Ex Parte 7544500 et al

Patent Trial and Appeal Board

Dec 10, 2012

90010765 (P.T.A.B. Dec. 10, 2012)

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.
90/010,765 01/11/2010 7544500 9901-36-1 9012
26158 7590 12/10/2012
WOMBLE CARLYLE SANDRIDGE & RICE, LLP
ATTN: IP DOCKETING
P.O. BOX 7037
ATLANTA, GA 30357-0037
EXAMINER
CAMPELL, BRUCE R
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
12/10/2012 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 TALECRIS BIOTHERAPEUTICS, INC.
Appellant
____________

Appeal 2012-009475
Reexamination Control 90/010,765
Patent U.S. 7,544,500 B2
Technology Center 3900
____________

Before LORA M. GREEN, RICHARD M. LEBOVITZ, and
RAE LYNN P. GUEST, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal by the Patent Owner from the Patent
Examiner’s rejections of claims 1, 4, 7-19, and 21-23 in an ex parte
reexamination of U.S. Patent No. 7,544,500, issued June 9, 2009. The
Board’s jurisdiction for this appeal is under 35 U.S.C. §§ 6 and 134. We
affirm.
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Patent U.S. 7,544,500 B2

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STATEMENT OF THE CASE
A request for ex parte reexamination of U.S. Patent 7,544,500
(hereinafter, “the ‘500 patent) was made by a Third Party Requester on
January 11, 2010 pursuant to 37 C.F.R. § 1.510. A Final Rejection rejecting
pending claims 1, 4, 7-19, and 21-23 was mailed by the Examiner on
September 24, 2010. Patent Owner appealed the Examiner’s adverse
decision to the Board of Patent Appeals and Interferences. Notice of
Appeal, dated February 22, 2011. An oral hearing was held October 3,
2012. A written transcript of the hearing will be entered into the record in
due course.
The claims are directed to methods of preparing a plasmin solution
comprising using an active plasmin-specific absorbent material comprising
benzamidine. The plasmin binds to the absorbent material and then is
buffered to a low pH to form a “reversibly inactive acidified plasmin
solution.” ‘500 patent Abstract.
According to the ‘500 Patent, plasmin can be used therapeutically to
lyse an intravascular blood clot known as a thrombus. ‘500 Patent, col. 2, ll.
35-41; col. 1, ll. 35-38.
The Patent Owner stated that the inventors discovered that reversibly
inactive acidified plasmin solution product of the claimed method can be
used directly for therapy without neutralization prior to administration to a
patient. Reply Br. 2. The instant claims, however, are directed to preparing
the plasmin solution, and are not restricted to a particular use of the plasmin.
The Examiner rejected the claims as follows:
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Patent U.S. 7,544,500 B2

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1. Claims 1, 7-15, 18, 19, 21, and 22 under 35 U.S.C. § 103(a) as
obvious over Robbins1 in view of Ito2 and Deacon.3 Answer 3.
2. Claims 4 under 35 U.S.C. § 103(a) as obvious over Robbins in
view of Ito, Deacon, and Haidacher.4 Answer 5.
3. Claims 16 under 35 U.S.C. § 103(a) as obvious over Robbins in
view of Ito, Deacon, and Abe.5 Answer 5-6.
4. Claims 17 under 35 U.S.C. § 103(a) as obvious over Robbins in
view of Ito, Deacon, and Jensen.6 Answer 6.
5. Claim 23 under 35 U.S.C. § 103(a) as obvious over Robbins in
view of Ito, Deacon, and Diedrichsen.7 Answer 7.
Claims 1 is the only independent claim on appeal and reads as
follows:

