PHARMATHEN S.A.

Patent Trials and Appeals Board

Nov 22, 2021

2021001636 (P.T.A.B. Nov. 22, 2021)

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.
15/326,531 01/16/2017 EVANGELOS KARAVAS PHARMA-131 7068
27769 7590 11/22/2021
AKC PATENTS
215 GROVE ST.
NEWTON, MA 02466
EXAMINER
GHALI, ISIS A D
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
11/22/2021 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):
acollins@akcpatents.com
aliki@alum.mit.edu
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte EVANGELOS KARAVAS, EFTHYMIOS KOUTRIS, VASILIKI
SAMARA, IONNA KOUTRI, ANASTASIA KALASKANI, LIDA
KALANTZI, ANDREAS KAKOURIS, AMALIA DIAKIDOU, GEORGE
GOTZAMANIS, ZAHARIAS GEORGOUSIS, and MANOLIS
FOUSTERIS
Appeal 2021-001636
Application 15/326,531
Technology Center 1600
BEFORE TINA E. HULSE, JOHN E. SCHNEIDER, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1, 3–6, 8, and 10. We have jurisdiction
under 35 U.S.C. § 6(b).

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a). Appellant identifies the real party in interest as Pharmathen, S.A.
Appeal Br. 2.
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We AFFIRM.
CLAIMED SUBJECT MATTER
The claims are directed to “a stable pharmaceutical formulation for
oral administration containing a therapeutically effective quantity of an
antiviral agent, and more particularly Valaciclovir or pharmaceutical
acceptable salt or derivative thereof.” Spec. 1. The pharmaceutical
composition masks the bitter taste of Valaciclovir improving its palatability.
Spec. 2. Claim 1, reproduced below, is illustrative of the claimed subject
matter:
1. A chewable tablet comprising Valaciclovir or
pharmaceutical acceptable salt thereof in a hydrogen-
bonding with a weak cationic acid ion exchange resin,
wherein the ratio of Valaciclovir to the ion exchange resin is
1:0.8 in order to obtain a palatable and patient-friendly
product.
Claim 6 is directed to a method for producing the composition and
read as follows:
6. A process for the preparation of a chewable tablet of
Valaciclovir or pharmaceutical acceptable salt thereof (Drug) in
a hydrogen-bonding with a weak cationic acid ion exchange
resin, comprising the following steps:
-Dry blending of the Drug directly with the ion exchange
resin in a ratio Drug: Ion Exchange Resin 1:0.8;
-Kneading the above blend with water in the ratio Drug:
Ion Exchange Resin: Water 1:0.8:0.5;
-Drying of the wet mass at 40°C;
-Milling of the Drug Resin Complex until particle size
gets less than 250μm;
-Dry mixing of the Drug Resin Complex and the
excipients of the internal phase;
-Mixing with the excipients of the external phase;
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-Sifting the powder to eliminate any clumps;
-Compressing into tablet dosage form;
wherein the tablet dosage form comprises a palatable and
patient-friendly product.

Appeal Br. 17–18 (Claims App.)
REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Carter et al. US 5,879,706 Mar. 9, 1999
Carter et al. US 6,107,302 Aug. 22, 2000
Tengler et al. US 2007/0092553 A1 Apr. 26, 2007
Pilgaonkar et al. US 2012/0093738 A1 Apr. 19, 2012
Karavas et al. WO 2009/049648 A2 Apr. 23, 2009
Michele et al. Safety of chewable tablets for children, 35 J. Asthma 391–
403 (2002)
Vijay et al., Ion Exchange Resins and Their Applications, 4 J. Drug. Del.
Therap. 115–123 (2014)2

REJECTIONS
The Examiner has rejected the pending claims as follows:
Claims 1, 3–5, and 10 have been rejected under 35 U.S.C. § 103 as
unpatentable over Pilgaonkar in view of Carter ’706, Tengler Karavas,
Sharma, and Michele. Final Act. 3–8.
Claims 6 and 8 have been rejected under 35 U.S.C. § 103 as
unpatentable over Pilgaonkar in view of Carter ’706, Sharma, Tengler,
Michele, Karavas and Carter ’302. Final Act. 8–23.

