UNITED STATES PATENT AND TRADEMARK OFFICE
__________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________
Ex parte SURESH KUMAR GIDWANI,
PURUSHOTTAM SINGNURKAR,
and PRASHANT KUMAR TEWARI
__________
Appeal 2010-005181
Application 10/272,812
Technology Center 1600
__________
Before DONALD E. ADAMS, MELANIE L. McCOLLUM, 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
metformin tablets. The Patent Examiner rejected the claims for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
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STATEMENT OF THE CASE
Claims 9, 16, and 21-35, which are all the pending claims, are on
appeal. Claims 9 and 21 are representative and read as follows:
9. A monolithic sustained release pharmaceutical composition as tablets
for once daily use, consisting essentially of 1000 mg metformin
hydrochloride as the active substance, 10 to 40% by weight of a
hydrophobic polymer and/or other hydrophobic material, 3 to 10% by
weight of a binder, 0.5 to 1.5% by weight of a glidant and 0.5 to 1.0%
by weight of a lubricant, said tablets having a film coating for taste
neutralization, the in-vitro drug release characteristics of said tablets
when tested in gastric fluid of pH 1.2 for the first hour and then in
phosphate buffer of pH 6.8 USP for the remaining 7 hours being as
follows:
time in
hours
% of drug
release
1 38 – 45 %
2 50 – 55 %
3 62 – 68 %
4 70 – 75 %
5 80 – 85 %
6 85 – 90 %
7 91 – 95 %
8 96 – 100 %
21. A pharmaceutical tablet comprising:
a. At least about one gram of metformin hydrochloride,
b. Hydrophobic material in an amount of up to about 40% (w/w)
of the amount of said metformin hydrochloride,
c. Hydrophilic material in an amount of not more than about 5%
(w/w) of said metformin hydrochloride,
d. Said pharmaceutical tablet providing extended release.
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The Examiner rejected the claims as follows:
• claims 9 and 16 under 35 U.S.C. § 103(a) as unpatentable over
Matharu
1
in view of Igari
2
or Timmins „004;
3
and
• claims 9 and 16 under 35 U.S.C. § 103(a) as unpatentable over
Timmins „128;
4
and
• claims 21-35 under 35 U.S.C. § 103(a) as unpatentable over
Timmins „128 and Evenstad.
5
OBVIOUSNESS
A. The rejection of claims 9 and 16 over Matharu in view of Igari or
Timmons.
The Issue
The Examiner‟s position is that Matharu described a monolithic
sustained release metformin composition as claimed but for a “film coating
for taste neutralization,” and the dissolution profile required. (Ans. 3-4.)
Finding that Igari and Timmins each taught masking the unpleasant taste of
metformin with a film coating, the Examiner concluded it would have been
obvious to use a film coating on Matharu‟s tablet. (Id. at 4-6.) The
Examiner found that Appellants‟ dissolution profile overlapped Matharu‟s
profile, and concluded that because “the tablet structures are similar and
both contain the same critical components,” “the manipulation of the
1
Amol Singh Matharu et al., Patent Appl. Publ. No. US 2003/0021841 A1,
published Jan. 30, 2003.
2
Yasutaka Igari et al., US Patent No. 5,665,394, issued Sept. 9, 1997.
3
Peter Timmins et al., US Patent No. 6,031,004, issued Feb. 29, 2000.
4
Peter Timmins et al., WO 99/47128, published Sept. 23, 1999.
5
Kenneth L. Evenstad et al., US Patent No. 5,126,145, issued Jun. 30, 1992.
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dissolution profile of the prior art‟s range is considered prima facie
obvious.” (Id. at 6-7.)
Appellants contend that “Matharu does not qualify as prior art because
Applicant antedates Matharu.” (App. Br. 14.) According to Appellants,
their Specification “asserts a 02 October 2000 effective filing date.” (Id.)
