Ex Parte Vogt

Patent Trial and Appeal Board

Nov 4, 2016

12158684 (P.T.A.B. Nov. 4, 2016)

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.
JCLA28570 1026
EXAMINER
BAEK, BONG-SOOK
ART UNIT PAPER NUMBER
1621
MAIL DATE DELIVERY MODE
12/158,684 08/25/2008
23900 7590
J C PATENTS
4 VENTURE, SUITE 250
IRVINE, CA 92618
11/07/2016
Birgit Vogt
11/07/2016 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BIRGIT VOGT
Appeal 2015-005540
Application 12/158,6841
Technology Center 1600
Before ERIC B. GRIMES, JOHN G. NEW, and DAVID COTTA,
Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of removing human C-reactive protein (CRP) extracorporeally from fluids of
a patient for treatment of cardiovascular diseases. The Examiner rejected
the claims on appeal as obvious under 35 U.S.C. § 103(a).
We affirm.
1 According to Appellant, the real party in interest is Pentracor GMBH.
App. Br. 1.
Appeal 2015-005540
Application 12/158,684
STATEMENT OF THE CASE
Claims 1—5 are on appeal. Claim 1 is the only independent claim and
reads as follows:
1. A method of specifically removing human C-
reactive protein (CRP) extracorporeally from biological
fluids of a patient for treatment of cardiovascular diseases,
comprising contacting the biological fluids with a matrix
containing compounds which have the characteristic to
specifically bind human C-reactive protein (CRP) at least
temporarily and removing human CRP extracorporeally
from biological fluids of the patient, wherein the
cardiovascular diseases are selected from the group
consisting of infarction, stroke, and myocardial infarction.
The Examiner rejected claims 1—5 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Kedar2 and Pepys.3
We affirm.
FINDINGS OF FACT
We adopt as our own the Examiner’s findings and analysis concerning
the scope and content of the prior art. The following findings are included
for emphasis and reference convenience.
1. Kedar discloses:
[A] method for removing C-reactive protein and
antiphosphorylcholine antibodies from the circulation of
patients with cancer by conducting extracorporeal
perfusion of a patient’s blood plasma through a
phosphorylcholine-matrix adsorption device so as to
improve the patient's cellular immune responses against
2 Kedar, WO 90/12632, published Nov. 1, 1990 (“Kedar”).
3 Pepys, US Patent Publication No. 2003/0171251 Al, published Sep. 11,
2003 (“Pepys”).
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Application 12/158,684
the cancer.
Kedar p. 1,11. 8—14.
2. Kedar discloses:
[PJumping blood from a patient through a cell separator]
which separates the cells into blood cells and plasma,
passing the blood plasma through a device, such as a
column, which contains adsorbent matrix material that
includes phosphorylcholine for removing C-reactive
protein and antiphosphorylcholine antibodies, and
recombining the plasma and cells before returning the
same to the patient.
Id. at p. 4,1. 34 — p. 5,1. 4.
3. Pepys discloses:
[I]t has been found for the first time that CRP does play a
direct pathogenetic [sic] role in a disease condition,
specifically by enhancing the extent of myocardial
damage produced by ischemic injury. This pathogenetic
[sic] role can be treated or prevented by the use of a drug
capable of inhibiting the binding of CRP to its target
ligand in vivo. . . . [I]t is thought that the inhibition of
binding of CRP to its target ligand in vivo would prevent
CRP from activating complement and thereby reduce or
eliminate the deleterious effects of CRP mediated
complement activation now thought responsible for
tissue damage.
Pepys 1 6.
4. Pepys discloses:
Once myocardial infarction has occurred, all patients
mount a major acute phase response of CRP and the peak
value attained is very significantly prognostic of
outcome, that is complications and death, over the
ensuing days, weeks and months. Given the universal co-
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Application 12/158,684
deposition of CRP and activated complement within the
infarct itself, this strongly suggests that CRP contributes
importantly to the extent and severity of the ischaemic
pathology.
Id. at 110.
5. Pepys discloses:
A method for the treatment or prevention of tissue
damage in a subject having a myocardial infarction,
which comprises administering to the subject an effective
amount of a compound capable of inhibiting binding of
C-reactive protein (CRP) to its autologous or extrinsic
ligand thereof at or after the onset of the infarction.
