Ex Parte O

Patent Trial and Appeal Board

Mar 20, 2013

12011773 (P.T.A.B. Mar. 20, 2013)

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.
12/011,773 01/28/2008 INV001Dermot Michael O'Hare STHP-012CON 9816
24353 7590 03/20/2013
BOZICEVIC, FIELD & FRANCIS LLP
Bozicevic, Field & Francis
1900 UNIVERSITY AVENUE
SUITE 200
EAST PALO ALTO, CA 94303
EXAMINER
ARNOLD, ERNST V
ART UNIT PAPER NUMBER
1613
MAIL DATE DELIVERY MODE
03/20/2013 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 DERMOT MICHAEL O‟HARE
__________

Appeal 2011-007784
Application 12/011,773
Technology Center 1600
__________

Before TONI R. SCHEINER, FRANCISCO C. PRATS, and
STEPHEN WALSH, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to drug delivery
systems. The Examiner entered a rejection for anticipation and a rejection
for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm the anticipation rejection.
We also affirm the obviousness rejection as to some claims, but
reverse it as to others.
We also enter a new ground of rejection.

Appeal 2011-007784
Application 12/011,773

2
STATEMENT OF THE CASE
“Layered double hydroxides (LDHs) are a class of compounds which
comprise two metal cations and have a layered structure. . . . The
hydrotalcites, perhaps the most well-known examples of LDHs, have been
studied for many years” (Spec. 1). “It is known that certain organic species
may be intercalated into the layers in some LDHs and into clays” (id.).
Appellant‟s invention is “based on the discovery that a
pharmaceutically-active compound having at least one anionic group can be
intercalated into an LDH compound and that the intercalate releases the
pharmaceutically-active compound in a controlled manner when subjected to
pH conditions that may prevail inside the stomach of a patient” (id. at 3).
Claims 1-13 stand rejected and appealed (App. Br. 3). Claims 1 and
12 illustrate the appealed subject matter and read as follows:
1. A drug delivery system comprising an intercalate of a layered
double hydroxide having, before intercalation, layers of metal
hydroxides, and having intercalated therein a pharmaceutically-active
compound having at least one anionic group, wherein said intercalate
is present in an oral dosage formulation.

12. The system according to claim 1, wherein the pharmaceutically-
active compound is selected from 4-biphenylacetic acid, Diclofenac,
Gemfibrozil, Ibuprofen, Naproxen, 2-propylpentanoic acid and
Tolfenamic acid.

The following rejections are before us for review:
(1) Claims 1, 4-7, 9, and 13, under 35 U.S.C. § 102(b) as anticipated
by Meyn
1
(Ans. 3-6); and

1
Martina Meyn et al., Anion-Exchange Reactions of Layered Double
Hydroxides, 29 INORG. CHEM. 5201-5207 (1990).
Appeal 2011-007784
Application 12/011,773

3
(2) Claims 1-13, under 35 U.S.C. § 103(a) as obvious over Meyn and
Miyata
2
(Ans. 6-9).
ANTICIPATION – MEYN
The Examiner found that Meyn described “the intercalation of
salicylate, a pharmaceutically active compound, into the double hydroxide
LiAl2(OH)6(NO3)nH2O (Page 5203, Table II). Since salicylate is a
biologically active compound[,] then the composition is inherently a drug
delivery system” (Ans. 5).
The Examiner also found that Meyn‟s methods of making the
intercalated organic acid included “dispersing the double hydroxide into an
aqueous solution of the organic acid and then decanting the supernatent [sic]
(separating) and reacting the solid material again with fresh salt solution
followed by washing and drying (page 5202, anion exchange)” (id.).
The Examiner‟s position is that “the aqueous solution reads on an oral
dosage form since aqueous solutions can be used for oral administration”
(id. (emphasis removed)).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
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.

We select claim 1 as representative of the rejected claims. See 37
C.F.R. § 41.37(c)(1)(vii).

