Ex Parte Filipcsei et al

Patent Trial and Appeal Board

Dec 5, 2017

13378640 (P.T.A.B. Dec. 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.
13/378,640 02/13/2012 Genoveva Filipcsei DAN-070 (110293) 8874
12495 7590 12/05/2017
Jason D. Voight
5100A MacArthur Boulevard, NW
Second Floor
Washington, DC 20016
EXAMINER
BROWE, DAVID
ART UNIT PAPER NUMBER
1617
MAIL DATE DELIVERY MODE
12/05/2017 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 GENOVEVA FILIPCSEI, ZSOLT OTVOS,
KATALIN PONGRACZ, and FERENC DARVAS1
Appeal 2017-002103
Application 13/378,640
Technology Center 1600
Before DEBORAH KATZ, ULRIKE W. JENKS, and JOHN E.
SCHNEIDER, Administrative Patent Judges.
KATZ, Administrative Patent Judge.
DECISION ON APPEAL
1 NanoForm Hungary Ltd. is reported to be the real party-in-interest. (App.
Br. 1.)
Appeal 2017-002103
Application 13/378,640
Appellants seek our review, under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 34, 36-38, and 54-57.2 (App. Br. 1.)
We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.
The Examiner rejected all of the claims under consideration under
35 U.S.C. § 112, second paragraph, as being indefinite. (Ans. 3-4.)
The Examiner also rejected all of the claims under consideration
under 35 U.S.C. § 103(a) as being obvious over Ryde3, Anderson4, and
Song5. (Ans. 4-7.)
Appellants do not argue for the separate patentability of any of the
rejected claims. Accordingly, we focus on independent claim 34 in our
review. See 37 C.F.R. § 41.37(c)(l)(iv).
Appellants’ Specification is directed to formulations of sildenafil
citrate, a drug known to be useful in the treatment of erectile dysfunction
and marketed under the name Viagra. (Spec. 2.)
Appellants’ claim 34, the only independent claim on appeal, recites:
A nanostructured sildenafil composition comprising:
(a) nanoparticles of sildenafil base or a pharmaceutically
acceptable salt or co-crystal thereof having an average particle size of
less than about 500 nm;
(b) an anionic polyelectrolyte or a non-ionic stabilizer or a
mixture thereof or an additional stabilizer,
2 Appellants have cancelled claims 1-33, 35, 39, 40, and 48-50 and have
withdrawn claims 41-47 and 51-53 from consideration. (See Amendment
filed October 26, 2015.)
3 U.S. Patent Application No. 2005/0042177 Al, published February 24,
2005.
4 U.S. Patent Application No. 2008/0199700 Al, published August 21, 2008.
5 U.S. Patent Application No. 2006/0014271 Al, published January 19,
2006.
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Application 13/378,640
wherein the composition is prepared in a microfluidic based
continuous flow reactor,
wherein the nano structured sildenafil composition has at least
partially amorphous structure,
wherein the polyelectrolyte is selected from the group
consisting of nucleic acids, proteins, teichoic acids, polypeptides,
polysaccharides, poly(sodium styrene sulfonate)-based polymers,
poly(sodium styrene sulfonate)-based copolymers,
poly(meth)acrylate-based polymers, poly(meth)acrylate-based
copolymers, poly(acrylic-acid) optionally cross-linked with allyl ester,
sucrose or pentaerythriol, and derivatives of poly( acrylic-acid)
optionally cross-linked with allyl ester, sucrose or pentaerythriol,
wherein the non-ionic stabilizer is selected from the group
consisting of poly(vinyl-pyrrolidone), poly(2-ethyl-2-oxazoline),
poly(methyl vinyl ether), polyvinyl alcohol, acetic acid ethenyl ester
polymers with l-ethenyl-2-pyrrolidinone (PVP/V A copolymers),
poly( ethylene-glycol), derivatives of poly(ethylene-glycol), ethylene
oxide/propylene oxide block copolymers, derivatives of ethylene
oxide/propylene oxide block copolymers, and polyoxyethylene
sorbitan fatty acid esters,
wherein the additional stabilizer is selected from the group
consisting of hydroxyl-propylcellulose derivatives, sodium lauryl
sulfate, sodium dodecyl benzene sulfonate, tocopheryl polyethylene
glycol succinates, polyethoxylated castor oils, derivatives of
polyethoxylated castor oils, and cationic stabilizers,
wherein the composition is not a gel, and
wherein the ratio of the sildenafil base or the pharmaceutically
acceptable salt or co-crystal thereof to the anionic polyelectrolyte or
the non-ionic stabilizer or the mixture thereof or the additional
stabilizer is from 10:1 to 100:1 by weight.
