Werner Beck et al.

Patent Trials and Appeals Board

Mar 10, 2021

2020001728 (P.T.A.B. Mar. 10, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/477,473 05/22/2012 Werner Beck 52759-220738 5355
23643 7590 03/10/2021
Barnes & Thornburg LLP (IN)
11 S. Meridian Street
Indianapolis, IN 46204
EXAMINER
PEO, JONATHAN M
ART UNIT PAPER NUMBER
1779
NOTIFICATION DATE DELIVERY MODE
03/10/2021 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):
INDocket@btlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte WERNER BECK and JUAN BOSCH
Appeal 2020-001728
Application 13/477,473
Technology Center 1700

Before CHRISTOPHER C. KENNEDY, JEFFREY R. SNAY, and
JENNIFER R. GUPTA, Administrative Patent Judges.

GUPTA, Administrative Patent Judge.

DECISION ON APPEAL1
Pursuant to 35 U.S.C. § 134(a), Appellant2 appeals from the
Examiner’s final decision to reject claims 1–6, 15–17, and 21. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 This Decision includes citations to the following documents: Specification
filed May 22, 2012 (“Spec.”); Final Office Action dated February 26, 2019
(“Final Act.”); Appeal Brief filed June 18, 2019 (“Appeal Br.”);
Supplemental Appeal Brief filed July 10, 2019 (“Supp. Appeal Br.”);
Examiner’s Answer dated October 21, 2019 (“Ans.”); and Reply Brief filed
December 23, 2019 (“Reply Br.”).
2 Appellant refers to “applicant” as defined in 37 C.F.R. § 1.42(a). Appellant
identifies the real party in interest as Gambro Lundia AB. Appeal Br. 2.
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CLAIMED SUBJECT MATTER
The claims are directed to a method for treating anemia in
hemodialysis (“HD”) patients. Spec. 1; Supp. Appeal Br. 3 (Claims App.).
Anemia, a condition in which the blood does not have enough red blood
cells, is known to be one of the major complications among HD patients.
Spec. 1, ll. 18–19, 22–24. Anemia in HD patients, which is characterized by
low erythropoietic activity, can be treated with erythropoietin stimulating
agents (“ESA”). Id. at 1, ll. 29–30, 2, ll. 9–20, 28–31. Some HD patients,
however, are resistant to ESA treatment; this resistance is sometimes
referred to as EPO hypo-responsiveness. Id. at 3, ll. 6–13; see also id. at 3, l.
33–4, l. 4.
The claimed method uses a high cut-off dialysis membrane to treat
chronic HD patients, especially erythropoietin (“EPO”) resistant dialysis
patients. Id. at 7, ll. 8–12. Using the high cut-off membrane was found to
improve EPO responsiveness and effectively treat anemia in HD patients. Id.
at 13–16. Claim 1, reproduced below, is illustrative of the claimed subject
matter:
1. A method of treating anemia in a chronic
hemodialysis patient, comprising withdrawing and bypassing
blood from the patient in a continuous flow into contact with
one face of a hemodialysis membrane, simultaneously passing
dialysate solution in a continuous flow on an opposite face of
the hemodialysis membrane to the side of the hemodialysis
membrane in contact with the blood, the flow of the dialysate
solution being countercurrent in a direction to the flow of
blood, and returning the blood into the patient, wherein the
hemodialysis membrane has a molecular weight cut-off in
water, based on dextran sieving coefficients, of between 90 and
200 kD and a molecular weight retention onset in water, based
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on dextran sieving coefficients, of between 10 and 20 kD, and a
∆MW of between 90 and 170 kD,
wherein the chronic hemodialysis patient suffers from
EPO hypo-responsiveness, and
wherein the method decreases hepcidin in the blood of
the chronic hemodialysis patient, and
wherein the method increases hemoglobin to above
11 g/dl in the blood of the chronic hemodialysis patient to treat
anemia.
Supp. Appeal Br. 3 (Claims App.).
REJECTIONS
The Examiner maintains the following rejections on appeal (Final Act.
12–24; Ans. 3):
Rejection 1: Claims 1, 4, 6 and 21 are rejected under pre-AIA 35
U.S.C. § 103(a) as unpatentable over de Francisco,3 Hutchison,4 as
evidenced by Magee,5 further in view of Buck,6 Markley,7 and Zaritsky.8

