Ex Parte De Vries et al

Patent Trial and Appeal Board

Jul 21, 2017

11955072 (P.T.A.B. Jul. 21, 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.
02911.008100.1 5009
EXAMINER
CRUZ, KATHRIEN ANN
ART UNIT PAPER NUMBER
1621
MAIL DATE DELIVERY MODE
11/955,072 12/12/2007 Tina De Vries
5514 7590 07/21/2017
FITZPATRICK CELLA HARPER & SCINTO
1290 Avenue of the Americas
NEW YORK, NY 10104-3800
07/21/2017 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TINA DE VRIES and BRIAN MCNAMEE
Appeal 2017-0034351
Application 11/955,072
Technology Center 1600
Before RICHARD M. LEBOVITZ, TAWEN CHANG and JOHN E.
SCHNEIDER, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to a method of administering
ethinyl estradiol to a patient with improved bioavailability. The Examiner
rejected the claims under 35 U.S.C. § 103 as obvious. We have jurisdiction
under 35 U.S.C. § 6(b). The rejection is affirmed.
1 The Appeal Brief (“Appeal Br.”) lists Warner Chilcott Company, LLC, as
the real-party-in-interest.
Appeal 2017-003435
Application 11/955,072
STATEMENT OF THE CASE
Claims 1, 3—5, 7, 8, 18, 19, 23, 24, and 26—28 stand rejected by the
Examiner under 35 U.S.C. § 103(a) over U.S. Patent No. 6,667,050 B1
(“Boissonneault”), U.S. Patent No. 5,478,571 (“Gala”), Ovcon® 35
Prescribing Information (“Ovcon 35”), and U.S. Patent No.6,451,778 B1
(“Gast”).
Independent claim 1 is reproduced below.
1. A method of administering ethinyl estradiol to a
patient with improved bioavailability comprising the step of
orally administering a solid dosage form containing ethinyl
estradiol that releases an effective amount of the ethinyl
estradiol in the oral cavity for absorption through the oral
mucosa so that the administered solid dosage form treats the
patient for a predetermined indication,
wherein at least about 15 percent of the ethinyl estradiol
contained in the solid dosage form is absorbed through the oral
mucosa,
wherein the patient orally administers the solid dosage
form with about 2 ounces of water or less, wherein the solid
dosage form is a chewable tablet comprising: (i) 0.5 to 15 pg of
ethinyl estradiol; (ii) about 0.3 mg to about 1.5 mg of
norethindrone acetate or norethindrone; and (iii) 30% to 90%
by weight of an oral dissolution enhancing carrier that is
mannitol, and
wherein the solid dosage form provides a bioequivalent
administration of ethinyl estradiol to the patient compared to a
non-chewable solid dosage form comprising ethinyl estradiol
taken with 8 ounces of water with at least 10 percent less
ethinyl estradiol than the nonchewable solid dosage form.
OBVIOUSNESS REJECTION
Independent claim 1 is directed to a method of administering a
chewable table comprising:
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(i) 0.5 to 15 pg of ethinyl estradiol;
(ii) about 0.3 mg to about 1.5 mg of norethindrone acetate or
norethindrone; and
(iii) 30% to 90% by weight of an oral dissolution enhancing carrier
that is mannitol.
The claim requires that “at least about 15 percent of the ethinyl
estradiol contained in the solid dosage form is absorbed through the oral
mucosa.” The claim also requires than the solid dosage form provides the
same bioequivalent amount of ethinyl estradiol than a non-chewable table
“with at least 10 percent less ethinyl estradiol.” In other words, the
chewable tablet delivers the same dosage ethinyl estradiol as a non-chewable
tablet but has less ethinyl estradiol than the non-chewable tablet.
The following findings of fact from Boissonneault (“B”) are pertinent:
B1. Boissonneault describes a chewable oral contraceptive tablet
comprising
an estrogen, a progestin, or a combination of an estrogen and a
progestin. In one embodiment, the oral contraceptive agent is an
estrogen selected from the group consisting of ethinyl estradiol,
estradiol, estradiol valerate, and estradiol acetate. Preferably,
the estrogen is ethinyl estradiol.