2 Both the Examiner and Appellant refer to this reference as “Sharma” which
is the first name of the first author. For consistency, we shall refer to the
reference as “Sharma.”
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OPINION
First Obviousness Rejection
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that the subject matter of
claims 1, 3–5, and 10 would have been obvious to one of ordinary skill in
the art at the time the invention was made over Pilgaonkar combined with
Carter ’706 and Tengler as evidenced by Karavas and Sharma.
The Examiner finds Pilgaonkar teaches a chewable tablet containing
an antiviral drug where the bitter taste of the drug is masked. Final Act. 4.
The Examiner finds Pilgaonkar teaches that one class of masking agent that
can be used is cationic ion exchange resins such as Indion® 204. Id. The
Examiner finds that Pilgaonkar teaches a ratio of masking agent to drug of
from 1:.01 to 1:20. Id.
The Examiner finds Carter ’706 teaches the preparation of a chewable
tablet comprising Valaciclovir. Id. at 5. The Examiner finds Karavas teaches
that Valaciclovir has a bitter taste. Id.
The Examiner finds that Tengler teaches a chewable formulation that
includes the use of cationic ion exchange resins to mask the taste of various
antiviral drugs. Id.
The Examiner finds Michele teaches “chewable tablets provide a safe,
well-tolerated alternative to traditional pediatric drug formulations and offer
significant advantage in children of age 2 years and older.” Id.
The Examiner concludes:
Therefore, it would have been obvious to one having
ordinary skill in the art before the effective filing date of the
present invention to provide formulation to deliver the bitter
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tasting antiviral agent including Valaciclovir complexed with
ion exchange resin at ratio of 1:0.1 to 1:20 wherein the
formulation can be chewable formulation as taught by
Pilgaonkar, evidenced by Karavas, and use the ion exchange
resin to complex with Valaciclovir taught by Carter. One would
have been motivated to do so because Carter teaches that
Valaciclovir shown to possess an improved bioavailability
whilst maintaining the potent antiviral activity of acyclovir, and
it can be delivered in chewable tablet. One would reasonably
expect formulating cost effective stable chewable tablet
comprising Valaciclovir complexed with ion exchange resin at
the claimed ratio wherein the tablet has improved
bioavailability and antiviral potency.
Further one having ordinary skill in the art would have
been motivated to deliver Valaciclovir complexed with ion
exchange resin taught by the combination of Pilgaonkar and
Carter, evidenced by Karavas, from chewable tablet as taught
by Tengler because Tengler teaches that ion exchange resin
complexed with the drug, including antiviral, masks the taste of
the drug while the formulation is free flowing and
compressible.
Furthermore, one having ordinary skill in the art would
have delivered Valaciclovir from chewable formulation as
taught by Michele TM to administer to pediatric patients above
2 years [o]f age because Michele TM teaches that chewable
tablets provide a safe, well-tolerated alternative to traditional
pediatric drug formulations and offer significant advantage in
children of age 2 years and older, and have the advantages of
palatability, stability, precise dosing, portability and ease of
delivery, and further teaches that medical issues related to
chewable formulation were extremely rare.
Regarding the claimed ratio of Valaciclovir to the ion
exchange resin of 1:0.8 as claimed by claim 1, Pilgaonkar
teaches 1:0.1 to 1:20 that embraces the claimed ratio. In the
case where the claimed ranges "overlap or lie inside ranges
disclosed by the prior art" a prima facie case of obviousness
exists. See MPEP 2144.05 [R-5].

