Ex Parte Parthasarashi Reddy et al

Patent Trial and Appeal Board

Mar 29, 2017

13696702 (P.T.A.B. Mar. 29, 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.
13/696,702 03/14/2013 Bandi Parthasarashi Reddy HET0098US 8434
23413 7590 03/31/2017
TANTOR TOT RTTRN T T P
EXAMINER
20 Church Street PARAD, DENNIS J
22nd Floor
Hartford, CT 06103 ART UNIT PAPER NUMBER
1612
NOTIFICATION DATE DELIVERY MODE
03/31/2017 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BANDI PARTHASARASHI REDDY, PODILI KHADGAPATHI,
and GOLI KAMALAKAR REDDY
Appeal 2016-0073471
Application 13/696,702
Technology Center 1600
Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to an oral composition
comprising amorphous daranavir. The Examiner rejected the claims as
obvious under 35 U.S.C. § 103. We have jurisdiction under 35 U.S.C. § 134.
The rejection is affirmed.
STATEMENT OF THE CASE
The claims are directed to a composition comprising darunavir.
Darunavir is an HIV-1 protease inhibitor. Spec. 1:8-10. It is used to treat
HIV infection. Id. at 1:19-20.
1 The Appeal Brief (“Appeal Br.”) 2 lists Hetero Research Foundation as the
real-party-in-interest.
Appeal 2016-007347
Application 13/696,702
Appellants appeal from the Examiner’s final rejection of claims 1-15
under pre-AIA35 U.S.C. § 103(a) as obvious in view of Voorpoels (WO
2009/000853 Al, publ. Dec. 31, 2008), Harbeson (US Pat. Appl. Publ.
2009/0131363 Al, publ. May 21, 2009), and Gopinathan (US Pat. Appl.
Publ. 2010/0021540 Al, publ. Jan. 28, 2010). Final Action (“Final Act.”)
2-3.
Claim 1, the only independent claim on appeal, is reproduced below:
1. An oral pharmaceutical composition comprises
amorphous darunavir having a ds>o particle size in the range of
about 150 pm to 250 pm.
REJECTION
The Examiner found that Voorspoels describes an oral composition
comprising a combination TMC114, also known as darunavir, and TMC125.
Final Act. 3. The Examiner found that Voorspoels describes a particle size
of from about 10 pm to about 150 pm, but not the claimed range of 150 to
250 pm. Id. at 3, 4. The Examiner also found that while Voorspoels teaches
an embodiment of TMC125 in amorphous form, Voorspoels did not specify
that darunavir is also in amorphous form. Id. at 4.
To meet these deficiencies, the Examiner further cited Harbeson and
Gopinathan. The Examiner relied upon Harbeson for its teaching “that a
known method of enhancing bioavailability is the use of an amorphous form
of the compound of the invention (i.e., darunavir and its derivatives) (para
[0091]).” Id. at 5. As to the claimed range of particles, the Examiner found
that Gopinathan describes particle ranges within 100-200 and 200-300 pm
of active agents, such as TMC-114 (darunavir), “that are not crystalline (i.e.,
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Application 13/696,702
amorphous)” which have good compression even without lubrication. Id. at
6.
Appellants did not provide evidence that the Examiner erred in
finding that darunavir can be in amorphous form. Appeal Br. 5 (“even if one
were to modify the dosage form of Voorspoels by using amorphous
darunavir as disclosed in Harbeson”). However, Appellants contend that
neither Harbeson nor Voorspoels disclose or suggest the claimed particle
size range of about 150 pm to 250 pm. Id. Appellants contend that the
“granules” described in Gopinathan include more than just the active
ingredient and the sizes are less than 1 pm in diameter, which is
substantially smaller than the claimed range. Id. at 6. Consequently,
Appellants conclude that there would have been no motivation to select the
larger sized particles nor the claimed range of 150 to 250 pm. Id.
Appellants also provide evidence of unexpected results which they contend
rebuts any prima facie case of obviousness. Id. at 6-7.
FINDINGS OF FACT
Voorspoels
FF1. Voorspoels describes a solid oral dosage form of the HIV
inhibitors TMC114 (darunavir) and TMC125. Voorspoels 1:2-3.
FF2. Voorspoels teaches:
The solid dispersion of TMC125 typically comprises particles
having an average effective particle size in the range of from
about 10 pm to about 150 pm, or about 15 pm to about 100 pm,
particularly about 20 pm to about 80 pm, or 30 pm to about 50
um, preferably about 40 pm.