3 Angel L. M. de Francisco et al., Inflammation and its Impact on Anaemia
in Chronic Kidney Disease: From Haemoglobin Variability to
Hyporesponsiveness, 2 [Suppl 1] NDT Plus i18–i26 (2009).
4 Hutchison et al., US 2010/0084339 A1, published April 8, 2010.
5 Core Concepts in Dialysis and Continuous Therapies 258–262 (Colm C.
Magee, J. Kevin Tucker & Ajay K. Singh eds., Springer 2016).
6 Buck et al., WO 2004/056460 A1, published July 8, 2004.
7 Markley, US 3,746,175, issued July 17, 1973.
8 Joshua Zaritsky et al., Reduction of Serum Hepcidin by Hemodialysis in
Pediatric and Adult Patients, 5 Clin. J. Am. Soc. Nephrol. 1010–1014
(2010).
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Rejection 2: Claims 2, 15, and 16 are rejected under pre-AIA 35
U.S.C. § 103(a) over de Francisco, Hutchison, Buck, Markley, and Zaritsky,
as evidenced by NPL-19 and NPL-2,10 and further in view of Krantz;11
Rejection 3: Claims 3 and 17 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as unpatentable over de Francisco, Hutchison, Buck, Markley,
Zaritsky, and NPL-3;12 and
Rejection 4: Claim 5 is rejected under pre-AIA 35 U.S.C. § 103(a) as
unpatentable over de Francisco, Hutchison, Buck, Markley, Zaritsky, and
Twardowski.13
DISCUSSION
Rejection 1 – Claims 1, 4, 6, and 21
Appellant’s arguments focus on claim 1. Appeal Br. 4–21. Although
claim 21 is presented in the Appeal Brief under a separate heading,
Appellant does not provide any substantively separate arguments regarding
claim 21 and instead relies on the arguments presented for claim 1. Id. at 21.
Thus, we select claim 1 as representative of the rejected claims, and claims

