Ex Parte Gleave et al

Patent Trial and Appeal Board

Apr 11, 2016

13404741 (P.T.A.B. Apr. 11, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/404,741 02/24/2012
57381 7590
Larson & Anderson, LLC
P.O. BOX 4928
DILLON, CO 80435
04/11/2016
FIRST NAMED INVENTOR
Martin Gleave
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.
UBC.P-030-DV 4 1014
EXAMINER
CHONG, KIMBERLY
ART UNIT PAPER NUMBER
1674
MAILDATE DELIVERY MODE
04/11/2016 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 MARTIN GLEAVE, BURKHARD JANSEN,
IOANNIS P. TROUGAKOS, EFSTATHIOS GONOS,
MAXIM SIGNAEVSKY, and ELIANA BERALDI
Appeal2013-008937
Application 13/404,741
Technology Center 1600
Before ERIC B. GRIMES, JACQUELINE T. HARLOW, and
ROBERT A. POLLOCK, Administrative Patent Judges.
POLLOCK, Administrative Patent Judge.
DECISION ON APPEAL
Appellants appeal under 35 U.S.C. § 134(a) from the final rejection of
claims 35-38, 42, 47, and 49. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
The Specification discloses "isolated RNA molecules which mediate
RN Ai. That is, the isolated RNA molecules of the present invention mediate
degradation of mRNA that is the transcriptional product of the ... target
gene." Spec. 5. Among the disclosed RNA molecules are siRNAs (small
interfering RNAs) "directed to mRNA encoding clusterin, ... [which] is
expressed in increased amounts by prostate tumor cells following androgen
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Application 13/404,741
withdrawal. Furthermore, it has been determined that antisense therapy
which reduces the expression of clusterin provides therapeutic benefits in the
treatment of cancer." Id. at 6. "These sequences can be used alone or in
combination with other chemotherapy agents or apoptosis inducing
treatment concepts in the treatment of prostate cancer, sarcomas such as
osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung
cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and
melanoma." Id.
Claim 35, the sole independent claim on appeal, reads as follows:
35. A method of treating a cancer that expresses clusterin,
comprising administering to an individual in need of
treatment a double-stranded RNA molecule effective to
inhibit expression of the secretory isoform of human
clusterin (s-CLU) but not the nuclear isoform of human
clusterin (n-CLU) said double stranded RNA molecules
consisting of Seq ID Nos 58 and 59, or Seq ID Nos. 61 and
62 or a combination Seq ID Nos 58 and 59, and Seq ID Nos.
61 and 62.
Depending from claim 35, claim 38 recites:
38. The method of claim 35, wherein the cancer is selected
from the group consisting of sarcomas, renal cell carcinoma,
breast cancer, bladder cancer, lung cancer, colon cancer,
ovarian cancer, anaplastic large cell lymphoma and
melanoma.
The Examiner rejects claims 35-38, 42, 47, and 49 under 35 U.S.C.
§ 112, first paragraph, as failing to comply with the enablement requirement.
Ans. 5. 1 The Examiner finds that the claims are directed to a method of
1 We cite herein to the Supplemental Examiner's Answer, which clarifies
that the Examiner's Answer dated March 22, 2013, incorrectly indicated that
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treating any type of cancer, and in particular several specific cancers (id.);
that "the state of the art linking clusterin expression and methods of
treatment for tumors or expression in certain tumors was unpredictable at the
time of filing" (id. at 6, citing Shannan2 and Nascimento3); and that the
Specification does not provide working examples that "include specific
embodiments wherein the skilled artisan could predictably use the claimed
method for treatment of cancer" (id. at 7). The Examiner finds that for the
claimed methods to be enabled "clusterin expression in all cancers is [sic,
must be] a predictable causative factor in the pathogenesis of the disease or
the reason cancer cells continue to proliferate or not killed by apoptosis such
that a decrease in this expression would lead to treatment effects." Id. at 9.
The Examiner finds that the Specification lacks support for such a causal
link and the prior art does not otherwise "allow one of skill in the art to use
the claimed invention to predictably treat all cancers that express clusterin
because it is not known whether clusterin expression is the reason for cancer
or cancer cell survival or proliferation of cancer cells." Id. The Examiner
thus concludes that undue experimentation would be required to practice the
claimed method. Id. at 8.
claim 49 was allowable. See Supplemental Examiner's Answer ("Answer")
at 1.
