Ex Parte Bohlmann et al

Patent Trial and Appeal Board

Oct 11, 2012

11321449 (P.T.A.B. Oct. 11, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ROLF BOHLMANN, DIETER BITTLER,
HERMANN KUENZER, PETER ESPERLING, HANS-PETER MUHN,
KARL-HEINRICH FRITZEMEIER, ULRIKE FUHRMANN,
KATJA PRELLE, and STEFFEN BORDEN
__________

Appeal 2011-012957
Application 11/321,449
Technology Center 1600
__________

Before ERIC GRIMES, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) from the rejection of
claims directed to a 18-methyl-19-nor-17-pregn-4-ene-21,17-carbolactone
compound and a pharmaceutical preparation. The Patent Examiner rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
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STATEMENT OF THE CASE
Compounds of the invention are said to have very strong gestagenic
action, to show a potassium-retaining, natriuretic (anti-mineralocorticoid)
action, and to be useful in pharmaceutical preparations for contraception and
treatment of premenstrual symptoms. (Spec. 6.) Claims 1, 6-18, 22, 24, and
26 are on appeal. Claim 1 is representative and reads as follows:
1. A 18-Methyl-19-nor-17-pregn-4-ene-21,17-carbolactone of general
formula I

Formula I
in which
Z means an oxygen atom,
R4 is a hydrogen atom,
R6 and R7 can be in α- or β-position, and, independently of one
another, mean a straight-chain or branched-chain alkyl group
with 1 to 4 carbon atoms, or
R6 means a hydrogen atom, and R7 means an α- or β-position,
straight-chain or branched-chain alkyl group with 1 to 4 carbon
atoms, or
R6 and R7 together mean an α- or β-position methylene group or an
additional bond.

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The Examiner rejected the claims as follows:
 claims 1, 6-11, 22, 24, and 26 under 35 U.S.C. § 103(a) as
unpatentable over Kandemirli1 and Petit;2
 claims 1, 6-18, 22, 24, and 26 under 35 U.S.C. § 103(a) as
unpatentable over Kandemirli, Petit, and Laurent;3 and
 claims 1, 6-18, 22, 24, and 26 under 35 U.S.C. § 103(a) as
unpatentable over Kandemirli, Petit, Laurent, and Nickisch.4

ISSUE
The Issue
The Examiner’s position is that Kandemirli described anti-aldosterone
17-spirolactone derivatives similar to Appellants’ compounds, but not the
particular claimed 18-methyl compounds. (Ans. 4-5.) Petit also described
similar anti-mineralocorticoid 17-spiro compounds, but not the particular
claimed 18-methyl compounds. (Id. at 5.) The Examiner found however
that a comparison of certain other 18-methyl compounds described by
Kandemirli and Petit established equivalency between methyl and hydrogen
in the 18-position. (Id. at 5-6, citing compounds.) The Examiner concluded:

1 Fatma Kandemirli et al., Investigation of structure-activity relationship on
17-spirolactone derivatives: the electronic-topological approach, 57 IL
FARMACO 601-607 (2002).
2 Francis Petit et al., US 6,147,066, issued Nov. 14, 2000.
3 Henry Laurent et al., US 6,177,416 B1, issued Jan. 23, 2001.
4 Klaus Nickisch et al., Aldosterone Antagonists. 4. Synthesis and Activities
of Steroidal 6,6-Ethylene-15,16-methylene 17-Spirolactones, 34 J. MED.
CHEM. 2484-2468 (1991).
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it would have been obvious to the skilled artisan in the art at the time
of the present invention to make any of the exemplified prior art
compounds having a 18-methyl group, such as,

with the reasonable expectation that the compound(s) would have
anti-mineralcorticoid activity as taught by the above cited references.

