[email protected] Paper No.

42
571.272.7822 Filed: September 26, 2017

UNITED STATES PATENT AND TRADEMARK OFFICE

____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD

____________

LUPIN LTD. and LUPIN PHARMACEUTICALS, INC.,

Petitioners,

v.

HORIZON THERAPEUTICS, INC.,

Patent Owner.
____________

Case IPR2016-00829
Patent 9,095,559 B2
____________

Before TONI R. SCHEINER, LORA M. GREEN, and DEBORAH KATZ,

Administrative Patent Judges.

KATZ, Administrative Patent Judge.

FINAL WRITTEN DECISION

35 U.S.C. 318 and 37 C.F.R. 42.73

I. Introduction
We instituted a trial under 35 U.S.C. 314 to review challenges
brought by Lupin Ltd. and Lupin Pharmaceuticals, Inc. (Lupin or
Petitioner) against claims 115 of U.S. Patent No. 9,095,559 B2 (Ex.
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Patent 9,095,559 B2

1001) (the 559 patent) in the Petition (Paper 3 (Pet.)). See Paper 13
(Institution Decision (DI)).
Horizon Therapeutics, Inc. (Horizon or Patent Owner) filed a
preliminary response under 37 C.F.R. 42.107 (Paper 9 (Prelim. Resp.))
and a response under 37 C.F.R. 42.120 (Paper 26 (PO Resp.)) to Lupins
challenges and Lupin filed a Reply (Paper 31 (Reply)).
Lupin also filed a motion to exclude Horizon Exhibits 2019 and 2041
(Paper 35). See also Patent Owners Opposition to Petitioners Motion to
Exclude (Paper 37) and Petitioners Reply in Support of Its Motion to
Exclude Evidence (Paper 38). These exhibits are discussed in footnotes
below.
Horizon does not seek to amend its challenged claims under 37 C.F.R.
42.121.
A hearing was held on July 28, 2017, and a transcript of the oral
argument was made of record (Paper 41).
We conclude that the challenged claims are unpatentable under 35
U.S.C. 103 over the cited prior art.
A.
Both Lupin and Horizon report that Horizon served Lupin with a
complaint in the District Court for the District of New Jersey (Case No.
1:15-cv-07624) alleging that Lupin infringed the 559 patent, as well other
related patents. Pet. 7; Prelim. Resp. 2.
Lupin also reports that U.S. Patent No. 8,404,215, which issued from
the parent application of the 559 patent, was the subject of IPR2015-01127,
filed by Par Pharmaceutical, Inc., and IPR2016-00284, filed by Lupin, which
was instituted and joined with the IPR2015-01127 proceeding. The claims

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challenged in that review are similar to the claims challenged in the present
review, wherein fasting blood ammonia levels are measured, compared to
the upper limit of normal, and an adjusted dose of drug is administered if
the fasting blood ammonia level is greater than half the upper limit of
normal for blood ammonia level. See Par Pharm., Inc. v. Horizon
Therapeutics, LLC, Case IPR2015-01127, slip op. at 67 (PTAB September
29, 2016) (Paper 49). Those claims were held to be unpatentable.
Lupin reports further that IPR2015-01117 and IPR2016-00283,
involving Horizons U.S. Patent 8,642,012 1, were instituted and joined.
That patent is not related by lineage to the 559 patent and it was held that
Petitioner did not show that the challenged claims were unpatentable. See
Par Pharm., Inc. v. Horizon Therapeutics, LLC, Case IPR2015-01117
(PTAB November 3, 2016) (Paper 53).
We note that Lupin has recently filed petitions for review of the
claims of U.S. Patent Nos. 9,254,278 and 9,326,966 (IPR2017-01159 and
IPR2017-01160, respectively), which are related as being issued from
continuations of the application from the currently challenged 559 patent.
In addition, on July 13, 2017, Par Pharmaceutical, Inc. filed petitions
for review of U.S. Patent Nos. 9,095,559, 9,254,278, and 9,326,966
(IPR2017-01768, IPR2017-01767, and IPR2017-01769, respectively).
Decisions on whether to institute trial based on these pending petitions
has not yet been issued.

1
The application that became U.S. Patent 8,642,012 was published as U.S.
Patent Publication 2010/0008859, which was cited as prior art in Petitioners
challenges. See Ex. 1007.
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B.
The claims of the 559 patent are directed to methods of using a drug,
glyceryl tri-[4-phenylbutryate] (HPN-100), to treat subjects with urea
cycle disorders. Individuals suffering from urea cycle disorders (UCDs)
are unable to remove excess nitrogen waste, which is normally excreted in
the urine. Ex. 1002 30; Ex. 2006 3132. When the body functions
normally, dietary amino acids are converted first to ammonia and then to
urea in the urea cycle and, finally, excreted in the urine. Ex. 1002 31; Ex.
2006 31. In individuals with UCDs, the enzymes controlling the urea
cycle are deficient, leading to high levels of ammonia in the blood. Ex. 1002
32; Ex. 2006 3233. This accumulation of ammonia at high
concentrations in the body is toxic. Ex. 1002 32; Ex. 2006 33. Patent
Owners witness, Dr. Gregory M. Enns 2, testifies that [i]ncreased blood
ammonia levels manifest mainly as central nervous system dysfunctions
such as stupor, convulsions, and coma. Ex. 2006 33.
The claims of the 599 patent are directed to methods wherein HPN-
100 is administered at an initial or increased dose when a patients fasting

2
Dr. Enns testifies that he is a Professor at the Stanford University School of
Medicine. Ex. 2006 8. Dr. Enns also testifies that he is Board Certified in
Clinical Genetics and Clinical Biochemical Genetics by the American Board
of Medical Genetics and Genomics. Ex. 2006 7. Dr. Enns testifies that he
has cared for approximately 70 to 100 UCD patients over the course of his
career and that for the UCD patients he manages he prescribes nitrogen
scavenging medications on nearly all patients who have not undergone liver
transplantation. Ex. 2006 11. To manage the care of his patients, Dr. Enns
testifies that he adjusts the dose of nitrogen scavenging medication as well
as tailors dietary treatment and provides emergency management. Ex. 2006
11. We find Dr. Enns to be qualified to provide opinions on the subject
matter at issue.

