Ex Parte Srinivasan et al

Patent Trial and Appeal Board

Oct 20, 2016

11115321 (P.T.A.B. Oct. 20, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111115,321 0412712005
13897 7590 10/24/2016
Abel Law Group, LLP
8911 N. Capital of Texas Hwy
Bldg 4, Suite 4200
Austin, TX 78759
FIRST NAMED INVENTOR
Viswanathan Srinivasan
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
3205-P2771 l 3040
EXAMINER
TCHERKASSKAYA, OLGA V
ART UNIT PAPER NUMBER
1615
NOTIFICATION DATE DELIVERY MODE
10/24/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
mail@Abel-IP.com
hmuensterer@abel-ip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte VISWANATHAN SRINIVASAN, RALPH BROWN,
DAVID BROWN, HIMANSHU PATEL, JUAN CARLOS MENENDEZ,
VENKATESH BALASUBRAMANIAN,
and SOMPHET PETER SUPHASA WUD 1
Appeal 2013-011051
Application 11/115,321
Technology Center 1600
Before ULRIKE W. JENKS, JACQUELINE T. HARLOW, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to
pharmaceutical dosage forms, which have been rejected as obvious. We
have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
1 Appellants identify the Real Party in Interest as Sovereign
Pharmaceuticals, LLC. (App. Br. 3.)
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Application 11/115,321
STATEMENT OF THE CASE
Appellants' "invention relates to pharmaceutical dosage forms which
comprise[] a first drug and a second drug, both of which are selected from
decongestants, antitussives, expectorants, analgesics and antihistamines.
The dosage form releases the first drug and the second drug so as to provide
pharmaceutically effective plasma concentrations of these drugs over similar
periods of time." (Spec. i-f 2.)
Claims 157-311 are on appeal. Claims 157 is illustrative:
157. A pharmaceutical dosage form comprising (a) a first drug
which is selected from decongestants, antitussives, expectorants,
analgesics, and antihistamines, and (b) a second drug which is of
a different type than the first drug and is selected from
decongestants, antitussives, expectorants, analgesics, and
antihistamines, wherein the dosage form provides a plasma
concentration within a therapeutic range of the second drug over
a period which is coextensive with at least about 70 % of a period
over which the dosage form provides a plasma concentration
within a therapeutic range of the first drug.
(App. Br. 27 (Claims App'x).)
The claims stand rejected as follows:
I. Claims 157-311 under 35 U.S.C. § 103(a) over Fanara,2
Findlay, 3 and Paradissis. 4
II. Claims 157-311 under 35 U.S.C. § 103(a) over Fanara and
Davis '508. 5
2 Fanara et al., US 6,699,502 Bl, issued Mar. 2, 2004 ("Fanara").
3 Findlay et al., US 4,650,807, issued Mar. 17, 1987 ("Findlay").
4 Paradissis et al., US 5,445,829, issued Aug. 29, 1995 ("Paradissis").
5 Davis et al., US 2003/0215508 Al, publ. Nov. 20, 2003 ("Davis '508").
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III. Claims 157-311under35 U.S.C. § 103(a) over Fanara and
Davis '318. 6
RELATED MATTERS
We note the updated disposition of the following related appeals and
applications:
1. Application No. 10/939,351. See Ex Parte Srinivasan, No. 2013-
009326 (PTAB decided June 23, 2016) (affirming rejections of claims
129-256 under§ 103(a); reversing as to claims 222, 227, and 244);
2. Application No. 11/012,267 (Appeal No. 2016-006545);
3. Application No. 10/736,902 (Notice of Appeal filed Sept. 22, 2016);
4. Application No. 11/102,726 (appeal withdrawn following Request for
Continued Examination ("RCE")); and
5. Application No. 10/798,884 (appeal withdrawn following RCE).
(See also App. Br. 3.)
I
Issue
Has the Examiner established by a preponderance of the evidence that
claims 157-311 would have been obvious over Fanara, Findlay, and
Paradissis?
6 Davis et al., US 2003/0049318 Al, publ. Mar. 13, 2003 ("Davis '318").
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Findings of Fact (FF)
FF 1. The Examiner's findings of fact and statement of Rejection I
may be found at pages 2-7 and 12-19 of the Final Action dated October 4,
2012. (See also Ans. 4--11.) We provide the following for emphasis.
