Ex Parte 6,514,531 et al

Patent Trial and Appeal Board

Mar 27, 2013

95000282 (P.T.A.B. Mar. 27, 2013)

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.
95/000,282 08/02/2007 6,514,531 SYL509 US REX 6236
5487 7590 03/27/2013
ANDREA Q. RYAN
SANOFI
55 Corporate Drive
MAIL CODE: 55A-505A
BRIDGEWATER, NJ 08807
EXAMINER
JONES, DWAYNE C
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
03/27/2013 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 PATENT TRIAL AND APPEAL BOARD
____________

SYNTHON PHARMACEUTICALS, INC.
Requester and Respondent

v.

SANOFI-AVENTIS U.S. L.L.C.
Patent Owner and Appellant
____________

Appeal 2013-000570
Reexamination Control 95/000,282
Patent 6,514,531 B1
Technology Center 3900
____________

Before, HUBERT C. LORIN, LORA M. GREEN, and RICHARD M. LEBOVITZ,
Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal by the Patent Owner from the Patent Examiner’s
decision to reject 1-47 in an inter partes reexamination of U.S. Patent No.
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6,514,531 B1. The Board’s jurisdiction for this appeal is under 35 U.S.C. §§ 6(b),
134, and 315. We reverse.

STATEMENT OF THE CASE
This is an inter partes reexamination of U.S. Pat. No. 6,514,531 B1, issued
February 4, 2003 (“the ‘531 patent”). A Request for Reexamination under 37
C.F.R. § 1.913 of the ‘531 patent was made by Synthon Laboratories, Inc., who is
the Third Party Requester and Respondent in this appeal. Request for Inter Partes
Reexamination (August 2, 2007). Reexamination was ordered and culminated in a
Right of Appeal Notice (“RAN,” dated August 19, 2010) which stated that pending
claims 1-47 were obvious in view of the cited prior art. The Patent Owner, Sanofi-
Aventis and Sanofi-Aventis U.S. LLC, appeals all the rejections. Appeal Br. 1
(December 1, 2010). An oral hearing was held on December 19, 2012.
The Examiner has rejected claims 1-47 as follows:
A. Claims 1, 2, 6, 7, 12, 18, 19, 28-31, 34, 35, 37-40, and 42-45 stand
rejected as obvious under 35 U.S.C. § 103(a) over Guittard
1
in view of Merlotti
2
or
Salva
3
as evidenced by Theeuwes.
4

B. Claims 3-5, 8-11, 13, 20, 21, 32, 33, 46, and 47 stand rejected as obvious
under 35 U.S.C. § 103(a) over Guittard in view of Merlotti or Salva as evidenced

1
George V. Guittard et al., U.S. 5,178,867 (Jan. 12, 1993).
2
Lori Merlotti et al., The Dose Effects of Zolpidem on the Sleep of Health
Normals, 9(1) J, Clin. Psychopharmacot 9 (Feb. 1989).
3
Pau Salva et al., Clinical Pharmacokinetics and Pharmacodynamics of Zolpidem,
29(3) Clin. Pharmacokinet 142 (1995).
4
Felix Theeuwes, U.S. 4,034,758 (July 12, 1977).
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by Theeuwes as applied to claims 1, 2, 6, 7, 12, 18, 19, 28-31, 34, 35, 37-40, and
42-45, further in view of Lachman.
5

C. Claims 15, 16, 25, and 26 stand rejected as obvious under 35 U.S.C.
§ 103(a) over Guittard in view of Merlotti or Salva as evidenced by Theeuwes as
applied to claims 1, 2, 6, 7, 12, 18, 19, 28-31, 34, 35, 37-40, and 42-45, further in
view of Conte.
6

D. Claims 17 and 27 stand rejected as obvious under 35 U.S.C. § 103(a)
over Guittard in view of Merlotti or Salva as evidenced by Theeuwes as applied to
claims 1, 2, 6, 7, 12, 18, 19, 28-31, 34, 35, 37-40, and 42-45, further in view of
Conte as applied to claims 15, 16, 25, and 27, and further in view of Bastin.
7

