Ex Parte KUFE et al

Board of Patent Appeals and Interferences

Sep 19, 2001

08309315 (B.P.A.I. Sep. 19, 2001)

The opinion in support of the decision being entered today was not written for
publication and is not binding precedent of the Board.

Paper No. 29

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DONALD W. KUFE, and RALPH R. WEICHSELBAUM
__________

Appeal No. 2001-0690
Application No. 08/309,315
__________

ON BRIEF1
__________

Before ROBINSON, ADAMS, and MILLS, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.

DECISION ON APPEAL2
This is a decision on the appeal under 35 U.S.C. § 134 from the
examiner’s final rejection of claims 7, 9, 12-14 and 22-24, which are all the
claims pending in the application.3

1 Pursuant to appellants request (Paper No. 26, received February 26, 1998) an oral
hearing for this appeal was scheduled (Paper No. 27, mailed April 18, 2001) for
Tuesday, September 11, 2001. However, we note appellants waived (Paper No. 28,
received May 9, 2001) their request for oral hearing. Accordingly, we considered this
appeal on Brief.
2 We note appellants’ statement, in Appeal No. 1999-1353 (Application No. 08/520,923),
that the instant appeal is related to Appeal No. 1999-1353 and Appeal No. 1999-1475
(Application No. 08/248,058). Accordingly, these appeals were considered together.
3 Appellants’ After Final amendment (Paper No. 20, received 3/19/97), inter alia,
cancelled claims 1-6, 10, 11 and 15-21. The examiner’s Advisory Action (Paper No. 21,
mailed April 7, 1997) approved entry of this amendment. The administrative file,
however, does not indicate that these claims were cancelled. Prior to any further action,
the examiner should insure that the administrative accurately reflects the correct status
of the claims.
Appeal No. 2001-0690
Application No. 08/309,315

2
Claims 7, 12 and 22 are illustrative of the subject matter on appeal and
are reproduced below:

7. A process of increasing cell death comprising the steps of:
(a) treating cells with a DNA damaging agent; and
(b) contacting the cells with a protein tyrosine kinase inhibitor.

12. A method for the treatment of neoplastic disease in a patient
comprising the steps of:
(a) administering to the patient a pharmaceutically acceptable
preparation which includes a therapeutically effective amount of
a tyrosine kinase inhibitor; and
(b) treating neoplastic cells with a therapeutically effective amount
of a DNA damaging agent.

22. A method of increasing the effect of ionizing radiation on cell killing,
comprising the steps of:
(a) treating the cells with a therapeutically effective amount of
ionizing radiation; and
(b) contacting the cells with a protein tyrosine kinase inhibitor.
The references relied upon by the examiner are:

Margolis et al. (Margolis) 5,262,409 Nov. 16, 1993

Uckun et al. (Uckun), “Ionizing radiation stimulates unidentified tyrosine-specific
protein kinases in human B-lymphocyte precursors, triggering apoptosis and
clonogenic cell death,” Proc. Natl. Acad. Sci. USA, Vol. 89, pp. 9005-9009 (1992)

Akinaga et al. (Akinaga), “Enhancement of antitumor activity of mitomycin C in
vitro and in vivo by UCN-01, a selective inhibitor of protein kinase C,” Cancer
Chemother. Pharmacol., Vol. 32, pp. 183-189 (1993)
GROUNDS OF REJECTION

Claims 7, 9 and 12-14 stand rejected under 35 U.S.C. § 103 as being
unpatentable over Margolis in view of Akinaga.
Claims 7, 9, 12-14 and 22-24 stand rejected under 35 U.S.C. § 103 as
being unpatentable over Uckun.
We reverse.
Appeal No. 2001-0690
Application No. 08/309,315

3
DISCUSSION
In reaching our decision in this appeal, we considered appellants’
specification and claims, in addition to the respective positions articulated by the
appellants and the examiner. We make reference to the examiner’s Answer4 for
the examiner’s reasoning in support of the rejections. We further reference
appellants’ Brief5 for the appellants’ arguments in favor of patentability.
THE REJECTION UNDER 35 U.S.C. § 103:
Margolis in view of Akinaga
The examiner refers (Answer, page 4) our attention to the statement of
the rejection set forth in the Final Rejection6.
We initially note that in contrast to the examiner’s position (Final
Rejection, page 3) appellants do not concede (See Brief, pages 10-11) that the
use of a tyrosine kinase inhibitor is not critical since the protein kinase inhibitor
may be a serine/threonine kinase inhibitor or a tyrosine protein kinase inhibitor.
Instead, appellants maintain (Brief, bridging sentence, pages 10-11) “there is no