1 Kenneth C. Robbins & Louis Summaria, Purification of Human
Plasminogen and Plasmin by Gel Filtration on Sephadex and
Chromatography on Diethylaminoethyl-Sephadex, 238 (3) J. Biological
Chem. 952 (Mar. 1963).
2 Naofumi Ito et al., Separation of Human Glu-Plasminogen, Lys-
Plasminogen and Plasmin by High-Performance Affinity Chromatography
on Asahipak Gs Gel Coupled with p-Aminobenzamidine, 348 J. of
Chromatography 199 (1985).
3 J.M. Deacon et al., Technetium 99m-Plasmin: a New Test for the Detection
of Deep Vein Thrombosis, 53 British J. of Radiology 673 (1980).
4 Dietmar Haidacher, Temperature Effects in Hydrophobic Chromatography,
93 (6) Proc. Natl. Acad. Sci. 2290 (Mar. 1996).
5 Izumi Abe et al., Immobilized Urokinase Column as Part of a Specific
Detection System for Plasminogen Species Separated by High Performance
Affinity Chromatography, 565 J. of Chromatography 183 (1991).
6 Villy Johannes Jensen, U.S. 3,950, 513 (Apr. 13, 1976).
7 Allan Diedrichsen et al., U.S. 4,462,980 (Jul. 31, 1984).
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Patent U.S. 7,544,500 B2

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1. A method for preparing a plasmin solution, the method
comprising:
cleaving a plasminogen in the presence of a plasminogen
activator to yield an active plasmin;
substantially removing the plasminogen activator from
the active plasmin by binding the active plasmin to an active
plasmin-specific absorbent material to form a bound plasmin
wherein the active plasmin-specific absorbent material
comprises benzamidine;
eluting the bound plasmin with an acidic buffer or an
omega-amino acid to form a plasmin solution; and
buffering the plasmin solution with a low pH, low
buffering capacity agent to form a reversibly inactive acidified
plasmin solution having a pH of about 2.5 to about 4.

REJECTION 1
Claims 1, 7-15, 18, 19, 21, and 22 stand rejected under 35 U.S.C.
§ 103(a) as obvious over Robbins in view of Ito and Deacon. Answer 3.

The claimed invention
Claim 1 is directed to a method for preparing a plasmin solution. The
method comprises four steps:
1) “cleaving a plasminogen in the presence of a plasminogen activator
to yield an active plasmin”;
2) “substantially removing the plasminogen activator from the active
plasmin” using a plasmin-specific absorbent material which comprises
benzamidine;
3) “eluting the bound plasmin” from the absorbent material; and
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4) “buffering the plasmin solution with a low pH, low buffering
capacity agent to form a reversibly inactive acidified plasmin solution
having a pH of about 2.5 to about 4.”

The Rejection
The Examiner found that Robbins discloses a method of preparing a
plasmin solution comprising a cleaving plasminogen in the presence of a
plasminogen activator as in step 1) of claim 1. Answer 4. The Examiner
also found that Robbins describes separating the plasminogen activator from
the plasmin, but not using the benzamidine absorbent as in steps 2) and 3).
Id. The step 4) of forming an acidified plasmin solution is also not
described in Robbins according to the Examiner. Id.
However, the Examiner made findings of fact that a second prior art
publication, Ito, described separating plasmin using a HPAC benzamidine
absorbent (steps 2) and 3)). Answer 4. The Examiner determined it would
have been obvious to have applied Ito’s purification method to Robbins
“because the science of chromatography advanced greatly between 1962 and
1985, and the HPAC separation method of Ito would be expected to be much
more efficient than the low pressure size exclusion chromatography of
Robbins.” Answer 4.
For step 4), the Examiner found that Deacon described an acidified
plasmin solution which meets the limitations of the claim. Answer 8-9. The
Examiner determined that it would have been obvious “to use the
purification methods of Robbins and Ito to produce the solution of Deacon.
Furthermore, because the reagent of Deacon is intended to be injected into
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human patients, there would be motivation to provide plasmin in a form as
pure as possible.” Id. at 9.

