton, and is capable of combining
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`teachings of the prior art. The “art” is the field of technology to which the
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`patent is a related.
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`39.
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`I have been informed that in determining the level of skill of a
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`POSA the following factors may be considered: (1) the levels of education and
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`experience of the inventor and other persons actively working in the field; (2)
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`the types of problems encountered in the field; (3) prior art solutions to those
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`problems; (4) rapidity with which innovations are made; and (5) the
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`sophistication of the technology.
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`40.
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`In my opinion, in the 2004/2005 timeframe, a POSA in the field of
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`the ’135 and ’268 patents would have had an M.D. and several years of
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`experience in treating patients with lipid disorders, including hyperlipidemia and
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`hypercholesterolemia. The POSA would also have had access to and worked
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`with individuals involved in drug discovery and development with degrees in
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`medicinal chemistry, pharmacology, or drug delivery sciences and several years
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`of experience in the development of drugs for the U.S. market.
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`41. Dr. Zusman asserts that a POSA would have had “graduate and/or
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`post-graduate education in a pertinent discipline such as medicine, medicinal
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`chemistry, pharmacology, or drug development and delivery.” Zusman ¶ 28. In
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`my view, the ’135 and ’268 patents are focused more on a treating physician, but
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`as noted above, that physician would have had access to and worked with
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`individuals having other areas of expertise. Dr. Zusman further opines that a
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`POSA “would remain a