Id. at claim 17.
6. Berrouschot4 discloses:
Objective - Can extracorporeal membrane differential
filtration be used on patients with acute stroke to
optimize their hemorheology without reducing the
number of oxygen carriers (erythrocytes) — and is this
form of treatment safe? . . . Results - Extracorporeal
membrane differential filtration treatment immediately
led to a significant and sustained drop in all
hemorheological parameters (fibrinogen by 54%, ci2-
macroglobulin by 76%, total cholesterol by 65%, LDL by
82%, and HDL by 38%). Plasma viscosity dropped from
1.3 to 1.1 mPas, erythrocyte aggregation by 57%. By
contrast, hematocrit and the erythrocyte count remained
constant. Treatment had no side-effects. Conclusions -
Extracorporeal membrane differential filtration is a safe
4 Berrouschot et al., Extracorporeal Membrane Differential Filtration —A
New and Safe Method to Optimize Hemorheology in Acute Ischemic Stroke,
97 ActaNeurologica Scandinavia 126-130 (1998) (“Berrouschot”).
The Examiner cited Berrouschot as evidence that “it had been known in the
art at the time of the invention that extracorporeal treatment could be used
safely for the patients with stroke or infarction.” Ans. 6.
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Application 12/158,684
method to optimize hemorheology in patients with acute
ischemic stroke.
Berrouschot Abstract.
7. Wang5 discloses that its invention “relates to pharmaceutically
acceptable compositions and combinations, and methods utilizing these
natural, recombinant or synthetic antiplatelet polypeptides in the treatment
[of] extracorporeal blood.” Wang 133. Wang further discloses that “[t]he
antithrombosis enzyme of this invention is effective for the treatment of
thrombotic diseases, including, but not limited to . . . myocardial infarction,
stroke. . . .” Id. at| 147.
8. Strahilevitz6 discloses:
A method of removing at least one species from a
mammal, the method comprising a first step of confining
in a device a binding compound, the binding compound
having affinity for a binding partner . . . wherein the
device is an extracorporeal treatment device, the device
being used for treatment of a mammal for a disease state
selected from: . . . acute myocardial infarction (Ml)...
Strahilevitz claim 29.
9. Fadul7 discloses:
5 Wang et al., US Patent Publication No. 2006/015381 Al, published July
13, 2006 (“Wang”). The Examiner cited Wang as evidence that “many
patent literatures have suggested the use of extracorporeal treatment for
patients with acute myocardial infarction or stroke.” Ans. 6.
6 Strahilevitz, US Patent Publication No. 2005/0271653 Al, published Dec.
8, 2005 (“Strahilevitz”). The Examiner cited Strahilevitz as evidence that
“many patent literatures have suggested the use of extracorporeal treatment
for patients with acute myocardial infarction or stroke.” Ans. 6.
7 Fadul et al., Identification of Complement Activators and Elucidation of the
Fate of Complement Activation Products During Extracorporeal Plasma
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Application 12/158,684
In this study, we have demonstrated that substantial
complement activation should be expected during
extracorporeal plasma purification therapy. The plasma
separator and the following filter or column play a major
role in the generation of CAPs [complement activation
products]. Different ECPP [extracorporeal plasma
purification] treatments may have different effects
regarding the levels of complement activation products.
On the other hand, different CAPs may affect the results
of the treatment. Further, in vitro and in vivo studies
should determine whether these properties can be used to
facilitate or prevent effective treatment.
Fadul 172.
ANAFYSIS
The Examiner found that Kedar taught a process for removing C-
reactive proteins (“CRP”) from biological fluid by extracorporeal perfusion.
Ans. 3. In Kedar, blood is pumped from a patient through a device
containing phosphorylcholine, a CRP adsorbent matrix material, in order to
treat diseases such as cancer. Id. Kedar, however, does not teach that its
method is useful for treatment of infarction or stroke.
