Court Opinion

ID: 2645632
Source: CourtListenerOpinion
Date Created: 2013-12-12 01:01:56.517952+00
Date Added: 2024-06-11T12:51:05.766275
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                ______________________

 GALDERMA LABORATORIES, L.P., GALDERMA
     S.A., AND GALDERMA RESEARCH AND
             DEVELOPMENT, S.N.C.,
                Plaintiffs-Appellees,

                           v.

                   TOLMAR, INC.,
                 Defendant-Appellant.
                ______________________

                      2013-1034
                ______________________

    Appeal from the United States District Court for the
District of Delaware in No. 10-CV-0045, Judge Leonard P.
Stark.
                 ______________________

              Decided: December 11, 2013
                ______________________

    CHARLES E. LIPSEY, Finnegan, Henderson, Farabow,
Garrett & Dunner, LLP, of Reston, Virginia, argued for
plaintiffs-appellees. With him on the brief were HOWARD
W. LEVINE, SANYA SUKDUANG, CORTNEY B. CASP, and
VICTORIA S. LEE, of Washington, DC.

    THOMAS P. STEINDLER, McDermott Will & Emery LLP,
of Washington, DC, argued for defendant-appellant. With
him on the brief were JEFFREY R. GARGANO and KEITH M.
STOLTE, of Chicago, Illinois.
2               GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

                  ______________________

    Before NEWMAN, BRYSON, and PROST, Circuit Judges.
    Opinion for the court filed by Circuit Judge PROST.
    Dissenting opinion filed by Circuit Judge NEWMAN.
PROST, Circuit Judge.
    In this patent infringement case, Tolmar, Inc. chal-
lenges the district court’s holding that the claims of U.S.
Patent Nos. 7,579,377 (’377 patent); 7,737,181 (’181
patent); 7,834,060 (’060 patent); 7,838,558 (’558 patent);
and 7,868,044 (’044 patent), which are owned by Galder-
ma Laboratories, L.P., Galderma S.A., and Galderma
Research and Development, S.N.C. (collectively, “Galder-
ma”) are not invalid under 35 U.S.C. § 103. We find that
the district court erred in finding the claims of the assert-
ed patents not invalid as obvious. Accordingly, we re-
verse.
                      I. BACKGROUND
    This Hatch-Waxman case is based on Tolmar’s filing
of an Abbreviated New Drug Application (“ANDA”) seek-
ing approval to market a generic version of Differin® Gel,
0.3%, which is a topical medication containing 0.3% by
weight adapalene approved for the treatment of acne. On
January 21, 2010, Galderma sued Tolmar in the United
States District Court for the District of Delaware, alleging
that Tolmar’s ANDA product infringed certain claims of
the ’377 patent. Galderma subsequently filed amended
complaints alleging infringement of each of the asserted
patents. After a bench trial, the district court ruled
against Tolmar on several issues of which only invalidity
under 35 U.S.C. § 103 is at issue in this appeal.
                 A. Patented Technology
   The asserted patents include both composition claims
and claims directed to methods of treating acne using
GALDERMA LABORATORIES, L.P.     v. TOLMAR, INC.                 3

pharmaceutical compositions. At trial, Galderma alleged
infringement of claims 35 and 36 of the ’181 patent,
claims 24 and 27 of the ’060 patent, claim 5 of the ’558
patent, and claims 40 and 41 of the ’044 patent. 1 Each of
the asserted claims requires an aqueous gel or cream that
includes 0.3% by weight of adapalene. The asserted
claims also recite one or more inactive excipients included
in the gel or cream. Claim 5 of the ’558 patent is repre-
sentative:
    5. A topically applicable pharmaceutical composi-
    tion comprising 0.3% by weight of [adapalene] rel-
    ative to the total weight of the composition,
    effective for the treatment of acne, formulated into
    a topically applicable, pharmaceutically accepta-
    ble medium therefor, said composition being in
    the form of a topically applicable, pharmaceutical-
    ly acceptable aqueous gel comprising at least one
    carbomer gelling agent and wherein the sole anti-
    acne ingredient is adapalene.
                         B. Prior Art
    Below, Tolmar based its obviousness argument pri-
marily on three pieces of prior art: U.S. Patent No.
4,717,720 (“Shroot ’720 patent”), U.S. Reissue No. 34,440
(“Shroot ’440 patent”), and the Differin® 0.1% Gel Data
Sheet (“Data Sheet”).
     The Shroot ’720 patent specifically discloses and
claims adapalene along with other inventive compounds.
Col. 3 ll. 9-10; col. 4 ll. 29-37; col. 9 ll. 39-54; col. 19 l.17-
col. 20 l. 19. Four of the seven composition examples in
the Shroot ’720 patent disclose adapalene as the active
ingredient, in concentrations of 0.001%, 0.1%, and 1%.
Col. 16 ll. 35-53; col. 17 ll. 20-52. The specification of the
Shroot ’720 patent states repeatedly that the inventive

    1   The ’377 patent was not asserted at trial.
4               GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

compounds are useful for the treatment of acne. See col. 4
ll. 53-59; see also col. 5 ll. 49-53. Moreover, the specifica-
tion states that the inventive compounds can be used in
concentrations “preferably between 0.01 and 1 weight
percent, based on the total weight of the composition.”
Shroot ’720 patent col. 5 ll. 61-64. Finally, the Shroot ’720
patent indicates that the inventive compounds “are less
irritating than known retinoids of analogous structure.”
Col. 4 ll. 48-51. The Shroot ’440 patent is largely similar
to the Shroot ’720 patent, but also contains claim 4, which
recites a preferred range of 0.01 to 1% for cosmetic compo-
sitions which include the inventive compounds, e.g.,
adapalene, as the active ingredient. Shroot ’440 patent
col. 20 ll. 15-18. Notably, prior to their expiration, the
Shroot patents were listed in the FDA’s Orange Book as
covering Galderma’s prior art Differin® 0.1% Gel as well
as Differin® Gel, 0.3%.
    The Data Sheet is the product insert for Galderma’s
earlier launched adapalene product. The Data Sheet
discloses 0.1% adapalene as a treatment for acne. It also
discloses all but one of the inactive ingredients listed in
the asserted claims. Other than the dosage of adapalene,
the only difference between the claimed formulations and
the formulation taught by the Data Sheet is that the Data
Sheet discloses “poloxamer 182,” while certain asserted
claims list “poloxamer 124.”
    In addition to the Shroot patents and the Data Sheet,
Tolmar provided other relevant evidence. For instance, a
1989 article by Jamoulle et al. describes the use of a lotion
containing 0.3% adapalene in an animal model to deter-
mine whether adapalene was suitable for the treatment of
acne. The authors concluded from this test that adapa-
lene was “particularly suitable for the treatment of acne.”
J.A. 13063. A series of other prior art articles demon-
strate that 0.03% and 0.1% adapalene products were
effective against acne and well tolerated. These articles
include: Verschoore et al., Efficacy and Safety of CD 271
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.             5

