Ex Parte IMHOF et al

Patent Trial and Appeal Board

Jul 18, 2018

13622727 (P.T.A.B. Jul. 18, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/622,727 09/19/2012
52034 7590 07/20/2018
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
AUSTIN, TX 78746
FIRST NAMED INVENTOR
Beat A. IMHOF
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.
CLFR.P03 l l US .D 1 5898
EXAMINER
HADDAD, MAHER M
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
07/20/2018 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):
docket@phiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BEAT A. IMHOF, MARIJANA MILJKOVIC-LICINA, and
PHILIPPE HAMMEL 1
Appeal2016-007345
Application 13/622,727
Technology Center 1600
Before FRANCISCO C. PRATS, RICHARD J. SMITH, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating cancer, which have been rejected as obvious and as non-enabled.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
"Angiogenesis is a multi-step cellular process of capillary sprouting
and formation of neo-vasculature from preexisting blood vessels." Spec. ,r 3.
1 Appellants identify the Real Party in Interest as Research Development
Foundation. Appeal Br. 3.
Appeal2016-007345
Application 13/622,727
"Angiogenesis is a prerequisite for tumor growth and blocking this process
could prevent further proliferation of tumor cells." Spec. ,r 6. The
Specification describes the use of an antibody for SRPX2, an angiogenesis
modulator, to treat angiogenesis-related conditions including cancer. Spec.
,r 2.
Claims 15, 18, 21, and 342 are on appeal. Claim 15 is illustrative and
reads as follows:
15. A method of treating cancer in a subject by
inhibiting the proliferation of non-tumor angiogenic cells that
express urokinase-type plasminogen activator receptor uP AR
comprising administering to the subject an amount of a
composition comprising an antibody or a fragment thereof that
binds to SRPX2 (SEQ ID N0:14) and inhibits the binding of
SRPX2 to uP AR that is effective to inhibit the proliferation of
non-tumor angiogenic cells that express uPAR in the subject.
The claims stand rejected as follows:
Claim 34 has been rejected under 35 U.S.C. § 112, for failure to
comply with the enablement requirement.
Claims 15, 18, and 21 have been rejected under 35 U.S.C. § 103(a) as
unpatentable over Tanaka 3 in view of Hillman. 4
2 Claim 33 is pending in the application but has been withdrawn from
consideration as being directed to a non-elected species. Final Act. 2.
3 Tanaka et al., SRPX2 is a Novel Therapeutic Target In Gastric Cancer,
98th AACR Annual Meeting, (2007) ("Tanaka").
4 Hillman et al., WO 00/43508, published July 27, 2000 ("Hillman").
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Claims 15, 18, and 21 have been rejected under 35 U.S.C. § 103(a) as
unpatentable over Guo 5 or Min6 in view of Hubbell7 and Royer-Zemmour. 8
Claim 34 has been rejected under 35 U.S.C. § 103(a) as unpatentable
over Guo or Min in view of Hubbell and Royer-Zemmour in further view of
Ranieri. 9
ENABLEMENT
Issue
The issue with respect to this rejection is whether claim 34 satisfies
the enablement requirement.
The Examiner finds that claim 34 recites treating lymphoma which
embraces both non-Hodgkin's lymphoma and Hodgkin's lymphoma. Non-
5 Guo et al., A Peptide Derived From the Nonreceptor Binding Region of
Urokinase Plasminogen Activator (uP A) Inhibits Tumor Progression and
Angiogenesis and Induces Tumor CellDeath In Vivo, 14 J. FASEB 1400-
1410 (2000) ("Guo").
6 Min et al., Urokinase Receptor Antagonists Inhibit Angiogenesis and
Primary Tumor Growth in Syngeneic Mice, 56 Cancer Res. 2428 (1996)
("Min").
7 Hubbell et al., US 5,567,440, issued Oct. 22, 1996 ("Hubbell").
8 Royer-Zemmour et al., Epileptic and Developmental Disorders of the
Speech Cortex: Ligand/Receptor Interaction of Wild-Type and Mutant
SRPX2 with the Plasminogen Activator Receptor uPAR, 17 Hum. Molecular
Genetics 3617 (2008) ("Royer-Zemmour").
9 Ranieri et al., Endothelial Area and Microvascular Density in a Canine
Non-Hodgkin's Lymphoma: An Interspecies Model of Tumor Angiogenesis,
46 Leukemia and Lymphoma 1639 (2005) ("Ranieri").
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Final Act. 10 3. The Examiner finds that Kuittinen 11 teaches that the extent of
neovascularization does not correlate with more advanced Hodgkin's disease
indicating that neovascularization is not critical in the progression of
Hodgkin's disease. Since the Specification teaches treating cancer by
controlling angiogenesis, the Examiner concludes that there is no reasonable
correlation between the scope of the claims and the scope of enablement. Id.
