BARASCH, Jonathan Matthew. et al.

Patent Trials and Appeals Board

Nov 7, 2019

14482193 - (D) (P.T.A.B. Nov. 7, 2019)

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.
14/482,193 09/10/2014 Jonathan Matthew BARASCH CHM-032BRD1 1033
38155 7590 11/07/2019
HASSE & NESBITT LLC
8837 CHAPEL SQUARE DRIVE
SUITE C
CINCINNATI, OH 45249
EXAMINER
FOSTER, CHRISTINE E
ART UNIT PAPER NUMBER
1641
NOTIFICATION DATE DELIVERY MODE
11/07/2019 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):
DFN@HN-IPLAW.COM
usptopair@hn-iplaw.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JONATHAN MATTHEW BARASCH, PRASAD DEVARAJAN,
THOMAS L. NICKOLAS, and KIYOSHI MORI1
____________

Appeal 2019-003727
Application 14/482,193
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R.
§ 1.42. Appellant identifies BioPorto Diagnostics A/S as the real party-in-
interest. App. Br. 3.

Appeal 2019-003727
Application 14/482,193

2

SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 50, 60, 61, 66, 68–70, and 72–84 as
unpatentable under 35 U.S.C. § 103(a) as being obvious over the
combination of Chibout et al. (WO 2004/005544 A2, January 15, 2004)
(“Chibout”), E. Harlow et al., ANTIBODIES: A LABORATORY MANUAL (Cold
Spring Harbor Laboratory Press 1988) (“Harlow”), Uttenthal et al. (WO
2006/066587 A1, June 29, 2006) (“Uttenthal”),2 M.S. Parmar, Chronic renal
disease, 325 BMJ 85–90 (2002) (“Parmar”), and P.S. Williams et al.,
Immunosuppression Can Arrest Progressive Renal Failure Due to
Idiopathic Membranous Glomerulonephritis, 4 NEPHROL. DIAL.
TRANSPLANT 181–186 (1988) (“Williams”). App. Br. 7; Final Act. 4–18.
Claims 58, 59, and 76 stand rejected as unpatentable over 35 U.S.C.
§ 103(a) as being obvious over the combination of Chibout, Harlow,
Uttenthal, Parmar, Williams, and I. Eichler et al., Human neutrophil
lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis,
14 EUR. RESPIR. J. 1145–1149 (1999) (“Eichler”). Final Act. 18–19.
Claims 61, 68–70, and 74–84 also stand rejected as unpatentable over
35 U.S.C. § 103(a) as being obvious over the combination of Chibout,

2 The Examiner cites to Uttenthal, which we find qualifies as prior art under
35 U.S.C. § 102(e)(pre-AIA) as of the filing date of provisional application
US Ser. No. 60/719,307, filed September 21, 2005 (“Uttenthal’307”),
contrary to Appellant’s argument that only the provisional application is
citable as prior art. See App. Br. 15; see Final Act. 8; see also MPEP
§ 2136.02 (II). For example, we find claims 1, 13, and 18 of Uttenthal are
supported by claims 1, 12, and 17 of Uttenthal ’307.
Appeal 2019-003727
Application 14/482,193

3

Harlow, Uttenthal, Parmar, Williams, and K. Mori et al., Endocytic delivery
of lipocalin-siderophoreiron complex rescues the kidney from ischemia-
reperfusion injury, 115 J. CLIN. INVEST. 610–621 (March 2005) (“Mori”).
Final Act. 19–31.
Claims 58, 59, and 76 also stand rejected as unpatentable over 35
U.S.C. § 103(a) as being obvious over the combination of Chibout, Harlow,
Uttenthal, Parma, Williams, Mori, and Eichler. Final Act. 31–32.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s invention is directed to a method of assessing the ongoing
kidney status of a mammal afflicted with or at risk of developing chronic
renal injury or disease by detecting the quantity of Neutrophil Gelatinase-
Associated Lipocalin (“NGAL”) in samples over time. Abstr.

