IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________________
`
`LUPIN LIMITED
`Petitioner
`v.
`JANSSEN SCIENCES IRELAND UC
`Patent Owner, based on Public Filings
`JANSSEN R&D IRELAND
`Patent Owner, based on Electronic Records of PTO
`U.S. Patent No. 8,518,987 B2 to Vermeersch et al.
`Issue Date: August 27, 2013
`Title: Pseudopolymorphic Forms of a HIV Inhibitor
`________________________________
`
`Inter Partes Review Trial No. TBD
`________________________________
`
`Declaration of Keith B. Leffler, Ph.D. In Support of Lupin Ltd.’s
`Petition for Inter Partes Review of U.S. Patent No. 8,518,987 B2
`
`Lupin Ex. 1062 (Page 1 of 22)
`
`
`________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________________
`
`LUPIN LIMITED
`Petitioner
`v.
`JANSSEN SCIENCES IRELAND UC
`Patent Owner, based on Public Filings
`JANSSEN R&D IRELAND
`Patent Owner, based on Electronic Records of PTO
`U.S. Patent No. 8,518,987 B2 to Vermeersch et al.
`Issue Date: August 27, 2013
`Title: Pseudopolymorphic Forms of a HIV Inhibitor
`________________________________
`
`Inter Partes Review Trial No. TBD
`________________________________
`
`Declaration of Keith B. Leffler, Ph.D. In Support of Lupin Ltd.’s
`Petition for Inter Partes Review of U.S. Patent No. 8,518,987 B2
`
`Lupin Ex. 1062 (Page 1 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`I, Keith B. Leffler, declare as follows:
`I.
`INTRODUCTION.
`
`1.
`
`I, Keith B. Leffler, have been retained by counsel for Lupin Limited
`
`(“Lupin”) in connection with a petition Lupin intends on filing for inter partes
`
`review of U.S. Patent No. 8,518,987 B2 (“the ‘987 patent”) (Ex. 1001).
`
`Specifically, I have been advised that Lupin intends on requesting that the United
`
`States Patent and Trademark Office (“PTO”) cancel claims 1-19 of the ‘987 patent
`
`as unpatentable for obviousness, amongst other grounds. I understand that this
`
`Declaration will be used to support unpatentability in any trial proceeding initiated
`
`in connection with these grounds. I reviewed the ‘987 patent prior to preparing
`
`this Declaration, and I reviewed each of the references cited in this Declaration.
`
`II. QUALIFICATIONS.
`
`2.
`
`I am currently an Emeritus Associate Professor of Economics at the
`
`University of Washington, where I was employed until I retired from teaching in
`
`2008. I received my Ph.D. degree in economics from the University of California
`
`Los Angeles in 1977. I have teaching and research experience in the areas of the
`
`government
`
`regulation of business, antitrust economics, and
`
`industrial
`
`organizations. I have taught classes in these areas at both the undergraduate and
`
`graduate levels for over thirty five years. I continue to research and publish in my
`
`
`
`2
`
`Lupin Ex. 1062 (Page 2 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`areas of specialization. A curriculum vitae summarizing my academic experience
`
`and publications has been filed as Exhibit 1063.
`
`3.
`
`I have been performing economic analysis in antitrust and patent cases
`
`for forty years. I have been qualified as an economic expert before federal courts,
`
`state courts, the Federal Trade Commission, and other federal and state regulatory
`
`agencies. Exhibit 1063 lists the major areas in which I have consulted and also the
`
`cases in which I have offered testimony in the last four years.
`
`4.
`
`I have an extensive background
`
`in
`
`the economics of
`
`the
`
`pharmaceutical
`
`industry.
`
` I was a visiting research scholar at Pfizer
`
`Pharmaceuticals in the academic year 1977-1978, during which time I studied
`
`competition, research and development, and marketing
`
`issues related
`
`to
`
`pharmaceuticals. I have published articles and presented research results
`
`concerning the economics of this industry.
`
`5.
