UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`TEVA PHARMACEUTICALS USA, INC.
`Petitioner
`
`v.
`
`CORCEPT THERAPEUTICS, INC.
`Patent Owner
`_____________________
`
`Case No PGR2019-00048
`U.S. Patent No. 10,195,214
`_____________________
`
`DECLARATION OF DR. ADRIAN DOBS, M.D.
`
`TEVA1068
`Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc.
`PGR2019-00048
`
`

`

`Patent 10,195,214 B2
`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`I, Adrian Dobs, M.D., hereby declare as follows:
`
`1.
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`I am over the age of eighteen (18) and competent to make this
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`declaration.
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`2.
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`I have been retained as an expert witness on behalf of Teva
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`Pharmaceuticals USA, Inc. for the above-captioned post-grant review (PGR). I am
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`being compensated for my time in connection with this PGR at my standard
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`consulting rate, which is $900 per hour.
`
`3.
`
`I understand that this Declaration accompanies a reply in support of a
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`petition for PGR involving U.S. Patent No. 10,195,214 (“the ’214 patent”)
`
`(TEVA1001). I also understand that the ’214 patent is currently assigned to
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`Corcept Therapeutics, Inc. The ’214 patent states that it is a continuation of
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`provisional application No. 62/465,772, which has a filing date of March 1, 2017. I
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`understand from counsel that that is the earliest date that Corcept can assert as a
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`priority date.
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`4.
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`In preparing this Declaration, I have reviewed the ’214 patent and
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`each of the documents cited in my declaration, in light of general knowledge in the
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`art before March 1, 2017. In formulating my opinions, I have relied upon my
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`experience, education, and knowledge in the relevant art. In formulating my
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`opinions, I have also considered the viewpoint of a person of ordinary skill in the
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`art (“POSA”) (i.e., a person of ordinary skill in the field, as defined further in the
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`following paragraph) prior to March 1, 2017.
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`5.
`
`I understand that a POSA is a hypothetical person who is presumed to
`
`be aware of all pertinent art, thinks along conventional wisdom in the art, and is a
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`person of ordinary creativity. I understand that Dr. Greenblatt has opined that a
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`POSA in the field of the ’214 patent
`
`would have had an M.D., a Pharm. D., and/or a Ph.D. in
`pharmacology or a related discipline, with at least four
`years of experience in treating patients with mifepristone
`and/or CYP3A inhibitors, or, alternatively, studying
`drug-drug interactions involving CYP3A inhibitors. A
`POSA would have had knowledge of the scientific
`literature and skills in those fields before March 15,
`2017. A POSA would have also had knowledge of
`laboratory techniques and strategies used in investigating
`drug-drug interactions. Also, a POSA may have worked
`as part of a multidisciplinary team and drawn upon not
`only his or her own skills, but also taken advantage of
`certain specialized skills of others on the team, e.g., to
`solve a given problem.
`
`TEVA1002, ¶18. I agree with this definition and use it for purposes of my analysis
`
`here.
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`6.
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`I understand that Corcept has argued that a POSA for purposes of the
`
`’214 patent would require experience prescribing mifepristone for Cushing’s
`
`syndrome. My opinions set forth in this declaration would not change if Corcept’s
`
`definition were used. I note that I am a POSA under both parties’ definitions and
`
`have been for some time.
`
`7.
`
`I am a physician and board-certified endocrinologist with expertise in
`
`endocrinology, diabetes and metabolism. I received a B.S. in Nutrition Sciences
`
`from Cornell University in 1973. I received my medical degree from Albany
`
`Medical College in 1978. Following medical school, I completed a residency
`
`program in internal medicine at the Albert Einstein College of Medicine in New
`
`York, where I was chief resident from 1981–1982. I thereafter completed a three-
`
`year fellowship in endocrinology at the Johns Hopkins University School of
`
`Medicine in Baltimore, Maryland. I also hold a Masters of Health Sciences from
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`the Johns Hopkins University School of Hygiene and Public Health.
`
`8.
`
`I currently serve as Professor of Medicine and Oncology and Director
`
`of the Johns Hopkins Clinical Research Network of the Johns Hopkins Institute for
`
`Clinical and Translational Research (JHCRN). I am also the Director of the Johns
`
`Hopkins Center for the Reduction of Cancer Disparities of the Johns Hopkins
`
`Comprehensive Cancer.
