Ex Parte Hasegawa et al

Patent Trial and Appeal Board

Sep 27, 2017

13642639 (P.T.A.B. Sep. 27, 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.
13/642,639 01/01/2013 Hiroyuki Hasegawa 95662-IN002-US 3463
90042 7590 09/29/2017
MANET T T NFT TFR PT T C EXAMINER
1725 I Street, N.W. IVANOVA, SVETLANA M
Suite 300
Washington DC, DC 20006 ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
09/29/2017 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):
melcher @ mdslaw .com
j effsmelcher @ att. net
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HIROYUKI HASEGAWA and SHIN AIZAWA
Appeal 2016-004524
Application 13/642,6391
Technology Center 1600
Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
DAVID COTTA, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a process of
treating depression. The Examiner rejected the claims for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The compound “sepiapterin,” sometimes referred to as “SP” in the
Specification and in Appellants’ briefings, “is an endogenous compound
which widely occurs as an animal pigment in a variety of animals including
humans and also contained in daily foods in trace amounts.” Spec. 116; see
also id. 1151 (referring to sepiapterin as “SP”); Appeal Br. 3 (same). “It is
1 Appellants state that “[tjhis application is owned by Hiroyuki Hasegawa.”
Appeal Br. 1.
Appeal 2016-004524
Application 13/642,639
known that sepiapterin is easily taken up into animal cells and converted to
tetrahydrobiopterin [“BH4”] through two-step enzymatic reactions. Id. ^ 18.
“Tetrahydrobiopterin (BH4)... is a coenzyme which is essential for
enzymatic reactions such as reactions for synthesis of tyrosine from
phenylalanine, synthesis of serotonin from tryptophan, synthesis of dopa
from tyrosine and synthesis of nitric oxide and citrulline from arginine.” Id.
112.
“[SJepiapterin passes through the blood-brain barrier on peripheral
administration of sepiapterin and is taken up into neurons in the brain and
also facilitates production of aromatic monoamines in the brain, thereby
increasing their bioavailability.” Id. 125 (emphasis omitted).
Claims 15 and 16 illustrate the appealed subject matter, and read as
follows (Appeal Br. 16):
15. A method for improving depression, the method
comprising administering to a patient suffering from depression
an effective dose of sepiapterin via a peripheral route of
administration, wherein the effective dose is from 0.1 to 100
mg/kg of body weight per day, and wherein the effective dose
increases the level of aromatic monoamines in the brain of the
patient.
16. The method of claim 15 wherein sepiapterin is
administered orally to the patient to provide a dose from 0.1 to
100 mg/kg of body weight per day.
2
Appeal 2016-004524
Application 13/642,639
The sole rejection before us for review is the Examiner’s rejection of
claims 15—18, 21, and 22, under 35 U.S.C. § 103(a) for obviousness over
Curtius2 and Clelland.3 Ans. 4—6.
OBVIOUSNESS
The Examiner’s Prima Facie Case
The Examiner found that Curtius discloses treating depression by
administering sepiapterin at a dosage rate encompassed by Appellants’
claims. Ans. 4.
As to the rejected claims’ “wherein” clause, requiring the effective
dose of the drug to increase the level of aromatic monoamines in the brain of
the patient, the Examiner “interprets this as a functional limitation in view of
well-established case law, which provides that Appellant’s mere discovery
of a previously unappreciated property of a prior art composition does not
render the old composition patentably new to the discoverers.” Id. at 4—5
(citing Atlas Powder Co. v. Ireco, Inc., 190 F.3d 1342, 1347 (Fed. Cir.
1999). The Examiner also concluded that the rejected claims’ “wherein”
clause was essentially “a whereby clause in a method claim [that] is not
given weight when it simply expresses the intended result of a process step
positively recited.” Id. at 5 (internal quotations omitted)
The Examiner found that Curtius differs from the rejected claims in
that “Curtius does not explicitly disclose intravenous administration.” Id.
To address that difference, the Examiner cited Clelland as disclosing
the treatment of a patient “at risk of or presence of schizophrenia or
schizoaffective disorder (which per Appellant’s specification further is
2 US 4,758,571 (issued July 19, 1988).
3 US 2012/0114767 A1 (published May 10, 2012).
3
Appeal 2016-004524
Application 13/642,639
cerebral dysfunction) with an effective amount of a pterin compound, such
as sepiapterin, wherein the administering can be intravenous or oral, (claim
15, [0085]).” Ans. 5. In addition, the Examiner found that Clelland
“provides for treatments such as biopterin, BH4 or other pterin species
(which have been successfully used to treat autism and other disorders in
children, and depression and other disorders in adults, and so safe
therapeutic doses have previously been determined). ([0024]).” Id.