`
`I have also served as a consultant dealing with competitive and patent
`
`issues in the pharmaceutical industry in a number of matters involving the entry of
`
`generics. My academic and consulting experience includes economic analysis
`
`related to the impact on sales of various business practices in the pharmaceutical
`
`industry, including how product characteristics, treatment guidelines and marketing
`
`interact to influence prescription drug sales. As a result of this experience, I have
`
`
`
`3
`
`Lupin Ex. 1062 (Page 3 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`become very familiar with the economics of pharmaceutical patents, U.S. Food and
`
`Drug Administration (“FDA”) regulations, and data concerning the pharmaceutical
`
`industry.
`
`6.
`
`Moreover, in my work as an economist, I have evaluated the HIV
`
`antiretroviral (“ARV”) protease inhibitors (“PIs”), and I have made detailed
`
`analyses of the PIs NORVIR® (ritonavir) and KALETRA® (lopinavir/ritonavir). In
`
`addition, I have previously studied PREZISTA®’s role in the HIV market as an
`
`economic expert in a prior court proceeding concerning other patents relating to
`
`PREZISTA®.1
`
` Accordingly, I am quite familiar with
`
`the markets for
`
`pharmaceuticals treating HIV and specifically with the economics of PREZISTA®.
`
`7.
`
`I am being compensated at my usual hourly fee at the time of my
`
`engagement of $650. My compensation is not dependent in any way upon the
`
`outcome of Lupin’s Petition.
`
`III.
`
`SUMMARY OF OPINIONS.
`
`8.
`
`I understand evaluation of commercial success is one of the secondary
`
`considerations of whether a patent is obvious. I have been asked to opine on
`
`whether the sales of darunavir, marketed in the United States under the brand name
`
`
`1 Janssen Prods., L.P. et al. v. Lupin Ltd. et al., No. 2:10-cv-5954-WHW-CLW
`
`(D.N.J.).
`
`
`
`4
`
`Lupin Ex. 1062 (Page 4 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`PREZISTA®, provides evidence of non-obviousness of the subject matter claimed
`
`in the ‘987 patent.
`
`9.
`
`I have reached the opinions discussed in this Declaration including:
`
`x During prosecution of the ‘987 patent, the Patent Owner did not
`
`present any evidence of a nexus between any sales of PREZISTA®
`
`and any of the claims of the ‘987 patent.
`
`x I understand the Patent Owner’s PREZISTA® utilizes darunavir
`
`ethanolate as its active pharmaceutical ingredient (“API”) and is
`
`not
`
`specifically
`
`directed
`
`to
`
`utilize
`
`darunavir
`
`in
`
`the
`
`pseudopolymorphic forms recited in the claims of the ‘987 patent.
`
`x At the time of the alleged invention of the ‘987 patent, no one had
`
`a significant economic
`
`incentive
`
`to develop
`
`the particular
`
`pseudopolymorphic forms of darunavir that I understand the ‘987
`
`patent purports to claim because of the so-called “blocking
`
`patents” purportedly directed to the darunavir molecule.
`
`
`
`5
`
`Lupin Ex. 1062 (Page 5 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`
`x There is no evidence in the public record demonstrating that any
`
`alleged commercial success of PREZISTA® renders the ‘987
`
`patent not obvious.2
`
`IV. UNDERSTANDING OF RELEVANT LEGAL PRINCIPLES.
`
`10.
`
`It is my understanding that the determination of whether an invention
`
`is obvious is a legal conclusion based on underlying factual inquiries including
`
`objective evidence of non-obviousness.3
`
`11.
`
`I understand that objective evidence of non-obviousness is sometimes
`
`referred to as “secondary considerations”4 and that this includes a number of
`
`factors which the Board may consider in determining the validity of a patent. I
`
`understand that evidence of the commercial success of a product is one type of
`
`secondary consideration.
`
`
`2 I understand that the other aspects of the obviousness analysis are being
`
`addressed by another expert.