Boissonneault, col. 3,11. 44^47 and 58—63.
B2. Boissonneault teaches:
In another embodiment, the oral contraceptive agent is a
progestin selected from the group consisting of norethindrone,
norethindrone acetate, desogestrel, levonorgestrel, ethynodiol
diacetate, norgestrel, norgestimate, gestodene, drospirenone,
trimegestone, levodesogestrel, gestodyne, and nesterone.
Preferably, the progestin is norethindrone.
Id., col. 3,1. 65—col. 4,1. 4.
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B3. Boissonneault teaches that ethinyl estradiol can be present in
1) a broad range of 0.01 to 0.075 mg per tablet or 10—75 pg per tablet;
2) an intermediate range of 0.015 to 0.050 mg per tablet or 15—50 pg
per tablet; and
3) a preferred range of 0.020 to 0.050 mg per tablet or 20-50 pg per
tablet.
Id., Table 1 (col. 4).
B4. Boissonneault teaches that norethindrone or norethindrone
acetate can be present in
1) a broad range of 0.1 to 2.5 mg per tablet;
2) an intermediate range of 0.25 to 2.0 mg per tablet; and
3) a preferred range of 0.4 to 1.5 mg per tablet.
Id., Table 1 (col. 4).
B5. Boissonneault teaches the chewable tablet comprises the
following:
Preferably, the estrogen is ethinyl estradiol and the progestin is
norethindrone. In a more preferred embodiment, the amount of
ethinyl estradiol in the tablet is about 10 micrograms to about
75 micrograms and the amount of norethindrone in the tablet is
about 0.1 milligram to about 2.5 milligrams.
Id., col. 4,11. 45-50.
B6. Examples 1—6 comprise 35 pg ethinyl estradiol and 0.40 mg
norethindrone. Id., cols. 9, 10, 11.
B7. Boissonneault discloses that the oral contraceptive agent may be
present in a “carrier” which “imparts chewable and palatable characteristics
to the tablet” and that the “primary ingredient of a carrier is one or more
diluents.” Id., col. 5,11. 1—16.
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B8. Among the list of diluents disclosed in Boissonneault is mannitol
and lactose. Id., col. 5,11. 17—22.
B9. Example 4 lists a table with 97 mg or 97 % mannitol as a diluent.
Id., col. 11. Example 5 lists a tablet with 60 mg or 60% dextrose and 37 mg
or 37% lactose as diluents for a total of 97% diluent. Id. Both tablets also
contain ethinyl estradiol (35 ug) and norethindrone (0.4 mg). Id.
Gala (“GL”) contains the following pertinent teachings:
GL1. Gala discloses that ethinyl estradiol and norethindrone acetate
are water-insoluble drugs administered orally as oral contraceptives and
hormone replacement therapy (HRT). Gala, col. 2,11. 56—67.
GL2. Gala teaches method of preparing tablets and capsules
comprising these contraceptive and HRT agents. Id., col. 2,11. 35—67; col. 3,
11. 58-63.
GL3. Gala discloses blending drug and carrier, where the carrier can
contain lactose. Id., col. 3,11. 28—32.
GL4. Gala teaches that the carrier can comprises about 75% to about
99% carrier, preferably 90% of the total amount. Id., col. 4,11. 10-13.
Gast (“GT”) contains the following pertinent teachings:
GT1. “When ethinyl estradiol is used as the estrogen, it is preferred
that the daily dosage of ethinyl estradiol is 10—20 pg, with 15 pg being more
preferred.” Gast, col. 6,11. 35—38.
GT2. Gast teaches dosages units comprising a progestin and estrogen.
Id., col. 7.11. 43^47.
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GT3. Gast teaches reducing the amounts of the estrogen and
progestin to minimize side effects. Id., col. 1,11. 26—38.
REJECTION
The Examiner found that Boisonneault describes a method of
administering a chewable tablet comprising all three of the recited
components, namely ethinyl estradiol, norethindrone, and mannitol. Ans. 2.