Alcoholic Gels in the Topical Treatment of Acne Vulgar-
is, 124 British J. of Derm. 368-71 (1991) (“Verschoore
1991”); Alirezai et al., Comparative Study of the Effective-
ness and Tolerance of 0.1 and 0.03 Percent Adapalene Gels
and of a 0.025 Percent Tretinoin Gel in the Treatment of
Acne, 123 Ann. Dermatol. Venereol. 165-70 (1996) (“Ali-
rezai 1996”); Allec et al., Skin Distribution and Pharma-
ceutical Aspects of Adapalene Gel, 35(6) J. Am. Acad. of
Dermatol. S119-25 (1997) (“Allec 1997”).
     The prior art also teaches the use of 0.3% adapalene
for other conditions without intolerable irritability. See
Verschoore et al., Adapalene 0.1% Gel Has Low Skin
Irritation Potential, 36(6) J. Am. Acad. of Dermatol. S104-
09 (1997) (“Verschoore 1997”); Goldfarb, Using Adapalene
to Treat Photodamage, Supp. to Skin & Aging 4-7 (Nov.
2000) (“Goldfarb Article”); Goldfarb et al., Photographic
Assessment of the Effects of Adapalene 0.1% and 0.3% Gels
and Vehicle on Photodamage Skin, 14 (Supp. 1) J. Eur.
Acad. Dermatol. Venerol. 315 (2000) (“Goldfarb Ab-
stract”); Euvrard, “How Adapalene Can Treat Actinic
Keratoses,” Supp. to Skin & Aging 12-15 (Nov. 2000)
(“Euvrard 2002”). 2 There was also an indication in the
prior art that dermatologists preferred other retinoids to
adapalene at least in part because they were available in
multiple concentrations whereas adapalene was only
available in one. Bershad et al., Topical Retinoids in the
Treatment of Acne Vulgaris, 64 (Supp. 2) Cutaneous Med.
for the Practitioner 8-19 (Aug. 1999) (“Bershad 1999”).
Finally, the prior art indicated that many skilled artisans
believed at the time of the invention that 0.1% was the
optimal concentration of adapalene for the treatment of

   2    Euvrard (2002) appears to have been published in
2000, not 2002. The district court, however, referred to
the article as Euvrard (2002). For the sake of consistency,
we do the same.
6               GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

acne. See Verschoore 1997; Allec 1997; Czernielewski et
al., Adapalene Biochemistry and the Evolution of a New
Topical Retinoid for Treatment of Acne, 15 (Supp. 3) J.
Eur. Acad. Dermatol. Venerol. 5-12 (2001) (“Czernielewski
2001”).
                     II. OBVIOUSNESS
    The determination of invalidity for reasons of obvi-
ousness under 35 U.S.C. § 103 is a legal conclusion based
on underlying facts. Graham v. John Deere Co., 383 U.S.
1, 17 (1966). Following a bench trial, we “review the
district court’s factual findings for clear error and its
conclusions of law de novo.” Winner Int’l Royalty Corp. v.
Wang, 202 F.3d 1340, 1344-45 (Fed. Cir. 2000).
    Factual considerations that underlie the obviousness
inquiry include the scope and content of the prior art, the
differences between the prior art and the claimed inven-
tion, the level of ordinary skill in the art, and any rele-
vant secondary considerations. See Graham, 383 U.S. at
17-18. Relevant secondary considerations include com-
mercial success, long-felt but unsolved needs, failure of
others, and unexpected results. KSR Int’l Co. v. Teleflex
Inc., 550 U.S. 398, 406 (2007); In re Soni, 54 F.3d 746, 750
(Fed. Cir. 1995). Because patents are presumed valid,
Tolmar was required to prove that the asserted claims
were obvious by clear and convincing evidence. See
Microsoft Corp. v. i4i Ltd. P’ship, 131 S. Ct. 2238, 2242
(2011).
    Tolmar presents an obviousness case that is both
straightforward and potent. At the time of the invention,
adapalene was a known compound and the prior art
Shroot patents disclose topical adapalene compositions for
the purpose of treating acne in a preferred range of
0.01%-1%, including several exemplary formulations
containing adapalene in various concentrations. The
asserted claims are directed to 0.3% topical adapalene
compositions for the treatment of acne, which fall within
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.            7

the concentration range disclosed in the Shroot patents.
Thus, the Shroot patents disclose all of the limitations of
the asserted claims, except for a precise teaching of 0.3%
adapalene and the specific inactive ingredients of the
asserted claims. The specific inactive ingredients of the
asserted claims are, however, taught by the Data Sheet.
     The Data Sheet discloses each of the inactive ingredi-
ents, except for poloxamer 124. However, the district
court found poloxamer 124 equivalent to poloxamer 182,
which is disclosed in the Data Sheet. Moreover, the
district court held that “the record evidence establishes
that the inactive ingredients in the claimed formulations
[were] routine and obvious, and, therefore, non-inventive.”
Galderma Labs., L.P. v. Tolmar, Inc., 891 F. Supp. 2d 588,
645 (D. Del. 2012). Notably, on appeal, the parties do not
dispute the obviousness of the inactive ingredients of the
formulation. Rather, the sole dispute between the parties
is whether it was obvious to use a 0.3% adapalene compo-
sition for the treatment of acne. Accordingly, Tolmar
argues that the asserted claims are obvious because they
claim nothing more than the use of an old compound for a
known purpose in a concentration that falls within a
range disclosed in the prior art as preferred for that
purpose.
    Tolmar buttresses its obviousness argument with oth-
er relevant evidence. This evidence includes a study that
used a lotion containing 0.3% adapalene in an animal
model to determine that adapalene was “particularly
suitable for the treatment of acne.” J.A. 13063. Addition-
ally, the prior art showed that 0.03% and 0.1% adapalene
products were suitable for the treatment of acne and that
0.3% adapalene products were suitable for the treatment
of other conditions without intolerable irritability. More-
over, the prior art indicated that dermatologists desired
acne treatments that came in varying concentrations.
According to Tolmar, this provides further motivation to
8               GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

