Ex Parte Pfrengle et al

Board of Patent Appeals and Interferences

Sep 29, 2010

11460996 (B.P.A.I. Sep. 29, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte WALDEMAR PFRENGLE and PETER SIEGER
__________

Appeal 2010-003933
Application 11/460,996
Technology Center 1600
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Before TONI R. SCHEINER, DONALD E. ADAMS, and DEMETRA J. MILLS,
Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 from the final rejection of
claims 1, 2, 4, 8-13, 15-21, and 23-37 on the ground of obviousness-type
double patenting. We have jurisdiction under 35 U.S.C. § 6(b).

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.

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Application 11/460,996

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STATEMENT OF THE CASE
Claims 1, 8, and 9 are representative2 of the subject matter on appeal:
1. A compound which is the monohydrochloride or dihydrochloride salt
of 1-[(3-cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-
amino-piperidin-1-yl)-xanthine.3

8. The compound of claim 1 in crystalline anhydrous form.

9. A compound which is the monohydrochloride salt of 1-[(3-cyano-
pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-
yl)-xanthine having a melting point of 260°C to 270°C.

Claims 1, 2, 4, 8-13, 15-21, and 23-37 stand rejected under the
doctrine of obviousness-type double patenting as unpatentable over claims
1-20 of U.S. Patent 7,501,426 (‘426).4
We affirm-in-part.
FINDINGS OF FACT
1. There is no dispute that claim 17 of the ‘426 patent is identical
in scope to claim 1 of the present application, except that the salt form of the
patented claims is defined generically. Patented claim 17 is as follows:
The compound 1-[(3-cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-
butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine in a physiologically
acceptable salt form with an inorganic or organic acid.

2 Appellants have divided the claims into three groups (1a. claims 1, 2, 4,
13, 20, 21, and 28-31; 1b. claims 9-12, 16-19, 24-27, and 32-37; and 1c.
claims 8, 15, and 23), and have provided separate arguments for each group
(App. Br. 4). We select claims 1, 8, and 9 as representative.
3 In the interests of brevity and simplicity, we will refer to the free base of
this compound as “Compound X” wherever appropriate.
4 U.S. Patent 7,501,426 B2, issued March 10, 2009 to Frank Himmelsbach,
Elke Langkopf, Matthias Eckhardt, Mohammad Tadayyon, and Leo
Thomas.
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2. Claim 18 of the ‘426 patent is directed to a pharmaceutical
composition comprising the same compound as patented claim 17 in a
physiologically acceptable salt form with an inorganic or organic acid, and
one or more inert carriers or diluents.
3. Thus, each of the claims of the present application is narrower
than the claims of the ‘426 patent in specifying that the compound is in the
form of a monohydrochloride or dihydrochloride salt (e.g., claim 1); or in
specifying that the compound is in crystalline anhydrous form (e.g., claim
8); or in specifying that the compound has a particular melting point range
and/or particular values on an x-ray powder diagram (e.g., claims 9 and 10).
4. There is ample evidence of record to establish that the
hydrochloride salts of basic drugs are very common pharmaceutically
acceptable salts, and that it was known in the art that a hydrochloride salt of
a given drug could be more or less hygroscopic than the parent free base
(Decl. 4; see also, the patent documents listed on pages 2 and 3 of the
Examiner’s Answer, as well as the patent documents listed on page 4 of the
Declaration of Dr. Peter Sieger).5
5. Dr. Sieger’s Declaration establishes that monohydrochloride
and dihydrochloride salts of Compound X are significantly less hygroscopic
than the parent free base (Decl. 2), and that this property was regarded in the
art as a distinct advantage for purposes of formulating pharmaceutical
compositions (id at 2-3).

