Ex Parte Gurewich et al

Board of Patent Appeals and Interferences

Aug 25, 2011

11447455 (B.P.A.I. Aug. 25, 2011)

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.
11/447,455 06/06/2006 Victor Gurewich TSI-13763 3483
23535 7590 08/25/2011
MEDLEN & CARROLL, LLP
703 Market STREET
SUITE 340
SAN FRANCISCO, CA 94103
EXAMINER
KOSSON, ROSANNE
ART UNIT PAPER NUMBER
1657
MAIL DATE DELIVERY MODE
08/25/2011 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte VICTOR GUREWICH, JIAN-NING LIU,
and PAOLO SARMIENTOS
__________

Appeal 2011-000906
Application 11/447,455
Technology Center 1600
__________

Before ERIC GRIMES, FRANCISCO C. PRATS, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of treating a heart attack patient, which the Examiner has rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The Specification discloses that several thrombolytic (clot-dissolving)
agents are known in the art but all have drawbacks that have prevented their
acceptance as a standard treatment for heart attacks (Spec. 2). One such
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thrombolytic agent is pro-urokinase (pro-UK) (id.). The Specification
discloses that a pro-UK mutant, “M5, which has the complete amino acid
sequence of wild-type pro-UK, but with one amino acid alteration,
Lys300 → His” (id. at 4) lyses clots that occlude blood vessels but not clots
that seal injured blood vessels (id. at 3).
Claims 16-21, 28, and 29 are on appeal. The claims have not been
argued separately and therefore stand or fall together. 37 C.F.R.
§ 41.37(c)(1)(vii). Claim 16 is representative and reads as follows:
16. A method of treating a patient with a heart attack, comprising:
a) intravenously administering a pro-urokinase mutant polypeptide to said
patient prior to catheterization of said patient for angioplasty, wherein said
mutant polypeptide has the amino acid Lysine replaced by the amino acid
Histidine at position 300 of the native pro-urokinase sequence
SEQ ID NO:5; and b) performing a percutaneous transluminal coronary
angioplasty on said patient after step a).
Issue
The Examiner has rejected claims 16-18 and 28 under 35 U.S.C.
§ 103(a) as obvious based on Herrmann1 and Liu2 (Answer 3), and has
rejected claims 19-21 and 29 under 35 U.S.C. § 103(a) as obvious based on
Herrmann, Liu, and Gurewich3 (Answer 4). Since Appellants have waived
any argument based on Gurewich (see Appeal Br. 10), we will consider the
rejections together.

1 Howard C. Herrmann et al., Facilitation of early percutaneous coronary
intervention after reteplase with or without abciximab in acute myocardial
infarction: Results from the SPEED (GUSTO-4 Pilot) trial, 36 J. AMER.
COLLEGE CARDIOL. 1489-1496 (2000)
2 Liu et al., US 5,472,692, Dec. 5, 1995
3 Gurewich US 5,626,841, May 6, 1997
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The Examiner finds that Herrmann discloses treating heart attack
patients with “a first step of administering i.v. a composition comprising a
therapeutically effective amount of t-PA (reteplase) that dissolves the arterial
clot. . . . In the second step, angioplasty was performed.” (Answer 3.) The
Examiner finds that Liu discloses the pro-UK mutant recited in the instant
claims as being “a superior drug compared to UK or pro-UK” because it
causes fewer side effects (id. at 3-4). The Examiner concludes that it would
have been obvious to use Liu’s mutant pro-UK in place of the t-PA used by
Herrmann “to reduce the risk of undesired bleeding” (id. at 4).
Appellants contend that it would not have been obvious to combine
Liu’s drug and Herrmann’s method with a reasonable expectation of success
(Appeal Br. 5-10). Appellants also contend that they have provided
objective evidence of nonobviousness that rebuts any prima facie conclusion
of obviousness (id. at 11-12).
The issues presented are: Does the evidence support the Examiner’s
conclusion that the teachings of Herrmann and Liu would have made the
method of claim 16 prima facie obvious at the time the claimed invention
was made? and, if so
Have Appellants provided evidence of nonobviousness that outweighs
the evidence supporting the Examiner’s prima facie case?
Findings of Fact
1. Herrmann discloses a study of “early percutaneous coronary
intervention (PCI) . . . after thrombolysis and glycoprotein IIb/IIIa inhibition
for acute myocardial infarction (MI)” (Herrmann 1489, “Objectives”).
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2. Percutaneous coronary intervention (PCI) and percutaneous
transluminal coronary angioplasty are synonymous. First Gurewich
Declaration,4 ¶ 2.
3. Herrmann states that “the term facilitated PCI . . . describe[s] early,
planned PCI after a pharmacological regimen intended to open the infarct-
related artery. Our hypothesis was that facilitated PCI incorporating stents
and platelet glycoprotein IIb/IIIa therapy would be safe and would improve
the . . . outcomes of patients.” (Id. at 1489-1490.)
4. Herrmann discloses that patients with acute MI were treated with
reteplase, alone or combined with another drug (abciximab) (id. at 1490,
left col.: patients “receive[d] full-dose reteplase . . . or . . . abciximab with
reduced-dose reteplase”).
5. The Examiner finds (Answer 3), and Appellants do not dispute,
that reteplase is another name for tissue plasminogen activator (tPA).
6. The Specification states that tPA and pro-urokinase (pro-UK) are
both thrombolytic drugs that were known at the time the instant application
was filed (Spec. 2: “Like t-PA, pro-UK is known to be selective for
plasminogen bound to blood clots.”).
7. Herrmann discloses that “[c]oronary angiography was performed
as early as possible after reperfusion [i.e., reteplase] therapy began; then PCI
was performed” (Herrmann 1490, left col.).
8. Herrmann discloses that “[t]here was a trend toward improved 30-
day outcomes in the patients receiving combination therapy . . . ; however, a

