Ex Parte Blye et al

Board of Patent Appeals and Interferences

Jun 29, 2009

11040964 (B.P.A.I. Jun. 29, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte RICHARD P. BLYE and HYUN K. KIM
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Appeal 2009-002563
Application 11/040,964
Technology Center 1600
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Decided:1 June 29, 2009
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Before ERIC GRIMES, LORA M. GREEN, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL

1 The two-month time period for filing an appeal or commencing a civil
action, as provided for in 37 C.F.R. § 1.304, begins to run from the decided
date shown on this page of the decision. The time period does not run from
the Mail Date (paper delivery) or Notification Date (electronic delivery).

Appeal 2009-002563
Application 11/040,964

This is a decision on appeal from the Patent Examiner’s final rejection
of claims 82-84. Jurisdiction for this appeal is under 35 U.S.C. § 6(b). We
affirm.
STATEMENT OF THE CASE
The claims are drawn to a single compound, 7α,11β-dimethyl-17β-
hydroxyestr-4-en-3-one 17-undecanoate in crystalline form. This compound
is a synthetic androgen which is used as a substitute for testosterone (Spec.
1:4 & 13). Claims 82-84 are pending.
Claims 82-84 were finally rejected by the Examiner as obvious under
35 U.S.C. § 103(a) over Cook et al. (U.S. Pat. No. 5,952,319, Sep. 14,
1999). This is the second time this rejection has been before us. Appeal No.
2007-1821 (“1821 Decision”), decided on June 1, 2007, involved the same
application as in the present proceeding. In that appeal, the rejection of
claims 82-842 over the Cook patent was affirmed – the same claims which
are now on appeal. Appellants had argued that the claimed compound had
“unexpected and superior properties” as compared to Cook’s 7α,11β-
dimethyl nortestosterone enanthate (1821 Decision 11). To support this
assertion, a declaration was provided by Dr. Richard P. Blye, a co-inventor.

2 The rejection of claims 75-80, 85, and 86 was also affirmed, but these
claims are not involved in the instant Appeal. A Request for Rehearing
(July 31, 2007) was filed on the affirmed rejection, but – as noted by
Appellants – has not been decided. To maintain the same time period for
appeal as set forth under 37 C.F.R. § 1.304 for all claims in the instant
application (i.e., claims 82-84 and claims 75-80, 85, and 86), a decision on
the July 31, 2007 Request for Rehearing will be deferred: 1) until the same
time as a decision is made on a Request for Rehearing, should Appellants
choose to file one, in the present appeal; or 2) until the time periods under
37 C.F.R. §§ 41.50 and 41.52 have expired, if no Request for Rehearing is
made in the present appeal.
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Application 11/040,964

Dr. Blye described an experiment in which the claimed compound (“CDB-
4521”) and Cook’s compound (“CDB-1422”) were tested for androgenic
activity in a ventral prostate assay (Blye 2 Declaration (dated stamped Sept.
14, 2006 and executed May 25, 2004) 2: ¶ 6; Decision 11). After reviewing
the declaration, we concluded that there was insufficient evidence that the
superiority of the claimed compound over Cook’s enanthate would have
been surprising to a person of ordinary skill in the art – a necessity to
establish unexpected results (Decision 14).
We stated:
Appellants have not explained the degree of difference between
the claimed compound and Cook’s. They show that its activity
[in the prostate assay] as determined by AUC [area under the
curve] is greater than Cook’s enanthate, but they do not explain
why an increase in activity would be surprising, rather than the
normal expected differences in activity between different
compounds.
. . .
[W]e find that Cook’s teaching that the 7α,11β-dimethyl-19-
nortestosterone enanthate was active over a ten-week period
would have led a person of ordinary skill in the art to
reasonably expect that claimed compound, which is structurally
similar to Cook’s compound, would possess long-acting
androgenic properties. Appellants have not demonstrated
against this baseline expectation that a person of skill in the art
would have found the results set forth in Blye 2 Declaration
unexpected and surprising to a person of ordinary skill in the
art.
(1821 Decision 14-15.)
Appellants filed a Request to Reopen Prosecution under 37 C.F.R.
§ 41.52 and provided a new declaration under 37 C.F.R. §1.132, again
executed by Dr. Richard P. Blye (Blye 3 Declaration, dated July 31, 2007).
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Application 11/040,964

The Examiner considered Dr. Blye’s testimony, but was not persuaded that it
established unexpected results for the claimed compound (Final Rejection 3,
dated Nov. 20, 2007).
Claim 82, which is representative of the appealed subject matter, reads
as follows:
82. 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one 17-
undecanoate (Compound II) in crystalline form.