FF 2. Fanara teaches pharmaceutical compositions "allowing for the
controlled release of at least one active substance." (Fanara Abstract.)
Fanara teaches "multi-layered pharmaceutical compositions, including at
least one layer of the inventive composition." (Id.) Fanara also teaches the
"release of active substances during oral administration can be controlled by
means of matrix-type pharmaceutical compositions." (Id. at col. 1, 11. 14--
16). For instance, Fanara teaches
pharmaceutical compositions which can be administered orally,
compnsmg
A. at least one layer comprising an active substance and
excipients which allow immediate release of the said
active substance after administration, and
B. at least a second layer which allows the controlled release
of the same or of a second active substance, comprising
the said same or second active substance, at least one
matrix-type excipient and at least one alkalinizing agent.
(Id. at col. 5, 11. 48-58; see also id. at claim 7.)
FF 3. Fanara teaches it is desirable "to control the release of
pharmaceutically active substances so that they can be administered in a few
daily doses, ideally in a single dose." (Id. at col. 1, 11. 11-13.) Fanara
teaches that its compositions "allow[] the controlled release of
pharmaceutically active substances such that a satisfactory therapeutic effect
is observed over fairly long periods, for example in only one or two daily
doses . . . and allow regular and continuous release of active substances
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over periods of at least 12 hours." (Id. at col. 3, 11. 24--32.) Fanara also
teaches
it is increasingly therapeutically advantageous to be able to
simultaneously administer by the oral route an active substance
released immediately after administration, and the same or a
second active substance released gradually and regularly after
administration. In the case where the same active substance is
simultaneously administered for immediate release and for
prolonged release, this makes it possible to rapidly release a
sufficient dose of active substance to trigger the desired effect
and to maintain this effect by a gradual and prolonged release of
the same active substance. In the case where an active substance
is released immediately and another active substance is released
gradually, this makes it possible to obtain combined therapeutic
effects by means of two active substances having very different
pharmacokinetic profiles.
(Id. at col. 2, 11. 36-50 (emphasis added).)
FF 4. Fanara teaches the active substances may include
"vasoconstrictors, antihistamines, analgesics, antitussives and the like." (Id.
at col. 4, 11. 57-58.) More specifically, Fanara discloses
[ n ]onlimiting examples of such active substances are
pseudoephedrine, ephedrine, phenylephrine,
phenylpropanolamine, trapidil, hydrocodone, cetlnzme,
efletirizine, hydroxyzine, meclizine, buclizine, pentoxyverine,
codeine, morphine, their optical ISomers or their
pharmaceutically acceptable salts.
As regards the dose of active substance used, it depends
on the effective dose and may therefore vary within very wide
limits depending on the said active substance.
(Id. at col. 4, 1. 62 through col. 5, 1. 3.) Fanara discloses working examples
with combinations of active substances, such as pseudoephedrine/cetirizine
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and immediate-release hydrocodone/prolonged-release hydrocodone. (Id. at
col. 6, 11. 20-29; id. at col. 9--10, Example 4; id. at col. 12-13, Example 7.)
FF 5. Findlay discloses antihistamines for human use and teaches that
such compounds may be used with other therapeutic agents, including
"decongestants pseudoephedrine or phenylpropanolamine, an antitussive
such as codeine, an analgesic such as acetaminophen, an antiinflamatory and
antipyretic such as aspirin, or an expectorant such as guaifenesin." (Findlay
col. 5, 11. 1-15.)
FF 6. Paradissis teaches "extended release pharmaceutical
formulation[ s] which [are] capable of approaching zero order release of drug
over a 12 to at least a 24 hour period." (Paradissis col. 3, 11. 21-24.)
Paradissis teaches formulations comprised of immediate- and extended-
release particles. (Id. at col. 3, 11. 25-32.) Paradissis further teaches the
drugs "may be selected from a wide variety of pharmaceutical formulations
with particular pharmaceutical compounds being analgesics, anti-
inflammatories, antihistamines, antitussives, expectorants, decongestants ...
and mixtures thereof." (Id. at col. 3, 11. 34--41; see also id. at col. 4, 11. 31-
64.) Paradissis teaches "the appropriate amounts of immediate and extended
release particles are mixed to achieve the desired activity and release pattern.