4 Declaration under 37 C.F.R. § 1.132 of Victor Gurewich, executed Feb. 26,
2009
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trend was apparent toward greater bleeding complications primarily at
vascular access sites with combination therapy” (id. at 1491, right col.).
9. Hermann discloses that its results “showed that the combination
strategy of potent platelet inhibition (abciximab) and reduced-dose
thrombolysis (reteplase) improves infarct-related artery patency . . . ,
compared with abciximab alone or full-dose reteplase” (id.).
10. Herrmann concludes that “[t]he results of PCI in this setting
appear to be both safe and effective” (id.).
11. Herrmann states that its “results contrast with previous studies of
angioplasty performed shortly after full-dose thrombolysis . . . [in which]
immediate angioplasty had a lower success rate . . . than did delayed
intervention or a conservative approach” (id.).
12. Herrmann states that the “most likely reasons for the better results
in the present trial include the use of abciximab, intracoronary stents,
optimization of heparin anticoagulation, and increased operator experience”
(id. at 1491-1492).
13. Herrmann states that its “data suggest multiple benefits from the
use of combination therapy with abciximab and reduced-dose thrombolysis
for ‘facilitated early PCI,’ a term we propose to refer to planned PCI after
pharmacological reperfusion therapy” (id. at 1492, right col.).
14. Herrmann states that “the mortality benefit and safety of
combined therapy with abciximab and a low-dose fibrinolytic must first be
validated in a large trial” (id. at 1494, right col.).
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15. Liu discloses “pro-UK mutants [that] cause lower non-specific
plasminogen activation and bleeding complications than native pro-UK
when administered to a patient” (Liu, col. 1, ll. 61-63).
16. Liu discloses that “[t]hese pro-UK mutants are superior
thrombolytic agents compared to native pro-UK” (id. at col. 1, ll. 64-65).
17. Liu discloses a pro-UK mutant with a Lys300 → His substitution
(id. at col. 6, ll. 29-51).
18. Liu discloses that its “pro-UK mutants are used and administered
as thrombolytic agents in the same way as pro-UK and UK” (id. at col. 16,
ll. 14-15).
Principles of Law
“A patent may not be obtained . . . if the differences between the
subject matter sought to be patented and the prior art are such that the
subject matter as a whole would have been obvious at the time the invention
was made to a person having ordinary skill in the art.” 35 U.S.C. § 103(a).
“The consistent criterion for determination of obviousness is whether
the prior art would have suggested to one of ordinary skill in the art that this
process should be carried out and would have a reasonable likelihood of
success, viewed in the light of the prior art.” In re Dow Chemical Co., 837
F.2d 469, 473 (Fed. Cir. 1988).
The expectation of success is assessed from the perspective of a
person of ordinary skill in the art, at the time the invention was made. See
Life Techs. Inc. v. Clontech Labs. Inc., 224 F.3d 1320, 1326 (Fed. Cir. 2000)
(“Reasonable expectation of success is assessed from the perspective of the
person of ordinary skill in the art. That the inventors were ultimately
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successful is irrelevant to whether one of ordinary skill in the art, at the time
the invention was made, would have reasonably expected success.” (citation
omitted)).
Analysis
Herrmann discloses a method similar to that of claim 16, except that
Herrmann administers tPA as a thrombolytic agent rather than the recited
pro-UK mutant. However, Liu discloses that the Lys300 → His pro-UK
mutant is a superior thrombolytic agent compared to native pro-UK because
it causes fewer bleeding complications. Both tPA and pro-UK were known
thrombolytic agents at the time the present application was filed, and Liu
suggests using its pro-UK mutants as thrombolytic agents. We agree with
the Examiner that it would have been obvious to modify Herrmann’s
