Amend fd: 11-13-2019
`
`Reply to 06-25—2019 OA
`
`Remarks
`
`Status of the Claims
`
`— 10 -
`
`Murase et a].
`
`Appl. No. 16/075,828
`
`Claims are 1-21 are pending. Claims 1-11, 13-15, 17—19 and 21 are withdrawn.
`
`Claims 12, 16 and 20 are active.
`
`The Amendments
`
`Support for the amendment to claim 12 is found, inter alia, at specification page
`
`22 (first and last paragraphs) and page 23 (first paragraph).
`
`Support for amending withdrawn claims 1-4 and 8 to refer to a “pharmaceutically
`
`acceptable carrier” is found, inter alia, in specification 1] [0042] on page 20.
`
`Support for amending active claim 12 and withdrawn claims 1-4, 10, 11 and 13 to
`
`refer to an effective amount is found, inter alia, in specification fl [0051] on page 28.
`
`No new matter has been added by any of the amendments.
`
`The Rejections
`
`Reconsideration of the application is respectfully requested.
`
`The Indefiniteness Rejections
`
`At Office action pages 4-7, claims 12, 16 and 20 are rejected as being indefinite.
`
`Applicant respectfully traverses these rejections.
`
`2537.1600002/MAC
`
`

`

`Amend fd: 11-13-2019
`
`Reply to 06—25—2019 OA
`
`“In need thereof”
`
`- 11 -
`
`Murase et a].
`
`Appl. No. 16/075,828
`
`The pending claims refer to a “subject in need thereof.” At Office action paragraph
`
`14, Examiner states that any person qualifies as a “subject in need thereof.”
`
`In the interests of advancing prosecution, claim 12 has been amended to recite that
`
`the subject desires to darken the subject’s skin or hair color at the site at which the
`
`compound(s) is applied. Support for this amendment is found, inter alia, on specification
`
`page 22, last paragraph, where the specification refers to the subject as being preferably a
`
`human who desires to produce the recited effect, for example, darkening the skin.
`
`“Ingesting”
`
`At Office action paragraph 22, Examiner states that “ingesting” is considered to
`
`encompass intravenous administration, topical administration and subcutaneous
`
`administration. In the interests of advancing prosecution, the claims have been amended to
`
`refer to “externally” applying or to an external preparation. Therefore, this rejection is
`
`believed to be moot.
`
`Claim 20
`
`Claim 20 is rejected for insufficient antecedent basis in reciting “when applied as an
`
`external preparation .
`
`.
`
`. .” Examiner notes that claim 20 depends from claim 12 and claim
`
`12 refers to “ingesting” the compound in an effective amount. In the interests of advancing
`
`prosecution, claim 12 (from which claim 20 depends) has been amended to refer to
`
`2537.1600002/MAC
`
`

`

`Amend fd: 11-13-2019
`
`Reply to 06-25-2019 OA
`
`— 12 -
`
`Murase et al.
`
`Appl. No. 16/075,828
`
`“externally applying” instead of “ingesting.” The phrase “as an external preparation” in
`
`claim 20 has been canceled because it is believed to be moot in View of the amendment to
`
`claim 12. Therefore, this rejection is believed to be moot.
`
`The First Novelty Rejection
`
`At Office action page 8, claims 12 and 16 are rejected as being anticipated by
`
`Reactions 1499: 8. This is an abstract of an article published in full as Amelot, A. er al.,
`
`”Phototoxic reaction associated with Malarone (atovaquone/proguanil) antimalarial
`
`prophylaxis.” J. Derm. 41 :346-348 (April 2014). Applicant respectfully traverses this
`
`rejection.
`
`Independent claim 12 has been amended to refer to “externally applying.” As noted
`
`in the “Reactions” abstract,
`
`the route by which the Malarone drug was taken was not stated
`
`in the article. According, the “Reactions” abstract does not detract from the novelty of the
`
`invention.
`
`The Second Novelty Rejection
`
`At Office action page 9, claim 12 is rejected as being anticipated by Browne et al.,
`
`Brit. Med. Journal 5225 : 5 50-5 51 (1961). Applicant respectfully traverses this rejection.
`
`As reported by Browne, the patient discussed in Case 1 took aspirin, mepacrine and
`
`proguanil (page 551, col. 1, “Previous History”). The route of administration is not stated.
`
`2537.1600002/MAC
`
`