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plasma ammonia level is less than the upper limit of the normal range for
ammonia, but greater than half that upper limit.
Claim 1 of the 559 patent is representative of the claims challenged
in Petitioners Ground 1 and recites:
A method for adjusting the dosage of glyceryl tri-[4-
phenylbutyrate] in a subject being treated for a urea cycle
disorder who has previously been administered an initial dosage
of glyceryl tri-[4-phenylbutyrate] and who has a fasting plasma
ammonia level less than the upper limit of normal for plasma
ammonia level, the method comprising:
(a) measuring a fasting plasma ammonia level for the
subject;
(b) comparing the fasting plasma ammonia level to the
upper limit of normal for plasma ammonia level; and
(c) administering an adjusted dosage of glyceryl tri-[4-
phenylbutyrate], wherein the adjusted dosage is greater than the
initial dosage if the fasting plasma ammonia level is greater
than half the upper limit of normal for plasma ammonia level.

Ex. 1001, 24:2839 (emphasis added). Independent claim 2, the only other
independent claim challenged in Ground 1, is similar to claim 1, differing in
the preamble among other small differences.
Claim 3 is challenged in Petitioners Ground 2 and recites:
A method of administering glyceryl tri-[4-
phenylbutyrate] to a subject having a urea cycle disorder, the
method comprising:
(a) measuring a first fasting plasma ammonia level for
the subject:
(b) comparing the first fasting plasma ammonia level to
the upper limit of normal for plasma ammonia level; and
(c) administering an initial dosage of glyceryl tri-[4-
phenylbutyrate] to the subject if the fasting plasma ammonia
level is greater than half the upper limit of normal for plasma
ammonia level and less than the upper limit of normal for
plasma ammonia level.

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Ex. 1001 at 24:4960. Claim 3 requires administering an initial dosage of

HPN-100 to a subject if the fasting plasma ammonia level is greater than
half, but less than the upper limit of normal for plasma ammonia.
C.
We instituted trial on the grounds of unpatentability asserted by
Petitioner. Both grounds were on the basis of obviousness under 35 U.S.C.
103 and are as follows:

Ground References Claims

1 Blau (Ex. 1006)3, Simell (Ex. 1005)4, and 1, 2, 4, 5, 710,
the 859 Publication (Ex. 1007)5 12, and 13
2 Blau, Simell, the 859 publication, and 3, 6, 11, 14, and
Brusilow 84 (Ex. 1004)6 15

II. Analysis
Under 35 U.S.C. 103, subject matter is unpatentable
if the differences between the subject matter sought to be
patented and the prior art are such that the subject matter as a
whole would have been obvious at the time the invention was
made to a person having ordinary skill in the art to which said
subject matter pertains.

3
PHYSICIANS GUIDE TO THE LABORATORY DIAGNOSIS OF METABOLIC
DISEASES, 26176 (Nenad Blau et al. eds., 2d ed. 1996).
4
Simell et al., Waste Nitrogen Excretion Via Amino Acid Acylation:
Benzoate and Phenylacetate in Lysinuric Protein Intolerance, 20 PEDIATRIC
RESEARCH 111721 (1986).
5
U.S. Patent Publication 2010/0008859 A1 was filed on January 7, 2009,
and published on January 14, 2010.
6
Brusilow et al., Treatment of Episodic Hyperammonemia in Children with
Inborn Errors of Urea Synthesis, 310 THE NEW ENGLAND JOURNAL OF
MEDICINE 163034 (1984).
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The Supreme Court explains that if the person of ordinary skill could have
arrived at the claimed subject matter using common sense to combine
different teachings of the prior art, that subject matter is likely obvious, not
innovative. See KSR Intl Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
To determine obviousness,
[o]ften, it will be necessary for a court to look to interrelated teachings
of multiple patents; the effects of demands known to the design
community or present in the marketplace; and the background
knowledge possessed by a person having ordinary skill in the art, all
in order to determine whether there was an apparent reason to
combine the known elements in the fashion claimed by the patent at
issue. To facilitate review, this analysis should be made explicit. . . .
As our precedents make clear, however, the analysis need not seek out
precise teachings directed to the specific subject matter of the
challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ.
Id. at 418. We analyze the evidence presented by Petitioner and Patent
Owner in light of the Supreme Courts guidance.
A.
The following findings of fact, like others in this opinion, are
supported by a preponderance of the evidence.
Petitioner points to the 859 publication for its teaching that nitrogen
scavenging drugs, including HPN-100, were known to treat UCDs. See Pet.
2223; Ex. 1007 8891, 9599, 107108, 226, and 232; Ex. 1002 53.
The 859 publication provides that HPN-100 is a phenylbutyric acid
(PBA) pro-drug of choice for individual management of patients with
these disorders. Ex. 1007 108; see Pet. 2122 (citing Ex. 1002 53). The
859 publication also teaches that increased dosages of nitrogen scavenging
drugs could be used to control plasma ammonia levels. Ex. 1007 83; see

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Pet. 2122. Thus, we agree with Petitioner and find that those of skill in the
art 7 would have known to use the drug recited in the challenged claims to
treat subjects with a UCD.
Petitioner also cites to the 859 publication for its teaching that
measuring plasma or blood levels of ammonia was known to be useful for
determining the effectiveness of the overall drug and dietary regimen for a
particular patient. Ex. 1007 8891; see Pet. 22, citing Ex. 1002 53.
Specifically, the 859 publication teaches
The plasma or blood level of ammonia is optionally also
determined, in addition to measuring urinary PAGN, to assess
the effectiveness of the overall drug and dietary regimen for a
particular patient. If the ammonia control is inadequate, the
dosage of the nitrogen scavenging drug may need to be
increased if that can be done, or the patient's dietary protein
intake can be decreased if that is feasible.

Ex. 1007 83. Furthermore, the 859 publication teaches a method of

individually adjusting the dose of a nitrogen scavenging drug, including
HPN-100, for a patient who had previously been treated with a drug,
including a) administering drug, b) measuring the amount of nitrogen waste
excreted, and
c) optionally measuring blood ammonia to determine if the
initial dosage is sufficient to control blood ammonia levels, or
to establish a suitable average ammonia level: and

d) adjusting the initial dosage of the new drug as needed to

provide an adjusted dosage based upon ammonia control,
dietary protein, and the amount of total waste nitrogen excreted
by the patient.