. . . When administered in proper dosage forms, the formulations are able to
deliver the drugs in zero order release rates to achieve from about 12 to 24
hours drug delivery." (Id. at col. 9, 11. 18-39.) Paradissis discloses working
examples, including a formulation with extended release particles of the
decongestant pseudoephedrine and the antihistamine chlorpheniramine,
blended with immediate release particles. (Id. at col. 10, 1. 64 through col.
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11, 1. 49; see also id. at col. 11, 1. 50 through col. 12, 1. 29 (Example 3,
disclosing immediate and extended release combination of
phenylpropanolamine hydrochloride and chlorpheniramine maleate ).)
Analysis
Claim 157
Except as discussed below, Appellants argue the patentability of
claims 157-311 as a group. We select claim 157 as representative. 7
The Examiner finds that Fanara teaches "oral pharmaceutical
compositions for controlled and immediate release of multiple active
substances" including "multi-layered formulations." (Final Act. 3.)
According to the Examiner, Fanara teaches "[t]he compositions can be
administered in a few daily doses, ideally in a single daily dose" and control
of release is provided by "matrix-type" compositions. (Id.) The Examiner
finds Fanara teaches its compositions "allow regular and continuous release
of active substances over periods of at least 12 hours." (Id. at 4.) The
Examiner also finds Fanara teaches that "[i]n the case where an active
substance is released immediately and another active substance is released
gradually, this makes it possible to obtain combined therapeutic effects by
means of two active substances having very different pharmacokinetic
profiles." (Id. at 3--4.)
7 Because Appellants' arguments focus on the extent of overlap between the
periods of therapeutic effect (see, e.g., App. Br. 7), we have selected claim
157. We note, however, that some claims on appeal do not require this
overlap, such as independent claim 237, which requires a bi-layer tablet
comprising first and second drugs. (App. Br. 41 (Claims App'x).)
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The Examiner finds "Fanara teaches characterizing bioavailability of
active ingredients in plasma by analyzing pharmacokinetic profile ...
[including] monitoring in vivo release kinetics of pseudoephedrine by
measuring drug concentration in plasma." (Ans. 5.)
The Examiner cites to the working examples in Fanara, in particular,
Example 4. (Final Act. at 4.) The Examiner finds this example discloses
"double-layered tablets containing 120 mg doses of controlled-release
pseudoephedrine (i.e. decongestant) and 5 mg of immediate-release
cetirizine (i.e., antihistamine[)]." (Id.) According to the Examiner, these
"bi-layered tablets provide an effective concentration of the second drug
over a period which is coextensive with 80% of a period over which the bi-
layered tablet provides a first drug .... For example, 83.7% of
pseudoephedrine was released after 4 hour[s], and the concentrations of both
released drugs during the next 8 [hours] are within therapeutic ranges." (Id.
at 4--5 [citing Table 10]; see also Ans. 7 ("These data demonstrate clearly
fast release of cetirizine and slow release of pseudoephedrine.").) Thus,
according to the Examiner, Fanara "teaches an objective similar to that being
claimed by Applicant." (Final Act. 5.)
The Examiner cites Findlay and Paradissis as teaching dosage forms
of combined active agents, some of which are not expressly disclosed in
Fanara. For example, the Examiner cites Findlay's teaching of dosage forms
including antihistamines like diphenhydramine and expectorants such as
guaifenesin. (Id. at 6.) The Examiner also finds that Paradissis discloses,
among other things, a working example that includes extended release
dosage forms of pseudoephedrine and chlorpheniramine. (Id. at 7.)
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The Examiner concludes "[i]t would have been obvious ... to employ
active agents as taught by Fundlay [sic] and Paradissis within the
formulation taught by Fanara." The Examiner reasons such combinations
would have been expected to "provid[ e] improved formulations for cough
suppression and the treatment of allergic conditions." (Id.) As to the extent
of therapeutic overlap between multiple drugs in a single-dose formulation,
the Examiner concludes "it would have been obvious ... to employ various
parameters of pharmacokinetic profile to characterize and optimize the
delivery of multiple drugs ... for providing a most effective dosage form
comprising multiple drugs." (Ans. 6.) To illustrate, the Examiner reasons
"that combination of drugs might require significant overlap of bio-
availabilities, particularly in cases involving pain relievers, i.e., the[] pain
reduction is required immediately whereas the other drug needs to be
release[d] over time." (Id. at 5.)
