Ex Parte Manosroi et al

Board of Patent Appeals and Interferences

Apr 19, 2010

11438193 (B.P.A.I. Apr. 19, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ARANYA MANOSROI, JIRADEJ MANOSROI,
DUANG BUDDHASUKH, PATTANA SRIPALAKIT,
ROLAND MAIER, and ROLF G. WERNER
__________

Appeal 2009-010495
Application 11/438,193
Technology Center 1600
__________

Decided: April 19, 2010
__________

Before ERIC GRIMES, LORA M. GREEN, and STEPHEN WALSH,
Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
process for the production of cyproterone acetate. The Patent Examiner
rejected the claims on the ground of obviousness. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.
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STATEMENT OF THE CASE
The Specification states that the invention “relates to improved
methods for synthesizing cyproterone acetate.” (Spec. 1:10-11.) Various
strategies for synthesizing the compound were known in the prior art. (Id. at
2:4-5.)
Claims 1-4, 12-14 and 30, which are all the pending claims, are on
appeal. Claims 1 and 2 are representative and read as follows:
1. Process for the production of cyproterone acetate (M), comprising

(a) converting 17α-acetoxy-6,7α-oxido-4-pregnene-3,20-dione (J2)
into chlormadinone acetate (K2) by a single step procedure;

(b) introducing a double bond at position 1 of (K2) to yield
delmadinone acetate (L2); and

(c) introducing a methylene group bridging positions 1 and 2 of
(L2) to yield cyproterone acetate (M).

2. Process according to claim 1, wherein 17α-acetoxy-6,7α-oxido-4-
pregnene-3,20-dione (J2) is produced by a process comprising

(d) introducing a double bond at position 6 of 17α-
acetoxyprogesterone (H) to convert it into 17α-acetoxy-4,6-
pregnadiene-3,20-dione (I2);

(e) converting the double bond at position 6 of (I2) into an epoxy
function to yield 17α-acetoxy-6,7α-oxido-4-pregnene-3,20-
dione (J2).

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The Examiner rejected claims 1-4, 12-14 and 30 under 35 U.S.C.
§ 103(a) as unpatentable over Neumann,1 Douglas,2 Kincl,3 Shibata,4 Wang,5
Van Kamp,6 and Arth.7
Claims 3, 4, 12-14 and 30 have not been argued separately and
therefore stand or fall with claim 1 or 2, according to their dependency on
claim 1 or 2. 37 C.F.R. § 41.37(c)(1)(vii).

OBVIOUSNESS
The Issue
The Examiner’s position is that each of the claimed process steps
would have been obvious over the prior art, and that the method as a whole
would have been obvious (Fin. Rej. 2-5). The Examiner found that
Neumann taught production of cyproterone acetate starting with 17α-
acetoxyprogesterone (id. at 3), but that Neumann’s process was “lengthy”
(id. at 5). The Examiner found that “the skilled artisan would be motivated
to obtain a shorter process” (id. at 5). Finding that teachings in prior steroid
synthesis references would be applicable to Neumann’s process, and that

1 F. Neumann et al., Cyproterone Acetate – Synthesis and possible uses of
an antiandrogen, 10 CHIMICA OGGI 27-34 (1986).
2 US Patent No. 3,644,440, issued to George H. Douglas et al., Feb. 22,
1972.
3 US Patent No. 3,280,114, issued to Fred A. Kincl, Oct. 18, 1966.
4 Kenyu Shibata et al., Antiandrogen. I. 2-Azapregnane and 2-Oxapregnane
Steroids, 40 CHEM. PHARM. BULL. 935-41 (1992).
5 Zhongqi Wang et al., Improved Synthesis of 1α,2α-Methylene
Chlormadinone Acetate, 4 CHINESE J. ORG. CHEM. 376-77 (1984).
6 US Patent No. 3,917,657, issued to Harmen Van Kamp et al., Nov. 4,
1975.
7 US Patent No. 3,753,979, issued to Glen E. Arth et al., Aug. 21, 1973.
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there would have been a reasonable expectation that the teachings would
have worked in a cyproterone acetate synthetic pathway, the Examiner
concluded that the claimed process would have been obvious.
Appellants contend that the Examiner did not show that a person of
ordinary skill in the art had a reason for making the particular selections and
combinations of the claimed invention. (App. Br. 7.) Thus, a prima facie
case of obviousness was not made. (Id.)
More specifically, Appellants contend (1) “[t]hat the prior art
discloses general reactions which may have some similar mechanisms but
using different materials does not support that they disclose the same steps
as the claimed invention” (id. at 5); and (2) there is “no evidentiary basis or
objective reasoning” to support the Examiner’s allegation that there would
have been a reasonable expectation that the proposed reactions would run
irrespective of starting material (id. at 6).
The issue on appeal is whether the evidence is sufficient to support a
conclusion of obviousness.

