UNITED STATES PATENT AND TRADEMARK OFFICE
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`____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`____________
`
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`MICRO LABS LIMITED AND MICRO LABS USA INC.,
`Petitioner,
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`v.
`
`SANTEN PHARMACEUTICAL CO., LTD. AND
`ASAHI GLASS CO., LTD.,
`Patent Owner.
`
`____________
`
`
`Case IPR2017-01434
`U.S. Patent No. 5,886,035
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`____________
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`SUPPLEMENTAL DECLARATION OF
`ROBERT D. FECHTNER, M.D.
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`Santen/Asahi Glass Exhibit 2029
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`TABLE OF CONTENTS
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`I.
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`INTRODUCTION ........................................................................................... 1
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`II.
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`LONG-FELT BUT UNMET NEED ............................................................... 2
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`III.
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`FAILURE OF OTHERS .................................................................................. 4
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`i
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`I, Robert D. Fechtner, M.D., declare and state as follows:
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`I.
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`INTRODUCTION
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`1.
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`I am Professor and Chair of Ophthalmology at SUNY Upstate
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`Medical University (Syracuse, NY).
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`2.
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`I have been retained on behalf of Patent Owners Santen
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`Pharmaceutical Co., Ltd. and Asahi Glass Co., Ltd. (together, "Patent Owner") as
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`an independent expert consultant in the above-referenced inter partes review
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`("IPR") proceeding, to provide information and opinions on the teachings of the
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`prior art and the state of the art, as relevant to the issued claims of U.S. Patent No.
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`5,886,035 ("the '035 Patent"). Ex.1001.
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`3.
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`I previously submitted a written declaration on these topics, which
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`was filed as Ex.2002. I hereby incorporate my previous declaration into this
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`declaration.
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`4.
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`I understand from counsel that one issue in this proceeding is whether
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`objective secondary considerations of nonobviousness (for example, commercial
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`success, copying, unexpected results, long-felt but unmet need, and failure of
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`others) support the nonobviousness of the claims of the '035 Patent. I have been
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`asked to opine as to whether there was a long-felt but unmet need for tafluprost and
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`whether there has been a failure of others to fill that long-felt but unmet need.
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`1
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`5. My opinions in this declaration are based on documents I have
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`reviewed in connection with this proceeding, and are further informed by my
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`knowledge and experience, including my decades of experience with glaucoma
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`research, diagnosis, treatment and prevention. An updated list of the documents
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`and materials that I considered in connection with the development of my opinions
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`set forth in this (and my previous) declaration is attached hereto as Exhibit B.
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`II. LONG-FELT BUT UNMET NEED
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`6.
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`In my opinion, as of December 26, 1996, tafluprost's unique receptor
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`profile and associated properties filled a previously long-felt but unmet need for an
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`effective prostaglandin analog that can be tolerated by patients unable to tolerate
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`other prostaglandin analogs.
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`7.
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`The therapeutic profile of prostaglandin analogs (and other drugs) are
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`typically defined in large clinical trials, which provide average results for the
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`population that was studied. Those clinical trials also typically report non-
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`responders and discontinuations for tolerability issues. In the context of
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`prescribing prostaglandin analogs to my patients, however, it is impossible to
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`predict in advance whether any given patient will be a responder or non-responder,
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`find the medication tolerable or intolerable, or be anywhere in between in either of
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`those respects. In other words, it is impossible to predict in advance (1) whether
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`and to what degree IOP will be lowered, and (2) the accompanying side effects. In
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`2
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`my opinion, the addition of tafluprost to our armamentarium provides better
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`outcomes and improved quality of life for patients that are prescribed it.
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`8.
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`Despite the lower cost of generic latanoprost, I still prescribe
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`Zioptan® (branded tafluprost in the US) to many of my patients, and in my
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`opinions, those patients are benefitting from the unique benefits of
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`Zioptan®/tafluprost. In my experience, Zioptan®/tafluprost provides
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`prostaglandin efficacy (understood in the field as 6-8 mm Hg lowering of IOP) and
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`superior tolerability in those patients for whom I have selected it. For example,
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`many of my patients have ocular surface disease or a history of adverse effects
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`with other glaucoma drugs (including prostaglandin analogs): for those patients, I
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`tend to prescribe Zioptan®/tafluprost, which is better tolerated and facilitates
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`compliance, and therefore better preserves the patients' quality of life.