E. Claims 14, 22-24, 36, and 41 1, 2, 6, 7, 12, 18, 19, 28-31, 34, 35, 37-40,
and 42-45 stand rejected as obvious under 35 U.S.C. § 103(a) over Guittard in
view of Merlotti or Salva as evidenced by Theeuwes as applied to claims 1, 2, 6, 7,
12, 18, 19, 28-31, 34, 35, 37-40, and 42-45, further in view of Kydonieus
8
or
Conte.
Claim 1 is representative and reads as follows:
1. A pharmaceutical controlled-release dosage form adapted to release
zolpidem or a salt thereof over a predetermined time period, according
to a biphasic in vitro profile of dissolution when measured in a type II
dissolution apparatus according to the U.S. Pharmacopoeia in 0.01M
hydrochloric acid buffer at 37° C., where the first phase is an
immediate release phase having a maximum duration of 30 minutes
and the second phase is a prolonged release phase, and wherein 40 to

5
The Theory and Practice of Industrial Pharmacy, 3
rd
Ed., Leon Lachman et al.,
eds. Varghese Pub. House (1986).
6
Ubaldo Conte et al., U.S. 5,681,583 (Oct. 28, 1997).
7
Richard James Bastin et al., U.S. 6,309,668 B1 (Oct. 30, 2001).
8
Treatise on Controlled Drug Delivery, Fundamentals, Optimization, Applications,
Agis Kydonieus, ed., Marcel Dekker (1991).
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70% of the total amount of zolpidem is released during the immediate
release phase and the time for release of 90% of the total amount of
zolpiderm [sic] is between 2 and 6 hours.

REJECTION A
1. Rejection
The Examiner found that Guittard describes a dosage form for administering
a therapeutically effective amount of a drug with 1) an osmotic controlled-release
core which is surrounded by 2) an immediate release coating. RAN 28.
The immediate release coating, according to the Examiner, is described by
Guittard as preferably releasing drug in 2-30 minutes, meeting the limitation of
claim 1 of an “immediate release phase having a maximum duration of 30 minutes.
Id. The Examiner also found an example in Guittard in which the total amount of
the exemplified drug was released within six hours, the same time in which claim 1
specifies that “90% of the total amount of zolpidem” is released. Id. The
Examiner concluded, based on these teachings, that Guittard describes a biphasic
dissolution profile as recited in claim 1.
The Examiner found that Guittard did not describe zolpidem, but “teaches
using any drug from the class of ‘hypnotics’ and ‘sedatives,’” of which zolpidem is
a “well-known hypnotic agent.” Id.
The Examiner cited Merlotti and Salva for disclosing zolpidem. Id. at 28-
29. Based on these teachings, the Examiner concluded “it would have been
obvious to one of ordinary skill in the art to select zolpidem hemitartrate as the
hypnotic drug to be used in the teachings of Guittard and thereby obtain a biphasic
controlled release zolpidem dosage form because zolpidem hemitartrate was a
known, commercially approved, fast acting hypnotic agent with little or no
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rebound and withdrawal effects when compared to earlier benzodiazepine-class
hypnotic agents as taught by Merlotti or Salva.” Id. at 29.
Patent Owner contends that the Examiner did not construe the scope of
claim 1 properly. First, Patent Owner contends that the Examiner improperly
interpreted the claimed term “0.01M hydrochloric acid” to embrace any “suitable”
media. Appeal Br. 6; RAN 24. Secondly, Patent Owner contends that the
Examiner ignored the meaning of the claim term “pharmaceutical,” reading the
claim to cover any dosage amount of zolpidem, rather than efficacious and safe
amounts. Appeal Br. 9-10; RAN 10-11.
Patent Owner also contends that the Examiner “incorrectly assumes that the
prolonged osmotic release component of the examples in Guittard would release
zolpidem in such a way as to meet the claim-mandated drug release of: (1) 40-70%
at 30 minutes and (2) 90% between 2 and 6 hours.” Appeal Br. 13. Patent Owner
argues that “because Guittard fails to disclose the environment or media used to
determine drug release rate, it is impossible to correlate or even estimate what the
amount of drug release of any such osmotic component would be in the claim-
mandated dissolution media” of 0.01 hydrochloric acid buffer. Id. Finally, Patent
Owner contends that there would have been no reason to have made the claimed
“controlled-release dosage form adapted to release zolpidem” because the prior art
had showed that “increasing and extending zolpidem blood plasma levels, by
increasing the immediate release dose, failed to improve sleep maintenance.” Id.