`
`3 Graham v. John Deere Co., 383 U.S. 1, 17 (1966); In re Huang, 100 F.3d 135,
`
`138 (Fed. Cir. 1996).
`
`4 Merck & Co. v. Teva Pharm. USA, Inc., 395 F.3d 1364, 1376 (Fed. Cir. 2005);
`
`McNeil-PPC, Inc. v. L. Perrigo Co., 337 F.3d 1362, 1368 (Fed. Cir. 2003).
`
`
`
`6
`
`Lupin Ex. 1062 (Page 6 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`
`12.
`
`I also understand that in order for the purported commercial success
`
`of a product to be relevant for the purpose of evaluating non-obviousness, the
`
`patentee must show a “nexus between sales and the merits of the invention.”5 I
`
`further understand that the alleged commercial success of a product must be driven
`
`by, and attributable to, a feature claimed in the patent as opposed to some feature
`
`of the product not part of the claims of the patent at issue or some other reason,
`
`such as a company’s marketing efforts. I am also informed that “if the commercial
`
`success is due to an unclaimed feature of the device, the commercial success is
`
`
`5 In re Youngblood, No. 98-1518, 1999 U.S. App. LEXIS 15024, at *25 (Fed. Cir.
`
`July 6, 1999) (citing Kansas Jack, Inc. v. Kuhn, 719 F.2d 1144, 1150-51 (Fed. Cir.
`
`1983)); see also Friskit, Inc. v. Real Networks, Inc., 306 F. App’x. 610, 617 (Fed.
`
`Cir. 2009) (commercial success must be due to the “subject matter that [the
`
`patentee] contends is nonobvious”); J.T. Eaton & Co. v. Atl. Paste & Glue Co., 106
`
`F.3d 1563, 1571 (Fed. Cir. 1997) (the commercial success must be “attributable to
`
`something disclosed in the patent that was not readily available in the prior art”);
`
`Sjolund v. Musland, 847 F.2d 1573, 1582 (Fed. Cir. 1988) (“Nor could the jury,
`
`from the bare evidence of units sold and gross receipts, draw the inference that the
`
`popularity of the [sold units] was due to the merits of the invention.”).
`
`
`
`7
`
`Lupin Ex. 1062 (Page 7 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`irrelevant.”6 Likewise, I have been instructed that if the feature that creates the
`
`commercial success was known in the prior art, the success is not pertinent.7
`
`13.
`
` In addition, when more than a single patent covers a successful
`
`product or process, proving nexus becomes economically difficult as it can be very
`
`difficult to attribute commercial success to any one of those patents as compared to
`
`the other patents.8
`
`14.
`
` The ‘987 Patent Owner had sued Lupin in a prior consolidated
`
`litigation, Janssen Products, L.P. et al. v. Lupin Ltd. et al., No. 2:10-cv-5954-
`
`WHW-CLW (D.N.J.) that is the subject of a pending appeal (“Prior Litigation”). I
`
`understand that the Patent Owner asserted U.S. Patent No. 7,700,645 B2 (“the ‘645
`
`
`6 Ormco Corp. v. Align Tech., Inc., 463 F.3d 1299, 1312 (Fed. Cir. 2006).
`
`7 See Ormco, 463 F.3d at 1312; Huang, 100 F.3d at 140 (commercial success is
`
`probative of non-obviousness “only if there is proof that the sales were a direct
`
`result of the unique characteristics of the claimed invention — as opposed to other
`
`economic and commercial factors unrelated to the quality of patented subject
`
`matter”).
`
`8 See In re Sneed, 710 F.2d 1544, 1551 (Fed. Cir. 1983) (rejecting evidence of
`
`gross sales of the product where the data was not apportioned as between the
`
`patent at issue and other contributing factors).
`
`
`
`8
`
`Lupin Ex. 1062 (Page 8 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`patent”)9 against Lupin in that Prior Litigation and that the ‘645 patent is related to
`
`the ‘987 patent which is at issue here.
`
`V.
`
`THE ‘987 PATENT.