(App. Br. 9-10, Claims App’x.)
One embodiment within claim 34 recites a nanoparticle composition
with the following structural features:
(a) nanoparticles of sildenafil base having an average particle
size of less than about 500 nm;
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(b) an anionic polyelectrolyte, specifically poly(acrylic-acid)
optionally cross-linked with allyl ester, sucrose or pentaerythriol;
wherein the nano structured sildenafil composition has at least
partially amorphous structure,
wherein the composition is not a gel, and
wherein the ratio of the sildenafil base to the anionic
polyelectrolyte is from 10:1 to 100:1 by weight.
35 U.S.C. § 112, second paragraph
The Examiner rejected Appellants’ claims as being indefinite because
the claimed sildenafil composition excludes gels (“wherein the composition
is not a gel”), but includes an anionic polyelectrolyte as recited in (b),
specifically poly(acrylic-acid) cross-linked with allyl ester, sucrose or
pentaerythriol, which was known to form gels. (See Ans. 3.) The Examiner
cites to Brown (U.S. Patent No. 2,798,053) as evidence of this knowledge.
Appellants do not dispute that Brown teaches that poly(acrylic-acid)
cross-linked with allyl ester, sucrose or pentaerythriol form a gel.
Appellants, however, argue that ordinarily skilled artisans would have
recognized that the polymers recited would only produce a gel under certain
pH conditions and concentrations and that these conditions were well-known
or readily ascertainable without undue experimentation. (App. Br. 3.)
Appellants do not direct us to evidence in their Appeal Brief to support the
assertion that the lack of a gel formation was well-known to the ordinary
artisan. Furthermore, Appellants’ claims are not limited to specific pH or
concentrations conditions.
Appellants cite support for this assertion only in their Reply Brief (see
Reply Br. 1-2), but this evidence is untimely. (See 37 C.F.R. § 41.41(b)(1)
(“A reply brief shall not include any new or non-admitted amendment, or
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Application 13/378,640
any new or non-admitted affidavit or other Evidence.”).) Specifically,
Appellants rely on “the enclosed article by Nikolopoulos found on the
Internet http://www.admix.com/carbopol” to argue that the specific cross-
linked polymer Carbopol would not form a gel under certain conditions.
(Reply Br. 2.) Appellants also argue that this polymer is used in Example 8
of their Specification to obtain a product that is a colloidal solution, not a
gel. According to Appellants, “it is within the knowledge of a skilled person
to make a non-gel solution including such polymers which are otherwise
capable of forming a gel under specific conditions.” (Id.)
Appellants’ argument is unpersuasive, whether we consider the
belatedly cited evidence or not, because it refers to only one cross-linked
polymer — Carbopol. In contrast, the Examiner’s rejection is based on the
knowledge in the art that poly(acrylic-acid) cross-linked with allyl ester,
sucrose or pentaerythriol was known to form gels. Thus, even if it was
known how to prevent one specific cross-linked polymer from forming a gel,
Appellants’ claims include other polymers within the scope of the claims
that were known to form gels.
Appellants’ argument that “the boundaries of what is encompassed by
the claim language ‘not a gel’ would be clear and precise to one possessing
ordinary skill in the art in view of the specification and prior art” (App. Br.