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`9.
`
`I have published extensively on topics that include sex hormones and
`
`their relationship to metabolic disorders. Journals publishing my research include
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`the New England Journal of Medicine, Journal of Clinical Endocrinology and
`
`Metabolism, JAIDS, and Journal of Andrology. I co-chair the International
`
`Registry for Hypogonadal Men.
`
`10.
`
`I have been involved with more than fifty clinical trials testing
`
`endocrine drugs and hormones, including studies designed to assess potential drug-
`
`drug interactions. In addition, I have participated in several FDA-panels and has
`
`presented in front of several FDA advisory boards.
`
`11.
`
`In my clinical practice, I have cared for patients with Cushing’s
`
`disease, Cushing’s syndrome, and other adrenal disorders. I have prescribed
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`multiple medications to Cushing’s syndrome patients, including dexamethasone,
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`mitotane, pasireotide, ketoconazole, mifepristone, and metyrapone.
`
`12.
`
`In addition to my educational training and professional and research
`
`experiences described above, I have kept abreast of new developments relating to
`
`my fields of expertise by reading scientific literature, conferring with colleagues in
`
`the field, attending and presenting at scientific conferences, and presenting at
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`invited lectures. Further information regarding my qualifications and credentials is
`
`set forth in my curriculum vitae, attached as Exhibit A to this declaration.
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`13. Accordingly, I am an expert in the diagnosis and treatment of
`
`endocrine disorders and have been since prior to March 1, 2017. I am also an
`
`expert in the design and execution of clinical studies, including clinical drug-drug
`
`interaction studies. For that reason, I am qualified to provide an opinion as to what
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`a POSA would have understood, known, or concluded before March 1, 2017.
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`14.
`
`I have testified as an expert witness at deposition or trial in several
`
`cases during the past few years. A list of those cases is attached as Exhibit B to this
`
`declaration.
`
`15.
`
`In formulating my opinions, I have considered all the references and
`
`documents cited herein, including those listed below.
`
`Exhibit No.
`1001
`
`1002
`1004
`1005
`
`1041
`
`1065
`
`Description
`Belanoff, J., “Concomitant Administration Of Glucocorticoid
`Receptor Modulators and CYP3A Inhibitors,” U.S. Patent No.
`10,195,214 (filed June 19, 2017; issued February 5, 2019)
`Declaration of David J. Greenblatt, M.D.
`Korlym Label (2012)
`Lee et al., Office of Clinical Pharmacology Review NDA 20687
`(Addendum, KorlymTM, Mifepristone) (2012)
`“Guidance for Industry Drug Interaction Studies — Study Design,
`Data Analysis, and Implications for Dosing and Labeling,” U.S.
`Department of Health and Human Services, Food and Drug
`Administration, Center for Drug Evaluation and Research
`(CDER)., Center for Biologics Evaluation and Research (CBER)
`(2006)
`Parks, M.H., Summary Review for Regulatory Action NDA
`202107 (KorlymTM, Mifepristone) (2012)
`[https://www.accessdata.fda.gov/
`drugsatfda_docs/nda/2012/202107Orig1s000SumR.pdf]
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`Exhibit No.
`2036
`
`2057
`2058
`
`Description
`E. Dunnigan et al., “Mifepristone (RU-486) in the treatment of
`Refractory Cushing’s Disease,” Endocrine Rev., Suppl. 1,
`31(3):S1201 (2010)
`Declaration of Ty Carroll, M.D.
`Declaration of Laurence Katznelson, M.D.
`
`
`
`
`
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`
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`16.
`
`I have been asked by counsel for Teva to respond to certain opinions
`
`set forth in the declarations of Ty Carroll, M.D. (EX2057) and Laurence
`
`Katznelson (EX2058). I disagree with several of the opinions of Drs. Carroll and
`
`Katznelson for the reasons set forth in this declaration.
`
`17.
