Ex Parte Padmanabhan et al

Patent Trials and Appeals Board

Apr 15, 2019

14437434 - (D) (P.T.A.B. Apr. 15, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/437,434 04/21/2015 Radhakrishnan Padmanabhan
23370 7590 04/17/2019
KILPATRICK TOWNSEND & STOCKTONLLP
Mailstop: IP Docketing - 22
1100 PEACHTREE STREET
SUITE 2800
ATLANTA, GA 30309
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
G2440-94191 l (034US1) 1391
EXAMINER
CRAIGO, BAHAR ALA WI
ART UNIT PAPER NUMBER
1623
NOTIFICATION DATE DELIVERY MODE
04/17/2019 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):
ipefiling@kilpatricktownsend.com
KTSDocketing2@kilpatrick.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RADHAKRISHNAN PADMANABHAN,
TADAHISA TERAMOTO, and MARK MANZANO
Appeal2018-006480
Application 14/437,434
Technology Center 1600
Before DEMETRA J. MILLS, ROBERT A. POLLOCK, and
DAVID COTTA, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a). The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm-in-part.
Appeal2018-006480
Application 14/437,434
STATEMENT OF CASE
The Specification discloses methods of treating a Flavivirus infection
by administering a therapeutically effective amount of Flavivirus inhibitors,
such as the Flavivirus protease inhibitor of Compound VI (Tolcapone ):
or a pharmaceutically acceptable salt thereof. Spec. 4--5.
The following claims are representative.
1. A method of treating a Flavivirus infection in a subject, comprising
administering to the subject a therapeutically effective amount of a
compound selected from the group consisting of:
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or a pharmaceutically acceptable salt thereof,
wherein the compound inhibits a Flavivirus protease.
8. The method of claim 1, wherein the Flavivirus is the West Nile
Virus.
14. The method of claim 1, further comprising administering a second
compound or composition, wherein the second compound or composition
includes an antiviral compound.
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15. The method of claim 14, wherein the second compound or
composition is a protease inhibitor.
16. A method of inhibiting a Flavivirus protease in a cell, comprising:
contacting a cell with an effective amount of a compound selected
from the group consisting of:
, and
or a pharmaceutically acceptable salt thereof.
Cited References
Padmanabhan et al., ("Padmanabhan") WO 2010/039538 A2 April 8, 2010
R. Pahwa et al., Practice Parameter: Treatment of Parkinson disease with
motor fluctuations and dyskinesia, American Academy of Neurology, pp.
983-95 (2006). ("Pahwa")
Stewart A. Factor, Treating the "off" periods in Parkinson's, Parkinson's
Disease Foundation (2016). ("Factor")
Paul J. Carson, Long-Term Clinical and Neuropsychological
Outcomes of West Nile Virus Infection, Infectious Diseases Society of
America, pp 723-30 (2006). ("Carson")
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Grounds of Rejection
1. Claims 1 and 8 are rejected under pre-AIA 35 U.S.C. § 103(a) as
being unpatentable over Pahwa as evidenced by Factor in view of
Carson.
2. Claims 1, 8, 14--16, and 24--26 are rejected under pre-AIA 35
U.S.C. § 103(a) as being unpatentable over Pahwa as evidenced
by Factor in view of Carson and Padmanabhan.
FINDINGS OF FACT
The Examiner's findings of fact are set forth in the Answer at pages
3-9. The following facts are highlighted.
1. Pahwa et al. teach administering the drug tolcapone (i.e., the same
as instant compound VI) 1, in connection with the treatment of
Parkinson disease, and that the drug was found to be effective in
decreasing off time (p.986, Table 1 and p.989, second paragraph).
Final Act. 2 4. According to Pahwa, off time "refers to periods of
return of [Parkinson disease] symptoms when medication effect
wears off." (p.984, col. 1 ).
