Ex Parte Castan et al

Patent Trial and Appeal Board

Oct 5, 2017

12905387 (P.T.A.B. Oct. 5, 2017)

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.
12/905,387 10/15/2010 Catherine Castan 022290.0195PTUS (01529) 7881
127044 7590 10/10/2017
Porzio, Bromberg & Newman P.C.
1200 New Hampshire Ave., NW
Suite 710
Washington, DC 20036
EXAMINER
FALKOWITZ, ANNA R
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
10/10/2017 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):
ipdocketing @ pbnlaw. com
pbn_docketing@cardinal-ip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CATHERINE CASTAN and
ANNE-SOPHIE DAVIAUD-VENET1
Appeal 2016-008209
Application 12/905,387
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, and DAVID COTTA,
Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a solid
oral form of a pharmaceutical, which have been rejected as obvious. We
have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
The Specification discloses
a solid oral pharmaceutical form containing at least one
viscosifying agent and an active ingredient formulated in the
1 Appellants identify the Real Party in Interest as FLAMEL IRELAND
LIMITED. (Appeal Br. 1.)
Appeal 2016-008209
Application 12/905,387
state of microparticles, the latter being resistant to crushing, in
order to avoid misuse and suitable for obtaining a specific
modified release profile comprising several release phases at
least one of which depends on the pH.
(Spec. 1:3-7.)
Claims 1, 3—5, 8—11, 13, 14, 16—19, 21—31, and 33 are on appeal.
Claim 1 is the only independent claim and reads as follows (emphasis
added):
1. Solid oral pharmaceutical form comprising:
at least microparticles comprising an active ingredient; and
at least one viscosifying agent in a form isolated from said
microparticles of active ingredient, wherein:
said microparticles of active ingredient are modified release
microparticles,
said microparticles of active ingredient are resistant to crushing,
said microparticles of active ingredient possess an average
diameter ranging from 100 to 600 pm, and are formed by a core containing
at least said active ingredient and coated with at least one coating layer,
said coating layer comprises:
- 25 to 70 % by weight relative to the total weight of said
coating of at least one polymer A which is insoluble in water, wherein
the polymer A is chosen from ethylcellulose, cellulose acetate
butyrate, cellulose acetate, ammonio (meth)acrylate copolymers,
poly(meth)acrylic acid esters, and mixtures thereof,
- 30 to 75 % by weight relative to the total weight of said
coating of at least one polymer B which is insoluble in water below
pH 5 and soluble in water above pH 7, wherein said polymer B is
chosen from methacrylic acid and methyl methacrylate copolymers,
methacrylic acid and ethyl acrylate copolymers, cellulose acetate
phthalate (CAP), cellulose acetate succinate (CAS), cellulose acetate
trimellitate (CAT), hydroxypropylmethylcellulose phthalate
(hypromellose phthalate) (HPMCP), hydroxypropylmethylcellulose
acetate succinate (hypromellose acetate succinate) (HPMCAS),
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Application 12/905,387
carboxymethylethylcellulose, shellac gum, polyvinyl acetate phthalate
(PVAP), and mixtures thereof, and
- 0 to 25 % by weight relative to the total weight of said coating
of at least one plasticizer,
said polymers A and B are in a polymers B / polymers A weight
ratio between 0.4 and 2, and
said coating layer represents at least 35 % by weight, relative to
the total weight of said microparticle,
said modified release of active ingredient from said modified
release microparticles is characterized in vitro by :
- in acid aqueous medium with a pH of less than 4.0, a latency
period of 1 to 12 hours, followed by the start of the release of the
active ingredient;
- after increasing the pH to pH greater than 7.0, an acceleration
of the release of the active ingredient.
DISCUSSION
The Examiner has rejected all of the claims on appeal under 35 U.S.C.
§ 103(a) as obvious based on Legrand,2 Guimberteau,3 and Morelia.4 (Non-
Final Action5 4.) The Examiner finds that “Legrand discloses a
microparticulate system for controlled release” that meets most of the
limitations of claim 1, including microparticles “coated with a film
2 Legrand et al., US 2005/0037077 Al, published Feb. 17, 2005.
3 Guimberteau et al., WO 2007/054378 Al, published May 18, 2007. The
Examiner relies on a partial translation of PCT/EP2006/062627 as an
English-language equivalent of Guimberteau. (Non-Final Action 4.)
Appellants do not dispute that the relied-upon application is an accurate
partial translation of Guimberteau.
4 Morelia et al., EP 0 609 961 Al, published Aug. 10, 1994.
5 Office Action mailed Aug. 25, 2015.
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Application 12/905,387
comprising hydrophilic polymer A and compound B (Abstract). Polymer A
of the prior art comprises mixtures of EUDRAGIT ® L and cellulose
acetate ([0098] - [0100]).” (Id. at 5.) The Examiner finds that Guimberteau
and Morelia teach the limitations that are missing from Legrand (id. at 5—6)
and concludes that the combined teachings of the cited references would
have made the invention of claim 1 obvious to a person of ordinary skill in
the art (id. at 8).