Id. at 6–7.
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Appellant contends that the combination of references do not render
the claimed composition obvious. Appeal Br. 6. Appellant contends
Pilgaonkar is limited to influenza antiviral drugs and there is no teaching or
suggestion that Valaciclovir is an anti-influenza drug. Id. Appellant contends
Valaciclovir has a different structure than the drugs recited in Pilgaonkar and
that one skilled in the art would not expect that Valaciclovir could be used
with the cationic ion exchange resins disclosed in Pilgaonkar. Id. at 6–7.
Appellant contends that Pilgaonkar teaches away from using the
cationic ion exchange resin with Valaciclovir in that Pilgaonkar teaches
“Not all taste-masking technologies, however, work with every drug. Taste-
masking technologies and processes employed to achieve the same, in
certain instances, interfere with disintegration, affect stability, provide
inadequate taste-masking for a given active or interfere with the
bioavailability or pharmacokinetic properties of the drug.” Id. at 7, quoting
Pilgaonkar ¶ 16.
Appellant contends that there is nothing in Pilgaonkar that teaches or
suggests that the taste-masking technology would work with Valaciclovir
and not interfere with its bioavailablilty or result in an appropriate release
profile. Id.
Appellant argues that while Valaciclovir is listed as an additional drug
that may be added to the composition of Pilgaonkar, there is no teaching in
Pilgaonkar that the Valaciclovir interacts with the ion exchange resin to
mask the taste of the Valaciclovir. Id. 7–8.
Appellant argues that while Pilgaonkar teaches an embodiment where
the ratio of influenza antiviral to resin varies from 1:0.1 to 1:20, there is no
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teaching that those ratios would be applicable to other antiviral drugs.
Appeal Br. 8.
Appellant contends:
A person skilled in the art would have to disregard the
fact that Pilgaonkar’s teachings are for influenza antivirals and
to decide to apply the teachings of Pilgaonkar to one of the
additional active agents that are listed in a long list of active
compounds in paragraph [0086] of the Pilgaonkar application.
Next, the person skilled in the art would have to choose an ion
exchange resin as a taste masking agent out of at least seven
proposed agents and ways of taste masking (see claim 5 of the
Pilgaonkar application), and finally choose a specific ratio of
1:0.8 from a broad range of 1:01 to 1:20. It is believed that it is
highly unlikely that a person skilled in the art would have
arrived to such unobvious combination without the hindsight
provided by the present invention. Rejections based on § l03(a)
must rest on a factual basis with these facts being properly set
forth and interpreted without hindsight reconstruction of the
invention from the prior art. See In re Warner, 379 F.2d 1011,
1017 (CCPA 1967).

Id. at 9.
Appellant contends that Carter ’706 does not teach the use of an ion
exchange resin and does not render the claims obvious. Id. at 10. Appellant
also contends that because Carter ’706 does not mention the taste of
Valaciclovir, there is no motivation to combine the teachings of Pilgaonkar
with Carter ’706. Id.
Appellant argues that since Carter does not mention the taste of
Valaciclovir, there is no reason to look to Karavas or Sharma for evidence
relating to the taste to the drug. Id. at 11.
Appellant argues that while Tengler teaches the use of cationic ion
exchange resins to mask the taste of various antiviral drugs, Tengler does not
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specifically mention Valaciclovir. Id. Appellant argues that given the
teaching in Pilgaonkar that not all masking technologies work with all drugs,
one skilled in the art would not apply the cationic ion exchange resin on
Tengler with Valaciclovir. Id.
Findings of Fact
We adopt the Examiner’s findings as our own, including with regard
to the scope and content of, and motivation to modify or combine, the prior
art. The following findings are included for emphasis and reference
purposes.
FF1. Pilgaonkar teaches the preparation of taste masked oral
formulations of influenza antivirals. Pilgaonkar, Abstr.
FF2. The oral formulation of Pilgaonkar can be a chewable tablet. Id.
FF3. Pilgaonkar teaches:
Further, taste is an important parameter governing the
compliance of patients of any age group. The unpleasant or
bitter taste or taste alteration associated with influenza antivirals
can lead to low patient compliance. Therefore, in order to use
them in convenient solid dosage forms that disintegrate rapidly
in the mouth or disperse rapidly in an aqueous medium, taste-
masking becomes very crucial.

Id.¶ 9.
FF4. Pilgaonkar teaches:
The present invention discloses influenza antiviral
formulations wherein the bitter, unpleasant or otherwise
undesirable taste of the active is masked without compromising
on the stability, handling characteristics, mechanical strength
and in vitro release profile of the formulations, using simple
and cost effective process.

Id. ¶ 17.
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FF5. Pilgaonkar teaches that in one embodiment, the taste masking
agent is a cationic ion exchange resin such as Indion® 204. Id. ¶ 40.
FF6. Pilgaonkar teaches that an ion exchange resin can be used in a
ratio of active to resin of from about 1:0.1 to 1:20. Id.
FF7. Carter ’706 teaches the preparation of a tablet comprising
Valaciclovir and colloidal silicon dioxide. Carter ’706, Abstr.
FF8. Carter ’706 teaches that the tablet can be a chewable tablet and
that the administration route will depend on the condition of the patient. Id.
at col. 5, ll. 38–47.
FF9. Karavas teaches that there is a need to mask the bitter taste of
Valaciclovir. Karavas, 2.
FF10. Tengler teaches compositions to reduce the taste of drugs in a
composition where the drug is released from the composition in the mouth.
Tengler, Abstr.
FF11. Tengler teaches
certain drugs produce an unpalatable taste associated with the
immediate release agent that are not effectively masked by
traditional taste masking techniques. The present invention
addresses the problems associated with the delivery of one or
more active agents in a solid dosage form under controlled
conditions. Solid, chewable formulations are often preferred by
many users due to the easy [sic] of delivery, namely, natural
chewing and swallowing thereby leading to increased
compliance with dosing regimens. Many children and adults
fail to comply with dosing instructions due to the size, shape,
taste and/or mouth-feel of, e.g., tablets, caplets and even
gelcaps.

