Ex Parte Frostegard

Board of Patent Appeals and Interferences

Jul 16, 2009

10814125 (B.P.A.I. Jul. 16, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte JOHAN FROSTEGARD
____________

Appeal 2009-002066
Application 10/814,125
Technology Center 1600
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Decided1: July 16, 2009
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Before TONI R. SCHEINER, DONALD E. ADAMS, and STEPHEN
WALSH, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims 1-14 and 16-26,
the only claims pending in this application. We have jurisdiction under 35
U.S.C. § 6(b).

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

Appeal 2009-002066
Application 10/814,125

STATEMENT OF THE CASE
The claims are directed to a method for diagnosing early
cardiovascular disease. Claims 1, 5, and 9 are illustrative:
1. A method for diagnosing early cardiovascular disease comprising
(a) contacting a sample of body fluid with phosphocholine and/or a
derivative thereof, (b) assessing the presence and/or concentration of
antibodies to phosphocholine and/or to said derivative in the sample by
measuring antibodies bound to phosphocholine and/or derivative thereof,
and (c) diagnosing early cardiovascular disease based on the presence and/or
concentration of said antibodies in the sample.

5. The method of claim [1, wherein said early cardiovascular disease
comprises atherosclerosis, hypertension or thrombosis and] wherein
measuring comprises a radioimmunoassay.

9. The method of claim 1, wherein measuring comprises an enzyme
linked immunosorbent assay.

The Examiner relies on the following evidence:
G. Ostermann, et al., The degradation of platelet-activating factor in serum
and its discriminative value in atherosclerotic patients, 52 Thrombosis
Research 529-540 (1988).

Mary A. Smal, et al., A specific, sensitive radioimmunoassay for platelet-
activating factor (PAF), 128 J. Immunol. Methods 183-188 (1990).

Jordi Barquinero, et al., Antibodies against platelet-activating factor in
patients with antiphospholipid antibodies, 3 Lupus 55-58 (1994).

G.I. Muzya, et al., Reaction of antiphosphatidylcholine antibodies with
thrombocyte-activating phospholipid factor and its structural cellular
analogues, 6 Immunologiya 9-16 (1997).
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Application 10/814,125

The rejections presented by the Examiner are as follows2:
1. Claims 1-3, 6-8, 11-14, 16, 17, 20-23, and 26 stand rejected under 35
U.S.C § 103(a) as unpatentable over the combination of Muzya and
Ostermann.
2. Claims 4, 9, 18, and 24 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Muzya, Ostermann, and Barquinero.
3. Claims 5, 10, 19, and 25 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Muzya, Ostermann, and Smal.
We reverse.

PRINCIPLES OF LAW
In proceedings before the Patent and Trademark Office, the Examiner
bears the burden of establishing a prima facie case of obviousness based
upon the prior art. In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992). On
appeal to this Board, Appellants must show that the Examiner has not
sustained the required burden. See Ex parte Yamaguchi, 88 USPQ2d 1606,
1608 and 1614 (BPAI 2008) (precedential); Ex parte Fu, 89 USPQ2d 1115,
1118 and 1123 (BPAI 2008) (precedential); Ex parte Catan, 83 USPQ2d
1569, 1570 and 1577 (BPAI 2007) (precedential); Ex parte Smith, 83
USPQ2d 1509, 1512-1514, 1519 (BPAI 2007) (precedential).
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).

2 We recognize the Examiner’s objection of claims 21-26 (Ans. 4). This
objection is a petitionable matter not subject to review on Appeal.
Accordingly, we will not address this objection.
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Application 10/814,125

When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that is was obvious under § 103.

Id. at 421. It is proper to “take account of the inferences and creative steps
that a person of ordinary skill in the art would employ.” Id. at 418. See also
id. at 421 (“A person of ordinary skill is also a person of ordinary creativity,
not an automaton.”). “In determining whether obviousness is established by
combining the teachings of the prior art, the test is what the combined
teachings of the references would have suggested to those of ordinary skill
in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal
quotations omitted).

Muzya and Ostermann:
ISSUE

Does the combination of Muzya and Ostermann make obvious the
diagnosis of early cardiovascular disease based on the presence and/or
concentration of antibodies to phosphocholine and/or a derivative thereof in
a sample of body fluid?