Appellants contend "[t]he rejection essentially alleges that FANARA
discloses all of the elements of the rejected claims at least inherently, with
the exception of explicitly disclosing [certain agents like chlorpheniramine
recited in dependent claims]." (App. Br. 6.) According to Appellants, the
rejection is flawed because "the present claims recite, inter alia, an overlap
of the periods within which the first drug and that at least one second drug
show a therapeutic effect ... of at least about 70%" and, Appellants argue,
"FANARA does not mention this element at all." (Id. at 8; Reply Br. 2.)
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This argument is unpersuasive. 8 Fanara teaches the administration of
different active substances in a single dosage form. (FF 2, 4.) Fanara
teaches compositions "allowing for the controlled release of at least one
active substance" such as, for example, in a "multi-layered pharmaceutical
compositions including at least one layer of the inventive composition." (FF
2.) Fanara teaches that, when different active substances are simultaneously
included, Fanara's compositions "make[] it possible to obtain combined
therapeutic effects by means of two active substances having very different
pharmacokinetic profiles." (FF 3.) Fanara further teaches that controlled
release formulations are desirable in order to limit administration to "a few
daily doses, ideally in a single daily dose." (Id.) Fanara thus teaches
compositions that exhibit a "satisfactory therapeutic effect ... over fairly
long periods ... [and] allow regular and continuous release of active
substances over periods of at least 12 hours." (Id.)
A person of ordinary skill in the art, considering these disclosures,
would have understood Fanara to teach that the therapeutic activity of
multiple drugs in a single-dosage form should substantially overlap within
the desired period of time. Appellants have offered no other persuasive
interpretation of Fanara's teachings. (FF 2--4; See App. Br. 11-12, 16-17.)
And, although Fanara does not state, on a percentage basis, the precise
degree to which the drugs' therapeutic activity should overlap, absent factual
evidence to the contrary, we agree with the Examiner that such percentages
8 We previously considered, but did not find persuasive, substantially the
same arguments raised in a related appeal (No. 2013-009326) where the
claims were rejected over Fanara, Findlay, Paradissis, and other references.
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would have been derived through predictable optimization. (Ans. 6-9.) See
In re Aller, 220 F.2d 454, 456 (CCPA 1955) ("[W]here the general
conditions of a claim are disclosed in the prior art, it is not inventive to
discover the optimum or workable ranges by routine experimentation.").
We also agree with the Examiner that the skilled artisan would have
predictably designed dosage forms of the cold and allergy drugs at issue here
so that the formulation exhibited "significant overlap in [the drugs'] bio-
availabilities." (Ans. 5.) Fanara expressly teaches the advantage of limiting
the number of daily doses and extending the therapeutic effectiveness of its
formulations, consistent with the desire to improve patient compliance and
maintain therapeutic activity over a longer period of time, such as over 12
hours. (FF 3.)9 To illustrate in the context relevant here, it would have been
desirable that a patient taking a single-dose formulation that includes a
decongestant and antitussive not have the therapeutic benefit of the
antitussive end within a few hours while the other drug remains
therapeutically active for several hours to come. Otherwise the patient
would require a separate dose of antitussive alone within a few hours to
remedy their persistent cough, yet no additional decongestant would be
needed because it is still fully active in the patient's system. 10 Instead, the
9 This was further well-known as evidenced by other art of record. (See,
e.g., Davis '508 i-fi-1 4, 18; Davis '318 i-fi-15, 7, 20.)
10 A desire to provide formulations with substantial therapeutic overlap
would have arisen with other relevant drug combinations, such as pain
reliever and a decongestant. We are not persuaded by Appellants'
suggestion to the contrary. (Reply Br. 2-3.). The skilled artisan would
desire to maintain pain relief (e.g., pain relief incident to a cold/flu) and
therapeutic activity of the other drug over an extended period, rather than
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skilled artisan would have predictably designed a controlled formulation that
provides substantial overlap in the drugs' therapeutic activity over the
desired period so that, at the end of the period, another single-dose with both
drugs could be taken as needed.