2 Shannan et al., Challenge and promise: roles for clusterin in pathogenesis,
progression and therapy of cancer, 13 Cell Death and Differentiation 12-19
(2006).
3 Nascimento et al., Clusterin, a Marker for Anaplastic Large Cell
Lymphoma, Immunohistochemical Profile in Hematopoietic and
Nonhematopoietic Malignant Neoplasms, 121 Am. J. Clin. Pathol. 709-717
(2004).
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Appellants respond that the Examiner's only evidence for
unpredictability "is that not all cancer cells express clusterin," which "does
nothing to undermine the asserted cytoprotective affect [sic] of clusterin
when it is in present, and casts no doubt on the statements of broad
applicability in the application." Reply Br. 1-2. Appellants also argue that
the prior art, and in particular, Shannan, refutes the Examiner's position
regarding the role of clusterin in cell survival, demonstrates the high level of
skill in the art, and supports the antiapoptotic role of the secreted form of
clusterin (sCLU) in tumorigenesis. Id. at 2-3.
We agree with Appellants (Reply Br. 1-3) that the Examiner has not
provided evidence that supports a prima facie case of nonenablement. See In
re Wright, 999 F.2d 1557, 1561---62 (Fed. Cir. 1993) ("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.").
In support of her conclusion that the claims on appeal are not enabled,
the Examiner finds that although
[t]he working embodiment in the instant application
illustrates a decrease in expression of prostate, lung, breast
and ovarian cancer cells in vitro after treatment with siRNA
molecules targeted to clusterin. . . . [it] does not include
specific embodiments wherein the skilled artisan could
predictably use the claimed method for treatment of cancer.
Ans. 7.
As we understand the rejection, the Examiner's concern is that undue
experimentation would be required to produce an effective cancer treatment
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based on the in vitro examples disclosed in the Specification. However, the
fact "[t]hat some experimentation may be required is not fatal; the issue is
whether the amount of experimentation required is 'undue."' In re Vaeck,
947 F.2d 488, 495 (Fed. Cir. 1991). "Usefulness in patent law, and in
particular in the context of pharmaceutical inventions, necessarily includes
the expectation of further research and development." In re Brana, 51 F.3d
1560, 1568 (Fed. Cir. 1995).4
In this case, the Examiner has not provided evidence to show that a
person of ordinary skill in the cancer treatment art would need to carry out
undue experimentation to extrapolate the in vitro experiments described in
the Specification to the claimed cancer treatment method. Although the
Examiner finds that the working examples would not allow a skilled artisan
to "predictably use the claimed method for treatment of cancer" (Ans. 7), the
Specification demonstrates that "CL-I and CL-II oligonucleotides [double-
stranded oligonucleotides comprising the SEQ ID NOs: 58 and 59, and SEQ
ID NOs: 61 and 62, respectively, as recited in claim 35] specifically knock-
down the secreted CL U ( s-CL U) protein form" in osteosarcoma and PC3
prostate cancer cells in vitro. Spec. 20-21; see id at 16-19 (Examples 2, 3),
21-22. The reduction in clusterin by these CL-I and CL-2 siRNAs also
rendered the cells "significantly more sensitive to [the anti-cancer drug
doxorubicin (DXR)] and a massive apoptosis was observed." Id. at 20; see
id. at 19-20 (Example 4); Fig. 3. Similarly, the reduction of clusterin levels
in cultured prostate cancer cells using other clusterin-specific siRNAs
4 Although the Brana court referred to "usefulness," the rejection on appeal
was based on lack of enablement. See id. at 1564.
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"significantly enhanced chemosensitiviy of Paclitaxel in a dose-dependent
manner." Id. at 22; see also id. at 25 (Stating that, "the siRNA and the Taxol
worked in synergy to reduce the number of viable cells."). We therefore
conclude that the Specification's working examples support enablement of
the claimed method.