`
`15.
`
`From my review of the ‘987 patent and discussions with counsel for
`
`Lupin, I understand
`
`the ‘987 patent
`
`is purportedly directed
`
`to specific
`
`pseudopolymorphic forms of darunavir, namely hydrates, and compositions
`
`thereof. The ‘987 patent contains 19 claims, and I understand that Janssen has
`
`asserted the ‘987 patent against Lupin in federal district court litigation. I have
`
`been advised that Janssen’s lawsuit against Lupin has been stayed.
`
`16. According to the face of the ‘987 patent, the ‘987 patent was filed on
`
`or about August 6, 2009, as U.S. Application No. 12/536,807, which was a
`
`divisional application of U.S. Application No. 10/514,352, filed on or about May
`
`16, 2003, which I understand claims priority to a foreign patent application, EP
`
`02076929.5, filed on or about May 16, 2002.10 The ‘987 patent issued on or about
`
`August 27, 2013, and names Hans Wim Pieter Vermeersch, Daniel Joseph
`
`
`9 Ex. 1022, ‘645 patent.
`
`10 See Ex. 1001, ‘987 patent at cover.
`
`
`
`9
`
`Lupin Ex. 1062 (Page 9 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`Christiaan Thone, Luc Donne Marie-Louise Janssens, and Piet Tom Bert Paul
`
`Wigerinck as inventors.11
`
`17.
`
`I understand that the ‘987 patent includes four independent claims:
`
`Claims 1, 2, 3, and 6, all of which relate to hydrated forms of darunavir. In
`
`addition, I understand that the ‘987 patent includes fifteen dependent claims.
`
`18.
`
`Independent claim 1 recites:
`
`19.
`
`Independent claim 2 recites:
`
`20.
`
`Independent claim 3 recites:
`
`
`11 Id.
`
`
`
`10
`
`Lupin Ex. 1062 (Page 10 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`
`21.
`
`Independent claim 6 recites:
`
`22. Dependent claim 4 refers back to claim 3, and dependent claim 5
`
`refers back to claim 4. Dependent claims 4 and 5 recite:
`
`23. Dependent claim 7 refers back to claim 6, and dependent claim 8
`
`refers back to claim 7. Dependent claims 7 and 8 recite:
`
`
`
`11
`
`Lupin Ex. 1062 (Page 11 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`
`24. Dependent claims 9-13 all refer back to claim 1. Dependent claims 9-
`
`13 recite:
`
`25. Dependent claims 14-19 all refer back to claim 3. Dependent claims
`
`14-19 recite:
`
`
`
`12
`
`Lupin Ex. 1062 (Page 12 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`
`VI. DARUNAVIR HYDRATE CLAIMED IN THE ‘987 PATENT IS NOT
`THE PRIMARY DARUNAVIR FORM USED IN THE PATENT
`OWNER’S DARUNAVIR PRODUCT, PREZISTA®, MARKETED IN
`THE UNITED STATES.
`
`26.
`
`The Patent Owner markets a darunavir product, PREZISTA®, in the
`
`United States.12 According to its labeling and representations in prior Court
`
`proceedings, PREZISTA® utilizes darunavir ethanolate as its active ingredient.13
`
`
`12 Ex. 1064, Prezista® Prescribing Information (Revised: March 2015) (“2015
`
`Prezista® PI”) at 7.
`
`13 Id. at 25; see also Ex. 1065, 8/14/2014 Trial Op. (public version) at 1, Janssen
`
`Prods. L.P. et al. v. Lupin Ltd. et al., No. 2:10-cv-5954-WHW-CLW (D.N.J. Sept.
`
`
`
`13
`
`Lupin Ex. 1062 (Page 13 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`
`27. As described above, it is my understanding that the forms of darunavir
`
`claimed in the ‘987 patent are not darunavir ethanolate, but are what are known as
`
`hydrated forms of darunavir.14 As such, the forms of darunavir claimed in the ‘987
`
`patent are not the form that the labeling and Patent Owner has previously identified
`
`is the active ingredient in the commercial darunavir product marketed and sold in
`
`the United States.