FINDINGS OF FACT
FF 1. Platelet aggregating or activating factor (PAF) “is the chemical 1-O-
alkyl-2-acetyl-sn-glycero-3-phosphocholine” and is therefore a derivative of
phosphocholine (Reply Br. 3; Spec. ¶ 0025).
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Application 10/814,125

FF 2. Muzya teaches that “[p]hospholipid PAF is involved in the
regulation of the blood clotting system, the cardio-vascular system and the
immune system and is a mediator of inflammation with a range of etiologies,
of allergic reactions and many other pathophysiological processes” (Muzya
9: 17-20; see also Ostermann 530: 2-5 (PAF “is an extremely potent lipid
mediator which is considered to be involved in various inflammatory,
respiratory, and cardiovascular disorders” (endnotes omitted)).
FF 3. The aim of Muzya’s “study was to investigate the reaction of blood
serum containing antiphosphatidylcholine antibodies with PAF and its
structural analogues” (Muzya 10: 5-6).
FF 4. Muzya teaches that “[t]o study the way antiphosphatidylcholine
(aPC) antibodies bind with phospholipid PAF and its structural analogues,
blood serum containing IgM, or IgM and IgG phosphatidylcholine
antibodies was taken from patients presenting with obstetric and
gynecological pathologies” (Muzya 11: 28-30).
FF 5. Muzya teaches the use of an enzyme immunoassay (EIA) “to study
the manner in which aPL antibodies (phospholipid antibodies) bind with
PAF and its structural analogues” (Muzya 11: 9-10).
FF 6. To perform the EIA Muzya teaches the adsorption of phospholipids
including, inter alia, PAF to the wells of polystyrene microplates and the
subsequent addition of blood serum samples to the microplate wells (Muzya
11: 10-26).
FF 7. Muzya teaches that the “results of the assay were considered positive
if the average OD of the assay sample was greater than the total of the
average OD for the negative controls and two average mean square
deviations” (Muzya 11: 24-26).
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Application 10/814,125

FF 8. Muzya teaches that “[t]he results of this study show that IgM and
IgG aPC antibodies in blood serum from patients with obstetric and
gynaecological pathologies are capable of binding in vitro with PAF and its
structural analogues which differ from PAF in the type of bond at the sn-1
position: a simple ether bond in the case of PAF and an ester bond in the
case of 1-acyl-PAF” (Muzya 14: 3-6).
FF 9. The Examiner finds that Muzya differs from the claimed invention
by not “teaching PAF as an indicator for cardiovascular diseases such as
atherosclerosis via PAF quantification in serum and plasma” (Ans. 5-6).
FF 10. Ostermann’s “study demonstrates a series of strong relationships
between serum lipoproteins, degradation of PAF and the manifestation of
coronary artery diseases” (Ostermann 536: 13-15).
FF 11. Ostermann teaches that “the degradation of PAF is catalyzed by a
specific acetylhydrolase” (Ostermann 536: 20 - 537: 1).
FF 12. Ostermann’s “study was undertaken to establish whether serum
PAF-acetylhydrolase is useful to discriminate between patients suffering
from cardiovascular disease and healthy subjects” (Ostermann 530: 27-30).
FF 13. Muzya teaches that “aPC antibodies can, apparently, bind with PAF
in the microenvironment of cells actively producing PAF. It can be
suggested that the formation of a compound with an antibody can inhibit the
cleavage of PAF by acetylhydrolase” (Muzya 14: 21-23).
FF 14. Ostermann teaches that “[c]onsidering the suggested role of PAF in
the development of atherosclerosis . . . it seems quite surprising that the
serum capacity to inactivate this highly proinflammatory phospholipid is
significantly increased in serum of patients suffering from coronary artery
diseases” (Ostermann 536: 16-20).
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Application 10/814,125

FF 15. Ostermann teaches that “[a]lthough there is no proof that the
relationships between the degradation of PAF in serum and atherosclerosis
are causative in nature there are some hints to a possible use of serum PAF-
acetylhydrolase as a risk indicator of atherosclerosis” (Ostermann 537: 17-
21).

ANALYSIS
Claim 1 is drawn to a method for diagnosing early cardiovascular
disease. All other claims on appeal depend directly or indirectly from claim
1. The method of claim 1 comprises the following three steps:
(a) contacting a sample of body fluid with phosphocholine and/or a
derivative thereof,
(b) assessing the presence and/or concentration of antibodies to
phosphocholine and/or to said derivative in the sample by measuring
antibodies bound to phosphocholine and/or derivative thereof, and
(c) diagnosing early cardiovascular disease based on the presence
and/or concentration of said antibodies in the sample.
PAF is a phosphocholine derivative (FF 1). Muzya teaches an ELISA
wherein PAF is absorbed to wells of a microplate that is subsequently
treated with a sample of a body fluid (FF 5-6). Accordingly, Muzya teaches
step (a) of Appellants’ claimed invention.
Muzya confirms the presence of antibodies to PAF in a sample by
measuring antibodies bound to PAF (FF 6-7). Appellants’ claims do not
require the antibodies to bind exclusively to phosphocholine (Cf. App. Br.
4). In this regard, we note that Muzya teaches that IgM and IgG
antiphosphatidylcholine (aPC) antibodies are capable of binding PAF, a
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Application 10/814,125