Appellants describe hypothetical scenarios they contend show overlap
between therapeutic periods would serve no useful purpose. (Appeal Br.
11-12.) These scenarios, however, are inconsistent with Fanara's teachings.
Example 4 of Fanara shows the combination of a controlled-release
decongestant (pseudoephedrine) and immediate-release antihistamine
(cetirizine- a known long-acting antihistamine). (See Fanara col. 9-10.)
By using controlled- rather than immediate-release pseudoephedrine, its
therapeutic activity is prolonged within the longer therapeutic window of
cetirizine. (See Ans. 5; Fanara Fig. 1 (comparing plasma concentration
curves of controlled- vs. immediate-release pseudoephedrine ).) So, the
formulation in Example 4 with controlled-release pseudoephedrine increases
the extent of overlap of the drugs' therapeutic activity. Appellants'
hypotheticals are thus unpersuasive as is their related argument that Fanara
suggests "that there needs to be (will be) only very little, if any, overlap of
the periods of therapeutic effectiveness." (App. Br. 18.)
Appellants further argue that, considering the entirety of Fanara's
disclosure, "the contribution to the art ... does not reside in the provision of
allow the level to drop below a therapeutic threshold at which point the pain
would return. (See, e.g., Vadino, US 4,777,050, issued Oct. 11, 1988 (cited
at Final Act. 12) (teaching sustained release dosage form with three
combined active agents: acetaminophen, pseudoephedrine, and
dexbrompheniramine).)
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dosage forms which provide immediate/controlled release of two different
active substances but rather ... in the provision of a new matrix
composition." (App. Br. 13.) This argument is unpersuasive. Appellants
dismiss Fanara's other material teachings, including those described above.
(FF 2--4.) Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed.
Cir. 1989) (holding that, in an obviousness analysis, the prior art must be
considered for all that it teaches and suggests to the skilled artisan).
We also recognize, but find unpersuasive, Appellants' arguments
concerning the difference between a period of release of a drug and the
period during which the plasma concentration of a drug is within a
therapeutic range. (App. Br. 8-10; Reply Br. 3.) Insofar as the Examiner
finds that Example 4 of Fanara discloses a multi-drug formulation exhibiting
the therapeutic overlap that is claimed (Final Act. 4--5), the burden is now on
Appellants to show otherwise.
Where . . . the claimed and prior art products are identical or
substantially identical . . . 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 and footnote
omitted)). Similarly, the Examiner has cited Example 2 of Paradissis, which
provides extended release pseudoephedrine and chlorpheniramine, and
describes the release profile of each drug over, for example, 8, 12, and 24
hours. (Final Act. 6-7; FF 6.) Yet Appellants have provided no evidence
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that this formulation, which discloses a combination of active agents
encompassed by claim 157, does not exhibit the period of therapeutic
overlap that is claimed.
For these reasons, we conclude that the Examiner established by a
preponderance of the evidence that claim 157 would have been obvious over
Fanara, Findlay, and Paradissis. Claims 157-215, 219-232, 235-239, 241-
243, 248-296, 299-304, and 306-311 have not been argued separately and
thus fall with claim 157. 37 C.F.R. § 41.37(c)(l)(iv).
Claim 216
Appellants argue the patentability of claims 216-218, 233, 234, 240,
244--247, 297, 298, and 305 as a group under a separate heading. (App. Br.
20.) In general, these claims recite a difference in the plasma half-lives of
the drugs. We select claim 216 as representative. It reads: "The dosage
form of claim 157, wherein a plasma half-life of the second drug differs
from a plasma half-life of the first drug by at least about 2 hours." (App. Br.
36 (Claims App'x).)
Appellants contend "the Examiner has failed to provide any (written
or other) evidence that two drugs whose combination in a single dosage
form is taught or suggested by FAN ARA, FINDLAY, and P ARADISSIS
have plasma half-lives which differ by several hours." (App. Br. 20.)