`
`I have reviewed the FDA Guidance document cited in Teva’s petition
`
`and Dr. Greenblatt’s declaration (TEVA1041). Drs. Carroll and Katznelson state in
`
`their declarations that “FDA Guidance is a September 2006 ‘draft guidance’
`
`document distributed by the FDA ‘for comment purposes only.’” EX2057, ¶55;
`
`EX2058, ¶¶43, 65. I note that many FDA Guidance documents are labeled as
`
`“drafts”; the term “draft” simply connotes that the FDA is accepting public
`
`comment on the document. Moreover, even those Guidance documents that are
`
`labeled “final” expressly state that their recommendations are non-binding. See
`
`U.S. Food and Drug Administration, What Is the Difference Between the Federal
`
`Food, Drug, and Cosmetic Act (FD&C Act), FDA Regulations, and FDA
`
`Guidance?,
`
`https://www.fda.gov/about-fda/fda-basics/what-difference-between-
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`federal-food-drug-and-cosmetic-act-fdc-act-fda-regulations-and-fda-guidance
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`(March 28, 2018). Nonetheless, FDA Guidance documents provide important
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`information to those in the field of drug development and clinical-trial design.
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`Pharmaceutical companies developing drugs for clinical use—and those who are
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`designing investigative studies and clinical trials intended to help bring those drugs
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`to market—generally follow the recommendations set forth in these guidance
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`documents unless there is a compelling reason not to.
`
`18. Dr. Carroll also states that “practicing medical doctors rarely rely on
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`FDA Guidances.” EX2057, ¶55. The audience for these guidance documents,
`
`however, are generally not “practicing medical doctors” per se, but rather
`
`companies and individuals who are developing pharmaceutical products and
`
`designing investigative studies and clinical trials related to those products. Indeed,
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`the document is entitled “Guidance for Industry” and the very first sentence of the
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`introduction states as follows: “This guidance provides recommendations for
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`sponsors of new drug applications (NDAs) and biologics license applications
`
`(BLAs) for therapeutic biologics who are performing in vitro and in vivo drug
`
`metabolism, drug transport, and drug-drug interaction studies.” TEVA1041, 4.
`
`Members of this target audience frequently rely on FDA Guidance documents and
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`generally follow their recommendations. I myself have frequently reviewed FDA
`
`Guidance documents in my work on clinical trials and have followed the
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`recommendations set forth in those documents. In my opinion, a POSA designing a
`
`clinical drug-drug interaction study prior to March 1, 2017 would have considered
`
`FDA Guidance 2006 and relied on it to inform the design of the study.
`
`19.
`
`I have also reviewed the 2012 prescribing information for Korlym
`
`(TEVA1004) and the Clinical Pharmacology Reviews that are part of the Korlym
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`Drug Approval Package (TEVA1005) (referred to in Teva’s petition as “Lee”).
`
`20. The 2012 Korlym Label states that “[c]aution should be used when
`
`Korlym is used with strong CYP3A inhibitors. Limit mifepristone dose to 300 mg
`
`per day when used with strong CYP3A inhibitors.” TEVA1004, 1.
`
`21. Lee states that “[t]he degree of change in exposure of mifepristone
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`when co-administered with strong CYP3A inhibitors is unknown and may present
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`a safety risk or deprive the patients on strong inhibitors the use of Mifepristone due
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`to a lack of knowledge of this potential drug interaction.” TEVA1005, 4–5.
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`Accordingly, Lee recommends that Corcept perform a drug-drug interaction study
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`involving mifepristone and ketoconazole in order to obtain “quantitative data for
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`effect of ketoconazole on the pharmacokinetics of mifepristone.” Id., 5. The
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`Summary Review for Korlym, in turn, states that, “depending on the results of this
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`study, updates to labeling may occur.” TEVA1065, 6.
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`22. Based on these documents, I would have understood that FDA
`
`believed that co-administration of 300 mg mifepristone and strong CYP3A
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`inhibitors would not present an undue risk of adverse consequences for patients. In
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`my experience, the FDA does not approve labels that permit dosing regimens that
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`the FDA believes present an unreasonable safety risk. I would further have
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`understood that the FDA contemplated increasing the permitted dose of
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`mifepristone when co-administered with strong CYP3A inhibitors if the results of
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`the clinical DDI study indicated that higher doses would be safe.
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`23. Practicing clinicians generally follow FDA-approved labels unless
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`there is a compelling medical reason to deviate from them. Accordingly, prior to
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`March 2017, had I been prescribing Korlym to a patient who was also taking a
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`strong CYP3A inhibitor, based on the Korlym Label, I would have adhered to the
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`300 mg dose limitation unless there was a compelling medical reason to exceed it.