`
`VII. TOTAL GROSS SALES ALONE DO NOT DEMONSTRATE
`“COMMERCIAL SUCCESS.”
`
`28.
`
`To the extent the Patent Owner, in response to Lupin’s Petition,
`
`contends that PREZISTA® is commercially successful because of its level of sales,
`
`I have reviewed the specification and prosecution history of the ‘987 patent and
`
`note that there is no discussion that any sales of PREZISTA® are linked to the
`
`alleged invention claimed in the ‘987 patent. It is my understanding that the Patent
`
`Owner did not submit any such evidence purporting to establish such a link.
`
`29. More importantly, gross sales alone cannot reflect “commercial
`
`success” without thorough analysis of the economic reasons for the level of sales
`
`and any resulting profits. In addition, for such sales and profits to have any
`
`23, 2014), ECF No. 998 (“Trial Op.”) (“Prezista is an ethanolate form of the
`
`chemical compound named darunavir.”).
`
`14 See, e.g., Ex. 1001, ‘987 patent at col. 30, 1. 63 – col. 32, 1. 36.
`
`
`
`14
`
`Lupin Ex. 1062 (Page 14 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`relevance to commercial success, analysis demonstrating the relationship of the
`
`sales and profits to the claimed features of the inventions must be provided.
`
`Because the Patent Owner has asserted PREZISTA®, as marketed in the United
`
`States, does not primarily consist of any of the hydrated forms of darunavir
`
`claimed in the ‘987 patent, I am not aware of how there could be any nexus
`
`between any commercial success of PREZISTA® and the ‘987 patent.
`
`30.
`
` In addition, even if there were some connection between the sales of
`
`PREZISTA® and the ‘987 patent, careful analyses of other factors that can
`
`influence the level of sales of a pharmaceutical product must be conducted. Such
`
`other factors include the promotional expenditures associated with the sales force
`
`and brand marketing of the product, the pricing of the product including the level
`
`of managed care discounts, the timing of the entry of the product onto the market
`
`compared to its therapeutic alternatives,15 inclusion of the product in influential
`
`
`15 The timing of the entry of an ARV onto the market is particularly relevant
`
`because of resistance/cross-resistance issues. This is to say that, in certain
`
`instances, where a patient develops resistance to a particular ARV, he or she may
`
`(or may not), by virtue thereof, likewise become resistant to one or more other
`
`ARVs (which may, for example, be within the same drug class).
`
`
`
`15
`
`Lupin Ex. 1062 (Page 15 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`treatment guidelines,16 and the relative value to patients of any products that must
`
`be co-administered with PREZISTA®.17 To the extent the Patent Owner attempts
`
`to use gross sales as evidence of commercial success without considering such
`
`factors, any such argument will be irrelevant here.
`
`
`16 Ex. 1066, Consolidated Guidelines on the Use of Antiretroviral Drugs for
`
`Treating and Preventing HIV Infection, WORLD HEALTH ORGANIZATION 242 (June
`
`2013) (“WHO Guidelines”) (listing “Darunavir + ritonavir”—Prezista®—as one of
`
`the recommended ARVs in Annex 7, Dosages of Recommended Antiretroviral
`
`Drugs); see also, e.g., Ex. 1067, Panel on Antiretroviral Guidelines for Adults and
`
`Adolescents, Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected
`
`Adults and Adolescents, DEPARTMENT OF HEALTH AND HUMAN SERVICES (last
`
`updated Nov. 13, 2014)
`
`(“DHHS
`
`Guidelines”), available at
`
`http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
`
`(“DHHS Guidelines”); Ex. 1067, DHHS Guidelines at E-1, F-7 (tbl. 6), H-4 &
`
`n.26, H-14, J-9 (tbl. 12), P-18 (App’x B, tbl. 7).
`
`17 Prezista® is approved for use only when co-administered with ritonavir. See Ex.