4 Paper No. 25, mailed December 23, 1997.
5 Paper No. 24, received September 15, 1997.
6 Paper No. 18, mailed December 18, 1996.
Appeal No. 2001-0690
Application No. 08/309,315

4
basis for concluding that serine/threonine protein kinases would act similarly to
tyrosine protein kinases in conjunction with a DNA damaging agent,” as claimed.
According to the examiner (Final Rejection, page 3) “Margolis and
Akinaga teach killing cells using a DNA damaging agent, combined with a protein
kinase inhibitor. Akinaga teaches that kinase inhibitors are routinely used in anti-
tumor therapy, i.e., in a treatment whereby cells are killed.” Therefore, the
examiner concludes “[o]ne would expect a reasonable expectation of success of
substituting the specific tyrosine kinase inhibitor claimed for the generic protein
kinase inhibitor taught by the references to achieve cell killing based on the fact
that the references teach that protein kinase inhibitors in general kill cells.”
According to appellants (Brief, page 11) “the teaching of Akinaga is clearly
that inhibitors of protein kinase C, a serine/threonine protein kinase, can
potentiate the effect of the antitumor agent MMC, but general inhibitors of protein
kinases do not have such an effect.” Accordingly, appellants argue (Brief,
bridging sentence, pages 11-12) that “the practitioner of the art would be led by
Akinaga to conclude only that selective inhibitors of serine/threonine protein
kinases could potentiate the effects of anti-cancer agents, while general
inhibitors of protein kinases, including tyrosine protein kinases would not have
such effects.”
Appellants further argue (Brief, page 12) “Akinaga [pages 183-184] clearly
demonstrates that the state of the art at the time of the instant invention was one
of uncertainty with regard to the effects of protein kinase inhibitors on anticancer
agents.” Accordingly appellants conclude (id.) “there could have been no
Appeal No. 2001-0690
Application No. 08/309,315

5
reasonable likelihood of success in predicting the combination of tyrosine protein
kinase inhibitors with DNA damaging agents.”
The examiner does not specifically address appellants’ argument.
Instead, the examiner argues (Answer, page 4) “[t]he references detail that the
inhibition of protein kinases adversely affects the cells’ multiplication and growth
and in doing so has a synergistic effect when used in combination with DNA
damaging agents.” We note the examiner’s reference to “protein kinases” and
not to “protein tyrosine kinases” which is, inter alia, the subject matter of
appellants’ claimed invention. This distinction is more pronounced in the
examiner’s argument (id.) that “PTK’s [protein tyrosine kinases] (e.g. the Src-
family), as with the protein kinases targeted in Margolis and Akinaga, are
instrumental in the proliferation of cells” [emphasis added].
Therefore, instead of identifying precisely where his supporting references
teach protein tyrosine kinases, the examiner enters into a discussion of the
involvement of protein tyrosine kinases in cell proliferation, and attempts to
connect this discussion with the teachings of Margolis and Akinaga. However,
as appellants point out (Brief, page 11) protein kinase C, the subject matter of
Akinaga, is not a protein tyrosine kinase; protein kinase C is a serine/threonine
protein kinase. With regard to Margolis, appellants point out (Brief, page 12) that
“there is no evidence of record to suggest that … [2-aminopurine and 6-
dimethylaminopurine] are tyrosine protein kinase inhibitors.”
On this record, the examiner failed to provide the factual evidence
necessary to establish a nexus between protein tyrosine kinase inhibitors and
Appeal No. 2001-0690
Application No. 08/309,315

6
the teachings of Margolis and Akinaga. We remind the examiner “[t]he Patent
Office has the initial duty of supplying the factual basis for its rejection. It may
not, because it may doubt that the invention is patentable, resort to speculation,
unfounded assumptions or hindsight reconstruction to supply deficiencies in its
factual basis.” In re Warner, 379 F.2d 1011, 1017, 154 USPQ 173, 178 (CCPA
1967), cert. denied, 389 U.S. 1057 (1968). In addition, as set forth in In re
Kotzab, 217 F.3d 1365, 1369-70, 55 USPQ2d 1313, 1316 (Fed. Cir. 2000):
A critical step in analyzing the patentability of claims pursuant to
section 103(a) is 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. … Close adherence to this methodology is especially
important in cases where the very ease with which the invention
can be understood may prompt one “to fall victim to the insidious
effect of a hindsight syndrome wherein that which only the
invention taught is used against its teacher.” …

Most if not all inventions arise from a combination of old elements.
… Thus, every element of a claimed invention may often be found
in the prior art. … However, identification in the prior art of each
individual part claimed is insufficient to defeat patentability of the
whole claimed invention. … Rather, to establish obviousness based
on a combination of the elements disclosed in the prior art, there
must be some motivation, suggestion or teaching of the desirability
of making the specific combination that was made by the applicant.
[citations omitted]