7
The level of ordinary skill in the art is discussed on pages 1415.
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Ex. 1007 9599. See also id. at 226 (The physician may also monitor
the plasma ammonia levels and dietary protein intake in the patient to
ascertain whether the patient's dietary protein intake and drug treatment
combined are producing the appropriate therapeutic effect) and 232
(Subsequent dose adjustment would be based on repeated measurement of
urinary PAGN as well as assessment of dietary protein and plasma
ammonia.). See Pet. 2223, citing Ex. 1002 53. From these teachings,
we agree with the Petitioner and find that the 859 publication teaches using
plasma ammonia levels to make adjustments in nitrogen scavenging drug
levels.
Petitioner also argues that the 859 publication indicates that
maintaining stable plasma ammonia levels is desirable. For example,
Petitioner cites to the teaching in the 859 publication that when the subject
is treated with the prodrug, which can be HPN-100, the subject will typically
achieve and maintain normal plasma ammonia levels. Ex. 1007 182; see
Reply 3. Similarly, the 859 publication teaches that only 23 doses of
HPN-100 can provide a stable level of plasma ammonia, and compares
this number to the 36 doses necessary with a different drug, PBA. See Ex.
1007 46; Reply 3. From these teachings, we agree with the Petitioner and
find that maintenance of normal plasma ammonia levels was a goal for those
of ordinary skill in the art.
The 859 publication discusses normal plasma ammonia levels. For
example, the 859 publication teaches
that for patients having ammonia levels above about 40 mol/L
when treated with sodium PBA, HPN-100 at equimolar dosages
provided superior control of ammonia, and consistently reduced
ammonia levels to below about 40 mol/L. Thus for patients
whose ammonia levels are abnormal (e.g. above about 40
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mol/L) when treated with sodium PBA, it is expected that

better ammonia control can be achieved with an equimolar
amount of HPN-100.

Ex. 1007 209; see Pet. 18. Similarly, the 859 publication teaches that
plasma levels of ammonia are acceptable when they are at or below a level
considered normal for the subject, and commonly this would mean plasma
ammonia level is below about 40 mol/L. Ex. 1007 94. See Pet. 18; see
also Ex. 1007 226 (Dietary protein intake or drug dosage or both could be
adjusted to attain a normal or desired plasma ammonia level, e.g., a level
below about 40 mol/L.). Based on these teachings we agree with
Petitioner and find that those of ordinary skill in the art knew plasma
ammonia levels below a level considered to be normal were acceptable, even
desirable.
The 859 publication refers to plasma ammonia levels at the upper
limits of normal, stating that [i]n certain clinical tests described herein the
upper limit of normal for the subjects was between 26 and 35 mol/L, and it
is recognized in the art that a normal ammonia level will vary depending
upon exactly how it is measured . . . . Ex. 1007 94. Elsewhere, the 859
publication provides that a normal plasma ammonia level is a level of less
than about 40 mol/L, or of not greater than 35 mol/L . . . . Ex. 1007
85; see PO Resp. 1617. These teachings indicate to us that recitation of
specific plasma ammonia levels are not necessarily useful in determining the
upper limit of normal because reported plasma ammonia levels may vary
depending on how they are measured.

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Nevertheless, we agree with the parties 8 that the claim term upper
limit of normal (ULN) means the highest value in a range of normal
values. See Pet. 10; PO Resp. 21. We determine that the plain meaning and
the broadest reasonable interpretation of the claim term less than the upper
limit of normal is any value less than the highest value in the range of
normal values. See Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131,
214446 (2016) (upholding the use of the broadest reasonable interpretation
standard); see 37 C.F.R. 42.100(b).
We also find, from the statement a plasma ammonia level of less
than about 40 mol/L, or of not greater than 35 mol/L would indicate the
treatment was effective (Ex. 1007 74; see also id. 85), that treatment
would be considered effective by those in the art when plasma ammonia
levels are below a level considered to be the upper limit of normal.
In summary, the 859 publication teaches that those of skill in the art
would have known to use HPN-100 to treat subjects with UCDs. It also
teaches that measuring plasma or blood level of ammonia was known to be
useful in determining the effectiveness of a drug regimen for a particular
patient and that measuring blood ammonia was a known step in adjusting
drug dosages. The 859 publication teaches that maintaining normal plasma
ammonia levels was desirable in the art. Although specific measurements of

8
Patent Owner notes that the parties do not dispute the meaning of any of
the claim terms. PO Resp. 2. Because the meaning of the terms in the
challenged claims are evident from their ordinary meaning and not
controversial, we need not provide a separate analysis of them. See
Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011)
(claim terms need only be construed to the extent necessary to resolve the
controversy. Vivid Techs., Inc. v. Am. Sci. & Engg, Inc., 200 F.3d 795, 803
(Fed. Cir. 1999).).
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plasma ammonia do not necessarily indicate the upper limit of normal

consistently across different ways of measuring it, the 859 publication
teaches that treatment would have been considered to be effective when
plasma ammonia levels were less than what is determined to be the upper
limit of normal in a given case.
In addition to the 859 publication, Petitioner relies on Blau and
Simell for the teaching to collect blood from UCD patients after a fast in
order to measure plasma ammonia levels. Ex. 1006 at 273 (Table 11.9); Ex.
1005 at 1118; see Pet. 2526 (citing Ex. 1002 58, 59); see also id. 1002
46, n.2 (citing Ex. 1015 at S11). Anticipating Patent Owners argument
that Blau relates to diagnosis not treatment of UCDs, Petitioner also cites to
Exhibits 1010 and 1015 as evidence that it was generally recommended to
measure plasma ammonia after a fast. See Pet. 16, n.2. Exhibit 1010 is a
Lab Update about measurement in ammonia in blood, and Exhibit 1015 is
a publication entitled Measurement of ammonia in blood. Both state that
most methods recommend collecting a sample from patients who have fasted
for at least 6 hours. See Ex. 1010, 4; Ex. 1015, 1. From this evidence, we
agree with Petitioner that those of skill in the art would have known that
measuring fasting serum ammonia levels, as taught in at least Simell and
Blau, was known to be useful with the methods taught in the 859
publication.
In regard to Ground 2, which challenges claim 3 and the claims that
depend on it, Petitioner cites Brusilow 84 for its teaching of measuring a
patients fasting plasma ammonia level when he or she is admitted,
presumably to a hospital, and, in response to elevated levels, treating with
the nitrogen scavenging drugs sodium benzoate and phenylacetate. See Pet.

