Ex Parte Houze

Board of Patent Appeals and Interferences

Mar 16, 2010

10330361 (B.P.A.I. Mar. 16, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DAVID HOUZE
__________

Appeal1 2009-008650
Application 10/330,361
Technology Center 1600
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Decided: March 16, 2010
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Before LORA M. GREEN, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134 involving claims to
transdermal steroid delivery compositions2. We have jurisdiction under 35
U.S.C. § 6(b). We reverse.

1 Oral Hearing held on March 9, 2009.
2 This Appeal is related to 2009-008867 and 2009-008869.
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Statement of the Case
Background
“Steroids such as estradiol and norethindrone are especially well
known for use in transdermal drug delivery systems, in particular, as
hormone replacement therapy” (Spec. 1 ¶ 0003). According to the
Specification, a “problem in the delivery of steroids from transdermal drug
delivery systems lies in the rate of drug release (commonly called ‘flux’ or
‘permeation rate’) from the transdermal system. Specifically, there are many
applications in which it would be desirable to have a greater flux of steroid
from the system” (Spec. 2 ¶ 0006).
The Specification teaches that “when the steroid is administered
together with its corresponding steroid derivative, a synergism in flux is
observed as well as a reduction in crystallization” (Spec. 6 ¶ 0026).
The Claims
Claims 1-10, 14-16, 19-22, 28, 66, 67, and 69-80 are on appeal3.
Claim 1 is representative and reads as follows:
1. A composition for the transdermal delivery of a drug
resulting from an admixture comprising:
a therapeutically effective amount of a drug that
includes a steroid and a corresponding steroid derivative that
provides a source of therapeutically active steroid; and
a pharmaceutically acceptable carrier,
wherein the steroid and the corresponding steroid
derivative are present in a weight/weight ratio of from 10:1
to 1:10 steroid:corresponding steroid derivative,
and wherein said steroid is selected from the group
consisting of anabolic steroids, androgenic steroids,
glucocorticoids and mineralcorticoids.

3 Claims 18, 32-65, and 81 are withdrawn (see App. Br. 6).
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The prior art
The Examiner relies on the following prior art references to show
unpatentability:
Sablotsky US 4,585,452 Apr. 29, 1986
Chiang et al. US 5,770,219 Jun. 23, 1998
Zoumas et al. US 5,849,729 Dec. 15, 1998
Miranda et al. US 5,958,446 Sep. 28, 1999

The issue
The Examiner rejected claims 1-10, 14-16, 19-22, 28, 66, 67, and 69-
80 under 35 U.S.C. § 103(a) as obvious over Chiang, Sablotsky, Miranda,
and Zoumas (Final Rej. 2-4).
The Examiner finds that the ordinary artisan “would have been
motivated to employ the Miranda's transdermal system for the actives of
[Chiang] and [Sablotsky] because the advantage of Miranda's system
possesses” (Final Rej. 4). The Examiner finds that the ordinary artisan
“would then incorporate the active steroid compounds of [Chiang] and
[Sablotsky] such as testosterone and its acetate to Miranda system in order to
easily control the rate of release of the steroid compounds” (Final Rej. 4).
The Examiner concludes that “the optimization of result effect parameters
(e.g., dosage range, dosing regimens) is obvious as being within the skill of
the artisan” (Final Rej. 4).
Appellant argues that “nothing in the cited references suggests
combining both a steroid and a corresponding steroid derivative in the same
composition. Thus, only impermissible hindsight leads to the claimed
invention” (App. Br. 11). Appellant argues that as “taught throughout the
specification as filed, admixing a steroid and a corresponding steroid
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derivative as claimed offers advantages such as improved flux and/or
reduced crystallization. The cited references do not suggest any advantage to
admixing a steroid and a corresponding steroid derivative, let alone these
specific effects” (Reply Br. 6).
In view of these conflicting positions, we frame the obviousness issue
before us as follows:
Does the evidence of record support the Examiner’s conclusion that
the cited references render obvious the composition of claim 1?
Findings of Fact (FF)
1. Miranda teaches “a transdermal drug delivery system wherein a
blend of at least two polymers having differing solubility parameters adjusts
the solubility of a drug in the polymeric blend and thereby modulates the
delivery of the drug from the system and through the dermis” (Miranda, col.
3, ll. 36-40).
2. Miranda teaches that “the bioactive agent may comprise a drug.
In particularly, preferred embodiments, the drug is a steroid, such as an
estrogen or a progestational agent, or combination thereof” (Miranda, col. 3,
ll. 59-62).
3. Miranda teaches that “[i]t should be noted that the bioactive
agents may be used singly or as a mixture of two or more such agents, and in
amounts sufficient to prevent, cure, diagnose or treat a disease, as the case
may be” (Miranda, col. 10, ll. 43-46).
4. Miranda teaches that an “estradiol/norethindrone acetate
combination-polymer mixture was prepared” (Miranda, col. 20, ll. 3-4).
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5. Chiang teaches “a transdermal drug delivery device for
administering a drug to a predetermined area of skin or mucosa of a patient”
(Chiang, col. 2, ll. 8-10).
6. Chiang teaches that:
Steroid drugs represent a preferred class of
drugs for use in conjunction with the drug delivery
device . . . Examples of steroid drugs useful herein
include: progestogens such as norethindrone,
norethindrone acetate, desogestrel, 3-keto desogestrel,
gestadene and levonorgestrel; estrogens such as
estradiol and its esters, e.g., estradiol valerate,
cyprionate, decanoate and acetate, as well as ethinyl
estradiol; androgens such as testosterone and its
esters; and corticosteroids such as cortisone,
hydrocortisone, and fluocinolone acetonide.