Appellants contend that the Specification provides substantial
information regarding the treatment of cancers which would enable one
skilled in the art to use the claimed method to treat lymphoma. Appeal Br.
5. Appellants point to the first Declaration of Mr. Imhof12 which shows that
the claimed method reduces the growth of tumors in mice as evidence that
the claims are enabled. Id. Appellants acknowledge that the data does not
report treatment of Hodgkin's disease, but argue that it does teach inhibition
of uP AR expressing cells which indicates that the method can be used to
treat cancer. Appeal Br. 6. Appellants also argue that the evidence or record
shows that the use of the claimed antibodies reduces neovascularization and
inhibits tumors. Id.
With respect to Hodgkin's disease, Appellants contend that while
Kuittinen may teach that neovascularization is not related to the progression
of the disease, the presence of at least some neovascularization at some stage
10 Non-Final Act. mailed July 21, 2014.
11 Kuittinen et al., Diverse role of MMP-2 and MMP-9 in the
clinicopathological behavior of Hodgkin's lymphoma, 69 Eur. J. Heamatol.
205 (2002) ("Kuittinen").
12 Inventor's Declaration Under 37 C.F.R. § 1.132 filed July 24, 2013
("Imhof Deel. I").
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of the disease means that the present method would be effective in treating
the disease. Appeal Br. 7. In support of this contention, Appellants cite to
the second declaration of Mr. Imhof. 13 Id. Appellants conclude by arguing
that the Examiner has failed to establish a prima facie case that claim 34 is
not enabled. Id.
Principles of Law
"When rejecting a claim under the enablement requirement of section
112, the PTO bears an initial burden of setting forth a reasonable explanation
as to why it believes that the scope of protection provided by that claim is
not adequately enabled by the description of the invention provided in the
specification of the application; this includes, of course, providing sufficient
reasons for doubting any assertions in the specification as to the scope of
enablement. If the PTO meets this burden, the burden then shifts to the
applicant to provide suitable proofs indicating that the specification is indeed
enabling." In re Wright, 999 F.2d 1557, 1561---62 (Fed. Cir. 1993).
Analysis
We agree with the Examiner's conclusion that claim 34 is not enabled
by the present Specification. Claim 34 is directed to treating lymphoma
using the specified antigens in an amount sufficient to inhibit
neovascularization. Appeal Br. 19 (Claims App.). Lymphoma includes both
Hodgkin's disease and non-Hodgkin's lymphoma. Non-Final Act. 3.
While the Specification mentions lymphoma and Hodgkin's disease as
13 Second Inventor's Declaration Under 37 C.F.R. § 1.132 filed Jan. 21,
2015. ("ImhofDecl. II").
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disorders that can be treated by the claimed method, Spec. ,r 125, there are
no working examples showing the effectiveness against Hodgkin's disease.
The Examiner has brought forth evidence that shows that neovascularization
does not play a role in Hodgkin's disease. Non-Final Act. 3, See Kuittinen,
Abstract. Since the claimed method specifically calls for using an antibody
which inhibits neovascularization and the evidence of record shows that
neovascularization plays no role in the progression of Hodgkin's disease, we
find that the Examiner has established a prima facie case that claim 34 is not
enabled for its entire scope in that the Specification does not teach how to
use the claimed antibody to treat Hodgkin's disease.
Appellants' arguments and the Declarations of Mr. Imhof do not
persuade us that claim 34 is enabled for its entire scope. The evidence
presented by Appellants shows that the claimed method is effective in
preventing or reducing neovascularization, however, as shown by Kuittinen,
neovascularization does not play a role in the progression of Hodgkin's
disease. Ans. 5.
Appellants point to the Second Declaration of Mr. Imhof as evidence
that neovascularization plays a role in Hodgkin's disease and therefore, the
claimed method would be effective in treating Hodgkin's disease. Appeal
Br. 7. We are not persuaded. In his second declaration Mr. Imhof states:
I submit that just because there is a lack of correlation
between neovascularization and HD progression does not mean
that neovascularization does not play a role in the disease.
Even a de minim us amount of neovascularization, at whatever
stage the HD may exist, is subject to effective treatment
according to the presently claimed methods. Indeed, the claims
do not set forth any particular level of treatment, nor
intervention at any particular stage of cancer.
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Imhof Deel. II ,r 7. This does not persuade us that neovascularization in fact
occurs in Hodgkin's disease and that the claimed method would be effective
in treating the disease.
Conclusion of Law
We conclude that claim 34 is not enabled for the full scope of the
claim.
OBVIOUSNESS
Tanaka and Hillman
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner's conclusion that the subject matter of
claims 15, 18, and 21 would have been obvious over Tanaka combined with
Hillman.
The Examiner finds that Tanaka teaches that SRPX2 is a therapeutic
target for treating gastric cancer. Non-Final Act. 4. The Examiner finds that
Tanaka teaches that siRNA which targets SRPX2 suppress production of
SRPX2 and suppresses tumor growth. Id. The Examiner finds that Hillman
teaches the use of antibodies which bind to the same sequence as recited in
claim 15. Id. The Examiner goes on to find that Hillman teaches that the
antibodies target SRPUL which is the same as SRPX2. Id. The Examiner
concludes that it would have been obvious to one skilled in the art to use the
antibodies in Hillman in the method of Tanaka to treat gastric cancer. Id. at
4--5.
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Appellants traverse the Examiner's posited substitution of Hillman's
antibodies for the siRNA of Tanaka. Appeal Br. 9. Appellants contend that
the antibodies of Hillman and the siRNA of Tanaka used different modes of
operation and that the proposed substitution would change the principle of
operation of Tanaka. Id. Appellants also argue that the teachings of
Hillman would not lead one skilled in the art to use the disclosed antibodies
to treat SRPX2 cancers. Appeal Br. 11. Finally, Appellants argue that the
Examiner improperly relied on inherency in finding that the anti-SRPX2
antibodies act by blocking interaction with uPAR on non-tumor angiogenic
cells. Appeal Br. 11-15.
Principles of Law
[T]he examiner bears the initial burden, on review of the
prior art or on any other ground, of presenting a prim a f acie
case ofunpatentability. If that burden is met, the burden of
coming forward with evidence or argument shifts to the
applicant.
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
"[W]hen a patent claims a structure already known in the prior art that
is altered by the mere substitution of one element for another known in the
field, the combination must do more than yield a predictable result." KSR
Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007), citing United States v.
Adams, 383 U.S. 39, 50-51 (1966).
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"Where ... the claimed and prior art products are identical or
substantially identical ... 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. ... [The] fairness [ of the burden-shifting] 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).
Analysis
We adopt the Examiner's findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Non-Final Action, the
Final Action, and Answer regarding this rejection. We find the Examiner
has established that the subject matter of the claims would have been
obvious to one skilled in the art at the time the invention was made over
Tanaka combined with Hillman. Appellants have not produced evidence
showing, or persuasively argued, that the Examiner's determinations on
obviousness are incorrect. Only those arguments made by Appellants in the
Briefs have been considered in this Decision. Arguments not presented in
the Briefs are waived. See 37 C.F.R. § 4I.37(c)(l)(iv) (2015). We have
identified claim 15 as representative; therefore, all claims fall with claim 15.
We address Appellants' arguments below.
Appellants contend that the antibodies of Hillman cannot be properly
substituted for the siRNA of Tanaka in that the antibodies and siRNA act in
a different way. Appeal Br. 9. Specifically, Appellants contend that the
siRNA of Tanaka acts to inhibit the production of SRPX2 whereas the
antibodies of Hillman act to prevent the SRPX2 from engaging its receptor.
Id. We are unpersuaded.
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As the Examiner points out, both the siRNAs and the antibodies act to
impede the function of SRPX2 in tumor growth. Ans. 12. Since both are
effective in treating SRPX2-expressing cancer, we agree with the Examiner
that one skilled in the art would consider one a substitute for the other. Id.
Appellants contend that the teachings of Hillman would not lead one
skilled in the art to use the antibodies disclosed in Hillman against SRPX2.
Appeal Br. 11. Appellants contend that the disclosure in Hillman with
respect to CAP- I antagonists' ability to treat various diseases would not lead
one skilled in the art to treat cancer as called for in the present claims. Id.
Again we are not persuaded.
Hillman teaches that the disclosed antibodies can be used to treat
SRPX2-expressing cancer. See, Hillman 2, 11. 13-21. We agree with the
Examiner that this teaching, combined with the teaching of Tanaka, would
lead one skilled in the art to the claimed method. Ans. 13.
Appellants contend that there is nothing in the references to suggest
that the antibodies of Hillman would inhibit the binding of SRPX2 to uP AR.
Appeal Br. 11. Appellants contend that the Examiner improperly relied on
inherency for this limitation. This argument is unpersuasive.
As the Examiner points out, the antibodies of Hillman are the same or
similar to the claimed antibodies. Ans. 20. Based on their similarities, one
skilled in the art would expect the antibodies to possess the same properties
including the inhibiting SRPX2 from binding to uP AR. Id. The burden
shifts to the Appellants to show that the antibodies in Hillman do not possess
the same properties as the claimed antibodies. In re Best, 562 F.2d at 1255.