phosphocholine derivative within the scope of Appellants’ claimed invention
(FF 1 and 8). Accordingly, Muzya teaches step (b) of Appellants’ claimed
invention.
Muzya does not, however, teach that early cardiovascular disease can
be diagnosed based on the presence and/or concentration of antibodies to
phosphocholine and/or a derivative thereof in a sample of body fluid (FF 9).
Ostermann fails to make up for this deficiency.
Ostermann teaches that a relationship exists between coronary artery
diseases and PAF degradation, which is catalyzed by a specific
acetylhydrolase (FF 10 and 11). Therefore, rather than looking at antibodies
that bound PAF, Ostermann’s study sought to determine if PAF-
acetylhydrolase is useful in detecting patients suffering from cardiovascular
disease (FF 12). Further, while Muzya suggests that antibodies that bind
PAF can inhibit the cleavage of PAF by acetylhydrolase (FF 13),
Ostermann reports that it is surprising that a patient’s serum capacity to
inactivate PAF is significantly increased in patients suffering from coronary
artery disease (FF 14). In sum, Ostermann fails to direct a person of
ordinary skill in this art to determine the presence and/or concentration of
antibodies to phosphocholine and/or a derivative thereof in a sample of body
fluid. Instead, Ostermann suggests the “use of serum PAF-acetylhydrolase
as a risk indicator of atherosclerosis” (FF 15; see generally App. Br. 5).

CONCLUSION OF LAW
The combination of Muzya and Ostermann fails to make obvious the
diagnosis of early cardiovascular disease based on the presence and/or
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Appeal 2009-002066
Application 10/814,125

concentration of antibodies to phosphocholine and/or a derivative thereof in
a sample of body fluid.
The rejection of claims 1-3, 6-8, 11-14, 16, 17, 20-23, and 26 under
35 U.S.C § 103(a) as unpatentable over the combination of Muzya and
Ostermann is reversed.

Muzya, Ostermann, and Barquinero:
ISSUE
Does Barquinero make up for the deficiencies in the combination of
Muzya and Ostermann?

FINDINGS OF FACT
FF 16. The Examiner finds that the combination of Muzya and Ostermann
differs “from the instant invention in not specifically teaching assay
measurements by enzyme-linked immunoassay” (Ans. 7).
FF 17. The Examiner relies on Barquinero to “teach an ELISA assay to
measure antibodies against platelet-activating factor (PAF) in patients with
autoimmune diseases” (id.).
FF 18. The Examiner finds that Barquinero teaches that PAF is
“significantly present in patients with syphilis” (id.).

ANALYSIS
Each of rejected claims 4, 9, 18, and 24 depend directly or indirectly
from claim 1. The combination of Muzya and Ostermann is discussed
above. As Appellants explain, “Barquinero is merely cited for teaching
ELISA’s. . . . Barquinero, whatever it might offer with regard to ELISA
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Application 10/814,125

formats, cannot rescue the deficiencies of the other references given that it is
directed to examining autoimmune disease, and not CVD” (App. Br. 7). We
agree.

CONCLUSION OF LAW
Barquinero fails to make up for the deficiencies in the combination of
Muzya and Ostermann.
The rejection of claims 4, 9, 18, and 24 under 35 U.S.C § 103(a) as
unpatentable over the combination of Muzya, Ostermann, and Barquinero is
reversed.

Muzya, Ostermann, and Smal:
ISSUE
Does Smal make up for the deficiencies in the combination of Muzya
and Ostermann?

FINDINGS OF FACT
FF 19. The Examiner finds that the combination of Muzya and Ostermann
differs “from the instant invention in not specifically teaching assay
measurements by radioimmunoassay” (Ans. 8).
FF 20. The Examiner finds that Smal teaches a “method to evaluate PAF in
a specific and sensitive radioimmunoassay [(RIA)]” (id.).
FF 21. The Examiner finds that Smal teaches that “RIA was at least as good
as the platelet-based assay for PAF but the RIA was simpler to perform, had
higher capacity and did not have the draw backs of the inherent variability
associated with the bioassay” (id.).
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Appeal 2009-002066
Application 10/814,125

ANALYSIS
Each of rejected claims 5, 10, 19, and 25 depend directly or indirectly
from claim 1. The combination of Muzya and Ostermann is discussed
above. The Examiner fails to establish that Smal makes up for the
deficiencies in the combination of Muzya and Ostermann by making
obvious the diagnosis of early cardiovascular disease based on the presence
and/or concentration of antibodies to phosphocholine and/or a derivative
thereof in a sample of body fluid.

CONCLUSION OF LAW
Smal fails to make up for the deficiencies in the combination of
Muzya and Ostermann.
The rejection of claims 5, 10, 19, and 25 under 35 U.S.C § 103(a) as
unpatentable over the combination of Muzya, Ostermann, and Smal is
reversed.

REVERSED

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