treatment method by using Liu’s Lys300 → His pro-UK mutant because Liu
suggests its use as a thrombolytic agent and discloses that it causes fewer
bleeding complications compared to native pro-UK.
Appellants argue that “[u]sing a thrombolytic before angioplasty is
contrary to accepted wisdom” because the literature prior to Herrmann
showed no benefit from the combination (Appeal Br. 5). Appellants argue
that the contrast between Herrmann’s results and earlier studies “would
cause one skilled in the art to question (at a minimum) Herrmann et al.’s
results” and negate a reasonable expectation of success (id. at 6).
This argument is not persuasive. Herrmann discloses that its therapy
was found to be safe and effective (FF 10) and provides multiple benefits
(FF 13). Herrmann acknowledges that its results were better than reported in
previous studies (FF 11), but provides several reasons for the improvement
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(FF 12). Thus, a skilled worker would reasonably conclude that Herrmann’s
results were reproducible, and therefore adequate to support a reasonable
expectation of achieving them.
Appellants also argue that Liu does not suggest using its pro-UK
mutant in combination with angioplasty (Appeal Br. 5) and Herrmann does
not recommend using a new thrombolytic instead of tPA (id. at 6-7). These
arguments are unpersuasive because they fail to address what the teachings
of the references, considered together, would have made obvious to a person
of ordinary skill in the art. See In re Young, 927 F.2d 588, 591 (Fed. Cir.
1991) (“The test for obviousness is what the combined teachings of the
references would have suggested to one of ordinary skill in the art.”).
Appellants also argue that Herrmann’s study lacked a critical control,
specifically angioplasty without any thrombolytic therapy (Appeal Br. 7)
and that its results showed a trend toward bleeding complications in patients
administered combination therapy (id. at 8). These arguments are not
persuasive. Herrmann’s data were derived from a scientifically conducted
study that was published in a reputable scientific journal, and therefore
would be considered reliable by those skilled in the art. In addition,
although Herrmann notes the trend toward greater bleeding complications
(FF 8), it concludes that the combination therapy provided multiple benefits
(FF 13) and was “safe and effective” (FF 10).
Appellants argue that Herrmann warned that its work must be validated
in a larger study and that “one skilled in the art understands that warning . . .
means that the results should not be taken at face value and are only
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‘preliminary’” (Appeal Br. 8, quoting the Fourth Gurewich Declaration,5 ¶ 2).
Appellants argue that the larger study was carried out and failed to validate
the results reported by Herrmann (Appeal Br. 8). Appellants point to Ellis6
and Stone,7 and argue that those studies concluded that treatment with
reteplase before angioplasty “cannot be justified” (id. at 9, quoting Ellis
2215) or causes increased mortality and complications (Appeal Br. 9, citing
Stone 544).
This argument is also not persuasive. Whether a claimed invention
would have been obvious under 35 U.S.C. § 103(a) , including whether there
would have had a reasonable expectation of successfully combining prior art
disclosures, is judged from the perspective of a person of ordinary skill in
the art at the time the invention was made; i.e., as of the application’s
effective filing date.
The analysis required by § 103 has been characterized as “casting the
mind back to the time of invention, to consider the thinking of one of
ordinary skill in the art, guided only by the prior art references and the then-
accepted wisdom in the field.” In re Dembiczak, 175 F.3d 994, 999 (Fed.
Cir. 1999) (emphasis added). For this reason, obviousness has been likened
to “the creature of an imagination projected upon the future out of materials
of the past.” Schaefer, Inc. v. Mohawk Cabinet Co., 276 F.2d 204, 207 (2d