select a 0.3% adapalene composition for the treatment of
acne.
    The district court rejected Tolmar’s obviousness case,
finding that Tolmar “failed to establish, by clear and
convincing evidence, that the claimed inventions would
have been obvious to a person of ordinary skill at the time
of the invention.” Galderma Labs., 891 F. Supp. 2d at
637. In reaching this conclusion, the district court relied
heavily on evidence showing that increasing the dose of
adapalene was likely to increase the incidence of certain
side effects and evidence showing that 0.1% was consid-
ered the optimal adapalene concentration for the treat-
ment of acne. Id. at 641-42. In addition, the court found
“that at least two secondary considerations, unexpected
results and commercial success, additionally support the
determination that the asserted claims are not invalid
due to obviousness.” Id. at 642-44.
    Prior to addressing the obviousness of the asserted
claims, we note an error in the district court’s obviousness
analysis. The district court framed the obviousness
inquiry as requiring Tolmar to provide motivation in the
prior art to triple the concentration of adapalene from
0.1% to 0.3%. Id. at 638. Tolmar carried no such burden.
Rather, Tolmar, like all those who seek to prove claims
obvious, was required to show that “the differences be-
tween the claimed invention and the prior art are such
that the claimed invention as a whole would have been
obvious before the effective filing date of the claimed
invention to a person having ordinary skill in the art to
which the claimed invention pertains.” 35 U.S.C. § 103.
Nothing in the statute or our case law requires Tolmar to
prove obviousness by starting with a prior art commercial
embodiment and then providing motivation to alter that
commercial embodiment. See KSR, 550 U.S. at 419 (“In
determining whether the subject matter of a patent claim
is obvious, neither the particular motivation nor the
avowed purpose of the patentee controls. What matters is
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.             9

the objective reach of the claim. If the claim extends to
what is obvious, it is invalid under § 103.”). This is par-
ticularly true where, as here, the prior art teaches a range
that encompasses both the prior art commercial embodi-
ment and the claimed invention.
     The relevant dispute in this case is thus not over
whether the prior art discloses all of the claim elements or
over the motivation to combine the prior art references.
Rather, the dispute is whether there was motivation to
select the claimed 0.3% adapalene composition in the
disclosed range. In these circumstances, where there is a
range disclosed in the prior art, and the claimed invention
falls within that range, the burden of production falls
upon the patentee to come forward with evidence that (1)
the prior art taught away from the claimed invention; (2)
there were new and unexpected results relative to the
prior art; or (3) there are other pertinent secondary con-
siderations. See Novo Nordisk A/S v. Caraco Pharm.
Labs., Ltd., 719 F.3d 1346, 1352-54 (Fed. Cir. 2013).
    Accordingly, Tolmar having demonstrated that the
prior art taught a range of concentrations of adapalene for
the treatment of acne that encompasses the claimed 0.3%
adapalene composition, we now examine the district
court’s findings with respect to the factors listed above to
determine whether the claims are invalid as obvious. The
ultimate burden of proving obviousness rests with Tol-
mar.
                    A. Teaching Away
    Despite express teachings in the Shroot patents indi-
cating that adapalene would be useful in concentrations
preferably between 0.01% and 1%, the district court found
that the prior art taught away from a 0.3% adapalene
composition. The district court based its conclusion
10               GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

primarily on two related grounds. 3 First, according to the
district court, the prior art taught “away from the selec-
tion of 0.3% adapalene for the treatment of acne, because
of dose-dependent increases in side effects.” Galderma
Labs., 891 F. Supp. 2d at 641 n.8. And second, the prior
art taught that 0.1% was the optimal concentration of
adapalene for the treatment of acne. Id. at 641-42. We
leave undisturbed the district court’s findings that in-
creasing the dose of adapalene would result in a concomi-
tant increase in side effects and that 0.1% was the
optimal concentration of adapalene for the treatment of
acne at the time of the invention. However, to the extent
the court found that these facts taught away from the
claimed invention, it clearly erred.
         A reference may be said to teach away when a
     person of ordinary skill, upon reading the refer-
     ence, would be discouraged from following the
     path set out in the reference, or would be led in a
     direction divergent from the path that was taken
     by the applicant. A reference does not teach
     away, however, if it merely expresses a general
     preference for an alternative invention but does
     not criticize, discredit, or otherwise discourage in-
     vestigation into the invention claimed.
Depuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567
F.3d 1314, 1327 (Fed. Cir. 2009). With respect to the

     3  The district court also relied on evidence that oth-
er commercially available, more irritating, topical retin-
oids were recently introduced in lower concentrations due
to tolerability issues. The district court, however, provid-
ed no rationale as to why one of ordinary skill would do
the same with adapalene, which is less irritating than
other retinoids.     Moreover, the higher concentration
formulations of the other topical retinoids remained
commercially available. J.A. 10343-44, 10519.
GALDERMA LABORATORIES, L.P.    v. TOLMAR, INC.                11

prior art teachings of dose-dependent side effects, the
district court relied on the Verschoore 1991 and Alirezai
1996 articles, which show that the increase in adapalene
concentration from 0.03% to 0.1% resulted in an increase
in side effects. Neither of these articles mentions 0.3%
adapalene compositions, nor do they expressly teach away
from the claimed invention. The district court inferred
that these references taught away from a further tripling
of the adapalene concentration. We cannot agree with
this inference.
    These articles show increased side effects associated
with 0.1% adapalene as compared to 0.03% adapalene, yet
they failed to discourage even the use of 0.1% adapalene.
To the contrary, as the district court found, 0.1% was the
optimal concentration of adapalene at the time of the
invention. Galderma Labs., 891 F. Supp. 2d at 641-42.
Moreover, there is nothing in either of these references to
indicate that increasing the concentration to 0.3% would
be unproductive, nor do these articles indicate in any way
that the side effects would be serious enough to dissuade
the development of a 0.3% adapalene product. Therefore,
the Verschoore 1991 and Alirezai 1996 articles fail to
teach away from the claimed invention.
      The district court relied on the Allec 1997, Verschoore
1997, and Czernielewski 2001 articles to demonstrate
that 0.1% was the standard or optimal concentration of
adapalene for the treatment of acne. The court concluded
that this fact teaches away from 0.3% adapalene composi-
tions. It does not. “A reference does not teach away . . . if
it . . . does not ‘criticize, discredit, or otherwise discourage’
investigation into the invention claimed.” Depuy Spine,
567 F.3d at 1327 (citing In re Fulton, 391 F.3d 1195, 1201
(Fed. Cir. 2004)). A teaching that a composition may be
optimal or standard does not criticize, discredit, or other-
wise discourage investigation into other compositions.
Accordingly, the Allec 1997, Verschoore 1997, and Czer-
12              GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