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3536, citing Ex. 1004 at 1631; see Ex. 1002 77. We agree with Petitioner
and find that Brusilow 84 teaches it was known to initiate drug therapy
when a patient presented with plasma ammonia levels above the upper limit
of normal. Pet. 3941, citing Ex. 1002 83.
B.
Petitioner also relies on the testimony of Dr. Vaux to demonstrate the
obviousness of the challenged claims. Dr. Vaux testifies that the objective
of therapy with nitrogen scavenging drugs was known to be maintenance of
ammonia levels within normal limits. Ex. 1002 54; see Pet. 24. This
testimony is reflected in the prior art, which teaches: The goal of treatment
is to maintain normal levels of plasma ammonia through the use of low
protein diet and medication while allowing for normal growth. Ex. 1016 at
S58.
Petitioner also relies on Dr. Vauxs testimony that ammonia levels
were known to vary during the day, for example after eating or because of
the time. See Pet. 2425, citing Ex. 1002 55. We credit Dr. Vauxs
testimony on this issue because it is supported by the prior art. Specifically,
the prior art teaches that postprandial ammonia levels were known to be
30-60 mol/L higher depending on time and N load. Ex. 1006, 268, Table
11.5; see Ex. 1002 55. Similarly, it was reported in the prior art that the
circadian rhythm has an effect on plasma ammonia levels. Ex. 1012, 213,
abstract. See also Ex. 1017, 164, Table II (providing plasma ammonia levels
after protein ingestion at different hours after protein load) and Ex. 1016 at
S58.
In light of this knowledge, Dr. Vaux testifies:
In order to maintain plasma ammonia levels within normal
limits, a person of ordinary skill in the art would have been
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motivated to administer more drug to reduce the ammonia

levels, even in cases where the fasting plasma ammonia level
was above half the ULN but below the ULN. A person of
ordinary skill in the art would have been motivated to maintain
a patient at normal plasma ammonia levels, and would have
known that variation of ammonia levels due to time of day
and/or ingestion of food would risk taking the patient outside of
normal levels. (Ex. 1006 at 268, Table 11.5.) For example, for
a patient with fasting plasma ammonia levels approaching the
ULN, a person of ordinary skill in the art would have desired to
maintain the patient at normal ammonia levels, and would have
known that variation in ammonia levels due to time of day
and/or ingestion of food would potentially take the patient
outside of normal levels. Thus, even though the patient's
fasting plasma ammonia level was already below the ULN, a
person of ordinary skill in the art would have been motivated to
increase the dose of drug to lower the patient's baseline
ammonia and to help ensure that the patient routinely stayed
within normal plasma ammonia limits.

Ex. 1002 55 (emphasis added); see also id. 51, 65; Pet. 2425, 2829.
Dr. Vauxs testimony indicates there would have been a reason for those of
ordinary skill in the art to have modified prior art methods of increasing
nitrogen scavenging drug dosage when a patients plasma ammonia levels
were approaching the upper limit of normal but had not yet exceeded it.
According to Dr. Vaux, those of ordinary skill in the art would have
understood that increasing the dosage would maintain ammonia levels in the
normal range after a meal or when influenced by daily rhythms.
Patent Owner argues that Dr. Vauxs testimony should be given little
weight because Dr. Vaux is not board certified in clinical genetics or clinical
biochemical genetics and has not published or spoken publicly about the
treatment of UCDs. According to Patent Owner, Dr. Vaux is not qualified

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as one of ordinary skill in the art on the subject matter of this review. PO
Resp. 20, 36.
Patent Owner and Petitioner define a person of ordinary skill in the art
as having similar qualifications (compare Pet. 89, citing Ex. 1002 19 with
PO Resp. 1516, citing Ex. 2006 26), but Patent Owner argues that the
ordinarily skilled artisan must additionally have at least three years of
residency/fellowship training in Medical Genetics, including Biochemical
Genetics, followed by certification in Clinical Genetics and Clinical
Biochemical Genetics by the American Board of Medical Genetics and
Genomics. PO Resp. 1516, citing Ex. 2006 26. We agree with the
qualifications on which the parties agree and find that one of ordinary skill
in the art would have an M.D. or equivalent degree, with a residency and
specialized training in the diagnosis or treatment of inherited metabolic
disorders, such as UCDs and other nitrogen retention disorders. See Pet. 8
9; PO Resp. 1516. We also agree with Patent Owner that one of ordinary
skill in the art would have experience treating patients with nitrogen
retention disorders, including UCDs. See PO Resp. 16.
We are not persuaded by Patent Owners argument that the lack of
specific residency/fellowship training or certification, disqualifies Dr. Vaux
from providing opinion testimony on the motivations, understandings, and
actions of those of ordinary skill in the art. Dr. Vaux testifies that he is a
medical doctor with specialty training in Pediatrics and Clinical Genetics
and is currently Professor and Clinical Chief of the Division of Medical
Genetics in the Department of Medicine at UC San Diego. Ex. 1002 1.
He also testifies:
Since 1994, I have regularly diagnosed and treated patients with
urea cycle disorders (UCD), and continue to do so today. In
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treating UCD patients, I regularly prescribe nitrogen scavenging

drugs and treat patients who are maintained on therapy with
nitrogen scavenging drugs.

Ex. 1002 1. Thus, Dr. Vaux has actually treated UCD patients for at least
five years (a requirement recited by Patent Owner, see PO Resp. 16),
including prescribing drugs. Patent Owner does not direct us to evidence
that Dr. Vauxs testimony is untruthful or that his treatment of UCD patients
is ineffective, indicating that he does not understand how to treat them.
Accordingly, even if Dr. Vaux does not have the specialized certificates or
particular training that Patent Owner argues are necessary, he has done the
job for over twenty years of one who would carry out the claimed methods.
We consider this experience more relevant than certificates or training.
Thus, we determine that Dr. Vaux is qualified to provide opinions about the
motivations, understandings, and actions of one of ordinary skill in the art.
C.
Even if Dr. Vaux were not qualified as one of ordinary skill in the art
about the subject matter of this proceeding, we still would accord weight to
his testimony because we find it to be supported by the prior art. For
example, despite Patent Owners arguments that no support exists for Dr.
Vauxs contention that a goal of nitrogen scavenging therapy is to maintain a
stable plasma ammonia level (see PO Resp. 34), the 859 publication
teaches that when treating with HPN-100 the subject will typically achieve
and maintain normal plasma ammonia levels. Ex. 1007 182. Similarly,
Berry (Ex. 1016) cited by Dr. Vaux, teaches that [t]he goal of treatment is
to maintain normal levels of plasma ammonia through the use of low-protein
diet and medication while allowing for normal growth. Ex. 1016, S58. We
find that these prior art references support Dr. Vauxs testimony that
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[m]aintenance of plasma ammonia levels within normal limits is one of the

objectives of therapy with nitrogen scavenging drugs. Ex. 1002 54. We
note that even Dr. Enns, Patent Owners witness, testifies that a number of
references repeat the idea that the goal is to maintain plasma ammonia
within normal limits. Ex. 2006 114, citing Ex. 1020 at 3328; Ex. 1016 at
S58; Ex. 2021 at 33.
Patent Owner argues that Dr. Vauxs testimony is not supported
because the prior art does not state that the goal of maintaining a normal
plasma ammonia level means staying within normal during the entire course
of every day. PO Resp. 34. We disagree that this accurately characterizes
Dr. Vauxs testimony or that the invention as recited in the559 patent
claims would have been obvious only if skilled artisans had a goal of
constant maintenance throughout the entire course of every day. Instead,
the challenged claims merely recite administering an adjusted dosage of
drug.
We are also not persuaded by Dr. Ennss testimony that the known
variability in plasma ammonia levels made it too difficult to try to achieve
stability in plasma ammonia levels when treating UCDs. PO Resp. 34,
citing Ex. 2006 41, 43, 8687. Because the prior art expressly provides
for a goal of maintaining normal levels of plasma ammonia at least in part
with medication (see Ex. 1016, S58), we are not persuaded that Dr. Vauxs
testimony lacks support.
Patent Owner argues further that there is no support for Dr. Vauxs
assumption that a physician would have taken any action when a patient had
a normal plasma ammonia level or that the action would have been to
increase drug dosage. PO Resp. 34, citing Ex. 2006 8687; see also PO

