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`DECLARATION OF DR. R. RANDALL WICKETT
`DECLARATIONOFDR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`REGARDINGU.S. PATENT NO. 6,645,513
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`PETITION FOR INTER PARTES REVIEW
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 6,645,513
`OF U.S. PATENT NO.6,645,513
`
`
`
`DECLARATION OF R. RANDALL WICKETT, PH.D.
`DECLARATION OF R. RANDALL WICKETT, PH.D.
`
`
`1
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`L'OREALUSA,INC. EX. 1010
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`L'OREAL USA, INC. EX. 1010
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`

`

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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`TABLE OF CONTENTS
`
`
`I. BACKGROUND AND QUALIFICATIONS ................................................. 4
`
`II. PRIOR TESTIMONY ...................................................................................... 7
`
`III. COMPENSATIONAND RELATIONSHIP TO THE PARTIES .............. 8
`
`IV. MATERIALS CONSIDERED ...................................................................... 8
`
`A. Relevant Law: ............................................................................................ 10
`
`a. Anticipation ............................................................................................. 10
`
`b. Obviousness ............................................................................................. 11
`
`B. Person of Ordinary Skill in the Art ......................................................... 13
`
`C. Claim Construction ................................................................................... 13
`
`i. “wherein the adenosine concentration applied to the dermal cells is 10-3 M
`to 10-7 M” ........................................................................................................... 14
`
`I. CLAIMS 1, 3–7, AND 9 OF THE ‘513 PATENT ARE NOT NOVEL IN
`VIEW OF JP ‘153 .................................................................................................. 19
`
`Claim 1 ................................................................................................................. 19
`
`Claim 3 ................................................................................................................. 27
`
`Claim 4 ................................................................................................................. 27
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`Claim 5 ................................................................................................................. 28
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`Claim 6 ................................................................................................................. 28
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`Claim 7 ................................................................................................................. 29
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`Claim 9 ................................................................................................................. 29
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`2
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`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
`
`
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`II. CLAIMS 1, 3-7 AND 9 OF THE ‘513 PATENT WOULD HAVE BEEN
`OBVIOUS OVER JP ‘153 AND DE ‘107 ............................................................ 32
`
`Claim 1 ................................................................................................................. 32
`
`Claim 3 ................................................................................................................. 39
`
`Claim 4 ................................................................................................................. 40
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`Claims 5 and 6 ..................................................................................................... 40
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`Claim 7 ................................................................................................................. 41
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`Claim 9 ................................................................................................................. 42
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`3
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`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`
`I, R. Randall Wickett, Ph.D., declare as follows:
`
`
`
`
`I, R. Randall Wickett, Ph.D., declare as follows:
`
`1.
`
`The opinions set forth below are based on my over 40 years of
`
`experience as an expert in formulating and testing skin care products, including
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`topical cosmetic compositions, and on the review of materials discussed herein.
`
`I. BACKGROUND AND QUALIFICATIONS
`
` 
`
`2. My curriculum vitae (“CV”) (a copy of which is attached) highlights
`
`my education, experience, and qualifications as an expert in formulating and
`
`testing skin care products, including topical products. Some of the information
`
`relevant to this case is summarized below.
`
`3.
`
`I received my Bachelor of Arts in Chemistry in 1968 from Western
`
`Washington State College. I received a Ph.D. in Biophysics from the Department
`
`of Biochemistry and Biophysics at Oregon State University in 1973. I was a
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`postdoctoral fellow at the University of Minnesota, Minneapolis in the Department
`
`of Chemistry from 1972-1974, where I studied protein conformational dynamics.
`
`4.
`
`I worked in the Cosmetics and Personal Care industry from 1974 to
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`1991, first at Procter and Gamble in Cincinnati, Ohio from 1974 to 1985 and then
`
`
`
`4
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`