`
`1064, 2015 Prezista® PI at 1 (“Due to the need for co-administration of PREZISTA
`
`with ritonavir . . . .”).
`
`
`
`16
`
`Lupin Ex. 1062 (Page 16 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`VIII. FACTORS OTHER THAN THE ‘987 PATENT DRIVE THE SALES
`OF PREZISTA®.
`
`31.
`
`I am not aware of any evidence that there is a nexus between
`
`PREZISTA® sales and the subject matter claimed in the ‘987 patent. As indicated
`
`above, I am likewise not aware of any argument to this effect having been made by
`
`the Patent Owner in the specification or during prosecution. More generally, the
`
`Patent Owner did not make any statements to the PTO during prosecution of the
`
`‘987 patent that sales of PREZISTA® are attributable to any particular form of
`
`darunavir.
`
`32.
`
`There is substantial evidence that factors entirely unrelated to the
`
`claimed invention of the ‘987 patent contribute to, and account for, sales of
`
`PREZISTA®. PREZISTA® is a pharmaceutical product with annual sales in the
`
`United States of over $1 billion.18 When used in conjunction with ritonavir,
`
`PREZISTA® treats HIV because of the ability of the molecule darunavir to block
`
`the protease enzyme critical to the replication of the virus.19 The hydrated form
`
`18 See Ex. 1068, Press Release, Lupin Pharmaceuticals, Inc., Lupin Receives
`
`Tentative Approval for Generic Prezista® Tablets, (Dec. 30, 2014), available at
`
`http://www.lupinpharmaceuticals.com/30dec2014.htm.
`
`19 Ex. 1024, Trial Tr. at 120:22 – 121:9 (Stoffels); id. at 2283:18 – 2284:8
`
`(Leffler).
`
`
`
`17
`
`Lupin Ex. 1062 (Page 17 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`claims of the ‘987 patent simply have nothing to do with this success – there is no
`
`nexus between the sales levels of PREZISTA® and the ‘987 patent.
`
`33. Moreover, there is no evidence that any sales of PREZISTA® are due
`
`to any conversion from the ethanolate form to the hydrate form. This is at least
`
`because there is no evidence that the sales of PREZISTA® are the result, even
`
`partially, of the specific form of darunavir used in the tablet.20
`
`34.
`
`Indeed, the pseudopolymorphic form that an API occurs in does not
`
`drive product sales.21 Physicians’ concerns are with efficacy and safety and not
`
`with the specific formulation of the drug.22
`
`35.
`
`PREZISTA® has also been deemed to be covered by 11 patents, not
`
`including those patents directed to processes for making darunavir and/or for
`
`
`20 Ex. 1024, Trial Tr. at 889:25 – 890:2 (Zingman) (testifying that the fact that the
`
`darunavir API of Prezista® is in the ethanolate form does not play a role in
`
`physicians’ decisions to prescribe Prezista®); see also id. at 859:25 – 861:15
`
`(Zingman).
`
`21 See Ex. 1024, Trial Tr. at 889:25 – 890:2, 859:25 – 861:15 (Zingman).
`
`22 See id.
`
`
`
`18
`
`Lupin Ex. 1062 (Page 18 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`making related chemical intermediates.23 Even if the ‘987 patent had some role to
`
`play in the ability of Janssen to market PREZISTA®, for which there is no
`
`evidence, establishing a nexus between any commercial success of PREZISTA®
`
`and the ‘987 patent would require complex and detailed analyses of the influence
`
`of each of the relevant patents. Indeed, I understand that a federal court has
`
`already found that a number of other patents are important to the sales of
`
`PREZISTA®.24
`
`36. Along these lines, the apparent absence of successful innovative
`
`activity by others regarding the claims of the ‘987 patent is well explained by the
`
`
`23 The search
`I
`ran on
`
`the DrugPatentWatch database
`
`(available at
`
`http://www.drugpatentwatch.com/ultimate/), returned 11 patents associated with
`
`the trade-name PREZISTA®, in contrast to the results from electronic version of
`
`FDA’s resource listing Approved Drug Products with Therapeutic Equivalence
`
`Evaluations (commonly referred to as the “Orange Book”), which lists 10
`
`unexpired patents for PREZISTA®.
