Ex Parte Rashid et al

Patent Trial and Appeal Board

Dec 12, 2018

14627589 (P.T.A.B. Dec. 12, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/627,589 02/20/2015
29880 7590 12/14/2018
FOX ROTHSCHILD LLP
PRINCETON PIKE CORPORATE CENTER
997 LENOX DRIVE
BLDG. #3
LAWRENCEVILLE, NJ 08648
FIRST NAMED INVENTOR
Abdul Rashid
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.
100867.00501 6302
EXAMINER
PROSSER, ALISSA J
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
12/14/2018 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):
ipdocket@foxrothschild.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ABDUL RASHID, DAHAI GUO,
MINH TRAN, and ZHANG JULIA ZHANG
(APPLICANT: Enspire Group LLC)
Appeal2017-008437
Application 14/627 ,589 1
Technology Center 1600
Before DONALD E. ADAMS, DEMETRA J. MILLS, and
JAMES A. WORTH, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This Appeal under 35 U.S.C. § 134(a) involves claims 1-15, 22, 23,
25, and 30-35 (Final Act. 2 2; Appeal Br. 3 3; Reply Br. 4 3). 5 Examiner
entered a rejection under 35 U.S.C. § 103(a). We have jurisdiction under 35
U.S.C. § 6(b). We AFFIRM.
1 Appellants identify "Enspire Group LLC" as the real party in interest
(Appeal Br. 3).
2 Office Action mailed September 9, 2016.
3 Appellants' February 8, 2017 Appeal Brief.
4 Appellants' May 9, 2017 Reply Brief.
5 Appellants' pending claims 16-21 and 24 stand withdrawn from
consideration (see Final Act. 2; Appeal Br. 3; Reply Br. 3).
Appeal2017-008437
Application 14/627,589
STATEMENT OF THE CASE
Appellants' disclosure "relates to bioavailable fill compositions
containing [] fexofenadine, soft gelatin capsules filled with the bioavailable
fexofenadine fill compositions, and methods of making same" (Spec. ,r 1 ).
Claim 1 is representative and reproduced below:
1. A bioavailable liquid softgel fill composition comprising:
a) 4-40% by weight of fexofenadine or a fexofenadine salt;
b) a matrix comprising:
i) 40-80% by weight of a pharmaceutically acceptable
poly(alkylene glycol);
ii) 5-30% by weight of a pharmaceutically acceptable
alkylene glycol;
iii) 1-10% by weight of a pharmaceutically acceptable
polymeric solubilizing agent; and
iv) 0.001- 0.4% by weight of a pharmaceutically
acceptable surfactant; and
c) 0.001-2% by weight of a pharmaceutically acceptable
acidulant;
based on the total weight of the composition,
provided that said fexofenadine or fexofenadine salt and said
pharmaceutically acceptable surfactant are present in a ratio of
about 40000: 1 to 30: 1 by weight.
(Appeal Br. 18.)
Appellants' claims stand rejected as follows:
Claims 1-15, 22, 23, 25, and 30-35 stand rejected under 35 U.S.C.
§ I03(a) as unpatentable over the combination ofVamvakas6 and Wilson. 7
6 Vamvakas et al., US 2015/0108033 Al, published Apr. 23, 2015.
7 Wilson et al., US 6,287,594 B 1, issued Sept. 11, 2001.
2
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Application 14/627,589
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Vamvakas discloses that "[ s ]olubilizing hydrophobic and
amphiphilic active drug substances for efficient oral delivery remains a
problem ... because of precipitation of the active" (Vamvakas ,r 3; see
Appeal Br. 5 ("fexofenadine is ... quite hydrophobic")).
FF 2. Vamvakas disclose that "there is an unmet need in the field for soft
capsule pharmaceutical formulations that are suitable for poorly soluble
active drug substances, which increase bioavailability and inhibit or reduce
the affinity of the P-gp transporter for poorly soluble active drug substances"
(Vamvakas ,r 7; see id. ,r 4 (Vamvakas discloses that "[s]oft capsules have
gained popularity and acceptance over tablets and hard capsules due to their
elegant and clear appearance")).