Patent Owner’s Arguments
Patent Owner made two principal arguments to distinguish the claims
over the prior art:
• The cited publications do not teach or suggest “substantially
removing the plasminogen activator from the active plasmin.” App. Br. 4
• The cited publications do not teach or suggest “buffering the plasmin
solution with a low pH, low buffering capacity agent to form a reversibly
inactive acidified plasmin solution having a pH of about 2.5 to about 4” in
the method of claim 1. Id.

• “substantially removing the plasminogen activator
from the active plasmin.”
Inherency
Step 2) of claim 1 reads “substantially removing the plasminogen
activator from the active plasmin by binding the active plasmin to an active
plasmin-specific absorbent material to form a bound plasmin wherein the
active plasmin-specific absorbent material comprises benzamidine.”
Emphasis added. The substantial removal of the plasminogen activator is
therefore a result of binding the active plasmin to the benzamidine
absorbent. Patent Owner contends that neither Robbins nor Ito describe the
substantial removal of the plasminogen activator from plasmin. However,
this argument is largely misplaced because once Ito’s teachings are applied
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to Robbins and Deacon, “substantially removing the plasminogen activator
from the active plasmin” would have been an inherent result of utilizing
Ito’s benzamidine absorbent to purify plasmin, whether the skilled worker
recognized it or not.
Patent Owner argues that Ito did not teach that plasminogen activator
was substantially removed from its plasmin solution and that the Examiner
did not meet the burden of showing that Ito’s method accomplished such
removing. We do not agree that the Examiner’s burden was not met.
Where, as here, the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed product.
. . .
Whether the rejection is based on “inherency” under 35 U.S.C.
§ 102, on “prima facie obviousness” under 35 U.S.C. § 103,
jointly or alternatively, the burden of proof is the same, and its
fairness is evidenced by the PTO’s inability to manufacture
products or to obtain and compare prior art products.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (footnote omitted).
The claimed absorbent material comprising benzamidine has not been
distinguished by Patent Owner from the benzamidine material described in
Ito. Thus, the Examiner had reasonable basis to believe they were the same
and would possess the same activity. Ito used such material to purify
plasmin. Accordingly, the Examiner had a credible basis upon which to
assert that Ito’s material would separate plasmin from plasminogen
activator, the same result described in the ‘500 Patent.
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Ito’s disclosure that closely related forms of plasminogen can be
separated from one another is further basis upon which a skilled worker
would have reasonably expected that plasmin could be separated from
plasminogen activator. Figure 3 of Ito shows the separation of two closely
related forms of plasminogen – Glu-Plg and Ly-Plg – from each other and
from plasmin using benzamidine absorbent chromatography. Ito, p. 201,
second full paragraph in Results section; Figure 3 showing separation of
Glu-Plg (“plasminogen”), Lys-Plg, and plasmin; Answer 10. If such closely
related forms of plasminogen could be separated from one another (Gly-Plg
and Lys-Plg) by plasmin, it would have been reasonable to presume that
benzamidine was capable separating unrelated proteins from plasmin, such
as a plasminogen activator. The burden therefore properly shifted to Patent
Owner to show that Ito’s did not inherently substantially separate plasmin
from plasminogen activator. Patent Owner, however, did not provide
persuasive evidence that Ito’s benzamidine absorbent – the same absorbent
which is claimed – would not have removed the plasminogen activator from
the active plasmin as claimed.
The result of using Ito for its known benefit in purifying plasmin
cannot serve as a basis for patentability, even if it had the added, but
unrecognized, advantage in separating the plasminogen activator from
plasmin. The case that comes to mind for this legal principle is In re Baxter
Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).
In Baxter, the applicant had argued that the claimed plasticized blood
donor bag comprised of DEHP had unexpected properties in suppressing
hemolysis of red blood cells stored inside it. Baxter, 952 F.2d at 389. The
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court found that such evidence did not rebut prima facie obviousness
because the prior art disclosed a DEHP-plasticized donor bag, and therefore,
Baxter’s blood bag had the same hemolytic-suppressing function as the prior
art – albeit unappreciated at the time of the invention. Baxter, 952 F.2d at
391. The court concluded that “[m]ere recognition of latent properties in the
prior art does not render nonobvious an otherwise known invention.”
Baxter, 952 F.2d at 392. Likewise, the claimed plasmin purification method
using benzamidine had been practiced in the prior art. The stated discovery
that plasminogen activator was separated by a benzamidine absorbent is
merely recognizing an inherent result of using Ito’s method.