In light of the references’ disclosures, the Examiner concluded that it
would have been obvious “to combine the teachings of Curtius and Clelland
in order to treat depression or an alternative cerebral dysfunction with a
reasonable expectation of success by either oral or intravenous
administration.” Id. at 6. The Examiner reasoned that a “person of skill in
the art would have been motivated to do so because both routes of
administration were already disclosed for the treatment of disorders of
cerebral dysfunction with the specific pterin sepiapterin.” Id.
Analysis
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.
Appellants do not argue any of the rejected claims separately. We
select claim 15 as representative of the rejected claims. 37 C.F.R.
§ 41,37(c)(l)(iv). Appellants do not persuade us that a preponderance of the
evidence fails to support the Examiner’s conclusion of obviousness as to
claim 15.
4
Appeal 2016-004524
Application 13/642,639
Claim 15 recites a method for improving depression. Appeal Br. 16.
Claim 15 requires administering sepiapterin to a patient suffering from
depression at a dosage rate of from 0.1 to 100 mg/kg of body weight per day.
Id. Claim 15 requires the sepiapterin to be administered “via a peripheral
route of administration.” Id. Claim 15 recites that the sepiapterin must
increase the level of aromatic monoamines in the brain of the patient. Id.
As required by claim 15, Curtius teaches administering sepiapterin to
a patient suffering from depression. Curtius, abstract (“L-sepiapterin . . . can
be used for the therapeutic treatment... of patients with depression.”); see
also id. at 1:17—54 (sepiapterin listed as one of four compounds, along with
BH4, useful for treating depression).
Curtius teaches administering its depression-treating compounds at
dosages falling within claim 15’s range of 0.1 to 100 mg/kg of body weight
per day:
Treatment of patients . . . with depression can start with
an initial dose of the order of 1 g/day (about 15 mg/kg of body
weight) and be continued, for example, with a dose of 500 mg
(about 7.5 mg/kg) on the second day and of 200 mg/day (about
3 mg/kg) from the third day.
Id. at 4:3—8.
Given these teachings, we agree with the Examiner that Curtius
teaches or suggests administering the agent required by claim 15, to the
patient required by claim 15, at a dosage encompassed by claim 15.
Although Curtius does not include working examples in which depression is
treated by administering sepiapterin, Curtius includes a number of examples
in which BH4 is administered to patients suffering from depression (id. at
2:15—52), and discloses that the BH4 was administered orally (id. at 1:55—
5
Appeal 2016-004524
Application 13/642,639
64). We, thus, also agree with the Examiner that Curtius suggests
administering sepiapterin orally in its methods of treating depression.
Appellants contend that oral administration of sepiapterin as
suggested by Curtius is “irrelevant to the claimed invention” because
claim 15 requires peripheral administration. Appeal Br. 5; see also id. at 3
(“A ‘peripheral route’ means injection intravenously through a peripheral
vein.”).
The Examiner responds that the peripheral route of administration
recited in claim 15 encompasses oral administration, as evidenced by
Appellants’ Specification, and also by the fact that claim 16, which depends
from claim 15, recites oral administration. Ans. 8.
Appellants do not reply to, or assert error in, the Examiner’s
contentions in the Answer as to this claim interpretation issue. See Reply
Br., generally.
We find that the Examiner has the better position.
It is well settled that during examination, the PTO must interpret
terms in a claim using “the broadest reasonable meaning of the words in
their ordinary usage as they would be understood by one of ordinary skill in
the art, taking into account whatever enlightenment by way of definitions or
otherwise that may be afforded by the written description contained in the
applicant’s specification.’ '’ In re Morris, 127 F.3d 1048, 1054 (Fed. Cir.
1997) (emphasis added).
Example 4 of Appellants’ Specification describes an experiment in
which sepiapterin and BH4 were administered orally to rats. Spec. 125—
128. In discussing the results of that experiment, the Specification states as
follows:
6
Appeal 2016-004524
Application 13/642,639
The above results have shown that peripheral
administration of sepiapterin increases the amount of
tetrahydrobiopterin in the brain. The results have also shown
that peripheral administration of tetrahydrobiopterin [BH4] at
the same dose does not increase the amount of
tetrahydrobiopterin in the brain.
The above results have suggested that on peripheral
administration of sepiapterin, a part of sepiapterin goes beyond
the blood-brain barrier to reach the brain, then, is taken up into
neurons capable of synthesizing aromatic monoamines in the
brain and converted to tetrahydrobiopterin, thus resulting in an
increase in the amount of serotonin in the brain. Furthermore,
peripheral administration of tetrahydrobiopterin at the same
dose does not significantly increase the amount of serotonin in
the brain, showing that tetrahydrobiopterin which has been
peripherally administered does not substantially reach aromatic
monoamine synthetic cells due to some hindrance.