The Examiner found that the amounts of ethinyl estradiol and norethindrone
described in Boisonneault overlap with the claimed amounts. Id., 3, 9. The
Examiner also cited Gast for teaching amounts of ethinyl estradiol which
meet the claimed amounts. Id., 4. However, the Examiner found that
Boisonneault does not teach the claimed dosage range of mannitol of 30% to
90%. Id., 3. To meet this deficiency, the Examiner cited Gala which the
Examiner found teaches that a drug carrier can comprise from about 75% to
about 99% of the pharmaceutical composition and most preferably will
comprise about 90% of the total amount. Id., 4. The Examiner found it
would have been obvious to optimize the amount of mannitol in the tablet.
Id., 5.
The Examiner acknowledged that the cited publications do not teach
the requirements in claim 1 that “at least about 15 percent of the ethinyl
estradiol contained in the solid dosage form is absorbed through the oral
mucosa” and that the solid dosage form provides the same bioequivalent
amount of ethinyl estradiol than a non-chewable table “with at least 10
percent less ethinyl estradiol.” However, the Examiner found that the
routinely formulated tablet would inherently possess these properties. Id.,
7-8, 9.
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Mannitol
Appellants contend that Boissonneault “does not disclose or suggest a
tablet with the . . . claimed amount of mannitol, which allows significant
dissolution of ethinyl estradiol in the oral cavity.” Appeal Br. 6. Appellants
also contend that mannitol was not recognized as a result-effective variable
that would allow for dissolution in the oral cavity permit lower levels of
ethinyl estradiol to achieve the same efficacy as higher amounts. Id., 7.
Appellants also argue that mannitol is among “a litany list of diluents as
potential carriers” with no recognition that it would achieve improved
bioavailability. Id., 8
We are not persuaded. To begin, Boissonneault teaches a chewable
tablet with 97% mannitol and with both ethinyl estradiol and norethindrone,
the same drugs which are claimed. B9. The amount of norethindrone in the
tablet is 0.4 mg (B9) which falls within the claimed range. The amount of
ethinyl estradiol is outside the range (B9) in this example, but lower amounts
and overlapping are disclosed by Boissonneault (B3, B5). This express
teaching of mannitol in a tablet having ethinyl estradiol and norethindrone
provides a strong reason to have included mannitol in a chewable table with
the claimed amounts of estradiol and norethindrone.
Appellants contend that the claimed tablet has superior properties with
respect to improved bioavailability because of its ability to be absorbed in
the orally in the mouth (“buccally, sublingually, or gingivally”). Appeal Br.
5). Appellants also assert that the mannitol “allows significant dissolution of
ethinyl estradiol in the oral cavity.” Id., 6.
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The tablets in Boissonneault contain even more mannitol at 97% by
weight of the tablet, providing a reasonable expectation that Boissonneault’s
tablet would at least meet the minimal absorption and bioequivalency
requirements of the claims, i.e., if 90% allows significant dissolution, it
would be reasonable that even high amounts of mannitol would also achieve
it, supporting the Examiner’s finding that the Boissonneault’s tablet would
have the dissolution properties recited in the claim.
A preponderance of the evidence also supports that Examiner’s
finding that it would been obvious to optimize the amounts of mannitol. The
Examiner cited the Gala publication which teaches a tablet comprising 75%
to about 99% carrier, preferably 90% of the total amount (GL4), which
overlaps with the claimed range of “30% to 90% by weight of an oral
dissolution enhancing carrier.” While Gala teaches that the carrier is lactose
(GL3), Boissonneault teaches that that both mannitol and lactose are drug
carriers (B7, B8; “diluents”), providing evidence of their interchangeability.2
Accordingly, the evidence establishes that the carrier recited in the claims is
present in conventional amounts known to one of ordinary skill in the art. In
addition to utilizing a conventional amount of carrier, Boissonneault teaches
that the carrier “imparts chewable and palatable characteristics to the tablet”
(B7), providing further evidence of a reason that would have prompted one
of ordinary skill in the art to optimize the amounts of mannitol to achieve the
desired chewable and palatable characteristics.
2 The Specification of the appealed application also discloses lactose and
mannitol in a list of carriers “that allow[ ] for significant dissolution of the
ethinyl estradiol in the oral cavity” and in the same range of amounts
described by Gala and as claimed. Spec. 126.
