Case 1:17-cv-00868-VAC-SRF Document 10-2 Filed 08/04/17 Page 1 of 6 PageID #: 188
`Case 1:17-cv—00868—VAC-SRF Document 10-2 Filed 08/04/17 Page 1 of 6 PageID #: 188
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`EXHIBIT B
`EXHIBIT B
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`Case 1:17-cv-00868-VAC-SRF Document 10-2 Filed 08/04/17 Page 2 of 6 PageID #: 189
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`03/12/02 TUE 13: 15 F~ 16175428906
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`~ 003
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`Anomey's DOcketN("7917-04S0021 (UMMC 97-32)
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFI~ r£
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`I ' (3 ;L
`
`Applicant
`
`Serial No.
`Filed
`Title
`
`James G. Dobson, Jr. and
`Michael F. Ethier
`09/672,348
`September 28, 2000
`TREATMENT OF SKIN Wlrn ADENOSlNE OR ADENOSINE ANALOG
`
`16415
`L. Charmavajjala
`
`Art Unit
`Examiner
`
`Commissioner for Patents
`Washington, D.C. 20231
`
`DECLARATION UNDER 37 e,r,R. § 1.132
`We, James G. Dobson, Jr., Ph.D. and Michael F. Ethier, declare that:
`1. We are the co-inventors of the subject matter clalmed in the patent application
`captioned above (lithe present applichtion").
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`- 2. The present application claims methods ofcnhancing the condition of unbroken skin
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`of a mammal~ but without increasjng de~al cell proliferation. Excess skin cell proliferation can
`cause scarring, discoloration, and a variety of other skin anomalies associated with hyperplasia.
`The method claims reclte applying to the skin a composition including a concentration of
`adenosine in an amount effective to enhance the condition of the skin without increasing dennal
`cell proliferation. These claims have been rejected by the U.S. Patent & Trademark Office
`Examiner in a Final Office Action dated October 10,2001. as allegedly anticipated by Gennan
`Patent No. DE 195 45 107 A 1 ("the German patent app)jcation) and by Hartzshtark et al.,
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`Experentia, 41 :378-379 (1985) ("Hartzshtark et a1.). We have reviewed these two references,
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`and based on a careful review of the references and our experimental test results, we believe that
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`they do not disclose the methods c:laimed in our present application.
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`3. We have conducted testing to show that an important feature of OUT claimed methods
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`is correct, i.e., that concentrations of adenosine recited in the pending claims do not increase
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`CE~TIFJCATE Of' MAILTNG BY FIRST CLASS MAIL
`I hereby certifY under 37 eFR fl.8(a) m.1 this oorrespondence is bein!
`deposited "lith the United SUlles Postal Service as first class mail "lith
`sufficient postall: on the: date indicated below and is addressed· to the
`Commi,sioncr fQr Patents, Washington. D.C. 10231.
`
`Date of Deposit
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`Feb,rU*l ,3 I 2..t1lJ 1.
`~ l/"'-.
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`

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`Case 1:17-cv-00868-VAC-SRF Document 10-2 Filed 08/04/17 Page 3 of 6 PageID #: 190
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`03/12/02 TUE 13; 15 'FAX 16175428906'
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`APplicant:
`Ethier
`Serial No. :
`Filed
`Page
`
`James G. DOb$on,l,..nd Mjchael F,
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`09/672,348
`September 28, 2000
`2
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`AnOmeY'5DOCke('''.' 07917-0450021 (UMMC 97~
`32)
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`141004
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`proliferation of a major type of dermal cells, i.e' 7 skin fibrob}asts. In this testing. we cultured
`skin fibroblasts from two subjects, a. '30 ye:ar·old female and an 84 year-old male. For ,each
`4
`experiment, we used 35 rom culture dishes plated with fibroblasts at a density of 1 X 10
`cells/cm2 • Adenosine was added to dishes the following day. For each adenosine-treated dish, a
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`matching control dish was treated with vehicle. After 5 days in culture, we counted the total
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`. number of cells in the control dish, and then in the test dish. For each pair of culture dishes, the
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`number of cells in the control dish was designated as 100% and the number of cells in the
`adenosine-treated dish was expressed as a percentage of the control dish. 'In each experiment,
`the mean and standard error fo:r aaenosine-treated dishes was generated from the total number of
`samples (n = 6 or 7) for each test and expressed as ~ percent ofthe control. The adenosine
`concentrations and results are listed iJ? Table 1 attached to this declaration as Exhibit A. As
`shown, adenosine concentrations of both 1 0 ~M (10.5 M) and 1 00 ~M (10-4 M) caused no
`significant change in cell proliferation, Le., the number of cells did not change. Based on these
`7
`results, we believe that lower adenosine concentrations. e.g., 10-6 M and 10-
`M, would also not
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`increase cell pi,oliferation.
`4. Hartzshtark et a1. states that certain concentrations of various agents, including
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`a.denosine, increase skin cyclic-AMP content and thus cause a decrease in skin indentation.
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`More specifically. Hartzshtark et a1. indicates in a Table on page 379 that the adenosine
`concentration effective to reduce indentation was 0.1 % (3.8 x 10.3 M). In addition, they note that
`they also tested adenosine "at one-third of the concentrations shown in the table [e.g., about 1.27
`x lO·3M], and at this level [adenosine was] ineffective" (bottom of page 378 to top of page 379).
`The presently pending claims recite a maximum concentration of adenosine of 10..4 M. and
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`require that there is no increase in dermal cell proliferation. The results in Hartzshtark indicate
`that a concentration of adenosine of 10-4 M or lower would be even less effective than one-third '
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`of 0.1 % (1.27 x 10-3 M), which was ineffective in their testing.
`5. We have obtained a translation of the German patent application, which is attached to
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`this declaration as Exhibit B. Our comments are based on this translation. The German patent
`application describes the use of adenosine for increasing cell proliferation in human skin (see,
`e.g., the title and claim 1). However, our testing~ ~s described above, has shown that low
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`