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Resp. 3941 (citing Ex. 2006 1314). We disagree because the 859
publication teaches that plasma levels of ammonia are acceptable when
they are at or below a level considered normal for the subject . . . . Ex.
1007 94. Thus, the 859 publication teaches that a known goal of
treatment is plasma levels that are below normal, not just below the upper
limit of normal.
Patent Owner argues that the prior art teaches only adjusting drug
dosages when plasma ammonia levels are far above the upper limit of
normal, not within the normal range, citing several references in support. PO
Resp. 3846. For example, Patent Owner cites to Brusilow 84 (Ex. 1004)
to show that ordinarily skilled artisans were concerned only when plasma
ammonia levels were three times normal or higher. PO Resp. 41 (citing Ex.
1004, 1631 and Ex. 2006 6768). We do not consider Brusilow 84 to
support Patent Owners argument because treatment of one or several
patients with high plasma levels of ammonia does not indicate skilled
artisans would always wait until plasma ammonia reached those levels.
Patent Owner also cites to Berry (Ex. 1016) for its discussion of
adjusting the dose of nitrogen scavenging drugs only when plasma ammonia
levels are more than three times the upper range of normal. PO Resp. 43
(citing Ex. 1016, S58S59); Ex. 2006 80, 114, and 119. The portion of
Berry cited by Patent Owner, though, refers to prophylactic treatment when
a patient is ill and therefore may not be indicative of all dosing decisions.
See Reply 78. In addition, Berry includes teachings to adjust drug dosage
at plasma levels within the claimed range because it applies to any plasma
level below three times the upper range of normal, a range that includes
below the upper limit of normal. Reply 78. Accordingly, we are not

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persuaded, based on Berrys teachings, that those of ordinary skill in the art
would not have had a reason to adjust drug dosage when plasma ammonia
levels were below the upper limit of normal.
For similar reasons, we are not persuaded by Patent Owners citations
to Batshaw (Ex. 2009), Feillet (Ex. 2018), and Barsotti (Ex. 1015). See PO
Resp. 44 (citing Ex. 2006 116, 119). Batshaw states: The aim of long-
term therapy has been to maintain metabolic control with plasma ammonia
concentrations less than twice normal . . . . Ex. 2009, S51 (emphasis
added). Feillet states: The aim should be to maintain good metabolic
control with plasma ammonia concentrations less than 80 mol/L (normal <
50 mol/L) . . . . Ex. 2018, 109 (emphasis added). Barsotti states: In the
venous blood of healthy adults and children, blood ammonia levels are
approximately 30 mol/L, and levels exceeding l mmol/L occur under
conditions of acute hyperammonemia. Ex. 1015, S11. Each of these
references teaches that a range of less than the upper limit of normal is
included in the targeted range. We agree with Petitioner that setting an
upper limit on tolerable plasma ammonia levels does not mean that those of
ordinary skill in the art would not have had a reason to adjust drug dosage at
lower plasma ammonia levels. See Reply 8.
Patent Owner also cites to a publication entitled Consensus statement
from a Conference for the Management of Patients With Urea Cycle
Disorders (Ex. 2025). PO Resp. 44. This publication teaches there was no
agreement on whether plasma ammonia levels greater than three times
normal require intravenous drug administration. Ex. 2025 at S3. Although
this may support Patent Owners argument to some extent, immediately after
this teaching, the publication states: Ammonia levels change rapidly. An

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elevated ammonia level during a clinic visit in a patient without symptoms,

however, does require adjustment of therapy or better compliance with the
recommended treatment regimen. Ex. 2025, S3; see Reply 8. We find this
passage to be in tension with the passage relied on by Patent Owner. The
second passage is more supportive of Dr. Vauxs testimony about the
reasons why ordinarily skilled artisans would have adjusted drug dosages
when plasma ammonia levels are approaching the upper limit of normal
because it refers to elevated ammonia levels in patients without symptoms,
without specifying that these levels would be above the upper limit of
normal. We give the second passage more weight because it expressly
supports Dr. Vauxs testimony, whereas the passage relied upon by Patent
Owner indicates only that there was disagreement in the art.
Patent Owner also cites to the 157 publication (Ex. 2012) to show
that ordinarily skilled artisans would not have had any reason to adjust drug
dosages until plasma levels were above the upper limit of normal. PO Resp.
42. Patent Owner asserts that the 157 patent teaches that no dosage
adjustments were needed for patients with ammonia levels under 30 mol/L
(reportedly below the average upper limit of normal). This does not
persuade us that the 157 publication demonstrates those of skill in the art
would not have considered adjusting the dose of drug when plasma ammonia
levels are below the upper limit of normal. Instead, as Petitioner notes, the
157 publication also teaches adjusting drug dosage to attain a normal or
desired plasma ammonia level, e.g. a level below about 40 mol/L. Ex.
2012 299; see Reply 7.
Patent Owner cites to other prior art references to show that above
normal plasma ammonia levels were acceptable. For example, Patent

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Owner argues that Table 4 of Hberle9 teaches increasing the dosage of

nitrogen scavenging drugs only when plasma ammonia is at a level above
the upper limit of normal, but not when it is within the normal range. PO
Resp. 4243 (citing Ex. 2019, 1975, Table 4). Table 4 of Hberle indicates
that its recommendations are for action in symptomatic patients with
increased levels of ammonia in their blood (hyperammonemia). See Ex.
2019, 1975, Table 4; Ex. 2006 118 (noting that Table 4 of Hberle
provides suggestions for action in symptomatic patients).
When we read Table 4 in the context of the rest of Hberle, we find
that it is referred to only in the context of [m]anagement of acute
hyperammonemia when a patient is in hyperammonemic crisis and being
transferred to a specialist centre with the possibility of coma. See Ex.
2019, 1974. We are not persuaded that these conditions are necessarily
relevant to the treatment discussed by Dr. Vaux in his testimony. That is,
Dr. Vaux refers to determination of drug dosage to help insure that the
patient routinely stayed with normal plasma ammonia limits. Ex. 1002
51, 55. Thus, whereas Hberle relates to crisis situations, Dr. Vauxs
testimony relates to routine management of UCD patients, who are not
necessarily symptomatic. Patent Owner has not directed us to evidence
showing how ordinarily skilled artisans would determine drug dosage in
other situations, for example when attempting to maintain normal levels of
plasma ammonia in non-symptomatic patients partaking in usual activities,
such as eating, over the course of a day.