The Examiner found that Pepys taught that increased production of
CRP was associated with atherothrombotic events, including myocardial
infarction and stroke. Id. at 4. Pepys further teaches that once myocardial
infarction has occurred, “all patients mount a major acute phase response of
CRP and the peak value attained is very significantly prognostic of
outcome.” Id. CRP production thus “contributes importantly to the extent
and severity of the ischaemic pathology.” Id. Pepys teaches a method of
Purification Therapy, 13 Journal of Clinical Apheresis 167—173 (1998)
(“Fadul”). Appellants cite Fadul as evidence that “it is known that
complement activation products produced by extracorporeal treatment are an
obstacle especially for intensive care patients.” App. Br. 4.
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Application 12/158,684
treating and preventing tissue damage in patients with myocardial infarction,
stroke and other conditions, by administering a compound that inhibits or
blocks the binding of CRP to its targets in order to “reduce or eliminate the
deleterious effects of CRP mediated complement activation now thought to
be responsible for tissue damage.” Id. at 3^4.
Based on the teachings of Kedar and Pepys, the Examiner concluded:
It would have been prima facie obvious to one of
ordinary skill in the art at the time the invention was
made to use the matrix comprising phosphorylcholine
taught by WO 90/12632 [Kedar] for the treatment of
infarction or stroke by removing CRP from biological
fluids such as human blood or plasma since US
2003/0171251 [Pepys] teaches that myocardial infarction
and stroke are associated with increased production of
CRP and removing CRP from biological fluid is
desirable for reducing tissue damage in a subject having
an inflammatory and/or tissue damaging condition
including myocardial infarction and stroke. The skilled
artisan would have been motivated to do so on the
reasonable expectation of success that the matrix
containing phosphorylcholine would be useful for
treating such diseases or conditions by removing
abnormally increased CRP from the biological fluids.
Id. at 5.
Appellant argues that the person of ordinary skill in the art would not
have considered extracorporeal removal of CRP as a treatment for a disease
with an acute onset such as an infarction or stroke because extracorporeal
treatment would “destabilize the patient.” App. Br. 4. To support this
assertion, Appellant asserts that “clinicians specialized in apheresis” avoid
extracorporeal blood purification in infarction patients “because of the
significant extracorporeal blood volume which would further destabilize the
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patient. . . [as] evidenced by the fact that even dialysis for infarction patients
with additional renal failure will be delayed as far as possible.” Id. In
addition, Appellant asserts that Fadul teaches that complement activation
products produced by extracorporeal treatment are known to be “an obstacle
especially for intensive care patients.” Id.8 We are not persuaded.
While extracorporeal purification may present some degree of risk to
the patient, the combined teachings of Pepys and Kedar provide strong
motivation to undertake the procedure. Pepys teaches that CRP “contributes
importantly to the extent and severity of the ischaemic pathology.” FF4.
Kedar teaches that CRP can be removed by extracorporeal perfusion. FF1.
Pepys also suggests that Appellant’s concerns regarding complement
activation may be reduced by the removal of CRP. FF3. The Examiner
explained:
US 2003/0171251 [Pepys] teaches that the inhibition of
binding of CRP to its target ligand in vivo would prevent
CRP from activating complement and thereby reduce or
eliminate the deleterious effects of CRP mediated
complement activation. Thus, one of ordinary skill in the
art would have expected that complement activation
would not occur by extracorporeal[ly] removing CRP
taught by WO 90/12632 [Kedar] since it removes the
agent mediating complement activation, which is CRP, as
evidenced by US 2003/0171251 [Pepys].
Ans. 7.
In addition, the record here includes substantial evidence that others
of skill in the art have, in fact, considered extracorporeal treatments for
patients with stroke or infarction. See FF6—8 (disclosures of Berrouschot,
8 Appellant cites the Declaration of the Dr. Ahmed Sheriff, filed Jan. 20,
2012, in support of these arguments. See, Sheriff Deck p. 3.
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Application 12/158,684
Wang and Strahilevitz). Berrouschot, in particular, teaches that
“extracorporeal membrane differential filtration is a safe method to optimize
hemorheology in patients with acute ischemic stroke.” FF6 (emphasis
added).
Appellant asserts that “a person skilled in the art at the priority date
would not transfer knowledge” from Berrouschot to “CRP elimination using
apheresis” because the extracorporeal treatment in Berrouschot involved
membrane differential filtration whereas the present invention involves
“absorption onto beads coated with an absorbent material and filtration.”