The Examiner responds that if Matharu is to be antedated the
Specification must identify the relationship between this Application and the
Application (09/857,077) to which priority is claimed. (Ans. 13-14.)
The issue with respect to this rejection is whether the Specification
perfected its priority claim.
Findings of Fact
1. The Specification begins:
CROSS-REFERENCE TO RELATED APPLICATIONS
Serial No. 09/857,077, filed April 2, 2002, for
SUSTAINED RELEASE PHARMACEUTICAL
COMPOSITIONS CONTAINING METFORMIN AND
METHOD OF THEIR PRODUCTION, now pending, which is
a national phase entry under 35 U.S.C. § 371 of
PCT/IB00/01404 filed October 2, 2000, now pending.
(Spec. 1, ll. 9-13.)
Principles of Law
[A]ny nonprovisional application . . . claiming the benefit of
one or more prior-filed copending nonprovisional applications .
. . must contain or be amended to contain a reference to each
such prior-filed application, identifying it by application
number (consisting of the series code and serial number) . . .
and indicating the relationship of the applications.
37 C.F.R. § 1.78(a)(2)(i).
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Analysis
First, we agree with the Examiner‟s findings concerning the
disclosures of the references, and conclude that the rejection presented a
prima facie case of obviousness, assuming Matharu is prior art.
Appellants‟ sole contention is that Matharu is not available as prior art
because the Specification “asserts” a 02 October 2000 effective filing date.
(App. Br. 14.) The Examiner disagreed that the earlier filing date inures to
the appealed claims because no relationship between the current and the
earlier Application is identified. The applicable regulation is entitled
“Claiming benefit of earlier filing date and cross-references to other
applications.” 37 C.F.R. § 1.78. The regulation requires the cross-reference
to identify the relationship of related applications (with one exception for
continuing prosecution applications that does not apply here). We agree
with the Examiner that Appellants‟ Specification does not identify a
relationship between this Application and Application No. 09/857,077 (see
FF1). Contrary to Appellants‟ contention, without a relationship, the
Specification does not “assert” an effective filing date for the invention
claimed other than the filing date of the Application on appeal. We
conclude that the claim to priority has not been perfected, and that until
properly antedated, Matharu is prior art. There being no dispute that the
merits of the rejection are otherwise correct, we affirm it.
B. The rejection of claims 9 and 16 over Timmins.
The Issues
The Examiner found that Timmins described “a biphasic controlled
release delivery system for metformin HCL for the treatment of non-insulin
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dependent diabetes wherein the dosage form has prolonged gastric
residence, allowing once-a-day administration.” (Ans. 7-8.) The Examiner
found that Timmins taught the same materials used in Appellants‟ tablet, in
overlapping amounts, and that Timmins taught administering metformin in a
dosage range from 150-3000 mg, and preferably from about 250 to about
2500 mg, in single or 2 to 4 divided doses. (Id. at 8.) The Examiner
explained why a 1000 mg tablet would have been an obvious choice. (Id. at
9.) Based on a finding that “[t]he instant dissolution profile and that of
Timmins are overlapping,” the Examiner concluded that “manipulation of
the dissolution profile of the prior art‟s range is considered prima facie
obvious absent the showing of the criticality . . . .” (Id. at 10.)
Appellants contend that “Timmins [] actively discourages a
monolithic tablet and a one-gram drug load, and fails to teach (nor enable)
the claimed drug release precision. Timmins thus fails to teach every
element of the claimed invention. Timmins thus fails to provide a prima
facie case of obviousness of claims 9 of 16.” (App. Br. 16-17.)
Further Findings of Fact
2. In its “Background of the Invention” section, Timmins stated:
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A further problem with highly water soluble drugs
formulated into a controlled release dosage form is that a
significant and variable "burst" of drug can occur from these
systems. . . . Thus, a readily hydrating polymer is required to
establish the desired stable release rate. However, if the
polymer used is slow to hydrate, then an undesireable variable
burst can occur.