Reason to combine
The remaining question therefore is whether it would have been
obvious to one of ordinary skill in the art to have applied Ito’s teaching of a
benzamidine absorbent for purifying plasmin. On this issue, Patent Owner
contends that Ito’s methods are analytic and preparative, and that the
ordinary skilled worker “would not assume any aspect of such methods to
apply to a method or process for production of a therapeutic protein.” App.
Br. 7. Patent Owner also argued that Deacon, relied upon by the Examiner
for its teaching of an acidified plasmin, is drawn to a diagnostic test and not
relevant to the therapeutic purposes described in the ‘500 Patent. Id. at 5.
Finally, Patent Owner argues that Ito does not teach or suggest removing
plasminogen activator from its plasmin solution, so there would have been
no reason to use it for this purpose.
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Patent U.S. 7,544,500 B2

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First, we note that the claims are drawn to methods of preparing a
plasmin solution, and are not limited to preparing a therapeutic plasmin
solution or a therapeutic amount of plasmin. Thus, it is immaterial that Ito’s
methods are “analytic” and “preparative,” and inapplicable to therapeutic
proteins as alleged, because the claim broadly covers plasmin purification
for any use, including for therapeutic, diagnostic, and analytical uses.
Similarly, while Deacon describes a diagnostic test which utilizes plasmin,
the claims do exclude the plasmin solution from being used for diagnostic
purposes.
Patent Owner contends that Ito does not teach or suggest separation of
plasminogen activator from plasmin.
Without the benefit of hindsight gained from the Patent
disclosure, it is the Appellants’ position that speculation based
on the specific purifications discussed in Ito (separation of
various plasminogen/plasmin species) does not amount to a
teaching or suggestion of “substantial” removal of plasminogen
activator as disclosed and claimed in the Patent.
App. Br. 7.
We agree with Patent Owner that Ito does not disclose that the
plasminogen activator used to activate its plasmin is subsequently removed
by the benzamidine absorbent. However, as found by the Examiner, Ito’s
method was known to be effective in purifying plasmin. It is obvious to use
a known method for its established purpose.
If a technique has been used to improve one device, and a
person of ordinary skill in the art would recognize that it would
improve similar devices in the same way, using the technique is
obvious unless its actual application is beyond his or her skill.
Sakraidai [425 U.S. 273] and Anderson’s-Black Rock [396 U.S.
57] are illustrative—a court must ask whether the improvement
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is more than the predictable use of prior art elements according
to their established functions.
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Since
“substantially removing the plasminogen activator” is an inherent result of
the recited “binding the active plasmin to an active plasmin-specific
absorbent material to form a bound plasmin,” it is inconsequential that
removing plasminogen activator is not taught by Ito because such result
would occur simply by using Ito’s technology.
Because the “substantially removing” is a result of carrying out the
obvious step of preparing plasmin using Ito’s method, it is not necessary that
we find a reason to have substantially removed the plasminogen activator
from plasmin as long as there was a reason to use Ito’s plasmin purification
method. This inherent result was not relied upon as a basis for
unpatentability as alleged by Patent Owner on pages 11-12 of the Reply
Brief. Rather, it was only necessary for the Examiner to find a reason to use
Ito’s method. The reason does not have to be the same reason the inventor
had in mind for making the invention. KSR Int’l Co. v. Teleflex, Inc., 550
U.S. 398, 419-20 (2007).
As another reason for applying Ito’s teaching to Deacon, the
Examiner found:
The evidence of record indicates that purity of the plasmin used
in Deacon's method is important. Deacon used a “kit containing
highly purified porcine plasmin” (p. 674, col. 1, emphasis
added). Diedrichsen, discussing the kit used by Deacon, states
that “highly purified plasmin ... is preferred” (col. 4, lines 10-
11).
Answer 9.
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Patent Owner contends that such so-called “purified” preparations
often contained plasminogen activator, and it was later recognized that
plasminogen activator accounted for the plasmin activity. Reply Br. 8-9.
The ‘500 Patent expressly teaches that plasmin had been used, or
suggested to be used, as both a therapeutic and diagnostic agent prior to its
filing date. ‘500 Patent, col. 2, ll. 31-60. The patent also teaches that
plasmin preparations were known to be contaminated with plasminogen
activators. ‘500 Patent, col. 2, l. 65 to col. 3, l. 2. It is surely medical
commonsense that the ordinary skilled worker, desiring to use plasmin as a
therapeutic or diagnostic agent, would want to utilize a purified and fully
characterized preparation to do so, if only to make sure that the observed
activity is caused by the plasmin rather than some other constituent in the
solution. This conclusion is fully supported by Deacon’s disclose of highly
purified plasmin, establishing the intent to administer pure plasmin –
whether or not the actual plasmin used by Deacon was in fact pure. The
purity of Deacon’s plasmin is not at issue, since the Examiner had cited Ito
for its disclosure of a method purifying the plasmin.