REPRESENTATIVE CLAIM
Claim 50 is representative of the claims on appeal and recites:
50. A method for assigning a diagnosis of a worsening chronic
renal injury to a human diagnosed with chronic renal injury and
treating said human, comprising the steps of:

(a) determining the level of Neutrophil Gelatinase-Associated
Lipocalin (NGAL) in a first sample selected from a serum sample
and a plasma sample, obtained from a human diagnosed with
chronic renal injury, by performing an immunoassay on the
sample that detects NGAL, wherein the immunoassay comprises
Appeal 2019-003727
Application 14/482,193

4

(i) contacting the sample with an antibody that detects NGAL,
and (ii) detecting binding to the antibody;

(b) determining the level of NGAL in a subsequent sample
obtained from the human after a period of time;

(c) assigning a diagnosis of a worsening chronic renal injury to
the human having a level of NGAL in the subsequent sample
which is higher than the level of NGAL in the first sample;

(d) treating the human with an assigned diagnosis of a worsening
chronic renal injury with a suitable treatment for chronic renal
injury, wherein the treatment is selected from the group
consisting of a treatment for hypertension, a treatment for
diabetes, and a treatment for blocking the renin-angiotensin
system.

App. Br. 26.

ISSUES AND ANALYSIS
We agree with, and expressly adopt, the Examiner’s findings,
reasoning, and conclusion that the claims are unpatentable as having been
obvious over the prior art. We address below the arguments raised by
Appellant.

A. Effective filing date of the claims
Issue 1
The Examiner finds the claims are entitled to different effective filing
dates. Final Act. 2–4.

Appeal 2019-003727
Application 14/482,193

5

Analysis
Appellant claims priority through a series of applications in two
different patent families to two initially-filed applications, International
Application No. PCT/US2006/040720 filed October 13, 2006 and U.S.
Application No. 11/374,285, filed October 13, 2005. Spec. ¶ 1.
The Examiner finds claims 58, 59, 61, 68–70, and 74–84 “have an
effective filing date of [October 13, 2006] as they appear to be supported by
PCT/US06/40720.” Final Act. 4. Conversely, claims 50, 60, 66, 72, and 73
are entitled to an earlier effective filing date of October 13, 2005. Id.
Appellant does not present arguments with respect to the Examiner’s
findings on the effective priority of the claims. “If an appellant fails to
present arguments on a particular issue … the Board will not, as a general
matter, unilaterally review those uncontested aspects of the rejection.” Ex
parte Frye, 94 USPQ2d 1072, 1075 (BPAI 2010) (precedential).
Accordingly, we adopt the Examiner’s findings with respect to the earliest
effective filing dates of the claims.

B. Rejection of the claims under 35 U.S.C. § 103(a) over Chibout,
Harlow, Uttenthal, Parmar, Williams, and Eichler
Issue 1
Appellant argues the prior art fails to teach “determining and
comparing an NGAL level in both a first and subsequent sample obtained
after a period of time from the same human, who is suffering from chronic
renal injury.” App. Br. 8 (emphasis omitted).

Appeal 2019-003727
Application 14/482,193

6

Analysis
The Examiner finds that Chibout teaches NGAL (also known as
Alpha-2u globulin related-protein (“Alpha-2u”)) is a marker of renal
diseases, injuries, or toxicities. Final Act. 5 (citing Chibout 1; 4; 41–42).
The Examiner finds Chibout teaches chronic kidney failure by defining
“‘renal toxicity’ or ‘renal injury’” as “renal or kidney failure or dysfunction
either sudden (acute) or slowly declining over time (chronic).” Id. at 6
(citing Chibout 10).
The Examiner finds Chibout teaches a method of monitoring subjects,
e.g., humans, receiving treatment of renal disease using a marker, e.g.,
NGAL, by: 1) obtaining a pre-administration sample from a subject before
treatment, 2) obtaining a sample after treatment, 3) detecting the levels of
the marker in the samples, and 4) comparing the levels of the marker. Final
Act. 6 (citing Chibout 10; 15–16). The Examiner finds Chibout teaches
modifying administration of an active agent to increase its effectiveness in
view of the testing. Id. at 7 (citing Chibout16).
The Examiner acknowledges that Chibout’s teachings of measuring
and comparing levels of markers in samples refer to renal disease or toxicity
generally, and do “not explicitly invoke chronic renal injury.” Final Act. 7.
However, the Examiner finds that Chibout teaches decreasing levels of
NGAL indicates amelioration of renal toxicity (Final Act. 6, citing Chibout
7; 18) and that “the ordinary artisan would have found it obvious to conclude
that the converse is true; i.e., that increased levels of NGAL are indicative of
worsening renal toxicity.” Id. at 11.
The Examiner finds Uttenthal teaches that “abnormal (elevated)
concentrations of NGAL in bodily fluids are indicative of disorders of the
Appeal 2019-003727
Application 14/482,193