2. Pahwa et al. teach that tolcapone is a catechol-0-methyl
transferase (COMT) inhibitor (p.989, second paragraph
3. As evidenced by Factor, "'off time is defined as 'a state of
decreased mobility"' (second paragraph). Id.
1 Appellants do not contest that Compound IV as set forth in independent
claims 1 and 16 is tolcapone. See Spec. p. 5.
2 Office Action mailed June 9, 2017 ("Final Act.").
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4. Pahwa et al. do not expressly disclose administering tolcapone to a
patient having West Nile Virus (instant claim 1 ). Id.
5. Carson et al. teach that movement disorders have been reported in
patients having West Nile Virus infection (p. 728, second
paragraph). Carson et al. teach that the studies citing the
movement disorders describe features consistent with
Parkinsonism (p.728, second paragraph). Id.
6. Carson et al. teach that movement disorders include bradykinesia,
rigidity, and postural instability (p.728, second paragraph). Id.
7. The Specification pages 12-13 states that,
As used herein the terms treatment, treat, or treating refer to a
method of reducing or delaying one or more symptoms of a
Flavivirus infection. Thus in the disclosed method, treatment can
refer to a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or
100% reduction in the severity or progression of one or more
symptoms of the disease or condition. For example, a method for
treating a disease is considered to be a treatment if there is a 10%
reduction in one or more symptoms or signs of the Flavivirus
infection in a subject as compared to a control.
PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007).
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Moreover, "obviousness requires a suggestion of all limitations in a
claim." CFMT, Inc. v. Yieldup Intern. Corp., 349 F.3d 1333, 1342 (Fed. Cir.
2003) (citing In re Royka, 490 F.2d 981,985 (CCPA 1974)).
Obviousness Rejection 1 - Claims 1, 8
Based on finding of fact 1-7 above, the Examiner concludes that
It would have been obvious at the time the invention was
made to administer tolcapone to a subject infected with West
Nile Virus [WNV] to treat Parkinson-type mobility disorders.
* * *
The recitation "treating ... a Flavivirus infection" is
defined in the instant Specification as "reducing or delaying one
or more symptoms of a Flavivirus infection" (see paragraph
[0047] of the instant PGPub). The symptoms of West Nile
Virus infection include the same or similar symptoms of
Parkinson's disease, so much so, that Carson et al. refer to the
mobility disorders observed in WNV patients as
"parkinsonism". The ordinary artisan would have been
motivated to treat WNV infected patients having parkinsonism
by administering tolcapone because Pahwa et al. teach
tolcapone can reduce "off' time, the state of decreased mobility
in patients with Parkinson's disease.
Final Act. 4, 5.
Appellants contend that, "[ n Jone of the cited references disclose or
suggest a method of treating a Flavivirus infection in a subject comprising
administering to the subject a therapeutically effective amount of the recited
compounds ( e.g., tolcapone) or a pharmaceutically acceptable salt thereof,
wherein the compound inhibits a Flavivirus protease." App. Br. 8.
Appellants also argue that, "[t]he Examiner also failed to demonstrate that
the limitation at issue is the natural result of the combination of elements
explicitly disclosed by the prior art references. The claim language requires
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the presence of a Flavivirus protease within the subject (i.e., the subject is
infected with a Flavivirus). Id.
ANALYSIS
Claims 1 and 8
In response to the election of species made in an Office Action dated
October 12, 2016, Appellants elected compound VI (tolcapone), and West
Nile Virus as thejlavivirus. Appellants' Response dated January 12, 2017,
p. 7. When the Examiner has required the applicant to elect single chemical
species for examination, the issue on appeal is the patentability of the single
elected species. It is appropriate to limit discussion to that single issue and
take no position respecting the patentability of the broader generic claims,
including the remaining, non-elected species. See, Ex parte Ohsaka, 2
USPQ2d 1461 (Bd. Pat. App. Int. 1987).
