Ex Parte Yeo et al

Board of Patent Appeals and Interferences

Feb 26, 2009

10966180 (B.P.A.I. Feb. 26, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte KIANG-TECH JERRY YEO AND MICHAEL SIMONS

Appellants
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Appeal 2008-6195
Application 10/966,180
Technology Center 1600
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Decided1: February 27, 2009
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Before RICHARD E. SCHAFER, RICHARD TORCZON, and SALLY
GARDNER LANE, Administrative Patent Judges.

LANE, Administrative Patent Judge.

DECISION ON APPEAL

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).

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I. STATEMENT OF THE CASE
The appeal, under 35 U.S.C. § 134(a), is from a Final Rejection of
Appellants’ claim 1, the sole pending claim in the application. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
Appellants’ application is directed to detection of cardiac collateral
artery formation, which Appellants explain “has been recognized as an
alternative source of blood supply to an ischemic[2] myocardial area.” (Spec.
1, ll. 6-8).
The Examiner rejected claim 1 under 35 U.S.C. § 103(a) over the
following references:
• Dahlen et al., US Patent Application Publication 2003/0022235,
“Use of B-Type Naturiuretic Peptide as a Prognostic Indicator in
Acute Coronary Syndromes,” published Jan. 30, 2003 (“Dahlen”);
• Heilmann, et al., “Collateral growth: cells arrive at the
construction site,” Cardiovascular Surgery, vol. 10, pp. 570-578
(2002) (“Heilmann”);
• Koerselman, et al., “Coronary Collaterals: An Important and
Underexposed Aspect of Coronary Artery Disease,” Circulation, vol.
107, pp. 2507-2511 (2003) (“Koerselman”);

2 We understand the term “ischemia” to mean “[a] localized anemia resulting
from mechanical obstruction of the blood supply.” Webster’s II New
College Dictionary 587 (1995).

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• Mukoyama, et al., “Brain Natriuretic Peptide as a Novel
Cardiac Hormone in Humans,” J. Clin. Invest., vol. 87, pp. 1402-12
(1991) (“Mukoyama”).
II. FINDINGS OF FACT
1. Appellants’ claim 1 recites3:
A method for detecting cardiac collateral artery
formation in an individual with chronic coronary artery disease
comprising
measuring the level of an N-terminal probrain natriuretic
peptide [“NT-pro-BNP”] or brain natriuretic peptide [“BNP”]
in a first sample isolated from a first individual suspected of
having chronic coronary artery disease and
comparing said level to a second sample isolated from a
second individual known to be free of coronary artery disease,
wherein an increase in the level of the N-terminal
probrain natriuretic peptide or brain natriuretic peptide in the
first sample by a factor of about 2-fold as compared to the level
in the second sample is indicative of collateral artery formation
in the first individual.

(App. Br. 14; Claims App’x.).

2. Dahlen teaches that “prior studies suggest that myocardial
ischemia may augment BNP synthesis and release, even in the absence of
myocardial necrosis or pre-existing left ventricular dysfunction. Reversible
ischemia may lead to transient increase in left ventricular wall stress, which
may be sufficient to cause BNP elevation.” (Dahlen ¶ [0049]).