STATEMENT OF ISSUE
The sole issue in this appeal is whether Appellants established that the
Examiner erred in concluding that the evidence in the Blye 3 Declaration
was insufficient to rebut the case of prima facie obviousness.
LEGAL PRINCIPLES
Once prima facie obviousness has been established, an applicant for a
patent can rebut it with
a showing of “unexpected results,” i.e., to show that the
claimed invention exhibits some superior property or advantage
that a person of ordinary skill in the relevant art would have
found surprising or unexpected. The basic principle behind this
rule is straightforward – that which would have been surprising
to a person of ordinary skill in a particular art would not have
been obvious.

In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995). To establish unexpected
results, the claimed subject matter must be compared with the closest prior
art. In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).

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Appeal 2009-002563
Application 11/040,964

FINDINGS OF FACT
Blye 3 Declaration
1. The claimed compound is 7α,11β-dimethyl-17β-hydroxyestr-4-en-3-one
17-undecanoate. This compound has an n-C10H21 alkyl group at its 17-
position (1821 Decision 4). Synonyms are: CDB-4521, dimethandrolone
undecanoate, and the 17-undecanoate ester (id.).
2. The compound in Cook is 7α,11β-dimethyl nortestosterone enanthate
(1821 Decision 4). This compound has an n-C6H13 alkyl group at its 17-
position (id.). Synonyms are: the enanthate ester of 7α,11β-dimethyl
nortestosterone, CDB-1422, dimethandrolone heptanoate, and the 17-
enanthate ester (id.).
3. The difference between the claimed compound and Cook is that the
claimed compound has an n-C10H21 alkyl group at its 17-position, while
Cook’s has an n-C6H13 alkyl group at its 17-position (1821 Decision 7). The
claimed compound therefore has a pendant alkyl group with a longer carbon
chain at the 17-position as compared to Cook.
4. Dr. Blye compared the activity of the claimed compound (“CDB-
4521A”) to Cook’s compound (“CDB-1422”) on rat ventral prostate weight
as a function of time (Blye 3 Declaration ¶ 6; Exhibit 1).
5. Dr. Blye stated that the activity of the claimed compound lasted for a
period of 14 weeks, while Cook’s compound “lasted only up to 10 weeks”
(Blye 3 Declaration ¶ 6).
6. Dr. Blye testified that the ventral prostate activity possessed by the
claimed compound as compared to Cook’s “would have been unexpected by
and surprising to those of ordinary skill in the art” (Blye 3 Declaration ¶ 7).
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Application 11/040,964

7. Dr. Blye provided Tables 1 and 2, summarizing data from a book titled
Androgens, published in 1956.
8. Based on the data in Tables 1 and 2, Dr. Blye testified that the activity of
the claimed compound was “unexpected and surprising.” (Blye 3
Declaration ¶ 9.)
ANALYSIS
The sole issue in this appeal is whether the Examiner erred in
concluding that the evidence in the Blye 3 Declaration was insufficient to
rebut the Examiner’s case of prima facie obviousness. We thus turn our
attention to Dr. Blye’s declaration.
Referring to Exhibit 1 of his declaration, Dr. Blye testified that the
activity for the claimed compound lasted for a period of 14 weeks, while
Cook’s activity “lasted only up to 10 weeks” (Blye 3 Declaration ¶ 6; FF5).
Exhibit 1 is a graph which shows the incremental increase in weight
of the ventral prostate over a 14-week period post-administration of the
claimed compound, with data reported for weeks 1, 2, 4, 6, 8, 10, 12, and 14.
For Cook’s compound, data was reported for weeks 1, 2, 4, 6, 8, and 10, but
there are no data points for weeks 12 and 14. Therefore, it is not clear on
what basis Dr. Blye concluded that Cook’s compound “lasted only up to 10
weeks.” No data points for it extended past ten weeks in the Exhibit 1
graph. The weight of the ventral prostate past ten weeks cannot be
ascertained. Because the data is incomplete, we cannot agree that it suffices
to establish “unexpected” and “surprising” results for the claimed compound
as compared to Cook’s with respect to duration of its activity.
In reaching our decision in the 2007-1821 Appeal, we criticized the
Blye 2 Declaration because it did not establish the baseline expectation of a
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Appeal 2009-002563
Application 11/040,964

person of ordinary skill in the art (1821 Decision 15). Appellants had
asserted that it was “surprising” that the claimed longer alkyl chain had more
activity than the shorter alkyl chain, but Dr. Blye had not identified any
reason as to why this difference would have been surprising, rather than the
normal expected differences in activity between different compounds (id. at
14). To remedy this deficiency, Dr. Blye submitted a third declaration in
which he reproduced data from a 1956 publication (FF7). Based on this
data, Dr. Blye testified that higher fatty acid esters – testosterone derivatives
with longer alkyl chains – were less active than the derivatives with shorter
alkyl chains (Blye 3 Declaration ¶ 9). Dr. Blye concluded that “the
expectation, if any, was that higher [alkyl chain] homologs would in fact
have reduced activity” (id.).
We have considered the evidence as summarized in paragraph 9 of the
Blye 3 Declaration, but remain unconvinced. Table 1, as testified by Dr.
Blye, shows that the longer alkyl chain testosterone derivatives possessed
less activity than testosterone substituted with shorter alkyl chains as
measured in the “Capon’s Comb” assay.3 For example, testosterone
butyrate with a four carbon chain required 60 micrograms to achieve its
maximal effect, while testosterone valerate with a five carbon chain required
200 micrograms to achieve its maximal effect. Based on this information,
Dr. Blye concluded that the claimed undecanoate compound with a 10
carbon chain would have been expected to “have little or no androgenic
activity.”