Reply Br. 2. Appellant contends that absorption onto beads creates “a
higher risk for complement activation,” and thus a person of ordinary skill in
the art would not apply the teachings of Berrouschot to extracorporeal
removal of CRP. Appellant also suggests that a “physician would not
conclude” that “extracorporeal treatment is feasible” based on the teachings
of Wang and Strahilevitz because they are “patent applications without any
experimental data.” Reply Br. 1—2. We are not persuaded.
As an initial matter, Appellant does not identify persuasive evidence
to support the argument that filtering using beads coated with an absorbent
material creates additional risks as compared to filtering through a
membrane (as disclosed in Berrouschot). See Johnston v. IVAC Corp., 885
F.2d 1574, 1581 (Fed. Cir. 1989) (“Attorneys’ argument is no substitute for
evidence.”); In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Moreover,
both the claimed method and the method of Berrouschot involve
extracorporeal filtration. And Berrouschot teaches that its extracorporeal
filtration method is “safe” for stroke patients. FF6. Considering this
teaching together with Wang’s and Strahilevitz’s disclosure of
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extracorporeal treatments of patients with stroke or infraction, and Kedar’s
teaching of extracorporeal removal of CRP, we conclude that a
preponderance of the evidence supports the Examiner’s finding that a person
of ordinary skill in the art would have reasonably expected that CRP could
successfully be removed in patients with stroke or infarction by
extracorporeal perfusion.
Appellant argues that the claimed method is not obvious because
Pepys “would have motivated a skilled person to search for an active agent
suitable for injection or oral[] application” not to pursue extracorporeal
treatments. App. Br. 5. Appellant argues that an oral treatment would be
preferred because it less invasive. Id. In addition oral treatments are less
expensive than extracorporeal treatment, id. at 6, and more practical, since
removal of CRP by extracorporeal purification “only transiently reduce[s]
the amount of CRP during apheresis hours, while the amount of CRP will
increase again when CRP apheresis stops.” Id. at 5. In view of these
advantages, Appellant argues that the person of ordinary skill in the art
would not have pursued extracorporeal treatment absent knowledge of the
inventor’s discovery that an oral treatment must be used in such a “high
molecular excess” as to render treatment impracticable. Id. at 6.
We agree with the Examiner that Appellant is improperly attacking
the references individually when the rejection is based on a combination of
references. Ans. 10; In re Keller, 642 F.2d 413, 425 (CCPA 1981). Here,
based on Pepys, the person of ordinary skill in the art would have recognized
that the increased production of CRP in patients with infarction or stroke
was a problem. See FF3 and FF4. The person of ordinary skill in the art
would have recognized that Kedar provides a solution; removing CRP from
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Application 12/158,684
the blood by extracorporeal perfusion. See FF1. The possibility that other
hypothetical potential solutions might also exist does not make Kedar’s
solution any less obvious.9
Appellant argues that Pepys 200610 calls into question the clinical
applicability of Pepys because the CRP blocker used in Pepys 2006 “had to
be administered before infarction and constantly afterwards.” App. Br. 6.
Appellant asserts that this approach would not work in humans because “a
prophylactic treatment is not feasible.” Id. We disagree that Pepys 2006
calls into question the teachings of Pepys. Pepys 2006 expressly states
“therapeutic inhibition of CRP is thus a promising new approach to
cardioprotection in acute myocardial infarction, and may also provide
neuroprotection in stroke.” Pepys 2006 Abstract. Moreover, as the
Examiner pointed out, the reason the investigators in Pepys 2006 chose to
administer the CRP blocker before infarction was to “closely replicat[e] the
initial dynamics of the endogenous human CRP response. Id. at 1219; Ans.
13. Accordingly, we find that Pepys 2006 does not detract from the
teachings of Pepys.
SUMMARY
For these reasons and those set forth in the Examiner's Answer, the
Examiner's final decision to reject claims 1—5 is affirmed.
9 We note that the Examiner found that the person of ordinary skill would
have expected that extracorporeal perfusion would be a faster and more
direct way to remove CRP from the blood than administering an oral
treatment. Ans. 12.
10 Pepys et al., Targeting C-Reactive Protein for the Treatment of
Cardiovascular Disease, 440 Nature 1217—1221 (2006) (“Pepys 2006”).
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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
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