3 Claim 1 has been reformatted, to add indentations. (See 37 C.F.R.
§ 1.75(i)).
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3. Dahlen reports the results of a study of “10,288 patients with
acute coronary syndromes. Patients were included if they presented within
72 hours of the onset of ischemic discomfort[,]” as well as other criteria.
(Dahlen ¶ [0058]).
4. Dahlen teaches that the “[m]ean concentration of BNP was
significantly higher among patients who died by 30 days (p<0.0001) or by
10 months (p<0.0001) vs those who were alive at either time point (table
3).” (Dahlen ¶ [0072]).
5. Table 3 of Dahlen is entitled “Association between baseline
BNP concentration (pg/mL) and outcomes.” Table 3 provides that after 30
days the mean ± SD of BNP concentration in patients who had died was 226
± 204, while in patients who were alive it was 113 ± 124. Table 3 also
provides that after 10 months the BNP concentration in patients who had
died was 228 ± 228, while in patients who were alive it was 110 ± 120.
(Dahlen Table 3).
6. From the data presented in Dahlen Table 3, mean BNP
concentrations were approximately two fold higher in patients who had died
than those who were alive after either 30 days or 10 months.
7. Koerselman teaches that “[r]ecurrent and severe myocardial
ischemia is assumed to stimulate the development of coronary collateral
circulation.” (Koerselman 2509, left col.).
8. Koerselman teaches that “[m]yocardial ischemia, per se, can be
a sufficient stimulus to induce coronary collateral development, possibly
through biochemical signals, including release of angiogenic growth
factors.” (Koerselman 2509, bridging left and right cols.).
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9. Heilmann teaches that an alternative to surgical and
pharmacological therapies for coronary artery disease and peripheral artery
occlusion disease “is to support the endogenous development of collateral
vessels occurring naturally after onset of ischemia.” (Heilmann 570, right
col.).
III. PRINCIPLES OF LAW
“[W]hen a patent ‘simply arranges old elements with each performing
the same function it had been know to perform’ and yields no more than one
would expect from such an arrangement, the combination is obvious.” KSR
Int’l v. Teleflex Inc., 127 S.Ct. 1727, 1740 (2007) (citing Sakraida v. Ag Pro,
Inc., 425 U.S. 273 (1976)).
IV. ISSUE
Would one of skill in the art have found it obvious to measure the
level of NT-pro-BNP or BNP in individuals with chronic coronary artery
disease and determine that a two fold increase over disease-free individuals
would indicate cardiac collateral artery formation?
V. ANALYSIS

Dahlen teaches that patients with acute coronary disease, including
ischemia, who have two fold higher increased levels of BNP are more likely
to die after 30 days or 10 months than patients with lower levels of BNP.4

4 The Examiner also relied on Mukoyama to teach that patients with chronic
heart failure also show a 2-fold increase of the level of BNP (see p. 1406. 2nd
col. 3rd paragraph)” (Ans. 8), but we find Dahlen alone is sufficient to teach
the claim element of a two-fold difference in BNP level.
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(FFs5 3-6). Appellants do not dispute this data. Dahlen also teaches that the
patients with acute coronary disease considered in this study included those
with ischemia. (FF 3). Thus, Dahlen teaches those in the art to consider the
level of BNP in assessing coronary disease.
Koerselman teaches that myocardial ischemia stimulates coronary
collateral circulation formation. (FFs 7 and 8). Similarly, Heilmann teaches
that collateral vessels are a natural result of ischemia. (FF 9).
From these teachings, the Examiner concluded that
it is obvious to use the increased level of BNP/NT-proBNP as
an indicator of detecting collateral artery formation in chronic
coronary artery disease since both patients with acute and
chronic coronary diseases develop increased levels of BNP/NT-
proBNP, develop collateral artery formation, and also have
stenosis, occlusion or myocardial ischemia, which are the
events to induce collateral artery formation.

(Ans. 10-11). We agree that the claimed method merely puts two previously
known elements – the increased levels of BNP in coronary disease and the
impact of coronary disease on collateral artery formation – together and,
thus, is obvious. See KSR, 127 S.Ct. at 1740.
Appellants argue that “the clinical end-point detected by Dahlen et al.
is morbidity or death and not acute coronary syndromes including ischemia.
Therefore, at best, Dahlen et al. can be said to teach the detection of
BNP/NT-proBNP levels in a subject.” (App. Br. 9 (emphasis in original)).
We are not persuaded that the specific end-point used by Dahlen limits the
implications of increased BNP levels in coronary disease patients. Dahlen

5 Findings of fact.
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reports that coronary diseased, including ischemic, patients having increased
BNP levels are more likely to die. (FFs 3 – 5). Thus, Dahlen teaches that
BNP is an indicator of increased coronary disease.
Appellants also argue that Dahlen and Koerselman
teach away from each other in terms of relating BNP/NT-
proBNP levels to collateral artery formation. Dahlen et al.
teaches that BNP levels increase in response to increases in
morbidity/mortality while Koerselman et al. teach that
decreases in mortality are associated with collateral artery
formation. Therefore, it would not be obvious to one of skill
that increased collateral artery formation, which leads to
decreased mortality, would be associated with increased levels
of BNP, which is indicative of increased mortality.