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`Case 1:17-cv-00868-VAC-SRF Document 10-2 Filed 08/04/17 Page 4 of 6 PageID #: 191
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`03/12/02 TUE 13:16 FAX 16175428906
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`Applicant; James G. DObson,end Michael F.
`Ethier
`Serial No. : 09/672,348
`Filed
`September 28, 2000
`Page
`3
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`Attorney's Docker) 07917·0450021 (UMMC 97-
`32)
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`141005
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`concentrations of adenosine do not increase derma} cell proliferation. Thus, when the German
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`patent application states that concentrations of adenosine as low as 0.001 % are useful for
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`increasing cell proliferation, we believe that the German patent application must be mjstaken.
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`There is one paragraph in the German patent application that states the 0.001 % number, and this
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`is in a very broad range from 0.001 to 10% by weight of a cosmetic compositi!Jn (at page 9, 4th
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`'full paragraph). Other sections ofthe German patent appJjcation recite higher concentrations.
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`For example. the claims, recite 0.01 to 10%, with a preferred concentration of 0.1 to 6%. More
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`importantly, each of the six Examples lists a relatively high concentration of 0.1 % adenosine.
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`Thus, based on our own testing,o/skin fibroblasts, which make up a large part of the dermis, we
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`believe that the extremely broad range of adenosine concentrations listed in the German patent
`application js not supported by reality. The low end of this unsupported range is 0.001 %, which
`corresponds to 3.8 x 10.5 M adenosine. This is between the 10.4 M and 1 D" M concentrations
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`recited in the claims ofthe present application. However, our claimed invention is based on the
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`demonstration that the recited concentrations of adenosine do not increase cell proliferation.
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`This is the exact opposite of the assertions in the German patent application. It is for these
`reasons that we believe the German patent app li cat jon recitation of adenosine concentrations less
`than 10-4 M (0.00265%) cannot be valid, and thus the German patent application does not
`
`. disclose the same invention as the claims in the present application.
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`We further dec::lare that all statements made herein of our knowledge are true and that all
`.
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`statements made on infonnation and belief are believed to be true; and further that these
`statements were made with the knowledge that willful false statements and the like so made are
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`punishable by fine or imprisonment, 'or both, under Section 1001 of Title 18 of the United States
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`Code and that such willful false statements may jeopardize the validity of the application or any
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`patent issuing thereon.
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`

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`Case 1:17-cv-00868-VAC-SRF Document 10-2 Filed 08/04/17 Page 5 of 6 PageID #: 192
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`03/12/02 TUB 13:16 FAX 16175428906
`Applicant; lame; G. Dobson,C\d Michael F.
`Ethier
`Serial No. :
`Filed
`Page
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`09/672,348
`September 28, 2000
`4
`-
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`Attorney's DOCker-) 07917·045002/ (UMMC 97-
`32)
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`141006
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`Date:
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`de:; /11!d ci
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`Date:~_"Z __ /_·\'......;\ I_D_2.. ____ _
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`20387642.doc
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`.J.~
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`MIchael F.·
`
`ier, Ph,D .
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`

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`Case 1:17-cv-00868-VAC-SRF Document 10-2 Filed 08/04/17 Page 6 of 6 PageID #: 193
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`03/~2/02 TUB 13:15 FAX 16175428906
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`U
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`Attorney's Docket 1" )7917-045002 I (UMMC 97-32)
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`141 002
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`IN THE UNITED STATES PATENT AND TRADEMARK. OFFICE
`
`Applicant
`
`Serial No.
`Filed
`Title
`
`James G. Dobson, Jr. and
`Michael F. Ethier
`09/672,348
`September 28, 2000 '
`TREATMENT OF SKIN WITH ADENOSINE OR ADENOSINE ANALOG
`
`1615
`L. Channavajjala
`
`Art Unit
`Examiner
`
`Commissioner for Patents
`Washington, D.C. 20231
`
`SUBMISSION OF SIGNED DELCMA TION
`.
`Applicants filed a Response on February 11, 2002 that included an unsigned declaration.
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`Applicants submit herewith the signed declaration for entry into the file along with the response.
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`No fees arc believed dUte. However, please apply any charges or credits to Deposit
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`Account No. 06-1050, referencing Attorney Docket No. 07917-045002.
`Respectfully submitted,
`
`Date:,~ __ f)_~_-_I_~_~_O~~~ ___ _
`
`Fish & Richardson P.C.
`225 Franklin Street
`Boston, Massachusetts 02110-2804
`Telephone: (617) 542-5070
`Facsimile: (617) 542-8906
`
`20J90012.doc
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`CERTIFICATE OF MAl UNO BY FIRST CLASS MAIL
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`