2. Claim interpretation
Since the meaning of claim 1 is in dispute, we begin with claim
interpretation. During reexamination, the PTO must give claims their broadest
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reasonable construction consistent with the specification. In re Am. Acad. of Sci.
Tech Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004); In re Suitco Surface, Inc., 603
F.3d 1255, 1259 (Fed. Cir. 2010); In re Abbott Diabetes Care Inc., 696 F.3d 1142
Fed. Cir. 2012).

A. Proper interpretation of “0.01M hydrochloric acid buffer”
Claim 1 recites that the claimed pharmaceutical controlled release dosage
form “biphasic in vitro profile of dissolution when measured in a type II
dissolution apparatus according to the U.S. Pharmacopoeia in 0.01M hydrochloric
acid buffer at 37° C.” The Examiner construed “0.01M hydrochloric acid buffer”
to be “interpreted in view of the specification to be a ‘suitable’ media (solution)
that is recognized by the skilled artisan to be used in a dissolution test, which
embraces suitable media such as 0.01 M HCl and a potassium phosphate buffer of
varying pH's and concentrations.” RAN 21. In other words, the Examiner
construed “0.01M hydrochloric acid buffer” to be any suitable buffer. Other than
state that the interpretation was based on the “broadest reasonable interpretation
consistent with the specification,” and quote from the ‘531 patent, the Examiner
did not provide an explanation for this broad construction. However, the Examiner
cited excerpts from the Third Party Requester’s comments after the Action Closing
Prosecution. Id. at 23. We explain the Requester’s position below that was
apparently adopted by the Examiner.
According to Requester, the phrase “0.01M hydrochloric acid buffer” is not
recited or described in ‘531 patent. Respondent Br. 5 (Jan. 3, 2011). Requester
argues that aqueous buffers are described in the ‘531 patent as suitable for carrying
out a dissolution test. Id. According to Requester, “hydrochloric acid,” but not
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“hydrochloric acid buffer,” is disclosed in Example 1 of the ‘531 patent which
“conducts the dissolution tests in buffers as well.” Id.at 5-6. Requester argues that
the dissolution properties in Example 1 and Comparative Example 1 are the same,
and that only the buffer makes a difference. Id. Since “buffer” is what is
“significant or meaningful to the invention,” Requester contends the Examiner was
correct in construing “0.01M hydrochloric acid buffer” to mean “0.01M
hydrochloric acid” or a “suitable media.” Id. at 6.
We do not agree.
It is true that the ‘531 patent does not describe or even use the phrase
“0.01M hydrochloric acid buffer.” However, the skilled worker, upon reading the
‘531 patent, would understand what it meant.
The ‘531 patent generally describes carrying out dissolution tests to
determine that the dosage form comprises a first phase with a dissolution profile of
0 to 30 minutes and a second phase whose complete dissolution times is between 2
and 6 hours. Col. 2, ll. 1-21. The patent states:
A suitable dissolution test is for example one of the method
described in example 1: method where measurement is carried out in
a type II dissolution apparatus according to U.S. pharmacopoeia in
aqueous buffer at 37° C., or variations on this as well known to one
who is skilled in the art.
Col. 2, ll. 3-8 (emphasis added).
Example 1 of the ‘531 patent describes two “dissolution media” for
determining dissolution profiles: “hydrochloric acid 0.01 M” and “pH 6.8
potassium phosphate 0.05 M buffer.” Col. 9, ll. 64-66. “0.01 M hydrochloric acid
medium” is used in Example 2 to test the dissolution of a tablet containing
zolpidem. Col. 10, ll. 45-50. Example 3 (col. 11, 26-29), Comparative Example 2
(col. 13, ll. 43-44), Comparative Example 3 (col. 14, ll. 14-16), and other examples
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in the ‘531 patent also describe determining the dissolution characteristics of
pharmaceutical tablets comprising zolpidem in 0.01 M hydrochloric acid. The only
media utilized in the ‘531patent that comprises 0.01 M hydrochloric acid is one
which is either referred to as “0.01 M hydrochloric acid” or “0.01 M hydrochloric
acid medium.” Thus, although the term “0.01M hydrochloric acid buffer” is not
used in the ‘531 patent, it is clear that it is a reference to the 0.01 M hydrochloric
acid media used in the examples of the ‘531 patent to determine the dosage form’s
dissolution characteristics. Indeed, this media is used throughout the ‘531 patent to
determine the dissolution characteristics of the zolpidem dosage forms.
There is additional support for interpreting “0.01M hydrochloric acid buffer”
to be the 0.01M hydrochloric acid media used throughout the ‘531 patent. At
column 2, lines 3-8, reproduced above, it stated that the dissolution test is carried
according to Example 1 in an “aqueous buffer.” There are only two media
described in Example 1 – “hydrochloric acid 0.01 M” and “pH 6.8 potassium
phosphate 0.05 M buffer.” Col. 9, ll. 62-66. Both media were used to carry out the
dissolution tests. Thus, referring to the “hydrochloric acid 0.01 M” as a “buffer” is
consistent in view of the disclosure at column 2 of the ‘531 patent referring to an
aqueous buffer of Example 1.
As pointed out by the Patent Owner, the ‘531 patent distinguished the
properties of various formulations based on their differential rates of release when
tested in potassium phosphate buffers and the claimed 0.01M hydrochloric acid.
For example, Figures 3 and 4 of the patent depict the different dissolution rates
obtained when the dissolution media were 0.01M hydrochloric acid and pH 6.8
phosphate buffer. (“FIG. 3 shows an in vitro dissolution profile of the tablets of
example 1, in 0.01 M hydrochloric acid and in pH 6.8 phosphate buffer, as
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described in example 1.” Col. 3, ll. 65-67.) See also Fig. 9 (col. 13, ll. 48-51). It is
therefore inconsistent to read “0.01M hydrochloric acid buffer” to encompass
phosphate buffer, as construed by the Examiner, because the two different media
are expressly distinguished from each other in the ‘531 patent. Moreover, contrary
to Requester’s statements, the ‘531 patent reveals a clear difference in the
dissolution profile when 0.01M hydrochloric acid is compared to a phosphate
buffer (see Fig. 3 & col. 13, ll. 48-51). To read “0.01M hydrochloric acid buffer”
as simply any suitable buffer would be ignoring the plain language of the claim as
it would be interpreted in view of the written description of the ‘531 patent.