7

kidney resulting in decreased renal function, including chronic renal failure.”
Final Act. 8 (citing Uttenthal 1, 3–5, 9–10; claims 1, 3; see also Uttenthal
’307 3, 4). The Examiner finds Uttenthal teaches NGAL may be more stable
in serum samples and may be measured using antibodies.3 Id. at 8–9 (citing
Uttenthal ’307 8, 9, 14). The Examiner finds Uttenthal provides “further
evidence of a known nexus between protein NGAL and chronic renal injury,
the same disease taught by Chibout.” Id. at 13.
The Examiner finds Parmar teaches that early identification and active
management of patients with chronic renal disease4 can prevent adverse
outcomes with relatively simple treatment. Final Act. 9 (citing Parmar 85,
89). The Examiner finds that Parmar teaches slowing the progression of
chronic renal disease by controlling blood glucose, controlling blood
pressure with angiotensin receptor blockers, and treating with
antihypertensive agents. Id. (citing Parmar 87).
The Examiner finds that “it would have been obvious to one of
ordinary skill in the art to conclude that a chronic renal failure patient whose
subsequent post-treatment NGAL levels are higher than baseline is not
responding to treatment and has experienced a worsening of their disease.”
Final Act. 11. The Examiner concludes that it would have been obvious for

3 The Examiner also finds Harlow teaches immunoassays, including two-
antibody sandwich assays, for detecting antigens, e.g., NGAL. Final Act.
8 (citing Harlow 559, 578–579).

4 The Examiner also finds Williams teaches membranous glomerulonephritis
as Appellant’s elected species of chronic renal injury. Final Act. 14 (citing
Williams 182, 185–186).
Appeal 2019-003727
Application 14/482,193

8

a person of ordinary skill in the art to administer the known treatments
taught by Parmar to treat chronic renal injury and prevent adverse outcomes
in chronic renal disease. Id. at 11–12. The Examiner further concludes that
a person of ordinary skill “would have been motivated to assess NGAL in
the context of chronic renal injury so that worsening of disease could be
identified and appropriate known treatments administered. Id. at 12.
Appellant contends Chibout teaches two different diagnostic methods.
See App. Br. 8–9. Appellant contends one diagnostic method involves
comparing samples of a first individual subject to renal toxicity to samples
of a second individual not subject to renal toxicity. Id. at 8 (citing Chibout
6–7). Appellant argues this method is not performed in the same human as
claimed. Id. Appellant contends Chibout’s alternative method involves
“monitoring the effectiveness of an active treatment agent that is
administered for treatment of renal disease or renal toxicity … but does not
teach or suggest detecting a worsening of a chronic renal injury.” Id. (citing
Chibout 15–16). Appellant contends “[i]t would be clear to a person of
ordinary skill in the art, reading the entire description in Chibout, that this
alternative method is limited to pre- and post-administration samples from
the same subject having a renal disease or renal toxicity, to track the success
of a treatment agent.” Id. at 9. Appellant contends that “the second
treatment embodiment of Chibout teaches away from the claimed method of
diagnosing a patient with worsening chronic renal injury, identified by a
higher level of NGAL in a second sample taken a period of time after a first
sample, and then treating the patient.” Reply Br. 4 (emphasis in original).
We are not persuaded. Appellant argues that Chibout must be
considered as a whole and then contradictorily argues Chibout’s teachings
Appeal 2019-003727
Application 14/482,193

