Ex Parte Paiement et al

Patent Trial and Appeal Board

Feb 21, 2019

15216903 (P.T.A.B. Feb. 21, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
15/216,903 07/22/2016
35684 7590
BUTZEL LONG, P.C.
IP DEPARTMENT
41000 Woodward A venue
Stoneridge West
Bloomfield Hills, MI 48304
02/25/2019
FIRST NAMED INVENTOR
Nadine Paiement
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.
Intelgenx 143939-0077 5159
EXAMINER
KASSA, TIGABU
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
02/25/2019 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):
PA TENT@BUTZEL.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte NADINE P AIEMENT, RODOLPHE OBEID, and BILLAL TIR
Appeal2018-004385
Application 15/216,903
Technology Center 1600
Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and
MICHAEL A. VALEK, Administrative Patent Judges.
VALEK, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellants submit this appeal under
35 U.S.C. § 134(a) involving claims to processes for preparing an oral film
dosage form. 1 Examiner rejected claims 1-10 as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify IntelGenx Technologies Corp. and IntelGenx Corp. as
the real parties in interest. App. Br. 3. Herein we refer to the Final Office
Action mailed April 21, 2017 ("Final Act."); Advisory Office Action mailed
August 11, 2017 ("Adv. Act."); Appeal Brief filed Oct. 6, 2017 ("App.
Br."); Examiner's Answer, mailed Jan. 26, 2018 ("Ans."); and Reply Brief
filed March 21, 2018 ("Reply Br.").
Appeal2018-004385
Application 15/216,903
STATEMENT OF THE CASE
Appellants' invention relates to "a process for preparing a product
containing a stable dispersion of non-solubilized amorphous or partially
amorphous particles (powders) of an active agent( s) in an oral film dosage
form." Spec ,r 10. According to the Specification, a "conventional
technique for incorporating an amorphous active agent( s) into an oral film
dosage form involves dissolving both the amorphous active agents(s)(s) [sic]
and film forming polymers into a solvent system and quickly evaporating the
solvent system and drying the resulting film." Id. ,r 6 (emphasis added).
However, in Appellants' process "a liquid film-forming formulation
including at least one film-forming polymer and a solvent system is prepared
independently" and the amorphous active agent "is then suspended in the
liquid film-forming formulation without solubilizing the amorphous or
partially amorphous active agent(s)." Id. ,r 10.
Claims 1-10 are on appeal, and can be found in the Claims Appendix
of the Appeal Brief. App. Br. 15-17. Claim 1 is representative of the claims
on appeal, and reads as follows:
1. A process for preparing an oral film dosage form
containing an active agent in an amorphous form, comprising:
providing an active agent in crystalline form;
converting the active agent in crystalline form into an
amorphous particle form having a mean particle size diameter D50
equal or less than 250 µm;
providing a liquid film-forming formulation including at
least one film-forming polymer and a solvent system including
at least one solvent, and optionally including one or more
pharmaceutically acceptable excipients selected from diluents,
plasticizers, surfactants, sweeteners and taste-masking agents;
suspending the active agent in the amorphous particle
form in the liquid film forming formulation without dissolving
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the active agent; and
removing the solvent system to form a film containing the
active agent in the amorphous form and retaining a mean particle
size diameter D50 equal or less than 250 µm.
App. Br. 15 (Claims Appendix).
Appellants seek review of Examiner's rejection of claims 1-10 under
35 U.S.C. § 103 as unpatentable over Dave,2 in view of Alfonzo. 3 App. Br.
7-13. The Appellants do not argue the claims separately, we focus our
analysis on claim 1, and claims 2-10 stand or fall with that claim. 3 7 C.F .R.
§ 41.37 (c)(l)(iv).
The issue is: Does the preponderance of evidence of record support
Examiner's conclusion the cited prior art renders obvious a process for
preparing an oral dosage film form containing an active agent in amorphous
form as claimed?
Findings of Fact
FF 1. Dave teaches solvent casting techniques for preparing strip films
containing particles of an active pharmaceutical ingredient ("API"). Dave 2.