5 Declaration under 37 C.F.R. § 1.132 of Dr. Peter Sieger executed July
16th, 2008, and originally submitted July 22, 2008 (“Decl.”).
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DISCUSSION
Domination, “by itself, does not give rise to ‘double patenting’.” In re
Kaplan, 789 F.2d 1574, 1577 (Fed. Cir. 1986); see also, In re Sarett, 327
F.2d 1005, 1007 (CCPA 1964). A proper obviousness-type double patenting
rejection “rest[s] on the fact that a patent has been issued and later issuance
of a second patent will continue protection, beyond the date of expiration of
the first patent, . . . of a mere variation of that invention which would have
been obvious to those of ordinary skill in the relevant art[.]” Kaplan, 789
F.2d at 1579-80 (emphasis omitted). That being the case, “there must be
some clear evidence to establish why the variation would have been
obvious” to one of ordinary skill in the art (id. at 1580).
Claims 1, 2, 4, 13, 20, 21, and 28-31
Representative claim 1 is directed to the mono- or dihydrochloride salt
of 1-[(3-cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-
amino-piperidin-1-yl)-xanthine (“Compound X”), the same compound
claimed in patented claim 17, but in the form of a salt of an unspecified acid.
The Examiner’s position is essentially that hydrochloride salts of
Compound X would have been obvious over the generic salts of Compound
X, because hydrochloride salts are the most common pharmaceutically
acceptable salts of basic drugs (Ans. 4).
Appellants acknowledge that it is “common to use hydrochloride salts
of compounds in the pharmaceutical arts” (App. Br. 11), but contend that
“the declaration [of Dr. Peter Sieger] establishes unexpected advantages for
the claimed selection invention which clearly and convincingly show that
the current claims are not an obvious variant of the more general ‘426
claims” (id. at 12).
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We have carefully considered Appellants’ evidence and arguments,
but are not persuaded that the Examiner’s conclusion regarding these claims
is in error. We acknowledge that Dr. Sieger’s Declaration establishes that
monohydrochloride and dihydrochloride salts of Compound X are much less
hygroscopic than the free base, and that this lower hygroscopicity would be
regarded as a distinct advantage in a pharmaceutical composition.
However, while it’s true that the precise hygroscopicity of a particular
salt of a particular free base compound cannot be predicted ahead of time,
there is evidence of record that it was commonly known (i.e., expected) to
differ from the free base compound, and it doesn’t necessarily follow that
the precise value, once empirically determined, would have been unexpected
or surprising.
Second, Appellants have not explained how comparing the presently
claimed monohydrochloride and dihydrochloride salts with the free base is
relevant to whether the monohydrochloride and dihydrochloride salts are
obvious over the generically claimed salts of the patent. The Declaration
does not, for instance, compare the mono- and dihydrochloride salts with
other pharmaceutically acceptable salts of Compound X (it is, after all, a salt
that is claimed in the ‘426 patent, not the free base), which would have been
a closer, and more illuminating comparison than a comparison with the free
base.
Having considered all the evidence of record, particularly Appellants’
evidence purporting to show unexpected results, we agree with the Examiner
that Appellants have not established that the presently claimed mono- and
dihydrochloride salts of 1-[(3-cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-
butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine have properties that
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would have been unexpected, and therefore unobvious, over the patented
generic salts of the same compound. Appellants have not provided separate
arguments for claims 2, 4, 13, 20, 21, and 28-31, so they fall according to
claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
Claims 8, 15, and 23
These claims require the monohydrochloride or dihydrochloride salt
of Compound X to be in crystalline anhydrous form.
According to the Examiner, “it is entirely possible, even likely, that
[the material discussed in the Specification’s Examples 3 and 4, and in the
Declaration] was not anhydrous” (Ans. 16). Thus, the Examiner
acknowledges that the monohydrochloride or dihydrochloride salts of
Compound X are not necessarily anhydrous (id.), but offers no evidence or
analysis establishing that this narrower form of a hydrochloride salt would
have been obvious over the generic salt.
On this record, we are constrained to reverse the rejection with respect
to claims 8, 15, and 23.
Claims 9-12, 16-19, 24-27, and 32-37
These claims require the monohydrochloride or dihydrochloride salt
of Compound X to exhibit a particular melting point range and/or particular
values on an x-ray powder diagram. The Examiner acknowledges that it
may (or may not) be possible to prepare polymorphs of the mono- and
dihydrochloride salts of Compound X. Nevertheless, the Examiner has not
established that these particular forms of the salt would have been obvious
over the generic salt of the ‘426 patent.
On this record, we are constrained to reverse the rejection with respect
to claims 9-12, 16-19, 24-27, and 32-37.
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SUMMARY
The rejection of claims 1, 2, 4, 8-13, 15-21, and 23-37 under the
doctrine of obviousness-type double patenting as unpatentable over claims
1-20 of U.S. Patent 7,501,426 is affirmed with respect to claims 1, 2, 4, 13,
20, 21, and 28-31, and reversed with respect to claims 8-12, 15-19, 23-27,
and 32-37.
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)(1)(iv)(2006).

AFFIRMED-IN-PART

cdc

MICHAEL P. MORRIS
BOEHRINGER INGELHEIM USA CORPORATION
900 RIDGEBURY RD
P O BOX 368
RIDGEFIELD, CT 06877-0368