FF 3. Vamvakas discloses "pharmaceutical formulations suitable for
poorly soluble active drug substances that in some embodiments may inhibit
or reduce the affinity of the P-gp transporter for the poorly active drug
substances" and "may further increase the permeability of the active drug
substances" (Vamvakas ,r 8; see also id. ,r 2 (Vamvakas discloses
"pharmaceutical compositions for the delivery of poorly soluble active
pharmaceutical ingredients" and "[i]n particular, a substantially clear
fexofenadine HCl[sJ solution in a soft gelatin capsule"); see id. ,r 50 ("The
8 See e.g., Appeal Br. 19 ("fexofenadine salt is fexofenadine
hydrochloride").
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Application 14/627,589
term 'substantially' as used [in Vamvakas] ... means to a great or
significant extent, but not completely")).
FF 4. Vamvakas discloses that "pharmaceutical excipients such as
surfactants, polyethylene glycols, solubilizing polymers, and classes of lipids
can indirectly reduce or inhibit P-gp transporter activity (Vamvakas ,r 70).
FF 5. Vamvakas discloses "[i]n one aspect, the solubility enhancing agent
comprises polyethylene glycol, propylene glycol, or glycerol. In another
aspect, the solubility enhancing agent comprises polyethylene glycol and
propylene glycol. In another aspect, polyethylene glycol has a molecular
weight of about 200 to about 1000" (Vamvakas ,r 10; see also id. ,r,r 63-64).
FF 6. Vamvakas discloses "[i]n one aspect, the surfactant comprises an
anionic surfactant," such as "sodium lauryl sulfate, sodium docusate, sodium
sterate, or ammonium lauryl sulfate" (Vamvakas ,r 12; see id. ,r 5 (Vamvakas
discloses that a surfactant disperses emulsions, generated by the
solubilization of an active ingredient in an oil phase, in an aqueous
environment); see also id. ,r,r 56-57).
4
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Application 14/627,589
FF 7. Vamvakas exemplifies a matrix fill that comprises:
[P]olyethylene glycol 400[9J comprises about 59% of the matrix
fill mass, propylene glycol[lOJ comprises about 15% of the
matrix fill mass, Povidone[llJ K 90 comprises about 3.3% of the
matrix fill mass, citric acid comprises about 1 % of the matrix
fill mass, sodium lauryl sulfate comprises about 4.2% of the
matrix fill mass, the active pharmaceutical ingredient comprises
about 15% of the matrix fill mass, and water comprises about
2.5% of the matrix fill mass.
(Vamvakas ,r 81; see id. ,r 51 ("The term 'about' as used [ in Vamvakas] ...
refers to any value that is within a variation of up to ± 10% of the value
modified by the term 'about'"); id. ,r 9 (V amvakas' matrix fill comprises
about 40-85% solubility enhancing agent, about 1-10% viscosity enhancing
agent, about 1-7% surfactant, about 1-3% pH-modifying agent, and about 5-
33% pharmaceutical ingredient); see Final Act. 5 (Examiner finds that "[t]he
ratio of the active pharmaceutical ingredient ( fexofenadine) to the matrix as
instantly claimed is 15/(59+15+3.3+4.2) = 15/81.5 which is equivalent to a
weight ratio of 1 :5.4); see also Final Act. 4---6 and 8.)
FF 8. Examiner finds that "Vamvakas do[es] not specifically teach or
exemplify [a composition] ... comprising 0.001 to 0.4 wt% of a surfactant
9 See e.g., Appeal Br. 19 ("pharmaceutically acceptable poly(alkylene
glycol) is selected from the group consisting of PEG 200 to PEG 8000, and
mixtures thereof'); see also Spec. ,r,r 9 and 12.
10 See e.g., Appeal Br. 19 ("pharmaceutically acceptable alkylene glycol is
propylene glycol"); see also Spec. ,r,r 9 and 12.
11 Examiner finds that "provodone" is otherwise known in the art as
"polyvinylpyrrolidone or PVP" (Final Act. 6); see also Appeal Br. 19
(pharmaceutically acceptable polymeric solubilizing agent is a
polyvinylpyrrolidone (PVP)); Spec. ,r 9 ("polyvinylpyrrolidone
(povidone)"); Spec. ,r 12 ("PVP is selected from the group consisting of ...
PVP K90")).
5
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Application 14/627,589
as required by [Appellants'] claim 1" and relies on Wilson to make up for
this deficiency in Vamvakas (Final Act. 6-7).