We are not persuaded. Instead, we agree with the Examiner that the
prior art teaches multi-drug dosage forms, and specifically teach the same
active ingredients as those being claimed so "the plasma half-lives would be
expected to be the same as that claimed herein by Applicant." (Final Act. 5;
Ans. 10; FF 2--4.) For instance, as discussed above, Fanara discloses a
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working example that combines pseudoephedrine (a shorter half-life drug)
and cetirizine (a longer half-life drug). (Final Act. 4; FF 4.) The plasma
half-lives of common cold and allergy drugs like these would have been
known to the skilled artisan. 11 Absent persuasive evidence to the contrary,
the dosage forms expressly disclosed in the prior art exhibit combinations of
drugs with differences in plasma half-lives encompassed by the scope of
claim 216. See In re Best, 562 F.2d at 1255.
Claims 217, 218, 233, 234, 240, 244--247, 297, 298, and 305 have not
been argued separately, and thus fall with claim 216.
II
Issue
Has the Examiner established by a preponderance of the evidence that
claims 157-311 would have been obvious over Fanara and Davis '508?
Findings of Fact (FF)
FF 7. The Examiner's findings of fact and statement of Rejection II
may be found at pages 7-9 and 20-21 of the Final Action dated October 4,
2012. (See also Ans. 11-12.) We incorporate Findings of Fact 1--4 above,
and provide the following for emphasis.
11 With respect to half-lives and plasma concentrations, Appellants cite to
Davis '508. (App. Br. 9-10.) Davis '508 teaches, for example,
pseudoephedrine is known to have a plasma half-life of approximately 4--6
hours and that guaifenesin has a typical plasma half-life of about 1 hour.
(See, e.g., Davis '508 i-fi-f 11-12.) See Ex Parte Srinivasan, No. 2013-
009326, at 14 ("Cetirizine, a drug taught by Fanara is known in the art to
have a half-life of 8 hours") (quoting 6/7 /2012 Adv. Act. 2)).
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FF 8. Davis '508 teaches "strategies and designs in formulations of
modified release guaifenesin and guaifenesin combination dosage forms."
(Davis '508 i-f 15.) Davis further teaches "a modified release composition
which comprises two portions (e.g. a bi-layer tablet, or capsule), an
immediate release formulation (IR) and a sustained release formulation
(SR)." (Id. at i-f 16; see also id. at i-f 17.)
FF 9. Davis '508 teaches "[t]he tablet is capable of releasing
therapeutically effective amounts of guaifenesin over an extended period,
e.g. twelve or more hours and at least one additional drug immediately, over
an extended period, or both." (Id. at i-f 15.) Similarly, Davis '508 teaches
[ t ]he bi-layer tablet also provides sustained release of guaifenesin
over about a twelve hour period from one dose ... [and] [i]n one
embodiment, the bi-layer tablet maintains serum concentration
levels of at least one additional drug at a therapeutically effective
level for about a twelve hour period without an increase m
dosage strength.
(Id. at i-f 18.)
FF 10. Davis '508 teaches
the sustained release formulation may comprise a combination of
guaifenesin and at least one additional drug . . . [that] may be
selected from, but is not limited to, an antitussive . . . a
decongestant . . . an antihistamine . . . an analgesic . . . or
combinations thereof. Preferably, the drug is dextromethorphan
hydrobromide, pseudoephedrine hydrochloride, or a combination
thereof.
(Id. at i-f 93.)
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Analysis
Claim 157
Except as discussed below, Appellants argue the patentability of
claims 157-311 as a group. We select claim 157 as representative.
The Examiner finds that Davis teaches a bi-layer tablet that maintains
serum concentration of guaifenesin and at least one other drug at a
therapeutically effective level for about twelve hours from a single dose.
(Final Act. 8-9.) The Examiner concludes "[i]t would have been obvious
... to employ strategy and design for multi-drug formulations taught by
Davis [] '508 within formulations taught by Fanara." (Id. at 9.) The
Examiner reasons the skilled artisan would have been motivated to make this
combination to "sustain[] therapeutic effect[] for extended periods of time
... [and to] provid[ e] maximum serum concentration equivalent to that of an
immediate release formulation ... for [the] most effective therapeutic result"
as taught in Davis '508. (Id.)
Appellants argue Davis '508 "is unable to cure the deficiencies of
FANARA" as discussed in connection with Rejection I. (App. Br. 21.)