(Timmins „128 at 3, ll. 21-35.)
3. Timmins disclosed:
The formulation of the invention (a) achieves extended gastric
residence by virtue of size but will degrade in vivo so as not to
have potential for causing gastric or intestinal obstruction, and
(b) controls drug release adequately where the initial burst of
drug is under control.
(Timmins „128 at 14, ll. 5-23.)
4. Timmins taught:
the preferred highly water-soluble drug will be metformin or a
salt thereof, which will be employed in a dosage range from
about 2 to about 43 mg/kg, preferably about 3 to about 36
mg/kg and more preferably from about 4.5 to about 30 mg/kg
(or from about 150 to about 3000 mg, preferably from about
250 to about 2500 mg) on a regimen in single or 2 to 4 divided
daily doses.
(Timmins „128 at 29, ll. 19-25.)
Principles of Law
“One of the ways in which a patent‟s subject matter can be proved
obvious is by noting that there existed at the time of invention a known
problem for which there was an obvious solution encompassed by the
patent‟s claims.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 419-20
(2007); see also Princeton Biochemicals, Inc. v. Beckman Coulter, Inc.,
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411 F.3d 1332, 1339 (Fed. Cir. 2005) (“the nature of the problem called for
exactly the solutions in the prior art”); accord, DyStar Textilfarben GmbH &
Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1366 (Fed. Cir.
2006) (“the „evidence‟ of motive will likely consist of an explanation of the
well-known principle or problem-solving strategy to be applied”).
A prior art reference is said to teach away from an Applicant‟s
invention “when a person of ordinary skill, upon reading the reference,
would be discouraged from following the path set out in the reference, or
would be led in a direction divergent from the path that was taken by the
applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). “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).
“[W]hen unexpected results are used as evidence of nonobviousness,
the results must be shown to be unexpected compared with the closest prior
art.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).
Analysis
We agree with the Examiner‟s findings concerning Timmins‟
disclosure (Ans. 7-10), and conclude that the rejection presented a prima
facie case of obviousness. We also agree with the Examiner‟s reasoning as
set out in the Response to Appellants‟ arguments. (Id. at 15-19.)
We have reviewed the passages in the Timmins reference that
Appellants point to, but cannot agree with the evidence support for
Appellants‟ contentions that “Timmins [] actively discourages a monolithic
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tablet and a one-gram drug load, and fails to teach (nor enable) the claimed
drug release precision.” (App. Br. 16.)
According to Appellants, Timmins “expressly” teaches away from
using monolithic tablets because Timmins says they may cause a drug
“burst.” (App. Br. 16, citing Timmins at 3, ll. 21-29.) We agree that the
cited passage of Timmins‟ “Background” section identified the “burst”
problem. (FF2.) However, the passage in question does not mention a
“monolithic” formulation, and we find no warning there, express or
otherwise, against monolithic formulations. Timmins described the “burst”
problem as a known problem to be addressed. Timmins then addressed and
solved the burst problem with its formulation (FF3), which supports the
obviousness rejection based on Timmins‟ disclosure. See Princeton
Biochemicals, 411 F.3d at 1339; DyStar, 464 F.3d at 1366.
Appellants contend that Timmins “expressly” teaches away from drug
loads over 500 mg because the patient could not absorb such large drug
loads. (App. Br. 16, citing Timmins at 1, ll. 23-26.) The passage Appellants
have selected from Timmins‟ “Background” section discussed previously
known problems associated with metformin, including the fact that
“difficulties are further compounded by the high unit dose, 500 mg per
tablet, usually required.” However, Timmins disclosed that its invention
addressed and solved those problems with a formulation that would be
preferably administered in a 250 to 2500 mg single dose. (FF4.) Although
Timmins addressed difficulties associated with prior 500 mg doses, there is
no “express” teaching away from 500 mg doses, and larger, as Timmins
formulates them. Because Timmins explicitly teaches using its own
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formulation in doses larger than 500 mg, Appellants‟ “teaching away”
argument is unpersuasive.