2
U.S. Patent No. 3,980,685 (issued September 14, 1976).
Appeal 2011-007784
Application 12/011,773

4
Appellant‟s arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner‟s finding that Meyn anticipates claim
1.
As the Examiner found, and as Appellant does not dispute, Meyn
describes an intercalate of salicylate, undisputedly a pharmaceutically active
compound, and a lithium/aluminum double hydroxide compound (see Meyn
5203 (Table II)). As the Examiner also found, and as Appellant also does
not dispute, Meyn discloses preparing its intercalates by dispersing the
double hydroxide compound in a solution of the acid salt in water, and
subsequently washing the intercalated product in water, thus producing an
aqueous solution containing the salicylate double hydroxide intercalate (see
id. at 5202 (section entitled “Anion Exchange”)).
Appellant initially argues that the salicylate-containing aqueous
solution described in Meyn cannot be considered an oral dosage formulation
as required by claim 1, because Meyn does not administer the formulation to
a patient, and because Meyn uses nitrate ion as the displaceable anion in all
of its double hydroxides (see App. Br. 8). Appellant argues that nitrate is
known in the art to be toxic, and cites several documents to support that
argument (see id. at 8-10 (citing ATSDR Nitrate/Nitrite Toxicity Case
Study,
3
the CERCLA Hazardous Substances list,
4
and the Shapiro article
5
)).

3
Agency for Toxic Substances and Disease Registry (ATSDR): Case
Studies in Environmental Medicine (CSEM): Nitrate/Nitrite Toxicity,
Course WB 1107 (Sept. 24, 2007) (available online at
http://www.atsdr.cdc.gov/csem/nitrate/n03cover.html).
4
Comprehensive Environmental Response, Compensation, and Liability Act
(CERCLA) Priority List of Hazardous Substances, 2007 (available online at
http://www.atsdr.cdc.gov/cercla/07list.html).
Appeal 2011-007784
Application 12/011,773

5
We are not persuaded. Appellant points to no evidence of record
suggesting that the aqueous solutions of Meyn cannot be administered
orally.
As to nitrate toxicity, as the Examiner points out, Appellant‟s claims 4
and 7 both list nitrate as the displaceable anion in the double hydroxide
compound (see App. Br. 19, 20). Indeed, Appellant‟s Specification lists
nitrate as a preferred anion (see Spec. 4).
Thus, because Meyn‟s salicylic acid intercalate of a lithium-aluminum
double hydroxide that contained nitrate as the anion would literally infringe
Appellant‟s claim 7, we are not persuaded that Appellant‟s claims exclude
nitrate. See Polaroid Corp. v. Eastman Kodak Co., 789 F.2d 1556, 1573,
(Fed. Cir. 1986) (“[T]hat which infringes if later anticipates if earlier.”).
Moreover, we are not persuaded that Appellant has appreciated the
full relevance of the documents cited to rebut the Examiner‟s prima facie
case. Although none of the rebuttal documents was cited in the Evidence
Appendix to the Appeal Brief, the Nitrate/Nitrite Toxicity Case Study and
the CERCLA Hazardous Substances list were entered into this application‟s
electronic filewrapper on August 10, 2010.
We acknowledge the inclusion of nitrate in the CERCLA list, and also
acknowledge the Case Study‟s disclosure that, when present at high levels in
the body, in vivo conversion of nitrates to nitrites can result in nitrite toxicity
(see Case Study at 15), which Appellant urges is described in Shapiro. As

5
Daniel B. Kim-Shapiro et al., The reaction between nitrite and
hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic
vasodilation, 99 JOURNAL OF INORGANIC BIOCHEMISTRY 237–246 (2005).
Appeal 2011-007784
Application 12/011,773

6
the Case Study points out, however, intake of some amount of nitrates is a
normal part of the nitrogen cycle in humans (see id.).
Indeed, nitrates are present in a number of foods, including
cauliflower, spinach, collard greens, broccoli, and root vegetables (see id. at
9). Nitrates are also used as preservatives and color enhancers in meat and
meat products (see id.).
Thus, it may be true that excessive intake of nitrates can result in toxic
levels of nitrites in the body. However, given Appellant‟s stated preference
for, and explicit inclusion of, that anion in the claimed double hydroxide
compounds, as well the presence of nitrates in everyday foods, we are not
persuaded that a preponderance of the evidence supports Appellant‟s
position that a nitrate-containing composition would not be considered a
suitable oral dosage form by a skilled artisan.
Appellant also argues that the aqueous solutions described in Meyn
would not be considered an oral dosage formulation because
[l]iquid oral formulations have many considerations, such as
concentration of the active agent, solubility of the active agent,
flavor, appearance, chemical stability, physical stability, and the
like. For example, liquid oral formulations typically include
taste masking components, such as sweetening agents, flavoring
agents and desensitizing agents that mask undesirable salty,
bitter, sweet or sour flavors that an active agent may have.