Appellants argue, among other things, that they have provided two
declarations under 37 C.F.R. § 1.132 to show that the disclosure of
“cellulose acetate” in Legrand is an obvious error. (Appeal Br. 11.)
Appellants argue that the declaratory evidence shows that “[o]ne of ordinary
skill in the art would recognize the obvious error and simply substitute the
correct compounds and/or disregard the listing of ‘cellulose acetate’.” (Id.,
citing In re Yale, 434 F.2d 666, 668-669 (CCPA 1970).)
We agree with Appellants that the rejection on appeal is not supported
by a preponderance of the evidence of record. “An examiner bears the
initial burden of presenting a prima facie case of obviousness.” In re Huai-
Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir. 2011). “After evidence or
argument is submitted by the applicant in response, patentability is
determined on the totality of the record, by a preponderance of evidence
with due consideration to persuasiveness of argument.” In re Oetiker, 977
F.2d 1443, 1445 (Fed. Cir. 1992).
The Examiner cites Legrand’s disclosure of a controlled release
system comprising microparticles of an active agent coated with a mixture of
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Application 12/905,387
“polymer A” and “compound B.” (See Legrand, abstract.) The Examiner
points to Legrand’s statement that
[according to one preferred characteristic of the invention, the
hydrophilic polymer A is selected from:
(meth)acrylic acid/alkyl (e.g. methyl) (meth-)acrylate
copolymers (EUDRAGIT® S or L) and mixtures thereof;
cellulose derivatives, preferably cellulose acetate and/or
phthalate, hydroxypropyl methyl cellulose phthalate and
hydroxypropyl methyl cellulose acetate and/or succinate;
and mixtures thereof.
(Id. 97—100, emphasis added.)
The Examiner finds that, based on this passage, Legrand discloses that
its polymer A can consist of a mixture of EUDRAGIT® L (a methacrylic
acid and methyl methacrylate copolymer) and cellulose acetate, thus meeting
the requirements of both the polymer A and polymer B recited in claim 1.
(Non-Final Action 5.)
Appellants, however, argue that they have “submitted two
declarations showing that one of ordinary skill in the art at the time of the
invention would have immediately recognized that the listing of ‘cellulose
acetate’ in paragraph [0099] of Legrand was an error.” (Appeal Br. 13.)
Specifically, Appellants cite the Castan Declaration6 and the Guillard
Declaration.7 (Id.)
6 Declaration under 37 C.F.R. § 1.132 of Catherine Castan, submitted Aug.
10, 2015.
7 Declaration under 37 C.F.R. § 1.132 of Herve Guillard, submitted Dec. 1,
2014.
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Application 12/905,387
Dr. Castan is one of the inventors of both the instant application and
the Legrand reference, and declares that “we (i.e., the inventors in Legrand)
intended polymer A to be cellulose acetate derivatives carrying groups that
are ionized at neutral pH and which are insoluble in acidic media at pH
below 5 and soluble in neutral media.” (Castan Decl. 1 8.) Dr. Castan also
declares that Legrand’s “wording . . . may have led to a misunderstanding
that ‘cellulose acetate’ . . . could be an example of a polymer A in Legrand.
This potential reading of paragraph 0099 in Legrand is incorrect, however,
based on the chemistry required for polymer A in Legrand.” (Id. 19.) Dr.
Castan notes that “[t]his rationale is clearly set forth in the previously
submitted Declaration of GUILLARD.” (Id.)
Dr. Guillard declares that, as a skilled artisan, he “understand^] that
film coatings are divided into different groups, depending on dissolution,
permeability and disintegration performance. This is well explained, for
instance, in the technical book ‘Coated Dosage Forms' at Chapter 4, from
page 65 to page 70 (See Exhibit 1).” (Guillard Decl. 19.) Dr. Guillard
declares that Legrand’s “hydrophilic polymer A carrying groups that are
ionized at neutral pH” (Legrand 190) fall into the category of “‘polymers
with free carboxylic groups (that) are insoluble in acid media and that
dissolve by salt formation above pH 5-6.’” (Guillard Decl. 110, quoting
Exh. I,8 p. 66.)
8 Bauer et al., Coated Pharmaceutical Dosage Forms: Fundamentals,
Manufacturing Techniques, Biopharmaceutical Aspects, Test
Methods and Raw Materials 65-71 (CRC Press, Boca Raton 1998).
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Dr. Guillard declares that “cellulose acetate is a hydrophobic and
insoluble cellulose polymer that does not contain any free carboxylic
groups. Cellulose acetate solubility is pH-independent.” (Id. 115.) Dr.