Turning to Appellants‟ contention that Timmins “fails to teach (nor
enable) the claimed drug release precision” (App. Br. 16), we agree, as did
the Examiner, that Timmins did not literally teach the claimed drug release
profile, or the precision derivable from that profile. However, the evidence
supports the Examiner‟s findings that Timmins‟ metformin release profile
overlaps Appellants‟ profile and that the release profile was a recognized
result-effective-parameter that would have been adjusted and optimized by a
person of ordinary skill in the art.
6
Appellants direct attention to the 2008 and 2007 Rule 132
Declarations of Dr. Omray. (App. Br. 16, citing the 2007 Decl.
7
at ¶ 5(a),
and the 2008 Decl.
8
at ¶¶ 12-15.) In the 2007 Declaration, Dr. Omray found
Appellants‟ tablet “clearly and unexpectedly superior” to that of Timmins
(2007 Decl. at ¶ 5). Using a table comparison said to show “release
variability,” Dr. Omray concluded that the amount released from Appellants‟
tablets is significantly more “precise” than that of Timmins (id.). The
Timmins data analyzed in the Declaration is from this passage appearing at
page 30 in Timmons:
6
Appellants‟ comment (App. Br. 16) that the Examiner does not dispute
their allegation that Timmins‟ fails to enable a precise release profile is
mistaken, as the Examiner maintained the rejection.
7
Declaration of Dr. Ashok Omray, Ph.D., submitted November 8, 2007.
8
Declaration of Dr. Ashok Omray, Ph.D., submitted September 16, 2008.
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The hours listed by Timmins in this particular table do not correspond to the
hours listed in Appellants‟ claims. In contrast to this selected Timmins data,
we note that Timmins‟ following Examples do present data for the missing
hours, but that data is not discussed in the Declaration. We find the
Declaration‟s selective comparison to a general teaching of a “useful”
profile is not a comparison to the closest prior art because it failed to
evaluate the precision Timmins achieved in the four working examples
Timmins disclosed as “preferred embodiments” (see Timmins „128 at 30-34)
which each report data at all the hours listed in Appellants‟ claims.
In the 2008 Declaration, Dr. Omray (i) again evaluates the
formulations Timmins described “useful” (2008 Decl. at ¶ 5, citing Timmins
at 30:24), (ii) analyzes the profile and states that Timmins “thus teaches that
the amount of drug released from his tablets varies by plus-or-minus nearly
ten percent” (id. at ¶ 6), (iii) acknowledges that “Timmins itself teaches that
„[t]he dose administered must be carefully adjusted” (id. at ¶ 11), and
(iv) states that “Timmins also teaches (at 30:24) that „careful adjustment‟ is
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not possible with his tablet” (id. at ¶ 11). According to Declarant,
Appellants‟ drug release is “four times more precise” (id. at ¶¶ 12-15) than
the Timmins data selected for comparison. As with the 2007 Declaration,
we place little confidence in the comparison because it fails to address the
working examples Timmins disclosed as “preferred embodiments”
(Timmins „128 at 30-34), and did not evaluate their release precision. We
find the Declaration‟s allegation that “Timmins also teaches . . . that „careful
adjustment‟ is not possible with his tablet” to be an inference deserving of
little weight because (1) it lacks objective support, and (2) appears to
overlook Timmins‟ working examples. In sum, we give little weight to the
Declarations because the Timmins data selected for comparison does not
seem fairly representative of the whole of the Timmins disclosure.
C. The rejection of claims 21-35 over Timmons and Evenstad.
The Issues
The Examiner found that the differences between Timmins‟ tablets
and Appellants‟ are that Timmins did “not teach the level of hydrophilic
materials of instant claims 21,” and “Timmins also fail[ed] to teach the
variability of release in claims 22-26, 29-35, Cmax of claim 27 and AUC of
claim 28.” (Ans. 11.) However, the Examiner found that Evenstad taught
how to solve problems associated with soluble medicaments, and concluded
that it would have been obvious to apply Evenstad‟s solutions to Timmins‟
metformin tablets. (Id. at 11-12.) According to the Examiner, a person of
ordinary skill in the art applying Evenstad‟s teachings to Timmins‟
metformin tablets would have produced the tablets defined in Appellants‟
claims.
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Appellants contend that “Timmons [sic] cannot, however, be properly
combined with Evenstad because (a) Timmins explicitly discourages the
combination; (b) the prior art fails to provide a motivation to combine
Timmins with Evenstad; and (c) the prior art fails to provide a reasonable
expectation of success.” (App. Br. 17.)
Further Findings of Fact
5. The Examiner relied on this definition of “monolithic” from the
Merriam-Webster Online Dictionary:
Function: adjective
1 a : of, relating to, or resembling a monolith : HUGE,
MASSIVE b (1) : formed from a single crystal
(2) : produced in or on a monolithic chip
2 a : cast as a single piece b :
formed or composed of material without joints or seams c : consisting of or constituting a
single unit
3 a : constituting a massive undifferentiated and often rigid
whole b : exhibiting or characterized by
often rigidly fixed uniformity
(Ans. 3.)
6. Matharu taught that its “invention relates to a process for preparing a
pharmaceutical tablet formulation of a poorly-compressible
pharmaceutical agent, for example, the drug metformin HCl
formulated as a monolithic or single phase homogenous system.”
(Matharu at 1, [0001].)
7. Matharu taught a process comprising:
(a) preparing a blend by combining the poorly-
compressible pharmaceutical agent, a hydrophilic
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erodible component and a hydrophobic component as a
monolithic or single phase homogenous system; and
(b) compressing the blend into a tablet.
(Id. at 1, [0007] – [0008].)
8. Evenstad taught: “tablets of the invention comprise about 5-30 percent
by weight hydroxypropyl methylcellulose with sustaining properties
and negligible binding properties.” (Evenstad, col. 3, ll. 5-20.)
9. Evenstad taught: “[t]he hydrophobic component should be present in
an amount effective to permit wet granulation of the controlled release
tablet. Such an amount is commonly 2-20 percent by weight of the
tablet depending on the solubility of the medicament.” (Id. at col. 5,
ll. 1-5.)
Principles of Law
Absent an express definition in their specification, the fact that
appellants can point to definitions or usages that conform to
their interpretation does not make the PTO's definition
unreasonable when the PTO can point to other sources that
support its interpretation.
In re Morris, 127 F.3d 1048, 1056 (Fed. Cir. 1997). “Absent claim language
carrying a narrow meaning, the PTO should only limit the claim based on
the specification or prosecution history when those sources expressly
disclaim the broader definition.” In re Bigio, 381 F.3d 1320, 1325 (Fed. Cir.
2004). Prior art references may be “indicative of what all those skilled in the
art generally believe a certain term means ... [and] can often help to
demonstrate how a disputed term is used by those skilled in the art.”
Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1584 (Fed. Cir. 1996).
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Analysis
We agree with the Examiner‟s findings concerning the disclosures of
the references, and conclude that the rejection presented a prima facie case
of obviousness. (See Ans. 11-12.) We also agree with the Examiner‟s
reasoning as set out in the Response to Appellants‟ arguments. (See id. at
19-27.)
According to Appellants, Evenstad taught a monophasic tablet made
by pressing a homogenous blended material, but Timmins taught a
heterogeneous two phase system, and thus Timmins teaches away from
using Evenstad‟s approach. (App. Br. 17-18.) Appellants‟ reference to
Matharu as purportedly defining monolithic to mean single phase is also
unpersuasive. Matharu‟s phrase “monolithic or single phase homogenous
system” may be reasonably read as listing “single phase” as an example of a
“monolithic” tablet, not as a limiting definition of monolithic. (FF6, 7.) The
Examiner relied on a general definition of monolithic that listed concrete as
an example of monolithic material. Appellants have not established that the
term has a more limited meaning in the pharmaceutical art.