(Id. at 6.) In the rejection applying the Nickisch reference, the Examiner
cited Nickisch’s statement that “[t]he highest progestational potency is found
when the 10-position is substituted by a hydrogen and the 13-position with
an ethyl group (e.g., norgestrel).16”5 (Id. at 9, quoting Nickisch.) Based on
that disclosure, the Examiner concluded:
the skilled artisan would have been motivated to modify the prior art
compounds by making the 13-ethyl derivatives thereof, i.e.,

with the reasonable expectation of obtaining increased progestational
potency.

(Id. at 9-10.)

5 Nickisch’s footnote 16 reads: “Wiechert, R. Hoppe-Seyler’s Z. Physiol.
Chem. 1981, 362, 367.” Nickisch 2465.
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Appellants acknowledge that Kandemirli described a compound,
identified as compound 40, “which is a methyl group apart from a claimed
compound.” (App. Br. 3.) However, Appellants contend that Petit’s
disclosure is “generic” and “merely teaches broadly that various length alkyl
substituents are possible on various steroid compounds without any teaching
regarding the equivalence thereof.” (Id.) According to Appellants, “the
claimed compounds possess significant unexpected advantages over the
closest prior art compound, and as such, that they do not have similar
properties to the compound of Kandemirli et al., which is the allegation
based on Petit et al.” (Id.)
More specifically, Appellants contend that a submitted declaration
demonstrates that
the progestagenic activity in vivo; pregnancy maintenance in the rat
(ED50) was almost 12 times higher for the compound of the claims
than for compound 40 of Kandemerli [sic] et al., i.e., 0.008 mg/kg/d
for the compound of the claimed invention while 0.094 mg/kg/d for
the compound of Kandemerli et al. Nothing in the prior art provides a
reason for one of ordinary skill in the art to expect such a significant
improvement for the compound of the claims over the compound of
Kandemerli et. al. As such, the results are unexpected.

(Id. at 5.) Appellants contend that Nickisch pertained to norgestrel, but that
norgestrel is not a relevant compound because Nickisch indicated the
importance of the 17α-position, that Nickisch’s best improvement was only
two-fold, and that Nickisch disclosed low solubility for a compound with a
13-position ethyl group. (Id. at 4.) Appellants contend that Nickisch does
not provide a reason to expect almost 12 times higher improvement in the
pregnancy test, and that the Declaration’s evidence is “adequately
representative” of the compounds claimed. (Id. at 5-7.)
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The Examiner responds that (i) the increase in progestational activity
would have been expected, in view of the Nickisch disclosure (Ans. 12-14),
and (ii) the declaration’s showing is not commensurate in scope with the
claims (id. at 15).
Appellants reply that the Examiner erred in discounting the magnitude
of the improvement shown. (Reply Br. 1, citing In re Soni, 54 F.3d 746
(Fed. Cir. 1995).)
The issues with respect to this rejection are:
whether the Kandemirli and Petit disclosures were sufficient evidence
of prima facie obviousness; and if so,
whether the totality of the record evidence supports a conclusion of
obviousness.

Findings of Fact
1. The record includes a “Declaration Under 37 C.F.R. §1.132” by
Steffen Borden, dated Dec. 22, 2009. (Decl.)
2. Declarant Borden states that “Compound 1,” said to be a compound of
the invention, was compared to “Compound 2,” said to Kandemirli’s
Compound 40, in several tests. (Decl. 2.)
3. According to Declarant Borden, “Compound 40 of Kandemirli et al. is
closest in structure to compounds of the claimed invention than any of
the other specific compounds (1-60) identified within the disclosure of
Kandemirli et al.” (Id.)
4. According to Declarant Borden, “Compounds 1 and 2 differ
structurally by only an ethyl group (Compound 1) versus a methyl
group (Compound 2) on carbon atom 13.” (Id.)
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5. Declarant Borden states that “Compound 1 shows 11.75 times higher
progestagenic activity in vivo compared to compound 2. (Compare the
ED50 of 0.008 mg/kg/d of compound 1 to the ED50 of 0.094 mg/kg/d
of compound 2.).” (Id.)
6. Declarant Borden states: “This difference in the level of
progestagenic activity would not be expected based on the teachings
within Kandemirli et at. (Farmaco, 2002), either alone or combined
with the teachings of Petit et al. (US 6,147,066) and/or Laurent et al.
(US 6,117,416).” (Id.)