nielewski 2001 articles do not teach away from the
claimed invention.
                  B. Unexpected Results
    The district court found that the comparable tolerabil-
ity of 0.1% and 0.3% adapalene was unexpected in view of
the prior art, since a skilled artisan would have expected
that tripling the concentration of adapalene would have
resulted in a clinically significant increase in side effects.
Galderma Labs., 891 F. Supp. 2d at 642-44. While we
agree that this result was unexpected, it does not consti-
tute an unexpected result that is probative of non-
obviousness.
    Unexpected results that are probative of non-
obviousness are those that are “different in kind and not
merely in degree from the results of the prior art.” Iron
Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322
(Fed. Cir. 2004) (citation omitted). Results which differ
by percentages are differences in degree rather than kind,
where the modification of the percentage is within the
capabilities of one skilled in the art at the time. See In re
Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005) (finding
increased efficacy, measured by percentages, to be a
difference of degree and not of kind); In re Budde, 319
F.2d 242, 246 (C.C.P.A. 1963) (finding no unexpected
results where ranges of reaction time and temperature
constituted only a difference in degree rather than in
kind); In re Aller, 220 F.2d 454, 456-57 (C.C.P.A. 1955)
(finding no unexpected results where improved yields over
the prior art, measured by percentages, reflect a differ-
ence in degree, not in kind). Thus, where an unexpected
increase in efficacy is measured by a small percentage, as
here, and the evidence indicates that skilled artisans were
capable of adjusting the percentage, the result constitutes
a difference in degree, not kind. So too, where an increase
by a percentage is expected but not found, that result is
also likely only a difference in degree. In this case, the
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.              13

expected result was an increase, by some percentage, in
the prevalence of certain side effects. The failure of that
percent increase to materialize, though unexpected,
constitutes only a difference in degree from the prior art
results. Accordingly, the comparable tolerability of 0.1%
and 0.3% adapalene does not indicate that the asserted
claims are non-obvious.
                  C. Commercial Success
     “Evidence of commercial success . . . is only significant
if there is a nexus between the claimed invention and the
commercial success.” Ormco Corp. v. Align Tech., Inc.,
463 F.3d 1299, 1311-12 (Fed. Cir. 2006). “When a patent-
ee can demonstrate commercial success, usually shown by
significant sales in a relevant market, and that the suc-
cessful product is the invention disclosed and claimed in
the patent, it is presumed that the commercial success is
due to the patented invention.” J.T. Eaton & Co. v.
Atlantic Paste & Glue Co., 106 F.3d 1563, 1571 (Fed. Cir.
1997). However, “if the feature that creates the commer-
cial success was known in the prior art, the success is not
pertinent.” Ormco Corp., 463 F.3d at 1311-12; see also
J.T. Eaton, 106 F.3d at 1571 (“[T]he asserted commercial
success of the product must be due to the merits of the
claimed invention beyond what was readily available in
the prior art”).
     The district court found that “[t]he commercial suc-
cess of Galderma’s 0.3% adapalene product also supports
a finding of nonobviousness.” Galderma Labs., 891 F.
Supp. 2d at 644. The district court gave two reasons for
its finding. First, Differin® 0.3%, Galderma’s commercial
embodiment of the claims, “quickly gained and main-
tained market share—even in the face of an overall de-
clining market and decreasing promotional expenditures,
and while facing competition from generic 0.1% adapalene
formulations.” Id. Second, the court found “that Tolmar
(along with another ANDA filer, Actavis) seeks to enter
14              GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

the market precisely because Differin® 0.3% has been
commercially successful.” Id. We discuss these findings
in reverse order.
    The mere fact that generic pharmaceutical companies
seek approval to market a generic version of a drug,
without more, is not evidence of commercial success that
speaks to the non-obviousness of patent claims. Plainly,
Tolmar believes that it can make a profit selling a generic
version of the claimed invention. This is likely true in all
Hatch-Waxman cases, if not all patent cases generally.
However, that fact tells us very little about the level of
commercial success of the patented invention relative to
the prior art or the extent to which the commercial suc-
cess of the branded drug is “due to the merits of the
claimed invention beyond what was readily available in
the prior art.” J.T. Eaton, 106 F.3d at 1571. As such, it
does not support a finding of non-obviousness.
    The court also relied on the fact that Differin® Gel,
0.3% quickly gained and maintained market share to find
commercial success. We do not disturb this finding.
However, we note that it is of limited value in determin-
ing whether or not the presently asserted claims are
obvious. “Commercial success is relevant because the law
presumes an idea would successfully have been brought to
market sooner, in response to market forces, had the idea
been obvious to persons skilled in the art.” Merck & Co. v.
Teva Pharm. USA, Inc., 395 F.3d 1364, 1376 (Fed. Cir.
2005). Where “market entry by others was precluded [due
to blocking patents], the inference of non-obviousness of
[the asserted claims], from evidence of commercial suc-
cess, is weak.” Id. at 1377. This principle applies force-
fully to the present case.
    The now expired Shroot patents blocked the market
entry of 0.3% adapalene products until their expiration in
2010, long after Galderma invented 0.3% adapalene
compositions of the asserted claims. As such, no entity
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.           15

other than Galderma could have successfully brought to
0.3% to market prior to 2010. Like the commercial suc-
cess described in Merck & Co., the commercial success of
Differin® Gel, 0.3% is of “minimal probative value.” Id. at
1376. Accordingly, we conclude the district court erred in
adjudging this factor as confirming its conclusion of non-
obviousness.
                     III. CONCLUSION
    For the foregoing reasons, we hold that claims 35 and
36 of the ’181 patent, claims 24 and 27 of the ’060 patent,
claim 5 of the ’558 patent, and claims 40 and 41 of the
’044 patent are invalid as obvious. We therefore reverse
the district court’s finding that the claims are valid.
                      REVERSED
  United States Court of Appeals
      for the Federal Circuit
                ______________________

 GALDERMA LABORATORIES, L.P., GALDERMA
     S.A., AND GALDERMA RESEARCH AND
             DEVELOPMENT, S.N.C.,
                Plaintiffs-Appellees,

                           v.

                   TOLMAR, INC.,
                 Defendant-Appellant.
                ______________________

                      2013-1034
                ______________________

    Appeal from the United States District Court for the
District of Delaware in No. 10-CV-0045, Judge Leonard P.
Stark.
                 ______________________

  Before NEWMAN, BRYSON, and PROST, Circuit Judges.
NEWMAN, Circuit Judge, dissenting.
    Without doubt, the question of obviousness here pre-
sented is a close call. However, when the question is
close, when it turns on findings and interpretations of
biologic and medicinal evidence, when the application of
law to fact invokes the policy of the patent statute to
advance the useful arts, then the findings and rulings of
the trial court warrant particular attention on appellate
review.
2               GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

    Here, the district court fully explored the evidence re-
lating to whether it would have been obvious to increase
by 300% the concentration of the active ingredient adapa-
lene without increasing its known adverse side effects.
The district judge held an eight-day bench trial, heard
thirteen live witnesses including expert witnesses of
stature and experience, and received evidence and argu-
ment from both sides. The court issued an opinion with
over 50 pages on the issue of obviousness, finding the
facts and weighing the evidence and applying the law
with thoughtful explanation and reasoning. 1
    My colleagues on this panel give scant attention to the
district court’s analysis, instead making their own find-
ings, and applying flawed procedural and substantive law.
My colleagues do not identify clear error in the district
court’s findings; instead they distort the burdens of proof
and production, ignore the applicable standard of proof
and rely on their own factual determinations and creative
theories of law, and eradicate the patent.
    The district court ruled that there was not clear and
convincing evidence of invalidity. By contrast, my col-
leagues announce their rule whereby a broad teaching
that includes the patented invention removes the statuto-
ry presumption of validity, and without more establishes
obviousness. See maj. op. at 9 (“where there is a range
disclosed in the prior art, and the claimed invention falls
within that range, the burden of production falls upon the
patentee…”). Although the majority mentions the re-
quirement of clear and convincing evidence of invalidity,
the majority presumes that the prior art establishes
invalidity, and places on the patentee the burden of
establishing patentability based on “secondary considera-

