Ex Parte Macchi

Patent Trial and Appeal Board

Sep 10, 2015

10561670 (P.T.A.B. Sep. 10, 2015)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/561,670 12/19/2005 Franco Macchi 207,380 5848
7590 09/10/2015
Jay S Cinamon
Abelman Frayne & Schwab
10th floor
666 Third Avenue
New York, NY 10017
EXAMINER
JIANG, SHAOJIA A
ART UNIT PAPER NUMBER
1673
MAIL DATE DELIVERY MODE
09/10/2015 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte FRANCO MACCHI1
__________

Appeal 2012-009666
Application 10/561,670
Technology Center 1600
__________

Before DONALD E. ADAMS, ERIC B. GRIMES, and MELANIE L.
McCOLLUM, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
recurrent oral aphthous ulcers treatment method. The Examiner has rejected
the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
affirm.

STATEMENT OF THE CASE
Claims 7–13 are pending and on appeal (Br. 5 & 8). Claim 7 is
representative and reads as follows:

1 Appellant identifies the real party in interest as Bioplax Limited (Br. 3).
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7. A method for the treatment of Recurrent Oral Aphthous Ulcers
(ROAU) comprising administering, as the sole active ingredient, hyaluronic
acid or a salt thereof, having an average molecular weight comprised
between 800,000 and 4,000,000, to a subject in need thereof.
Claims 7–13 stand rejected under 35 U.S.C. § 103(a) as obvious over
Di Schiena2 in view of Saxen3 (Ans. 4).
The Examiner relies on Di Schiena for teaching “pharmaceutical
compositions comprising 0.2 to 10% sodium hyaluronate having molecular
weight between 800,000-4,000,000, preferably 1,000,000-2,000,000 . . . for
the treatment and prophylaxis of inflammatory affections of the oral cavity”
(id. at 4–5). However, the Examiner finds that “Di Schiena does not
exemplify the treatment of recurrent oral aphthous ulcers using the
composition” (id. at 5).
The Examiner relies on Saxen for teaching “that recurrent aphthous
ulcers are a common disorder, causing pain derived from inflammatory
sensitization of nerve endings” (id.). In particular, the Examiner finds that
Saxen teaches:
Adults having aphthous ulcers were treated with 3% diclofenac
in 2.5% hyaluronan, 2.5% hyaluronan, or 3% viscous lidocaine.
A 48% reduction in pain was observed 10 minutes after
application with no significant difference between the three
topical agents . . . . Ulcers were smaller after treatment with
[hyaluronan] . . . . The blunting action of hyaluronan may be
due to the coating action over the ulcer . . . , and the protective

2 Di Schiena, EP 0 444 492 A1, Sept. 4, 1991.
3 Mark A. Saxen et al., Sustained Relief of Oral Aphthous Ulcer Pain from
Topical Diclofenac in Hyaluronan, 84 ORAL SURG. ORAL MED. ORAL
PATHOL. ORAL RADIOL. ENDOD. 356–61 (1997).
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layering of the ulcer was a significant component of the overall
treatment effect.
(Id.) The Examiner concludes that it would have been obvious “to use Di
Schiena’s composition for the treatment of recurrent aphthous ulcers of
Saxen” (id.).