Appellants do not argue individual claims of rejection 1, therefore we
select claim 1 as representative claim for this rejection. We agree with the
Examiner's fact finding, statement of the rejection and responses to
Appellants' arguments as set forth in the Answer. We find that the
Examiner has provided evidence to support a prima facie case of
obviousness. We provide the following additional comments on the
Examiner's argument set forth in the Final Rejection and Answer.
Claim Interpretation
Claim 1 is directed to, "a method of treating a Flavivirus infection in a
subject." We look to the Specification to determine the meaning of the term
"treating" as claimed. During ex parte prosecution, claims are to be given
their broadest reasonable interpretation consistent with the description of the
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invention in the specification. See, Cuozzo Speed Technolgies, LLC v. Lee,
136 S. Ct. 2131, 2144 (2016); In re Zletz, 893 F.2d 319, 321 (Fed. Cir.
1989).
The Specification, pages 12-13, defines the term "treating" as
refer[ing] to a method of reducing or delaying one or more
symptoms of a Flavivirus infection. Thus in the disclosed
method, treatment can refer to a 10%, 20%, 30%, 40%, 50%,
60%, 70%, 80%, 90%, or 100% reduction in the severity or
progression of one or more symptoms of the disease or
condition. For example, a method for treating a disease is
considered to be a treatment if there is a 10% reduction in one
or more symptoms or signs of the Fla vi virus infection in a
subject as compared to a control.
Thus, we interpret the term "treating" in claim 1, consistent with the
Specification and the Examiner's claim interpretation, to include reducing or
delaying one or more symptoms of a Flavivirus infection. Ans. 4.
Carson discloses that movement disorders, and tremor occurred in
20% of West Nile Virus patients. P. 728, cols. 1 and 2. "Movement
disorders have been frequently reported for patients with WNV [West Nile
Virus] infection." P. 728, col. 2. West Nile Virus studies also "describe
bradykinesia, rigidity, postural instability, and other features that are
consistent with parkinsonism." P. 728, col. 2. Therefore, Carson evidences
that movement disorders are symptoms of West Nile Virus.
Pahwa discloses medications that reduce motor fluctuations and
dyskinesia. Abstract. In particular, Pahwa generally discloses
PD [Parkinson's disease] is a progressive
neurodegenerative disorder with cardinal motor features of
tremor, bradykinesia, and rigidity. Although initially effective,
dopaminergic therapies are eventually complicated by motor
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fluctuations, including off time (periods of return of PD
symptoms when medication effect wears off) and dyskinesia
( drug-induced involuntary movements including chorea and
dystonia) in most patients. These motor complications can
impair quality of life and cause significant disability.
P. 9 84, col. 1, italicized emphasis added. Pahwa discloses that
Tolcapone 100 mg TID decreased off time 32% (2.3 hours),
tolcapone 200 mg TID decreased off time 48% (3.2 hours), and
placebo decreased off time 20% (1.4 hours) (p < 0.01 for the
tolcapone 200 mg TID group). At both tolcapone doses, a
significant improvement in investigator global score occurred,
as well as a significant decrease in levodopa dose (:S 200 mg)
and number of levodopa doses per day ( decreased by
approximately one).
P. 989, col. 1; see also P. 984, col. 1 (indicting that "off time" is associated
with motor fluctuations). Therefore, it was known to those of ordinary skill
in the art at the time of the invention that tolcapone, a COMT inhibitor,
could reduce symptoms associated with time off of Parkinson medications,
including motor fluctuation symptoms. Because movement disorders and
parkinsonism symptoms are also associated with West Nile Virus, it would
have been obvious to one of ordinary skill in the art to select a movement
disorder treatment drug, such as tolcapone, to treat movement disorders
associated with West Nile Virus.
Appellants argue that, "[ n Jone of the cited references disclose or
suggest a method of treating a Flavivirus infection in a subject comprising
administering to the subject a therapeutically effective amount of the recited
compounds ( e.g., tolcapone) or a pharmaceutically acceptable salt thereof,
wherein the compound inhibits a Flavivirus protease." App. Br. 8.