3 No explanation whatsoever is provided by Dr. Blye of what constitutes the
Capon’s comb assay.
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Appeal 2009-002563
Application 11/040,964

This argument is not persuasive. It was not established that persons of
ordinary skill in the art would have expected the structure/activity
relationship demonstrated for testosterone derivatives in the “Capone’s
comb” assay to have the same relationship as different compounds tested in
a different assay. Table 1 is said to show that increasing alkyl chain length
leads to less activity in the “Capone’s Comb” assay. However, there is no
evidence that persons of ordinary skill in the art would have expected the
relationship between activity and alkyl chain length to be conserved when
the assay is performed in the ventral prostate test - the test relied upon by
Appellants for unexpected results.
Appellants’ own evidence does not support this extrapolation. Table
2 of the Blye 3 Declaration is said to show the structure/activity relationship
of fatty acid testosterone derivatives “on Rat Seminal Vesicles.” Contrary to
the results shown in Table 1, the lowest chained alkyls had less activity than
some longer chained derivatives. For example, testosterone formate with
one carbon had the second worst (8) maximum effect, while the longer
chained isobutyrate derivative with four carbons had the best (1) maximum
effect. Thus, there were instances where a longer alkyl chain derivative had
more activity than a shorter chain derivative – the same result asserted to be
unexpected in this proceeding.
Although activity decreased as the alkyl chain was shortened for the
lower alkyl compounds, the opposite effect was observed for the higher
alkyl compounds. Following the isobutyrate testosterone derivative, the
activity of progressively longer alkyl chain derivatives is shown in Table 2
to have decreased as the alkyl chain was lengthened. In other words, in the
same assay, two different effects of alkyl chain length were observed.
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Appeal 2009-002563
Application 11/040,964

In sum, the structure/activity relationship for the Capone’s comb assay
(Table 1) was not strictly adhered to in the Rat Seminal Vesicle assay (Table
2). Therefore, the evidence suggests that activity obtained in one assay does
not necessarily predict the activity in a completely different assay.
Secondly, because the testosterone derivatives in Tables 1 and 2 have
not been tested in the ventral prostate assay, the relative activity of the
claimed compound cannot be ascertained. Relying on the results
summarized in Tables 1 and 2, Dr. Blye concluded that the claimed
compound would have been expected to have “little or no androgenic
activity.” The phrase “little . . . androgenic activity” as used in the Blye 3
Declaration appears to refer to a compound’s relative activity as compared to
other compounds. Testosterone n-decanoate is characterized by Dr. Blye as
having “little activity” because it is more than ten times less active (350)
than the shorter chained formate (20), acetate (20), and propionate (20)
derivatives. The Exhibit 1 graph depicts the activity of the claimed
compound, but it cannot be said whether this activity is “little” because it
has not been compared to any of the testosterone derivatives which, in Table
1, are shown to be more than ten times more potent than the longer chained
derivatives.
Furthermore, the Blye 3 Declaration has data only for testosterone
ester derivatives, but Cook’s compound is the dimethyl-19-nortestosterone
ester derivative. Cook shows that the nortestosterone derivative has greater
potency and longer duration than the corresponding testosterone derivative
(Table 2 and col. 18, ll. 49-51).
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Appeal 2009-002563
Application 11/040,964

Appellants contend that a further advantage to the claimed compound
is that it would be administered as an aqueous suspension and therefore
“there would be less pain during injection” (App. Br. 5).
To rebut prima facie obviousness, the evidence must be of an
unexpected difference in properties as compared to the prior art, not merely
a showing of an advantage. See In re Hoch, 428 F.2d 1341, 1343 (CCPA
1970). Here, Appellants have not provided evidence that Cook’s compound
could not be administered as aqueous suspension nor that a subject would
experience less pain than with another form of delivery. Attorney argument
is not evidence. In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Nor can
it take the place of evidence lacking in the record. Meitzner v. Mindick, 549
F.2d 775, 782 (CCPA 1977).

CONCLUSION OF LAW
The Examiner did not err in concluding that the evidence in the Blye 3
Declaration was insufficient to rebut the Examiner’s case of prima facie
obviousness.

SUMMARY
The obviousness rejection of clam 82 is affirmed. Claims 83 and 84
fall with claim 82 because separate arguments for their patentability were
not provided. 37 C.F.R. § 41.37(1)(c)(vii).

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
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Appeal 2009-002563
Application 11/040,964

AFFIRMED

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