In other words, “there still must be evidence that ‘a skilled artisan, . . . with
no knowledge of the claimed invention, would select the elements from the cited
prior art references for combination in the manner claimed.’” Ecolochem Inc. v.
Southern California Edison, 227 F.3d 1361, 1375, 56 USPQ2d 1065, 1075-76
(Fed. Cir. 2000). On this record, the examiner did not provide the factual
evidence necessary to establish that absent appellants’ disclosure, a person of
Appeal No. 2001-0690
Application No. 08/309,315

7
ordinary skill in the art would have combined the elements from the cited prior art
in a manner that would have resulted in appellants’ claimed invention.
The initial burden of presenting a prima facie case of obviousness rests
on the examiner. In re Oetiker, 977 F.2d 1443, 1445, 24 USPQ2d 1443, 1444
(Fed. Cir. 1992). On these circumstances, it is our opinion that the examiner
failed to provide the evidence necessary to support a prima facie case of
obviousness. Where the examiner fails to establish a prima facie case, the
rejection is improper and will be overturned. In re Fine, 837 F.2d 1071, 1074, 5
USPQ2d 1596, 1598 (Fed. Cir. 1988). Accordingly, we reverse the rejection of
claims 7 and 9-14 under 35 U.S.C. § 103 as being unpatentable over Margolis in
view of Akinaga.
Uckun
The examiner refers (Answer, page 4) our attention to the statement of
the rejection set forth in the Final Rejection. According to the examiner (Final
Rejection, page 5):
Uckun states that the cells were irradiated. Clearly, if cells are
irradiated, they are killed. On page 9006, column 1, the phrase
“[a]poptosis [a]ssays” is recited. This is further proof that Uckun
intended to kill the cells. In addition, on page 9008, column 1,
Uckun states that “these findings provide direct evidence that
ionizing radiation stimulates PTKs” and that “tyrosine
phosphorylation plays an important role in the initiation of apoptosis
in human B-lymphocyte precursors exposed to ionizing
radiation”….

According to appellants (Brief, page 8) “Uckun teaches that tyrosine
phosphorylation plays an important role in the initiation of apoptosis. Apoptosis
is a descriptive term for programmed cell death. Thus, according to Uckun, the
Appeal No. 2001-0690
Application No. 08/309,315

8
initiation of cell death is dependent upon having active tyrosine kinases present
in the cell….” Therefore, appellants conclude (id.) that the “entire process
[taught by Uckun] would be expected to be reversed by the tyrosine kinase
inhibitors that are the subject of the instant invention.” We agree.
In response, the examiner argues “there is a myriad of protein tyrosine
kinases … with a plurality of functions within the cells. … Uckun discovered that
ionizing radiation also had the effect of stimulating unidentified PTK’s….
Therefore … it would be obvious to combine a PTK [inhibitor] with radiation….”
We cannot agree with the examiner’s position.
Uckun clearly teaches (page 9008, column 1, third full paragraph):
genistein [a claimed protein tyrosine kinase inhibitor, see
e.g. appellants’ claim 9] prevented … apoptosis-related
morphologic changes in irradiated cells, with <25% of cells
showing apoptosis-related changes in morphology…
providing evidence that tyrosine phosphorylation plays an
important role in the initiation of apoptosis in human B-
lymphocyte precursors exposed to ionizing radiation.

Accordingly we agree with appellants’ argument (Brief, page 8) that
“Uckun teaches away from the present invention.” We remind the examiner, that
in determining whether the claimed invention is obvious, a prior art reference
must be read as a whole and consideration must be given where the reference
teaches away from the claimed invention. Akzo N.V., Aramide Maatschappij
v.o.f. v. United States Int’l Trade Comm’n, 808 F.2d 1471, 1481, 1 USPQ2d
1241, 1246 (Fed. Cir. 1986).
On these circumstances, it is our opinion that the examiner failed to
provide the evidence necessary to support a prima facie case of obviousness.
Appeal No. 2001-0690
Application No. 08/309,315

9
Where the examiner fails to establish a prima facie case, the rejection is
improper and will be overturned. See Fine. Accordingly, we reverse the
rejection of claims 7, 9-14 and 22-24 under 35 U.S.C. § 103 as being
unpatentable over Uckun.
REVERSED

Douglas W. Robinson )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Donald E. Adams )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Demetra J. Mills )
Administrative Patent Judge )

DA/dym
Appeal No. 2001-0690
Application No. 08/309,315

10
Gary J. Sertich
Arnold, White & Durkee
P.O. Box 4433
Houston, TX 77210-4433