9

are limited to a single embodiment divorced from the teachings of the
combined cited prior art. In a specific embodiment, Chibout teaches
detecting and comparing NGAL levels in an individual to determine the
effectiveness of a therapeutic agent. Chibout 15–16. Appellant argues this
embodiment teaches away from using NGAL to diagnose an individual with
worsening chronic renal injury prior to treatment. See Reply Br. 4.
However, “[t]he prior art’s mere disclosure of more than one alternative
does not constitute a teaching away from … alternatives because such
disclosure does not criticize, discredit, or otherwise discourage the solution
claimed.” In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). Indeed,
Chibout’s disclosure begins by recognizing the interconnectedness of the
disclosed methods, teaching that the “present invention relates to methods
for the monitoring, prognosis, diagnostic and/or treatment of renal
disorders” (Chibout 1; emphasis added).
Appellant points to no teaching or suggestion of Chibout
demonstrating that detecting and comparing NGAL during treatment would
have discouraged one of ordinary skill in the art from measuring NGAL in
an individual as a mean of diagnosing worsening chronic renal injury prior
to treatment. Rather, we find that measuring NGAL to determine the
progression of chronic renal injury before and during treatment is the type of
inference and creative step that would have been obvious to a person of
ordinary skill in the art. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
For example, Chibout teaches “prophylactic and therapeutic methods
of treating a subject having, or at risk of having a kidney disorder.” Chibout
16–17. Chibout teaches that administering “a prophylactic agent can occur
Appeal 2019-003727
Application 14/482,193

10

prior to the manifestation of symptoms characteristic of the kidney disorder,
such that development of the kidney disorder is prevented or delayed in its
progression.” Id. Therefore, Chibout further provides motivation to use the
disclosed markers, including NGAL, to identify a patient having or at risk of
chronic renal injury to prevent or delay progression of the disorder.
Furthermore, Appellant disputes the teachings of Chibout alone and
not in combination with those of the combined prior art cited by the
Examiner. “Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. … [The reference] must be read, not in isolation,
but for what it fairly teaches in combination with the prior art as a whole.”
In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Uttenthal also teaches measuring NGAL as a marker of renal
disorders, defined as including “chronic renal failure (CRF) of whatever
cause.” Uttenthal ’307 4. Uttenthal teaches monitoring the onset of a renal
disorder in a human by repeatedly measuring NGAL over a given time
wherein increasing NGAL in later samples is indicative of renal disorder.
See Uttenthal 31, claim 18; Uttenthal ’307 19–20, claim 17. Taken together
with Chibout, Uttenthal confirms that NGAL was a known marker of renal
injury, including chronic renal injury.
Parmar teaches the need for early detection and intervention in
chronic renal disease to prevent further injury and progressive renal
function. Parmar 86. Taken together with Chibout, Parmar confirms the
need for a marker of early renal injury in order to monitor at-risk patients.
Given the need for early detection, we conclude that a person of ordinary
Appeal 2019-003727
Application 14/482,193

11

skill in the art would have been motivated to determine the level of NGAL
in a human patient over time to diagnose chronic renal injury.
Issue 2
Appellant argues the prior art does not teach detecting a chronic renal
injury or a worsening of chronic renal injury. App. Br. 9.

Analysis
Appellant contends that: “Chibout does not in fact address the
detection of a chronic renal injury, let alone a worsening chronic renal
injury.” App. Br. 9. Appellant contends that apart from the definition for
renal injury or toxicity, “[n]owhere else in the entire specification … does
Chibout address or distinguish between acute renal injuries and chronic renal
injuries, or the difficulties and distinctions in detecting these injuries, or
detecting a worsening of these injuries, and in particular, a worsening of a
chronic renal injury.” Id. at 9–10. Appellant argues “the entire teaching in
Chibout regarding measuring levels of markers in baseline and post-
administration samples, or in first and second samples, relates to an acute
condition (acute renal injury and acute renal toxicity) that has an onset
within two weeks.” Id. at 10.
Appellant argues that Uttenthal “makes no specific, or implicit, or
express, teaching concerning chronic renal injuries.” Id. at 16. Rather,
Appellant contends that “[t]hroughout the disclosure, [Uttenthal ’307] refers
generally to renal injury, renal function, renal disorder, and renal affection,
but [Uttenthal ’307] addresses only acute renal injuries when addressing the
specifics.” Id. at 15.
Appeal 2019-003727
Application 14/482,193