Appellants also refer to “Omray, Declaration (2009)”
9
(App. Br. 18),
which the Examiner found unpersuasive. The 2009 Declaration states that
Timmins teaches that a “burst” can occur from monophasic systems, and
that for highly soluble drugs monophasic systems can require large amounts
of polymer. (2009 Decl. at ¶ 4.) The Declaration states that because
Evenstad taught a monolithic tablet, the artisan would read Timmins to teach
away from combining Timmins‟ teachings with Evenstad‟s. (2009 Decl. at
9
“Affidavit” by Ashok Omray, Ph.D., dated Jan. 19, 2009.
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¶¶ 4-7.) Like the Examiner, we disagree because Timmins taught how to
solve those problems. In other words, the rejection was based on combining
Timmins‟ solutions to the burst problem, and others, with the materials
Evenstad used.
Appellants contend that Timmins and Evenstad taken together fail to
teach each claim limitation, pointing to the assertion that Appellants‟ drug
release rate is four times more precise than the prior art, and the prior art
fails to enable the more precise release profile. (App. Br. 21-23, citing
Omray 2008 Declaration.) We continue to find this argument unpersuasive,
for the reasons already discussed in part “B” above.
Appellants argue that Timmins teaches away from the claimed blood
levels as evidenced by Timmins‟ discussion of problems in the prior art.
(App. Br. 23, citing Timmins 1:23-26.) We continue to find reliance on the
“Background” section in Timmins unpersuasive because the “Background”
section is not where Timmins taught the advantages of Timmins‟ own
formulation, which was said to address and solve prior art problems.
According to Appellants, neither Timmins nor Evenstad teaches a
tablet with a full one-gram load (App. Br. 24), and Timmins says a patient
could not absorb a full gram of extended-release metformin, and a 1-gram
metformin tablet would be too large and would be futile. (App. Br. 26,
citing Timmins 1:19-30). We continue to be unpersuaded for the same
reason the Examiner gave: the argument merely contradicts Timmins‟
explicit teaching of single doses of 150 to 3000 mg metformin. (FF4.)
Appellants contend that the art teaches away from the claimed ranges
of hydrophilic and hydrophobic materials. (App. Br. 28.) In pertinent part,
Claim 21 recites:
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b. Hydrophobic material in an amount of up to about 40% (w/w)
of the amount of said metformin hydrochloride,
c. Hydrophilic material in an amount of not more than about 5%
(w/w) of said metformin hydrochloride.
Claim 32 does not limit the hydrophobic materials and recites, in pertinent
part:
b. Hydrophilic material in an amount of not more than about 5%
(w/w) of said metformin hydrochloride.
The Examiner found that the ranges claimed “overlapped” the prior
art ranges for these materials. (Ans. 11.) Evenstad taught using “about 5-
30%” HPMC (FF8), and Appellants claim using “Hydrophilic material in an
amount of not more than about 5%.” Evenstad taught using “2-20 percent”
hydrophobic component and Appellants claim using “up to about 40%.”
Contrary to Appellants‟ contention, we see no “teaching away” by the prior
art. Appellants have not produced evidence that the prior art would have led
a person of ordinary skill in the art away from the claimed amounts. See
Gurley, 27 F.3d at 553.
SUMMARY
We affirm the rejection of claims 9 and 16 under 35 U.S.C. § 103(a)
as unpatentable over Matharu in view of Igari or Timmins „004.
We affirm the rejection of claims 9 and 16 under 35 U.S.C. § 103(a)
as unpatentable over Timmins „128.
We affirm the rejection of claims 21-35 under 35 U.S.C. § 103(a) as
unpatentable over Timmins „128 and Evenstad.
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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
cdc