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Ethinyl estradiol
The range of ethinyl estradiol recited in the claims of 0.5 to 15 pg is
encompassed by the “broad” range described in Boissonneault. B3, B5.
Gast also teaches an overlapping range of “10-20 pg, with 15 pg being more
preferred.” GT1. It is well established that, when there is a range disclosed
in the prior art, and the claimed invention overlaps or falls within that range,
there is a presumption of obviousness. In re Peterson, 315 F.3d 1325, 1329
(Fed. Cir. 2003); Iron Grip, 392 F.3d 1322. Gast further teaches reducing
the amounts of the estrogen to minimize side effects, providing additional
express reason to have formulated a composition with the recited amount of
ethinyl estradiol. GT3.
Appellants contend that, in Gast, low amounts of ethinyl estradiol are
combined with progestins other than the claimed norethindrone and
norethindrone acetate. Appeal Br. 12. We have considered this argument
but do not find it persuasive because the background section of Gast
describes such amounts of ethinyl estradiol (“EE”) with norethindrone
(“NE”) (Gast, col. 3,11. 28-30; col. 4,11. 32-34; col. 4,11. 36-A2), as well
does Boissonneault (B5). Thus, a preponderance of the evidences supports
the findings that the claimed amounts of ethinyl estradiol and norethindrone
are conventionally used for the known purposes for which these drugs are
administered.
Properties
Appellants contend that the Examiner did not recognize the
advantages of the claimed invention with respect to increased oral cavity
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absorption and bioavailability. Appeal Br. 4. Appellants assert that
“Chewing a tablet followed by 2 ounces of water produces unexpectedly
superior results when compared to swallowing a comparative tablet with 8
ounces of water.” Id., 5. Appellants based this statement on experiments
disclosed in the Specification for Tablet A containing lactose and Table B
containing mannitol.
Appellants assert
Table 3, at page 11, shows that when Tablet B was chewed and
administered with 2 ounces (59 milliliters) of water, the
maximum plasma concentration was 160% that of Tablet A,
which was swallowed with 8 ounces (236 milliliters) of water.
In addition, paragraph [0039] states that if 2 ounces (59
milliliters) of water were administered, the effective amount of
ethinyl estradiol may be reduced by 22% and remain
bioequivalent to a swallowed tablet with 8 ounces (236
milliliters) of water.
Id., 5.
This evidence does not persuade us that the claimed method is not
obvious in view of the cited publications.
A showing of “unexpected results” can be used to demonstrate the
non-obviousness of the claimed invention. In re Soni, 54 F.3d 746, 750
(Fed. Cir. 1995) (“One way for a patent applicant to rebut a prima facie case
of obviousness is to make a showing of ‘unexpected results,’ i.e., to show
that the claimed invention exhibits some superior property or advantage that
a person of ordinary skill in the relevant art would have found surprising or
unexpected.”). Those results must be “surprising or unexpected” to one of
ordinary skill in the art when considered in the context of the closest prior
art. Soni, 54 F.3d at 750; Iron Grip Barbell Co., Inc. v. USA Sports, Inc.,
392 F.3d 1317, 1322 (Fed. Cir. 2004) (A showing of “new and unexpected
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results” must be “relative to the prior art.”); In re Baxter Travenol Labs., 952
F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as
evidence of nonobviousness, the results must be shown to be unexpected
compared with the closest prior art”). To establish unexpected results, the
claimed subject matter must be compared with the closest prior art. Id. The
results must also be “commensurate in scope with the degree of protection
sought by the claimed subject matter.” In re Harris, 409 F.3d 1339, 1344
(Fed. Cir. 2005).
In this case, a statement has not been made that the results would have
been surprising or unexpected to one of ordinary skill in the art. Soni, 54
F.3d at 750. Such statement is made in the Appeal Brief, but it has not been
established that the attorney is one of ordinary skill in the art.
In addition to this, the alleged showing of unexpected results was not
made with a tablet within the scope of the claim. The Specification
describes:
1) Tablet A containing 1 mg of norethindrone acetate, 35 pg of ethinyl
estradiol, and 67.53% w/w lactose; and
2) Tablet B containing 1 mg of norethindrone acetate, 35 pg of ethinyl
estradiol, and 69.53% w/w mannitol. Spec. 129.
