`Case 1:17-cv—00868—JFB-SRF Document 18-1 Filed 08/23/17 Page 1 of 15 PageID #: 377
`
`EXHIBIT A
`
`EXHIBIT A
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 2 of 15 PageID #: 378
`
`Attorney's DocketN" . <07917·045002/ (UMMC97-32)
`\
`
`Applicant
`
`Serial No.
`Filed
`Title
`
`I .
`
`,
`
`~
`HE UNITED STATES PATENT AND TRADEMARK OFF~
`~a
`~ ~ ~
`Art Unit
`: 1615
`James G. Dobson, Jr. and
`Examiner: L. Channavajjala ~ &.> ~
`Michael F. Ethier
`~ ~ ' ( )
`..
`09/672,348
`. {jJ
`P
`September 28, 2000
`TREATMENT OF SKIN WITH ADENOSINE OR ADENOSINE ANALOG ~
`~
`/() / (!, #djL
`. I ~ C?{E)
`
`BOXAF
`Commissioner for Patents
`Washington, D.C. 20231
`
`RESPONSE TO FIN'AL OFFICE ACTION DATED OCTOBER 10,2001
`
`PURSUANT TO 37 C.F.R. 1.1l6(A)
`
`Please amend the application as indicated below, and consider the following remarks.
`
`I
`
`In the claims
`
`/
`
`/
`
`Cancel claims 54 to?ithout prejudice as directed to a non-elected invention.
`
`Amend claim 70 as follows.
`
`:
`1
`-ixf. (Amended) 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, 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.
`
`\
`
`CERTIFICA IE OF MAILING BY FIRST CLASS MAIL
`
`I hereby certify under 37 CFR § 1.8(a) that this correspondence is being
`deposited with the United States Postal Service as first class mail with
`sufficient postage on the date indicated below and is addressed to the
`
`C(d12VW2::1ingti D.C.~~ .
`
`s;ttzwqt
`
`Typed or Pnnted Name of Person Signing Certificate
`
`Slgnate ~
`t-4~aL2' Gra~
`
`c
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 3 of 15 PageID #: 379
`
`App,licant :
`Ethier
`Serial No. :
`Filed
`Page
`
`James G. Dobson, ',' and Michael F.
`
`Attorney's Docke~, ,,'.: 07917-045002/ (UMMC 97-
`32)
`
`09/672,348
`September 28, 2000
`2
`
`REMARKS
`
`Claims 70 to 79 are pendin.g in this application. Applicants propose canceling daims 54
`
`to 69 as allegedly directed ,to a non-elected invention. Applicants also propose to amend claim
`
`70. This amendment would add no new matter, as it merely includes a range of concentrations
`
`of adenosine recited in dependent claims and in the specification at page 3, lines 15-18.
`
`In addition, the amendment set forth above would raise no new issues that would require
`, .
`further consideration and/or search. Applicants submit that this amendment would place the
`
`'
`
`claims into condition for allowance, or at least present the rejected claims in better form for
`
`consideration on appeal, and sh<mld therefore be entered after the final rejection under 37 C.F.R.
`
`§ 1.116 (a).
`
`Restriction
`
`Applicants disagree with the Examiner's conclusion that' the present claims 54 to 69 are
`
`directed to a separate invention than that claimed in claims 70 to 79, because all are based on the
`
`application of certain: concentrations of adenosine to the skin to achieve certain results.
`
`Nevertheless, applicants propose to cancel these claims as directed to a non-elected invention
`
`unless the Examiner reconsiders and withdraws this restriction. Thus, claims 70 to 79 would be
`
`pending.
`
`35 U.S.C. § 112, First Paragraph
`
`Claims 70 to 79 have been rejected as allegedly containing subject matter that was not
`
`described in the specification in such a way as to enable one skilled in the art to make and/or use
`
`the invention. Applicants traverse this rejection in view of experimental test results as described
`
`in a declaration (attached hereto) by the two co-inventors of this application, Dr. James G.
`
`Dobson, Jr. and Dr. Michael F. Ethier ("the Declaration").
`
`According to the Office Action, applicants state that adenosine does not cause cell
`
`proliferation of dermal cells, but the application provides no experimental evidence to show
`
`whether there is an increase or decrease in the cell proliferation. Applicants now provide that
`
`evidence. As described in the Declaration, applicants conducted tests of skin fibroblast cells, c
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 4 of 15 PageID #: 380
`
`Applicant: .James G. Dobson,.. .... and Michael F.