    1  Galderma Laboratories, L.P. v. Tolmar, Inc., 891
F. Supp. 2d 588 (D. Del. 2012) (“DCt. Op.”).
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.             3

tions.” The majority goes on to impose a new and unprec-
edented view of these considerations.
    For example, although the panel majority concedes
that there are unexpected results for the concentration
selected by the patentee, see maj. op. at 12 (“we agree that
this result was unexpected”), my colleagues do not require
the patent challenger to show any reason in the prior art
(or common sense) for selection of this embodiment with
its unexpected properties. Rather, they hold that unless a
skilled artisan was not “capable of adjusting the percent-
age,” id., the extent of the change in percentage (here
300%) and the unexpected results and properties are
irrelevant to patentability.
    In refusing to credit any of the demonstrated “second-
ary considerations” my colleagues foreclose patentability
to a vast body of improvement patents. In the field of
medicaments, the denial of patentability for improve-
ments is a disincentive to the development of such im-
provements. The losers are those afflicted with disease. I
respectfully dissent.
                       DISCUSSION
    Particularly for close questions of patentability, the
district court’s findings and assessments of credibility and
weight of evidence, and the district court’s application of
law to found facts, compel appellate attention. The role of
the trial court in considering the evidence that each party
provides through examination and cross-examination of
witnesses and documents, with judicial elaboration and
interaction, cannot be matched on appeal. As the Su-
preme Court stated in Anderson v. Bessemer City, “dupli-
cation of the trial judge’s efforts in the court of appeals
would very likely contribute only negligibly to the accura-
cy of fact determination at a huge cost in diversion of
judicial resources.” 470 U.S. 564, 574-75 (1985).
4              GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

    Clear and convincing evidence is required to overcome
the statutory presumption of validity of a duly granted
patent. See 35 U.S.C. §282 (a patent is presumed valid);
Cardinal Chem. Co. v. Morton Int'l, 508 U.S. 83, 93 n.15
(1993) (invalidity must be proved by clear and convincing
evidence). Here the panel majority does not provide clear
and convincing evidence of invalidity. Instead, the major-
ity discards the trial judge’s findings on the premise of a
presumption of invalidity that the majority applies to
“selection” inventions, that is, inventions within a known
class or range of technology, for which the majority dis-
cards the established procedural and substantive bur-
dens. The majority makes its own factual findings, and
writes new law.
     In contrast to the panel majority’s dismissive analy-
sis, the district court’s findings reflect careful examina-
tion of all of the evidence. Nonetheless, my colleagues
conclude that the selection of a 300% increase in dosage
was obvious, after the unexpected properties of the in-
crease were discovered by this patentee. I summarize
some of the evidence before the district court, whose
findings well support the conclusion that invalidity on the
ground of obviousness was not established by clear and
convincing evidence:
                             I
                     THE PRIOR ART
     In this Hatch-Waxman case, Tolmar, Inc. seeks to in-
validate Galderma’s patents on the commercially success-
ful acne medication whose active ingredient is the retinoid
adapalene in 0.3% concentration. There was extensive
prior art showing retinoids including adapalene in a
range of concentrations for various uses, and showing the
prior selection of 0.1% adapalene for treatment of acne
because higher concentrations were shown to be unduly
irritative to acne-ridden skin.
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.             5

     The district court found that the knowledge in the
field taught away from the 0.3% concentration, based on
the expert testimony and documentary evidence at trial.
The district court, applying the correct standard, held
that Tolmar did not prove invalidity by clear and convinc-
ing evidence.
   The Shroot Patents (1988, 1992, 1993) 2
    These are Galderma’s now-expired patents on ben-
zonaphthalene derivatives including adapalene, and their
use to treat acne. The issue is the selection of the 0.3%
adapalene concentration in the patents-in-suit.
    The district court found that “the [Shroot] range of
0.0005% to 5% for topical compositions covers four orders
of magnitude (or a 10,000-fold dosage range)” and that
“even the ‘preferred’ range of 0.01% to 1% is a hundred-
fold dosage range.” DCt. Op. at 609. The district court
found that “[f]rom this large genus of potential treat-
ments, Galderma selected 0.1% adapalene as the concen-
tration of adapalene with which to begin development of a
topical treatment for acne.” Id. at 603. Dr. Shroot testi-
fied that the 0.1% dosage was considered the optimal dose
for tolerance in a rabbit irritation study. Tr. at 1841:12-
17.
    The district court found that “[t]he broad disclosure of
the Shroot patents provides no motivation or suggestion
to select 0.3% adapalene for the treatment of acne.” Id. at
608-609. The correctness of these findings is not chal-
lenged by the panel majority.

   2   U.S. Patent Nos. 4,717,720; 5,098,895; Reissue
Patent No. 34,440.
6               GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

    The Verschoore article (1991)
                                     3

     Verschoore (1991) discusses a Phase II clinical trial
where 0.03% and 0.1% adapalene formulations, along
with 0.025% tretinoin (a retinoid previously approved for
topical use) were tested on the faces of patients with acne.
The test data showed that the 0.1% adapalene formula-
tion caused increased irritation compared to the 0.03%
formulation. DCt. Op. at 604. Galderma’s expert testified
that persons of ordinary skill in this art would view these
data as suggesting that “a significant increase in tolera-
bility measures” would result from a further tripling of
the adapalene dose from 0.1% to 0.3%. Tr. at 1230:15-20.
    The district court found, supported by the expert tes-
timony, that “[t]he results of this study suggest that
increasing the concentration of adapalene beyond 0.1%
would result in significantly increased irritation.” DCt.
Op. at 604. My colleagues disagree with what they call
the district court’s “inference” that Verschoore (1991) and
Alirezai (1996) (see infra) taught away from a further
tripling of the dose. Thus my colleagues replace the
testamentary and documentary expertise that supports
the district court’s findings, with the expertise of the
panel majority.