9 Guideline 14: Causes of an Inadequate Response to Epoetin Treatment, 14
[Suppl 5] Nephrol. Dial. Transplant 25–27 (1999).
10 Alexander Kainz et al., Association of ESA Hypo-responsiveness and
Haemoglobin Variability with Mortality in Haemodialysis Patients, Nephrol.
Dial. Transplant 1–6 (2010).
11 Sanford B. Krantz, MD, Pathogenesis and Treatment of the Anemia of
Chronic Disease, 307 (5) Am. J. Med. Sci. 353–359 (1994).
12 NKF KDOQI Guidelines (2006), http://www2.kidney.org
/professionals/KDOQ/guidelines_anemia/ped32.htm (last visited March 2,
2015).
13 Twardowski, US 5,484,397, issued January 16, 1996.
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4, 6, and 21 will stand or fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv)
(2018).
Upon consideration of the evidence on this record and each of
Appellant’s arguments, we find that the preponderance of evidence supports
the Examiner’s conclusion that the subject matter of claim 1 is unpatentable
over the applied prior art. We sustain the Examiner’s § 103(a) rejection
essentially for the reasons set out by the Examiner in the Final Office Action
and the Answer. We add the following.
The Examiner finds that de Francisco in combination with Hutchison,
as evidenced by Magee, Buck, and Markley, teach claim 1’s method of
treating anemia in a chronic HD patient using the claimed (“high cut-off”)
hemodialysis membrane, but does not explicitly teach that de Francisco’s
modified method “decreases hepcidin in the blood of the chronic
hemodialysis patient.” Final Act. 12–16.
Hepcidin is a regulator of systemic iron availability and may be used
as a marker for EPO responsiveness. Spec. 7, ll. 32–33–8, l. 4; Zaritsky,
Abstr., 1010. The Examiner finds that Zaritsky teaches hepcidin is decreased
in the blood of a chronic HD patient. Id. at 17 (citing Zaritsky 1013 (“The
findings of this study clearly demonstrated that hepcidin itself is removed by
HD.”)). The Examiner finds that Zaritsky teaches that “[t]he end result of
lowering hepcidin levels would be improved erythropoiesis and potentially
decreased use and safer dosing of ESA and iron therapies.” Id. (citing
Zaritsky 1014). Based on Zaritsky’s teachings, the Examiner finds that one
of ordinary skill in the art would have used de Francisco’s modified method
of treating anemia to decrease the hepcidin in the blood of the chronic
hemodialysis patient to enhance the response to ESA in HD patients, which
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is discussed in de Francisco. Id.; de Francisco i18 (“[V]arious options for
intervention to enhance the response to ESAs in haemodialysis patients with
inflammation are considered.”). The Examiner finds that “Zaritsky[]
demonstrates that removing and reducing hepcidin from the blood of a
patient via hemodialysis is an expected result.” Id. at 8.
Appellant argues that the Examiner’s rejection of claims 1, 4, 6, and
21 is improper for at least three reasons: (A) A prima facie case of
obviousness has not been established; (B) The prior art teaches away from
the claimed invention; and (C) The claimed invention has unexpected
properties compared to the teachings of the cited art. Appeal Br. 4. We
address each of these reasons in turn below.
A. No Prima Facie Case of Obviousness
Appellant argues that “a prima facie case of obviousness has not been
established because a person of ordinary skill would not have been
motivated to modify de Francisco according to the teachings of Hutchison,
Magee, Buck, Markley, and Zaritsky.” Appeal Br. 13. Specifically,
Appellant argues that “the Examiner has not provided reasoning sufficient to
explain why a person of ordinary skill would have combined de Francisco
with Hutchison.” Id. at 14; see also id. at 20. Appellant argues that “the
Examiner’s alleged motivation in de Francisco is [based on a] highly edited
citation from de Francisco . . . [and t]his portrayal of the teachings of de
Francisco has been grossly oversimplified . . . to establish the alleged prima
facie case of obviousness.” Id. at 15.
Appellant’s arguments are not persuasive. Hutchison teaches that
there was a global decrease in pre-dialysis serum concentrations of pro-
inflammatory cytokines in patients that received two weeks of treatment
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using a high cut-off hemodialyser, HCO 1100TM. Hutchison ¶¶ 79–81. De
Francisco teaches that “[p]ossible future pharmacological interventions for
inflammation-associated hyporesponsiveness to ESA therapy include anti-
cytokine and anti-oxidative treatment strategies.” De Francisco i24. Based
on those teachings, the Examiner finds that one of ordinary skill in the art
would have used a HCO 1100TM membrane, as taught by Hutchison, in
Francisco’s method of treating anemia in a chronic hemodialysis patient to
decrease pro-inflammatory activity and hypo-responsiveness to ESA. See
Final Act. 14–15. Thus, the Examiner has provided a sufficient reason,
supported by factual evidence, for combining de Francisco and Hutchison.
Appellant also argues that “the Examiner has not provided reasoning