The amount of ethinyl estradiol present in the tablet of 35 ug falls
outside the scope of all the claims, which require a range of 0.5 to 15 pg.
Appellants have not demonstrated nor provided evidence that the same
results would be observed with amounts of ethinyl estradiol within the scope
of the claims. Indeed, Appellants specifically attempt to distinguish “the
only example” of “Boissonneault with mannitol discloses 35 micrograms of
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ethinyl estradiol, which is outside the presently claimed range.” Appeal Br.
7.
In addition to these deficiencies, the comparison was not side-by-side
so it cannot be determined that the mannitol is responsible for the described
results, rather than another component in Tablet B. Specifically, swallowed
Tablet A also contains 20% w/w cellulose, 10% w/w cornstarch, while
chewed Tablet B having mannitol also contains 12.39% w/w lactose, 10%
w/w cellulose, 2% w/w starch glycolate, 0.06% w/w povidone, and 0.04%
w/w sucralose. Spec. 129. Tablet B thus contains a different amount of
cellulose and starch than Tablet A, and also includes povidone and sucralose
which are absent from Tablet A. Tablet B also contains lactose.
Consequently, it cannot be concluded that the mannitol alone is responsible
for the results, rather than the lactose, starch, cellulose, povidone, and
sucralose, alone, or in combination with each other.
The results are also not commensurate in scope with the claim
because the claim has a range of 30% to 90% mannitol, while only one
amount of mannitol was tested of 69.53%. Id. One data point is
insufficient to “to ascertain a trend in the exemplified data which would
allow [one having ordinary skill in the art] to reasonably extend the
probative value thereof.” In re Kollman, 595 F.2d 48, 56 (Fed. Cir. 1979).
Thus, even were unexpected results established for this one data point, it is
not commensurate with the full scope of the claim. Appellants have not
provided evidence that that one of ordinary skill in the art would have
reasonably expected that entire claimed range would exhibit the reported
dissolution properties.
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We have considered Appellants’ argument about lactose not showing
the claimed improvement as does mannitol (Appeal Br. 8), but do not find it
persuasive because Boissonneault discloses mannitol in combination with
the claimed ethinyl estradiol and norethindrone.
Inherency
The Examiner found that the claimed dissolution and bioequivalent
limitations of claims 1 and 24 would have been an inherent property a tablet
with the obvious amounts of ethinyl estradiol and mannitol. Ans. 7—8.
Appellants challenge the Examiner’s finding, stating that publications,
particularly Boissonneault and Gala, do not “recognize the improved
bioavailability achieved through the present invention. As they do not
recognize the problem solved they cannot suggest the solution.” Appeal Br.
10.
Gala expressly teaches a carrier that overlaps with the claim range.3
GL4. Lactose is one example of a carrier in Gala, but other carriers are
known, particularly mannitol as described by Boissonneault. When
mannitol is employed as a carrier in the conventional amounts described in
Gala, it would necessary confer the recited properties on the tablet because
the amounts overlap with those recited in the claim. Obviousness does not
require that the improved bioavailability was recognized because the amount
3 Peterson, 315 F.3d at 1329 (Fed. Cir. 2003); Iron Grip, 392 F,3d 1322.
Even when the values do not precisely overlap, if they “are so close that
prima facie one skilled in the art would have expected them to have the
same properties,” the burden shifts to the applicant to show they are
different. Titanium Metals Corp. v. Banner, 778 F.2d 775, 783 (Fed. Cir.
1985).
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of mannitol recited in the claims are the same amounts conventionally
utilized a carriers in pharmaceutical formulations. “Mere recognition of
latent properties in the prior art does not render nonobvious an otherwise
known invention.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed.
Cir. 1991).
While Boissonneault discloses an amount of 97% outside the claimed
range of 90%, Appellants have not explained why increasing amounts of
mannitol from 30% to 90% mannitol would possess the claim property,
while 97% would not.
SUMMARY
For the foregoing reasons, the obviousness rejection of claim 1 is
affirmed. Claims 3—5, 7, 8, 18, 19, 23, 24, and 26—28 were not argued
separately and fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l)(iv).
AFFIRMED
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