`Ethier
`Serial No. : 09/672,348
`Filed
`September 28, 2000
`3'
`Page
`
`Attorney's Docket, ,0.: 07917-0450021 (UMMC 97-
`•
`3~
`
`which make up a significant portion of dermal cells, from two different donors (an 84 year-old
`man and 30 year-old female), with varying concentrations of adenosine (10-4 or 10-5 M). The
`
`added adenosine had no significant effect on cell proliferation over a 5 day period, i.e." the
`adenosine did not increase cell proliferation at concentrations of 10-4 or 10-5 M (see Declaration,
`
`paragraph 3).
`
`Although applicants believe that claim 70 as written covers this result by functional
`
`.
`
`language, in the interests of moving this application towards allowance, they have proposed to
`
`amend claim 70 to reflect this experimental result. Based on this new information, applicants
`
`request the Examiner to reconsider and withdraw this rejection under Section 112, first
`
`paragraph.
`
`As for the Office's assertion that "it is well ,known in the art that adenosine stimulates
`
`proliferation of cells, such as endoth~lial cells or in particular cells in the skin" based on German
`
`patent DE 19545107, applicants will discuss this reference in more detail below in relation to the
`
`alleged anticipation.
`
`35 U.S.C. § 102
`
`Claims 70, 74 to 76, and 78 have been rejected as allegedly anticipated by DE 19545109
`
`(the German patent application). Applicants traverse this rejection in view of the ne,w data
`
`described in the enclosed Declaration.
`
`According to the Office Action, the German patent application "discloses a cosmetic and
`
`dermatological preparation containing adenosine for the treatment of natural, chemical induced
`
`or UV -induced skin aging and its sequelae. While DE states that adenosine stimulates cell
`
`proliferation, DE does not state that adenosine increases cell proliferation .. ,. Accordingly, DE
`
`anticipates the instant method" (Office Action, page 4). Applicants submit that this rejection is
`
`base,d on information in the German patent application that contradicts applicants' test results,
`
`and request the Examiner to reconsider this rejection in view of applicants testing, the
`
`Declaration, and the following comments.
`
`Applicants have obtained a translation of the German patent application, which is
`
`attached to the Declaration as Exhibit B. Applicants' comments in their Declaration and here are
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 5 of 15 PageID #: 381
`
`· Applicant
`Ethier
`Serial No. :
`Filed
`Page
`
`James G. Dobson, •.. and Michael F.
`
`Attorney's Dockel
`
`.0.: 07917-0450021 (UMMC 97-
`32)
`
`,
`09/672,348
`September 28, 2000
`4
`.
`
`based on this translation. As the Examiner has noted, 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, applicants' claims require no increase in dermal cell proliferation, because such
`
`excess cell proliferation can cause scarring, discoloration, and a variety of other skin anomalies
`
`associated with hyperplasia. See, Declaration at paragraph 2.
`
`Furthermore, applicants' testing, as described above, has shown that low concentrations
`
`of adenosine do not increase dermal cell proliferation. Thus, when the German patent
`
`application states that concentrations of adenosine as low as 0.001 % can be used for increasing
`
`cell proliferation, the German patent application must be mistaken in that adenosine was not
`
`likely actually administered at this low concentrati,on. There is. one paragraph in the German
`
`patent application that recites the 0.0,01 % number, and this is in an extremely broad range from
`
`0.001 to 10% by weight of a cosmetic composition (at page 9, 4th full paragraph). Other
`
`sections of the German patent application recite higher concentrations for a lower limit of
`
`adenosine. For example, the claims, recite 0.01 to 10%, with a preferred concentration of 0.1 to
`
`6%. More importantly, each of the six Examples at pages 9 to 12 in the translation lists a
`
`relatively high concentration of 0.1 % adenosine. See also the Declaration at paragraph 5.
`
`Thus, based on applicants' test results, applicants submit that the extremely ~road range
`
`of adenosine concentrations listed in the German patent application is not supported by reality.
`~-rhe 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 10-5 M concentrations recited in the claims of the present
`'-'
`application. However, the presently claimed invention is based on the demonstration that the
`
`)
`
`recited concentrations of adenosine do not increase cell proliferation. This is the exact opposite
`
`of the assertions in the German patent application. It is for these reasons that the German patent
`
`application 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 proposed
`
`claims in the present application. See Declaration, paragraph 5.
`
`In addition, applicants submit that the dependent claims 74 to 76, and 78 are also not
`
`anticipated for the same reasons discussed above for independent claim 70. Thus, applicants
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 6 of 15 PageID #: 382
`
`ApIDlicant :
`Ethier
`Serial No. :
`Filed
`Page
`
`James G. Dobson, J •• and Michael F.
`
`Attorney's Docket. ,J.: 07917-0450021 (UMMC 97-
`32)
`
`09/672,348
`September 28, 2000
`5
`'
`
`respectfully request that the Ex~ip.er reconsider and withdraw the rejection of the claims in
`
`view of the German patent application.
`
`Next, claims 70 and 76 have been rejected as being allegedly anticipated by Hartzshtark
`
`et al. (Experentia, 1985). Applicants disagree for the following reasons.
`
`According to the Office Action, Hartzshtark discloses that the application of adenosine
`
`along with isoproterenol bitartarate, terbutaline sulfate, papavarine etc., reduced the degree of
`
`skin indentation, which is an indication ofa firmer and younger skin (Office Action, page 4).
`
`The Examiner concedes that Hartzshtark does not discuss whether the addition of adenosine
`
`(ncreases or decreases cell proliferation, but states, "[a]bsent showing evidence on the contrary, it
`
`is the position of the examiner that adenosine treatment of Hartzshtark et aI, does not increase the
`
`stimulation of dermal cell proliferation and therefore, Hartzshtark et al. anticipates the instant
`
`method" (Office Action, pages 4-5).
`
`As discussed above, applicants have demonstrated that certain low concentrations of
`
`adenosine do not increase cell proliferation. In the enclosed Declaration, applicants describe
`
`their review of the two main prior art references, and the testing they have done that supports the
`
`present claims.
`
`Hartzshtark states that certain concentrations of various agents, including adenosine,
`
`increase skin cyclic-AMP content and thus cause a decrease in skin indentation. Specifically,
`
`Hartzshtark indicates in the Table on page 379 that the adenosine concentration effective to
`reduce indentation was 0.1 % (3.8 x 10-3 M), but also notes that they tested adenosine "at one-
`•
`third of the concentrations shown in the table [e.g., about 1.27 x 10-3 M], and at this level
`
`[adenosine was] ineffective" (bottom of page 378 to top of page 379). Applicants discuss these
`
`results of Hartzshtark in their Declaration, at paragraph 4.
`
`The proposed amended claims would recite a maximum concentration of adenosine of
`10-4 M. The results in Hartzshtark indicate that a concentration of adenosine of 10-4 M or lower
`would be even less effective than one-third of 0.1 % (1.27 x 10-3 M), which was ineffective in
`
`their testing. See Declaration, paragraph 4., Thus, Hartzshtark does not anticipate claim 70 as
`
`amended, and does not anticipate dependent claim 76, which depends from claim 70.
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 7 of 15 PageID #: 383
`
`Applicant :
`Ethier
`Serial No. :
`Filed
`Page
`
`James G. Dobs~m, ... and Michael F.
`
`Attorney's Docket. J.: 07917-045002/ (UMMC 97·
`32)
`
`09/672,348
`September 28, 2000
`6
`.
`
`35 U.S.C § 1'03
`Claims 70 and 72 to 78 have been rejected as allegedly obvious over the combination of
`
`the German patent application and Hartzshtark. Applicants traverse this rejection for the reasons
`
`stated above and as follows.
`
`The Office Action states that "[n]either reference discloses the exact amounts of
`
`adenosine," but concludes that "it would have been obvious for a skilled artisan at the time of the
`
`instant invention to optimize the amounts of adenosine such that the cAMP levels of skin
`
`increase and thus contribute for the reduced skin indentation and hence a firmer skin" (Office
`
`Action, page 5).
`
`As discussed above, Hartzshtark indicates that adenosine was effective at a concentration
`of 0.1 %, which is 3.8 x 10-3 M. However, when they tested adenosine at a lower concentration,
`at one-third of 0.1 %, there was no effect. Thus, applicants submit that one skilled in this field
`
`would not have "optimized" the concentrations described in Hartzshtark to lower them even
`
`further. Thus, there would have been no suggestion or motivation in any of the cited references
`for one of skill in this field to us~ a maximum concentration of 10-4 M adenosine as recited in
`applicants' claim 70. Thus, claim 70, and dependent claims 72 to 78, are not obviollS in view of
`
`the cited prior art.