9
Petitioner disputes the admissibility of Hberle as prior art in its Motion to
Exclude. Paper 35 at 39. As discussed in the main text, above, we do not
consider Hberle to be persuasive of the non-obviousness of the challenged
claims. Accordingly, Petitioners arguments are moot.
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Patent Owner argues that clinicians typically use the lowest dosage
possible of medication to avoid side effects, indicating that there would not
have been motivation to increase drug dosage when a patients plasma
ammonia levels were not above the upper limit of normal. PO Resp. 4445
(citing Ex. 2006 121). Patent Owner and Dr. Enns cite to the severe
toxicity that can result from massive overdosing in response to prescription
or pharmacy errors. PO Resp. 4445. The references Patent Owner cites10
do not report such problems with HPN-100 overdosing. See Ex. 1006 at 262
(regarding phenylbutyrate); Ex. 2031 at S64 (regarding phenylbutyrate); Ex.
2032 at S79S85 (regarding sodium phenylbutyrate and sodium
phenylacetate); Ex. 1014, 1019 (regarding phenylbutyrate). See Reply 9.
Instead, the 859 publication teaches:
[I]t has also been found that HPN-100 exhibits no indications of
toxicity at equimolar doses when compared to the approved
PBA [phenylbutyric acid] dosage of 20 g/day and a dose 2-3
times the equivalent of 20 grams of PBA is unlikely to produce
PAA blood levels leading to [adverse effects]. Moreover,
tolerability of taking HPN-100 is much higher than for PBA . . .
. In some patients or clinical settings, HPN-100 doses well
above the approved PBA dosage are expected to be beneficial[.]

Ex. 1007 86.

Furthermore, although Patent Owner argues that artisans would have
wanted to avoid the risks of massive overdoses (PO Resp. 4445), the
challenged claims encompass only slight drug dosage adjustments. Patent
Owner has not directed us to evidence that slight increases in HPN-100

10
Patent Owner argues that the 859 publication at paragraph 83 teaches
limiting the dosage of HPN-100 to not exceed that of phenylbutyrate at
paragraph 83 (PO Resp. 45), but this paragraph does not mention dosing of
either drug specifically.
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would have been considered to be dangerous. Accordingly, we are not

persuaded by Patent Owners arguments regarding the risks of toxicity of
nitrogen scavenging drugs.
Patent Owner relies on Dr. Ennss testimony to argue that those of
ordinary skill in the art would not have relied on a normal plasma ammonia
level to adjust a patients drug dosage because such plasma ammonia levels
were known to be variable. PO Resp. 46 (citing Ex. 2006 100101).
According to Dr. Enns, plasma ammonia levels were not used as the basis of
adjusting drug dosage. See Ex. 2006 101. The 859 publication teaches
otherwise. Specifically, the 859 publication expressly provides a method to
individually adjust the dose of a nitrogen scavenging drug, including
optionally measuring blood ammonia to determine if the initial dosage is
sufficient to control blood ammonia levels, or to establish a suitable average
ammonia level and then adjusting the dosage of the new drug as needed
. . . . Ex. 1007 9599; see also id. 8891. Although the method
taught in the 859 publication also teaches measuring the amount of total
waste nitrogen and/or PAGN excreted, Patent Owners challenged claims
are open to additional steps because of the comprising transitional
language. In contrast to Dr. Ennss testimony, we find that the prior art
taught using plasma ammonia levels as the basis, at least in part, for
adjusting nitrogen scavenging drug dosages.
Patent Owner argues further that the variability of plasma ammonia
levels throughout the day counsels against relying on them to adjust drug
dosage. PO Resp. 4748, citing Ex. 2006 102. Instead, because high
ammonia levels are toxic to the patient and can lead to coma (see Ex. 1002
32; Ex. 2006 33), we are more persuaded by Dr. Vauxs testimony (see

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Ex. 1002 51, 55) that ordinarily skilled artisans would consider this
variability to be a reason to increase drug dosage when plasma ammonia
levels approach the upper limit of normal.
In general, Patent Owner argues there is no teaching in the prior art to
increase drug dosage for subjects whose plasma ammonia levels are less
than the upper limit of normal. See PO Resp. 5154 (citing Ex. 2006 59
84). We are not persuaded by this argument. The prior art need not
expressly teach what is recited in the challenged claims. Instead, Petitioner
need only show that there would have been a reason for ordinarily skilled
artisans to modify what was taught in the prior art and that there would have
been a reasonable expectation of success in doing so. As the Supreme Court
noted, [i]n many fields it may be that there is little discussion of obvious
techniques or combinations, and it often may be the case that market
demand, rather than scientific literature, will drive design trends. KSR, 550
U.S. at 419. In light of the teachings in the prior art regarding measuring
plasma ammonia levels in a fasting state and using this information to adjust
drug doses, along with Dr. Vauxs testimony, we are persuaded that
Petitioner has established that one of ordinary skill in the art would have had
a reason to increase drug dosage for subjects whose plasma ammonia levels
are less than the upper limit of normal.
D.
Patent Owner also argues that there would not have been a reason to
combine the teachings of the 859 publication with those of Simell, Blau, or
Brusilow 84 to achieve the claimed invention. PO Resp. 2433. Petitioner
asserts that one of ordinary skill in the art would have combined the
teachings of these references based on Dr. Vauxs testimony that each