Spec. 134—138 (emphasis added).
Thus, Appellants’ Specification repeatedly refers to oral
administration as peripheral administration. Moreover, as the Examiner
contends, and as seen above, claim 15 recites administration via a peripheral
route, and claim 16, which depends from claim 15, recites oral
administration. Appeal Br. 16. In addition, Appellants do not advance any
specific evidence supporting their contention that an ordinary artisan would
have understood that the term “peripheral route of administration” in claim
15 would exclude the oral administration of sepiapterin suggested by
Curtius.
In sum, for the reasons discussed, we agree with the Examiner that
Curtius teaches or suggests administering the agent required by claim 15, to
the patient required by claim 15, at a dosage encompassed by claim 15,
using a route of administration encompassed by claim 15.
7
Appeal 2016-004524
Application 13/642,639
As to claim 15’s “wherein” clause requiring the administered
sepiapterin to increase the level of aromatic monoamines in the brain
(Appeal Br. 16), we agree with the Examiner that the clause simply recites a
result of performing the positive process steps recited in the remainder of the
claim. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d
1165, 1172 (Fed. Cir. 1993) (“A ‘whereby’ clause that merely states the
result of the limitations in the claim adds nothing to the patentability or
substance of the claim.”).
Because Curtius teaches or suggests a process having all of the steps
and features required by claim 15, we find that the Examiner that has
advanced evidence sufficient to show that the process recited in claim 15
would have been prima facie obvious to an ordinary artisan.
Appellants’ arguments do not persuade us to the contrary.
Appellants contend, for a number of reasons, that Curtius does not
enable treating depression with sepiapterin. Appeal Br. 5, 11—14; Reply Br.
3—6. Appellants summarize their contentions in that regard as follows:
1. The experimental evidence of record shows that SP
surprisingly passes the blood brain barrier and converts to BH4
in the brain. BH4 does not pass the blood brain barrier like SP.
Curtius does not disclose this difference. Curtius provides
experimental evidence for BH4 and then merely concludes that
SP is an equivalent to BH4.
2. The Examiner admits that BH4 is not an equivalent to SP, so
the teaching Curtius that BH4 and SP are equivalents is wrong.
3. The inventors of Curtius, Dr. Curtius and Dr. Niederwi[e]ser,
admit in later publications that the ranges for BH4 in the main
reference Curtius are erroneous and do not work.
Reply Br. 4.
Appellants may rebut the Examiner’s prima facie case of obviousness
by showing that the cited prior art did not “enable one skilled in the art to
8
Appeal 2016-004524
Application 13/642,639
produce the now-claimed invention ... by presenting sufficient reason or
authority or evidence, on the facts of the case, to show that the prior art
method would not produce or would not be expected to produce the claimed
subject matter.” In re Kumar, 418 F.3d 1361, 1368 (Fed. Cir. 2005) (citing
In re Payne, 606 F.2d 303, 314—15 (CCPA 1979); but see Amgen, Inc. v.
Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1357 (Fed. Cir. 2003)
(remanding case to district court to reconsider obviousness without reference
to whether patent at issue was enabled, explaining “[ujnder § 103,... a
reference need not be enabled; it qualifies as a prior art, regardless, for
whatever is disclosed therein”); see also In re Antor Media Corp., 689 F.3d
1282, 1292 (Fed. Cir. 2012) (“[A] non-enabling reference may qualify as
prior art for the purpose of determining obviousness under § 103.”) (quoting
Symbol Techs. Inc. v. Opticon Inc., 935 F.2d 1569, 1578 (Fed. Cir. 1991).
In the present case, we are not persuaded that Appellants have
advanced sufficient evidence to show that orally administering sepiapterin at
the dosage levels taught in Curtius would not treat, or would not be expected
to treat, depression. Even assuming, for the sake of argument, that
sepiapterin unexpectedly passes the blood brain barrier, Appellants fail to
explain how that property demonstrates that orally administering sepiapterin
at the dosage levels taught in Curtius would not treat, or would not be
expected to treat, depression.
Similarly, that the Examiner might have conceded that sepiapterin and
BH4 are not equivalent in some respect, or that Curtius might have failed to
recognize the different properties of sepiapterin and BH4, does not provide
an adequate evidentiary basis for concluding that orally administering
sepiapterin at the dosage levels taught in Curtius, precisely as required by
9
Appeal 2016-004524
Application 13/642,639
Appellants’ claim 15, would not treat, or would not be expected to treat,
depression.