`
`Claim 71 has been rejected as being allegedly unpatentable over a combination of the
`German patent application of DE 1955107 and Hartzshtark in view of Brown, U.S. Patent No.
`
`5,618,544 ("Brown"). Similarly, claims 78 and 79 have been rejected as obvious over the
`
`combination of the German patent application and Hartzshtark in view of Porter, U.S. Patent No.
`
`5,785,978 ("Porter").
`Claims 71, 78, and 79 depend from claim 70, which is patentable for all the reasons
`
`discussed above. Thus, these dependent claims are also patentable. However, applicants note
`
`further that Brown's suggestion to apply epidermal and fibroblast growth factors to the skin
`
`would not lead one of skill in the art to avoid an increase in cell proliferation, as recited in
`
`applicants' claims, because these growth factors are known to increase cell proliferation (Brown'
`
`notes that these factors increase "the rate of cellular replication," at column 3, lines 25-26).
`
`Thus, applicants see no suggestion or motivation to combine Brown with any of the other cited
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 8 of 15 PageID #: 384
`
`N;~licant :
`Ethier
`Serial No. :
`Filed
`Page
`
`James O. Dobson, J •• and Michael F.
`
`Attorney's Docket
`
`.J.: 07917-0450021 (UMMC 97·
`32)
`
`091672,348
`September 28, 2000
`7
`
`references, and even if such a combination were made, one would not have achieved the claimed
`
`invention.
`As for Porter, if one of skill.in the art were to use the trans dermal patch that this patent
`
`describes, the dosage of adenosine would, according to the cited prior art, cause an increase in
`
`. skin cell proliferation andlor provide a higher concentration of adenosine than 'recited in
`
`applicants' claims. Thus, applicants submit that even if Porter were combined with the German
`
`o '
`
`•
`
`patent application or Hartzshtark, the result would not be the presently churned invention.
`
`CONCLUSION
`
`Attached is a marked-up version of the changes being made by the current amendment.
`
`Applicants request that the proposed claim amendment be entered and that all pending
`
`claims then be allowed. No excess claims fee is required. Applicantsenclose a $55.00 check
`
`and a Petition for Extension of Time. Please apply any other charges or credits to Deposit
`
`Account No. 06-1050; referencing Attorney Docket No. 07917-045002.
`
`Respectfully submitted,
`
`er Fasse
`1.
`Reg. No. 32,983
`
`Date: ___ /)_:2._-_I/_-_tJ_Z-___ _
`
`Fish & Richardson P.C.
`225 Franklin Street
`Boston, Massachusetts 02110-2804
`Telephone: (617) 542-5070
`Facsimile: (617) 542-8906
`
`70021823.doc
`
`c,
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 9 of 15 PageID #: 385
`
`Ap';'>licant
`Ethier
`Serial No. :
`Filed
`'
`Page
`
`James O. Dobson, J •• and Michael F.
`
`Attorney's Docket .. J.: 07917-0450021 (UMMC 97-
`32)
`
`09/672,348
`September 28, 2000
`8
`.
`
`Version with Markin2;s to Show Chan2;es Made
`
`In the claims:
`
`Claims 54 to 69 have been cancelled as directed to a non-elected invention.
`
`Claim 70 has been amended as follows.
`
`70. (Amended) A method for enhancing the condition of unbroken skin of a mammal by
`
`~educing one or more of wrinkling, roughness, dryness, or laxity of the skin, without increasing
`
`dermal cell proliferation, 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.
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 10 of 15 PageID #: 386
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 10 of 15 PageID #: 386
`
`EXHIBIT B
`
`EXHIBIT B
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 11 of 15 PageID #: 387
`
`03/12/02 TUE 13: 15 F~ 16175428906
`
`~ 003
`
`.
`
`("
`
`Anomey's DOcketN("7917-04S0021 (UMMC 97-32)
`
`.
`.
`/J~
`IN THE UNITED STATES PATENT AND TRADEMARK OFFI~ r£
`
`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").