12

We are not persuaded. Both Chibout and Uttenthal teach NGAL as a
marker of renal injury. See supra. Both Chibout and Uttenthal define renal
injury as including chronic renal injury. See supra. Chibout teaches that
chronic renal toxicity may be triggered by a number of disease or disorder
processes including: “long-standing hypertension, diabetes, congestive heart
failure, lupus, or sickle cell anemia.” Chibout 10. As we explained supra,
Chibout teaches administering a prophylactic agent prior to the
manifestation of symptoms characteristic of kidney disorder. Id. p. 16, ll.
13–17. Parmar teaches that “symptoms are not often apparent” in the early
stages of chronic renal disease. Parmar 85. Therefore, we conclude that a
person of ordinary skill in the art would have recognized that the prior art
suggests identifying and treating pre-symptomatic kidney disorders, e.g.,
chronic renal injury.
Likewise, Uttenthal teaches comparing concentrations of NGAL to
discriminate “between different types of renal disorder[s].” Uttenthal ’307
4–5. Uttenthal teaches a cutoff value that designates “lower concentrations
of NGAL associated with renal disorders that are not [acute tubular necrosis]
ATN or [acute tubulo-interstitial nephropathy] ATIN.” Id. A person of
ordinary skill in the art would have inferred that lower concentrations of
NGAL associated with renal disorders that are not acute would have
included chronic renal injury.
Accordingly, the prior art teaches a need for early detection of chronic
renal injury as well as a marker useful for identifying chronic renal injury,
specifically NGAL. The prior art further teaches increasing levels of NGAL
are indicative of worsening renal injury. See supra. Therefore, we are not
Appeal 2019-003727
Application 14/482,193

13

persuaded that the Examiner erred in finding the prior art teaches
determining the level of NGAL to diagnose worsening chronic renal injury.

Issue 3
Appellant argues that the prior art does not provide “a finite number
of identified, predictable alternatives with a reasonable expectation of
success.” App. Br. 12.

Analysis
Appellant contends that “Chibout provides no reasonable expectation
of success, if not a lack of success, based on the actual teaching of Chibout,
for the use of NGAL as a serum or plasma marker of chronic renal injury or
worsening chronic renal injury.” App. Br. 12. Appellant argues that
Chibout contains no data on chronic renal injury, nor data on NGAL
expression in samples from blood or urine, particularly human samples. Id.
at 13. Appellant contends that Chibout’s data with respect to a different
marker, clusterin, “is inconclusive at best” and “Chibout does not
demonstrate any success, or failure, for any of the other markers, which
serve as the alleged ‘finite number of identified, predictable alternatives,’
thereby showing no predictability of success for such number.” Id. at 14.
The Examiner responds that “the teachings of Chibout are not limited
to their working examples; there is no requirement under § 103 that a
reference supply actual data or exemplify all embodiments taught.” Ans. 37.
We are not persuaded by Appellant’s arguments. “[T]o have a
reasonable expectation of success, one must be motivated to do more than
merely to vary all parameters or try each of numerous possible choices until
Appeal 2019-003727
Application 14/482,193

14

one possibly arrived at a successful result, where the prior art gave either no
indication of which parameters were critical or no direction as to which of
many possible choices is likely to be successful.” Pfizer, Inc. v. Apotex,
Inc., 480 F.3d 1348, 1365 (Fed. Cir. 2007). This is not a case where there
are numerous parameters to try without direction from the prior art. Rather,
the combined prior art of Chibout and Uttenthal teach that: 1) NGAL was a
known marker for renal injury, 2) renal injury includes chronic renal injury,
and 3) changing levels of NGAL indicate improving or worsening renal
injury. See supra.
Therefore, the evidence shows that the skilled artisan would have had
a reasonable expectation of success in determining NGAL levels over time
to diagnose worsening chronic renal injury. “[T]he expectation of success
need only be reasonable, not absolute.” Pfizer, 480 F.3d at 1364. Appellant
has not presented any evidence supporting their contention that a person of
ordinary skill in the art would not have expected, contra the teachings of the
prior art, that increasing NGAL levels would be indicative of worsening
chronic renal disease. Attorney arguments and conclusory statements that
are unsupported by factual evidence are entitled to little probative value. In
re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997).
Accordingly, we are not persuaded that the Examiner erred in finding
a reasonable expectation of success and we affirm the Examiner’s rejection
of claims 50, 60, 72, and 73 as obvious over the prior art. With respect to
claim 66, Appellant repeats the same argument against Chibout with respect
to detecting worsening chronic renal injury. App. Br. 19. Accordingly,
claim 66 falls with claim 50 for the reasons set forth supra.