    3   Verschoore et al., Efficacy and Safety of CD 271
Alcoholic Gels in the Topical Treatment of Acne Vulgar-
is, 124 British J. of Derm. 368–71 (1991).
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.             7

    The Alirezai article (1996)
                                  4

     The district court found that “the trend of increased
irritation between the 0.03% and 0.1% dosages disclosed
in Verschoore (1991) was later confirmed in the same
dosages in aqueous gels in a publication by Alirezai et al.
entitled ‘Comparative Study of the Effectiveness and
Tolerance of 0.1 and 0.03 Percent Adapalene Gels and of
0.025 Percent Tretinoin Gel in the Treatment of Acne.’”
DCt. Op. at 604. The district court found that this article
disclosed that “severe burning was seen in no patients
treated with the 0.03% adapalene, but was seen in 13% of
patients treated with the 0.1% adapalene aqueous gel”
and that “significantly higher levels of ‘average’ burning
and itching after application were observed with the 0.1%
formulation as compared to the 0.03% formulation.” Id.
at 605.
    The district court found that “[t]his study, conducted
on the faces of acne patients, demonstrates that the
tolerability of the 0.1% dosage was different than the
0.03% dosage.” Id. The correctness of this finding is not
challenged by my colleagues. In concluding that Alirezai
(1996) does not teach away from the claimed invention,
my colleagues ignore the district court’s finding that
significantly higher levels of burning and itching were
observed upon increasing the adapalene concentration of
the formulation.

    4   Alirezai et al., Comparative Study of the Effective-
ness and Tolerance of 0.1 and 0.03 Percent Adapalene Gels
and of a 0.025 Percent Tretinoin Gel in the Treatment of
Acne, 123 Ann. Dermatol. Venereol. 165–170 (1996).
8               GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

    The Allec article (1997)
                               5

     This article, entitled “Skin Distribution and Pharma-
ceutical Aspects of Adapalene Gel,” is discussed by the
district court as “describ[ing] the results of in vivo models
used to select the optimal concentration of adapalene for
efficacy and safety…”. DCt. Op. at 605 (emphasis in
original). The article concludes that “[b]ased on these in
vivo results, 0.1% was considered as the optimal concen-
tration of drug for adapalene gel. This choice was subse-
quently confirmed in clinical trials of safety and efficacy.”
Id. at 606, quoting Allec (1997) at S123.
     The district court found that “[a] person of ordinary
skill in the art would have recognized these statements as
a conclusion of the company that developed adapalene
had determined, from all the data it had on hand, that
0.1% was the optimal concentration for acne treatment,
balancing efficacy and safety.” Id. at 606. My colleagues
concede, citing Allec (1997), that “the prior art indicated
that many skilled artisans believed at the time of inven-
tion that 0.1% was the optimal concentration of adapalene
for the treatment of acne.” Maj. op. at 5-6. My colleagues
do not explain the grounds for their belief contrary to that
of “many skilled artisans.”
    The Verschoore article (1997)
                                      6

    This article describes Phase I clinical trials conducted
by Galderma on healthy subjects. The article states:

    5   Allec et al., Skin Distribution and Pharmaceutical
Aspects of Adapalene Gel, 35(6), J. Am. Acad. of Dermatol.
S119–S125 (1997).
    6  Verschoore et al., Adapalene 0.1% Gel Has Low
Skin Irritation Potential, 36(6) J. Am. Acad. of Dermatol.
S104–109 (1997).
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.            9

   We carried out 13 different controlled, random-
   ized, intraindividual comparison phase I studies
   in 339 healthy human volunteers to investigate
   the cutaneous safety of adapalene []. The irrita-
   tion potential of adapalene 0.03%, 0.1%, and 0.3%
   gels was found to be low, whether tested under oc-
   clusive or nonocclusive conditions on a variety of
   sites (face, chest, back, and buttocks).
Verschoore (1997) at S104. At the trial Tolmar stressed
the testing by Verschoore of the 0.3% formulation. The
district court found that “[t]he Phase I irritation test
described in Verschoore (1997) was a screening test done
on uncompromised healthy skin on the back as a prel-
ude—not a substitute—to clinical testing on the face or on
patients with disease. . . . A skilled person would under-
stand that data from these Phase I studies conducted on
healthy skin cannot be extrapolated to how the product
will work in acne patients.” DCt. Op. at 610. The district
court found that “Verschoore (1997) demonstrates that
Galderma decided to pursue and obtain clinical approval
for 0.1% adapalene. Further the mention of the 0.3%
concentration in the article demonstrates to one skilled in
the art that the 0.3% adapalene was tried and rejected as
the dosage to pursue for further clinical testing.” Id. at
606-607.
    The district court received testimony from experts on
both sides. Galderma’s expert testified that a skilled
person would know that patch testing on the backs of
healthy volunteers is a “poor predictor” of the irritation
experienced by facial skin damaged by acne. Tr. at
1244:19-1245:6. Tolmar’s expert had previously written7

   7    Saqib J. Bashir & Howard I. Maibach, Methods
for Testing the Irritation and Sensitization Potential of
Drugs and Enhancers, in Biochemical Modulation of Skin
10             GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

that this type of irritation test “had failed to predict
adverse reactions to skin damaged by acne or shaving, on
sensitive areas such as the face.” DCt. Op. at 610 (empha-
sis in original). Although Tolmar’s expert stated a differ-
ent opinion at trial, the district court found that the
witness did not refute the views he had previously pub-
lished on the non-predictive nature of patch tests on the
backs of healthy individuals. Id. at 622.
    These district court findings are not challenged by my
colleagues.
     The Czernielewski article (2001)
                                        8

    This article summarizes the results of adapalene
studies including those reported in Alirezai (1996) and
Verschoore (1997). The article explains that the “primary
objective in the development of adapalene was to create a
topical agent with retinoid therapeutic effects that is
considerably less irritating than topical tretinoin.” DCt.
Op. at 640. The court states: “Adapalene 0.1% became the
standard concentration for subsequent adapalene formu-
lations.” Id.
     The district court found that “[t]he Czernielewski ar-
ticle suggests that 0.1% adapalene is the optimal dose for
the treatment of acne,” and that the article “does not
disclose any information about any doses higher than
0.1% adapalene.” DCt. Op. at 607. My colleagues do not
challenge the district court’s findings that the prior art,

Reactions: Transdermals, Topicals, Cosmetics 45, 50 (Agis
F. Kydonieus & John J. Wille eds., 2000).
     8  Czernielewski et al., Adapalene Biochemistry and
the Evolution of a New Topical Retinoid for Treatment of
Acne, 15 (Suppl. 3) J. Eur. Acad. Dermatol. Venerol. 5–12
(2001).
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.            11

including Czernielewski (2001), shows that 0.1% was
believed to be the optimal adapalene dose.
   The Goldfarb article (2000)
                                    9

    This article describes a study of the treatment of pho-
todamaged skin with 0.1% and 0.3% adapalene formula-
tions. The authors describe both of these adapalene
concentrations as being “tolerated well.” DCt. Op. at 613.
    The district court again received evidence and testi-
mony from experts for both sides. Galderma’s expert
explained the differences between photodamaged skin and
skin with acne, and the different patient populations. Tr.
at 1290:1-1293:1. The district court found that publica-
tions by Tolmar’s expert showed that “one of ordinary
skill in the art would understand older skin with photo-
damage and actinic keratosis to be less sensitive to the
retinoid reaction compared to younger skin with acne.”
Id. The expert’s contrary testimony at trial did not refute
his prior published statements. Credibility findings are
the particular province of the trial judge.
    The district court found that the results of this study
“are not predictive of how the same drug would affect
patients with acne. One of ordinary skill in the art would
know that these results on photodamaged skin should not
be extrapolated to acne.” Id. Without either acknowledg-
ing or disputing this finding, my colleagues cite Goldfarb
as teaching that 0.3% adapalene can be used for “other
conditions” without intolerable irritability. Maj. op. at 5.