`
`- 2. The present application claims methods ofcnhancing the condition of unbroken skin
`
`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.,
`
`Experentia, 41 :378-379 (1985) ("Hartzshtark et a1.). We have reviewed these two references,
`
`and based on a careful review of the references and our experimental test results, we believe that
`
`they do not disclose the methods c:laimed in our present application.
`
`3. We have conducted testing to show that an important feature of OUT claimed methods
`
`is correct, i.e., that concentrations of adenosine recited in the pending claims do not increase
`
`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
`
`Feb,rU*l ,3 I 2..t1lJ 1.
`~ l/"'-.
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 12 of 15 PageID #: 388
`
`03/12/02 TUE 13; 15 'FAX 16175428906'
`
`APplicant:
`Ethier
`Serial No. :
`Filed
`Page
`
`James G. DOb$on,l,..nd Mjchael F,
`
`09/672,348
`September 28, 2000
`2
`
`AnOmeY'5DOCke('''.' 07917-0450021 (UMMC 97~
`32)
`
`141004
`
`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
`
`matching control dish was treated with vehicle. After 5 days in culture, we counted the total
`
`. number of cells in the control dish, and then in the test dish. For each pair of culture dishes, the
`
`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
`
`increase cell pi,oliferation.
`4. Hartzshtark et a1. states that certain concentrations of various agents, including
`
`a.denosine, increase skin cyclic-AMP content and thus cause a decrease in skin indentation.
`
`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
`
`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 '
`
`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
`
`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
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 13 of 15 PageID #: 389
`
`03/12/02 TUE 13:16 FAX 16175428906
`
`Applicant; James G. DObson,end Michael F.
`Ethier
`Serial No. : 09/672,348
`Filed
`September 28, 2000
`Page
`3
`
`Attorney's Docker) 07917·0450021 (UMMC 97-
`32)
`
`141005
`
`concentrations of adenosine do not increase derma} cell proliferation. Thus, when the German
`
`patent application states that concentrations of adenosine as low as 0.001 % are useful for
`
`increasing cell proliferation, we believe that the German patent application must be mjstaken.
`
`There is one paragraph in the German patent application that states the 0.001 % number, and this
`
`is in a very broad range from 0.001 to 10% by weight of a cosmetic compositi!Jn (at page 9, 4th
`
`'full paragraph). Other sections ofthe German patent appJjcation recite higher concentrations.
`
`For example. the claims, recite 0.01 to 10%, with a preferred concentration of 0.1 to 6%. More
`
`importantly, each of the six Examples lists a relatively high concentration of 0.1 % adenosine.
`
`Thus, based on our own testing,o/skin fibroblasts, which make up a large part of the dermis, we
`
`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
`
`recited in the claims ofthe present application. However, our claimed invention is based on the
`
`demonstration that the recited concentrations of adenosine do not increase cell proliferation.
`
`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.
`
`We further dec::lare that all statements made herein of our knowledge are true and that all
`.
`,
`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
`
`punishable by fine or imprisonment, 'or both, under Section 1001 of Title 18 of the United States
`
`Code and that such willful false statements may jeopardize the validity of the application or any
`
`patent issuing thereon.
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 14 of 15 PageID #: 390
`
`03/12/02 TUB 13:16 FAX 16175428906
`Applicant; lame; G. Dobson,C\d Michael F.
`Ethier
`Serial No. :
`Filed
`Page
`
`09/672,348
`September 28, 2000
`4
`-
`
`Attorney's DOCker-) 07917·045002/ (UMMC 97-
`32)
`
`141006
`
`Date:
`
`de:; /11!d ci
`
`Date:~_"Z __ /_·\'......;\ I_D_2.. ____ _
`
`20387642.doc
`
`.J.~
`
`MIchael F.·
`
`ier, Ph,D .
`
`
`
`Case 1:17-cv-00868-JFB-SRF Document 18-1 Filed 08/23/17 Page 15 of 15 PageID #: 391
`
`03/~2/02 TUB 13:15 FAX 16175428906
`
`U
`
`Attorney's Docket 1" )7917-045002 I (UMMC 97-32)
`
`141 002
`
`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.
`
`Applicants submit herewith the signed declaration for entry into the file along with the response.
`
`No fees arc believed dUte. However, please apply any charges or credits to Deposit
`
`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
`
`CERTIFICATE OF MAl UNO BY FIRST CLASS MAIL
`
`