sufficient to explain why a person of ordinary skill would have combined
‘modified’ de Francisco with Zaritsky.” Appeal Br. 20. Appellant argues that
one of ordinary skill in the art would not have modified de Francisco based
on Zaritsky because the patients evaluated in Zaritsky were not anemia
patients suffering from EPO hypo-responsiveness. Id. at 20–21.
Appellant’s arguments are not persuasive. Although Zaritsky may not
exclusively focus on anemia patients suffering from EPO hypo-
responsiveness, Zaritsky’s study investigated the contribution of hepcidin to
iron maldistribution and anemia in HD patients and teaches or at least
suggests that lower hepcidin levels improve ESA responsiveness. Zaritsky
Abstr. (Background), 1010 (“[I]ncreased serum hepcidin . . . could play a
major role in . . . erythropoiesis-stimulating agents (ESA)); see also id. at
1010 (“The improvement in ESA responsiveness [was] reported in
prolonged dialysis regimens[,]” which increased the removal of hepcidin.).
As discussed above, the Examiner finds that one of ordinary skill in the art
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would have used de Francisco’s modified method of treating anemia to
decrease the hepcidin in the blood of the chronic hemodialysis patient to
enhance the response to ESA in HD patients, which is discussed in de
Francisco. Final Act. 17; de Francisco i18 (“[V]arious options for
intervention to enhance the response to ESAs in haemodialysis patients with
inflammation are considered.”). Thus, the Examiner has provided a
sufficient reason, supported by factual evidence, for combining de Francisco
and Zaritsky.
B. Teaching Away
Appellant argues that Zaritsky teaches that hemodialysis patients
undergoing “prolonged dialysis regimens” were reported to have an
“improvement in ESA responsiveness.” Appeal Br. 10 (emphasis omitted).
Appellant argues that based on Zaritsky’s teaching “a person of ordinary
skill in the art . . . would not [have been] led to treat anemia in . . . [a]
chronic hemodialysis [patient] suffering from EPO hypo-responsiveness.”
Id. at 10–11.
Appellant’s argument is not persuasive of reversible error because
Appellant fails to persuasively identify any disclosure in Zaritsky that
criticizes, discredits, or otherwise discourages treating anemia in a chronic
hemodialysis patient that is EPO resistant. See In re Fulton, 391 F.3d 1195,
1201 (Fed. Cir. 2004) (explaining that a reference teaches away when it
criticizes, discredits, or otherwise discourages the claimed solution).
Zaritsky teaches that hepcidin, the principal regulator of iron
homeostasis, may play a critical role in the response of patients with anemia
to ESA therapy. Zaritsky 1010. Zaritsky teaches that “the clearance of
hepcidin via HD suggests a therapeutic intervention in which patients with
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anemia and high hepcidin levels are changed to a more intensive dialysis
regimen to lower circulating hepcidin concentrations, release iron from
stores, and increase enteral iron absorption.” Id. at 1014. Zaritsky further
teaches that “[t]he end result of lowering hepcidin levels would be improved
erythropoiesis and potentially decreased use and safer dosing of ESA and
iron therapies.” Id. Thus, a preponderance of the evidence supports the
Examiner’s finding that, based on Zaritsky’s teachings, one of ordinary skill
in the art would have been led to decrease hepcidin in the blood of a chronic
hemodialysis patient suffering from EPO hypo-responsiveness.
Appellant also argues that de Francisco teaches that patients receiving
on-line haemofiltration exhibited micro-inflammation to a lesser degree than
patients on high-flux HD. Appeal Br. 11 (citing de Francisco i23). Based on
that teaching, Appellant argues that “a person of ordinary skill in the art . . .
would [have been] led to contemplate using hemofiltration in patients
instead of hemodialysis.” Id. (emphasis omitted).
Appellant’s argument is not persuasive of reversible error because the
disclosure identified by Appellant does not criticize, discredit, or otherwise
discourage hemodialysis. “[J]ust because better alternatives exist in the prior
art does not mean that an inferior combination is inapt for obviousness
purposes.” In re Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012).
C. Unexpected Properties
Appellant argues that the Examiner’s finding that Zaritsky
demonstrates removing and reducing hepcidin from the blood of a patient
via hemodialysis is an “expected result” is flawed for three reasons. Appeal
Br. 6.
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Appellant first argues that “the patients that were evaluated in
Zaritsky were not anemia patients suffering from EPO hypo-
responsiveness.” Id. at 6 (emphasis omitted). Appellant’s argument is not
persuasive or well-taken because, as discussed above, Zaritsky’s study
investigated the contribution of hepcidin to iron maldistribution and anemia
in HD patients and teaches or at least suggests that lower hepcidin levels