(Chiang, col. 3, ll. 31-45).
7. Sablotsky teaches “transdermal administration of a drug to a
patient over a prolonged period of time” (Sablotsky, col. 1, ll. 49-50).
8. Sablotsky teaches that “[m]ixtures of drugs are also
contemplated, such as for the estrogen embodiment a mixture of estradiol
itself and its benzoate ester” (Sablotsky, col. 8, ll. 12-14).
9. The Examiner finds that Zoumas teaches that “testosterone and
its acetate can be delivered through the skin after localized application”
(Final Rej. 4).
10. The Specification teaches that “[a]s Figure 3 indicates, the flux
for the combined testosterone/testosterone acetate of Example 3 was
significantly higher than the Testoderm® composition. Also, the individual
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fluxes of the testosterone and testosterone acetate of Example 3 were each
greater than the flux of Testoderm®” (Spec. 18 ¶ 0068).
11. Figure 3 of the Specification is reproduced below:

“FIGURE 3 is a graph illustrating the drug flux of combined
testosterone/testosterone acetate from a composition containing
testosterone/testosterone acetate, the flux of testosterone acetate from the
same composition, the flux of testosterone from the same composition and
the flux of testosterone from a transdermal drug delivery system called
Testoderm ®” (Spec. 3 ¶ 0014).
12. The Specification teaches preparation of various combinations
of steroids and steroid derivatives as shown below:
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(Spec. 18 ¶ 0069).
13. The Specification teaches that “[e]xamples 4-1 and 4-2 had
crystals after 3 days. Examples 4-3 and 4-4 had no crystals at 13 days. From
these results the acetate ester of estradiol is not as effective in inhibiting
crystals, whereas, the propionate and enanthanate are effective in inhibiting
crystals” (Spec. 18 ¶ 0070).

Principles of Law
As the Supreme Court pointed out in KSR Int' l Co. v.
Teleflex Inc., 550 U.S. 398, 418 (2007), “a patent composed of
several elements is not proved obvious merely by demonstrating
that each of its elements was, independently, known in the prior
art.” Rather, the Court stated:
[I]t can be important to identify a reason that would
have prompted a person of ordinary skill in the
relevant field to combine the elements in the way the
claimed new invention does . . . because inventions in
most, if not all, instances rely upon building blocks
long since uncovered, and claimed discoveries almost
of necessity will be combinations of what, in some
sense, is already known.