Appeal 2019-003727
Application 14/482,193

15

Issue 4: Obviousness of dependent claims 61 and 76
Appellant contends the prior art does not teach the step of “assigning
to the human a diagnosis of no acute renal injury when the human is not
experiencing an acute renal injury.” App. Br. 18.

Analysis
The Examiner finds “when working with patients with chronic renal
injury according to one embodiment of [Chibout], it would have been
obvious to ascertain that the patients actually have chronic renal injury as
opposed to acute renal injury to be sure of the patient’s correct diagnosis.”
Final Act. 16.
Appellant contends that “[a]n acute renal injury is a condition that
disguises or overwhelms a diagnosis of a chronic renal injury based on a
renal injury marker, including NGAL, as described in Appellant’s paragraph
[0018] and [0070].” App. Br. 18. Appellant’s Specification further states
that:
[T]he practice of the present invention typically involves the
selection or identification of a mammalian subject that is not
experiencing an acute renal injury. Typically, the clinician or
physician can determine clinically whether or not a subject is
experiencing an acute renal injury, by means well known in the
art, such as by excluding recent events such as surgeries,
ischemia, dehydration, sepsis, and nephrotoxin use.

Spec. ¶ 72. Appellant argues that because “Chibout provides no teaching of
detecting of a chronic renal injury,” Chibout cannot teach or suggest
excluding patients with no acute renal injury. App. Br. 19.
Appeal 2019-003727
Application 14/482,193

16

We are not persuaded. As discussed supra, we do not agree that the
combined prior art does not teach diagnosing worsening chronic renal injury.
Rather, Chibout suggests diagnosis and treatment of patients prior to
symptomatic kidney disorder. See Chibout 15–16. Symptomatic kidney
disorder includes acute renal injury, whereas pre-symptomatic kidney
disorder may include the early stages of chronic renal injury, which Chibout
teaches may be asymptomatic. Therefore, Chibout suggests identifying
humans without acute renal injury.
Moreover, Uttenthal expressly teaches cut-off levels that differentiate
between acute and non-acute renal disorders. Uttenthal ’307 4–5.
Therefore, Uttenthal teaches assigning to a human a diagnosis of no acute
renal injury based on NGAL levels. Parmar further teaches evaluating high-
risk chronic renal disease patients for risk factors associated with kidney
damage, such as autoimmune diseases, primary glomerulopathies, and
nephrotoxic agents. Parmar 86. The combined prior art teaches that it
would have been obvious to distinguish between humans having acute renal
injury and non-acute, e.g., chronic renal injury. We are therefore not
persuaded by Appellant’s arguments and, consequently, we affirm the
Examiner’s rejection of claims 61 and 76.

Issue 5: Obviousness of dependent claims 68–70 and 78–84.
Appellant contends the prior art “does not teach, and does not make
obvious or predictable, the feature asserted in the rejection of selecting a
period of time or time interval for sampling of a subject’s plasma or serum
for detecting a worsening of a chronic renal injury.” App. Br. 19 (emphasis
omitted).
Appeal 2019-003727
Application 14/482,193