Such techniques generally involve the preparation of "suspensions or
solutions" containing the API and a polymer that are then cast on a substrate
and dried to yield a film. Id. The resulting strip film is "used for the oral ...
delivery of APL" Id. at 21, 11. 27-28. Dave's thin films allow for "poorly
water-soluble active pharmaceutical ingredients (APis) to achieve improved
2 Dave et al., WO 2014/145699 Al; published Sept. 18, 2014 ("Dave").
3 David E. Alonzo et al., Understanding the Behavior of Amorphous
Pharmaceutical Systems during Dissolution, PHARMACEUTICAL RESEARCH,
Vol. 27, No. 4 (2010) ("Alonzo").
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Application 15/216,903
active content uniformity and very fast dissolution from poorly water soluble
actives." Id. at 16, 11. 15-17. Dave expressly names both felodipine and
indomethacin as examples of poorly water soluble drugs that are suitable for
its film preparation techniques. See id. at 22.
FF2. In particular, Dave teaches techniques wherein a water soluble
polymer is dissolved in aqueous solution and then mixed with a poorly water
soluble active agent to form "a stable aqueous suspension of nano and/or
micro sized [ API] particles, the particles ranging from about 10 nm to about
10 microns, more preferably, from about 50 nm to about 5 micron in size."
Id. at 17, 11. 6-9; and 23-24 (Exemplary embodiment in which polymer is
dissolved in water before the addition of API to form a "drug suspension.").
Dave teaches that this suspension may additionally include, inter alia, flavors
and taste-masking agents. Id. at 18. The suspension is mixed to evenly
distribute the undissolved API particles and then dried to form a film "where
improved drug content uniformity and fast dissolution are achieved." Id. at
18.
FF3. Dave teaches that the API particles in its "stripfilm based
pharmaceutical product" may be "in crystalline or amorphous form or
combinations thereof." Id. at 8, and 18 ("[T]he drug materials are in
crystalline or amorphous form, or can be a combination thereof.").
FF 4. Alonzo teaches the conversion of crystalline active agent, specifically
felodipine and indomethacin, into an amorphous form. Alonzo 609. Alonzo
teaches that "[ a ]morphous materials are attractive for solubility
enhancement" and increased bioavailability as compared the crystalline
counterparts of such APis. Alonzo 608. Alonzo further teaches that for
amorphous materials "polymers are usually incorporated into the matrix as
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stabilizers" to prevent crystallization both during storage and during
dissolution when the drug is administered. Id. at 609.
Analysis
Examiner finds that Dave teaches all of the elements of the claimed
process, other than providing an API in crystalline form and converting it
into an amorphous form, which is taught in Alonzo. Final Act. 7-8; see also
Ans. 5. Examiner determines that a skilled artisan would have been
motivated to convert the crystalline API into amorphous form for increased
solubility in the body and bioavailability. Ans. 5-7; see also Adv. Act. 2.
Appellants contend that the cited art: ( 1) does not teach or suggest a
process for preparing a film by "suspending the active agent in the
amorphous particle form in the liquid film-forming formulation without
dissolving the active agent;" (2) does not teach that "the active agent is in an
amorphous form in the final product, or that a step is taken to maintain the
active in the amorphous form;" and (3) does not provide a teaching,
suggestion or motivation to make a film oral dosage form using the claimed
steps. App. Br. 7-13.
We conclude that the preponderance of the evidence supports
Examiner's conclusion of obviousness. We are not persuaded by
Appellants' argument that the cited art does not disclose the step of
suspending without dissolving an amorphous API (i.e., an "active agent").
According to Appellants' Specification, "[t]he term 'suspended' (and
variations thereof) refers to a dispersion of solid material ( e.g., particles or
powder) in a bulk liquid medium, in which the solid material is not
completely dissolved on a molecular level, and will eventually settle out of
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the liquid in the absence of agitation. In a suspension, the suspended
material is not dissolved in the liquid." Spec. ,r 30. Dave specifically
teaches a suspension in which a poorly water soluble API is suspended in an
aqueous solution containing a film-forming polymer. See FF2. Because the
API is poorly water soluble, it would not dissolve in aqueous media, but
rather forms a "stable aqueous suspension" of API particles. Id. Indeed,
Dave distinguishes between solvent casting techniques involving "solutions"
in which the API is dissolved and "suspensions" in which API particles are
suspended, but not dissolved. See FF 1.