FF 9. Wilson "relates to pharmaceutically elegant compositions for oral
administrations," wherein such "compositions ... include at least one
pharmaceutically active agent having at least one acid moiety, preferably a
carboxylic acid moiety," such as "fexofenadine" (Wilson 1: 11--47; id. at
3:45-54 ("Active Ingredients for [Wilson's] compositions ... [include]
fexofenadine"); id. at 4:37-39 (Wilson discloses the use of an Active
Ingredient at a concentration range "from about 5 percent to about 25
percent (w/w)); see Appeal Br. 14 ("fexofenadine contains a free carboxylic
acid group"); see Final Act. 7).
FF 10. Wilson discloses:
soft gelatin capsules ... comprising:
one or more pharmaceutically active agents wherein said
pharmaceutically active agent is selected from the group
consisting of said agents wherein at least one of said agents
having at least one acid moiety, and
at least one of said agents having at least one ester group or
other chemically active moiety in which the terminal moiety
to said ester group or other chemically active moiety is
hydrolyzed or otherwise removed in situ or in vivo forming
at least one acid moiety; and wherein said pharmaceutically
active agent is soluble in acid at a ratio of about 3: 1 ( acid to
solute) to about 10,000: 1 ( acid to solute) or a
pharmaceutically acceptable salt thereof (hereinafter, the
"Active Ingredient");
at least one dispersing agent; and
at least one solubilizing agent; and, optionally,
at least one surfactant; and, further optionally,
at least one plasticizing agent.
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Application 14/627,589
The present invention further relates to the use of the
compositions of the present invention for improving adsorption
of the Active Ingredients.
(Wilson 2:33-55; see Final Act. 7.)
FF 11. Wilson discloses the PVP is a dispersing agent within the scope of
its invention and exemplified the use of PVP at a concentration of 4%, 6.3%,
10%, and 15% (w/w) (Wilson 4:40-50; 12: 1-13; 12:40-50; 13: 10-20;
10:48-59; see Final Act. 7).
FF 12. Wilson discloses that "[d]ispersing polymers generally are selected
to ensure appropriate uniformity using viscosity while providing a
pharmaceutically elegant appearance to the resulting solution" (Wilson
4:60-63; see Final Act. 7).
FF 13. Wilson discloses that "polyethylene glycols (PEG) having molecular
weights from about 200 to about 8,000" are solubilizing agents within the
scope of its invention and are used in a concentration "from about O percent
(Oust greater than zero) to about 99 percent (w/w)" (Wilson 5:16-46; id. at
20:1-16; see Final Act. 7).
FF 14. Wilson discloses the "propylene glycol" is a plasticizing agent
within the scope of its invention and are used in a concentration "from about
zero percent [(]Oust greater than zero) to about 25% (w/w)" (Wilson 5:50-
63; id. at 20:1-16; see Final Act. 7).
FF 15. Wilson discloses the use of surfactants "well known in the
pharmaceutical formulation art" in a "concentration ranging from about zero
percent to about 10 percent (w/w) of the total composition" (Wilson 6:7-17;
id. at 20: 1-16; see Final Act. 7 and 9).
FF 16. Wilson discloses the use of reagents to maintain the composition at a
proper pH (see Wilson 6:24--54).
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Appeal2017-008437
Application 14/627,589
ANALYSIS
Based on the combination of V amvakas and Wilson, Examiner
concludes that, at the time Appellants' invention was made, it would have
been prima facie obvious
to modify the amount of surfactant or sodium lauryl sulfate
[ (SLS)] in the soft capsule matrix fill compositions of
Vamvakas ... because Wilson teach[ es] it is known in the art to
formulate soft matrix fills comprising fexofenadine, PVP, PEG
400, propylene glycol and water in combination with
( optionally) at least one surfactant from zero to about 10%.
(Final Act. 8-9; see FF 1-16).
In addition, Examiner reasons that Appellants'
claimed ratio of ratio of fexofenadine to surfactant/SLS of
about 40000:1 to 30:1, about 40000:1 to 30:1, because the
combined teaching of Vamvakas in view of Wilson render
obvious compositions comprising 5 to 25 wt% fexofenadine
HCl and surfactants inclusive of SLS from O to 10 wt%, the
combine teachings of the prior art render obvious a ratio of
about infinity ( dividing either 5 or 25 wt% fexofenadine by
zero) to about 0.5 which overlaps [Appellants'] ... claimed
range(s).