Id. ¶ 10
FF12. Tengler teaches:
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Examples of active agents that may be provided as part
of the chewable formulations of the present invention include
vitamins, minerals, nutritional supplements, herbal extracts,
gums, gels, oils, salts, mixtures and combinations thereof.
Pharmaceutical active agents may include, e.g., protein,
peptide, carbohydrate, polysaccharide, glycoprotein, lipid,
hormone, growth factor, cytokine, interferon, receptor, antigen,
allergen, antibody, antiviral, antifungal, antihelminthic,
substrate, metabolite, cofactor, inhibitor, drug, nutrient, toxin,
poison, explosive, pesticide, chemical warfare agent, biowarfare
agent, biohazardous agent, infectious agent, prion, radioisotope,
vitamin, heterocyclic aromatic compound, carcinogen,
mutagen, narcotic, amphetamine, barbiturate, hallucinogen.

Id. ¶ 17 (emphasis added).
FF13. Tengler teaches that the drug-resin complex of the invention
“includes an exchange resin, e.g., cationic exchange resin.” Id. ¶ 38, claim 9.
FF14. Sharma teaches “Synthetic ion exchange resins have been used
in pharmacy and medicine for taste making or controlled release of drug.”
Sharma Abstr.
FF15. Sharma teaches:
Certain drugs that have very bitter taste can be made
relatively tasteless by adsorbing the drug on ion exchange resin
although all the ion exchange resins can be useful for this
purpose, the proper selection on ionic character of drug and
release characteristics. Weak cation exchange resins can be
used to formulate chewable or dispersible tablet of bitter drugs,
for example Rodec decongestant tablet containing
pseudoephedrin. Weak cation exchangers are most preferable
for their ability to remain undissociated at alkaline pH of
mouth, and thus masking the taste of bound drug and further
releasing it rapidly at acidic pH of stomach. Avari and Bhalekar
reported taste masking of highly bitter antibiotic, sparfloxacin
with Indion 204 weak cation exchanger. Resins have been used
with success to prepare stable and tasteless dosage forms. Taste
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masking in chewable tablets having amino containing drugs
like dextromethorphon, ephedrine, pseudoephedrine, etc. have
been successfully carried out by using weak cation exchange
resin.