We are likewise unpersuaded by Appellants' argument that the cited
art fails to teach the presence of amorphous active agent particles in the final
film product. Appellants concede that Dave teaches an API in amorphous
form, but contend this disclosure refers only to the starting material and not
the API particles in the final strip film product. Reply 4. We disagree and
find that Appellants' argument is premised on an overly narrow reading of
Dave. See FF3. Dave refers to "drug materials" and "a stripfilm based
pharmaceutical product" with active agent particles in amorphous form. Id.
That disclosure cannot be read to draw the distinction between starting
materials and the final oral dosage film product that Appellants advance.
And, in the face of the evidence provided by the Examiner, Appellants
haven not offered sufficient rebuttal evidence to show that the skilled artisan
would read Dave as narrowly as they urge.
Moreover, even if Dave's disclosure were as limited as Appellants
contend, Appellants fail to explain why one of ordinary skill would not
reasonably expect the amorphous API in Dave's "stable aqueous
suspension" to remain sufficiently amorphous to meet the claimed
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"amorphous" limitation in the final film product. Appellants' Specification
broadly defines "amorphous" to include active agents "that exhibit[] 30% or
more than 3 0% of amorphous material." Spec ,r 21. Appellants offer no
evidence why one of ordinary skill in the art starting with an entirely or
substantially amorphous API would not reasonably expect the API particles
in final film to remain above that 30% threshold, particularly where Dave
teaches the same step of suspending without dissolving the active agent as in
the claims. Instead, Appellants cite to examples where both the starting
material and the API in the final film were in crystalline form. Reply 2-3;
Dave 94 ("[T]he initial drug crystal form is retained in the films."). But
Dave's teachings are broader than the examples Appellants rely upon and
also teach films with active agent particles in amorphous form. See FF3.
Finally, we are unpersuaded by Appellants' contention that there is no
motivation to convert a crystalline active agent into amorphous form before
suspending it in the liquid film forming formulation. As Examiner explains,
Alonzo teaches that using an amorphous form of certain APis is "attractive"
because they show increased solubility and bioavailability as compared to
their crystalline counterparts. Ans. 6. Indeed, Appellants concede that
Alonzo teaches both "the desirability of providing active agents in an
amorphous form to improve solubility and bioavailability" and the
conversion of particular crystalline active agents into their amorphous form.
App. Br. 11. We therefore agree that one of ordinary skill would be
motivated to use an amorphous API to form the suspension taught in Dave.
See FF 1 and FF3. Moreover, one would reasonably expect that Alonzo's
teaching regarding the conversion of crystalline felodipine and indomethacin
into their amorphous form would be successfully employed with Dave's
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method because Dave identifies the same compounds as exemplary APis for
use in that method. See FFl and FF4.
Appellants' other arguments that Alonzo does not itself teach an oral
film dosage form or a process for making such, see App. Br. 11-13, are
inapposite because Examiner's rejection is based on the combination of
Dave and Alonzo. "[N]on-obviousness cannot be established by attacking
references individually where the rejection is based on the teachings of a
combination of references." Soft Gel Techs., Inc. v. Jarrow Formulas, Inc.,
864 F.3d 1334, 1341 (Fed. Cir. 2017) (quoting In re Merck & Co., 800 F.2d
1091, 1097 (Fed. Cir. 1986)). As explained above, Dave teaches the claimed
process for making an oral film dosage form wherein amorphous API
particles are suspended and not dissolved in a film forming formulation. See
FF 1-FF3. Alonzo teaches the initial claim steps of providing and converting
crystalline API to amorphous form and offers an express motivation to use
the amorphous form in Dave's process. FF4. Appellants' argument fails to
persuade us that Examiner erred in rejecting the claims. 4 Accordingly, we
affirm.
SUMMARY
We affirm the rejection of claims 1-10 under AIA 35 U.S.C. § 103
over Dave and Alonzo.
4 Inasmuch Appellants contend they were prejudiced by the timing of
Examiner's discussion of the "without dissolving" element in Examiner's
Answer, Appellants could have petitioned to re-open prosecution (i.e., to
have the alleged new rationale from Examiner be designated new grounds).
37 C.F.R. § 41. 40. They did not, but instead filed their Reply Brief, thus
maintaining the appeal. 37 C.F.R. § 4I.39(b)(2).
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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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