However, we agree with the Examiner that, "[t]he recitation 'wherein the
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compound inhibits a Flavivirus protease' is a latent property of the
compound [tolcapone] when administered to a subject infected with a
Flavivirus, including WNV." Final Act. 5. "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)
(citing In re Prindle, 297 F.2d 251, 254 (CCPA 1962)).
The motivation to combine references does not have to be identical to
the applicants to establish obviousness. In re Kemps, 97 F.3d 1427, 1430,
40 USPQ2d 1309, 1311 (Fed. Cir. 1996). "It is a general rule that merely
discovering and claiming a new benefit of an old process cannot render the
process again patentable." In re Woodruff, 919 F.2d 1575, 1578, 16
USPQ2d 1934, 1936 (Fed. Cir. 1990). Because it was well known to those
of ordinary skill in the art at the time of the invention to administer
tolcapone for the treatment of movement disorders and parkinsonism
generally, which are also symptoms of West Nile Virus, the claimed
treatment method/process is an old process known in the art. Claiming the
new benefit, that the tolcapone product also inhibits Flavivirus protease,
cannot render the known process patentable again. "From the standpoint of
patent law, a compound and all of its properties are inseparable; they are one
and the same thing." In re Papesch, 315 F.2d 381, 391, 137 USPQ 43, 51
(CCP A 1963). Therefore, the administration of tolcapone to a West Nile
Virus patient with a movement disorder or parkinsonism symptoms meets
the claim.
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Rejection 2
Claims 1, 8, 14-15
We affirm the Examiner's rejection of claims 1, 8, and 14-16.
The Examiner concludes that, "[i]t would have been obvious at the
time the invention was made to administer tolcapone in combination with
the compounds of Padmanabhan et al. to treat a subject having WNV
infection." Final Act. 7.
Appellants argue that, "Pahwa, Factor, Carson, and Padmanabhan fail
to disclose or suggest using tolcapone to inhibit a Flavivirus protease." App.
Br. 11.
ANALYSIS
Claims 1, 8, 14 and 15
The basis for affirming the rejection of claims 1, 8, 14, and 15 is
essentially the same as for rejection 1. Pahwa, Factor, Carson treat a
symptom of West Nile virus, and Padmanabhan treats or ameliorates
Flavivirus infection. Abstract. This type of motivation has been recognized
often by the predecessor of our reviewing court, which has held that it is
prima facie obvious to combine two compositions each of which is taught by
the prior art to be useful for the same purpose, in order to form a third
composition which is to be used for the same purpose. In re Susi, 440 F.2d
442,445 (CCPA 1971); In re Crockett, 279 F.2d 274, 276-77 (CCPA 1960).
The idea of combining them flows logically from their having been
individually taught in the prior art. In re Kerkhoven, 626 F .2d 846, 850, 205
USPQ 1069, 1072 (CCPA 1980).
The rejection of claims 14-15 is affirmed.
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Claims 16, 24-26
Claims 16 and 24--26 are rejected under pre-AIA 35 U.S.C. § 103(a)
as being unpatentable over Pahwa as evidenced by Factor in view of Carson
and Padmanabhan.
The Examiner adds Padmanabhan to rejection 1 as the foundation for
rejection 2. The Examiner finds that
Padmanabhan et al. teach methods of treating a
Flavivirus infection in a subject by administering a
therapeutically effective amount of novel Flavivirus inhibitor,
specifically Flavivirus serine protease inhibitors for the
treatment of West Nile Virus infection (p.8, lines 25-29).
Padmanabhan et al. teach administering the compound of claim
1 to a subject having a Flavivirus infection ( claim 1 ), wherein
the Flavivirus infection includes West Nile Virus.
Padmanabhan et al. teach the compounds were effective in vitro
(p.46-48, Example 1 ).
Final Act. 7.
The Examiner concludes that, "[i]t would have been obvious at the
time the invention was made to administer tolcapone in combination with
the compounds of Padmanabhan et al. to treat a subject having WNV
infection." Final Act. 7.