(Final Act. 9.)
Appellants contend that "[t]he mere fact that Wilson describes oral
liquid compositions with a surfactant about zero percent to about 10% does
not provide the necessary motivation for one of ordinary skill in the art to us
0.001-[] 0. 4 % surfactant in the context of the V amvakas composition"
(Appeal Br. 9; Reply Br. 3--4 and 6-8). In this regard, Appellants contend
that Vamvakas and Wilson address different problems relating to
pharmaceutical formulations (Appeal Br. 9-10; Reply Br. 4). We are not
persuaded.
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Application 14/627,589
As Examiner explains,
the logic of the rejection does not hinge on the mere fact that
Wilson describes oral liquid compositions comprising about 0
to about 10% surfactant. Rather, the rejection is predicated on
the fact that Wilson, like Vamvakas, render obvious a
pharmaceutical composition comprising an active agent such as
fexofenadine, at least one dispersing agent such as PVP, at least
one solubilizing agent such as PEG 400 and water, at least one
surfactant, and at least one plasticizing agent such as propylene
glycol.
(Ans. 3.) Thus, notwithstanding Appellants' contentions to the contrary,
Vamvakas and Wilson both related to pharmaceutically elegant soft gel
capsules comprising fexofenadine, polyethylene glycol, propylene glycol,
PVP, and a surfactant (see FF 1-16). Therefore, a person of ordinary skill in
this art would have had a reason and motivation to consider Vamvakas and
Wilson in combination when preparing pharmaceutically elegant soft gel
capsule formulations comprising the foregoing ingredients (see Ans. 3
("Wilson is indisputably analogous to Vamvakas")).
We are not persuaded by Appellants' contention that a person of
ordinary skill in this art would not have been motivated to reduce the amount
of surfactant disclosed by Vamvakas, because Vamvakas discloses that
surfactant is important in solubilizing fexofenadine and "can indirectly
reduce or inhibit P-gp transporter activity" (Appeal Br. 10-12). Vamvakas
discloses that "pharmaceutical excipients such as surfactants, polyethylene
glycols, solubilizing polymers, and classes of lipids can indirectly reduce or
inhibit P-gp transporter activity" (FF 4; see Ans. 5-6; cf Appeal Br. 12
("there is no teaching from the cited art that an increase in PEGs or PVPs (if
any) could offset the decrease in surfactant at the same magnitude in terms
of the P-gp transporter inhibiting activity")). Thus, notwithstanding
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Application 14/627,589
Appellants' contentions to the contrary, Vamvakas expressly discloses that,
inter alia, PEG can be used to indirectly reduce or inhibit P-gp transporter
activity. Thus, we find no err in Examiner's reasoning, as quoted by
Appellants, that "any loss on the P-gp transporter inhibiting activity due to
decrease in surfactant's percentage of the Vamvakas composition would be
offset by PEGs" (Appeal Br. 12; see Ans. 12 6).
Consistent with Vamvakas' disclosure, Wilson discloses a soft gel
capsule comprising fexofenadine, wherein the concentration ranges of PEG,
propylene glycol, PVP, and surfactant overlap and are broader than those
disclosed in Vamvakas (see FF 10-15; cf FF 7). Included in Wilson's
disclosed ranges is a range of surfactant "from about zero percent to about
10 percent" (FF 15). As discussed above, Examiner explains that a person
of ordinary skill in this art would have recognized from Vamvakas that when
the concentration of surfactant is reduced, "any loss on the P-gp transporter
inhibiting activity due to [a] decrease in [the] surfactant's percentage" would
be offset by an increase in the concentration of PEG and PVP within the
ranges disclosed by Vamvakas and Wilson (see Appeal Br. 12; FF 4, 7, and
10-15). See Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322
(Fed. Cir. 2004) ("[W]here there is a range disclosed in the prior art, and the
claimed invention falls within that range, there is a presumption of
obviousness."); see also 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."). Thus, we are not are not persuaded by Appellants'
12 Examiner's March 22, 2017 Answer.
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Application 14/627,589
contentions regarding In re Patel, 566 Fed. Appx. 1005 (Fed. Cir. 2014)
(Appeal Br. 13-14; Reply Br. 9).