5 Declaration under 37 C.F.R. § 1.132 of Victor Gurewich, executed Feb. 14,
2010
6 Stephen G. Ellis et al., Facilitated PCI in Patients with ST-Elevation
Myocardial Infarction, 358 NEW ENGLAND J. MED. 2205-2217 (2008)
7 Gregg W. Stone et al., Facilitated angioplasty: paradise lost, 367 LANCET
543-545 (2006)
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Cir. 1960)(Learned Hand, J.). A determination of obviousness is based only
on knowledge available at the time the claimed invention was made.
The instant application has an effective filing date at least as early as
April 16, 2004. Stone was published in 2006; Ellis was published in 2008.
Thus, the disclosures of Ellis and Stone were not available at the time the
instant application was filed, and their later disclosures casting doubt on
Herrmann’s conclusions would not have been known to a hypothetical
person of ordinary skill in the art at the relevant time for determining
whether the claims of the application on appeal would have been obvious.
Rather, the hypothetical person of ordinary skill in the art, at the time
the invention was made, would have been aware of Herrmann’s disclosure
that treatment with tPA and abciximab before angioplasty provides “multiple
benefits” (FF 13), and would have been aware of Liu’s disclosure that its
pro-UK mutant causes fewer bleeding complications than native pro-UK
(FF 15), which was known to be a thrombolytic agent like tPA (FF 6).
Therefore, “at the time the invention was made,” 35 U.S.C. § 103(a), the
prior art would have provided a reasonable expectation that substituting
Liu’s pro-UK mutant for the tPA in Herrmann’s method would successfully
treat a patient with a heart attack. Although Herrmann noted that a larger
study would be needed to verify its results, § 103 does not require absolute
predictability, only a basis for a reasonable expectation of success. See In re
O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988).
The same problem pertains to Appellants’ arguments based on
evidence of nonobviousness (Appeal Br. 11-12). The evidence cited to show
“failure of others” and “skepticism of experts” is based on evidence from
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after the filing date of the instant application, and therefore does not show
that at the time the invention was made experts were skeptical of its success
or that others had tried but failed to effectively treat heart attack patients
with a combination of thrombolysis and angioplasty.
As evidence of “long-felt but unsolved needs” Appellants cite the
First Gurewich Declaration (Appeal Br. 11). That declaration, however,
relies almost entirely on evidence that was not available as of the effective
filing date of the instant application (cited references numbered 3-6 and 8) or
is not of record in the official file (cited references numbered 1, 2, and 7).
The declaration does include a copy of a document apparently intended to
show that pro-UK was “rejected for use by the EMEA in 1999” (First
Gurewich Declaration, ¶ 8). However, the attached document refers to a
product named “Rescupase” or “Saruplase” and Appellants have provided
no evidence to show that that product is pro-UK. The evidence provided by
First Gurewich Declaration therefore is entitled to little weight and does not
outweigh the evidence supporting the prima facie case of obviousness.
Appellants cite Environmental Designs, Ltd. v. Union Oil Co. of Cal.,
713 F.2d 693, 698 (Fed. Cir. 1983), in support of their position that the post-
filing evidence is relevant to the issue of obviousness, arguing that “[i]n the
Environmental Designs case, the evidence came from testimony in a lawsuit
many years after the invention was made” (Appeal Br. 12).
We are not persuaded. In Environmental Designs, the evidence
showed “disbelief by the chemical experts for both sides.” 713 F.2d at 697.
While that evidence came in a lawsuit filed after the patent in suit had been
issued, the evidence pertained to the experts’ opinions “[b]efore learning of
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the [claimed] process.” Id. The Environmental Designs court held that the
district court’s “conclusion that the invention as a whole would not have
been obvious at the time it was made to one of ordinary skill in the art was
eminently correct.” Id. at 698 (emphasis added). Environmental Designs
does not support Appellants’ position that evidence of the post-filing state of
the art is relevant to a determination of obviousness.
Conclusion of Law
The evidence supports the Examiner’s conclusion that Herrmann and
Liu would have made the method of claim 16 prima facie obvious at the
time the claimed invention was made. Appellants have not provided
evidence of nonobviousness that outweighs the evidence supporting the
Examiner’s prima facie case.
SUMMARY
We affirm the rejection of claims 16-18 and 28 under 35 U.S.C.
§ 103(a) based on Herrmann and Liu and the rejection of claims 19-21 and
29 under 35 U.S.C. § 103(a) based on Herrmann, Liu, and Gurewich.
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).

AFFIRMED

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