FINDINGS OF FACT
1. The Specification discloses “a double blind, single centre,
parallel group design to determine the efficacy of a gel formulation
[containing hyaluronic acid] in relieving the symptoms in subjects with
recurrent oral aphthous ulceration” (Spec. 4 & 6).
2. The Specification also discloses that the study involved
application of the hyaluronic acid gel or placebo 2–3 times daily for seven
days (id. at 6–7).
3. In addition, the Specification discloses that, in this study, the
primary efficacy parameter was the patients’ discomfort/soreness scores
during the first hour post initial application and the secondary efficacy
parameter was the patients’ overall assessment of the gel at the end of seven
days (id. at 7–8).
4. The Specification also discloses “that if compared to placebo
composition the gel composition containing hyaluronic acid proved able to
reduce significantly the number of ulcers already in the fifth day, and also
evidenced an overall beneficial effect in every investigated [recurrent oral
aphthous ulcers] symtphomatology [sic]” (id. at 8).
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5. Di Schiena discloses:
It has now been surprisingly found that hyaluronic acid in
sodium salt form and characterised by a molecular weight of
between 800,000 and 4,000,000 . . . can be used as active
principle in the preparation of pharmaceutical compositions for
topical administration in the treatment and prophylaxis of
inflammatory affections [sic, afflictions?] of the oral cavity.
(Di Schiena 2: 45–48.)
6. Di Schiena also discloses: “The compositions according to the
present invention for therapeutic use are advantageously used for gingival
affections, characterised by inflammatory manifestations of the gingival
tissue, such as gingivitis, stomatitis, irritations due to mechanical causes
such as fixed or mobile prostheses or surgical operations etc.” (Id. at 3: 14–
17.)
7. In addition, Di Schiena discloses:
The chosen patients showed various degrees of
parodontal pathology. The first group comprising 6 patients
suffered from simple marginal gingivitis, whereas the second
group comprising the remaining 4 patients had undergone
parodontal surgery.
With the first group it was noted that the topical use of
the gingival paste containing hyaluronic acid resulted always by
the second day in a reduction in symptomatology, characterised
essentially by hypersensitivity to heat stimuli and slight
bleeding on brushing, with complete recovery within one week.
With the second group examined, recovery was slower
due essentially to the fact that a surgical wound was present
which alone required about one week for recovery.
For this reason the compound was applied only during
the latter stages of recovery mainly because the wound was
protected by a parodontal compress. A clear improvement in
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condition was also noted in this group, to the extent that on
termination of treatment the mucosa at the wound level was
trophic and pink-coloured.
In conclusion the product was of considerable help in
recovery, in that with the first group it participated in normal
oral hygiene and with the second group it facilitated the normal
physiological reparation [sic] processes.
(Id. at 5: 3–17.)
8. Saxen discloses that “[r]ecurrent aphthous ulcers are a common
disorder . . . , which typically manifest as a small erosion of the epidermal
layer of the nonkeratinized oral mucosa” (Saxen 356).
9. Saxen also discloses:
The pain of aphthous ulcers derives from inflammatory
sensitization of small diameter afferent nerve endings that form
a plexus at the junction of the epithelial and subepithelial
layers. Branches of this plexus extend upward, into the
epithelial layer; thus, aphthous ulceration produces a
superficial, focal, inflammatory lesion that is directly associated
with sensory nerve endings.
(Id.)
10. In addition, Saxen discloses:
A randomized, double-blind, single dose study of 60 healthy
adults with aphthous ulcers in three treatment groups—3%
diclofenac in 2.5% hyaluronan, 2.5% hyaluronan, 3% viscous
lidocaine—was undertaken. Visual analogue scale pain scores
were obtained before and after gel application and hourly, for
up to 8 hours after gel application. . . . A 48% overall reduction
in pain (p < 0.01) was observed 10 minutes after gel
application; however, no significant difference was found
between the three topical agents.
(Id.)
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11. Saxen also discloses: “A highly significant treatment effect
was observed (p = 0.01) in which diclofenac/hyaluronan was significantly
better than lidocaine or hyaluronan alone at 2 through 6 hours after
application. Neither lidocaine nor hyaluronan were significantly different
from baseline pain level at 1 through 8 hours after application.” (Id. at 359.)
12. In addition, Saxen discloses that the “blunting action of
hyaluronan, an agent with no known analgesic or anesthetic activity, is
probably due to the coating action over the ulcer” (id. at 360).
13. Saxen states that, in light of the similar properties of hyaluronic
acid and carboxymethylcellulose (the vehicle for lidocaine in its study), “one
could postulate that protective layering of the ulcer was a significant
component of the overall treatment effect” (id.).
14. Nolan,4 submitted by Appellant, discloses that “[p]atients
treated with topical [hyaluronic acid] recorded few ulcers on day 5 of the
investigation than those treated with placebo (P < 0.001)” (Nolan, Abstract).

ANALYSIS
Di Schiena discloses the use of “hyaluronic acid in sodium salt form
and characterised by a molecular weight of between 800,000 and 4,000,000
. . . as active principle in the preparation of pharmaceutical compositions for
topical administration in the treatment and prophylaxis of inflammatory
affections [sic, afflictions?] of the oral cavity” (Finding of Fact (FF) 5).

