Ex Parte Bernstein

Patent Trial and Appeal Board

Aug 6, 2014

12761953 (P.T.A.B. Aug. 6, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte JOEL E. BERNSTEIN
__________

Appeal 2014-000362
Application 12/761,953
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a
composition and method of treating acne vulgaris and acne rosacea. The
Examiner rejected the claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.

1 Appellant identifies the Real Party in Interest as Elorac, Inc. (See
App. Br. 2).
Appeal 2014-000362
Application 12/761,953

2
Statement of the Case
Background
“In an effort to successfully treat acne vulgaris and rosacea, without
risk of serious systemic side effects, nutritional supplements containing high
dosages of nicotinamide (also known as niacinamide) have been employed”
(Spec. 2 ¶ 0004). The Specification teaches that “by combining a high
dosage of nicotinamide with a relatively low dosage of azelaic acid . . . for
oral ingestion, and administering such to patients with acne vulgaris or
rosacea, treatment results comparable to or better than oral antibiotics are
produced without any serious systemic side effects” (Spec. 2 ¶ 0005).
The Claims
Claims 1, 3–6, and 9–11 are on appeal. Claim 1 is representative and
reads as follows:
1. A method of treating acne vulgaris and acne rosacea,
the method comprising administering pharmaceutical
formulations suitable for oral administration wherein the
formulations contain high dosages of nicotinamide
combined with much lower dosages of azelaic acid wherein
high dosages of nicotinamide are in a range of about 100 mg
to 1000 mg per unit dosage of the formulations and lower
dosages of azelaic acid are present in a range of about 1 mg
to 50 mg per unit dosage of the formulations.

The Issue
The Examiner rejected claims 1, 3–6, and 9–11 under 35 U.S.C.
§ 103(a) as obvious over Bernstein ’896,2 Bernstein ’948,3 Sefton,4 Hebert,5
Gupta ’672,6 Gupta ’507,7 Ward,8 and Ansel9 (Ans. 3–11).

2 Bernstein, J., US 4,505,896, issued Mar. 19, 1985.
Appeal 2014-000362
Application 12/761,953

3
The Examiner finds that:
1. The art fairly teaches and suggests oral dosage forms of
nicotinamide and other active agents for treating acne
(Bernstein ‘896).
2. The art fairly teaches and suggests the specific
combination nicotinamide and azelaic acid for treating acne
vulgaris and acne rosacea (Bernstein [’948]).
3. The art fairly teaches and suggests the amount of azelaic
acid to use in methods of treating acne (Sefton).
4. The art fairly teaches and suggests the specific use of
azelaic acid in oral pharmaceutical dosage forms to treat
acne and rosacea (Hebert).
5. The art fairly teaches and suggests glycyrrhetinic acid,
glycyrrhizinic acid, folic acid, vitamins, minerals, zinc,
resveratrol and carbenoxolone in compositions and methods
for the treatment of acne vulgaris and acne rosacea (Gupta
[’762], Gupta ‘507 and Ward et al.).

(Non-Final Rej. 7.) The Examiner finds that “the ordinary artisan
understands that both azelaic acid and nicotinamide are both useful to treat
acne vulgaris and rosacea and can both be formulated for oral administration
and their combination is expected to be more effective than either agent
alone” (Non-Final Rej. 9). The Examiner finds that because “the art of
Sefton teaches using azelaic acid in the range of 0.1 to 30 wt% . . . it is
nothing more than routine optimization of the amount of azelaic acid in the

3 Bernstein, J. US 2005/0169948 A1, published Aug. 4, 2005.
4 Sefton, J., US 6,262,117 B1, issued July 17, 2001.
5 Hebert, R., US 2001/0034321 A1, published Oct. 25, 2001.
6 Gupta, S., US 2004/0081672 A1, published Apr. 29, 2004.
7 Gupta, S., US 2008/0139507 A1, published June 12, 2008.
8 Ward et al., US 2003/0119715 A1, published June 26, 2003.
9 Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery
Systems 122 (1999).
Appeal 2014-000362
Application 12/761,953

4
composition to arrive at the instant amount, in the absence of evidence to the
contrary, to treat acne vulgaris and acne rosacea” (Non-Final Rej. 9).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the combination of Bernstein
’896, Bernstein ’948, Sefton, Hebert, Gupta ’672, Gupta ’507, Ward, and
Ansel render claim 1 obvious?
Findings of Fact
1. Bernstein ’896 teaches that “nicotinic acid and nicotinamide are
useful in the treatment of acne vulgaris by administering a therapeutically
amount either topically or orally” (Bernstein ’896, col. 1, ll. 47–50).
2. Bernstein ’896 teaches that “nicotinamide is administered orally
in doses of 100 to 600 milligrams (mg) per day in divided doses taken 2 to 4
times per day” (Bernstein ’896, col. 2, ll. 5–7).
3. Example 2 of Bernstein ’896 teaches that “100 milligrams of
Nicotinamide . . . was orally administered to a 120 pound, 21 years old,
female patient suffering from acne vulgaris. . . . These daily doses were
required over a period of 14 days to effect a decrease in inflammatory
lesions” (Bernstein ’896, col. 2, ll. 44–50).
4. Bernstein ’896 teaches “[s]olid dosage [forms] for oral
administration where applicable include capsules, tablets, pills, powders and
granules. . . . Liquid dosage forms for oral administration where applicable
include pharmaceutically acceptable emulsions, solutions, suspensions,
syrups, and elixirs” (Bernstein ’896, col. 5, ll. 14–27).
5. Bernstein ’948 teaches a “method of treating acne vulgaris and
acne rosacea comprising applying to the skin of patients afflicted with such
Appeal 2014-000362
Application 12/761,953