improve ESA responsiveness in HD patients with anemia. Zaritsky, Abstr.
(Background), 1010 (“[I]ncreased serum hepcidin . . . could play a major
role in . . . erythropoiesis-stimulating agents (ESA)); see also id. at 1010
(“The improvement in ESA responsiveness [was] reported in prolonged
dialysis regimens[,]” which increased the removal of hepcidin.).
Appellant next argues that “the membranes utilized in Zaritsky are not
encompassed by the claimed invention.” Appeal Br. 7 (emphasis omitted).
Appellant also argues that “a person of ordinary skill in the art, upon reading
Zaritsky, would not [have been] led to use the membranes specified by
claim 1 but, instead, would [have been] led to use a high flux filter.” Id. at
11.
Appellant’s arguments are not persuasive of reversible error because
the Appellant is attacking the references individually when the rejection is
based upon a combination of prior art disclosures. In re Keller, 642 F.2d
413, 426 (CCPA 1981) (“[O]ne cannot show non-obviousness by attacking
references individually where, as here, the rejections are based on
combinations of references”). The Examiner does not rely on Zaritsky for
claim 1’s hemodialysis membrane. Rather, the Examiner finds, and
Appellant does not dispute that Hutchison, not Zaritsky, teaches claim 1’s
hemodialysis membrane. Compare Final Act. 13–15, and Ans. 19, with
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Appeal Br. 4–21. The Examiner relies on Zaritsky “to disclose that dialyzers
naturally remove hepcidin during hemodialysis treatment.” Ans. 19.
Appellant argues that “the Polyflux/Revaclear high flux membranes
utilized in Zaritsky have been shown to not result in a sustainable decrease
of pre-dialysis levels of hepcidin in patients suffering from EPO hypo-
responsiveness,” as evidenced by the Declaration under 37 C.F.R. § 1.132 of
Dr. Werner Buck (“the Buck Declaration”) filed October 26, 2018. Appeal
Br. 7 (emphasis omitted); Buck Decl. ¶ 9.
Appellant’s evidence is not persuasive because it does not provide a
comparison with the closest prior art. In re Baxter Travenol Labs., 952 F.2d
388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as evidence
of nonobviousness, the results must be shown to be unexpected compared
with the closest prior art.”). Hutchinson discloses a hemodialysis membrane
as recited in claim 1. Ans. 19; Final Act. 10–11. The “control group” used in
the study in the Buck Declaration, however, received treatment with
dialyzers such as Revaclear and Polyflux. Appeal Br. 7.
The Buck Declaration admits that de Francisco suggests a correlation
between hepcidin and pro-inflammatory cytokines. Buck Decl. ¶ 6.
Although the study in the Buck Declaration did not find any association
between the concentration of hepcidin and pro-inflammatory cytokines in
patients when using the claimed method (Buck Decl. ¶ 10), Zaritsky
expressly discloses that using Polyflux/Revaclear membranes with HD
treatment results in hepcidin removal. Zaritsky 1013 (“The findings of this
study clearly demonstrated that hepcidin itself is removed by HD . . . .”).
Further, because a preponderance of the evidence supports the Examiner’s
determination that de Francisco’s method, as modified by Hutchison,
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Magee, Buck, and Markley, is the same as claim 1’s method, a
preponderance of the evidence supports the Examiner’s finding that
decreasing hepcidin in the blood of the chronic hemodialysis patient would
have been an expected or “natural result” of de Francisco’s modified
method. PAR Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1195–96
(Fed. Cir. 2014) (explaining that inherency may supply a missing claim
limitation in an obviousness analysis when “the limitation at issue
necessarily must be present, or the natural result of the combination of
elements explicitly disclosed by the prior art.”).
In sum, on this record, a preponderance of the evidence supports the
Examiner’s conclusion that the subject matter of claims 1, 4, 6, and 21
would have been obvious over de Francisco, Hutchison, Magee, Buck,
Markley, and Zaritsky.
Rejections 2–4 – Claims 2, 3, 5, and 15–17
Claims 2, 3, 5, and 15–17 depend from claim 1. Although set forth
under separate headings, Appellant does not present additional substantive
arguments for the patentability of dependent claims 2, 3, 5, and 15–17.
Appeal Br. 22–23. Because we do not find Appellant’s arguments regarding
claim 1 persuasive for the reasons discussed above, we also sustain the
rejections of claims 2, 3, 5, and 15–17 over the cited art.
CONCLUSION
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 4, 6, 21 103(a) de Francisco,
Hutchison, Magee,
1, 4, 6, 21
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Buck, Markley,
Zaritsky
2, 15, 16 103(a) de Francisco,
Hutchison, Buck,
Markley, Zaritsky,
NPL-1, NPL-2,
Krantz
2, 15, 16
3, 17 103(a) de Francisco,
Hutchison, Buck,
Markley, Zaritsky,
NPL-3
3, 17
5 103(a) de Francisco,
Hutchison, Buck,
Markley, Zaritsky,
Twardowski
5
Overall
Outcome
1–6, 15–17,
21

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED