Ex Parte Wang

Patent Trial and Appeal Board

Jun 21, 2016

12519294 (P.T.A.B. Jun. 21, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/519,294 06/15/2009 Bingcheng Wang
68705 7590 06/23/2016
TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP
1300 EAST NINTH STREET
SUITE 1700
CLEVELAND, OH 44114
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
CWR-018055US PCT 1748
EXAMINER
HALVORSON, MARK
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
06/23/2016 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):
rkline@tarolli.com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BINGCHENG W ANG1
Appeal2013-008736
Application 12/519,294
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, and TA WEN CHANG,
Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of treating a neoplastic disorder, which have been rejected as obvious. We
have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
STATEMENT OF THE CASE
EphA2 belongs to a class of enzymes known as tyrosine kinase, which
functions by attaching a phosphate group to a tyrosine amino acid on a
1 Appellant identifies the Real Party in Interest as Case W estem Reserve
University. (Appeal Br. 2.)
Appeal2013-008736
Application 12/519,294
protein. (Kinch2 1 :53-58.) According to the Specification, activation of
EphA2 by an agonist such as ephrin-Al inhibits cell growth, demonstrating
that EphA2 acts as a tumor suppressor. (Spec. i-fi-f 128-129.)
mTOR is an enzyme that has been implicated in the development and
progression of neoplastic disease. 3 (Id. at i-f 80.) Further according to the
Specification, use of ephrin-Al in combination with rapamycin, an
immunosuppressant and mTOR inhibitor, leads to cooperative inhibitory
effects on cell proliferation. (Id. at i-fi-183, 156.)
Claims 1-5 and 7-19 are on appeal. Claim 1 is illustrative and reads
as follows:
1. A method of treating a neoplastic disorder in a subject
compnsmg:
administering to an Eph kinase expressing neoplastic cell of the
subject being treated therapeutically effective amounts of an EphA
agonist and an mTOR inhibitor.
The claims stand rejected as follows:
Claims 1-5 and 7-19 are rejected under 35 U.S.C. § 103(a) as obvious
over the combination of Kinch and Neel. 4
DISCUSSION
Issue
The Examiner has rejected claims 1-5 and 7-19 under 35 U.S.C.
§ 103(a) as obvious over the combination of Kinch and Neel. The Examiner
finds that Kinch discloses inhibition of breast cancer by ephrin-Al, an EphA
2 Kinch et al., US 6,927,203 Bl, issued Aug. 9, 2005 ("Kinch").
3 mTOR stands for mammalian Target Of Rapamycin. (Spec. i-f 80.)
4 Neel et al., US 2006/0094674 Al, published May 4, 2006 ("Neel").
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Application 12/519,294
agonist. (Ans. 4.) While the Examiner finds that Kinch does not disclose
the use of an mTOR inhibitor with the EphA agonist, the Examiner finds
that Neel disclose treating cancer, including breast cancer, using an mTOR
inhibitor such as rapamycin together with a protein kinase inhibitor. (Id.)
The Examiner finds that it would be prima facie obvious to combine Kinch's
ephrinAl and Neel's rapamycin in the treatment of cancer, as both are taught
to be useful for that purpose. (Id. at 4, 9.)
Appellant contends that the claims are patentable over Kinch and Neel
because Neel teaches away from combining an EphA agonist, such as that
disclosed in Kinch, with the mTOR inhibitor of Neel. (Appeal Br. 5-10.)
Appellant further contends that the subject matter of the claims exhibits
unexpected results. (Id. at 5, 10-17.)
Because Appellant argues claims 1 and 13 together, 5 and does not
separately argue claims 2-5, 7-12, and 14--19 (id. at 18), we decide the
appeal of the rejected claims on the basis of claim 1. The issues with respect
to this rejection are (1) whether the evidence of record supports the
Examiner's prima facie case of obviousness, (2) whether the prior art
teaches away from the invention recited in claim 1, and (3) whether
Appellant has presented evidence of unexpected results that, when weighed
with the evidence supporting obviousness, shows claim 1 would not have
been obvious.
5 Claims 1 and 13 differ only in that claim 1 relates to a method of treating a
"neoplastic disorder" by administering therapeutic agents to a "neoplastic"
cell, whereas claim 13 relates to a method of treating "cancer" by
administering therapeutic agents to a "cancer" cell.
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Findings of Fact
FF 1. Kinch teaches diagnosing and treating metastatic disease by
targeting EphA2, a receptor tyrosine kinase that is overexpressed in
metastatic cells such as lung, breast, colon, and prostate tumors. (Kinch
1:17-20, 1:61---64, 2:1-3; see 6:30-32, 6:56---60, 6:64---65, 6:66-7:6, 7:27-
31.)
FF2. Kinch teaches that stimulation of EphA2 is sufficient to reverse
malignant growth and invasiveness in cells that overexpress EphA2 (id. at
1 :64---67) and teaches treating cancer by using agonists to alter EphA2
expression in metastatic cells. (Id. at 2:27-39.)
FF3. Kinch discloses ephrin-Al as an agonist that can be used to
reverse malignant behavior in EphA2 transformed cells. (Id. at 2:27-34,
Example 8; see 3:14--15, 5:27-35.)
FF4. Neel teaches "methods and compositions including an mTOR
inhibitor and a tyrosine kinase inhibitor for reducing the proliferation of and
enhancing the apoptosis of neoplastic cells." (Neel Abstract.)
FF5. Neel teaches that "the combination of an mTOR inhibitor and a
tyrosine kinase inhibitor is more effective than mTOR inhibitor
monotherapy or tyrosine kinase inhibitor monotherapy for reducing the
proliferation of and enhancing the apoptosis of cancer cells." (Id. at i-f 12.)
FF6. Neel teaches rapamycin as an mTOR inhibitor. (Id. at i-f 9.)
FF7. Neel teaches using the methods of its invention to treat, among
others, cancers of the breast, colon, lung, and prostate. (Id. at i-f 17.)
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Analysis
Kinch teaches treating cancer, a neoplastic disorder, by targeting
EphA2 and administering EphA2 agonists. (FF1-FF3.) Neel teaches
treating cancer by administering mTOR inhibitors. (FF4, FF7.)
Accordingly, we find that the Examiner has established a prima facie case of
obviousness as to claim 1, because combining Kinch's EphA2 agonist with
Neel's mTOR inhibitor to treat neoplastic disorder is a "predictable use of
prior art elements according to their established functions." KSR Int 'l Co. v.
Teleflex, Inc., 550 U.S. 398, 417 (2007).
Appellant contends in the arguments regarding unexpected results that
absent hindsight a skilled artisan would not have combined the references to
arrive at the claimed invention, because the compounds at issue are not
taught in the prior art for "the same specific purpose for additive effects on
the same biological targets." (Appeal Br. 14--15.) To the extent this is an
argument against the sufficiency of the prima facie case, we note but do not
find the argument persuasive. "A person of ordinary skill is ... a person of
ordinary creativity, not an automaton." KSR, 550 U.S. at 421.
Likewise, Appellant suggests in the arguments regarding unexpected
results that a skilled artisan would not have combined rapamycin and ephrin-
A 1 based on Neel and Kinch because, prior to the disclosures in the
Specification, there was no suggestion in the art that "an EphA agonist can
be administered to a neoplastic cell expressing Eph kinase for the purpose of
suppressing [certain oncoprotein] activities by disrupting the ... feedback
loops induced by rapamycin." (Appeal Br. 15.) This is similarly
unpersuasive. In obviousness determinations it is not necessary that a
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skilled artisan combine the claimed elements for the same reasons as
Appellant. KSR, 550 U.S. at 419-20.
Teaching Away
Appellant contends that claim 1 is patentable over the cited art
because Neel teaches away from the claimed invention. (Appeal Br. 5-10.)