5
disorders a topical composition comprising an amount of nicotinamide
combined with less than 1 % by weight of nicotinic acid” (Spec. 1–2,
Bernstein ’948, claim 1).
6. Bernstein ’948 teaches that formulations containing
nicotinamide and small amounts of nicotinic acid “could be combined with
other known chemical agents known to be effective in treating acne and such
resulting formulations would be more effective at treating acne than would
be expected by treatment with the individual agents themselves. Such
formulations include . . . azelaic acid” (Bernstein ’948 1 ¶ 0005).
7. Sefton teaches “a method for treating acne vulgaris by topically
applying a composition of benzoyl peroxide and azelaic acid, serially, in a
therapeutically effective amount” (Sefton, col. 2, ll. 21–24).
8. Sefton teaches that the “amount of the compositions to be
administered will obviously be an effective amount for the desired result
expected therefrom. This, of course, will be ascertained by the ordinary skill
of the practitioner” (Sefton, col. 3, ll. 4–7).
9. Hebert teaches that “[a]zelaic acid has been used clinically for
many years in the treatment of acne vulgaris as well as in hyperpigmentary
skin disorders” (Hebert 1 ¶ 0007).
10. Hebert teaches that “the new water-soluble azelaic acid salts
may be more bioavailable when administered by routes other than the topical
one” (Hebert 2 ¶ 0014).
11. Hebert teaches that “a new azelaic acid salt is administered to a
warm blooded animal to prevent and or treat the following conditions: . . .
acne” (Hebert 2 ¶ 0016).
Appeal 2014-000362
Application 12/761,953

6
12. Hebert teaches “wherein the compound is administered in a
pharmaceutically acceptable form selected from the group consisting of a
tablet, a capsule, a syrup, a dragee, a suspension, an elixir” (Hebert 3, claim
6).
13. Gupta ’672 teaches that a preparation of “niacinamide, niacin,
and niacin esters with certain organic acids, and their application in topical
cosmetic and pharmaceutical compositions that provide synergistic treatment
and regulation of topical disorders of skin such as skin aging, wrinkles, acne,
rosacea” (Gupta ’672 1 ¶ 0008).
14. Gupta ’672 teaches that:
Additional skin, hair, and body beneficial ingredients,
such as other anti-aging ingredients, vitamins, hormones,
analgesics, anesthetics, sun screens, skin whiteners, anti-
acne agents, anti-bacterial agents, anti-fungal agents,
botanical extracts, pharmaceuticals, processing-aids,
minerals, plant extracts, concentrates of plant extracts,
emollients, moisturizers, skin protectants, humectants,
silicones, skin soothing ingredients, colorants, perfumes, and
like can be added to the formulation. The quantities of such
ingredients can be as needed, and not limited to any specific
limits.

(Gupta ’672 6 ¶ 0043.)
15. Gupta ’672 teaches the use of niacinamide folate, methyl niacin
glycyrrhetinate, niacinamide glycyrrhetinate, and “niacinamide
glycyrrhizinate” (see Gupta ’672 7 ¶ 0046).
16. Gupta ’507 teaches treatment with zinc zeolite resveratrol (see
Gupta ’507 6 ¶ 0051).
Appeal 2014-000362
Application 12/761,953

7
17. Ward teaches that “[c]arbenoxolone which may be used at 0.5
mM in vitro-microsomes” (Ward 7 ¶ 0084).
18. Ansel teaches that “[d]rugs are administered by the oral route in
a variety of pharmaceutical forms. The most popular are tablets, capsules,
suspensions, and various pharmaceutical solutions” (Ansel 122).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “It is prima facie
obvious to combine two compositions each of which is taught by the prior
art to be useful for the same purpose, in order to form a third composition to
be used for the very same purpose.... [T]he idea of combining them flows
logically from their having been individually taught in the prior art.” In re
Kerkhoven, 626 F.2d 846, 850 (CCPA 1980).
Analysis
Bernstein ’948 teaches the treatment of acne vulgaris and acne
rosacea with a topical treatment combining nicotinamide and azelaic acid
(FF 5–6). Sefton also teaches treatment of acne vulgaris with a composition
including azelaic acid (FF 7) and that effective treatment amounts are
subject to ordinary optimization (FF 8).
Bernstein ’896 teaches that acne vulgaris may be treated with oral
nicotinamide (FF 1) using doses of 100 to 600 milligrams (FF 2–3) in
dosage forms including capsules and tablets (FF 4). Hebert teaches
treatment of acne vulgaris with azelaic acid (FF 9) using bioavailable azelaic
acid salts in non-topical treatment routes (FF 10) including administration of
Appeal 2014-000362
Application 12/761,953