Findings of Fact
1. We adopt the Examiner’s findings concerning the scope and content
of the prior art as set out in the Answer, with the following clarification. In
the Final Rejection, the Examiner wrote that “[e]ach of the claimed reaction
steps are also known in the art as evidence[d] by the cited references” (Fin.
Rej. 3-4). Taken literally, the sentence was not correct for two reasons:
(i) while Neumann and Wang provided prior art cyproterone acetate
synthetic pathways, Appellants’ method diverges from the known pathways
and thus involves some different reactants and products, and (ii) the other
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synthetic steroid references relied on disclosed analogous reactions but with
different steroid reactants and products. We agree with Appellants that
when reactants and products in a reaction are different, the reactions are not
identical. (See App. Br. 6.) The Examiner acknowledged as much: “the
skilled artisan in the chemical art would have a reasonable expectation that
irrespective of starting material the reaction will run to completion.” (Fin.
Rej. 4.) We discount the Examiner’s internally contradictory statement that
“[a]lthough the starting material of each of the cited reference[s] differs from
those recited by the instant invention, each chemical reaction is identical.”
(Ans. 10.) We treat the reactions as a matter of obviousness, as the
Examiner more properly wrote: “[e]ach of the claimed reactions steps for the
production of cyproterone acetate from 17α-acetoxyprogesterone is obvious
based on the prior art as indicated below . . . .” (Ans. 3.)
2. Appellants’ “Figure 1 A-B outlines the conventional 18 step synthesis
of cyproterone acetate from solasodine.” (Spec. 12:25-26.)
3. Appellants’ Figure 2 is said to be an overview of Appellants’
synthesis routes (id. at 12:28-29), and shows Appellants’ Routes A, B, and C
diverging from the conventional synthesis after 17α-acetoxyprogesterone.
4. Appellants’ “Figure 4 A-B outlines cyproterone acetate synthesis from
solasodine according to Route B of the present invention.” (Id. at 13:4-5.)
5. The steps in claims 1 and 2 correspond to steps outlined in Figure 4B.

Principles of Law
A rejection for obviousness must include “articulated reasoning with
some rational underpinning to support the legal conclusion.” KSR Int’l Co.
v. Teleflex Inc., 550 U.S. 398, 418 (2007), quoting In re Kahn, 441 F.3d 977,
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988 (Fed. Cir. 2006). “The combination of familiar elements according to
known methods is likely to be obvious when it does no more than yield
predictable results.” KSR, 550 U.S. at 416. “[I]f a technique has been used
to improve one device, and a person of ordinary skill in the art would
recognize that it would improve similar devices in the same way, using the
technique is obvious unless its actual application is beyond his or her skill.”
KSR, 550 U.S. at 417. The obviousness “analysis need not seek out precise
teachings directed to the specific subject matter of the challenged claim, for
a court can take account of the inferences and creative steps that a person of
ordinary skill in the art would employ.” Id. at 418.
“The prior art’s mere disclosure of more than one alternative does not
constitute a teaching away from any of these alternatives because such
disclosure does not criticize, discredit, or otherwise discourage the solution
claimed.” In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Two criteria have evolved for determining whether prior art is
analogous: (1) whether the art is from the same field of endeavor, regardless
of the problem addressed, and (2) if the reference is not within the field of
the inventor’s endeavor, whether the reference still is reasonably pertinent to
the particular problem with which the inventor is involved. In re Clay,
966 F.2d 656, 658-9 (Fed. Cir. 1992).

