Flygare, John A. et al.

Patent Trials and Appeals Board

Oct 18, 2019

13650277 - (R) (P.T.A.B. Oct. 18, 2019)

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.
13/650,277 10/12/2012 John A. Flygare 215050-0002-00-
US-538466
7476
55694 7590 10/18/2019
DRINKER BIDDLE & REATH (DC)
1500 K STREET, N.W.
SUITE 1100
WASHINGTON, DC 20005-1209
EXAMINER
KOSTURKO, GEORGE W
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
10/18/2019 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
DBRIPDocket@dbr.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte JOHN A. FLYGARE, JANET L. GUNZER-TOSTE,
THOMAS PILLOW, PHILIP WILSON HOWARD,
and LUKE MASTERSON
__________

Appeal 2017-008476
Application 13/650,277
Technology Center 1600
__________

Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
DAVID COTTA, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON REQUEST FOR REHEARING
Appellants request rehearing of the decision entered July 9, 2019
(“Decision”) that entered a new ground of rejection under 35 U.S.C.
§ 103(a).
We deny the requested relief.

DISCUSSION
Appellants “disagree that the Kamal reference ‘teaches the chemistry
of asymmetric attachment of a conjugate to a PBD dimer to the N10
position’” (Req. 3). Appellants contend “the synthesis route in Kamal starts
with an asymmetric compound (5a) and finishes with an asymmetric
compound” (Req. 5). Appellants contend “Kamal discloses only the
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inclusion of a protecting group. There are no conjugates disclosed or even
remotely suggested in the Kamal reference” (Req. 5).
We are not persuaded. Appellants argue Kamal alone without
reference to Hartley’s teaching that “the rationally designed
pyrrolobenzodiazepine dimer, SJG-136, is the lead clinical candidate” (Dec.
11, FF 11) and to Chari’s teaching to make conjugates using
pyrrolobenzodiazepine dimers (Dec. 11, FF 12–13). It is the combination of
these references that renders a conjugated PBD dimer obvious, not Kamal
alone. Prior art “must be read, not in isolation, but for what it fairly teaches
in combination with the prior art as a whole.” In re Merck & Co., Inc., 800
F.2d 1091, 1097 (Fed. Cir. 1986).
In addition, Kamal evidences that asymmetric conjugate dimers can
be synthesized (Dec. 14, FF 22) as even Appellants acknowledge (see Req. 5
“finishes with an asymmetric compound”). However, Appellants do not
require any particular route of synthesis in this product claim. Appellants
provide no persuasive evidence that there would not have been a reasonable
expectation, based on the teachings of Kamal, of successfully synthesizing
an asymmetric SJG-136 PBD compound consistent with the teachings of
Hartley and Kamal, and containing conjugates as suggested by Chari (Dec.
11, FF 12–13). “Obviousness does not require absolute predictability of
success . . . all that is required is a reasonable expectation of success.” In re
Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009).
Appellants “disagree that Vlahov is sufficient to form the suggestion
relied upon by the Board in formulating a rejection based on a combination
of four references” (Req. 5). Appellants contend “chemical mechanisms are
necessarily different in light of the hydrazide being used in the Vlahov
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reference, thus providing no indication for use of the same linking
mechanism on an imine bond and no reasonable expectation of success in
the combination of the two references” (Req. 5).
We are not persuaded because this argument fails to combine the
teachings of the prior art. See In re Keller, 642 F.2d 413, 425 (CCPA 1981)
(“The test for obviousness is not whether the features of a secondary
reference may be bodily incorporated into the structure of the primary
reference; nor is it that the claimed invention must be expressly suggested in
any one or all of the references. Rather, the test is what the combined
teachings of the references would have suggested to those of ordinary skill
in the art.”)
As to Appellant’s argument that the ordinary artisan would not have
expected success in linking the known linker of Vlahov to the known N10
linker position disclosed in Kamal because the chemical mechanisms differ,
we note that Chari discloses that chemotherapeutic drugs that may be linked
to crosslinkers include ethyleneimines as well as 2-ethylhydrazide (Chari
¶ 148). Appellants provide no persuasive evidence that there would be any
difficulty in crosslinking either compound using the known crosslinker of
Vlahov and “Attorney’s argument in a brief cannot take the place of
evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). No
persuasive evidence rebutting the Examiner’s position is currently of record
in this application.
Appellants contend the “specific combination would not have been
suggested to the skilled artisan without the benefit of the instant
specification. Therefore, for at least this added reason reconsideration of the
new ground for rejection is respectfully requested” (Req. 6). Appellants
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contend “there is no indication in any of those references even as to how an
asymmetrically modified symmetric PBD dimer such as required herein
could be made, let alone why such a substitution should be made” (Req. 6).
Appellants note that we cited the Examiner in the related 13/641,1981
application including a statement that “other methods of synthesizing
asymmetric PBD dimers were known, because US 7,429,658 and US
7,049,311 disclose such asymmetric PBD dimers” (Req. 7). Appellants
contend that “those references do not actually show the skilled artisan how
to make such asymmetric modifications, let alone provide suggestion to do
so, while leaving a free imine bond on one side” (Req. 7).
We do not find these arguments persuasive because our reasoning
“takes into account only knowledge which was within the level of ordinary
skill at the time the claimed invention was made and does not include
knowledge gleaned only from applicant’s disclosure.” In re McLaughlin,
443 F.2d 1392, 1395 (CCPA 1971). As discussed in the Decision:
Hartley’s PBD dimer named SJG-136 is reasonably
considered a “lead clinical candidate” (FF 11). Chari teaches
targeting cancer compounds including PBD dimers (FF 13–14)
by conjugation to antibodies for “greater potency” and “greater
aqueous solubility” (FF 12) and in order to treat cancer (FF 16).
Thus, Chari provided the ordinary artisan reason to conjugate
antibodies to PBD dimers such as SJG-136.
Chari teaches that the ordinary artisan would have been
able to conjugate “the cytotoxic agents described herein”,
including PBD dimers (FF 13–14), “in such a manner that the
resulting compound still retains the specificity and/or activity of
the starting compound” (FF 17). In the previous appeal,
Appellants noted that based on the patents cited by Chari
regarding PBD dimers, “there may be a suggestion to modify