(Reply Br. 2.)
We are not persuaded. Claim 1 does not require the presence of any
of the ingredients urged by Appellant as being in an oral dosage form, and
Appellant points to no evidence of record suggesting that the aqueous
solutions of Meyn cannot be administered orally.
Appeal 2011-007784
Application 12/011,773

7
In sum, as Appellant‟s arguments do not persuade us that the
Examiner erred in maintaining the anticipation rejection of claim 1 over
Meyn, we affirm that rejection. As they were not argued separately, claims
4-7, 9, and 13 fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(vii).
OBVIOUSNESS – MEYN AND MIYATA
In rejecting claims 1-13 as obvious over Meyn and Miyata, the
Examiner found, presumably as to claim 3, that Meyn did not expressly
teach an intercalate of a pharmaceutically active compound into a double
hydroxide compound containing magnesium and aluminum (Ans. 10).
The Examiner also found that Meyn did not “expressly teach an
embodiment with the actives in claim 12. This deficiency in Meyn et al. is
cured by the teachings of Miyata” (id.).
The Examiner thus reasoned:
[T]he concept of intercalating a pharmaceutical with carboxylic
acid functional groups into a double hydroxide is established by
the [Meyn] reference and guidance to the type of active to
select (those with anionic carboxylic or dicarboxylic groups) is
taught. Miyata et al. establish that salicylic acid, ibuprofen,
indomethacin and ibufenac, for example, as organic compounds
with carboxylic groups that can be used as intercalating anions.
It is therefore not a stretch of the imagination by one of
ordinary skill in the art to select other known pharmaceutical
agents with carboxylic functional groups and intercalate them
into the double hydroxides.

(Id. at 11.)
The Examiner also found, presumably as to claim 8, that Meyn did not
describe an intercalate with the double hydroxide LiAl2(OH)6(Cl)H2O (id. at
10), but reasoned that an ordinary artisan would have considered it obvious
to produce an intercalate using that compound, “because Meyn et al. teach
Appeal 2011-007784
Application 12/011,773

8
using chloride as an anion in the synthesis of the double hydroxides” (id. at
11).
The Examiner also found, presumably as to claims 10 and 11, that
Meyn did not “expressly teach an embodiment with a non-toxic compound
having an anion which is capable of displacing the pharmaceutically active
compound from the intercalate such as magnesium carbonate, magnesium
hydrogen carbonate, calcium carbonate or calcium hydrogen carbonate” (id.
at 10).
The Examiner found that an ordinary artisan would have been
prompted to include the additional anionic compounds recited in Appellant‟s
claims 10 and 11 in Meyn‟s compositions because “clearly in Figure 1 Meyn
et al. teach displacing carbonate anion from the double layered hydroxide.
The presence of the carbonate anion is capable of displacing the
pharmaceutically active compound” (id. at 12). Therefore, the Examiner
reasoned, “[s]ince the double layered hydroxides are made with calcium and
magnesium, it stands to reason that these elements would serve as counter
cations to the carbonate in solution” (id.).
Appellant argues the claims subject to this rejection in three groups:
(I) claims 1, 2, 4-7, 9, and 13, (II) claims 3, 8, and 12, and (III) claims 10
and 11 (App. Br. 6).
As to group I, as noted above, we agree with the Examiner that Meyn
anticipates claim 1. As the Federal Circuit has stated, “[i]t is well settled
that „anticipation is the epitome of obviousness.‟” In re McDaniel, 293 F.3d
1379, 1385 (Fed. Cir. 2002) (quoting Connell v. Sears, Roebuck & Co., 722
F.2d 1542, 1548 (Fed. Cir. 1983)).
Appeal 2011-007784
Application 12/011,773