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contributes to beneficial aspects of adjusting the dosage of a nitrogen

scavenging drug. See Pet. 1920 (citing Ex. 1002 4750). Specifically,
Dr. Vaux explains that the 859 publication provides guidance on choosing a
dosage of nitrogen scavenging drug, while Simell and Blau provide guidance
on measuring plasma ammonia levels. See id.
Patent Owner challenges Dr. Vauxs assertions by arguing that Simell
measured fasting blood ammonia for reasons unrelated to the treatment of
UCD patients with nitrogen scavenging drugs. See PO Resp. 2630 (citing
Ex. 2006 8, 9192). Specifically, Patent Owner argues that Simell
teaches administering drugs other than HPN-100 and administering them
intravenously in patients with artificially induced hyperammonemia, in
contrast to the 859 publication, which teaches oral HPN-100 for long-term
management of UCD patients. See PO Resp. 2627. Patent Owner argues
further that Simell refers to a different condition, lysinuric protein
intolerance, which Patent Owner asserts is not a type of UCD. See PO Resp.
2729 (citing Ex. 2006 at 9394).
Patent Owner argues further that Blau teaches only methods of
diagnosis of metabolic diseases, rather than treatment of UCDs. PO Resp.
32 (citing Ex. 2006 96). Regarding Brusilow 84, Patent Owner argues
that the reference teaches a different drug to treat episodic hyperammonemia
in UCD and does not emphasize measuring fasting plasma ammonia levels.
PO Resp. 3031 (citing Ex. 2006 97).
We are not persuaded by Patent Owners arguments because even if
Simell, Blau, and Brusilow 84 are not directed to the exact same aspects of
UCDs as the 859 publication, they reflect the knowledge of those with
ordinary skill in the art with respect to measuring plasma ammonia levels

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after a fast. 11 As discussed above, Exhibits 1010 and 1015 provide further
evidence that the use of fasting ammonia levels in Simell, Blau, and
Brusilow 84 was not limited to the exact circumstances reported in these
references. See Pet. 16, n.2. Accordingly, we are persuaded that the
preponderance of the evidence supports the finding that those of skill in the
art would have considered it obvious to modify the teachings of the 859
publication by using fasting serum ammonia levels as taught in at least
Simell and Blau.
E.
According to Patent Owner, the skilled artisan would have considered
a successful outcome to be reducing the incidence and frequency of
hyperammonemia. PO Resp. 56. Patent Owner argues that Petitioner fails
to prove that one of ordinary skill in the art would have had a reasonable
expectation of success in combining the teachings of the cited references to
achieve the claimed invention, specifically in treating UCDs with the
claimed methods. PO Resp. 5557. Specifically, Patent Owner argues that
before the data in the 859 patent was known, a skilled artisan would not
have expected that an increased dosage of nitrogen scavenging drug would
lower a patients baseline when the plasma ammonia level was already
within normal limits. PO Resp. 57. The challenged claims do not require
that the recited methods result in any specific efficacy or any specific level

11
Petitioner argues that Exhibit 2041, which Patent Owner cites in support
of its arguments about the inapplicability of Simell (see PO Resp. 26),
should be excluded because it does not qualify as prior art. See Paper 35 at
910. Even if we found Ex. 2041 to be admissible, we are not persuaded by
the argument Patent Owner presents in reliance on it. Accordingly,
Petitioners arguments regarding Ex. 2041 are moot.
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Patent 9,095,559 B2

of reduction of the incidence or frequency of high plasma ammonia levels.

Thus Petitioner need not show that any specific result, such as lowering a
baseline, would have been expected.
Patent Owner argues further that Dr. Vauxs testimony regarding the
knowledge to administer HPN-100 to lower plasma ammonia levels is not
sufficient evidence of a reasonable expectation of success. See PO Resp. 55,
citing Ex. 1002 67. In contrast, Patent Owner asserts that Dr. Enns has
observed plasma ammonia levels increasing or remaining unchanged with
increased drug dosage. See PO Resp. 56 (citing Ex. 2006 119).
We credit Dr. Vauxs testimony over Dr. Ennss on this point because
Dr. Vaux supports his testimony with reference to the prior art. For
example, Dr. Vaux cites the portion of 859 publication that explains how
nitrogen scavenging drugs, such as HPN-100, act to reduce high levels of
endogenous ammonia by providing phenylacetic acid in vivo, which is
metabolized efficiently to form phenylacetyl glutamine, a compound that
removes nitrogen from ammonia and allows it to be excreted in the urine.
See Ex. 1002 67 (citing Ex. 1007 2123).
In contrast, the paragraph of Dr. Ennss testimony to which Patent
Owner directs us discusses only the teachings of the prior art regarding drug
dosages determinations when plasma ammonia levels are higher than the
upper limit of normal. See Ex. 2006 119. We note that in paragraph 123
of his declaration (Ex. 2006), Dr. Enns testifies that [i]t is all too possible
that administration of nitrogen scavenging drugs will increase or remain
unchanged with increased drug dosageit is not an easy linear
relationship. This testimony appears to be merely speculative and conflicts
with the teachings of the prior art.

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Patent Owner also cites Dr. Ennss testimony to argue that one of
ordinary skill in the art would not have understood the correlation between a
specific fasting plasma ammonia level and daily average ammonia levels
and maximum plasma ammonia levels without the detailed statistical
analysis presented in the 559 patent. See PO Resp. 56 (citing Ex. 2006
124). According to Dr. Enns,
[w]ithout this data, one of ordinary skill would have no expectation
that an increased dosage of nitrogen scavenging drug would lower a
patient's baseline when their plasma ammonia level was already
within normal limits. In addition, given the known variability and
unreliability of plasma ammonia values, one would not have had any
expectation that an increased dosage of nitrogen scavenging drug
would ensure they stayed within the normal limits.

Ex. 2006 124. We are not persuaded by either Patent Owners argument or
Dr. Ennss testimony because the challenged claims do not require that the
subjects baseline plasma ammonia levels be lowered or that plasma
ammonia levels stay within normal limits for any specific amount of time.
Thus, we are not persuaded that the statistical analysis presented in the 559
patent was necessary to carry out the methods of the challenged claims.
To the extent the methods of the challenged claims require any
efficacy in treating a subject, they would encompass reducing plasma
ammonia levels to some minimal extent. Because Dr. Vaux testifies, based
on the 859 publication teaching that the action of HPN-100 is to remove
endogenous ammonia by providing a pathway for its excretion, we are
persuaded that one of ordinary skill in the art would have had a reasonable
expectation of success in reducing plasma ammonia levels using an
administering step as recited in the claims. Indeed, the 859 publication is
directed to using HPN-100 to treat patients with UCDs. Furthermore, as
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Petitioner notes, reduction of plasma ammonia levels below half the upper
limit of normal after administration of HPN-100 is exemplified in Figure 12
of the 859 publication. See Reply 23.
Accordingly, we are persuaded that the ordinary artisan would have
had a reasonable expectation of success in combining the prior art teachings
to achieve the claimed methods.
F.
We are persuaded by the arguments and supporting evidence
presented by Petitioner that independent claims 1, 2, and 3 of the 559 patent
would have been obvious over the prior art.
G.
Claim 5 of the 559 patent recites the methods of claim 1 or 2 further
comprising repeating the measuring, comparing, and administering steps
until the subject exhibits a fasting plasma ammonia level at or below half the
upper limit of normal. See Ex. 1001 at 24:6467. Petitioner challenges
claim 5 of the 559 patent based on the cited prior art discussed above and
Dr. Vauxs testimony that there is no minimum level of blood ammonia that
must be maintained for normal body function. Pet. 31 (citing Ex. 1002
68).
With respect to claim 5, Patent Owner contends there is no prior art
that suggests targeting an ammonia level below half of the upper limit of
normal and that normal ranges were considered to be acceptable. PO Resp.
58.
We are not persuaded by these arguments because, as Petitioner
argues, the 859 publication and other prior art teach that maintaining
plasma ammonia levels below ranges considered to be normal was desirable.