B. Proper interpretation of “pharmaceutical”
Claim 1 is directed to a “pharmaceutical controlled-release dosage form
adapted to release zolpidem or a salt thereof over a predetermined time period.”
The claim does not recite specific amounts of the zolpidem which are present in
the dosage form, but rather only recites that the pharmaceutical has a “biphasic in
vitro profile of dissolution” which has a first “immediate release phase” and a
second “prolonged release phase” with prescribed dissolution times.
The Examiner found that claim 1 “does not require dosage amounts of
zolpidem.” RAN 11, ¶ 17; 53: ¶ 111. Patent Owner contends that this
interpretation is not proper, and the claimed dosage forms “must be able to induce
and maintain sleep while eliminating the drug to a sufficiently low level as to avoid
hangover effects.” Appeal Br. 9. Patent Owner contends that because the claim is
drawn to a pharmaceutical, it is must be interpreted to have the specific activity of
the zolpidem described in the ‘531 patent. Id. To resolve this issue, we first turn
to the written description of the ‘531 patent.
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In the “Brief Description of the Invention” of the ‘531 patent, it is stated:
The new dosage forms according to the present invention enable to
sustain release over a period compatible with the desired time of sleep
and the time needed for elimination of the drug from the human body
to a sufficiently low level.
Col. 1, ll. 55-58.
To achieve this purpose, the ‘531 patent states:
Therefore, as a first object, the present invention provides controlled-
release dosage forms comprising zolpidem or salts thereof adapted to
release over a predetermined time period, according to a biphasic
profile of dissolution, where the first phase is an immediate release
phase and the second phase is a prolonged release phase.
Col. 1, ll. 59-64.
Following this statement, the ‘531 patent describes the biphasic profile of
dissolution:
The first phase or immediate release phase is that part of the
dissolution profile from 0 to 30 minutes in a suitable in vitro
dissolution test.
. . .
The second phase or prolonged release phase is that part of the
dissolution profile which is after 30 minutes, measured in a suitable in
vitro dissolution test, such as described in example 1. The present
invention then proposes dosage forms of the drug whose complete
dissolution time for the second phase is between 2 and 6 hours, and
preferably between 2.25 and 3.5 hour.
Col. 2, ll. 1-21. The latter description corresponds to the dissolution profile recited
in claim 1.
The ‘531 patent therefore expressly characterizes its invention as a “new
dosage form” which is able “to sustain release over a period compatible with the
desired time of sleep,” consistent with the activity of zolpidem as a “hypnotic” that
induces sleep of a patient. Col. 1, ll. 30-31, 9-54, & 55-58. The only purpose that
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is recited in the ‘531 patent for the dosage form with the claimed dissolution
profile is to induce and maintain sleep:
The rapid release in the first phase induces the immediate sleep of the
patient and the second phase allows the drug blood level to be
maintained at or below the peak level, but higher than the level
obtained with an immediate release dosage form, at the same time
after dosing, with the objective of maintaining sleep.
Col. 2, ll. 50-54.
This objective is achieved with a dosage form which has the claimed
dissolution profile. Col. 2, ll. 56-63; claim 1.
We agree with Patent Owner that the recitation of “pharmaceutical” imports
the only purpose disclosed in the ‘531 patent for the dosage form into the claim.
The term “pharmaceutical” means a drug or relating to drugs.
9
Thus, a
“pharmaceutical controlled-release dosage form adapted to release zolpidem,”
when read in light of the written description of the ‘531 patent, would be
interpreted to mean a drug with the specific “drug” activity associated with
zolpidem: to induce and maintain sleep – the only purpose for the claimed
pharmaceutical described in the ‘531 patent. Accordingly, the claimed dosage
form must comprise amounts of zolpidem which induce and maintain sleep when
administered to a subject.