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`However, I would have known based on Lee that the limitation was included in the
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`label because of a lack of data on the potential drug-drug interaction. I would also
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`have known that the FDA required a clinical study to quantify the extent of that
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`interaction. Accordingly, I would have known that co-administration of more than
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`300 mg mifepristone and strong CYP3A inhibitors would not necessarily be
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`unsafe, and I would have reasonably expected that the permitted dose could be
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`revised upward depending on the results of the clinical study. This is consistent
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`with the statements of the author of the Summary Review for Korlym: “A DDI
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`study with ketoconazole will be required. Depending on the results of this study,
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`updates to labeling may occur.” TEVA1065, 6.
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`24. Drs. Carroll and Katznelson state that, “based on the available
`
`information, the maximum dose of mifepristone that actual prescribers expected
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`could be safely and effectively co-administered with a strong CYP3A inhibitor was
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`300 mg mifepristone.” EX2057, ¶84; EX2058, ¶91. I disagree. As discussed in the
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`preceding paragraph, based on the available information, a prescriber would have
`
`understood that the degree of the potential drug-drug interaction was unknown.
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`Accordingly, a prescriber would not have known the maximum dose of
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`mifepristone that could be safely and effectively co-administered with a strong
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`CYP3A inhibitor. A prescriber would have known, however, that the FDA had
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`instructed Corcept to run a clinical DDI study in order to identify that maximum
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`dose.
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`25.
`
`I have also reviewed the case report called “Dunnigan” (EX2036)
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`cited in the declarations of Drs. Carroll and Katznelson, in which a patient
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`administered 600 mg mifepristone and ketoconazole developed adrenal
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`insufficiency. EX2057, ¶¶71–72, EX2058, ¶¶77, 92. Drs. Carroll and Katznelson
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`state that, based on this case report, a POSA would have expected that “a clinically
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`significant DDI, and unacceptable side effects, would result” from co-
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`administration of 600 mg mifepristone and ketoconazole. EX2057, ¶72; see also
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`EX2058, ¶¶77, 92.
`
`26.
`
`I disagree. Dunnigan presented data from a single patient who
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`received 600 mg mifepristone and ketoconazole. In my opinion, it would not have
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`been possible for a POSA to form an expectation about the extent and clinical
`
`significance of the drug-drug interaction between mifepristone and strong CYP3A
`
`inhibitors based on this one data point. Instead, a POSA would have awaited the
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`results of the clinical DDI study that the FDA asked Corcept to perform and then
`
`formed an opinion about the extent of the DDI. Indeed, the FDA itself was aware
`
`of this case report and concluded that “reasonable interpretation” of the results was
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`“not possible.” TEVA1005, 38. I agree with the FDA’s assessment.
`
`27.
`
`It is also my opinion, based on my experience in designing and
`
`administering clinical studies, including clinical DDI studies, that a POSA
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`following the FDA’s instructions and performing a mifepristone-ketoconazole DDI
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`study would have been likely to test co-administration of 600 mg mifepristone and
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`ketoconazole. A POSA would have known based on the 2012 Korlym Label that
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`co-administration of 300 mg mifepristone and strong CYP3A inhibitors was
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`already thought to be safe. TEVA1004, 1. Mifepristone is typically administered as
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`doses of 300 mg, 600 mg, 900 mg, and 1200 mg. Id. Accordingly, the most
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`reasonable choice in conducting a DDI study would have been to test co-
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`administration of ketoconazole with the next-highest dose of mifepristone (i.e., 600
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`mg).
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`Patent 10,195,214 B2
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`TEVA1068 – Declaration of Dr. Adrian Dobs, M.D.
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`I hereby declare that all statements made herein of my own knowledge are
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`true and that all statements made on information and belief are believed to be true,
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`and further that these statements were made with the knowledge that willful false
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`statements and the like so made are punishable by fine or imprisonment, or both,
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`under Section 1001 of Title 18 of the United States Code.
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`
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`Respectfully submitted,
`
`
`
`___________________
`Adrian Dobs, M.D.