1 We note that this application is now abandoned.
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both N10 positions based on the configuration of protecting
groups used in the synthesis of SJG-136” (Appeal 2017-
001647; App. Br. 10).
Vlahov teaches linkage using a linker consistent with
claim 1 (FF 20) and Kamal teaches the chemistry of
asymmetric attachment of a conjugate to a PBD dimer to the
N10 position (FF 21–22), demonstrating that the N10 position
is a site that would “give one skilled in the relevant chemical art
the motivation to make close relatives (homologs, analogs,
isomers, etc.) of the prior art” SJG-136 compound. In re
Dillon, 919 F.2d 688, 696 (Fed. Cir. 1990).

(Dec. 14–15). The logic in the decision provides reasons why the
substitution should be made, and Kamal demonstrates that asymmetric
dimers could be made.
As to the citation to the related case, we were simply pointing out how
that Examiner had, in our view, persuasively addressed Declarations filed in
the related 13/641,198 application. The only point relevant to the prima
facie case of obviousness here is the recognition that the prior art disclosed
that asymmetric PBD dimers were known to the ordinary artisan, a point not
disputed by Appellants. We have already explained that Kamal provides a
reasonable expectation of success in generating an asymmetric PBD dimer.
As noted in the Decision, Eigenbrot, cited in the instant application,
recognizes that U and U’ linked to the PBD dimer at the N10 positions may
be “the same or different” and one of the two may simply be an H, resulting
in an asymmetric PBD dimer (see Eigenbrot 6). And because only attorney
argument, not evidence, rebuts that position based on the express disclosure
in Kamal, we find the argument unpersuasive.
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CONCLUSION
We have reviewed the original opinion in light of Appellants’ request,
but we find no point of law or fact which we overlooked or misapprehended
in arriving at our decision. Therefore, Appellants’ request is denied with
respect to making any modifications to the decision entering a new ground
of rejection.

Outcome of Decision on Rehearing:
Claim 35 U.S.C. § Basis Granted Denied
1 103 Hartley, Chari,
Vlahov, Kamal
1

Final Outcome of Appeal after Rehearing
Claim 35 U.S.C. § Basis Affirmed Reversed New Ground
1 103 Hartley, Chari,
Vlahov, Kamal
1

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

REHEARING DENIED