`

`Amend fd: 11—13—2019
`Reply to 06-25-2019 OA
`
`- 13 -
`
`Murase et a1.
`Appl. No. 16/075,828
`
`In trying to find the causative agent for the patient’s epidermal necrolysis, a “patch
`
`test” was performed with “all of the drugs” the patient had taken (page 551, col. 1,
`
`“Subsequent History”). The results of the patch tests for aspirin, mepacrine and proguanil
`
`were negative.
`
`In the interests of advancing prosecution, independent claim 12 has been amended to
`
`recite “darkening the subject’s skin or hair color at [the application] site as a result of the
`
`applying.” Browne does not disclose the claim element that recites “darkening that the skin
`
`or hair color as a result of the applying” because the patch test for proguanil in Browne was
`
`negative. Also, Browne does not disclose that the subject desires to darken the subject’s skin
`
`or hair color at the application site. Accordingly, Browne does not detract from the novelty
`
`of the claimed invention and this rejection can be withdrawn.
`
`The Obviousness Rejection
`
`At Office action page 10, claims 12, 16 and 20 are rejected as being unpatentable
`
`over the combination of Van Neste er a1 (Micron 35:193-200 (2004), Hue et al., (FR
`
`2901133 A1; published November 23, 2007) and Chulay (US 6,413,993; published July 2,
`
`2002). Applicant respectfully traverses this rejection.
`
`Preliminarily, Examiner is respectfully asked to note that, as shown on the cover
`
`page of the document, the first named inventor of FR 2901133 A1 is “Breton,” not Hue.
`
`“Hue” is the last named inventor of FR 2901133 A1. To avoid confusion though, in the
`
`discussion below, FR 2901133 A1 is referred to as “Hue” as in the Office action.
`
`2537.1600002/MAC
`
`

`

`Amend fd: 11-13-2019
`Reply to 06—25-2019 0A
`
`— 14 -
`
`Murase et a].
`App]. No. 16/075,828
`
`Van Neste is focused on hair follicle melanogenesis. Examiner relies on Van Neste,
`
`inter alia, as evidence that the loss of skin color and hair graying occurs with age, and that
`
`people who are aging represent subjects in need of darkening skin and hair. Proguanil is not
`
`mentioned.
`
`Hue is relied on as teaching treating aging skin and hair, and promoting keratinocyte
`
`proliferation, by administering a glycolysis inducer (proguanil) to “control differentiation”
`
`of epidermal cells and to increase proliferation of young keratinocyte cells.
`
`Hue discloses that inducing glycolysis in epidermal cells limits the ability of
`
`epidermal cells to differentiate, and specifically, limits the differentiation of keratinocytes.
`
`As a result, by inducing glycolysis, a basal pool of “young,” proliferating keratinocytes can
`
`be maintained in the skin. At translation page 3, first paragraph, Hue states:
`
`By limiting and / or delaying the passage of the cells in the
`differentiation phase, the pool of young cells is maintained. It
`is therefore important to preserve this pool of proliferative
`cells, avoiding or delaying their differentiation, in order to
`help delay the appearance of signs of aging.
`
`Hue does not suggest that Hue’s method darkens skin or hair or that it has any effect
`
`on skin or hair darkening. Instead, the compositions are said to be intended to prevent or
`
`reduce wrinkles, fine lines, thinning of the skin, “against soft,” faded skin, hair loss
`
`“promoting the hair follicle” alopecia, etc. (translation page 9). Hue mentions melanocytes
`
`only once, in the background of the invention. Melanocytes are listed as being one of three
`
`types of epidermis cells: keratinocytes, melanocytes and Langerhans cells. Hue does not
`
`suggest that melanosomes have any effect on keratinocytes.
`
`2537.1600002/MAC
`
`

`

`Amend fd: 11-13-2019
`
`Reply to 06-25-2019 OA
`
`- 15 -
`
`Murase et a].
`
`Appl. No. 16/075,828
`
`Chulay discloses the use of a composition that comprises proguanil and other active
`
`agents for the treatment of malaria. The composition can be taken internally or applied to the
`
`skin. Chulay is relied on as evidence that the disclosed doses of proguanil are known to be
`
`safe and effective.
`
`In Office action 1i 47, Examiner concludes that it would have been primafacie
`
`obvious to administer proguanil to aging patients who are in need of treating aging skin and
`
`hair in View of Van Neste and Hue in order to arrive at the instantly claimed methodology.
`
`Examiner states that motivation to administer proguanil flows logically from the fact that
`
`proguanil was recognized in the art to effectively treat chronobiologically aging skin and
`
`hair, dry skin and the promotion of keratinocyte proliferation and promoting the levels of
`
`hair follicles. Examiner views the property such as darkening the hair or skin as a
`
`characteristic feature of the claimed process of administering proguanil.
`
`Reconsideration is respectfully requested. Claim 12 has been amended to recite that
`
`the compound(s), such as proguanil, is applied externally to a site on the skin where the
`
`subject desires to darken the skin or hair at that site. As shown below,
`
`the property such as
`
`darkening skin or hair cannot be considered to be a characteristic feature of the process of
`
`administering proguanil that was known or suggested in the art.
`
`Examiner’s attention is respectfiilly to an article by Choi et al., ”Melanosome uptake
`
`is associated with the proliferation and differentiation of keratinocytes,” Arch Dermatol Res
`
`2537.1600002/MAC
`
`