`

`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
`
`
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`at S.C. Johnson Wax in Racine, Wisconsin until 1991. I performed research on
`
`skin and hair care products at both of these companies.
`
`5.
`
`Since 1991, I have had an extensive consulting practice in which I
`
`have performed consulting and training for cosmetic and pharmaceutical
`
`companies, including Procter and Gamble, DuPont, Estee Lauder, 3M, Unilever,
`
`Clairol, Pfizer, Wyeth Consumer Products, Hill Top Research, Bioscreen and
`
`many others.
`
`6.
`
`I am currently Emeritus Professor of Pharmaceutics and Cosmetic
`
`Science, University of Cincinnati, College of Pharmacy. I joined the University of
`
`Cincinnati, College of Pharmacy as Associate Professor of Pharmaceutics and
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`Cosmetic Science in 1991 and was promoted to Professor of Pharmaceutics and
`
`Cosmetic Science in 1998. In that capacity I teach graduate classes on cosmetic
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`science including, among other topics, skin care science. The Cosmetic Science
`
`Program at the University of Cincinnati is one of the few graduate programs in the
`
`United States offering a M.S. or Ph.D. degree in pharmaceutical sciences with
`
`emphasis in cosmetic science.
`
`7.
`
`I have given more than 100 invited lectures and taught classes and
`
`workshops in the United States and abroad, including in Thailand, Taiwan, Israel,
`
`South Africa, Brazil, Argentina, Guatemala, Chile, Scotland, Estonia, South Korea,
`
`
`
`5
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`

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`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`
`The Netherlands, Germany, Russia, Romania, Canada and France. The lectures
`
`and classes covered topics on various aspects of cosmetic science and cosmetic
`
`product technology.
`
`8.
`
`I was elected as a fellow of the Society of Cosmetic Chemists in 1996.
`
`I served as the Editor of the Journal of the Society of Cosmetic Chemists from
`
`1991 to 1997 and as the Chairman of the International Society for Bioengineering
`
`and the Skin from 2000-2005. I was President of the Society of Cosmetic
`
`Chemists in 2011 and am currently chairman of the International Society for
`
`Stratum Corneum Research.
`
`9.
`
`I have received numerous technical awards from the Society of
`
`Cosmetic Chemists including the Maison G. deNavarre Medal Award, the
`
`Society's highest honor, awarded to me in 1997 for technical contributions to
`
`cosmetic science. I was appointed an International Corresponding Member of the
`
`Chilean Academy of Pharmaceutical Sciences, August 7, 2009.
`
`10.
`
`I have more than 100 scientific publications. My research has
`
`included making and testing all manner of cosmetics and personal care products.
`
`Publications that I have authored or co-authored within the preceding ten years are
`
`listed on my curriculum vitae.
`
`
`
`6
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`

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`
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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`I am a named inventor on four United States patents and two
`
`11.
`
`European patents.
`
`12. Of particular relevance to this matter, I have evaluated transdermal
`
`delivery systems. I have also researched ingredients to enhance topical penetration
`
`of pharmaceutical compositions.
`
`II. PRIOR TESTIMONY
`
`
`
`13.
`
`I have testified as an expert in several cases, including: International
`
`Flora Technologies, Inc. v. Desert Whale Jojoba Company, Inc. (TTAB
`
`Cancellation Proceeding No. 92048012) (deposition); Shen Wei (USA), Inc. et al.
`
`v. Sempermed, Inc. (N.D. Ill.) (deposition); International Flora Technologies, Inc.
`
`v. Desert Whale Jojoba Company, Inc. (TTAB Cancellation Proceeding No.
`
`92045327) (deposition); and Laboratory Skin Care, Inc., and Zahra Mansouri v
`
`Limited Brands, Inc. and Bath & Body Works Inc. (D.Del.) (deposition and trial
`
`testimony);and Bayer Healthcare Pharmaceuticals, inc v. River’s Edge
`
`Pharmaceuticals, LLC, et al. Case No. 1:11-cv-01634-LMM (by deposition).
`
`14.
`
`I have also testified before the National Advertising Division (NAD)
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`of the Council of Better Business Bureaus and Federal Trade Commission on claim
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`support matters.
`
`
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`7
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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`I also provided testimony in L’Oréal USA, Inc., v. Liqwd, Inc.,
`
`15.
`
`PGR2018-00023, PGR2018-00024, PGR2018-00025.
`
`III. COMPENSATIONAND RELATIONSHIP TO THE PARTIES
`
`16.
`
`I am being compensated at an hourly rate of $400 for the time I spend
`
`studying materials and issues associated with this matter and for the time I spend
`
`providing testimony. This rate is my standard consulting rate. My compensation is
`
`not contingent upon the outcome of this matter.
`
`17.
`
`It is my understanding that University of Massachusetts is the
`
`assignee of the ‘513 patent. Prior to this matter, I have not worked for University
`
`of Massachusetts, and am aware of no financial interest that I have in the
`
`University of Massachusetts.
`
`IV. MATERIALS CONSIDERED
`18.
`I have reviewed U.S. Patent No. 6,645,513, as well as the file history
`
`thereof. I have also reviewed the documents listed in the following table:
`
`Exhibit No.
`
`Description
`
`1001
`
`1002
`
`1004
`
`U.S. Patent No. 6,423,327 to Dobson et al.
`
`U.S. Patent No. 6,645,513 to Dobson et al.
`
`Certified Translation of DE 198459107 with Affidavit attesting
`to accuracy under 37 CFR 42.63(b)
`
`1006
`
`Certified Translation of JP-H-09-157153 with Affidavit
`
`
`
`8
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`