The Examiner's non-enablement rejection is also not supported
adequately by the Shannan and Nascimento references. The Examiner finds
that Shannan "teach[ es] conflicting results for increased expression of
clusterin in prostate cancer and teach[ es] clusterin expression [is] decreased
in skin cancer (see Table l)." Ans. 6. The Examiner finds that Nascimento
"teach[ es] that clusterin expression in not necessarily characteristic for
anaplastic large cell lymphoma and ... that testicular cancer is associated
with a decrease in clusterin (see pages 715-716)." Id. We do not entirely
agree with the Examiner's characterization of the art.
Shannan discloses that "[c]lusterin (CLU) has been implicated in
various cell functions involved in carcinogenesis and tumour progression.
There are two known CLU protein isoforms generated in human cells. A
nuclear form of CLU protein (nCLU) is proapoptotic, and a secretory form
(sCLU) is prosurvival." Shannan, Abstract. Shannan discloses that these
two forms of clusterin may explain the association of clusterin expression
with apparently contradictory functions (id. at 12, right col.) and that anti-
cancer strategies targeting CLU "should make sure that nCLU is not
eliminated or reduced" (id., Abstract).
Shannan also discloses that "[i]t is now accepted that the primary
function of sCLU in distinct genetic backgrounds of cancer cells is
antiapoptotic." Id. at 15, left col; see also id. at 16, right col. ("It is now
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accepted that the primary function of the [] sCLU protein form is
cytoprotective and it is well known that resistance to cancer treatment is
mediated, at least in part, by enhanced expression of cell survival proteins
that help facilitate tumour progression."). This primary anti-apoptotic
function is consistent with Appellants' claimed use of an siRNA to mediate
degradation of sCLU in tumor cells so that these tumor cells become more
sensitive to apoptosis. Shannan states that "overexpression of sCLU was
shown in the majority of tumours investigated including prostate cancer,
breast carcinoma, lung, bladder, and colon cancers" and that only a "few
reports ... suggest decreased sCLU levels in specific cancers, including
nonmelanoma skin cancer, oesophageal squamous cell carcinoma,
neuroblastoma, prostate, and pancreatic cancer." Id. at 16, left col. (citations
omitted). Notably, the list of cancers for which Shannan reports decreased
clusterin expression do not include any of the specific cancer types recited in
claim 38.
Shannan also states that "[r]ecent scientific findings demonstrate that
drugs targeting sCLU expression, including CLU silencing using antisense
oligonucleotides (ASO) or short interfering double-stranded RNA, may
become promising tools for cancer therapy." Id. at 16, right col. Shannan
lists several studies using clusterin ASOs, including some in phase I clinical
trials (id. at 17, Table 2). In our view, although Shannan indicates that
research into clusterin and its silencing was ongoing, its disclosure overall
indicates that those skilled in the art considered the claimed treatment
method to show promise for treating a variety of, though not all, types of
cancer.
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Nascimento describes a study "to evaluate the specificity of clusterin
as a biomarker for ALCL [ anaplastic large cell lymphoma] in distinguishing
this tumor from poorly differentiated neoplasms of other cell lineages" and
found that a "characteristic Golgi staining pattern for clusterin was observed
only for ALCLs" among the tumor types studied. Nascimento 715, right col.
Accordingly, Nascimento's disclosure relates to diagnosing a specific type
of tumor based on a characteristic pattern of clusterin expression, not
treating cancer by reducing clusterin expression. Nascimento does not
provide evidence that casts doubt on the effectiveness of the claimed
method. In any event, to the extent that the cited references indicate that
some experimentation would be required to practice the claimed, a
disclosure does not have to describe a claimed method in all its particulars in
order to be enabling. See Amgen Inc. v. Hoechst Marion Roussel, Inc., 314
F.3d 1313, 1334 (Fed. Cir. 2003) ("The specification need not explicitly
teach those in the art to make and use the invention; the requirement is
satisfied if, given what they already know, the specification teaches those in
the art enough that they can make and use the invention without 'undue
experimentation."'); see also Brana, 51 F .3d at 1568 ( enablement,
particularly in the pharmaceutical field, "necessarily includes the expectation
of further research and development").
[T]he examiner bears the initial burden ... of presenting a prim a
facie case of unpatentability ... 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). In this case, the
Examiner's rejection is not supported by a preponderance of the evidence in
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the record. We therefore reverse the rejection of claims 35-38, 42, 47, and
49 for lack of enablement.
REVERSED
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