Purification
Patent Owner contends that “substantially removing” was not
accomplished by Robbins as that phrase would have been reasonably
interpreted in light of the ‘500 Patent. Reply Br. 5-7.
We find this attempt to distinguish Robbins unpersuasive since the
Examiner had relied upon Ito for the purification scheme, not Robbins.
Thus, we find it unnecessary to address Patent Owner’s discussion of the
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experiments performed by Robbins and what they did, or what they did not,
reveal. See App. Br. 6; Reply Br. 6.
Patent Owner also argues that Deacon does not show separation of
plasmin from plasminogen activator. Reply Br. 9. However, the Examiner
did not rely on Deacon for this teaching, but rather Ito. This argument is
therefore not persuasive.

• “buffering the plasmin solution with a low pH, low buffering capacity
agent to form a reversibly inactive acidified plasmin solution having a pH of
about 2.5 to about 4.”
Although Patent Owner contends that the recited buffering step is not
taught or suggested by the prior art, it does not appear that Patent Owner
provided substantive arguments as to why it would not have been obvious to
have made a purified acidified plasmin solution as taught by Deacon. App.
Br 4; Deacon, p. 674, Table I.

Summary
For the foregoing reasons, we affirm the obviousness rejection of
claim 1 as unpatentable over Robbins, Ito, and Deacon. As Patent Owner
did not provide separate patentability arguments for claims 4, 7-19, and 21-
23, these claims fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).

REJECTIONS 2-5
The Examiner made specific findings of fact on each Rejections 2-5
and provided a logical reason as to why one of ordinary skill in the art would
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have made the subject matter of the claims based on the prior art teachings.
Answer 5-7. Patent Owner did not identify a defect in the Examiner’s
reasoning. As we find none, we affirm Rejections 2-5 of claims 4, 16, 17,
and 23 for the reasons given by the Examiner.

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
ack
cc:
Patent Owner:
WOMBLE CARLYLE SANDRIDGE & RICE, LLP
ATTN: IP DOCKETING
P.O. BOX 7037
ATLANTA, GA 30357-0037

Third Party Requester

B.J. SADOFF
NIXON & V ANDERHYE, PC
901 NORTH GLEBE ROAD, 11 TH FLOOR
ARLINGTON, VA 22203