3-4) is unpersuasive because it fails to direct us to portions of the
Specification or teachings in the prior art in support. Accordingly, this
argument is merely conclusory.
35 U.S.C. § 103(a)
The Examiner cites Ryde for its teaching of a composition of
sildenafil base and an anionic stabilizer in nanoparticles that form an
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amorphous colloid instead of a gel. (Ans. 4-5, citing, inter alia, Ryde
abstract and Tflf 91, 122, 138-39, claims 13, 14, 16.) Ryde does not
expressly teach that the anionic polyelectrolyte stabilizer is a poly(acrylic
acid) polymer or that the particles are prepared in a microfluidic based
continuous flow reactor.
The Examiner finds that one of ordinary skill in the art would have
looked to the teachings of Anderson to include a poly(acrylic acid) as a
stabilizer in the nanoparticles of Ryde because Anderson teaches that
poly(acrylic acid) improves nanoparticle solubility, prevents nanoparticle
aggregation, and allows tailoring of the drug release profile, for example to
achieve sustained-release. (Anderson || 33 and 40; see Ans. 5-6.)
The Examiner also finds that those of ordinary skill in the art would
have considered it obvious to have used a microfluidic based continuous
flow reactor as taught in Song to synthesize the nanoparticles of Ryde
because Song teaches a method for manufacturing nanoparticles with a
narrow size distribution that is fast, inexpensive, and highly precise. (See
Ans. 5 and 11; Song, abstract and Tflf 0013-0014, 0065.)
Appellants discuss the differences between the method of stabilizing
drugs taught in Ryde and Appellants’ continuous flow nanoprecipitation
technique. (See App. Br. 4-5.) To the extent that Appellants argue any
alleged differences in the methods indicate the claims currently under
consideration are patentable, we are not persuaded. Appellants claim a
composition, not a method of making a composition. Thus, we are not
persuaded by arguments that refer only to the differences in the methods
used in the prior art.
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For example, Appellants argue that the micro fluidic based continuous
flow reactor method taught in Song relates to a different technical field and
discloses the preparation of palladium nanoparticle, which, according to
Appellants, is a very different type of nanoparticle. (App. Br. 6.) We are
not persuaded that recitation of this process of making the nanoparticle
composition product Appellants claim creates a patentable difference over
the cited prior art. (See Ans. 10 (“The instant claims are directed to a
‘product-by-process.’ The determination of patentability is based on the
product, and does not depend on its method of production. Indeed, if the
product is the same as or obvious from a product of the prior art, the claim is
unpatentable even though the prior art product was made by a different
process.”).)
As the Examiner found, Ryde teaches nanoparticles with the same
characteristics Appellants claim: less than about 500 nm, at least partially
amorphous, not a gel, as well as being soluble and redispersible. (See Ans.
10-11; see Ryde §§ 91, 122, 192, 194, 195.) “Where a product-by-process
claim is rejected over a prior art product that appears to be identical,
although produced by a different process, the burden is upon the applicants
to come forward with evidence establishing an unobvious difference
between the claimed product and the prior art product.” In re Marosi, 710
F.2d 799, 803 (Fed. Cir. 1983). Appellants fail to direct us to evidence that
the nanoparticles of Ryde modified as taught in Anderson would be different
from those prepared in a microfluidic based continuous flow reactor.
Appellants argue that the technique taught in Ryde produces a product
with solubility that differs from the solubility of the claimed composition.
(App. Br. 5.) Appellants also argue that Anderson teaches nanoparticles of
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metals and metal alloys, not sildenafil and does not suggest using a stabilizer
polymer with sildenafil to increase its solubility. (Id.) Appellants argue
further that Song does not teach anything about the preparation of
nanoparticles of organic compounds. (App. Br. 6.)
Each of these arguments addresses the prior art references
individually. The rejection is based on the obviousness of modifying the
nanoparticles taught in Ryde according to the teachings of Anderson and
Song. “Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references.” In re Merck & Co., Inc., 800 F.2d 1091, 1097
(Fed. Cir. 1986).