3. Findings of Fact (“FF”)
We begin our analysis of the prior art by making specific findings of fact for
the cited Guittard publication.

9
http://www.thefreedictionary.com/pharmaceutical
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FF1
Another object of the present invention is to provide a dosage form for
administering a therapeutically effective drug immediately from the
external surface of the dosage form followed by administering a
therapeutically effective dose of drug from inside the dosage form
from ten minutes up to eight hours for producing a preselected
therapeutic effect.
Guittard, col. 2, ll. 32-37 (emphasis added).
FF2
The quick release coat 14 releases drug 15 in from greater than one
second up to one hour, and in a presently preferred quick release dose
of from two minutes, up to thirty minutes.
Guittard, col. 4, ll. 36-39.
FF3
Guittard discloses a list of drugs. Guittard, col. 6, ll. 21-68. Hypnotics are
listed among the disclosed drugs. Id. at col. 6, l. 27.
FF4
Example 5 describes a dosage form of cimetidine that delivers the cimetidine
in six hours. Guittard, col 11, ll. 40-42. Example 5 does not disclose how the
dissolution profile was determined.
FF5
Example 6 describes a dosage form of cimetidine that delivers the external
dose of cimetidine in 20 minutes. Guittard, col 11, ll. 56-57. Example 6 does not
disclose how the dissolution profile was determined.
FF6
FIG 2 is a view of a dosage form provided by invention comprising an
exterior dosage amount of drug for an initial burst dose of a drug to
the gastrointestinal tract consisting of the stomach and the small
intestine.
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Guittard, col. 3, ll. 51-54.