Id. at 11:6-9.
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FF3. Voorspoels teaches:
The average effective particle sizes mentioned herein may be
related to weight distributions of the particles. In that instance,
by “an average effective particle size of about 150 pm” it is
meant that at least 50% of the weight of the particles has a
particle size of less than the effective average of 150 pm, and
the same applies to the other effective particle sizes mentioned.
Id. at 11:13-17.
FF4. Voorspoels teaches TMC125 and TMC114 in tablet form,
individually and in combination. Id. at 4: 23-5:10.
Gopinathan:
FF5
[0027] The present invention also features a tabletting process
using a pre-tabletting material that has reduced particle sizes.
Where a pre-tabletting material contains granules of small sizes
and is compressed at a relatively low pressure, the resulting
tablets surprisingly contain significantly less or no detectable
internal fractures, even when the compression is carried out in
an unlubricated die and using unlubricated punches
FF6
[0030] In one embodiment, 90% of the particles in the granular
or powdery material is smaller than 300 pm, such as smaller
than 200 pm, or smaller than 100 pm. The present invention
also contemplates the use of a pre-tabletting material where the
mean particle size of the pre-tabletting material is no greater
than 200 pm, preferably no greater than 150 pm, and more
preferably no greater than 100 pm. Any pre tabletting material
described herein can be subject to particle size reduction and
then used to make tablets with reduced or eliminated internal
fractures.
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FF7
[0101] ... In another embodiment, at least 90% of the granules
in a pre-tabletting material are greater than 10 pm (or greater
than 20, 50, 100, 150, or 200 pm).
FF8
[0103] Accordingly, the present invention features a process of
making tablets from a granular pre-tabletting material, where
90% of the granules in the pre-tabletting material are smaller
than 400 pm, preferably smaller than 300 pm, highly preferably
smaller than 200 pm, and most preferably smaller than 100 pm.
FF9
[0120] HIV protease inhibitors suitable for use in the present
invention include, but are not limited to . . . TMC-114.
DISCUSSION
Appellants dispute the Examiner’s determination that the claimed
range of “dw particle size in the range of about 150 pm to 250 pm” of
amorphous darunavir would have been obvious to one of ordinary skill in
the art. Appeal. Br. 5.
The Examiner found that Gopinathan describes particles comprising
an active agent in the claimed range (FF6, FF7, FF8), where the active agent
can be selected from a list that includes darunavir (TMC-114) (FF9).
Appellants contend that Gopinathan’s particles comprise more than just an
active ingredient and are typically less than 1 pm. Appeal Br. 6. Appellants
further contend that Gopinathan “recites a myriad of mean particle sizes for
granules of the pre-tabletting material, and provides no motivation to select
specifically granules of size 100-200 and 200-300 pm.” Id.
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Appellants’ argument are not supported by adequate evidence.
Although Gopinathan describes dispersions with particles of less than 1 pm
in diameter (Gopinathan 76), there is explicit disclosure of particle ranges
which overlap with the claimed range of 150-250 pm (FF6, FF7, FF8), i.e.,
“where 90% of the granules in the pre-tabletting material are smaller than
400 pm, preferably smaller than 300 pm, highly preferably smaller than 200
pm.” FF8. As noted by the Examiner, “disclosed examples and preferred
embodiments do not constitute a teaching away from a broader disclosure or
nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA
1971).” Final Act. 7. It is well established that, when there is a range
disclosed in the prior art, and the clai med invention overlaps or falls within
that range, as there is here, there is a presumption of obviousness. In re
Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003); Iron Grip Barbell Co, v.
USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004). Even if the particle
size values do not precisely overlap, they “are so close that prima facie one
skilled in the art would have expected them to have the same properties,”
shifting the burden to the applicant to show they are different. Titanium
Metals Corp. v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). Accordingly,
we conclude that a preponderance of the evidence supports the Examiner’s
determination that the claimed range would have been obvious to one of
ordinary skill in the art.