In particular, because Neel discloses that rapamycin combined with a
tyrosine kinase inhibitor is more effective than rapamycin alone in treating
cancer, Appellant argues that a skilled artisan would not look to combine
rapamycin with Kinch's ephrin-Al, which activates rather than inhibits the
tyrosine kinase EphA2. (Id.; Reply Br. 5---6.)
We are not persuaded. While Neel teaches using several tyrosine
kinase inhibitors with rapamycin to treat neoplasms having cells
characterized by abnormally high levels of tyrosine kinase activity, Neel is
silent with respect to Eph kinase, the particular tyrosine kinase at issue in
claim 1. (Ans. 6.) Neither does Neel suggest that rapamycin can only be
combined effectively with tyrosine kinase inhibitors. (Id.) Silence does not
constitute teaching away. Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d
1371, 1380 (Fed. Cir. 2005).
Even assuming that Neel teaches away from the claimed invention,
moreover, "[w]here the prior art contains 'apparently conflicting'
teachings[,] each reference must be considered 'for its power to suggest
solutions to an artisan of ordinary skill .... consider[ing] the degree to
which one reference might accurately discredit another."' Medichem, S.A. v.
Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006) (quoting In re Young,
927 F2d 588, 591 (Fed. Cir. 1991)). Here, Kinch specifically teaches
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treating cancer by stimulating EphA2 with an agonist. (FF2, FF3.) In light
of Neel's silence with respect to EphA kinase and Kinch's specific teaching
regarding the same, we find that a skilled artisan reviewing the prior art as a
whole would not have been dissuaded from combining the disclosures of
Kinch and Neel to arrive at the claimed invention. See, e.g., Dome Patent
L.P. v. Lee, 799 F.3d 1372, 1381-1382 (Fed. Cir. 2015) (citation omitted)
(affirming conclusion that a skilled artisan would not have been dissuaded
from making the claimed lens material because, even though one prior art
reference warns of difficulty in using claimed materials, other references
teach that such material could be used effectively).
Unexpected Results
Appellant argues that, even if claim 1 is prima facie obvious, the
claim is nonetheless patentable because ephrin-Al and rapamycin
synergistically suppressed neoplastic cell proliferation. (Appeal Br. 11-12.)
We are not persuaded. Appellant relies on the data set forth in Figures
4 and 13 of the Specification. These figures generally show greater
inhibition of proliferation in EphA2-transfected cells when ephrin-Al and
rapamycin are administered together rather than separately. However, both
ephrin-Al and rapamycin are known to inhibit cell proliferation. (FF3, FF4,
FF6.) Appellant has not persuasively shown that the enhanced inhibition
when the two compounds are applied together is synergistic rather than
merely additive. Indeed, the Specification itself suggests that the enhanced
inhibition resulting from combination of ephrin-Al and rapamycin may be
additive or synergistic. (Spec. at i-f 156 ("We conclude that ephrin-Al and
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[ r ]apamycin cotreatment could additively or synergistically suppress
proliferation of lung cancer cells.").)
We note but do not find persuasive Appellant's contention that the
effects of combining an EphA agonist with an mTOR inhibitor are
necessarily synergistic and unexpected because, prior to the invention,
EphA2' s role in regulating tumors was unclear and its specific mechanism of
action was unknown, whereas the Specification showed for the first time that
"an EphA agonist and an mTOR inhibitor of the invention ... interact
pharmacologically and affect each other's actions." (Appeal Br. 13-14, 16-
17; Reply Br. 7.) Unexpected results must be established by factual
evidence. In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984). Here, the
objective evidence in the Specification, such as Figures 4 and 13, does not
suffice to establish that the results of combining an EphA agonist and an
mTOR inhibitor is different than the additive effect that might be expected. 6
Appellant argues that, even if the data only shows an additive effect in
combining ephrin-Al and rapamycin, the Examiner has not provided
evidence that such an effect would be expected. (Appeal Br. 15.) We are
not persuaded: Appellant, not the Examiner, bears the burden with respect
to unexpected results once the Examiner has established a prima facie case
of obviousness. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir.
