Ex Parte Konofal

Patent Trials and Appeals Board

May 22, 2019

10559293 - (D) (P.T.A.B. May. 22, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/559,293 01/19/2006
38824 7590 05/24/2019
NORTON ROSE FULBRIGHT US LLP
Attn: MN IP Docket
98 San Jacinto Boulevard
Suite 1100
Austin, TX 78701-4255
FIRST NAMED INVENTOR
Eric Konofal
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.
CABR-022/US 1547
EXAMINER
KASSA, TIGABU
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
05/24/2019 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):
mnipdocket@nortonrosefulbright.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ERIC KON OF AL
Appeal2018-007451
Application 10/559,293 1
Technology Center 1600
Before DONALD E. ADAMS, ELIZABETH A. LA VIER, and
RYAN H. FLAX, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This Appeal under 35 U.S.C. § 134(a) involves claims 1, 5-9, and 23-
25 (Ans. 2 3). Examiner entered rejections under 35 U.S.C. § 103(a). We
have jurisdiction under 35 U.S.C. § 6(b ).
We REVERSE.
1 Appellant identifies "NLS Pharma AG" as the real party in interest
(Appellant's January 8, 2018 Appeal (Br.) 2).
2 Examiner's May 3, 2018 Answer.
Appeal2018-007451
Application 10/559,293
STATEMENT OF THE CASE
Appellant's disclosure "relates to the use of iron or of a
pharmaceutically acceptable salt thereof, alone or in combination with one
or more psychostimulant compounds, for preparing a medicinal product for
use in the treatment of ADHD and of the associated symptoms" (Spec. 1: 8-
12). Claims 1, 5-8, 24, and 25 are representative and reproduced below:
1. A method for the treatment of attention deficit hyperactivity
disorder (ADHD) as defined in the DSM IV in a patient in need
thereof comprising administering an effective amount of an iron
supplement in the form of a pharmaceutically acceptable iron
salt or organic iron or iron atom to said patient wherein said
patient is a child of between 5 and 12 years old affected by a
ferritin deficiency with a serum ferritin concentration of less
than 50 µg/L and who also has a normal serum concentration of
soluble transferrin receptors, and wherein iron is administered
in a dosage that corresponds to a daily intake of ferrous sulfate
of between 100 mg and 2 g per day, in one or more intakes, in
the absence of another active agent.
(Br. 9.)
(Id.)
(Id.)
(Id.)
5. The method as claimed in claim 1, wherein the
pharmaceutically acceptable iron salt is selected from ferrous
salts and ferric salts.
6. The method as claimed [in] claim 24, wherein the iron salt is
ferric sulfate.
7. The method as claimed in claim 1, wherein the
pharmaceutically acceptable iron atom is in the form of iron
dextran, iron sucrose, iron polymaltose or iron sorbitol.
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(Id.)
(Id.)
(Id.)
8. The method as claimed in claim 1, wherein the
pharmaceutically acceptable organic iron is in the form of iron
biglycinate, iron glycinate or iron protein succinylate.
24. The method of claim 5, wherein the pharmaceutically
acceptable iron salt is selected from the group consisting of
ferric ammonium citrate, ferric pyrophosphate, ferritin,
ferrocholinate, ferrous ascorbate, ferrous aspartate, ferrous
chloride, ferrous sulfate, ferrous tartrate, ferrous fumarate,
ferrous gluconate, ferrous gluceptate, ferrous glycine sulfate,
ferrous lactate, ferrous oxalate and ferrous succinate.
25. The method of claim 6, wherein the ferrous sulfate is
gastroprotected.
Grounds of rejection before this Panel for review:
I. Claims 1, 5, 6, 9, 23, and 24 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination ofBruner, 3 Yehuda, 4
Goldman, 5 Arnold, 6 and Beguin. 7
3 Bruner et al., Randomised study of cognitive effects of iron
supplementation in non-anaemic iron-deficient adolescent girls, 348 THE
LANCEt 992-96 (1996).
4 Yehuda et al., Brain Iron: [A] lesson from animal models, 50 AM J. CLIN.
NUTR. 618-29 (1989).
5 Goldman et al., Diagnosis and Treatment of Attention-
Deficit/Hyperactivity Disorder in Children and Adolescents, 279 JAMA
1100----07 (1998).