Further, although we acknowledge Appellants’ contentions that
Brand4 and the other publications Appellants cite (Appeal Br. 12—14; Reply
Br. 5—6) suggest that the dosages taught in Curtius were too low for BH4,
we do not find those contentions persuasive as to claim 15. We first note
that, contrary to the alleged ineffectiveness of BH4 at the dosages described
in Curtius, Curtius discloses that positive results were obtained when
treating patients with BH4 according to the disclosed dosages. See, e.g.
Curtius 1:60—64 (“After oral administration of one gram of BH4 (stabilized
against oxidation by the addition of 100 mg of ascorbic acid) in orange juice,
a prompt improvement in the clinical picture of severe depression occurred
after about 4—5 hours.”); see also id. at 2:15—52 (result shown in two
patients). Appellants, moreover, do not advance specific evidence
suggesting that any later-discovered deficiencies as to the BH4 dosages
taught in Curtius would have suggested to an ordinary artisan that
sepiapterin, a different compound, would also fail to treat depression at the
dosages taught in Curtius.
Thus, Curtius expressly describes successful results using BH4 at the
dosage rates taught therein, and Appellants do not advance a specific
evidentiary basis for concluding that any later-discovered deficiencies as to
Curtius’s dosages with respect BH4 would also be deficient as to
sepiapterin, a different compound. Appellants, therefore, do not persuade us
4 Michael P. Brand et al., Neurochemical Effects Following Peripheral
Administration of Tetrahydropterin Derivatives to the hvh-1 Mouse, 66 J.
Neurochem. 1150-1156 (1996).
10
Appeal 2016-004524
Application 13/642,639
that they have advanced evidence sufficient to show that orally
administering sepiapterin at the dosage levels taught in Curtius, precisely as
required by Appellants’ claim 15, would not treat, or would not be expected
to treat, depression.
We acknowledge, but do not find persuasive, Appellants’ argument
that Curtius does not teach or suggest a method of increasing the levels of
aromatic monoamines in the brain. See Appeal Br. 14—15; Reply Br. 7. As
noted above, we agree with the Examiner that claim 15’s wherein clause,
requiring the sepiapterin to increase the level of aromatic monoamines in the
brain, simply recites a result of performing the positive process steps recited
in the remainder of the claim. See Texas Instruments, Inc. v. International
Trade Comm., 988 F.2d at 1172.
That is, claim 15 requires no action, other than administering
sepiapterin at the claimed dosage, by the claimed route of administration, to
the claimed patient, to achieve the claimed increase in brain aromatic
monoamines. As discussed above, we agree with the Examiner that Curtius
teaches or suggests administering sepiapterin at the claimed dosage, by the
claimed route of administration, to the claimed patient.
In other words, Curtius suggests performing the sole active process
step required by claim 15. Thus, that Curtius might not mention or
recognize that administering sepiapterin to a patient suffering from
depression would increase the level of aromatic monoamines in the brain
does not demonstrate that the process recited in claim 15 would have been
unobvious. See In re Baxter-Travenol Labs., 952 F.2d 388, 392 (Fed. Cir.
1991) (“Mere recognition of latent properties in the prior art does not render
nonobvious an otherwise known invention.”); see also, In re Woodruff, 919
11
Appeal 2016-004524
Application 13/642,639
F.2d 1575, 1577—78 (Fed. Cir. 1990) (obviousness rejection affirmed where
using claimed elements in the manner suggested by the prior art necessarily
resulted in claim-recited effect).
We acknowledge, but find unpersuasive, Appellants’ contentions that
sufficient evidence of unexpected results has been advanced to outweigh the
evidence of prima facie obviousness. See Appeal Br. 6—11 (citing Examples
1, 3, 4, 5, and 6 from the Specification); Reply Br. 8—11.
We have carefully reviewed the evidence of unexpected results
advanced by Appellants. It is well settled, however, that “[ejvidence of
secondary considerations must be reasonably commensurate with the scope
of the claims.” In re Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011)
In the present case, claim 15 is directed to improving depression.
Appeal Br. 16. Example 6 is the only one of the examples cited by
Appellants that is described in the Specification as relating directly to
treating depression. See Spec. 1148 (Example 6) (“The forced swim test of
the mice is a test method for evaluating antidepressant effects, and length of
‘immobile’ time is a criterion of depression. Evaluation is made in such a
manner that the shorter the ‘immobile’ time is, the greater the antidepressant
effects are.”).
The remaining examples cited by Appellants are not directed to
treating depression, nor are they directed to an animal model of the disorder.