9
Accordingly, we affirm the Examiner‟s rejection of claim 1 as
obvious over Meyn and Miyata. As they were argued in the same grouping,
claims 2, 4-7, 9, and 13 fall with claim 1.
As to group II, however, we find that Appellant has the better
position, at least with respect to claims 3 and 12.
In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007), the
Supreme Court emphasized “an expansive and flexible approach” to the
obviousness question, but also reaffirmed the importance of determining
“whether there was an apparent reason to combine the known elements in
the fashion claimed by the patent at issue.” Id. at 418.
Ultimately, therefore, “[i]n determining whether obviousness is
established by combining the teachings of the prior art, the test is what the
combined teachings of the references would have suggested to those of
ordinary skill in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir.
1995) (internal quotations omitted).
Meyn is directed, essentially, to a study of the behavior and physical
properties of layered double hydroxides when reacted with different organic
anions (see, e.g., Meyn 5201 (“Secondary alkanesulfonates and technical
anionic surfactants, which are mixtures of isomers and of compounds with
different chain lengths, aggregate in the interlayer spaces forming
bimolecular films of constant thickness, and well-ordered organo-double
hydroxides are formed, which produce integral series of basal reflections in
the X-ray diagrams.”) (Abstract)).
Thus, while Meyn tests salicylate as one of its intercalating
compounds among many other non-pharmaceutically active compounds,
including a number of surfactants (see id. at 5203 (Tables II and III)), Meyn
Appeal 2011-007784
Application 12/011,773

10
does not mention the use of the layered double hydroxides as carriers for
pharmaceutically active compounds, nor does Meyn focus on
pharmaceutically active compounds, such as those present in the intercalates
described in Miyata. Moreover, the Examiner points to no clear or specific
teaching in either reference, or in the knowledge generally available to an
ordinary artisan, suggesting that the pharmaceutical compounds in Miyata‟s
intercalates would have been useful in the study described in Meyn.
Accordingly, we are not persuaded that the Examiner has adequately
explained why Meyn and Miyata would have suggested using the
therapeutic compounds described by Miyata in Meyn‟s study of the behavior
of double hydroxide compounds. Because the Examiner‟s conclusion of
obviousness as to claims 3 and 12 requires the combination of these two
references, we reverse the Examiner‟s obviousness rejection as to those
claims.
As to claim 8, however, as the Examiner points out, Meyn‟s salicylate
intercalate of LiAl2(OH)6(NO3)nH2O (see Meyn 5202, 5203 (Table II))
differs from the claimed LiAl2(OH)6(Cl)•H2O compound only as to the
substitution of nitrate as the interlayer anion rather than chloride. As the
Examiner also points out, Meyn discloses that both chloride and nitrate were
suitable as the interlayer anion in layered double hydroxide compounds (see
id. at 5201 (“X = interlayer anion (Cl
-
, NO3
-
, ClO4
-
, CO3
2-
, SO4
2-
, and many
other inorganic anions”)).
Given this teaching of the equivalence of a number of interlayer
organic anions, including nitrate and chloride, we agree with the Examiner
that an ordinary artisan would have considered it obvious to produce Meyn‟s
salicylate intercalate-containing aqueous solution using a
Appeal 2011-007784
Application 12/011,773

11
LiAl2(OH)6(Cl)•H2O compound, in light of Meyn‟s disclosure of using the
equivalent double hydroxide LiAl2(OH)6(NO3)nH2O compound. We
therefore agree with the Examiner that claim 8 would have been prima facie
obvious to an ordinary artisan in view of Meyn.
We note, as Appellant argues (App. Br. 14, Reply Br. 7), that Meyn
was unable to produce salicylate intercalates using the Mg-Al and Ca-Al
double hydroxides (Meyn 5203 (Table II)). Meyn did, however, produce a
salicylate intercalate using the nitrate-containing Li-Al compound, which
differs only from the compound of claim 8 as to the substitution of chloride
for nitrate, as discussed above.
Appellant points to no evidence of record suggesting that an ordinary
artisan lacked a reasonable expectation that the chloride Li-Al double
hydroxide compound would have functioned in a manner equivalent to the
nitrate-containing compound used in Meyn‟s example. Thus, as Appellant‟s
arguments do not persuade us that the Examiner erred in concluding that
claim 8 would have been obvious to an ordinary artisan, we affirm the
Examiner‟s rejection of that claim over Meyn and Miyata.
As to group III, claims 10 and 11, we note, as the Examiner points
out, that carbonate is one of the known interlayer anions in layered double
hydroxide compounds, and is the anion present in hydrotalcite (see Meyn,
5201, 5202). We are not persuaded, however, that the known presence of
carbonate anions in double hydroxide compounds would have prompted an
ordinary artisan to include additional intercalate-displacing salts as required
by claim 10, or the carbonate salts recited in claim 11, in the aqueous milieu
used by Meyn to produce its salicylate intercalates. We therefore reverse the
Appeal 2011-007784
Application 12/011,773