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`Date: June 4, 2020
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`Adrian S. Dobs, MD MHS
`Curriculum Vitae – Page 1
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`Updated: 4 June 2020
`
`signature
`
`
`
`Home Address
`3510 Anton Farms Road
`Baltimore, MD 21208
`Tel.: 410.653-3049
`
`Nutrition Sciences
`Medicine
`
`Internal Medicine
`
`Internal Medicine
`
`Endocrinology
`
`Cardiovascular Epidemiology
`
`
`
`CURRICULUM VITAE
`
`
`
`
`
`
`
`ADRIAN SANDRA DOBS, MD MHS
`
`
`
`CURRENT APPOINTMENTS
`
`Professor of Medicine and Oncology
`Division of Endocrinology, Diabetes and Metabolism
`
`Director, Johns Hopkins Clinical Research Network
`Johns Hopkins Institute for Clinical and Translational Research (ICTR)
`The Johns Hopkins University School of Medicine
`
`Director, Johns Hopkins Center for the Reduction of Cancer Disparities
`The Johns Hopkins Bloomberg School of Public Health
`
`
`PERSONAL DATA
`
`Business Address
`Division of Endocrinology, Diabetes and Metabolism
`The Johns Hopkins University School of Medicine
`1830 E. Monument St, Suite 333
`Baltimore, MD 21287
`Tel.: 443.287-4000
`Fax
`410.955-8172
`e-mail: adobs@jhu.edu
`
`
`EDUCATION AND TRAINING
`1973
`BS
`Cornell University; Ithaca, NY
`1978
`MD
`Albany Medical College; Albany, NY
`Residency Albert Einstein College of Medicine; Montefiore
`Hospital; Bronx, NY
`Albert Einstein College of Medicine; Montefiore
`Hospital; Bronx, NY
`The Johns Hopkins University School of Medicine;
`Baltimore, MD
`The Johns Hopkins University School of Hygiene
`and Public Health; Baltimore, MD
`
`1978-1981
`
`1981-1982
`
`Chief
`Resident
`
`1982-1985
`
`Fellowship
`
`1990
`
`MHS
`
`
`
`
`Exhibit A
`
`

`

`
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`1987-1993
`
`1993-2000
`
`1997-2002
`
`2000-2007
`
`Adrian S. Dobs, MD MHS
`Curriculum Vitae – Page 2
`
`
`
`PROFESSIONAL EXPERIENCE
`1981-1982
`Instructor in Medicine; City College of New York Physicians Assistant Program; New York, NY
`1985-1987
`Instructor, Division of Endocrinology and Metabolism; Department of Medicine; The Johns
`Hopkins University School of Medicine; Baltimore, MD
`Assistant Professor of Medicine; The Johns Hopkins University School of Medicine; Baltimore,
`MD
`Associate Professor of Medicine; The Johns Hopkins University School of Medicine; Baltimore,
`MD
`Deputy Director for Clinical Research; Department of Medicine; The Johns Hopkins University
`School of Medicine
`Principal Investigator; Johns Hopkins Center for Complementary and Alternative Medicine in
`Cancer
`2000-present Professor of Medicine and Oncology; Johns Hopkins University School of Medicine; Baltimore,
`MD
`Vice Chair for Faculty Development; Department of Medicine; The Johns Hopkins University
`School of Medicine
`Program Director, Johns Hopkins Center for the Reduction of Cancer Disparities; The Johns
`Hopkins Cancer Center; The Johns Hopkins University School of Medicine
`2012-present Director; Johns Hopkins Clinical Research Network; Johns Hopkins Institute for Clinical and
`Translational Research (ICTR); The Johns Hopkins University School of Medicine
`2012-present Principal Investigator/Program Director, Johns Hopkins Center for the Reduction of Cancer
`Disparities; The Johns Hopkins Cancer Center; The Johns Hopkins University School of
`Medicine
`Director, Johns Hopkins- SunYet Sen (China) Collaboration in Clinical Research, Johns Hopkins
`International
`
`2000-2015
`
`2010-2012
`
`2013-2016
`
`
`
`RESEARCH ACTIVITIES
`
`Publications
`
`Peer-Reviewed Scientific Articles
`Howard L, Dobs A, Chodos R, Chu R, Loludice T: A comparison of administering protein alone and
`1.
`protein plus glucose on nitrogen balance. Am J Clin Nutr 1978 Feb; 31 (2): 226-229. PMID: 623044.
`Dobs AS, Phillips JA 3rd: Diagnosis of human endocrine disorders using recombinant DNA techniques.
`Clin Endocrinol Metab 1985 Feb; 14 (1): 273-294. Review. PMID: 2990778.