(App. Br. 10 (emphasis in original)). “A reference may be said to teach
away when a person of ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or would be led
in a direction divergent from the path that was taken by the applicant.” In re
Gurley, 27 F3d. 551, 553 (Fed. Cir. 1994). The coexistence of Dahlen,
Koerselman, and Heilmann demonstrates that those of skill in the art would
appreciate that BNP might signal both the harmful effects of ischemia and
the beneficial effects of collateral arteries, which are formed in response to
ischemia. Thus, we are not persuaded that the teachings of
morbidity/mortality in Dahlen would discourage those of skill in the art from
measuring BNP levels as a determination of collateral artery formation. See
Syntex LLC v. Apotex, Inc. 407 F.3d 1371, 1380 (Fed. Cir. 2005) (“What a
reference teaches or suggests must be examined in the context of the
knowledge, skill, and reasoning ability of a skilled artisan. What a reference
teaches a person of ordinary skill is not . . . limited to what a reference
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specifically ‘talks about’ or what is specifically ‘mentioned’ or ‘written’ in
the reference.”).
Appellants also argue that “in relying on data from papers discussing
acute cardiac conditions, one of skill would not assume that these data would
apply to chronic cardiac disease conditions.” (App. Br. 10 (emphasis in
original)). Appellants note that the Examiner refers to references6, other
than those relied upon in the rejection, that teach BNP levels in congestive
heart failure, which they argue is not a chronic coronary artery disease.
(Id.).
We are not persuaded that information about congestive heart failure
demonstrates that Appellants’ claim method is not obvious. Dahlen,
Koerselman, and Heilmann each report the implications and effects of
ischemia in coronary patients. Whether or not the diseases that caused
ischemia were chronic or acute, those of skill in the art knew from these
references that BNP levels in coronary patients, including those with
ischemia, indicated a higher risk of death and that ischemia can cause
collateral artery formation. Appellants have not directed us to evidence
showing that the cause of ischemia affects either the implications of a
patient’s BNP levels or collateral artery formation.
Finally, Appellants argue that “Koerselman et al. teach that while
‘[r]ecurrent and severe myocardial ischemia is assumed to stimulate the

6 Safley and McCullough, “The Emerging Role of Brain Natriuretic Peptide
in the Management of Acute and Chronic Heart Failure in Outpatients,”
Heart Fail. Monit., vol. 4, pp. 13-20 (2003).
McCullough, “B-type Natriuretic peptides,” Minerva Cardioangiologica,
vol. 51, pp. 121-29 (2003).
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development of coronary collateral circulation . . . the growth of collateral
arteries through arteriogenesis is not dependent on ischemia." See the
paragraph bridging columns 1 and 2 at page 2509 (emphasis added).’” (App.
Br. 11). According to Appellants, “if ischemia is sufficient to induce
collateral artery formation, then 100% of the patients described in the
specification as filed, with diagnosed chronic coronary artery disease, should
have exhibited collateral artery formation.” (App. Br. 12). The statement
of Koerselman referred to by Appellants only indicates that conditions other
than ischemia may cause arteriogenesis. Appellants have not claimed a
method that detects every occurrence of cardiac collateral artery formation.
Thus, this statement does not detract from the obviousness of Appellants’
claimed method.
Appellants have not convinced us that the Examiner erred in rejecting
claim 1 under 35 U.S.C. § 103(a) over Dahlen, Heilmann, Koerselman, and
Mukoyama.

VI. ORDER
Upon consideration of the record and for the reasons given,
the Examiner’s rejection of claim 1 under 35 U.S.C. § 103(a) over
Dahlen, Heilmann, Koerselman, and Mukoyama is AFFIRMED.
It is FURTHER ORDERED that no time period for taking any
subsequent action in connection with this appeal may be extended under
37 C.F.R. § 1.136(a).
AFFIRMED

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MAT

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