`

`Amend fd: 11-13-2019
`
`Reply to 06-25-2019 OA
`
`— 16 -
`
`Murase et al.
`
`Appl. No. 16/075,828
`
`2014, 306:59-66. (A copy of Choi is submitted as document NPL9 in the accompanying
`
`IDS.)
`
`It should be recalled that melanocytes produce melanosomes. The melanosomes are
`
`transferred from melanocytes to neighboring keratinocytes, thus pigmenting those
`
`keratinocytes. Therefore, conditions that promote the transfer of melanosomes into
`
`keratinocytes are desired if one wants to darken skin or hair keratinocytes.
`
`Choi examined melanosome uptake in differentiating and in proliferating
`
`keratinocytes. In the abstract, Choi summarizes the results stating:
`
`o
`
`“melanosome uptake was higher in differentiating keratinocfles compared to
`
`non-differentiating keratinocytes”; and
`
`o melanosomes inhibit keratinocyte proliferation.
`
`These effects of melanosomes are the opposite of the effects of proguanil as reported
`
`by Hue. The combination of the cited art does not suggest or lead to the conclusion that
`
`darkening skin or hair is a natural result or characteristic feature that flows from
`
`administering proguanil. In fact, Hue’s teachings are inconsistent with an expectation of
`
`darkening skin or hair because Hue teaches proguanil will “limit and/or delay” the passage
`
`of keratinocyte cells into the differentiation phase and maintain them in the proliferative
`
`stage — thus opposing the effects that melanosomes would be inducing in the keratinocyte
`
`population.
`
`The results of two competing mechanisms on the keratinocytes population,
`
`2537.1600002/MAC
`
`

`

`Amend fd: 11-13-2019
`Reply to 06-25—2019 OA
`
`- l7 -
`
`Murase et a1.
`Appl. No. 16/075,828
`
`that is, the presence of both a glycolysis inducer such as pro guanil and the presence of
`
`melanosomes could not have been predicted.
`
`The discussion above shows that the artisan did not have a reasonable expectation of
`
`success in reaching an invention in which the skin or hair is darkened by administration of
`
`proguanil based on the teachings of Hue, Van Neste and Chulay. The rational underpinning
`
`of the articulated reasoning presented by Examiner does not support the legal conclusion of
`
`obviousness. The evidence of record, and above, establishes that the invention, even if
`
`characterized as a combination of familiar elements, yields more than predictable results.
`
`Primafacie obvious is not established, or, if it has been established, it has been
`
`overcome. Accordingly, this rejection can be Withdrawn.
`
`Conclusion
`
`It is respectfially believed this application is now in condition for allowance.
`
`Early notice to this effect is earnestly solicited.
`
`It is not believed that extensions of time
`
`or additional fees are required, beyond those that may otherwise be provided for in
`
`accompanying documents. Any required fees are hereby authorized to be charged to our
`
`Deposit Account No. 19-0036. If additional extensions of time are necessary to prevent
`
`abandonment of this application, then such extensions of time are hereby petitioned under
`
`37 C.F.R. § 1.136(a).
`
`2537.1600002/MAC
`
`

`

`Amend fd: 11-13-2019
`Reply to 06-25-2019 OA
`
`- 18 -
`
`Murase et al.
`Appl. No. 16/075,828
`
`Respectfully submitted,
`
`STERNE, KESSLER, GOLDSTEIN & Fox P.L.L.C.
`
`Michele A. Cimbala
`
`’“" L“
`
`Attorney for Applicant
`Registration No. 33,851
`
`Date: Warm/W 23% § 11»; 2.23 g a
`1100 New York Avenue, NW.
`Washington, DC. 20005—3934
`(202) 371-2600
`
`l36ll701.1
`
`2537‘1600002/MAC
`
`

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.