Id. at 120.
FF16. Michele teaches “The advantages of chewable tablets include
palatability, stability, precise dosing, portability, and ease of delivery. It is
concluded that the available literature suggests that chewable tablets provide
a safe, well-tolerated alternative to traditional pediatric drug formulations
and offer significant advantages in children 2 years of age and older.”
Michele, Abstr.
Analysis
We find the Examiner has established a prima facie showing that the
subject matter of the claims would have been obvious over Pilgaonkar
combined with Carter ’706 and Tengler as evidenced by Karavas and
Sharma to a person of ordinary skill in the art at the time the invention was
made. Appellant has not produced evidence showing, or persuasively
argued, that the Examiner’s determinations on obviousness are incorrect.
Only those arguments made by Appellant in the Briefs have been considered
in this Decision. Arguments not presented in the Briefs are waived. See 37
C.F.R. § 41.37(c)(1)(iv) (2015). We have identified claim 1 as
representative; therefore, all claims fall with claim 1. We address
Appellant’s arguments below.
Appellant contends that Pilgaonkar is directed to taste masking for
influenza antivirals and there is no teaching or suggestion that the taste
masking technology taught by Pilgaonkar is applicable to other antiviral
drugs, particularly Valaciclovir. Appeal Br. 6. Appellant contends given the
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different structure of Valaciclovir as compared to the antivirals in
Pilgaonkar, one would not expect the taste-masking cationic ion exchange
resins to work for Valaciclovir. Id. at 6–7.
We are not persuaded by this argument. Appellant is attacking the
individual teachings of Pilgaonkar and not the combined teachings of all the
references. “Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. . . . [The reference] must be read, not in
isolation, but for what it fairly teaches in combination with the prior art as a
whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Carter ’706 teaches a chewable drug composition comprising
Valaciclovir. FF7 & 8. Tengler and Sharma teach the use of cationic ion
exchange resins to mask the taste of a broad range of drugs including
antivirals in general. FF10–15. Thus it is the combined teachings of the
references which renders the claimed composition obvious.
Appellant argues that Pilgaonkar teaches away from random
combinations of drugs and taste masking technologies in that Pilgaonkar
teaches that taste masking technologies do not work with all drugs. Appeal
Br. 7. Again we are not persuaded by this argument.
As noted above, Tengler and Sharma both teach that cationic ion
exchange resins work with a broad variety of drugs including antivirals.
FF10–15. We agree with the Examiner that one skilled in the art would have
had a reasonable expectation of success in using a cationic ion exchange
resin to mask the taste of Valaciclovir. See Ans. 10–11.
Appellant contends that there is no teaching in Pilgaonkar that the
taste masking technology of Pilgaonkar would work with Valaciclovir or
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that it would not interfere with the action of Valaciclovir. Appeal Br. 7. This
argument is also unpersuasive.
Tengler and Sharma teach the broad applicability of cationic ion
exchange resins for taste masking in drugs, including antivirals. FF10–15.
Sharma teaches that weak cationic ion exchange resins release the drug
rapidly when it enters the stomach indicating that the resin does not interfere
with the action of the drug. FF15.
Appellant contends that while Pilgaonkar teaches a ratio of influenza
antiviral to resin of from 1:0.1 to 1:20, there is nothing in the references to
suggest that the recited ratio would be applicable to Valaciclovir. Appeal Br.
7–8; 12–13. This argument is also unpersuasive.
The ratio recited in the present claims, 1:0.8 falls within the ratio
recited in Pilgaonkar. FF6. “A prima facie case of obviousness typically
exists when the ranges of a claimed composition overlap the ranges
disclosed in the prior art.” In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir.
2003).
“[A] prima facie case of obviousness [based on overlapping ranges]
can be rebutted if the applicant (1) can establish ‘the existence of unexpected
properties in the range claimed’ or (2) can show ‘that the art in any material
respect taught away’ from the claimed invention.” In re Geisler, 116 F.3d
1465, 1469 (Fed. Cir. 1997) (quoting In re Malagari, 499 F.2d 1297, 1303,
(CCPA 1974)). In this case, we do not discern any persuasive evidence of
either unexpected properties nor a teaching away from the claimed
invention. Appellant contends that the rejection relies on the impermissible
use of hindsight in that it requires:
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A person skilled in the art to disregard the fact that Pilgaonkar’s
teachings are for influenza antivirals and to decide to apply the
teachings of Pilgaonkar to one of the additional active agents
that are listed in a long list of active compounds in paragraph
[0086] of the Pilgaonkar application. Next, the person skilled in
the art would have to choose an ion exchange resin as a taste
masking agent out of at least seven proposed agents and ways
of taste masking (see claim 5 of the Pilgaonkar application),
and finally choose a specific ratio of 1:0.8 from a broad range
of 1:01 to 1:20. It is believed that it is highly unlikely that a
person skilled in the art would have arrived to such unobvious
combination without the hindsight provided by the present
invention.