See id. ]Hf 89, 115 (Examples 1 and 3 involving cultured cells); ]Hf 125—139
(Example 4 measuring amount of brain BH4, serotonin, and serotonin
metabolite resulting from oral administration of sepiapterin and BH4 to rats;
no mention of relationship to depression); || 140—146 (Example 5
measuring amount of brain serotonin resulting from oral administration of
12
Appeal 2016-004524
Application 13/642,639
sepiapterin and BH4 to mice; no direct mention of relationship to
depression; rather, stating “the above results have suggested that peripheral
administration of sepiapterin may also be effective in improving central
mental disorders and central motor disorders which are involved in
decreased levels of dopamine, noradrenaline and adrenaline in the brain”
(emphasis added)).
Thus, because Appellants’ Examples 1,3,4, and 5 are not directed to
treating depression, nor are they directed to an animal model of the disorder,
Examples 1,3,4, and 5 do not involve results that come from a process
encompassed by representative claim 15. Appellants do not persuade us,
therefore, that the results shown in Examples 1,3,4, and 5 are
commensurate in scope with the process recited in representative claim 15.
As to Appellants’ Example 6, we are not persuaded that Appellants
have shown that the results were actually unexpected.
We acknowledge Appellants’ assessment in their Specification of the
results in Example 6:
As shown in Fig. 7, a group [of mice] treated with
sepiapterin was significantly short in “immobile” time as
compared with a group treated with tetrahydrobiopterin [BH4]
and the control group. Thus, anti-depressant effects were
obtained. Furthermore, the group treated with sepiapterin was
also effective in shortening “immobile” time to an extent
similar to the positive control group [which received the known
antidepressant despiramine].
Spec. 1152 (emphasis added).
We acknowledge also Appellants’ assessment that the results in
Example 6, when viewed alongside the results of Examples 1—5, that “have
suggested that the present invention is effective in preventing, improving
and treating central mental disorders such as depression . . . .” Spec. 1154.
13
Appeal 2016-004524
Application 13/642,639
As our reviewing court has advised, however, “any superior property
must be unexpected to be considered as evidence of non-obviousness.”
Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007).
In the present case, as discussed above, Curtius teaches that
administering sepiapterin at a dosage encompassed by claim 15 is effective
to treat depression. Given Curtius’s teachings, Appellants do not persuade
us that it was unexpected that antidepressant effects were obtained when
administering sepiapterin in an animal model of depression.
Moreover, “[m]ere improvement in properties does not always suffice
to show unexpected results. . . . [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.” In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995).
In the present case, as noted above, rather than stating that the results
obtained were unexpected or surprising, the Specification states merely that
“anti-depressant effects were obtained” (Spec. 1152) and that the results
“have suggested that the present invention is effective in preventing,
improving and treating central mental disorders such as depression” {id.
1154 (emphasis added)).
We acknowledge Appellants’ contention that, because sepiapterin
performed better than BH4 in the experiments in Appellants’ examples, and
because Curtius allegedly treats sepiapterin and BH4 as equivalents,
Appellants’ examples provide evidence of unexpected results sufficient to
outweigh the evidence of prima facie obviousness. See Appeal Br. 9; Reply
Br. 10.
14
Appeal 2016-004524
Application 13/642,639
However, the only assertions that the superior properties of
sepiapterin as compared to BH4 were unexpected appears in Appellants’
briefs, in the form of argument by counsel. That is, Appellants do not
identify in the record any statements, which are not attorney argument,
averring that the results shown in the cited examples in the Specification
were actually unexpected. Argument by counsel is not an adequate
substitute for actual evidence that the results presented constitute an
unexpected result over the prior art. See In re Geisler, 116 F.3d 1465, 1471
(Fed. Cir. 1997).
In sum, for the reasons discussed, Appellants do not persuade us that a
preponderance of the evidence fails to support the Examiner’s conclusion
that representative claim 15 would have been prima facie obvious to an
ordinary artisan in view of Curtius. Because, for the reasons discussed,
Appellants’ asserted evidence of unexpected results does not outweigh the
evidence of prima facie obviousness, we affirm the Examiner’s rejection of
claim 15 over Curtius and Clelland. Because they were not argued
separately, claims 16—18, 21, and 22 fall with claim 15. 37 C.F.R.
§ 41.37(c)(l)(iv).
SUMMARY
For the reasons discussed, we affirm the Examiner’s rejection of
claims 15—18, 21, and 22, under 35 U.S.C. § 103(a) for obviousness over
Curtius and Clelland.
15
Appeal 2016-004524
Application 13/642,639
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).
AFFIRMED
16