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Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner's conclusion that the subject matter of claims 15 would have been
obvious over Tanaka combined with Hillman.
Claims 18 and 21 have not been argued separately and therefore fall
with claim 15. 37 C.F.R. § 4I.37(c)(l)(iv).
Guo, Min, Hubbell and Royer-Zemmour
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner's conclusion that the subject matter of
claims 15, 18, and 21 would have been obvious over Guo or Min combined
with Hubbell and Royer-Zemmour.
The Examiner finds that Guo teaches that a peptide derived from the
non-receptor region of urokinase plasminogen activator (uP A) inhibits tumor
growth and angiogenesis. Non-Final Act. 6. The Examiner finds that Min
teaches the uP A is involved with angiogenesis related to tumor growth and
that urokinase receptor antagonists inhibit angiogenesis. Id. at 7. The
Examiner finds that Royer-Zemmour teaches that SRPX2 is a ligand for
uP AR which represents a novel target for therapeutic molecules that can be
used to regulate various processes including angiogenesis. Id. The Examiner
finds that Royer-Zemmour teaches an anti-SRPX2 antibody. Id. The
Examiner concludes
Those of skill in the art would have had reason to use the
anti-SRPX2 antibody of the Royer-Zemmour et al as a
substitute for the treatment taught in Guo et al and Min et al
because, like the compounds taught in Guo and Min et al, anti-
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Id.
SRPX2 antibodies inhibits the interaction of uP AR receptor and
it ligand, SRPX2. Substituting a known element for another, to
yield the known result, is obvious.
Appellants contend that there is no scientific basis for finding that one
skilled in the art could use the antibodies of Royer-Zemmour in place of the
peptides of Guo in that there is no reason to believe that the molecules
would behave in the same way. Appeal Br. 16 Appellants also argue that
one skilled in the art would not expect the peptides and antibodies to
perform in the same way and the peptides act through an allosteric
mechanism whereas the antibodies act in a steric fashion. Id. at 17.
Analysis
We again adopt the Examiner's findings of fact, reasoning on scope
and content of the prior art, and conclusions set out in the Final Action and
Answer regarding this rejection. We find the Examiner has established that
the subject matter of the claims would have been obvious to on skilled in the
art at the time the invention was made over Guo or Min combined with
Hubbell and Royer-Zemmour. Appellants have not produced evidence
showing, or persuasively argued, that the Examiner's determinations on
obviousness are incorrect. Only those arguments made by Appellants in the
Briefs have been considered in this Decision. Arguments not presented in
the Briefs are waived. See 37 C.F.R. § 4I.37(c)(l)(iv) (2015). We have
identified claim 15 as representative; therefore, all claims fall with claim 15.
We address Appellants' arguments below.
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Appellants contend that there is no scientific basis for substituting the
antibodies of Royer-Zemmour for the peptides of Guo or the blocking uP A
antagonists of Min. Appeal Br. 16. We are not persuaded.
Each of the compounds act by blocking the binding of SRPX2 with
uP AR which results in reduced angiogenesis. See Guo 1400, Min 2428. We
agree with the Examiner that these teachings would lead one skilled in the
art to substitute the SRPX2-binding antibodies of Royer-Zemmour for the
peptide of Guo or the antagonists of Min, with an expectation that antibody
binding would block SRPX2-uP AR interaction. Ans. 21.
Appellants argue that one skilled in the art would not deem the
antibodies to be substitutes for the peptides in that the peptides act in an
allosteric fashion and the antibodies act in a steric fashion. Appeal Br. 1 7.
Again, we are not persuaded.
As stated above, all three compounds act would have been expected to
inhibit the interaction between SRPX2 and uP AR, resulting in reduced
angiogenesis. Given the teachings that the peptides and antibodies would be
expected to produce the same desired effect, we agree with the Examiner
that one skilled in the art would deem the antibodies of Royer-Zemmour to
be effective substitutes for the peptides of Guo. Ans. 22.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner's conclusion that the subject matter of claim 15 would have been
obvious over Guo or Min combined with Hubbell and Royer-Zemmour.
Claims 18 and 21 have not been argued separately and therefore fall
with claim 15. 37 C.F.R. § 4I.37(c)(l)(iv).
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Guo, Min, Hubbell, Royer-Zemmour, and Ranieri
Appellants' only argument with respect to this rejection is that Ranieri
does not remedy the deficiencies of the other references. Appeal Br. 1 7. As
discussed above, we do not find the teachings of Guo or Min combined with
Hubbell and Royer-Zemmour to be deficient. We therefore affirm this
rejection.
SUMMARY
We affirm the rejection under 35 U.S.C. § 112, first paragraph.
We affirm the rejections under 35 U.S.C. § 103(a).
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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