17

Analysis
The Examiner finds although Chibout does “not specify specific time
periods for the post-administration samples, time was recognized in the prior
art to be a result-effective variable, for example in this case as the follow-up
time would have been recognized to have impacts [sic] on the patient’s
prompt treatment.” Final Act. 17. The Examiner finds it “would have been
obvious to arrive at time periods within the claimed ranges out of the course
of routine optimization, i.e., by selecting a time period for follow-up.” Id.
Appellant contends “Chibout teaches nothing whatsoever concerning
the period of time between a first sample of serum or plasma for a human
diagnosed with a chronic renal injury, and a second subsequent sample, to
assess if the chronic renal injury has worsened.” App. Br. 20. Appellant
argues that the time period in Chibout between the time of administering a
treatment agent and measuring a therapeutic effect “has no nexus to a time
period within which a worsening of a chronic renal injury might occur.” Id.
We are not persuaded. Chibout teaches a method of monitoring a
patient with a renal injury by comparing patient samples from two different
times to measure effectiveness of treatment. Chibout and Uttenthal teach
measuring NGAL to identifying improving or worsening chronic renal
injury. Uttenthal specifically teaches NGAL “can be monitored daily or
at shorter intervals” (Uttenthal 11:16–17), demonstrating that time periods
were a known optimizable parameter. Parmar teaches chronic renal disease
is a progressive disorder with multiple stages. Given the need in the prior art
to monitor patients with chronic renal injury to identify worsening disease it
would have been obvious to optimize the time periods of Chibout and
Uttenthal for long term monitoring. “[W]here the general conditions of a
Appeal 2019-003727
Application 14/482,193

18

claim are disclosed in the prior art, it is not inventive to discover the
optimum or workable ranges by routine experimentation.” In re Aller, 220
F.2d 454, 456 (C.C.P.A. 1955). Appellant has not submitted any evidence
that the claimed time intervals are critical. We are therefore not persuaded
that the Examiner erred and, consequently, we affirm the Examiner’s
rejection of claims 68–70 and 78–84.

Issue 6: Obviousness of claims 58, 59 and 76
Appellant argues the prior art does not teach diagnosing that the
subject is not experiencing a lung injury or an acute bacterial infection.
App. Br. 21.

Analysis
The Examiner acknowledges the combination of Chibout, Harlow,
Uttenthal, and Parmar does “not specifically teach also assessing the
presence of an acute bacterial or viral infection or acute inflammation … nor
do the references explicitly specify that the mammal is not experiencing
another condition such an acute bacterial or viral infection or acute
inflammation.” Final Act. 19. However, the Examiner finds “it was known
that NGAL is also elevated in the context of cystic fibrosis (i.e., lung injury)
as well as in acute bacterial infections.” Id. (citing Eichler 1145). The
Examiner finds “it would have been further obvious to one of ordinary skill
in the art to diagnose that the mammal is not experiencing cystic fibrosis
(i.e., lung injury) or an acute bacterial infection” when assessing chronic
renal injury. Id. By identifying non-renal conditions as sources of NGAL,
one of skill in the art would be able to draw conclusions about a patient’s
Appeal 2019-003727
Application 14/482,193

19

chronic renal injury without misdiagnosis due to other non-renal conditions.
Id.
Appellant contends Chibout addresses only acute renal injuries and
not chronic renal injury. App. Br. 21. Appellant contends that “Uttenthal-
Prov also demonstrates that its disclosed techniques and methods were not
recognized to distinguish between an acute renal injury and a chronic renal
injury.” Id. Appellant argues that:
[T]he level of NGAL taught by Uttenthal for a “renal injury,”
which is higher than levels of NGAL that result from
inflammatory, infective or cancerous conditions that do not
affect renal function, cannot then include a level of NGAL
attributable to a chronic renal injury, since such other conditions
(inflammatory, infective or cancerous conditions) can contribute
an amount of NGAL into the blood stream that can make it
difficult to distinguish such NGAL from NGAL that is expressed
as a direct result of the chronic renal injury.