Appellants argue that, "Pahwa, Factor, Carson, and Padmanabhan fail
to disclose or suggest using tolcapone to inhibit a Flavivirus protease." App.
Br. 11.
ANALYSIS
While at first it may seem inapposite based on our conclusion with
respect to rejection 1, we do not find that the Examiner has provided
evidence to support a prima facie case that the elected species, tolcapone,
inhibits a Flavivirus protease, as claimed. Unlike claim 1, claim 16 is
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directed to a method of inhibiting a Flavivirus protease in a cell, comprising:
contacting a cell with an effective amount of a tolcapone compound or a
pharmaceutically acceptable salt thereof. We find that the preamble claim
language, "a method of inhibiting a Flavivirus protease in a cell," is
necessary to give life and meaning to the claim. Seachange International,
Inc. v. C-Cor Inc. (Fed. Cir. 2005) (preamble a limitation where it provides
antecedent basis for terms in the claim body). The preamble of claim 16
provides antecedent basis for the effective amount of tolcapone compound
claimed (effective amount to inhibit Flavivirus protease in a cell.)
Unlike rejection 1, we do not find that the Examiner has provided a
legally sufficient rationale, motivation or reason to combine the cited
references to reject claim 16. Padmanabhan discloses that Flavivirus
protease inhibitors other than tolcapone were known to those of ordinary
skill in the art, and that they were known to treat Flavivirus infection.
Padmanabhan, p. 8. The Examiner does not point to any specific compound
in Padmanabhan having the structure of tolcapone that functions as a
Flavivirus protease inhibitor. The Examiner argues that Pahwa, Factor, and
Carson, disclose the administration of tolcapone in an effective amount to
treat movement disorders and parkinsonism, including movement disorders
common to patients having West Nile Virus. However, the Examiner has
not provided persuasive evidence that the ordinary artisan would have
expected that tolcapone would function as a Flavivirus protease inhibitor, as
required by claim 16.
The Examiner argues that, "[t]he skilled artisan would have been
motivated to administer the combination of tolcapone with the antiviral
compounds of Padmanabhan et al. because the combination would have
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been expected to treat both the WNV infection and the Parkinsonism
symptom of WNV infection." Final Act. 8.
What is missing from the Examiner's analysis is why one of ordinary
skill in the art, desiring to inhibit a Flavivirus protease, would have
combined Padmanabhan, disclosing Flavivirus protease inhibitors (not
indicated by the Examiner to include the elected species of Flavivirus
protease inhibitor, tolcapone ), with three references disclosing the treatment
of movement disorders (a symptom of Flavivirus infection). The Examiner
cannot rely on the inherent protease-inhibiting properties of tolcapone here
without a sufficient reason to administer tolcapone in the first place. Nor
can the Examiner rely on obviousness without a motivation to combine the
cited references, or a nexus between the references that evidences that
tolcapone functions as a Flavivirus protease inhibitor, as required by claim
16.
In other words, claim 16 requires that the elected species, tolcapone,
function as a Flavivirus protease inhibitor (not just that tolcapone treat a
symptom of Flavivirus infection). We do not find the Examiner's rationale
that the cited references each treat Flavivirus infection or its symptoms, to
be a legally sufficient rationale for selecting tolcapone, a known movement
disorder drug, and combining it with a Flavivirus protease inhibitor (not the
elected species), to meet the claim requirement that tolcapone is a Flavivirus
protease inhibitor.
The rejection of claims 16, and 24-26 is reversed.
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CONCLUSION OF LAW
The cited references support the Examiner's obviousness rejection 1,
which is affirmed for the reasons of record. The rejection of claims 14 and
15 is also affirmed. The rejection of claims 16, and 24-26 is reversed. We
limit this Decsision to the single issue of the elected species and take no
position respecting the patentability of the broader generic claims, including
the remaining, non-elected species.
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-IN-PART
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