6 L. Eugene Arnold, Alternative Treatments for Adults with Attention-Deficit
Hyperactivity Disorder (ADHD), 931 ANNALS NEW YORK ACADEMY OF
SCIENCES 310--41 (2001).
7 Yves Beguin, Soluble transferrin receptor for the evaluation of
erythropoiesis and iron status, 329 CLINICA CHEMICA ACTA 9-22 (2003).
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Application 10/559,293
II. Claim 7 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Bruner, Y ehuda, Goldman, Arnold, Beguin, and
Barton. 8
III. Claim 8 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Bruner, Y ehuda, Goldman, Arnold, Beguin, and
Pineda. 9
IV. Claim 25 stands rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Bruner, Y ehuda, Goldman, Arnold,
Beguin, and Horvath. 10
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Bruner discloses that "[i]ron deficiency is a systemic condition,
which has many non-haematological consequences: it impairs physical
endurance, work capacity, infant growth and development, and depresses
immune function" and "people who receive iron for iron-deficiency anaemia
8 Barton et al., Intravenous Iron Dextran Therapy in Patients with Iron
Deficiency and Normal Renal Function Who Failed to Respond to or Did
Not Tolerate Oral Iron Supplementation, 109 AM. J. MED. 27-32 (2000).
9 Pineda et al., Effectiveness of Treatment of Iron-Deficiency Anemia in
Infants and Young Children With Ferrous Bis-glycinate Chelate, 17
NUTRITION 381-84 (2001).
10 Horvath et al., Tardyferon therapy in hyposiderosis of infancy and
childhood, 40 THER. HUNG. 40--3 (1992). Consideration limited to PubMed
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1585284 (last
accessed March 19, 2014).
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commonly report improved memory, attention, mood, and energy before any
improvement in haemoglobin indices." (Bruner 992; see Final Act. 3).
FF 2. Bruner discloses that "[d]ecreased brain iron stores may impair the
activity of iron-dependent enzymes necessary for the synthesis, function, and
degradation of neurotransmitters, such as dopamine, serotonin, and
noradrenaline" (Bruner 992; see Final Act. 3).
FF 3. Bruner provides a "[ r ]andomised study of cognitive effects of iron
supplementation in non-anaemic iron-deficient adolescent girls," wherein
"[p]articipants were randomly assigned oral ferrous sulphate (650 mg twice
daily) or placebo for 8 weeks" and observed that "[a]fter the 8-week
intervention, the treatment group had a significantly higher mean serum
ferritin concentration than the control group" and "even in the absence of
anaemia, iron supplementation improves some aspects of cognitive
functioning in iron-deficient adolescent girls" (Bruner, Title; id. at 992, 994,
and 995; see Final Act. 3).
FF 4. Examiner finds that Bruner does not disclose "iron supplementation
of individuals with ADHD" or a "patient population having [an] age
between 5 and 12 years old" (Final Act. 4).
FF 5. Yehuda discloses:
Iron deficiency (ID) and anemia are the most prevalent
nutritional disorders in the world. The behavioral changes
induced by ID in adults include unusual lethargy, irritability,
apathy, listlessness, fatigue, lack of ability to concentrate,
pagophagia (pathological craving for ice) and pica, inattention,
hypoactivity, and sometimes a decreased IQ. In children ID
may be one of the causes of hyperactivity.
(Yehuda 618; see Final Act. 4.)
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FF 6. Y ehuda discloses:
Nutritionally induced ID in rats can serve as a very useful
model for ID in humans. Not only does this model appear to
mimic the mode of action of ID ( decrease in the functional
activity of the D2 dopaminergic system, as evident from the
changes in thermoregulation, motor activity, stereotypy, and
pain threshold), but ID rats exhibited cognitive deficits in
learning and memory tasks that involve attention, as do humans
suffering from ID. A positive correlation was found between
the behavioral changes, the length of the feeding period, and the
level of Hb in the blood.
(Y ehuda 624; see Final Act. 4; cf Y ehuda 618 ("there are many differences
between the rates of neuronal and biochemical development in rats and in
humans"); id. at 622 (Yehuda's "results showed that ID rats learning
capacity was significantly inferior to that of control rats. The longer the
rates were kept on the ID diet, the greater the deficit in learning" and ID rats
"fed an iron-supplemented diet and [ water maze tested] 2, 4, 6 or 8 wk later
[exhibited] [n]o restoration of learning and/or memory").)
FF 7. Goldman discloses that "[ e ]pidemiologic studies using standardized
diagnostic criteria suggest that 3% to 6% of the school-aged population
( elementary through high school) may suffer from ADHD, although the
percentage of US youth being treated for ADHD is at most at the lower end
of this prevalence range" (Goldman 1100; see Final Act 5 (Goldman's
disclosure that "3% to 6% of the school-aged population (elementary school
through high school) may suffer from ADHD which clearly overlaps with
[Appellant's] age group [of] between 5 and 12") (emphasis omitted)).
FF 8. Examiner finds that
Arnold sites the research of Bruner et al. in the context of
ADHD. Arnold, furthermore notes that in a trial of
gastroprotected ferritin in 33 iron-deficient children, Burattini et
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al. found a decrease of hypreractivity. Arnold concludes that
iron supplementation may be particularly relevant for ADHD
women of menstruation, whose iron stores are often
compromised (Iron Supplementation, p 319). Arnold,
furthermore, indicates that the review depends mostly on
research in children/adolescents (top of page 311 ).
(Final Act. 5 ( emphasis omitted).)
FF 9. Examiner finds that the combination of Bruner, Y ehuda, Goldman,
and Arnold does not "teach the normal serum concentration of soluble
transferrin receptors" and finds that Beguin makes up for this deficiency
(Final Act. 6 (citing Beguin § 4.1 and Figure 3)) (Examiner finds that
"Beguin teaches serum [transferrin] levels are marginally increased in
nonanemic iron-deficient subjects but more dramatically so in patients with
iron deficiency anemia. Therefore, the serum levels of [ transferrin] may
be ... within the range that is considered normal")).
ANALYSIS
Rejection I:
Based on the combination of Bruner, Y ehuda, Goldman, Arnold, and
Beguin, Examiner concludes that, at the time Appellant's invention was
made, it would have been prima facie obvious "to provide iron
supplementation to iron deficient individuals with ADHD because Y ehuda et
al. teach the link between iron deficiency and hyperactivity in children" and
to
provide iron supplementation to individuals with ADHD having
ages between 5 and 12 because Goldman ... indicates that ...
3% to 6% of the school-aged population (elementary school
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through high school) may suffer from ADHD which clearly
overlaps with the age group between 5 and 12.
(Final Act. 6-7 ( emphasis omitted)). Examiner also concludes that, at the
time of Appellant's claimed invention, it would have been prima facie
obvious to a person of ordinary skill in this art to "optimize the dosage of
iron since routine optimization is within the purview of the ordinarily skilled
artisan" and "provide iron supplements to patients with iron deficiency and
normal serum [transferrin] levels [because] iron deficient individuals need
supplementation with iron even if serum [transferrin] levels are within
normal range" (id. at 8). We are not persuaded.
Appellant and Examiner both appreciate that "Bruner, is not directed
towards treatment of ADHD" or a "patient population having [an] age
between 5 and 12 years old" (FF 4; see also Br. 3). To the contrary, as
Appellant explains, "Bruner examines the cognitive effects of iron
supplementation in a group that is at risk of developing iron deficiency
because of increased demand during puberty and menstrual losses" (Br. 3;
see id. ("the cohort examined by Bruner is a group of high school girls aged
13-18," which is outside the age range set for the in Appellant's claimed
invention)). Appellant further explains that, in contrast to Appellant's
claimed invention, "the cohort examined by Bruner is merely supplemented
with iron because it is a high iron-demand group" that "did not present
ADHD symptoms" (id.; see id. ("The tests employed by Bruner did not seek
to examine or address" the clinically recognized "criteria for diagnosis of
ADHD")). Thus, Appellant contends "treating ADHD in children between
the ages of 5 and 12 years old[, as set forth in Appellant's claimed
invention,] is different from supplementing iron in the high iron-demand
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group of pubescent girls that are outside of the presently claimed age range"
(Br. 3).
Appellant explains that, as with Bruner, "Y ehuda [also] does not focus
on a young, developing patient population that presents ADHD," but instead
"employs a post-developmental rat model in which behavioral changes are
induced by iron deficiency" (Br. 4). Thus, Appellant contends that
Yehuda's "non-developmental cohort of rats provides subjects with neuronal
physiologies that are distinct from the 5 to 12 year-old children population
recited in ... [Appellant's] claims" (id.; see also id. at 4--5 (Yehuda
concedes "that the rate of neuronal development is different between rats
and humans" and found that feeding ID rats an iron-supplemented diet failed
to restore learning and/or memory of the ID rats); FF 6; cf Ans. 7-8 and 9-
10). For the foregoing reasons, we agree with Appellant's contention that
"Y ehuda does not cure the deficiencies of Bruner" (Br. 5).