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See Reply 1011; see, e.g., Ex. 1007 74 (a plasma ammonia level of less
than about 40 mol/L, or of not greater than 35 mol/L would indicate the
treatment was effective.). These teachings conflict with Dr. Ennss
testimony that those of ordinary skill in the art would not have had any
motivation to target plasma levels below half of the upper limit of normal.
See Ex. 2006 12527. Even if the prior art does not expressly teach the
limitations of the challenged claims, we are persuaded that it supports
Petitioners argument that ordinarily skilled artisans would have had reason
to target any level below the upper limit of normal. As Petitioner argues,
Patent Owner has not submitted any evidence that the claimed ammonia
value exhibits unexpected results over the prior art disclosure of ammonia
values that are less than the ULN. Reply 11.
H.
Petitioner includes the claims dependent on claims 1, 2, and 3 in the
patentability challenges. See Pet. 3035 and 4446.
Dependent claim 4 recites the method of claim 1 or 2 and requires that
the administered dose of HPN-100 produces a normal average daily
ammonia level in the subject. Ex. 1001 at 24:6163. We find that, as
Petitioner argues, it was known to administer HPN-100 to lower plasma
ammonia levels (see Ex. 1007 2123) and maintenance of plasma
ammonia levels within the normal limits was a goal of drug therapy (see id.
83; Ex. 1016, S58). Accordingly, we agree with Petitioner that those of
skill in the art would have had reason to administer HPN-100 to achieve a
normal average daily ammonia level in the subject and would have
considered the method of claim 4 to have been obvious. See Pet. 30. Patent
Owner does not argue to the contrary in regard to claim 4.

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Dependent claim 6 recites the method of claim 3, further comprising

repeating the steps of claim 3 a second time and administering an adjusted
dosage of HPN-100 that is greater than the initial dosage recited in claim 3.
Ex. 1001 at 25:111. We agree with Petitioner that claim 6 would have been
considered obvious by those of ordinary skill in the art for the same reasons
claim 3 would have been considered to be obvious. See Pet. 44. Patent
Owner does not argue to the contrary in regard to claim 6.
Claims 7, 8, and 9 recite the methods of claims 13 wherein the upper
level of normal is 35 mol/L, is specific to the laboratory in which the
fasting plasma ammonia level is measured, or is determined in an extra
method step prior to step (b) of the dependent claim. See Ex. 1001 at 25:12
18. We agree with Petitioner that the 859 publication teaches that 35
mol/L was considered to be an upper limit of normal under some testing,
but that such levels could vary with different laboratories. See Pet. 3233
(citing Ex. 1007 94). We also agree that the prior art teaches that it was
known that different patients could have different upper limits of normal
plasma ammonia levels, for instance according to their age. See Ex. 1006,
273 (Table 11.5) (teaching that the upper limit of normal for neonates is 80
mol/L and for 4-month olds is 50 mol/L). Accordingly, we agree that
claims 7, 8, and 9 would have been obvious. Patent Owner does not argue to
the contrary in regard to claim 7, 8, or 9.
Claim 10 recites the method of claim 1 or claim 2 with additional
steps to calculate the adjusted dosage of HPN-100 based on based on a
mean conversion of glyceryl tri-[4-phenylbutyrate] to urinary PAGN of 60
to 75%. Ex. 1001, 25:1926:5. Claim 11 recites similar steps as additional
limitations to claim 3 for a method of calculating the initial dosage of HPN-

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100. Ex. 1001, 26:612. We agree with Petitioner that the 859 publication
teaches that HPN-100 converts into urinary PAGN at a rate of 6075% and
that this rate may be used to determine an effective dose of HPN-100, thus
rendering claim 10 obvious. See Pet. 34 (citing Ex. 1007 43, 144156.
Patent Owner does not argue to the contrary in regard to claim 10.
Claims 12, 13, 14, and 15 depend on claims 1, 2, 3, and 6 respectively
and require that the adjusted or initial dosage of HPN-100 is administered
orally. Ex. 1001, 26:1419. We agree with Petitioner that the 859
publication teaches oral administration of HPN-100, rendering these claims
obvious. See Pet. 35 and 4546 (citing Ex. 1007 2021). Patent Owner
does not argue to the contrary in regard to claims 1215.
III. Conclusion
Petitioner has demonstrated, by a preponderance of the evidence, that
claims 1, 2, 4, 5, 710, 12, and 13 of the 559 patent are unpatentable over
the 859 publication, Blau, and Simell under 35 U.S.C. 103(a).
Petitioner has also demonstrated, by a preponderance of the evidence,
that claims 3, 6, 11, 14, and 15 of the 559 patent are unpatentable over the
859 publication, Blau, Simell, and Brusilow 84 under 35 U.S.C. 103(a).
In consideration of the foregoing, it is hereby:
ORDERED that claims 115 of the 559 patent are unpatentable;
FURTHER ORDERED that Petitioners motion to exclude is
dismissed as moot, as discussed above.
This is a final decision. Parties to the proceeding seeking judicial
review of the decision must comply with the notice and service requirements
of 37 C.F.R. 90.2.

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For Petitioner:

Elizabeth J. Holland
Cynthia Lambert Hardman
GOODWIN PROCTOR LLP
[email protected]
[email protected]

For Patent Owner:

James B. Monroe
Maureen D. Queler
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER, LLP
[email protected]
[email protected]

Matthew Phillips
LAURENCE & PHILLIPS IP LAW LLP
[email protected]

Robert Green
Emer Simic
Jessica Tyrus
GREEN, GRIFFITH & BORG-BREEN, LLP
[email protected]
[email protected]
[email protected]

Dennis Bennett
GLOBAL PATENT GROUP LLC
[email protected]

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