Appellants’ argument that Gopinathan’s particles comprise more than
just an active ingredient is not persuasive. Appeal Br. 6. The issue in this
rejection is the obviousness of using “amorphous darunavir having a ds>o
particle size in the range of about 150 pm to 250 pm.” Voorspoels teaches
an oral composition comprising darunavir, but does not disclose its particle
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size. Gopinathan was cited by the Examiner for teaching a particle size
which overlaps with the claimed range. The question is whether it would
have been obvious to one of ordinary skill in the art to have used this particle
size in Voorspoels’ composition. Gopinathan provides an explicit reason to
do so: to reduce internal fractures when compressing material to make
tablets.2 FF5, FF6. See Final Rej. 8. Voorspoels describes darunavir in
tablet form. FF4. Thus, the ordinary skilled worker would have had reason
to utilize the particle size described by Gopinathan in Voorspoels’ tablets.
The rejection is not based on utilizing Gopinathan’s particles in Voorspoels’
tablet, but rather in using the particle size of Gopinathan for the darunavir
present in the Voorspoels composition.
Appellants contend that the teachings in Gopinathan have been
misinterpreted. Reply Br. 8. However, paragraphs 30, 101, and 103 (FF6,
FF7, FF8, respectively) clearly refer to a particle size which overlaps with
the claimed range and which reduces or eliminates fractures during tableting.
To rebut the presumption of obviousness, Appellants provided a
declaration by Dr. Goli Kamalakar Reddy (“Reddy Decl.”) in which he
declared that “it was unexpectedly found that the claimed particle size range
of 150-250 pm provided unexpectedly good results compared to both
smaller and larger particle sizes.” Reddy Decl. ^ 3. Dr. Reddy is also a co­
inventor of the application in this appeal.
Once prima facie obviousness has been established, an applicant for a
patent can rebut it with “a showing of “unexpected results,” i.e., to show that
2 We note that Voorspoels discloses in its discussion of the prior art that a
spray-dried dispersion of RMC125 is “difficult to compress.” Voorspoels
3:9-12.
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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. The basic principle behind this rule is straightforward -that
which would have been surprising to a person of ordinary skill in a particular
art would not have been obvious.” In re Soni, 54 F.3d 746, 750, (Fed. Cir.
1995). “[W]hen an applicant demonstrates substantially improved results . .
. and states that the results were unexpected, this should suffice to establish
unexpected results in the absence of evidence to the contrary.” Soni, 54 F.3d
at 751. “Unexpected results” must be commensurate in scope with the claim
to ensure that such results are representative of the entire claim scope to
which a patentee is entitled. In re Harris, 409 F.3d 1339, 1344 (Fed. Cir.
2005).
We do not find Dr. Reddy’s declaration persuasive.
Dr. Reddy states that “the claimed particle size range of 150-250 pm
provided unexpectedly good results compared to both smaller and larger
particle sizes.” Reddy Decl. ^ 3. However, the only evidence of a “smaller”
sized particle inferior to the claimed range is in a statement by Dr. Reddy
that “it was found that particle sizes of amorphous darunavir below 150 pm
resulted in flow issues from the hopper during compression. When standard
techniques such as usage of lubricants ranging from lowest possible limit to
maximum allowable limit were tried to improve the flow, no improvement
was observed.” Id., ^ 4. Dr. Reddy did not provide the data from which this
conclusion was drawn, such as the range of particles for which the flow
issue was observed, how much improvement was found, and how the flow
was measured. Unexpected results must be established by factual evidence.
M.P.E.P. § 716.01(c) (Ninth Edition); Soni, 54 F. 3d at 750. Dr. Reddy also
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did not describe how many particle sizes above or below 150 pm were tested
so it cannot be ascertained whether the results are commensurate in scope
with the claim. Harris, 409 F.3d at 1344.
In addition to this, it cannot be discerned what was compared in the
“Comparative dissolution data” reported by Dr. Reddy. Reddy Decl. ^ 5.
The particle sizes are listed as “400-600,” “250^100,” and “150-250,” but it
is not clear whether a single sample was tested having the listed range, or
whether multiple samples within the range were tested. Id. For example,
the Specification discloses examples with one discrete size, e.g., 195 pm and
210 pm, and not a range. Spec. 4. Without knowing exactly what was
tested by Dr. Reddy, we cannot conclude that such results were unexpected
and commensurate in scope with the claims. Soni, 54 F. 3d at 750; Harris,
409 F.3d at 1344.
For the foregoing reasons, the obviousness rejection of claim 1 is
affirmed. Claims 2-15 were not separately argued and therefore fall with
claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
DECISION
The Examiner’s decision rejecting claims 1-15 is affirmed.
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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