4 A. Nolan et al., The Efficacy of Topical Hyaluronic Acid in the
Management of Recurrent Aphthous Ulceration, 35 J. ORAL PATHOL. MED.
461–65 (2006).
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Saxen discloses that recurrent oral aphthous ulcers is an inflammatory
affliction of the oral cavity (FF 8–9). In view of these teachings, we
conclude that the Examiner has set forth a prima facie case that it would
have been obvious to use Di Schiena’s composition to treat recurrent oral
aphthous ulcers.
Appellant argues, however, that “Recurrent Aphthous Stomatitis
(RAS), also know[n] as . . . Recurrent Oral Aphthous Ulceration (ROAU)[,]
is a clinical condition, a disease . . . that is not an inflammatory disease of
the gingival tissue as gingivitis, but is an idiopathic disease” (Br. 10). We
are not persuaded.
Di Schiena refers generally to the “treatment and prophylaxis of
inflammatory affections of the oral cavity” (FF 5). In addition, Di Schiena
discloses that the compositions “are advantageously used for gingival
affections, characterised by inflammatory manifestations of the gingival
tissue, such as gingivitis, stomatitis, irritations due to mechanical causes
such as fixed or mobile prostheses or surgical operations etc.” (FF 6
(emphasis added).) Thus, although Di Schiena may not specifically recite
ROAU, we agree with the Examiner that it would have been prima facie
obvious to treat ROAU in view of Saxen’s teaching that aphthous ulceration
produces inflammatory lesions (FF 9).
Appellant also argues:
Saxen et al. fail to teach a method of administering solely HA
[hyaluronic acid] for treating ROAU. ROAU is characterized
by episodes of aphthous ulcers for 7-14 days . . . . From a
medical point of view it is of no relevance if Saxen’s treatment
solely with HA is effective for relieving pain for 10 minutes,
because this cannot be a treatment for a pathology characterized
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by 2-4 episodes of formation of aphthous ulcers that typically
persist for 7-14 days.
(Br. 11.) We are not persuaded. Instead, we agree with the Examiner that
the combination of references suggests the use of Di Schiena’s composition
for the treatment of ROAU for the reasons discussed above.
In addition, Appellant argues that “there is no apparent reason to
select, modify and combine the cited art elements in the manner suggested
by the Examiner or otherwise to arrive at the presently claimed invention”
(Br. 13). We are not persuaded. Instead, we agree with the Examiner that
one of ordinary skill in the art would have combined these disclosures in
order to treat ROAU.
Appellant also argues that “the sole use of HA as such has been found
by Saxen et al. to be unsatisfactory for the purposes of the claimed
invention” and that “[t]his consideration would have made any expectation
of success of the method of treating ROAU with HA as the sole active
ingredient fall completely flat, thus teaching away from the content of
claim 7” (Br. 16). We are not persuaded.
Saxen discloses a decrease in pain 10 minutes after application of HA
(FF 10). Saxen also discloses that HA did not provide a significantly
different pain level as compared to baseline pain level 1 hour after
application (FF 11). However, Saxen provides no indication that HA does
not decrease pain between 10 minutes and an hour post application, which is
one of the efficacy parameters relied upon by Appellant (FF 3).
In addition, Di Schiena suggests that HA may actually improve
inflammatory conditions of the oral cavity (FF 6–7). Saxen provides no
indication that HA does not improve ROAU, which is one of the efficacy
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parameters relied upon by Appellant (FF 3–4). Saxen teaches, in fact, that
the coating action of HA may be a “significant component of the overall
treatment effect” (FF 13).
For at least these reasons, we do not agree that Saxen teaches away
from the treatment of ROAU using hyaluronic acid or a salt thereof. In
addition, Appellant has not adequately explained why there would not have
been a reasonable expectation for success.
In particular, Di Schiena discloses the use of “hyaluronic acid in
sodium salt form and characterised by a molecular weight of between
800,000 and 4,000,000 . . . as active principle in the preparation of
pharmaceutical compositions for topical administration in the treatment and
prophylaxis of inflammatory affections of the oral cavity,” such as stomatitis
(FF 5–6). Appellant does not adequately explain why one of ordinary skill
in the art would not have expected it to work on ROAU.
In addition, Appellant argues:
[S]ince Saxen fails to teach that HA is effective in the reduction
of lesion size, the skilled person having read Saxen would,
without doubt, be led to disregard its teachings and would not
be encouraged to use HA for reducing mouth lesions with a
reasonable expectation of achieving the desired result.
(Br. 20.) We are not persuaded.
Saxen discloses a “randomized, double-blind, single dose study of 60
healthy adults with aphthous ulcers” (FF 10 (emphasis added)). Saxen,
however, provides no indication of the effect of multiple applications of HA
over the course of several days, as was described in the present application
(FF 2). Thus, although Saxen may fail to specifically teach that HA is
significantly effective in the reduction of lesion size, we do not agree with
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any implication that one of ordinary skill in the art would have been
discouraged by Saxen from using HA alone in the treatment of ROAU.
Appellant also argues that the claimed invention shows unexpected
results (Br. 15). In particular, Appellant argues that “the claimed method
allows ROAU to be treated successfully as shown in the present application
and in ANNEX 1 [Nolan] filed as further evidence of the results achieved”
(id. at 16). We are not persuaded.
Nolan, as well as the Specification, discloses that “[p]atients treated
with topical [hyaluronic acid] recorded few ulcers on day 5 of the
investigation than those treated with placebo (P < 0.001)” (FF 14 & 4).
However, Di Schiena discloses the use of “hyaluronic acid in sodium salt
form and characterised by a molecular weight of between 800,000 and
4,000,000 . . . as active principle in the preparation of pharmaceutical
compositions for topical administration in the treatment and prophylaxis of
inflammatory affections of the oral cavity” (FF 5). Specifically, Di Schiena
discloses that its “product was of considerable help in recovery” from
gingivitis and parodontal surgery (FF 7). In view of these teachings, we
agree with the Examiner that Appellant has not adequately explained why a
treatment effect for ROAU would have been unexpected (Ans. 7).

CONCLUSION
The evidence supports the Examiner’s conclusion that Di Schiena and
Saxen suggest the method of claim 7. We therefore affirm the obviousness
rejection of claim 7. Claims 8–13 have not been argued separately and
therefore fall with claim 7. 37 C.F.R. § 41.37(c)(1)(vii).
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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

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