Appeal Br. 9. We remain unpersuaded that the rejection is in error.
As stated above, Appellant is attacking the teachings of Pilgaonkar
alone and not the combination of references. Moreover “[a]ny judgment on
obviousness is in a sense necessarily a reconstruction based upon hindsight
reasoning, but so long as it takes into account only knowledge which was
within the level of ordinary skill at the time the claimed invention was made
and does not include knowledge gleaned only from applicant’s disclosure,
such a reconstruction is proper.” In re McLaughlin, 443 F.2d 1392, 1395,
(CCPA 1971). As discussed above, the elements missing from Pilgaonkar
are taught by the other references, specifically Carter ’706, Tengler and
Sharma. And we find the examiner has shown sufficiently that a person of
ordinary skill in the art would have had a reason to combine the cited
references to reach the claimed invention with a reasonable expectation of
success. Appellant has not persuasively demonstrated that the rejection is
based on knowledge gleaned only from Appellant’s disclosure.
Appellant argues that Carter ’706 does not teach or make obvious the
claimed invention in that Carter does not teach the use of an ion exchange
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resin. Appeal Br. 10. Once again, this argument focuses on the teachings of
the individual references and not on the combination of references cited by
the Examiner. The Examiner cited Carter ’706 for the teachings of preparing
a chewable tablet containing Valaciclovir. Final Act. 5. As discussed above,
Pilgaonkar, Tengler and Sharma all teach the use of cationic ion exchange
resins to mask the taste of drug compounds in chewable tablet drug
formulations.
Appellant contends that Carter ’706 does not teach or suggest that
Valaciclovir has an unpleasant taste, therefore there is no reason to combine
Carter ’706 with Pilgaonkar. Appeal Br. 10–11. While we agree with
Appellant that Carter ’706 does not teach that Valaciclovir has an unpleasant
taste, Karavas evidences that it was known in the art at the time the
invention was made that Valaciclovir has a bitter taste that needs to be
masked. FF9. Thus Carter ’706 as evidenced by Karavas teaches the need to
mask the bitter taste of Valaciclovir providing the reason to use the taste
masking technology of Pilgaonkar.
Appellant contends that one skilled in the art would not have applied
the teachings of Tengler to a formulation comprising Valaciclovir as
Pilgaonkar teaches that not all taste masking technologies can be used with
every drug. Appeal Br. 11. We are not persuaded by this argument.
While Pilgaonkar includes that statement that not all taste masking
technologies will work with all drugs, Tengler teaches that the ion exchange
resins do work with a broad variety of drug compositions including
antivirals. FF12. This is reinforced by the teachings of Sharma that cationic
ion exchange resins work with a variety of drugs. FF15.
Conclusion
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Based on the foregoing we conclude that a preponderance of the
evidence supports the Examiner’s conclusion that the subject matter of
claims 1, 3–5, and 10 would have been obvious to one of ordinary skill in
the art at the time the invention was made over Pilgaonkar combined with
Carter ’706 and Tengler as evidenced by Karavas and Sharma.
Second Obviousness Rejection
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that the subject matter of
claims 6 and 8 would have been obvious to one of ordinary skill in the art at
the time the invention was made over Pilgaonkar in combination with Carter
’706, Tengler, Michele, Karavas, and Carter ’302.
The Examiner finds Pilgaonkar teaches
[a] method of preparing the formulation comprising the steps of
blending or complexing the antiviral drug with the taste
masking agent (¶¶ 0070, 0071, 0075, 0076). The reference
further teaches complexing the antiviral drug with the ion
exchange resin, i.e. taste masking agent, in the ratio of 1:1.0 to
about 1:20, and teaches kneading and grinding the mixture, and
drying the mixture (¶ 0040). The reference teaches sieving the
mixture, and compressing the table into the dosage form (¶¶
0040, 0073, 0079). The reference further teaches granulating
and sifting the blend (¶¶ 0021, 0022, 0035, 0089, 0098). The
reference teaches lubricating the dry mixture (¶¶ 0072, 0078).
The reference teaches step of mixing with excipients (¶¶ 0071,
0076).

Final Act. 9–10.
The Examiner finds that Carter ’706 teaches a
process of making the formulation comprising the steps of
forming granules of the drug, blending the granules with the
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colloidal silicone and microcrystalline cellulose, milling, drying
by heating at 60°C, filtration, and compressing (examples,
claims 26-28). The reference teaches milling of the drug and
forming particles having an average size less than 50 μm (col.7,
lines 46-47; examples).

