Ex Parte Houze

Board of Patent Appeals and Interferences

Mar 16, 2010

10330360 (B.P.A.I. Mar. 16, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DAVID HOUZE
__________

Appeal1 2009-008869
Application 10/330,360
Technology Center 1600
__________

Decided: March 16, 2010
__________

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 methods
for enhancing transdermal delivery of a steroid drug2. 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 2009-008650 and 2009-008867.
Appeal 2009-008869
Application 10/330,360

2
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 26, 32-36, 40, 42-49, and 55-57 are on appeal3. Claim 26 is
representative and reads as follows:
26. A method for enhancing the transdermal delivery of a
steroid drug, comprising administering the steroid drug in a
pharmaceutically acceptable carrier that comprises a
combination of:
a therapeutically effective amount of at least one
steroid; and
a corresponding steroid derivative that provides a
source of therapeutically active steroid,
wherein the steroid and the corresponding steroid
derivative are present in a weight/weight ratio of 10:1 to
1:10 steroid: corresponding steroid derivative,

3 Claims 37-39, 41, and 50-53 are withdrawn (see App. Br. 6).
Appeal 2009-008869
Application 10/330,360

3
wherein the steroid comprises a ring having a free
hydroxy group at a position on the ring.

The prior art
The Examiner relies on the following prior art references to show
unpatentability:
Chiang et al. US 5,770,219 Jun. 23, 1998
Jain et al. US 5,780,050 Jul. 14, 1998
Miranda et al. US 5,958,446 Sep. 28, 1999

The issues
The Examiner rejected claims4 26, 32-36, 40, 42-49, and 55-57 under
35 U.S.C. § 103(a) as obvious over Miranda and Chiang (Final Rej. 2-4).
The Examiner rejected claims 26, 32-36, 40, 42-49, and 55-57 under
35 U.S.C. § 103(a) as obvious over Miranda and Jain (Final Rej. 4-6).
The Examiner concludes that the ordinary artisan would have found it
obvious “to employ the Miranda’s transdermal system for the actives of
[Chiang], especially the testosterone and its ester such as acetate. It would
have been obvious to one of ordinary skill in the art at the time of invention
to adjust the weight amount of the active ingredients” (Final Rej. 3).
The Examiner also concludes that the ordinary artisan would have
found it obvious “to employ the Miranda’s transdermal system for the
actives of [Jain], especially the testosterone and its ester such as acetate. It
would have been obvious to one of ordinary skill in the art at the time of

4 Claim 54, listed in the Final Rejection, was canceled by
Appellant’s amendment of November 16, 2006.
Appeal 2009-008869
Application 10/330,360

4
invention to adjust the weight amount of the active ingredients” (Final Rej.
5).
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 the “Examiner’s Answer
does not recognize or address the unexpected results achieved by the present
invention, e.g., enhanced drug delivery. The cited references do not teach or
suggest that using a combination comprising a steroid and a corresponding
steroid derivative would achieve enhanced drug delivery” (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).
Appeal 2009-008869
Application 10/330,360

5
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).
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. Jain teaches that the “delivery of drugs through the derma, i.e.
skin and mucosa, provides many advantages over other routes of
administration” (Jain, col. 2, ll. 6-8).
8. Jain teaches that “[e]xamples of such androgens include
testosterone, methyltestosterone, fluoxymesterone, methandrostenolone,
nandrolone, norethandrolone, and esters and mixtures thereof. Testosterone
Appeal 2009-008869
Application 10/330,360

6
and esters thereof are preferred androgens having the requisite 3-keto-4-en
functional group” (Jain, col. 5, ll. 4-8).
9. 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).
10. 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).

Appeal 2009-008869
Application 10/330,360

7
11. The Specification teaches preparation of various combinations
of steroids and steroid derivatives as shown below:

(Spec. 18 ¶ 0069).
12. 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.
Appeal 2009-008869
Application 10/330,360

8

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).

Appeal 2009-008869
Application 10/330,360

9

Analysis
Miranda, Chiang, and Jain teach transdermal patches with steroids (FF
1-8). None of the cited references teach the use of steroid mixture
comprising the steroid and the corresponding steroid derivative.
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. 7). The Examiner
uses similar reasoning for both rejections with Miranda and Chiang, and
Miranda and Jain.
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, and Jain 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 1-8).
Appeal 2009-008869
Application 10/330,360

10
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 9-
10). 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 11-12).
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 rejections.
Appeal 2009-008869
Application 10/330,360

11
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the cited references render obvious the composition of claim 26.

SUMMARY
In summary, we reverse the rejection of claims 26, 32-36, 40, 42-49,
and 55-57 under 35 U.S.C. § 103(a) over Miranda and Chiang. We reverse
the rejection of claims 26, 32-36, 40, 42-49, and 55-57 under 35 U.S.C.
§ 103(a) over Miranda and Jain.

REVERSED

alw

FOLEY AND LARDNER, LLP
SUITE 500
3000 K STREET NW
WASHINGTON DC 20007