4. Analysis
Claim 1 is directed to a “pharmaceutical controlled-release dosage form
adapted to release zolpidem or a salt thereof over a predetermined time period.”
The dosage form is recited in the claim to release the zolpidem “according to a
biphasic in vitro profile of dissolution when measured in a type II dissolution
apparatus according to the U.S. Pharmacopoeia in 0.01M hydrochloric acid buffer
at 37° C.” The dissolution profile of zolpidem is also recited in the claim.
The Examiner’s position is that Guittard describes a dosage form with the
same biphasic dissolution profile recited in claim 1, but just doesn’t teach zolpidem
as the specific drug which is to be included in it. To make up for this deficiency,
the Examiner cited evidence that there would have been reason to formulate
Guittard’s dosage form with zolpidem, a well-known hypnotic used to induce
sleep.

Biphasic in vitro profile of dissolution
Guittard describes a controlled release dosage form with immediate (“quick
release”) and prolonged release times (FF1-FF5) having an overlapping dissolution
profile with the profile recited in claim 1. However, Guittard does not teach the
assay in which the dissolution profile measured. FF4 & FF5. Thus, while Guittard
may teach a biphasic profile, Guittard does not describe how this profile was
determined. Particularly, there is no disclosure of measuring the profile in “a type
II dissolution apparatus according to the U.S. Pharmacopoeia in 0.01M
hydrochloric acid buffer at 37° C” as required by claim 1.
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The Examiner noted the difference between the claim and what is taught in
Guittard, stating that “[o]ne having ordinary skill in the art would recognize that
different dissolution media (solutions) can produce (result in) different release rate
profiles for some dosage forms.” RAN 30, ¶ 67. In addition, the Examiner stated,
“the determination of a suitable media (solution), such as a hydrochloric acid
buffer, and test conditions for a dissolution profile test would have been obvious
and within the skill level of the artisan in the absence of evidence to the contrary.”
Id. at 30, ¶ 68; 67, ¶ 140.
Patent Owner contends that the Examiner erred and that because “Guittard
fails to disclose the environment or media used to determine drug release rate, it is
impossible to correlate or even estimate what the amount of drug release of any
such osmotic component would be in the claim-mandated dissolution media” of
0.01 hydrochloric acid buffer. Appeal Br. 13.
Requester states that the Patent Owner “offers no data or evidence to prove
the lack of inherency of the obvious Guittard zolpidem product in their claimed
dissolution test. Thus the inherency stands unrebutted and the claims are prima
facie obvious.” Respondent Br. 16
We agree with Patent Owner that the Examiner has not established that
subject matter of claim 1 is prima facie obvious in view of Guittard and the other
cited publications. While Guittard describes a dissolution profile that overlaps
with the claimed profile, there is no evidence that Guittard’s profile would be
achieved “in vitro . . . when measured in a type II dissolution apparatus according
to the U.S. Pharmacopoeia in 0.01M hydrochloric acid buffer at 37° C.” To
establish inherency, there must be a reasonable basis for the Examiner to believe
that the dissolution profile in Guittard corresponds to that which is claimed. See In
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re Best, 562 F.2d 1252, 1255 (CCPA 1977); In re Spada, 911 F.2d 705, 708 (Fed.
Cir. 1990). However, in this case, the Examiner did not attempt to establish
inherency, or provide compelling evidence of such, but rather argued it would have
been obvious to determine a suitable media in which to test for the dissolution
profile. RAN, 30, ¶ 68; 67, ¶ 140.
The weakness in the Examiner’s argument is that Guittard does not teach
what media was used to achieve its dissolution profile. FF1-FF5. The ordinary
skilled worker, reading Guittard, might at most have reason to believe that the
dissolution profile corresponds to one that would be achieved in the
gastrointestinal tract comprising the stomach and small intestine. FF6. However,
there is no evidence that the amounts of drug released by Guittard’s dosage form
would be same as the amounts released in vitro in 0.01M hydrochloric acid, using
a type II dissolution apparatus, where
the first phase is an immediate release phase having a maximum
duration of 30 minutes and the second phase is a prolonged release
phase, and wherein 40 to 70% of the total amount of zolpidem is
released during the immediate release phase and the time for release
of 90% of the total amount of zolpidem is between 2 and 6 hours.
Thus, even if the skilled worker had reason to formulate zolpidem in a
biphasic controlled release dosage as taught by Guittard, there is insufficient
information to determine whether a zolpidem dosage form formulated according to
Guittard, e.g., as in Examples 5 and 6, would meet the dissolution profile
specifically recited in the claims. The Examiner did not meet the burden in
providing a reasonable basis upon which to believe that the limitation would be
met by Guittard.
A recent case from the Federal Circuit is consistent with our determination
that the Examiner’s burden was not met. In In re Kao, 639 F.3d 1057 (Fed. Cir.
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2011), the claimed invention had a dissolution profile as measured by the Paddle
Method. Kao, 639 F.3d at 1061-62. However, the prior art method was measured
by the Basket Method. Id. In finding the claimed invention obvious, the Board
relied on a correlation between the Paddle and Basket Methods, which the Board
found established that the dissolution profile of the prior art would fall within the
claimed dissolution profile when measured using the Paddle Method. Id at 1062-
63. The Federal Circuit held that Board’s correlation was not supported by
substantial evidence and vacated the rejection. Id.at 1065-66. Similarly, here, the
Examiner did not provide sufficient evidence of a correlation between dissolution
profiles as measured by in a type II dissolution apparatus according to the U.S.
Pharmacopoeia in 0.01M hydrochloric acid buffer at 37° C and the profile
disclosed in Guittard. In fact, Guittard does not even mention dissolution testing in
vitro, let alone an apparatus or medium for determining the dissolution profile.
With the respect to the obviousness of achieving the claimed dissolution
profile in 0.01M hydrochloric acid, the Examiner has not given a reason to make a
dosage form with a dissolution profile as measured in 0.01M hydrochloric acid.
The Examiner argued that Theeuwes showed the “osmotic release of the
pharmaceutically active agent is released in a controlled and continuous rate that is
independent of conditions, in particular stirring speed (rate) or pH dependency
(See column 1, lines 14-17; column 2, lines 20-24 and 35-40).” RAN, 33, ¶ 76. In
other words, the dissolution media doesn’t matter. It would be the same in
hydrochloric acid and the same in whatever media Guittard used.
The evidence does not fully support this view since, as argued by Patent
Owner, “Figures 3 and 4 [of the ‘531 patent] depict the different dissolution results
obtained when the dissolution medium was 0.01M hydrochloric acid as compared
Appeal 2013-000570
Reexamination Control 95/000,282
Patent 6,514,531 B1