Id. at 10.
The Examiner finds that neither Carter ’706 nor Pilgaonkar teach
kneading using water or a drying temperature of 40° C. The Examiner finds
that Karavas teaches kneading a mixture of a Valaciclovir with a binder in
the presence of water to produce a tablet. Final Act. 10. The Examiner finds
that Carter ’302 teaches drying a damp mixture containing Valaciclovir at a
temperature of from 30°C to 70°C. Id. at 11.
The Examiner concludes:
Therefore, it would have been obvious to one having
ordinary skill in the art before the effective filing date of the
present invention to make the chewable tablet by the process
comprising the steps taught by the combination of Pilgaonkar,
Carter ’706, evidenced by Karavas, Tengler, and Michele TM,
and use water to wet the mixture of the drug with other
ingredients as taught by Karavas. One would have been
motivated to do so because Karavas teaches that Valaciclovir
contained in a dosage form produced by this method is
bioavailable, and is released from the dosage form, absorbed
and reaches, at least the same, concentration levels in plasma as
any of the marketed products containing the same quantity of
the same active ingredient and intended for the same use. One
would reasonably expect making a dosage comprising
valaciclovir and ion exchange resin wherein water is used as a
wetting agent for kneading wherein valaciclovir is bioavailable,
and provides the therapeutically effective plasma levels.
Further, one having ordinary skill in the art before the
effective filing date of the present invention would have used
drying temperature in the process of making the dosage form of
between 30°C to 70°C as taught by Carter ’302 because Carter
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’302 teaches suitability of such temperature to dry dosage form
comprising valaciclovir wherein the dosage form is storage
stable.
Regarding the claimed ratio of ingredients as claimed by
claim 6, one having ordinary skill in the art would have
determined the ratio based on the final product to be achieved.
Regarding the claimed temperature of 40°C as claimed
by claim 6, Carter ’302 teaches overlapping temperature of
30°C to 70°C. In the case where the claimed ranges “overlap or
lie inside ranges disclosed by the prior art” a prima facie case of
obviousness exists. See MPEP 2144.05 [R-5].

Id. at 11–12.
Appellant contends that the cited references do not teach or suggest all
of the steps of the method recited in claim 6. Appeal Br. 13. Appellant
contends that Pilgaonkar does not teach or suggest the recited method as
Pilgaonkar is directed to influenza antivirals and not Valaciclovir. Id. at 14.
Appellant contends that Pilgaonkar does not teach or suggest blending
Valaciclovir with an ion exchange resin in a ratio of 1:0.8. Id.
Appellant also contends that none of the references teach or suggest
kneading a mixture of Valaciclovir and ion exchange resin with water at a
ratio drug: ion exchange resin ; water of 1:0.8:0.5. Appellant contends that
this ratio produces an optimal dissolution profile which is unexpected. Id. at
15.
Appellant contends that Carter ’302 does not teach the specific drying
temperature of 40°C. Id.
Finally, Appellant urges that the claims should be allowed as the
International Searching Authority (“ISA”) and the European Patent Office
(“EPO”) have allowed claims 1–8.
Findings of Fact
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FF17. Pilgaonkar teaches:
In one embodiment, ion exchange resin can be used for
complexation with influenza antiviral in a ratio of active to
resin of about 1:0.1 to about 1:20. These drug resinates can be
prepared by methods such as, but not limiting to, blending,
kneading, grinding, sieving, filling, compressing,
lyophilization, spray-drying, fluid-bed drying or centrifugal
granulation.

Pilgaonkar ¶ 40.
FF18. Pilgaonkar teaches:
The present invention further discloses a process for
preparing a taste-masked pharmaceutical formulation of an
influenza antiviral comprising:
(a) physically mixing an influenza antiviral with at least
one taste-masking agent;
(b) blending the mix of step (a) with other excipients,
except lubricant, to form a uniform powder mix;
(c) lubricating the powder mix of step (b); and
(d) compressing the powder mix of step (c) into a
dispersible tablet composition.