`
`24 These patents include U.S. Patent Nos. 7,126,015 B2 and 7,772,411 B2, as well
`
`as the related ‘645 ethanolate form patent. Ex. 1065, Trial Op. at 28-30, 56, 65-67,
`
`70.
`
`
`
`19
`
`Lupin Ex. 1062 (Page 19 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`original darunavir compound patents that each claim the darunavir molecule.25
`
`G.D. Searle had exclusive rights to the purported inventions claimed in those
`
`molecule patents during the relevant time period. During that period, no one could
`
`make, use, offer to sell, or sell darunavir in the United States, or import darunavir
`
`into the United States, without permission from G.D. Searle. Thus, there was little
`
`or no economic incentive to invest effort in pursuing an alternative form of
`
`darunavir such as the hydrated forms of the ‘987 patent.
`
`IX. CONCLUSION.
`
`37.
`
`The relevance of a commercial success analysis to non-obviousness is
`
`premised on the assumption that the possibility of achieving commercial success
`
`provides an economic incentive for a new development or new product. The
`
`inference that an invention was not obvious because of its commercial success
`
`flows from the premise that others did not make the invention. If such invention
`
`was obvious, it is presumed that the available profits would have motivated others
`
`to make the invention. In certain circumstances, therefore, absent regulatory or
`
`other barriers to pursuing the claimed subject matter (such as, for example,
`
`blocking patents), the fact that others apparently did not develop the subject matter
`
`
`25 These are U.S. Patent Nos. 5,843,946; 6,248,775; RE42,889 E; and RE43,596 E.
`
`
`
`20
`
`Lupin Ex. 1062 (Page 20 of 22)
`
`
`
`Declaration of Keith B. Leffler, Ph.D. (Ex. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of U.S. Patent No. 8,518,987 B2
`
`claimed in the patent(s) under consideration might contribute to a finding of
`
`nonobviousness.
`
`38.
`
` Here, however, the publically available evidence shows no nexus
`
`between sales of PREZISTA® and the ‘987 patent. Moreover, any sales of
`
`PREZISTA® appear to be attributable not to the alleged inventions set forth in the
`
`claims of the ‘987 patent, but likely to other factors (as discussed above) such as
`
`the efficacy of the darunavir molecule, the inclusion of PREZISTA® in influential
`
`treatment guidelines, and the timing of the entry of PREZISTA® onto the market,
`
`among other factors.
`
`39.
`
`In addition, even were there some connection between sales of
`
`PREZISTA® and the ‘987 patent claims (for which there is no evidence), the
`
`contribution of the ‘987 patent in particular relative to the contributions of the
`
`other darunavir-related patents would need to be assessed in order to determine
`
`precisely the degree to which the ‘987 patent can be said to be responsible for
`
`PREZISTA® sales. Based on the existence of darunavir-related patents, I do not
`
`believe the Patent Owner can properly do so.
`
`40.
`
`In sum, for at least the reasons discussed above, I believe that any
`
`commercial success of PREZISTA® is not probative of non-obviousness of the
`
`‘987 patent.
`
`
`
`21
`
`Lupin Ex. 1062 (Page 21 of 22)
`
`
`
`Declaration of Keith B. Leffler, PhD. (EX. 1062),
`In Support of Lupin Limited’s Petition for Inter Partes Review
`of US. Patent No. 8,518,987 B2
`
`I swear under penalty of perjury that the foregoing is true and correct.
`
`fag/vi,
`Keith B. Leffler
`
`ggi'tl:
`7 Date
`
`22
`
`Lupin Ex. 1062 (Page 22 of 22)
`Lupin Ex. 1062 (Page 22 of 22)
`
`
`
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