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`9.
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`The only other prostaglandin analog available outside the US as of
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`December 26, 1996 was isopropyl unoprostone, which has been reported to be
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`well-tolerated. But, it requires twice-daily dosing, which is undesirable compared
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`to the once-daily dosing of the other commercially-available prostaglandin
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`analogs, including tafluprost. Compare Ex.2042 (Rescula®/isopropyl unoprostone
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`label), 1 with Ex.2032 (Zioptan®/tafluprost label), 1; Ex.2037
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`(Xalatan®/latanoprost label), 1; Ex.2038 (Lumigan®/bimatoprost 0.03% label), 1;
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`3
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`Ex.2039 (Lumigan®/bimatoprost 0.01% label), 1; Ex.2040 (Travatan®/travoprost
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`label), 1; Ex.2041 (Travatan Z®/travoprost label), 1.
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`10. Zioptan®/tafluprost is also likely to be a better option than the
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`bimatoprost and travoprost prostaglandin analogs (which came on the market after
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`December 26, 1996) for patients that have ocular surface disease or a history of
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`adverse effects with other glaucoma drugs; for example, bimatoprost and
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`travoprost are each associated with a very high risk of hyperemia. Ex.2038
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`(Lumigan®/bimatoprost 0.03% label), 1, 3 (45% hyperemia and approximately 3%
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`of patients discontinued therapy due to conjunctival hyperemia); Ex.2039
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`(Lumigan®/bimatoprost 0.01% label), 3 (31% hyperemia and approximately 1.6%
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`of patients discontinued therapy due to conjunctival hyperemia); Ex.2040
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`(Travatan®/travoprost label), 3 (30% to 50% hyperemia and up to 3% of patients
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`discontinued therapy due to conjunctival hyperemia); Ex.2041 (Travatan
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`Z®/travoprost label), 3 (same); Ex.2032 (Zioptan®/tafluprost label), 2 (only 4% to
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`20% hyperemia and approximately 1% of patients discontinued therapy due to
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`ocular adverse reactions).
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`III. FAILURE OF OTHERS
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`11. Other glaucoma medications have been unsuccessful in the market
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`because of intolerable side effects (such as hyperemia and allergy), or poor
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`efficacy. As discussed in my previous declaration (Ex.2002, ¶18), PGF2α (salt or
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`4
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`isopropyl ester) were deemed unacceptable because of intolerable side effects
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`(including hyperemia) in human studies in the 1980s. PGE2 was also abandoned
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`after human studies in the 1980s that showed an unexpected hypertensive response.
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`See, e.g., Wang et al., "Effect of 8-iso prostaglandin E-2 on aqueous humor
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`dynamics in monkeys," Arch. Ophthalmol. 116(9):1213-1216 (1998) (Ex.2034), 2
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`(differentiating 8-iso PGE2 over PGE2 based on lack of "initial ocular
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`hypertension"). I occasionally prescribed Rescula®/isopropyl unoprostone when it
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`was first launched (prior to the release of Zioptan®) because of its reported
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`tolerability, but never considered unoprostone to be particularly useful because of
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`its relatively low efficacy. See, e.g., Aung et al., "A randomized double-masked
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`crossover study comparing latanoprost 0.005% with unoprostone 0.12% in patients
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`with primary open-angle glaucoma and ocular hypertension," Am. J. Ophthalmol.