2007) (finding that patentee's evidence of unexpected results fails because
6 Appellant correctly points out that evidence of unexpected results may be
presented in the Specification. (Appeal Br. 18.) However, the evidence in
the Specification must be factual. Mere arguments or conclusory statements
in the Specification, as elsewhere, do not suffice. In re Geisler, 116 F.3d
1465, 1470 (Fed. Cir. 1997).
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the record is devoid of evidence of what the skilled artisan would have
expected). Moreover, the Examiner has cited to evidence showing that a
combination of two treatment agents would be expected to have additive
effect. (Ans. 15.)
Appellant further argues that even an additive effect is unexpected
because such an effect was previously unknown (Reply Br. 7-8), because
Neel suggests the combination of rapamycin with a tyrosine kinase agonist
would have antagonistic rather than additive effect (id. at 7; Appeal Br. 15-
16), and because treatment with rapamycin alone usually results in
diminishing effects due to rapamycin's upregulation of certain oncoprotein
activities over time (Appeal Br. 12-13, 16).
These arguments are likewise unpersuasive. The fact that an effect is
previously unknown does not mean that it is necessarily unexpected.
PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1363-1364
(Fed. Cir. 2012) ("Scientific confirmation of what was already believed to be
true may be a valuable contribution, but it does not give rise to a patentable
invention."). Similarly, for all the reasons already discussed, the cited art
does not teach away from the claimed invention and would not lead a skilled
artisan to expect rapamycin and ephrin-Al to have an antagonistic effect.
Indeed, Neel supports the Examiner's position that combining rapamycin
with other agents that inhibit cell proliferation would be expected to lead to
enhanced treatment effect, as Neel teaches that rapamycin is more effective
when combined with another such agent. (FF5.) Finally, even if treatment
with rapamycin alone leads to diminishing effect, the data cited by Appellant
does not suggest that rapamycin's effect completely vanishes over time.
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Figure 4C, for instance, shows that both 1 OnM and 1 OOnM rapamycin
continues to suppress cell proliferation after 6 days. Thus, a skilled artisan
would expect some additive enhancement in treatment effect when
rapamycin is combined with ephrin-Al.
In any event, unexpected results must be commensurate with the
scope of the claim. Claim 1 claims administering therapeutically effective
amounts of an EphA agonist and an mTOR inhibitor to an Eph kinase
expressing neoplastic cell. Even assuming the data cited by Appellant from
the Specification shows unexpected results, such results are not
commensurate with the scope of claim 1. As an example, the Specification
provides data only for the combination of a single mTOR inhibitor,
rapamycin, with a single EphA agonist, ephrin-Al. This is particularly
problematic because the Specification defines mTOR inhibitors broadly
(Spec. i-fi-183-87) but fails to show that rapamycin's alleged mechanism of
action is representative of all such inhibitors. Likewise, claim 1 includes in
its scope administering the claimed combination of treatment agents to any
"Eph kinase expressing neoplastic cell," without limitation as to the amount
of Eph kinase expressed. However, as shown by Figure 4C and
acknowledged by the Specification, "proliferation of ... cells expressing
low levels of EphA2 was minimally affected by ephrin-Al .... " (Spec.
i-f 126.) Accordingly, Appellant has not presented evidence of unexpected
results that, when weighed with the evidence supporting obviousness, shows
that claim 1 would not have been obvious.
Appellant argues claim 13 together with claim 1; we sustain the
rejection of claim 13 for the same reasons as discussed above. Claims 2-5,
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7-12, and 14--19 have not been argued separately and therefore fall with
claims 1and13. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm the rejection of claims 1-5 and 7-19 as obvious under
35 U.S.C. § 103(a) over Kinch and Neel.
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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