We are not persuaded by Appellants' contention that increasing the
relative amounts of components, such as PEG and PVP, would necessarily
result in an increase in the relative amount of fexofenadine (Reply Br. 8).
As discussed above, Vamvakas discloses that "pharmaceutical excipients
such as surfactants, polyethylene glycols, solubilizing polymers, and classes
of lipids can indirectly reduce or inhibit P-gp transporter activity" (FF 4; see
also Ans. 5-6). Thus, notwithstanding Appellants' contention to the
contrary, a person of ordinary skill in this art would have found it prima
facie obvious, in view of the combination of Vamvakas and Wilson, to
increase the amount of PEG relative to surfactant without increasing the
amount of fexofenadine in the composition (see Ans. 6-7; see also FF 1-
16).
There is no requirement in Appellants' claimed invention that the
claimed composition is clear (see Appeal Br. 18; see also Reply Br. 4--5). In
this regard, Appellants do not identify, and we do not find, a disclosure in
Appellants' Specification relating to a clear composition. Thus, we are not
persuaded by Appellants' contentions or Zhang's statements relating to a
clear composition (see Appeal Br. 14--15; Zhang Dec. 13 ,r 5). See In re
Greenfield, 571 F.2d 1185, 1189 (CCPA 1978) (In order to establish
unexpected results for a claimed invention, objective evidence of non-
obviousness must be commensurate in scope with the claims which the
evidence is offered to support.).
13 March 2, 2016 Declaration of Zhang Julia Zhang.
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Application 14/627,589
We are not persuaded by Zhang' s statement:
It was unexpected that the specific combination of
poly(alkylene glycol) ... , propylene glycol, a solubilizing
polyer (such as polyvinylpyrrolidone), water, and acidulant
(such as citric acid), in the presently claimed proportions by
weight, provided a solubilizing matrix that is useful for
dissolving fexofenadine HCl with only a low wt% (0.001 %-
0.5%) of a surfactant (such as sodium lauryl sulfate).
(Zhang Dec. ,r 9; cf FF 1-16.) As discussed above, Wilson discloses
solubilizing fexofenadine in a composition comprising PEG, propylene
glycol, and PVP in concentrations encompassing Appellants' claimed range,
with surfactant at a concentration "from about zero percent to about 10
percent (w/w)" (FF 10-15). Thus, as discussed above, the combination of
Vamvakas and Wilson makes obvious the solubilization of fexofenadine in a
composition falling with the scope of Appellants' claimed invention (see FF
1-16). Therefore, we are not persuaded by Zhang's assertion that such a
result would have been unexpected on this record (see Zhang Dec. ,r 9; see
also Reply Br. 5-7 and 9-10).
We are not persuaded by Zhang's reliance on Patel, 14 which does not
address compositions comprising PEG, propylene glycol and PVP (see
Zhang Dec. ,r 5). In this regard, we note that Vamvakas discloses that
"surfactant disperses emulsions, generated by the solublization of an active
ingredient in an oil phase, in an aqueous environment" (FF 6) and Wilson
discloses the use of PVP as a dispersing agent "to ensure appropriate
uniformity using viscosity while providing a pharmaceutically elegant
appearance to the resulting solution" (FF 11-12).
14 Patel et al., Preparation and evaluation of self microemulsifying drug
delivery system for fexofenadine hydrochloride, 3 J. DRUG DELIVERY &
THERAPEUTICS 26-32 (2013).
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For the foregoing reasons we are not persuaded by Appellants'
contentions that Examiner's rejection is based in improper hindsight (Reply
Br. 10-11).
Arguments made, for the first time, in Appellants' Reply Brief are not
timely filed and were not included in our deliberations (see e.g. Reply Br. 5-
6 (citing Savjani 15)). See Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI
2010) (informative) (Appellant fails to "explain what 'good cause' there
might be to consider the new argument. On this record, Appellant's new
argument is belated.").
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 1 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Vamvakas and Wilson is
affirmed. Claims 2-15, 22, 23, 25, and 30-35 are not separately argued and
fall with claim 1.
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
15 Savjani et al., Drug Solubility: Importance and Enhancement Techniques,
ISRN PHARMACEUTICS (2012).
13