`

`
`
`
`
`
`
`1007
`
`1008
`
`1009
`
`1012
`
`1013
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`attesting to accuracy under 37 CFR 42.63(b)
`
`U.S. Patent No. 5,091,182 to Ong et al.
`
`File History of U.S. Patent No. 6,645,513
`
`File History of U.S. Patent No. 6,423,327
`
`PCT Publication WO1996014822A1 Porter et al.
`
`U.S. Patent No. 6,316,012 to N’Guyen et al.
`Robert J. Scheuplein, Permeability of the Skin: A Review of
`Major Concepts and Some New Developments, 67 J.
`INVESTIGATIVE DERMATOL. 672, 672-76 (1976).
`
`
`Karen A. Holbrook & George F. Odland, Regional Differences
`in the Thickness (Cell Layers) of the Human Stratum Corneum:
`An Ultrastructural Analysis , 62 J. Investigative Dermatol. 415,
`415-22 (1974).
`
`C. Lotte et al., In vivo relationship between transepidermal
`water loss and percutaneous penetration of some organic
`compounds in man: effect of anatomic site, 279 Arch Dermatol
`Res 351, 351-6 (1987).
`
`H. Koizumi et al., Adenosine Deaminase in Human Epidermis
`from Healthy and Psoriatic Subjects, 275 Arch Dermatol Res
`310, 310-14 (1983).
`
`P. Singh & M.S. Roberts, Skin Permeability and Local Tissue
`Concentrations of Nonsteroidal Anti-Inflammatory Drugs after
`Topical Application, 268 J. Pharmacol. Exp. Ther 144, 144-51
`(1994).
`
`Gary L. Grove et al., Use of nonintrusive tests to monitor age-
`associated changes in human skin, 32 J. Soc. Cosmet. Chem.
`15, 15-26 (1981).
`
`9
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`

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`
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`A. Relevant Law:
`
`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`19. Although I am not a lawyer, I have been advised on certain relevant
`
`legal principles that I accept for the purpose of my analysis. Specifically, I am
`
`informed that 35 U.S.C. § 102 governs the determination of anticipation and that
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`35 U.S.C. § 103 governs the determination of obviousness. These are outlined
`
`below.
`
`a.
`
`Anticipation
`
`20.
`
` It is my understanding that for a patent claim to be invalid as
`
`anticipated in the context of an Inter Partes Review, it must be shown by a
`
`preponderance of the evidence (“more likely than not”) that all limitations of the
`
`claim are disclosed in a single prior art reference, either expressly or inherently.
`
`21.
`
` A claim limitation is inherent in the prior art if it is necessarily
`
`present in the prior art reference. This can occur, for example, (1) when the natural
`
`result flowing from an express disclosure in the prior art would result in the
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`performance of the inherent feature, even if that result would not have been
`
`appreciated by a skilled artisan at the time of the invention; or (2) in situations
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`where the common knowledge of technologists is not recorded in the reference,
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`such as where technological facts are known to those in the field of the invention
`
`but not to lay persons.
`
`
`
`10
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`

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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`22. A prior art reference does not need to anticipate every possible
`
`embodiment within the scope of the claim; it anticipates if it discloses an
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`embodiment that is within the scope of the claim.
`
`23. Anticipation does not require actual performance of the teachings of a
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`reference, nor are the anticipatory disclosures of a prior art reference limited to the
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`reference’s preferred embodiments. Anticipation requires only that the reference
`
`describe the claimed invention in a manner to have placed the public in possession
`
`of it. Such possession is achieved if a skilled artisan at the time of the invention
`
`could have combined the reference’s description of the invention with his own
`
`knowledge to make the claimed invention without undue experimentation.
`
`b. Obviousness
`
`24.
`
`It is my understanding that in order to invalidate a patent claim as
`
`obvious in the context of an Inter Partes Review, it must be shown by a
`
`preponderance of the evidence that the claim would have been obvious to a skilled
`
`artisan at the time the invention was made. The prior art does not need to render
`
`obvious every possible embodiment within the scope of the claim. Rather, the
`
`prior art renders the claim obvious if the combined teachings disclose an
`
`embodiment that is within the scope of the claim. In determining whether a patent
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`claim is invalid because of obviousness, one must consider the scope and content
`
`
`
`11
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`

`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
`
`
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`of the prior art, the differences between the prior art and the claimed invention, and
`
`the level of ordinary skill in the art.
`
`25.
`
`I am also informed that obviousness can be established by combining
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`or modifying the teachings of the prior art to produce the claimed invention where
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`there is some teaching, suggestion, or motivation to do so; and that a reasonable
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`expectation of success in achieving the subject matter of the claim at issue must
`
`also be shown. Further, I am informed that the teaching, suggestion or motivation
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`test is flexible and that an explicit suggestion to combine the prior art is not
`
`necessary—the motivation to combine may be implicit and may be found in the
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`knowledge of one of ordinary skill in the art, from the nature of the problem to be
`
`solved, market demand, or common sense.
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`26. A prior art reference is pertinent to the obviousness analysis if it
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`discloses information designed to solve the same problems faced by the patent’s
`
`inventors or if the reference discloses information that has obvious uses beyond its
`
`main purpose that a skilled artisan would reasonably examine to solve the same
`
`problems faced by the inventors.
`
`27.
`
`In undertaking an obviousness analysis, I also understand that I may
`
`take into account the inferences and creative steps that a skilled artisan would have
`
`employed in reviewing the prior art at the time of the invention. If the claimed
`
`invention combines elements known in the prior art and the combination yields
`
`
`
`12
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`

`

`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
`
`
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`results that would have been predictable to a skilled artisan at the time of the
`
`invention, then this evidence would make it more likely that the claim was
`
`obvious.
`
`Person of Ordinary Skill in the Art
`
`B.
`
`28. A person having ordinary skill in the art (POSITA or skilled artisan)
`
`at the time of the alleged invention for the ‘513 patent (in 1998 up to and including
`
`the October 26, 1998 filing date of the ‘006 application) would have a Bachelor’s
`
`degree in Biochemistry or Chemistry with some academic exposure to, or industry
`
`courses or research in, topical delivery of drugs or cosmetic ingredients.
`
`C. Claim Construction
`
`29.
`
`I understand that in the context of an Inter Partes Review, the Patent
`
`Trial and Appeal Board of the USPTO is charged with applying the “broadest
`
`reasonable interpretation” of the claims “consistent with the specification,” and
`
`that the claim language should read in light of the specification as it would be
`
`understood by a skilled artisan at the time of the invention. However, I am
`
`informed that the ‘513 patent will expire in October 2018, which may be prior to
`
`the conclusion of a proceeding based on the Petition. Thus, I have been asked to
`
`consider the claims using a more narrow standard: that claims are generally given
`
`their ordinary and customary meaning in light of the specification, which is the
`
`meaning that the term would have to a person of ordinary skill in the art in
`
`
`
`13
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`

`

`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`
`question at the time of the invention, i.e., as of the effective filing date of the patent
`
`application. I am informed that the file history is to be considered and that
`
`arguments and statements made during the prosecution of the patent application
`
`can inform a skilled artisan of the meaning of the claims. Further, I am informed
`
`that arguments made during prosecution of related applications should be
`
`considered and can inform a skilled artisan of the meaning of the claims. In
`
`reaching my conclusions expressed below, I have interpreted the challenged claims
`
`consistent with these standards and requirements. I further note that my opinions
`
`below would not change under either the BRI or narrower standard.
`
`i.“wherein the adenosine concentration applied to the dermal cells is 10-3
`M to 10-7 M”
`
`30. Claim 1 of the ‘513 patent recites that “the adenosine concentration
`
`
`
`applied to the dermal cells is 10-3 M to 10-7 M.” For the reasons that follow, it is
`
`my opinion that term “wherein the adenosine concentration applied to the dermal
`
`cells is 10-3 M to 10-7 M” would have been interpreted by a skilled artisan in
`
`October 1998 to mean “the concentration of adenosine in the composition that is
`
`topically applied to the unbroken epidermal layer of a region of the skin containing
`
`the dermal cells is 10-3 M to 10-7 M (i.e., 0.0265 wt% to 0.00000265 wt %)1.”
`
`
`1 During prosecution of the parent of the ‘513 patent, the inventors of the ‘513
`patent submitted a declaration asserting that a concentration of adenosine of 10-4 M
`
`
`
`14
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`

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`
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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`31. Skin is comprised of many layers, including an outer, epidermal layer,
`
`which covers multiple inner layers (including the dermal layers). (Ex. 1002, col. 1,
`
`ll. 25-30). I note that ‘513 patent describes the skin as having “a surface layer,
`
`known as the epidermis, and a deeper connective tissue layer, known as the
`
`dermis.” (Id.) Further, the ‘513 patent discloses that the “dermis is composed of a
`
`variety of cell types, including fibroblasts.” (Id.) Thus, a skilled artisan would
`
`have understood that dermal fibroblasts are covered by the outer, epidermal layer
`
`of the skin. (Id.)
`
`32.
`
`I note that claim 1 requires topical application to “unbroken skin.”
`
`Thus, a skilled artisan would have understood that because the epidermal layer is
`
`“unbroken,” the dermal layer is not exposed, and adenosine cannot be directly
`
`applied to dermal cells located in the dermal layer through a topical application.
`
`Rather, the adenosine concentration would necessarily be applied to the epidermal
`
`layer (i.e., the outermost layer of the skin). The top layer of the epidermis, the
`
`Stratum Corneum (SC) is a significant barrier to the ingress of exogenous
`
`chemicals to the skin. (Ex. 1016). Accordingly, a skilled artisan would not have
`
`understood the limitation “the adenosine concentration applied to the dermal cells
`
`is 10-3 M to 10-7 M” to mean a direct application of the concentration of adenosine
`
`
`corresponded to 0.00265 wt%. (Ex. 1009, at 91). Thus, the claimed range of 10-3
`M to 10-7 M corresponds to a range of 0.0265 to 0.00000265 wt %.
`
`
`
`15
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`

`

`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`
`to dermal cells. I note that there is no disclosure in the ‘513 patent regarding direct
`
`topical application of adenosine to dermal cells. In fact, direct application to the
`
`dermal cells would require intradermal methods of application, which the ‘513
`
`patent distinguishes from topical application. (Ex. 1002, col. 5, ll. 17-36). Further,
`
`the ‘513 patent discloses ex vivo administration of adenosine to dermal cell
`
`cultures. (Ex. 1002, col. 1, ll. 43-45; col. 2, ll. 15-19). However, a skilled artisan
`
`would have understood that administration of adenosine to ex vivo cultures is not
`
`topical application of adenosine to unbroken skin. Thus, a skilled artisan would
`
`have understood that topical application to unbroken skin requires a topical
`
`application to the epidermal layer of the skin.
`
`33. Regarding the concentration of adenosine in the claims, I have
`
`reviewed the prosecution file history for the ‘327 patent (the parent of the ‘513
`
`patent) and note that the Patent Owner added the limitation “the adenosine
`
`concentration applied to the dermal cells is 10-4 M to 10-7 M” and made arguments
`
`to overcome prior art references. In particular, the Patent Owner argued that
`
`adenosine concentration of the prior art composition of Hartzshtark (i.e., 0.1%)
`
`was outside the scope of the claimed range of 10-4 M to 10-7 M. (Ex. 1009, 83-87).
`
`Thus, based on Patent Owner’s arguments, a skilled artisan would have understood
`
`that the claimed concentration of adenosine is the amount in the composition that
`
`is topically applied, and not an amount that reaches the dermal cells.
`
`
`
`16
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`

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`
`
`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`34. Further, in my opinion, an interpretation that the claimed
`
`concentration is the concentration that reaches the dermal cells is incorrect. In
`
`1998, a skilled artisan would have understood that it was not possible to calculate
`
`with any reasonable certainty an amount of adenosine that reaches the dermal cells
`
`when topically applied in view of the numerous variables that would need to be
`
`identified and factored into any such calculation. For example, a skilled artisan
`
`would have understood that the following is a non-exclusive list of variables that
`
`would influence any such calculation: the thickness of the stratum corneum, the
`
`condition of the skin, the age of the skin, the vehicle in which the adenosine is
`
`applied, the manner in which the adenosine is applied, the area in which it is
`
`applied, the time it left on the skin, etc. (Ex. 1017). Some of these factors are
`
`recognized in the ‘513 patent without any indication as to how they would affect
`
`the claimed concentration of adenosine. (Ex. 1002, col. 5, lines 37-42). In
`
`addition, several of these factors vary depending on the part of the body on which
`
`the composition is applied (e.g., elbow, foot, forehead, etc.). This is because the
`
`stratum corneum layer is thicker and less permeable on some portions of the body
`
`than others. (Ex. 1018). In addition, a skilled artisan would have been aware that
`
`many of these factors vary from individual to individual. (Ex. 1017). Further, a
`
`skilled artisan would have known that adenosine may metabolize in the epidermis
`
`prior to reaching the dermis. (Ex. 1019). A skilled artisan would have also known
`
`
`
`17
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`DECLARATION OF DR. R. RANDALL WICKETT
`
`REGARDING U.S. PATENT NO. 6,645,513
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`
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`that the upper part of the dermis contains a network of small capillaries that
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`transport substances that have penetrated the epidermis into the blood stream.
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`Attempting to account for capillary clearance is extremely complex.(Ex. 1020)
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`35.
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`I note that the ‘513 patent does not provide any guidance or
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`suggestion as to how such a calculation or measurement of the actual concentration
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`reaching the “dermal cells” could be done. Thus, in view of Patent Owner’s
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`arguments distinguishing the claimed concentration over concentrations in the
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`compositions of the prior art, and the general knowledge of a skilled artisan in
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`1998, it is my opinion that the only way the claimed concentration would make any
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`sense (i.e., be capable of being determined) is the claimed concentration of
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`adenosine is the amount in the composition that is topically applied, and not an
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`amount that reaches the dermal cells.
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`36.
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`In view of the foregoing, it is my opinion that a skilled artisan having
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`considered the language of the claims, the specification, and the prosecution file
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`history of the ‘513 patent would have understood the phrase “the adenosine
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`concentration applied to the dermal cells is 10-3 M to 10-7 M” to mean the
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`concentration of adenosine in the composition that is topically applied to the
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`unbroken epidermal layer of a region of the skin containing the dermal cells is
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`10-3 M to 10-7 M (i.e., 0.0265 to 0.00000265 wt %).
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`18
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`I.
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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`CLAIMS 1, 3–7, AND 9 OF THE ‘513 PATENT ARE NOT NOVEL IN
`VIEW OF JP ‘153
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`37. For the reasons that follow, claims 1, 3-7, and 9 are not novel in view
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`of JP ‘153.
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`38.
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`JP’153 relates to compositions for application to the skin to prevent
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`and treat effects of skin aging, such as wrinkling. (Ex. 1006, 5:14-20, 12:4-8.)
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`JP’153’s skin compositions include adenosine or adenosine derivatives. (Id., 5:22-
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`32, Examples 8, 11, 12.) The skin compositions may be a skin cosmetic such as a
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`beauty serum or lotion, and may contain adenosine in an amount ranging from
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`about 0.01%-10% by weight. (Id., 8:21-9:8.)
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`Claim 1
`
`39.
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`JP ‘153 discloses cosmetic compositions comprising adenosine and
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`adenosine derivatives, such as adenosine monophosphate (“AMP”) for the
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`treatment of skin aging and wrinkles. (Ex. 1006, Abstract, ¶ [0012]). JP ‘153
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`teaches that AMP in combination with adenosine leads to improved cosmetic
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`properties compared to adenosine alone. (Ex. 1006, Examples 11-12, Table 7). For
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`the reasons that follow, it is my opinion that JP ‘153 discloses every limitation of
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`claim 1. The following Table summarizes where each element of claim 1 of the
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`‘513 patent is found in JP ‘153:
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`19
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`
`
`Claim
`1. A method for enhancing the
`condition of unbroken skin of a
`mammal by reducing one or more of
`wrinkling, roughness, dryness, or laxity
`of the skin, without increasing dermal
`cell proliferation,
`
`
`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`JP ‘153
`JP ‘153 discloses a cosmetic product for
`the treatment of wrinkles.
`
`“To offer preparations for external use
`on the skin which have a synergically
`intensified activated oxygen species
`eliminating action, and can prevent skin
`ageing and injury caused by intra- and
`extracorporeal oxidation stress.”
`(Ex. 1006, at Abstract, emphasis added )
`
`“As the inclusion rates of adenosine or
`a derivative thereof, and
`hamamelitannin, etc., in the external
`preparation or cosmetic base, about
`0.01-10 wt% and 0.0001-10 wt%,
`respectively, are suitable, considering
`the effect of the base and the effective
`dose for an action on the skin, etc.”
`(Ex. 1006, at ¶[0012] , emphasis added)
`
`[Example 12] Skin cream
`(1) beeswax
`
` 6.00
`(wt%)
`
`
`
`20
`
`