Id. at 22 (citing Uttenthal ’307 p. 3, l. 32–p. 4, l. 2).
We are not persuaded. As discussed supra, Chibout and Uttenthal
teach NGAL as a marker for renal injury, defined as including chronic renal
injury. Uttenthal specifically states that “[e]levated levels of NGAL are
indicative of renal injury if they are higher than specified less elevated levels
of NGAL that may result from inflammatory or infective conditions or
cancers that do not affect renal function.” Uttenthal ’307 4. Uttenthal
continues:
Furthermore, the present invention, in one embodiment,
allows the discrimination between different types of renal
disorder. Thus, e.g., in one embodiment, the method of the
invention comprises a further step of comparing said
Appeal 2019-003727
Application 14/482,193

20

concentration with a second cutoff value, said second cutoff
value being chosen to exclude lower concentrations of NGAL
associated with renal disorders that are not ATN or ATIN,
wherein a concentration above the cutoff value is indicative of
ATN or ATIN.

Uttenthal ’307 4–5 (emphasis added). Therefore, Uttenthal teaches that
NGAL levels may be used as a marker to distinguish between different types
of renal disorders, as well as between renal injury and inflammatory or
infective conditions. Likewise, Parmar teaches evaluating high-risk chronic
renal disease patients for factors such as systemic infection. Parmar 86.
Moreover, given that lower NGAL levels may indicate non-acute renal
injury or non-renal injury, e.g., lung injury as taught by Eichler, it would
have been obvious to a person of ordinary skill in the art to exclude non-
renal injuries before diagnosing worsening chronic renal injury.
Accordingly we are not persuaded that the Examiner erred, and we affirm
the Examiner’s rejection of claims 58, 59, and 76.

B. Rejection of the claims under 35 U.S.C. § 103(a) over Chibout,
Uttenthal, Harlow, Parmar, Eichler, Williams, and Mori

Issue 1
Appellant contends Mori does not teach a nexus between NGAL and
chronic renal injury that confers a reasonable expectation of success in using
NGAL to diagnose worsening chronic renal injury. App. Br. 22–23
(emphasis omitted).

Appeal 2019-003727
Application 14/482,193

21

Analysis
The Examiner finds Mori teaches “that the NGAL protein is elevated
in serum in both acute and chronic renal disease (Figure 1C). [Mori]
therefore provides further evidence of a known nexus between protein
NGAL and chronic renal injury, the same disease taught by Chibout.” Final
Act. 22 (citing Mori 611).
Appellant acknowledges that Mori teaches a detectable level of serum
NGAL in a sample taken from a subject having a chronic renal injury. See
App. Br. 23. Appellant contends:
However, Mori does not teach or make obvious or predictable, a
step of evaluating and assigning to a human subject, who has
been diagnosed with a chronic renal injury, a further diagnosis of
no acute renal injury when the human is not experiencing an
acute renal injury, in order, further, to assign a diagnosis of
worsening chronic renal injury.

Id. Appellant contends “Mori does not teach, and does not make obvious or
predictable, of any nexus between protein NGAL and chronic renal injury
that could predictably confer a ‘reasonable expectation of success’ for the
use of NGAL to diagnose a worsening of a chronic renal injury. Id.
We are not persuaded. Appellant argues against Mori alone and not
the combination of the art. See Merck, 800 F.2d at 1097. Mori confirms the
teachings of Chibout and Uttenthal, that NGAL is a marker of chronic renal
injury as discussed supra. Accordingly, we are not persuaded that the
Examiner erred and, we affirm the Examiner’s rejection of claims 58, 59, 61,
58–70, and 74–84, over the combination of prior art including Mori.

Appeal 2019-003727
Application 14/482,193

22

CONCLUSION

The rejection of claims 50, 58–61, 66, 68–70, and 72–84 as
unpatentable under 35 U.S.C. § 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).

AFFIRMED

Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed
50, 60, 61,
66, 68–70,
72–84
103(a) Chibout, Harlow,
Uttenthal, Parma,
Williams
50, 60, 61,
66, 68–70,
72–84

58, 59, 76 103(a) Chibout, Harlow,
Uttenthal, Parma,
Williams, Eichler
58, 59, 76
61, 68–70,
74–84
103(a) Chibout, Harlow,
Uttenthal, Parma,
Williams, Mori
61, 68–70,
74–84

58, 59, 76 103(a) Chibout, Harlow,
Uttenthal, Parma,
Williams, Mori, Eichler
58, 59, 76
Overall
Outcome
50, 58–61,
66, 68–70,
72–84