`Dobs AS, Phillips JA 3rd, Mallonee RL, Saudek CD, Ney RL: Pedigree analysis of the 5' flanking region
`of the insulin gene in familial diabetes mellitus. Metabolism 1986 Jan; 35 (1): 13-17. PMID: 3001475.
`Dobs AS, Dempsey MA, Ladenson PW, Polk BF: Endocrine disorders in men infected with human
`immunodeficiency virus. Am J Med 1988 Mar; 84 (3 Pt 2): 611-616. PMID: 3348269.
`Dobs AS, Broussolle C, Lane MD: Regulation of insulin synthesis in an insulin-producing cell line
`(RINm5F): long-term experiments. In Vitro Cell Dev Biol 1989 Feb; 25 (2): 112-114. PMID: 2646270.
`Margolis S, Dobs AS: Nutritional management of plasma lipid disorders. J Am Coll Nutr 1989; 8
`Suppl: 33S-45S. Review. PMID: 2553790.
`Hunninghake DB, Knopp RH, Schonfeld G, Goldberg AC, Brown WV, Schaefer EJ, Margolis S, Dobs
`AS, Mellies MJ, Insull W Jr, et al: Efficacy and safety of pravastatin in patients with primary
`
`2.
`
`3.
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`4.
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`5.
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`6.
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`7.
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`8.
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`9.
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`12.
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`10.
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`Adrian S. Dobs, MD MHS
`Curriculum Vitae – Page 3
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`hypercholesterolemia. I. A dose-response study. Atherosclerosis 1990 Nov; 85 (1): 81-89. PMID:
`2126437.
`Dobs AS, Levine MA, Margolis S: Effects of pravastatin, a new HMG-CoA reductase inhibitor, on
`vitamin D synthesis in man. Metabolism 1991 May; 40 (5): 524-528. PMID: 1902546.
`Dobs AS, Sarma PS, Guarnieri T, Griffith L: Testicular dysfunction with amiodarone use. J Am Coll
`Cardiol 1991 Nov 1; 18 (5): 1328-1332. PMID: 1918711.
`Dobs AS, Sarma PS, Wilder L: Lipid-lowering diets in patients taking pravastatin, a new HMG-CoA
`reductase inhibitor: compliance and adequacy. Am J Clin Nutr 1991 Oct; 54 (4): 696-700. PMID:
`1910254.
`11. Wand GS, Dobs AS: Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking
`alcoholics. J Clin Endocrinol Metab 1991 Jun; 72 (6): 1290-1295. PMID: 2026749.
`Dobs AS, Sarma PS, Schteingart D: Long-term endocrine function in hypercholesterolemic patients
`treated with pravastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Metabolism
`1993 Sep; 42 (9): 1146-1152. PMID: 8412767.
`13. Masters RB, Stillman FA, Becker DM, Margolis S, Dobs AS: The use of focus groups in the design of
`cholesterol education intervention programs. Am J Health Promot 1993 Nov-Dec; 8 (2): 95-97. PMID:
`10146822.
`Pravastatin Multicenter Study Group II (Dobs AS): Comparative efficacy and safety of pravastatin and
`cholestyramine alone and combined in patients with hypercholesterolemia. Pravastatin Multicenter
`Study Group II. Arch Intern Med 1993 Jun 14; 153 (11): 1321-1329. PMID: 8507122.
`Blevins LS Jr, Dobs AS, Wand GS: Naloxone-induced activation of the hypothalamic-pituitary-adrenal
`axis in suspected central adrenal insufficiency. Am J Med Sci 1994 Sep; 308 (3): 167-170. PMID:
`8074133.
`Dobs AS, Masters RB, Rajaram L, Stillman FA, Wilder LB, Margolis S, Becker DM: A comparison of
`education methods and their impact on behavioral change in patients with hyperlipidemia. Patient Educ
`Couns 1994 Oct; 24 (2): 157-164. PMID: 7746765.
`Herrington DM, Kim LS, Miller ME, Mitchell SE, Walford GD, Dobs AS: Visual and quantitative
`computerized assessment of disease severity on peripheral angiograms. J Vasc Interv Radiol 1994
`Jul-Aug; 5 (4): 595-602. PMID: 7949717.