Appellants argue further that Anderson relates to CdTe-CdS
photoluminescent quantum dots and that the nanoparticles it teaches have a
metal core, which would not be useful for pharmaceutically active
compounds. (App. Br. 5.) Again, Appellants do not address the Examiner’s
rejection.
The test for obviousness is not whether the features of a
secondary reference may be bodily incorporated into the
structure of the primary reference; nor is it that the claimed
invention must be expressly suggested in any one or all of the
references. Rather, the test is what the combined teachings of
the references would have suggested to those of ordinary skill
in the art.
In re Keller, 642 F.2d 413, 425 (C.C.P.A. 1981).
According to Appellants, the metallic core of the particles taught in
Anderson are essential and only hindsight based on Appellants’
Specification indicates that one of ordinary skill in the art would attempt to
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use the stabilizer of Anderson with the nanoparticles of Ryde, which lack a
metallic core. (App. Br. 5-6.) We are not persuaded by this argument
because Anderson teaches that “[a] wide variety of molecules can be used to
form the nanoparticle” surrounded by the stabilizer layer of the invention,
including nanoparticles of organic or inorganic charged ions or combinations
thereof. (See Anderson 136.) Because Anderson is not limited to
nanoparticles with a metallic core, we are not persuaded by Appellant’s
argument that it is essential to the use of a poly(acrylic acid) polymer as
taught in Anderson.
Appellants also argue that the claimed nano structured sildenafil
compositions demonstrate unexpected results that indicate they are
patentable over the prior art. (App. Br. 7.) Appellants argue that “the very
high increase in solubility supported by example 2 of the present application
[6.8-times (i.e. 680 %) increase in solubility!] should be regarded as an
unexpected, ‘non-obvious’ result” because none of the references cited by
the Examiner report a similar increase in solubility. (App.Br. 7.) Appellants
argue further that other “excellent physical properties,” including enhanced
redispersibility and wettability, enhanced lipophilicity through the cell
membranes, and preferred serum concentration profile both in fasted and fed
state. (App. Br. 7.)
We are not persuaded by these arguments because Appellants do not
direct us to evidence that one of ordinary skill in the art would have found
any of these characteristics to be unexpected over the combination of the
teachings of the cited prior art. Although Examples 2, 5, and 6 of
Appellants’ Specification reports solubility of nano structured sildenafil
citrate to be 6.8 times higher than the solubility of sildenafil citrate in
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distilled water (see Spec. 10:9-10), increased redispersibility (see id.
11:30-12:10), and enhanced wettability (see id. 13:10-20), the Specification
does not indicate that these results were unexpected and Appellants do not
direct us to other evidence, such as the testimony of one of skill in the art.
Furthermore, as the Examiner explained, Example 2 of Appellants’
Specification compares nanostructured sildenafil with stabilizer to sildenafil
citrate that is not in particulate form and is not formulated with a stabilizer.
(See Ans. 13.) Ryde teaches that nanostructured sildenafil base exhibits
increased bioavailability, improved pharmacokinetic profiles, and
advantages over non-nanoparticulate sildenafil compositions or
nanoparticulate sildenafil citrate compositions. (See Ryde Tflf 57 and 67.)
Appellants’ evidence does not provide a comparison between the claimed
composition and that of the prior art, for example the composition of Ryde.
Accordingly, we are not persuaded that Appellants’ claimed invention
demonstrates results that would not have been expected by those of ordinary
skill in the art.
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CONCLUSION
Upon consideration of the record and for the reasons given, the
rejection of claims 34, 36-38, and 54-57 under 35 U.S.C. § 103(a) over 35
U.S.C. § 112, second paragraph, is sustained. The rejection of the same
claims under 35 U.S.C. 35 U.S.C. § 103(a) is also sustained.
Therefore, we affirm the decision of the Examiner.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.
AFFIRMED
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