As Appellant explains, although "Goldman indicates 3% to 6% of the
school-aged population may suffer from ADHD," "Goldman ... does not
teach or suggest that iron may be used to treat ADHD patients" (Br. 5; see
FF 7; Ans. 8). Thus, we find that Goldman fails to make up for the
deficiencies in the combination of Bruner and Y ehuda. Similarly, Examiner
fails to establish that Arnold's conclusion "that iron supplementation may be
particularly relevant for ADHD women of menstruation, whose iron stores
are often compromised" makes up for the foregoing deficiencies in the
combination of Bruner, Y ehuda, and Goldman (see FF 8; see also Ans. 8-9
an dlO; see generally Br. 5-6). The same is true of Examiner's reliance on
Beguin, which, as Appellant explains, "does not teach or suggest that iron
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administration may be used to treat ADHD in children" (Br. 6; see FF 9;
Ans. 11).
Thus, for the foregoing reasons, we find that Examiner failed to
establish an evidentiary basis on this record to support a conclusion that the
combination of Bruner, Yuhdua, Goldman, Arnold, and Beguin makes
obvious Appellant's claimed invention. In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992) ("[E]xaminer bears the initial burden, on review of the prior
art or on any other ground, of presenting a prima facie case of
unpatentability."); see also In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006)
("[R ]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.").
Re} ection II:
Based on the combination of Bruner, Y ehuda, Goldman, Arnold,
Beguin, and Barton Examiner concludes that, at the time Appellant's
invention was made, "[i]t would have been [prima facie] obvious to ...
supplement individuals with iron dextran who have iron deficiency
[because] Barton ... [discloses] iron dextran to be safe and effective
treatment for iron deficiency" (Final Act. 10). We are not persuaded
because Examiner failed to establish that Barton makes up for the foregoing
deficiency in the combination of Bruner, Y ehuda, Goldman, Arnold, and
Beguin (see Br. 7).
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Rejection III:
Based on the combination of Bruner, Y ehuda, Goldman, Arnold,
Beguin, and Pineda, Examiner concludes that, at the time Appellant's
invention was made, it would have been prima facie obvious "to use iron
bis-glycinate for the treatment of iron deficiency [because] Pineda ...
[disclose] that ferrous bis-glycinate chelate was absorbed or retained 3, 4
times greater than ferrous sulfate making it the iron of choice for treatment"
(Final Act. 11 ). We are not persuaded because Examiner failed to establish
that Pineda makes up for the foregoing deficiency in the combination of
Bruner, Y ehuda, Goldman, Arnold, and Beguin (see Br. 7).
Re} ection IV:
Based on the combination of Bruner, Y ehuda, Goldman, Arnold,
Beguin, and Horvath, Examiner concludes that, at the time Appellant's
invention was made, it would have been prima facie obvious "to select
tardyferon as the source of ferrous sulfate and thus produce the instantly
claimed invention because Bruner et al. already teaches administration of
ferrous sulfate" and Horvath discloses the use of "tardyferon for controlling
iron deficiency in children and infants" (Final Act. 13). We are not
persuaded because Examiner failed to establish that Horvath makes up for
the foregoing deficiency in the combination of Bruner, Y ehuda, Goldman,
Arnold, and Beguin (see Br. 8).
CONCLUSION
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness.
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Rejection I, the rejection of claims 1, 5, 6, 9, 23, and 24 under 35
U.S.C. § 103(a) as unpatentable over the combination of Bruner, Yehuda,
Goldman, Arnold, and Beguin, is reversed.
Rejection II, the rejection of claim 7 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Bruner, Y ehuda, Goldman, Arnold,
Beguin, and Barton, is reversed.
Rejection III, the rejection of claim 8 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Bruner, Y ehuda, Goldman, Arnold,
Beguin, and Pineda, is reversed.
Rejection IV, the rejection of claim 25 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Bruner, Y ehuda, Goldman, Arnold,
Beguin, and Horvath, is reversed.
REVERSED
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