`Dobs AS, Prasad M, Goldberg A, Guccione M, Hoover DR: Changes in serum lipoprotein(a) in
`hyperlipidemic subjects undergoing long-term treatment with lipid-lowering drugs. Cardiovasc Drugs
`Ther 1995 Oct; 9 (5): 677-684. PMID: 8573550.
`Arver S, Dobs AS, Meikle AW, Allen RP, Sanders SW, Mazer NA: Improvement of sexual function in
`testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal
`system. J Urol 1996 May; 155 (5): 1604-1608. PMID: 8627833.
`Dobs AS, Few WL 3rd, Blackman MR, Harman SM, Hoover DR, Graham NM: Serum hormones in
`men with human immunodeficiency virus-associated wasting. J Clin Endocrinol Metab 1996 Nov; 81
`(11): 4108-4112. PMID: 8923868.
`21. Meikle AW, Arver S, Dobs AS, Sanders SW, Rajaram L, Mazer NA: Pharmacokinetics and metabolism
`of a permeation-enhanced testosterone transdermal system in hypogonadal men: influence of
`application site- -a clinical research center study. J Clin Endocrinol Metab 1996 May; 81 (5): 1832-
`1840. PMID: 8626843.
`Arver S, Dobs AS, Meikle AW, Caramelli KE, Rajaram L, Sanders SW, Mazer NA: Long-term efficacy
`and safety of a permeation-enhanced testosterone transdermal system in hypogonadal men. Clin
`Endocrinol (Oxf) 1997 Dec; 47 (6): 727-737. PMID: 9497881.
`Cofrancesco J Jr, Whalen JJ 3rd, Dobs AS: Testosterone replacement treatment options for HIV-
`infected men. J Acquir Immune Defic Syndr Hum Retrovirol 1997 Dec 1; 16 (4): 254-265. PMID:
`9402072.
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`Curriculum Vitae – Page 4
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`Lehmann LS, Brancati FL, Chen MC, Roter D, Dobs AS: The effect of bedside case presentations on
`patients' perceptions of their medical care. N Engl J Med 1997 Apr 17; 336 (16): 1150-1155. PMID:
`9099660.
`25. Meikle AW, Arver S, Dobs AS, Adolfsson J, Sanders SW, Middleton RG, Stephenson RA, Hoover DR,
`Rajaram L, Mazer NA: Prostate size in hypogonadal men treated with a nonscrotal permeation-
`enhanced testosterone transdermal system. Urology 1997 Feb; 49 (2): 191-196. PMID: 9037280.
`Zheng ZJ, Sharrett AR, Chambless LE, Rosamond WD, Nieto FJ, Sheps DS, Dobs A, Evans GW,
`Heiss G: Associations of ankle-brachial index with clinical coronary heart disease, stroke and
`preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study.
`Atherosclerosis 1997 May; 131 (1): 115-125. PMID: 9180252.
`Dobs AS: Androgen therapy in AIDS wasting. Baillieres Clin Endocrinol Metab 1998 Oct; 12 (3): 379-
`390. PMID: 10332560.
`Dobs AS, El-Deiry S, Wand G, Wiederkehr M: Central hypogonadism: distinguishing idiopathic low
`testosterone from pituitary tumors. Endocr Pract 1998 Nov-Dec; 4 (6): 355-359. PMID: 15251707.
`Dobs AS, Hoover DR, Chen MC, Allen R: Pharmacokinetic characteristics, efficacy, and safety of
`buccal testosterone in hypogonadal males: a pilot study. J Clin Endocrinol Metab 1998 Jan; 83 (1): 33-
`39. PMID: 9435413.
`Laube BL, Benedict GW, Dobs AS: The lung as an alternative route of delivery for insulin in controlling
`postprandial glucose levels in patients with diabetes. Chest 1998 Dec; 114 (6): 1734-1739. PMID:
`9872209.
`Laube BL, Benedict GW, Dobs AS: Time to peak insulin level, relative bioavailability, and effect of site
`of deposition of nebulized insulin in patients with noninsulin-dependent diabetes mellitus. J Aerosol
`Med 1998 Fall; 11 (3): 153-173. PMID: 10186961.
`32. Meikle AW, Dobs AS, Arver S, Caramelli KE, Sanders SW, Mazer NA: Androgen replacement in the
`treatment of Klinefelter's syndrome: efficacy and safety of a nonscrotal permeation-enhanced
`testosterone transdermal system. Endocr Pract 1998 Jan-Feb; 4 (1): 17-22. PMID: 15251759.