`

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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
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`(2) cetanol
`(3) reduced lanolin
`(4) squalane
`(5) glyceryl fatty acid ester
`(6) lipophilic glycerol
`monostearate
`(7) polyoxyethylene
`(20EO) sorbitan
`monolaurate
`(8) propylene glycol
`(9) methyl paraoxybenzoate
`(10) adenosine
`(11) witch hazel 50 wt%
`ethanol extract
`(12) thioredoxin-
`thioredoxin reductase
`complex
`(13) fragrances
`(14) pure water
`
` 5.00
` 8.00
`37.50
` 4.00
` 2.00
`
` 2.00
`
` 5.00
` 0.10
` 0.02
` 0.01
`
` 0.10
`
` 0.15
`30.12
`
`
`(Ex. 1006, at ¶[0022] , emphasis added)
`
`“Usage tests were carried out on the
`aforementioned example 8 to example
`13 of the present invention. In the usage
`tests, there were groups of 20 panellists
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`21
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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`ordinarily employed for field tests, the
`different groups used the examples and
`comparative examples separately in a
`blinded fashion on the face and hands,
`and evaluation was carried out by
`observing changes in wrinkling and
`skin elasticity. The period of use was 1
`year, from April to March. Wrinkling
`was evaluated by 5 stages "decrease",
`"slight decrease", "no change", "minute
`increase in wrinkling", and "clear
`increase in wrinkling", skin elasticity
`was evaluated by 5 stages "raised",
`"slightly raised", "no change", "slight
`decrease", and "decrease", each
`evaluation is presented in Table 7 as the
`numbers of panellists giving each
`score.”
` (Ex. 1006, at ¶[0024] , emphasis added)
`
`Table 7 discloses that 60% (12/20) of
`the panelists evaluated demonstrated a
`reduction in wrinkling using Example
`11.
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`Further, 90% (18/20) of the panelists
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`22
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`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`demonstrated an increase in skin
`elasticity (decreased laxity). (Ex. 1006,
`at ¶[0026], Table 7)
`
`Table 7 discloses that 25% (5/20) of the
`panelists evaluated demonstrated a
`reduction in wrinkling using Example
`12. Further, 50% (18/20) of the panelists
`demonstrated an increase in skin
`elasticity (decreased laxity). (Id.)
`
`As reported in Table 7, none of the
`panelists using Example 11 or 12
`demonstrated an increase in wrinkling
`or a decrease in skin elasticity (i.e.,
`increase in laxity). (Id.)
`
`JP ‘153 does not disclose the treatment
`of wounds or broken skin, so a skilled
`artisan would understand JP ‘153 to
`disclose and include treatment of
`unbroken skin.
`
`
`23
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`

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`
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`the method comprising topically
`applying to the skin a composition
`comprising a concentration of adenosine
`in an amount effective to enhance the
`condition of the skin without increasing
`dermal cell proliferation, wherein the
`adenosine concentration applied to the
`dermal cells is 10−4 M to 10−7 M.
`
`DECLARATION OF DR. R. RANDALL WICKETT
`REGARDING U.S. PATENT NO. 6,645,513
`
`
`JP ‘153 discloses topically applying to
`the skin a composition comprising a
`concentration of adenosine to prevent
`aging and treatment of wrinkles.
`
`The claimed range converted to wt. % is
`0.00265% to 0.00000265%. (Ex. 1009,
`at 84)
`
`“As the inclusion rates of adenosine or
`a derivative thereof, and
`hamamelitannin, etc., in the external
`preparation or cosmetic base, about
`0.01-10 wt% and 0.0001-10 wt%,
`respectively, are suitable, considering
`the effect of the base and the effective
`dose for an action on the skin, etc.”
`(Ex. 1006, at ¶[0012] , emphas