   9  Goldfarb, Using Adapalene to Treat             Photo-
damage, Supp. to Skin & Aging 4–7 (Nov. 2000).
12              GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

     The Euvrard article (2002)
                                  10

     Euvrard (2002) describes a study using 0.1% and 0.3%
adapalene to treat “actinic keratosis on the hands and
forearms of organ transplant patients who were presuma-
bly on immunosuppressive drugs.” DCt. Op. at 614. The
district court summarized the Euvrard conclusion that
“[t]olerance was excellent everywhere” and “[t]aking into
account the good tolerance of adapalene, these results
encourage further studies on the use of adapalene at . . .
higher dosage regimens.” Id.
    There was expert testimony from both sides, and the
district court found, as with Goldfarb, that “[d]ifferences
exist between the properties of facial skin and skin on the
extremities, such as the hands and forearms studied in
Euvrard. Facial skin, more traditionally afflicted with
acne, is much more prone to irritation and often thinner
than skin on extremities.” Id. The district court found
that “[b]ased on these differences, one of ordinary skill in
the art would not conclude from Euvrard that adapalene
0.3% gel would result in the same tolerability profile in
patients with acne vulgaris.” Id.
    The correctness of this finding is not disputed by my
colleagues. Instead, without acknowledging or correcting
the district court’s findings, my colleagues cite Euvrard
(2002) as teaching the use of 0.3% adapalene for “other
conditions” without intolerable irritability. However, the
issue here is acne vulgaris, not “other conditions.”
     Differin 0.1% Gel Data Sheet (1996)
    Differin® is the trademark for Galderma’s adapalene
products. The data sheet for 0.1% Differin cautioned
against “overdosage,” stating that: “If the medication is

     10 Euvrard, How Adapalene Can Treat Actinic Kera-
toses, Supp. to Skin & Aging 12–15 (Nov. 2000).
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.            13

applied excessively, no more rapid or better results will be
obtained and marked redness, peeling, or discomfort may
occur.” DCt. Op. at 607. Galderma cited the overdosage
warning as evidence of teaching away from higher adapa-
lene concentrations. The district court did not appear to
give weight to the data sheet, explaining that the warning
was required by law. Id. at 642 n.11 (citing 21 C.F.R.
§ 201.56).
   The Bershad article (1999) 11
    This article describes a “roundtable” meeting of der-
matologists. Referencing the commercial 0.1% adapalene
product, Bershad (1999) states that “[a]lthough adapalene
is commonly believed to be one of the least irritating
topical retinoids, the perception of many dermatologists is
that this advantage is at least partially negated by a
relatively lower efficacy compared with the other topical
retinoids.” Bershad (1999) at 11. The district court did
not discuss Bershad, although it is cited by the panel
majority.
    Tolmar contends that this article provides motivation
to increase the concentration of adapalene. Galderma
responds that this article does not show any expectation
or understanding that the concentration of adapalene
could be increased three-fold without the predicted irritat-
ing side effects. At trial, Tolmar’s expert opined that this
article suggested using doses of adapalene higher than
0.1%. Tr. at 1301:14-16. Galderma’s expert disagreed,
stating that the authors were merely discussing the
characteristics of the various available acne treatments.
Tr. at 1301:21-23. This roundtable discussion does not
render obvious the three-fold increase in dosage, when so

   11   Bershad et al., Topical Retinoids in the Treatment
of Acne Vulgaris, 64 (Suppl. 2) Cutaneous Med. for the
Practitioner 8-19 (Aug. 1999).
14              GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

many publications cautioned against the increased irrita-
bility of higher dosages.
     The Jamoulle article (1989) 12
    This article describes a study involving the applica-
tion of a formulation containing 0.3% adapalene to hair-
less rats. The district court did not discuss this article.
The panel majority states that Jamoulle (1989) teaches
the use of 0.3% adapalene to treat acne. Maj. op. at 4.
However, results in hairless rats were not shown to
establish dosage and tolerance on human skin, much less
skin sensitized by acne.
                            II
           THE “SECONDARY CONSIDERATIONS”
     Commercial Success
    The district court found that despite late entry into a
crowded market for treatment of acne, Galderma’s Differ-
in® 0.3% gel quickly gained and maintained market
share, despite an overall declining market. The district
court agreed with Galderma that Tolmar seeks to sell the
0.3% formulation precisely because that formulation is
preferred by consumers over the 0.1% formulation. The
court found that the availability of cheaper generic 0.1%
adapalene after the expiration of the Shroot patents did
not appear to have affected consumer demand for the
Differin® 0.3% product, whose market share and revenue
were not explained by promotional activity, which had
actually decreased. Clear error has not been shown in
these findings.

     12  Jamoulle et al., Follicular Penetration, Distribu-
tion and Migration of CD271, a New Napthoic Acid Deriv-
ative for Topical Acne Treatment, 3 Pharmacol. & the Skin
198-200 (1989).
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.          15

    My colleagues discount the factor of commercial suc-
cess, arguing that the entry of 0.3% adapalene products,
by Tolmar or others, had previously been blocked by the
Shroot patents. Maj. op. at 14. However, the evidence in
the district court was that the 0.3% product was success-
ful against the 0.1% product and other acne medications.
The district court did not err in including evidence of
commercial success in its evaluation of the question of
obviousness.
   Teaching Away
    The district court found, based on the prior art and
the expert testimony presented by both sides, that the
evidence as a whole taught away from increasing the
concentration of adapalene above 0.1%. The district court
found that “[t]he increased irritation observed in
[Verschoore (1991) and Alirezai (1996)] when tripling the
concentration of adapalene from 0.03% to 0.1% effectively
taught away from again tripling the concentration from
0.1% to 0.3%, given the potential for increased side ef-
fects.” DCt. Op. at 641-42.
    The district court also found that Allec (1997),
Verschoore (1997) and Czernielewski (2001) “would also
have taught away from tripling the concentration of
adapalene from 0.1% to 0.3%, which would have been a
significant deviation from the then-understood optimal
concentration.” DCt. Op. at 642. The court found that the
experience of those skilled with other topical retinoids
that had been approved for human use, such as tretinoin
and tazarotene, further taught away from tripling of the
concentration of adapalene. The court explained that
both tretinoin and tazarotene faced tolerability problems
which required the manufacturers to decrease their
concentration in products for the treatment of acne. Clear
error has not been shown in these findings.
16              GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