`33. Miller LR, Partin AW, Chan DW, Bruzek DJ, Dobs AS, Epstein JI, Walsh PC: Influence of radical
`prostatectomy on serum hormone levels. J Urol 1998 Aug; 160 (2): 449-453. PMID: 9679896.
`Stein EA, Davidson MH, Dobs AS, Schrott H, Dujovne CA, Bays H, Weiss SR, Melino MR,
`Stepanavage ME, Mitchel YB: Efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic
`patients. The Expanded Dose Simvastatin US Study Group. Am J Cardiol 1998 Aug 1; 82 (3): 311-
`316. PMID: 9708659.
`Barzilay JI, Spiekerman CF, Wahl PW, Kuller LH, Cushman M, Furberg CD, Dobs A, Polak JF, Savage
`PJ: Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes
`Association criteria for diabetes mellitus with WHO criteria. Lancet 1999 Aug 21; 354 (9179): 622-625.
`PMID: 10466662.
`Basaria S, Dobs AS: Risks versus benefits of testosterone therapy in elderly men. Drugs Aging 1999
`Aug; 15 (2): 131-142. PMID: 10495072.
`Cushman M, Meilahn EN, Psaty BM, Kuller LH, Dobs AS, Tracy RP: Hormone replacement therapy,
`inflammation, and hemostasis in elderly women. Arterioscler Thromb Vasc Biol 1999 Apr; 19 (4): 893-
`899. PMID: 10195915.
`Dobs AS: Is there a role for androgenic anabolic steroids in medical practice? JAMA 1999 Apr 14; 281
`(14): 1326-1327. PMID: 10208149.
`Dobs AS, Cofrancesco J, Nolten WE, Danoff A, Anderson R, Hamilton CD, Feinberg J, Seekins D,
`Yangco B, Rhame F: The use of a transscrotal testosterone delivery system in the treatment of
`patients with weight loss related to human immunodeficiency virus infection. Am J Med 1999 Aug; 107
`(2): 126-132. PMID: 10460042.
`Dobs AS, Meikle AW, Arver S, Sanders SW, Caramelli KE, Mazer NA: Pharmacokinetics, efficacy,
`and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly
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`Adrian S. Dobs, MD MHS
`Curriculum Vitae – Page 5
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`injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab
`1999 Oct; 84 (10): 3469-3478. PMID: 10522982.
`Dobs AS, Nieto FJ, Szklo M, Barnes R, Sharrett AR, Ko WJ: Risk factors for popliteal and carotid wall
`thicknesses in the Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol 1999 Nov 15;
`150 (10): 1055-1067. PMID: 10568620.
`Schoen RE, Tangen CM, Kuller LH, Burke GL, Cushman M, Tracy RP, Dobs A, Savage PJ: Increased
`blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst 1999 Jul 7; 91
`(13): 1147-1154. PMID: 10393723.
`Smith NL, Heckbert SR, Bittner VA, Savage PJ, Barzilay JI, Dobs AS, Psaty BM: Antidiabetic
`treatment trends in a cohort of elderly people with diabetes The cardiovascular health study, 1989-
`1997. Diabetes Care 1999 May; 22 (5): 736-742. PMID: 10332674.
`44. Wisniewski AB, Nguyen TT, Flannery TW, Dobs AS: Hypogonadal status and functional cerebral
`lateralization in adult men. Brain Cognition 1999; 40 (1): 276-281.
`Ariyo AA, Haan M, Tangen CM, Rutledge JC, Cushman M, Dobs A, Furberg CD: Depressive
`symptoms and risks of coronary heart disease and mortality in elderly Americans. Cardiovascular
`Health Study Collaborative Research Group. Circulation 2000 Oct 10; 102 (15): 1773-1779. PMID:
`11023931.
`Basaria S, Ayala AR, Guerin C, Dobs AS: A rare pituitary lesion. J Endocrinol Invest 2000 Mar; 23 (3):
`189-192. PMID: 10803478.
`Basaria S, Dobs AS: Treatment of hyperlipidemia in women. Int J Fertil Womens Med 2000 Jan-Feb;
`45 (1): 22-33. PMID: 10721741.
`Dobs AS, Miller S, Neri G, Weiss S, Tate AC, Shapiro DR, Musliner TA: Effe