17
to pH 6.8 phosphate buffer. See Patentee’s June 18, 2008 Response at pages 7-8;
see also Figures 8 and 10; col. 13, ll. 49-51; col. 12, ll. 59-63; col. 14, ll. 17-19.”
Appeal Br. 7. That is, the dissolution media matters and affects the dissolution
profile.
For the foregoing reasons, we reverse the rejection of claim 1, and
dependent claims 2, 6, 7, 12, 18, 19, 28-31, 34, 35, 37-40, and 42-45.

REJECTIONS B-E
Rejections B-E each involves claims which are dependent on claim 1. The
Examiner did not present evidence that the prior art cited in Rejections B-E made
up for the deficiencies in Guittard as to the dissolution profile. RAN 86, 91, 94, &
96. We therefore reverse these rejections as well.

TIME PERIOD FOR RESPONSE
Requests for extensions of time in this inter partes reexamination
proceeding are governed by 37 C.F.R. § 1.956. See also 37 C.F.R. § 41.79.

REVERSED

ack

Appeal 2013-000570
Reexamination Control 95/000,282
Patent 6,514,531 B1

18
Third Party Requester:

Mark. B. Buscher
371 Atlas Walk Way
#136
Gainsville, VA 20155

Patent Owner:

Andrea Q. Ryan
Sanofi
55 Corporate Drive
Mail Code: 55A-505A
Bridgewater, NJ 08807