8
tablets and capsules (FF 12). Ansel evidences that tablets and capsules are
popular pharmaceutical forms for administration of drugs by the oral route
(FF 18).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that an ordinary artisan would have reasonably found it obvious
that “azelaic acid and nicotinamide are both useful to treat acne vulgaris and
rosacea and can both be formulated for oral administration and their
combination is expected to be more effective than either agent alone” (Ans.
9; FF 1–12, 18). Such a combination is merely a “predictable use of prior art
elements according to their established functions.” KSR, 550 U.S. at 417.
Appellant contends that Sefton “is not a suitable basis for rejection of
an oral medication for the same reasons that the Bernstein publication ‘948
is not suitable for the obviousness rejection of oral compositions – these
publications relate to topical administration, topical and oral product
compositions and methods of use are not equivalent or interchangeable”
(App. Br. 4).
We are not persuaded. Bernstein ’948 and Sefton both teach the
topical use of azelaic acid for the treatment of acne, and Bernstein ’948
further teaches the topical combination of azelaic and nicotinamide for acne
treatment (FF 5–8). With this foundation, the Examiner then reasonably
relies upon Bernstein ’896 to teach that nicotinamide may be orally
administered (FF 1–4) and relies upon Hebert as evidenced by Ansel to
suggest oral administration of azelaic acid (FF 9–12, 18). Having
established that the combination functions to treat acne, and that both
components may be separately orally administered for treatment, we agree
Appeal 2014-000362
Application 12/761,953

9
with the Examiner’s conclusion that the ordinary artisan would have found it
obvious to formulate the combination of azelaic acid and nicotinimide for
oral administration for treatment of acne (see Ans. 9).
Appellant contends that “[t]opical preparations cannot be assumed
safe for oral ingestion. Therefore, art cited that reports topical
pharmaceutical compositions cannot be extrapolated to methods or
compositions suitable for oral administration as claimed in the present case”
(App. Br. 6–7). Appellant contends that “[c]ontrary to the examiner’s
allegation on page 10, he has not shown evidence of ‘what is predictable’ as
a treatment from combining azelaic acid and nicotinamide in an oral
preparation” (App. Br. 8).
We are not persuaded. In “[r]esponding to concerns about uncertainty
in the prior art influencing the purported success of the claimed
combination, the Federal Circuit has stated: “‘[o]bviousness does not require
absolute predictability of success ... all that is required is a reasonable
expectation of success.”’ In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009)
(citing In re O’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988)). Contrary
to Appellant’s assertion, based on the prior art applied by the Examiner there
is no need for extrapolation to oral administration. Here, the prior art
recognized that the combination of azelaic acid and nicotinimide
administered topically functioned to treat acne (FF 5), that azelaic acid may
be administered by routes other than topical (FF 10) using tablets, which are
ordinarily administered orally (FF 12, 18), and that nicotinimide may also be
administered orally (FF 1). We therefore conclude that the facts support the
Appeal 2014-000362
Application 12/761,953

10
conclusion that there would have been a reasonable expectation of success in
administering both azelaic acid and nicotinimide orally.
Appellant contends that the “examiner has used unacceptable
hindsight in picking out publications that have claim elements e.g., azelaic
acid, without considering the reality of the total ingredients and forms -
topical or oral, that in reality those of skill would consider” (Reply Br. 5).
While we are fully aware that hindsight bias often plagues
determinations of obviousness, Graham v. John Deere Co., 383 U.S. 1, 36
(1966), we are also mindful that the Supreme Court has clearly stated that
the “combination of familiar elements according to known methods is likely
to be obvious when it does no more than yield predictable results.” KSR,
550 U.S. at 416.
In this case, we conclude that the person of ordinary skill would have
recognized that modifying the topical administration route of the
nicotinimide and azelaic acid combination to an oral administration route
would have been an obvious modification since both of the individual
components were already taught to have oral administration routes (FF 1, 10,
12, 18). Appellant has not rebutted the Examiner’s prima facie obviousness
showing with any evidence of secondary considerations.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that
Bernstein ’896, Bernstein ’948, Sefton, Hebert, Gupta ’672, Gupta ’507,
Ward, and Ansel render claim 1 obvious.

Appeal 2014-000362
Application 12/761,953

11
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Bernstein ’896, Bernstein ’948, Sefton, Hebert,
Gupta ’672, Gupta ’507, Ward, and Ansel. Pursuant to 37 C.F.R. § 41.37(c)
(1)(iv), we also affirm the rejection of claims 3–6 and 9–11, as these claims
were not argued separately.

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

cdc