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`131(5):636-642 (2001) (Ex.2035), 1 ("Latanoprost once daily was significantly
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`more effective in reducing intraocular pressure compared with unoprostone twice
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`daily . . ."); Aung et al., "Additive effect of unoprostone and latanoprost in patients
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`with elevated intraocular pressure," Br. J. Ophthalmol. 86:75–79 (2002) (Ex.2036),
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`1 ("Latanoprost once daily causes additional IOP lowering in eyes which were
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`being treated with unoprostone twice a day. However, there was no additional IOP
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`lowering when unoprostone was added to eyes which were being treated with
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`latanoprost."). Drug classes other than prostaglandins, e.g., adrenergic agonists,
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`5
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`also failed in the market. For example, Iopidine® was quickly replaced in the
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`market by other adrenergic agonists, because of its unexpectedly high levels of
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`hyperemia and allergy. See, e.g., Ex.2043 (Iopidine®/apraclonidine label), 2
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`("incidence of ocular allergic responses and systemic side effects may limit the
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`utility of IOPIDINE 0.5% Ophthalmic Solution").
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`6
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`IPR Page 8/12
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`IPR Page 8/12
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`IPR Page 9/12
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`Santen/Asahi Glass Exhibit 2029
`Micro Labs v. Santen Pharm. and Asahi Glass
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`IPR Page 9/12
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`Exhibit B
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`IPR Page 10/12
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`Santen/Asahi Glass Exhibit 2029
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`IPR Page 10/12
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`Exhibit
`No.
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`Updated List of Materials Considered
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`Document
`
`N/A
`
`N/A
`
`2003
`
`2011
`
`2013
`
`2014
`
`2017
`
`2032
`
`2034
`
`Petition for Inter Partes Review of U.S. Patent No. 5,886,035 by
`Micro Labs Ltd. (IPR2017-04343)
`Institution Decision for Inter Partes Review of U.S. Patent No.
`5,886,035 by Micro Labs Ltd. (IPR2017-04343) (Paper 11)
`1001 U.S. Patent No. 5,886,035
`EP0639563A2 to Klimko et al.
`1003
`1005 U.S. Patent No. 5,292,754 to Kishi et al.
`1027 Declaration of Mitchell deLong, Ph.D.
`1028 Declaration of Aron D. Rose, M.D.
`Camras et al., "Reduction of intraocular pressure by prostaglandins
`applied topically to the eyes of conscious rabbits," Invest. Ophthalmol.
`Vis. Sci. 16:1125-1134 (1977)
`Giuffrè, "The effects of prostaglandin F2α in the human eye," Graefe's
`Arch. Clin. Exp. Ophthalmol. 222:139-141 (1985)
`Villumsen and Alm, "Prostaglandin F2α-isopropylester eye drops:
`effects in normal human eyes," Br. J. Ophthalmol. 73:419-26 (1989)
`Villumsen and Alm, "Ocular effects of two different prostaglandin F2α
`esters: a doublemasked cross-over study on normotensive eyes," Acta
`Ophthalmol. 68:341-343 (1990)
`European Patent Application No. 0364417 A1
`Zioptan® (tafluprost) Product Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202514s0
`03s004lbl.pdf
`Wang et al., "Effect of 8-iso prostaglandin E-2 on aqueous humor
`dynamics in monkeys," Arch. Ophthalmol. 116(9):1213-1216 (1998)
`Aung et al., "A randomized double-masked crossover study comparing
`latanoprost 0.005% with unoprostone 0.12% in patients with primary
`open-angle glaucoma and ocular hypertension," Am. J. Ophthalmol.
`131(5):636-642 (2001)
`Aung et al., "Additive effect of unoprostone and latanoprost in patients
`with elevated intraocular pressure," Br. J. Ophthalmol. 86:75–79
`(2002)
`Xalatan® (latanoprost) Product Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020597s0
`51lbl.pdf
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`2035
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`2036
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`2037
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`IPR Page 11/12
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`Document
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`Lumigan® (bimatoprost) 0.03% Product Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021275s0
`27lbl.pdf
`Lumigan® (bimatoprost) 0.01% Product Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022184s0
`06lbl.pdf
`Travatan® (travoprost) Product Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021257s0
`25lbl.pdf
`Travatan Z® (travoprost) Product Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021994s0
`12lbl.pdf
`Rescula® (isopropyl unoprostone) Product Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021214s0
`06s007lbl.pdf
`Iopidine® (apraclonidine) Product Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020258s0
`30lbl.pdf
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`Exhibit
`No.
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`2038
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`2039
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`2040
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`2041
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`2042
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`2043
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`IPR Page 12/12
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