Guillard points to the Guillard Declaration’s Exhibits 59 and 610 as showing
that the structural formula of cellulose acetate lacks any free carboxylic
groups (id.) and to the Guillard Declaration’s Exhibit 2* 11 as “present[ing]
cellulose acetate as an insoluble polymer.” (Id.)
Dr. Guillard concludes that “[tjherefore, one of ordinary skill in the
art would understand that cellulose acetate clearly does not correspond to
the hydrophilic polymer A carrying groups that are ionized at neutral
pH as required by Legrand.” (Id. 117.)
The Examiner responds that “Appellants[’] attempt to only limit
Legrand to cellulose acetate derivatives with ionized groups at a neutral pH,
is not consistent with the text of Legrand.” (Ans. 6.) The Examiner states
that “[t]he prior art has been interpreted in light of what it actually reads, in
this case cellulose acetate.” (Id. at 7.)
However, “the meaning of a prior art reference requires analysis of the
understanding of an artisan of ordinary skill.” Finisar Corp. v. DirecTV
Group, Inc., 523 F.3d 1323, 1336 (Fed. Cir. 2008). “[T]he test [for
obviousness] is what the combined teachings of the references would have
9 Rowe et al., Handbook of Pharmaceutical Excipients 141-143
(Pharmaceutical Press, London 6th Edition) (2009).
10 Eastman Cellulose Esters for Pharmaceutical Drug Delivery 1-
13 (Eastman Chem. Co. 2006).
11 Qiu et al., Developing Solid Oral Dosage Forms: Pharmaceutical
Theory and Practice 484-485 (Academic Press, Burlington, MA 2009).
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Application 12/905,387
suggested to those of ordinary skill in the art.” In re GPAC Inc., 57 F.3d
1573, 1581 (Fed. Cir. 1995) (internal quotations omitted).
In this case, Appellants have presented evidence—two declarations
supported by documentary evidence—showing that a person of ordinary
skill in the art would have known that Legrand’s recitation of “cellulose
acetate and/or phthalate” as one possible polymer A constituent of its
coating was an obvious error because cellulose acetate does not have the
property that Legrand previously disclosed as necessary for its polymer A;
namely, a hydrophilic polymer carrying groups that are ionized at neutral
pH.
Dr. Guillard declared that a skilled artisan would have recognized
Legrand’s polymer A as a polymer with free carboxylic groups that are
insoluble in acid media and that dissolve by salt formation above pH 5—6.
(Guillard Decl. 110.) Dr. Guillard cited documentary evidence supporting
this position. (Id.) Dr. Guillard also cited evidence to show that cellulose
acetate does not have this property, because it is insoluble. (Id. 115.) The
Examiner has not provided evidence to contradict Dr. Guillard’s declaration
and supporting evidence.
We agree with Appellants that a preponderance of the evidence of
record shows that a person of ordinary skill in the art would have recognized
the recitation of cellulose acetate for Legrand’s polymer A was an obvious
error. In re Yale, 434 F.2d 666 (CCPA 1970), is therefore on point.
In Yale, the claimed invention was the compound CF3CF2CHClBr and
its use as an anesthetic. Id. The claims were rejected based on a reference
(Clements) that recited the same compound. Id. at 667. The Appellant
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Application 12/905,387
argued, and presented supporting evidence, that the recitation of this
compound in the reference was an obvious error and that a skilled artisan
would have recognized that CF3CHClBr was intended. Id.
The Yale court concluded that
not only is the listing of CF3CF2CHClBr in Clements a
typographical error but also this fact would be apparent to one of
ordinary skill in the art when reading the Clements article. Since
it is an obvious error, it cannot be said that one of ordinary skill
in the art would do anything more than mentally disregard
CF3CF2CHClBr as a misprint or mentally substitute CF3CHClBr
in its place. Certainly he would not be led by the typographical
error to use the erroneous compound as an anesthetic
Id. at 668—669.
Just as in Yale, the evidence here shows that Legrand’s error in listing
cellulose acetate as polymer A would have been apparent to one of ordinary
skill, because the properties desired for polymer A are not possessed by
cellulose acetate. Thus, the skilled worker would either mentally disregard
the listing of cellulose acetate as a misprint or mentally substitute the
appropriate polymer (apparently cellulose acetate phthalate) in its place. In
any case, the skilled worker would not have been led to use cellulose acetate
in a mixture with EUDRAGIT® L as the polymer A component of
Legrand’s coating.
The Examiner has not pointed to any disclosure in Guimberteau or
Morelia that makes up for the deficiency in Legrand. Thus, the Examiner
has not shown that the cited references would have made obvious one of
claim 1 ’s polymer A components with one of the polymer B components in
a coating layer for microparticles in a pharmaceutical dosage form. We
therefore reverse the rejection of claim 1, and dependent claims 3—5, 8—11,
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13, 14, 16—19, 21—31, and 33, under 35 U.S.C. § 103(a) based on Legrand,
Guimberteau, and Morelia.
REVERSED
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