Principles of Law
[S]tructural similarity between claimed and prior art subject matter,
proved by combining references or otherwise, where the prior art
gives reason or motivation to make the claimed compositions, creates
a prima facie case of obviousness. The “reason or motivation” need
not be an explicit teaching that the claimed compound will have a
particular utility; it is sufficient to show that the claimed and prior art
compounds possess a “sufficiently close relationship ... to create an
expectation,” in light of the totality of the prior art, that the new
compound will have “similar properties” to the old. . . . Once such a
prima facie case is established, it falls to the applicant or patentee to
rebut it, for example with a showing that the claimed compound has
unexpected properties.

Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499 F.3d 1293, 1301
(Fed. Cir. 2007) (citations omitted).
“One way for a patent applicant to rebut a prima facie case of
obviousness is to make a showing of ‘unexpected results,’ i.e., to show that
the claimed invention exhibits some superior property or advantage that
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person of ordinary skill in the relevant art would have found surprising or
unexpected.” In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995).
“Establishing that one (or a small number of) species gives
unexpected results is inadequate proof, for it is the view of this court that
objective evidence of non-obviousness must be commensurate in scope with
the claims which the evidence is offered to support.” In re Greenfield,
571 F.2d 1185, 1189 (CCPA 1978) (quotations omitted).
“If an applicant demonstrates that an embodiment has an unexpected
result and provides an adequate basis to support the conclusion that other
embodiments falling within the claim will behave in the same manner, this
will generally establish that the evidence is commensurate with [the] scope
of the claims.” In re Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011).

Analysis
Absent evidence provided in the Borden Declaration and considering
only the cited prior art, we agree with the Examiner that there would have
been a prima facie case of obviousness for the claimed compounds.
However, the Declaration evidence establishes that a compound of the
invention showed an increase in progestational activity an order of
magnitude greater than the closest prior art compound. (FF 5.) As
Appellants admit, Nickisch suggested the possibility of obtaining a two-fold
increase, but on this record, there is no evidence that close to a 12-fold
increase would have been expected. (See App. Br. 5-6.) Taking all the
record evidence into account, a conclusion of obviousness lacks support.
We agree with the Examiner that evidence of unexpected results must
be commensurate in scope with the claims. See, e.g., Greenfield, 571 F.2d at
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1189. Appellants point out, however, that the claimed compounds vary only
at R6 and R7, and not broadly, and vary less than the prior art compounds.
(App. Br. 6-7.) Appellants contend that, absent a reason to expect a different
result, the Declaration’s comparative evidence is adequate. (Id., quoting In
re Saunders, 144 F.2d 599 (CCPA 1971).) In addition to the passage
Appellants quote from Saunders, the court noted that “homology may be
used by an applicant as well as against him.” 444 F.2d at 605 n.6.
Appellants’ arguments about the scope of the comparative evidence are
persuasive in light of the small genus claimed by claim 1. See Kao,
639 F.3d at 1068. The rejections are reversed.

SUMMARY
We reverse the rejection of claims 1, 6-11, 22, 24, and 26 under
35 U.S.C. § 103(a) as unpatentable over Kandemirli and Petit.
We reverse the rejection of claims 1, 6-18, 22, 24, and 26 under
35 U.S.C. § 103(a) as unpatentable over Kandemirli, Petit, and Laurent.
We reverse the rejection of claims 1, 6-18, 22, 24, and 26 under
35 U.S.C. § 103(a) as unpatentable over Kandemirli, Petit, Laurent, and
Nickisch.

REVERSED

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