12
Examiner‟s obviousness rejection of claims 10 and 11 over Meyn and
Miyata.
NEW GROUND OF REJECTION – ANTICIPATION
Under the provisions of 37 C.F.R. § 41.50(b), we enter the following
new ground of rejection:
Claims 1-3 and 12 are rejected under 35 U.S.C. § 102(b) as
anticipated by Miyata.
Miyata describes double hydroxide magnesium-aluminum complexes
with a number of anionic pharmaceutically active compounds, including
ibuprofen (see Miyata, col. 9, ll. 43-44 (Table 2); see also id. at col. 17, ll.
35-67).
Miyata explains that the “new complex of the invention is valuable for
use as a central nervous system medicament, and especially as an
antipyretic, analgesic, antirheumatic and anti-flammatory [sic] agent. It is
administered to the patients orally” (id. at col. 9, ll. 25-29).
Miyata further explains that the “new complex of the invention can be
regarded as being a compound in which the carbonate ion of hydrotalcite has
been substituted by a specific organic anion” (id. at col. 3, ll. 62-64).
Accordingly, because hydrotalcite is a layered double hydroxide (see
Spec. 1), and because the anionic pharmaceutically active compound
ibuprofen in Miyata‟s compositions replaces the interlayer carbonate ion
normally present in hydrotalcite, and because Miyata describes its product as
being in an oral dosage form, Miyata describes a composition having all of
the elements of Appellant‟s claims 1 and 12, and therefore anticipates those
claims.
Appeal 2011-007784
Application 12/011,773

13
As Miyata‟s magnesium/aluminum-containing hydrotalcite complexes
inherently meet claim 2‟s recitation of the general formula of layered double
hydroxide compounds composed of divalent/trivalent species (see Spec. 1),
and as Miyata‟s magnesium-aluminum complexes contain the magnesium
and aluminum recited in claim 3, Miyata also anticipates claims 2 and 3.
SUMMARY
We affirm the Examiner‟s anticipation rejection of claims 1, 4-7, 9,
and 13 over Meyn.
We also affirm the Examiner‟s obviousness rejection of claims 1, 2,
4-9, and 13 over Meyn and Miyata.
However, we reverse the Examiner‟s obviousness rejection as to
claims 3 and 10-12.
We enter a new ground of rejection as to claims 1-3 and 12 under
35 U.S.C. § 102(b) for anticipation.

TIME PERIOD FOR RESPONSE
Regarding the affirmed rejection(s), 37 CFR § 41.52(a)(1) provides
“[a]ppellant may file a single request for rehearing within two months from
the date of the original decision of the Board.”
In addition to affirming the examiner's rejection(s) of one or more
claims, this opinion contains a new ground of rejection pursuant to 37 CFR §
41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960 (August 12,
2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)). 37 CFR §
41.50(b) provides “[a] new ground of rejection pursuant to this paragraph
shall not be considered final for judicial review.”
Appeal 2011-007784
Application 12/011,773

14
37 CFR § 41.50(b) also provides that the appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of the
claims so rejected or new evidence relating to the claims so rejected, or both,
and have the matter reconsidered by the examiner, in which event the
proceeding will be remanded to the examiner. . . .

(2) Request rehearing. Request that the proceeding be reheard under §
41.52 by the Board upon the same record. . . .

Should the Appellant elect to prosecute further before the examiner
pursuant to 37 CFR § 41.50(b)(1), in order to preserve the right to seek
review under 35 U.S.C. §§ 141 or 145 with respect to the affirmed rejection,
the effective date of the affirmance is deferred until conclusion of the
prosecution before the examiner unless, as a mere incident to the limited
prosecution, the affirmed rejection is overcome.
If the appellant elects prosecution before the examiner and this does
not result in allowance of the application, abandonment or a second appeal,
this case should be returned to the Board of Patent Appeals and Interferences
for final action on the affirmed rejection, including any timely request for
rehearing thereof.

AFFIRMED-IN-PART, 37 C.F.R. § 41.50(b)

cdc