     Unexpected Results
     The district court found that it was unexpected that
the tolerability profile of 0.3% adapalene was not statisti-
cally different from that of 0.1% adapalene. Tolmar had
argued—and repeats on appeal—that at most the tolera-
bility profile of 0.3% adapalene represents a difference in
degree, not in kind. However, based on expert testimony
from both sides, the district court found that “[w]hereas
the prior art suggested a dose-dependent, clinically mean-
ingful increase in side effects would result from increasing
the concentration of adapalene from 0.03% to 0.1%, the
claimed inventions achieved a difference in kind by dis-
continuing that trend.” Id. at 643.
     The district court explained that differences in degree
occur when the invention is merely a continuation of a
trend previously described in the prior art. Id. at n. 14
(citing In re Huang, 100 F.3d 135 (Fed. Cir. 1996); Iron
Grip Barbell Co., Inc. v. USA Sports, Inc., 392 F.3d 1317,
1323 (Fed. Cir. 2004)). Here, the prior art showed a trend
to increased adverse side effects with increased concen-
tration, while Galderma’s products violated that trend.
This was a difference in kind, not in degree.
    Clear error has not been shown in these findings, all
of which are discounted or ignored by the panel majority.
                            III
                 THE DECISION AT TRIAL
    The district court considered all of the evidence and
argument, and concluded that the claims to the 0.3%
adapalene formulations had not been proved invalid by
clear and convincing evidence. The court acknowledged
Tolmar’s argument that obviousness should be presumed:
Tolmar argued that “because 0.3% adapalene falls within
the 0.01%-1.0% range previously disclosed in Galderma’s
Shroot patents the claimed inventions are prima facie
obvious,” and that “‘evidence of secondary considerations
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.             17

simply cannot overcome the presumption’ of obviousness.”
DCt. Op. at 637 (quoting Tolmar’s trial brief). The district
court, unlike the panel majority, correctly recognized that
a prima facie showing is not a presumption of obvious-
ness, and does not change the placement of the burden of
proof. The district court recited:
    Recently, the Federal Circuit rejected such an ap-
    proach to obviousness in the context of litigation.
    The Federal Circuit noted that the Supreme Court
    “has never spoken in terms of a legally rebuttable
    presumption with respect to obviousness;” nor has
    it provided any “indication that it believes the
    burden of persuasion should shift to the patentee
    at [any] point to prove nonobviousness.”
DCt. Op. at 637-638 (quoting In re Cyclobenzaprine Hy-
drochloride Litigation, 676 F.3d 1063, 1078 (Fed. Cir.
2012)).
    The district court correctly explained that “the proper
analysis of obviousness under 35 U.S.C. §103 requires
that ‘all evidence relevant to obviousness or nonobvious-
ness be considered, and be considered collectively,’ with-
out resort to presumptions of prima facie obviousness or
burden-shifting.” DCt. Op. at 638 (quoting Cycloben-
zaprine, 676 F.3d at 1078). This is the correct standard,
established in Graham v. John Deere and reiterated
consistently and exhaustively.
    The dispositive findings in this case, viz. the content
of the prior art, whether the prior art taught away,
whether the invention produced unexpected results, and
whether there was commercial success, involve factual
inquires that must be accepted on appeal unless clearly
erroneous. See In re Applied Materials, Inc., 692 F.3d
1289, 1294 (Fed. Cir. 2012) (“Obviousness is a question of
law with several underlying factual inquiries, including
what a reference teaches, whether a reference teaches
away, and whether there is commercial success.”) (citing
18              GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.

Graham v. John Deere Co. of Kan. City, 383 U.S. 1, 17-18
(1966)). Clear error has not been shown in the district
court’s findings. Instead, on highly selective snippets of
the information that was before the district court, my
colleagues simply make their own findings.
    The burden of overcoming a district court’s factual
findings is heavy. See Anderson v. Bessemer City, N.C.,
470 U.S. 564, 574 (1985) (“Where there are two permissi-
ble views of the evidence, the factfinder’s choice between
them cannot not be clearly erroneous.”). Based on the
expert testimony, the documentary evidence, and the
factual findings of teaching away, unexpected results, and
commercial success, the district court concluded that
Tolmar failed to prove by clear and convincing evidence
that the inventions of the patents-in-suit would have been
obvious to a person of ordinary skill in the field of the
inventions. For the reasons discussed by the district
court, the judgment requires affirmance.
    Tolmar was required to provide clear and convincing
evidence that the selection of 0.3% from within the broad
range in the prior art was obvious in view of the entirety
of the evidence. The evidence at trial was that the in-
crease in adapalene concentration was viewed skeptically,
and that the combination of efficacy and safety of the
0.3% dose was unexpected to the experts. The experts at
trial agreed that the beneficial combination of properties
of the 0.3% dose could not have been predicted in advance
– indeed the opposite was predicted. The resultant prod-
uct was commercially successful despite the cheaper prior
product at lower dosage.
    The panel majority mentions but does not apply the
presumption of validity. My colleagues hold that for
inventions “where there is a range disclosed in the prior
art, and the claimed invention falls within that range,”
the burden falls upon the patentee to support patentabil-
ity. Maj. op. at 9. This is not just a shift in the burden of
GALDERMA LABORATORIES, L.P.   v. TOLMAR, INC.            19

production; the majority never requires that Tolmar meet
its burden of persuasion. Instead, once Tolmar had
demonstrated that the invention fell within a broad range
disclosed in the prior art, according to the panel majority,
Tolmar met its evidentiary burden. My colleagues do not
require that the prior art provide some reason for selec-
tion of the patented embodiment. Instead, the court
places the burden of “rebuttal” on the patentee, and limits
rebuttal to the “secondary considerations.”
    The panel majority also makes creative new rules,
ruling that patentability is negated “where the modifica-
tion of the percentage is within the capabilities of one
skilled in the art at the time.” Maj. op. at 12. The holding
that since “skilled artisans were capable of adjusting the
percentage,” the product containing 300% more active
ingredient, “although unexpected” in properties, id., is
unpatentable, is new and incorrect law. A skilled artisan
will nearly always be “capable” of adjusting a percentage
of an ingredient; this fact does not render unexpected
results not probative of unobviousness.
    Thus the court places new obstacles in the path of im-
provement patents, a change of law that is particularly
pernicious in the arts where small differences may have
large consequences or benefits. This rule is of further
mischief now that the nation has adopted a first-to-file
law with its pressures for early filing, possibly before all
embodiments have been fully explored.
    The district court applied the correct law to a vast
body of evidence, most of which is not discussed by the
panel majority. The district court properly applied stat-
ute and precedent. From my colleagues’ inappropriate
rulings, I respectfully dissent.