Id. ¶¶ 69–73.
FF19. Carter ’706 teaches a process for making tablets containing
Valaciclovir comprising the steps of forming granules of the drug, blending
the granules with the colloidal silicone and microcrystalline cellulose,
milling, drying by heating at 50°C, filtration, and compressing the mixture.
Carter ’706, col. 11, l. 45 – col. 12, l. 55; Claims 26–28.
FF20. Carter ’706 teaches an average particle size for the blended
product of 50µm. Id. Footnote 3 to tables.
FF21. Karavas teaches a method for preparing tablets containing
Valaciclovir comprising the steps of kneading the mixture of drug and
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binder with composition comprising water; sieving the wetted mass through
a sieve and forming granules, drying the granules; sieving the dried granules
through a sieve to achieve the desired granule size; forming a blend with
excipient; and forming the dosage form either by compressing it into a
desired tablet form or by filling capsules or sachets. Karavas 3.
FF22. Carter ’302 teaches a method for preparing tablets containing
Valaciclovir which includes the step of drying a damp mixture at from 30°C
to 70°C.
Analysis
We find the Examiner has established a prima facie showing that the
subject matter of the claims would have been obvious over Pilgaonkar in
combination with Carter ’706, Tengler, Michele, Karavas, and Carter ’302 to
a person of ordinary skill in the art at the time the invention was made.
Appellant has not produced evidence showing, or persuasively argued, that
the Examiner’s determinations on obviousness are incorrect. Only those
arguments made by Appellant in the Briefs have been considered in this
Decision. Arguments not presented in the Briefs are waived. See 37 C.F.R.
§ 41.37(c)(1)(iv) (2015). We have identified claim 6 as representative;
therefore, claim 8 falls with claim 6. We address Appellant’s arguments
below.
Appellant argues that Pilgaonkar does not teach all of the steps recited
in claim 6. Appeal Br. 14. As with the product claims addressed above,
Appellant contends that Pilgaonkar is directed to influenza antivirals and not
Valaciclovir. Id. Appellant argues that there is no teaching in Pilgaonkar to
blend Valaciclovir with an ion exchange resin in a ratio of 1:0.8. Id.
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Appellant is again attacking the teachings of the individual reference
and not the combination of references relied upon by the Examiner. As
discussed above, Carter ’706 teaches the use of Valaciclovir and Tengler
teaches the application of ion exchange resins to antivirals broadly. FF7 &
12.
Appellant argues that the references do not teach kneading the blend
of Valaciclovir with the ion exchange resin with water in the ratio of Drug:
Ion Exchange Resin: Water 1:0.8:0.5. Appeal Br. 15. Appellant contends
that this ratio produces an optimal dissolution profile that is unexpected. Id.
We have considered Appellant’s argument, but we are not persuaded
that the rejection is in error. Pilgaonkar teaches a ratio of Drug to resin of
from 1:0.1 to 1:20 which overlaps with the drug to resin ratio recited in the
claims. This renders the recited ratio prima facie obvious. In re Peterson,
315 F.3d at 1329. With respect to the amount of water, use of water during
the kneading step is taught by Karavas. FF21. As the Examiner points out,
“Finding the optimal dissolution profile is within the grasp of one of
ordinary skill in the art in view of the known properties of the drug.” Ans.
23. “[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.” In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Appellant argues that it was unexpected that the recited ratio would
lead to the optimum dissolution profile. Appeal Br. 15. We are not
persuaded. Appellant has not pointed to any persuasive evidence to support
its contention that it was unexpected that the recited ratio produced an
optimum dissolution rate. “[I]t is well settled that unexpected results must be
established by factual evidence. ‘Mere argument or conclusory statements in
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the specification does not suffice.’” In re Geisler, 116 F.3d 1465, 1470 (Fed.
Cir. 1997) (quoting In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)).
Appellant contends that Carter ’302 does not teach drying the wet
mass at a temperature of 40°C. Appeal Br. 15. We are not persuaded by this
argument. Carter ’302 teaches drying the wet mixture at a temperature of
from 30°C to 70°C. FF22. This range overlaps with the temperature cited in
claim 6 supporting a conclusion of obviousness. In re Peterson, 315 F.3d at
1329.
Appellant’s argument regarding the findings of the ISA and EPO are
not persuasive. As the Examiner points out, the present rejections are based
on different references than those cited by either the ISA or the EPO. Ans.
24. Moreover the law regarding obviousness differs between the United
States and the EPO.
Conclusion
Based on the foregoing we conclude that a preponderance of the
evidence supports the Examiner’s conclusion that the subject matter of
claims 6 and 8 would have been obvious to one of ordinary skill in the art at
the time the invention was made over Pilgaonkar in combination with Carter
’706, Tengler, Michele, Karavas, and Carter ’302.
CONCLUSION
The Examiner’s rejections are AFFIRMED.
The rejection of claims 1, 3–5, and 10 under 35 U.S.C. § 103 as
unpatentable over Pilgaonkar in view of Carter ’706 and Tengler as
evidenced by Karavas and Sharma is affirmed.
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The rejection of claims 6 and 8 under 35 U.S.C. § 103 as unpatentable
over Pilgaonkar in view of Carter ’706, Tengler, Michele, Karavas, and
Carter ’302 is affirmed.
DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 3–5, 10 103 Pilgaonkar, Carter
’706, Tengler,
Karavas, Sharma,
Michele
1, 3–5, 10
6, 8 103 Pilgaonkar, Carter
’706, Tengler,
Michele, Karavas,
Carter ’302
6, 8
Overall
Outcome
1, 3–6, 8, 10

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED