Ex Parte Ziegler et al

Board of Patent Appeals and Interferences

Sep 24, 2010

10084676 (B.P.A.I. Sep. 24, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/084,676 02/28/2002 Iris Ziegler 029310.50932US 2539
23911 7590 09/27/2010
CROWELL & MORING LLP
INTELLECTUAL PROPERTY GROUP
P.O. BOX 14300
WASHINGTON, DC 20044-4300
EXAMINER
FUBARA, BLESSING M
ART UNIT PAPER NUMBER
1613
MAIL DATE DELIVERY MODE
09/27/2010 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte IRIS ZIEGLER and JOHANNES BARTHOLOMAEUS
__________

Appeal 2009-014562
Application 10/084,676
Technology Center 1600
__________

Before TONI R. SCHEINER, MELANIE L. McCOLLUM, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL1,2
This is an appeal under 35 U.S.C. § 134 involving claims to an oral
pharmaceutical formulation of tramadol and diclofenac. The Examiner
rejected the claims as indefinite, anticipated, and obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.

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.
2 Oral Hearing waived.
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Statement of the Case
The invention “relates to partially sustained-release, oral
pharmaceutical forms of administration in which the active substance,
tramadol, is present at least partially as a compound formed in situ which
has a water solubility of <100 mg/ml, and to processes for their preparation”
(Spec. 1 ¶ 0002).
The Claims
Claims 17 and 38 are on appeal. Claims 17 and 38 read as
follows:
17. A sustained-release, oral pharmaceutical
formulation of tramadol, comprising a compound
of tramadol hydrochloride and diclofenac sodium,
wherein said compound is formed in situ, said
compound having a water solubility of ≤100
mg/ml, and wherein at least part of the tramadol
and at least part of the diclofenac are released at
the same rate.

38. A method for preparing an oral
pharmaceutical formulation, the method
comprising:
mixing tramadol hydrochloride and
diclofenac sodium to form a mixture;
moistening the mixture; and
repeating the above mixing and moistening
steps and formulating the mixture under an energy
input.

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The issues
A. The Examiner rejected claim 17 under 35 U.S.C. § 112, second
paragraph as indefinite (Ans. 4-5).
B. The Examiner rejected claim 17 under 35 U.S.C. § 102(e) as
anticipated by Mauskop3 (Ans. 5-7).
C. The Examiner rejected claim 38 under 35 U.S.C. § 103(a) as obvious
over Mauskop (Ans. 8-9).
A. 35 U.S.C. § 112, second paragraph
The Examiner finds that “the individual compounds, tramadol and
diclofenac appear to be present in the claimed compound as identifiable
compounds; secondly the formation of the claimed compound does not
appear to involve the appearance of a new compound that is separate from
the individual tramadol and diclofenac” (Ans. 5)
Appellants contend that the claim language
describes that “said compound” is formed in situ and that the
compound has a water solubility of ≤100 mg/ml. Thus, the
skilled artisan would readily understand that the claim is
directed to a compound of tramadol hydrochloride and
diclofenac sodium and not a simply mixture of these two
ingredients . . . To read the language of claim 17 to cover a
simple mixture of tramadol hydrochloride and diclofenac
sodium improperly requires a complete disregard of the
multiple recitations of the word “compound”

(App. Br. 4).

3 Alexander Mauskop, US 5,914,129, issued Jun. 22, 1999.
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The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the use of the word “compound”
renders claim 17 indefinite?
Findings of Fact
1. The Specification describes “the preparation of at least partially
sustained-release, oral pharmaceutical formulations of tramadol, in which
the sustained-release portion of the active substance is present as a
[sparingly water-soluble] compound, formed in situ, of tramadol and another
active substance and/or auxiliary substance with a water solubility of ≤ 100
mg/ml” (Spec. ¶¶ 9, 11).
2. In Example 1 of the Specification:
125 g of tramadol hydrochloride, 125 g of
diclofenac sodium and 250 g of microcrystalline
cellulose . . . were homogeneously mixed . . . for 10
minutes and then granulated with water in an amount
sufficient for moistening. The sticky lumpy mass of
granules was then extruded . . . with a 1.0 mm
extrusion die. While the rods of extrudate were
initially still extremely sticky, they changed in the
course of the extrusion process to a very dry extrudate
with insufficient plasticity for subsequent
spheronization. The extrudate was moistened and
granulated again. The resulting granules were
extruded again . . . and the moist extrudate was then
converted to round pellets of uniform size . . . . The
pellets were dried in a drying cabinet at a temperature
of approx. 50°C and fractionated into sieve fractions,
≥90% of the pellets falling within the desired sieve
class of 800 - 1250 μm.
(Spec. ¶ 54.)
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3. “For the pellets produced above, the water solubility of the
active substance tramadol from the compound formed in situ was found to
be 0.36 mg/ml” (Spec. ¶ 56 (emphasis added)), and the release profile was as
follows:

(Spec. ¶ 57.)
4. Dr. Iris Ziegler4 describes a series of experiments
demonstrating the different properties of tablets “identical in size and shape
and . . . made from identical amounts of the same raw ingredients . . .
[which] differed only in their manner of processing” (Decl. 5).
5. Dr. Ziegler prepared three different compositions. First, section
I(a) of the Declaration describes the preparation of tablets according to the
process described in Mauskop (Decl. 2). Second, section I(b) of the
Declaration describes the preparation of tablets according to the process of
the instant application (Decl. 3). Third, section II(c)(i) of the Declaration
describes preparation of the salt of Tramadol and Diclofenac (Decl. 7).
6. Exhibits A-E, which accompanied Dr. Ziegler’s Declaration
show the results of Differential Scanning Calorimetry (DSC) thermal
analyses of the three formulations of tramadol-hydrochloride and diclofenac-

4 Declaration of Dr. Iris Ziegler, dated December 14, 2006, and
initially submitted in the present application on December 15, 2006
under the provisions of 37 C.F.R. § 1.132 (“Decl.”).
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sodium, including the tablets of I(a), of I(b)(i), and a tramadol-diclofenac
salt.
7. Dr. Ziegler concluded:
The different release profiles of the Tramadol
and Diclofenac from the tablets of I(b) . . . compared
to the tablets of I(a) . . . containing a mixture of
Diclofenac-sodium and Tramadol-hydrochloride, are
indicative of a significant difference in solubility and
demonstrate that the Diclofenac and Tramadol must
be present in a physical/chemical form which is
different from a mixture . . . . The different
differential scanning calorimetry results of the pellets
of I(b)(i) produced according to the present invention
compared to the tablets of I(a) containing a mixture of
Diclofenac-sodium and Tramadol-hydrochloride . . .
and particularly the endothermic peak at
approximately 292°C which has no counterpart in the
DSC of the crushed tablets of I(a), corroborate the
presence of a different physical/chemical species in
the product of the present invention which is not
present in the tablets containing a mixture of
Diclofenac-sodium and Tramadol-hydrochloride . . .
These results evidence that the product of the present
invention contains an in situ formed compound of
Diclofenac-sodium and Tramadol-hydrochloride
which is not present in the tablets containing a
mixture of Diclofenac-sodium and Tramadol-
hydrochloride . . .
(Decl. 9).
Principles of Law
“The test for definiteness is whether one skilled in the art would
understand the bounds of the claim when read in light of the specification.”
Miles Laboratories, Inc. v. Shandon Inc., 997 F.2d 870, 875 (Fed. Cir.
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1993). “The purpose of claims is not to explain the technology or how it
works, but to state the legal boundaries of the patent grant. A claim is not
‘indefinite’ simply because it is hard to understand when viewed without
benefit of the specification.” S3 Incorporated v. NVIDIA Corp., 259 F.3d
1364, 1369 (Fed. Cir. 2001).
Analysis
While we appreciate the Examiner’s concerns, we are not persuaded
that the use of the word “compound” renders claim 17 indefinite. Appellants
have provided specific evidence that at least three different physical entities
can be formed using Tramadol and Diclofenac: a simple mixture as in
Mauskop; a Tramadol/Diclofenac salt; and a third physical entity which is
the inventive combination of Tramadol and Diclofenac (FF 5). Dr. Ziegler’s
Declaration provides evidence that the three forms differ in at least some
physical properties (FF 6-7).
Thus, while the physical entity of Claim 17 has not been described by
its precise chemical structure, the issue is not whether “compound” is the
best of all possible words to describe what is claimed. It may be that further
research would show the physical entity to be a coordination compound, an
inclusion compound, a sandwich compound, a clathrate, or some other form.
The issue is whether one of skill in the art would understand what the word
“compound” means when read in the context of the Specification.
We find that one skilled in the art would understand that, in this
context, the word “compound” refers to physical entity, composed of
tramadol hydrochloride and diclofenac sodium, formed in situ, with a water
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solubility of ≤100 mg/ml, that is the product of the compounding process
described in the Specification.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the use of the word “compound” renders claim 17 indefinite.
B. 35 U.S.C. § 102(e) over Mauskop
The Examiner finds that “Mauskop discloses a combination of opioid
analgesic and non-opioid analgesic to synergistically act to relieve pain
(column 3, lines 47-54) and tramadol hydrochloride and diclofenac sodium
are included in the list provided” (Ans. 6). The Examiner finds that the
“property of a composition is not separable from the composition and how a
composition is made has no patentable weight in a composition/product
claim” (Ans. 6).
Appellants contend that the “different release profile and the different
DSC spectrum obtained for the claimed compound show that the claimed
compound is different from a simple mixture of the two active substances”
(App. Br. 7).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the composition of Mauskop is
inherently the same as the composition of Claim 17?
Findings of Fact
8. Mauskop teaches that “[c]ompressed tablets may be prepared
by compressing in a suitable machine the mixture of one or more analgesic,
magnesium salt, stimulant, optionally an effervescing agent, and a
pharmaceutically acceptable carrier” (Mauskop, col. 6, ll. 20-24).
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9. Mauskop teaches non-opioid analgesics such as dichlophenac
and opioid analgesics such as tramadol (see Mauskop, col. 3, ll. 1-8).
Principles of Law
Where … the claimed and prior art products are identical or
substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not
necessarily or inherently possess the characteristics of his
claimed product. Whether the rejection is based on
“inherency” under 35 U.S.C. § 102, on “prima facie
obviousness” under 35 U.S.C. § 103, jointly or alternatively,
the burden of proof is the same, and its fairness is evidenced
by the PTO’s inability to manufacture products or to obtain
and compare prior art products.

In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (citations omitted).
Analysis
The Examiner asserts that the Specification and claims are directed to
a simple mixture of tramadol and diclofenac (see Ans. 7). There is no
apparent dispute about Mauskop’s disclosure - Appellants and the Examiner
agree that Mauskop discloses a simple mixture of tramadol and diclofenac
(FF 8-9). However, the Examiner has failed to come to grips with the
evidence of record which is consistent with Dr. Ziegler’s conclusion (and
Appellants’ assertion) that there is “a different physical/chemical species in
the product of the present invention which is not present in . . . tablets
containing a mixture of Diclofenac-sodium and Tramadol-hydrochloride”
(FF 4-7), and which has a substantially different solubility and release
profile than a simple mixture of tramadol and diclofenac (id.).
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In the instant case, the Examiner’s initial action reasonably challenged
Appellants to prove that the prior art differs from the claimed product.
Appellants however, met that challenge, demonstrating with evidence in the
Ziegler Declaration that the prior art products differ in several characteristics
from the claimed product (FF 4-7). The Examiner has not rebutted this
evidence, nor explained why the products would have been expected to be
the same in spite of their different release profiles and different differential
scanning calorimetry results.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the composition of Mauskop is inherently the same as the composition
of Claim 17.
C. 35 U.S.C. § 103(a) over Mauskop
The Examiner finds that Mauskop “discloses forming tablets by
conventional method of compression and molding and specifically discloses
that molded tablets can be optionally moistened with an inert liquid diluent”
(Ans. 8). The Examiner finds that the “instant method comprises a
moistening step which the prior art discloses. Repeating the mixing and
moistening steps is an obvious variant of the method at the disposal of the
person of ordinary skill in the art or to the skilled artisan whereby the steps
are repeated as necessary for the production of the desired tablet” (Ans. 8).
Appellants contend that “the rejection fails to explain why the skilled
artisan would be inclined to repeat the above mixing and moistening steps
and formulate the mixture under an energy input as is required in claim 38”
(App. Br. 9). Appellants contend that neither “Mauskop nor any other
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evidence of record discloses or suggests the possibility that these steps might
yield a compound as contemplated in the present application” (App. Br. 9).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that repeating the mixing and moistening
steps would have been obvious over Mauskop?
Principles of Law
An invention
composed of several elements is not proved
obvious merely by demonstrating that each of its
elements was, independently, known in the prior
art …. [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.

KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
We find that Appellants have the better position. The Examiner
acknowledges that “Mauskop does not describe repeating mixing and
moistening steps” (Ans. 12). The Examiner has provided no evidence or
reason why the ordinary artisan would have performed the steps of
repeatedly mixing and moistening a mixture of tramadol hydrochloride and
diclofenac sodium (as required by claim 38) when Mauskop does not teach
or suggest this element.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that repeating the mixing and moistening steps would have been obvious
over Mauskop.
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SUMMARY
In summary, we reverse the rejection of claim 17 under 35 U.S.C. §
112, second paragraph.
We reverse the rejection of claim 17 under 35 U.S.C. § 102(e) as
obvious over Mauskop.
We reverse the rejection of claim 38 under 35 U.S.C. § 103(a) as
obvious over Mauskop.

REVERSED

alw

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INTELLECTUAL PROPERTY GROUP
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