Analysis
The prior art synthesis of cyproterone acetate used 17α-
acetoxyprogesterone as an intermediate, as does Appellants’ method. See
Fig. 2. According to Fig. 1B (and using the letter labels from Fig. 4B), after
making 17α-acetoxyprogesterone (compound H) the prior art treated it with
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chloranil, making compound I2, and then treated compound I2 with peracid,
making compound J2. Compare Fig. 1B and Fig. 4B. We find that the steps
recited in claim 2 are the first two prior art steps after the 17α-
acetoxyprogesterone, i.e., from compound H to compound I2 to compound
J2.
The steps recited in claim 1 are the last three steps shown in Fig. 4B.
Claim 1 recites the steps functionally, but the Examiner analyzed the
preferred way of carrying out the steps by naming the reagents.
Summarizing with the symbols in Fig. 4B, the claimed steps using the
preferred reagents are: (a) treating compound J2 with “HCl (gas)”
(anhydrous hydrogen chloride gas) to make compound K2, (b) treating K2
with “DDQ” (2,3-dichloro-5,6-dicyanobenzoquinone) to make compound
L2, and (c) treating L2 with “TMSI/NaH” (trimethyl sulfonium iodide and
sodium hydride) to make compound M. The Examiner found that anhydrous
HCl gas, DDQ and TMSI/NaH were reagents known in the art for modifying
steroid molecules.
For step “a)” of claim 1, the portion of Douglas on which the
Examiner relied (cols. 5-6) taught the reaction of formula IV pregnenes
having variable substituents (including, generically, Appellants’ J2) with
anhydrous HCl gas to introduce chloride at C6, producing formula Ih
(including, generically, Appellants’ K2). Appellants argue that “the starting
material used [by Douglas] is different from the starting material chlorinated
according to [A]ppellants’ invention and the resulting steroid of formula I is
distinct from cyproterone acetate. In Douglas there is no 1,2-methylene
bridged group.” (App. Br. 5.) Douglas’ formula generically included
Appellants’ J2, but J2 was a known intermediate in the prior art synthesis of
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cyproterone acetate. We do not see the relevance of Appellants’ argument
about a 1,2 bridged group because there is no 1,2-methylene bridged group
in Douglas’ formula Ih or in Appellants’ J2. Appellants’ step (a) is simply
the application of Douglas’ step to a compound within Douglas’ generic
disclosure, a compound already known as an intermediate in the cyproterone
acetate synthesis pathway.
Regarding step “b)” of claim 1, Appellants argue that “Shibata
discloses adding a double bond on a steroid derivative which has a 2-aza or
2-oxo pregnane derivative heteroatom structure distinct from the material
used in Appellants’ step (b).” (App. Br. 5.) However, the Examiner did not
rely on Shibata’s description of the new 2-azapregnane or 2-oxapregnane
products. Instead, the Examiner pointed to the compound Shibata started
with. Shibata’s synthetic pathway began with a compound Shibata labeled
“1.” (Shibata 935, Chart 1.) Shibata’s compound “1” is identical to
Appellants’ K2 of Fig. 4B. Shibata described treating that compound with
DDQ to produce compound “2,” the same compound Appellants label L2 in
Fig. 4B. Shibata’s first reaction is the reaction Appellants claim as step
“b).” That is, Shibata taught Appellants’ step “b)” but did not teach using it
in cyproterone acetate synthesis. Thus, we do not agree with Appellants’
argument about step “b)” that “in each case the [prior art] starting material
and obtained product are distinct from those in this step of the claimed
invention.” (App. Br. 5.)
Regarding step “c)” Appellants argue that “the compounds used in the
prior art steps are distinct from those used in the claimed invention and the
steps are, thus, different.” (App. Br. 5.) Appellants argue that Wang added
the methylene group bridging positions 1 and 2 before chlorination, and Van
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Kamp and Arth added the methylene group bridging positions 1 and 2 to a
molecule that did not have a chlorine. (Id.) First, we do not agree that
because the antiandrogenic steroids in the references had slightly different
structures they must be treated as “very distinct steroid structures” as
Appellants argue. The references are in the same field, synthesis of steroid
antiandrogens, and their disclosures are pertinent to each other and to
Appellants’ claims. See Clay, 966 F.2d at 658-9. The fact that differences
can be found is not, by itself, enough to be persuasive of nonobviousness.
Appellants argue that “[i]t cannot simply be conclude[d] from the fact
that the reaction works for the prior art starting material that the same
reaction would work for materials needed to conduct the claimed invention.”
(Reply Br. at 2.) That may be so, but there is no evidence that the reactions
in this case would have been unlikely to work. For example, the reaction
shown in Douglas is generic to the reaction defined in step “(a),” and the
reaction shown in Shibata is identical to the reaction defined in step “(b).”
To establish that it would not have been obvious to follow the prior art
instructions for performing those reactions, Appellants must do more than
assert the matter isn’t simple. On this record, we are not persuaded that the
Examiner’s citation of In re Mostovych, 339 F.2d 455 (CCPA 1964) as in
accord with the reasonable expectation of success was wrong.
Claim 2 defines steps “(d)” and “(e),” which are steps that precede
and provide the starting material for the steps recited in claim 1. Steps (d)
and (e) were known in the prior art synthetic pathway for cyproterone
acetate, illustrated in Fig. 1. (FF2.) It would have been obvious to retain the
known steps.
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Finally, Appellants do “not dispute that there would be a general
motivation” in the art to achieve a result in fewer steps, but they do dispute
that there was a “suggestion from the prior art to select the particular
combination of steps as claimed from among all the possibilities available to
the synthetic chemist.” (Reply Br. 2.) Given the general motivation, we
think that a person of ordinary skill in the art would look to modify any step
in a synthetic method.
CONCLUSION
The evidence is sufficient to support a conclusion of obviousness.
SUMMARY
We affirm the rejection of claims 1-4, 12-14 and 30 under 35 U.S.C.
§ 103(a) as unpatentable over Neumann, Douglas, Kincl, Shibata, Wang,
Van Kamp, and Arth.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED
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