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Id. at 418-419 (emphasis added); see also id. at 418 (requiring a
determination of “whether there was an apparent reason to combine the
known elements in the fashion claimed by the patent at issue”) (emphasis
added).
KSR recognized that “the fact that a combination was obvious to try
might show that it was obvious under § 103.” Id. at 421. In Kubin, the
Federal Circuit recognized that KSR “resurrects this court’s own wisdom in
In re O’Farrell” and addressed the question of “when is an invention that
was obvious to try nevertheless nonobvious?” In re Kubin, 561 F.3d 1351,
1359 (Fed. Cir. 2009) (citing In re O'Farrell, 853 F.2d 894, 903
(Fed.Cir.1988)).
Kubin stated that
[t]o differentiate between proper and improper
applications of ‘obvious to try,’ this court outlined
two classes of situations where ‘obvious to try’ is
erroneously equated with obviousness under § 103. In
the first class of cases,

what would have been ‘obvious to try’
would have been to vary all parameters
or try each of numerous possible choices
until one possibly arrived at a successful
result, where the prior art gave either no
indication of which parameters were
critical or no direction as to which of
many possible choices is likely to be
successful.

In re Kubin, 561 F.3d at 1359 (citing In re O'Farrell, 853 F.2d at 903).
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Analysis
Miranda, Chiang, and Zoumas teach transdermal patches with steroids
(FF 1-6 and 9). Sablotsky teaches transdermal patches and does teach an
exemplary mixture of estradiol and its benzoate ester (FF 8). However,
Claim 1 does not encompass estradiol or estradiol derivatives at all, and
Claim 66 excludes the benzoate ester of estradiol (see Claims 1 and 66).
The Examiner concludes that it would have been obvious to the
ordinary artisan to “employ the combination of any steroids disclosed in the
specification, including testosterone and its esters, into Miranda's system and
the resulting effect is considered accomplished” (Ans. 6).
Appellant argues that “nothing in the cited references suggests
combining both a steroid and a corresponding steroid derivative in the same
composition. Thus, only impermissible hindsight leads to the claimed
invention” (App. Br. 11).
We conclude that the Appellant has the better position. In Kubin, the
court made clear that “where a defendant merely throws metaphorical darts
at a board filled with combinatorial prior art possibilities, courts should not
succumb to hindsight claims of obviousness.” Kubin, 561 F.3d at 1359.
This rejection is such a situation, where the prior art gives an immense
number of possible drug compounds, including a large number of different
steroids. Miranda, Chiang, Zoumas and Sablotsky do not provide any
guidance on which drugs were critical and no direction on which members
of the immense genus of possible drug combinations is likely to be
successful (FF 1-9).
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However, beyond the prima facie case of obviousness, this
Specification provides specific evidence of unexpected results for one
member of three different classes of steroids, with the androgen,
testosterone, the estrogen, estradiol, and the progestigen, norethindrone (see
Spec. 16-18). For example, the Specification teaches that “[a]s Figure 3
indicates, the flux for the combined testosterone/testosterone acetate of
Example 3 was significantly higher than the Testoderm® composition. Also,
the individual fluxes of the testosterone and testosterone acetate of Example
3 were each greater than the flux of Testoderm®” (Spec. 18 ¶ 0068; FF 10-
11). This provides specific evidence that the combination of testosterone
and testosterone acetate provide superior delivery over a commercially
available composition containing only testosterone.
The Specification provides a specific reason why the combination of
the steroid and its corresponding derivative has the unexpectedly improved
flux, which is that this combination reduces the crystallization of the steroid
or steroid derivative in the transdermal patch delivery device (see Spec. 6 ¶
0026). The Specification provides experimental evidence which shows that
crystallization is a real concern, noting that “[e]xamples 4-1 and 4-2 had
crystals after 3 days. Examples 4-3 and 4-4 had no crystals at 13 days. From
these results the acetate ester of estradiol is not as effective in inhibiting
crystals, whereas, the propionate and enanthanate are effective in inhibiting
crystals” (Spec. 18 ¶ 0070; FF 12-13).
Considered as a whole, we are persuaded that the evidence of record,
including the teachings of the prior art and the results detailed in the
Specification, warrant reversal of the obviousness rejection.
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Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the cited references render obvious the composition of claim 1.
SUMMARY
In summary, we reverse the rejection of claims 1-10, 14-16, 19-22, 28,
66, 67, and 69-80 under 35 U.S.C. § 103(a) over Miranda, Chiang,
Sablotsky, and Zoumas.

REVERSED

alw

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