Appellants contend Davis '508 is "not concerned with the relationship
between two drugs but rather with dosage forms that contain specific
sustained release formulations of guaifenesin and at least one additional
drug." (Id.) Appellants further argue the Examiner is applying hindsight
because Davis '508 "is completely silent with respect to the overlap of the
periods of therapeutic effectiveness of guaifenesin and the at least one
additional drug." (Id; see also Reply Br. 4.)
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We are not persuaded. First, as discussed above, we do not find
persuasive Appellants' arguments that Fanara is deficient. Second, the
teachings of Davis '508 are not limited to what it is "concerned with."
Merck, 874 F.2d at 807 ("[I]n a section 103 inquiry, the fact that a specific
[embodiment] is taught to be preferred is not controlling, since all
disclosures of the prior art, including unpreferred embodiments, must be
considered." (citation and internal quotation marks omitted)). Although
Davis '508 focuses on sustained-release formulations containing
guaifenesin, it expressly teaches formulations that include guaifenesin
combined with other drugs, such as antitussives and decongestants. (FF 8-
10.) And, compositions with the active agents preferred in Davis (e.g.,
guaifenesin combined with dextromethorphan) (FF 10) are expressly
encompassed by Appellants' claims. (See, e.g., App. Br. 29 (claims 157 and
171-174).) Third, Davis '508 is not "completely silent" about the period of
therapeutic overlap in its combined drug formulations. To the contrary,
Davis '508 discloses that guaifenesin and at least one second drug of the
sustained-release formulation remain therapeutically effective for twelve
hours. (FF 10.) In other words, Davis '508 expressly teaches formulations
with at least two drugs having periods of therapeutic effect that substantially,
if not completely, overlap.
Accordingly, the preponderance of the evidence supports the
Examiner's conclusion that claim 157 would have been obvious over Fanara
and Davis '508. Claims 157-215, 219-232, 235-239, 241-243, 248-296,
299-304, and 306-311 have not been argued separately and thus fall with
claim 157.
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Application 11/115,321
Claim 216
Appellants argue the patentability of claims 216-218, 233, 234, 240,
244--247, 297, 298, and 305 as a group under a separate heading. (App. Br.
20.) As discussed above, these claims relate to differences in the plasma
half-lives of the drugs in the claimed dosage forms. We select claim 216 as
representative.
Appellants essentially repeat the argument described above
concerning claim 216 - contending the Examiner has failed to provide
evidence in Fanara or Davis '508 of two drugs in a single dosage form
having half-lives that differ by several hours. (App. Br. 22.)
As above, we are unpersuaded. The same active drugs combinations
described in the prior art are encompassed by the present claims, and so the
drugs would be expected to exhibit the half-lives claimed. (Final Act. 5; FF
7-10.) Moreover, the plasma half-lives of the relevant drugs would have
been known to the skilled artisan. For example, Davis '508 teaches that the
plasma half-life of guaifenesin and pseudoephedrine are about 1 hour and 4--
6 hours respectively. (Davis '508 i-fi-f 11-12.) Accordingly, the combination
of Fanara and Davis teaches "a plasma half-life of the second drug differs
from the plasma half-life of the first drug by at least about 2 hours" as
recited in claim 216. Claims 217, 218, 233, 234, 240, 244--247, 297, 298,
and 305 have not been argued separately, and thus fall with claim 216.
III
The Examiner rejected claims 157-311 over Fanara and Davis '318.
The Examiner's statement of the rejection (Final Act. 10-11, 20-21; Ans.
12-14) is similar to Rejection II. Also, the relevant teachings of Davis '318
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Application 11/115,321
are substantially the same as those in Davis '508. (See, e.g., Davis '318 i-fi-1
17-20, 45.) We adopt the Examiner's findings, reasoning, and conclusion
that claims 157-311 would have been obvious over Fanara and Davis '318.
Appellants' arguments concerning this rejection are repetitive to their
arguments concerning Rejections I and II (App. Br. 22-24), and are
unpersuasive for the reasons previously discussed.
SUMMARY
We affirm the rejection of claims 157-311under35 U.S.C. § 103(a)
over: (i) Fanara, Findlay, and Paradissis; (ii) Fanara and Davis '508; and (iii)
Fanara and Davis '318.
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).
AFFIRMED
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