Ex Parte Blanck et al

Board of Patent Appeals and Interferences

Dec 22, 2008

10711101 (B.P.A.I. Dec. 22, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte GEORGE BLANCK, KIMBERLY PALUBIN and AARON
OSBORNE
__________

Appeal 2008-5485
Application 10/711,101
Technology Center 1600
__________

Decided: December 22, 2008
__________

Before ERIC GRIMES, RICHARD M. LEBOVITZ, and STEPHEN
WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating a tumor. The Examiner rejected the claims as lacking written
description and enablement. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm-in-part and reverse-in-part.
STATEMENT OF THE CASE
Appellants claim a method for treating a tumor in a patient comprising
administering a therapeutically effective amount of an Oct-1 inhibitor. The
Examiner required restriction between a method that inhibits Oct-1 binding
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activity (Claims 9 and 10) and a method that inhibits Oct-1 mRNA function
(Claims 9 and 11-13). (Office communication mailed 8/28/2006,
designating Claim 9 as a “linking claim”). Appellants elected the method
that inhibits Oct-1 mRNA function for examination. (Paper filed
9/27/2006.) Claim 10 was accordingly withdrawn from examination. 1
(Ans. 2.)
Claims 9 and 11-13 are on appeal. The claims have not been argued
separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii).
Claim 11 is representative of the subject matter elected for examination.
Claims 9 and 11 read:
9. A method for treating a tumor in a subject in need thereof,
comprising administering a therapeutically effective amount of
an Oct-1 inhibitor.

11. The method of claim 9 wherein an Oct-1 inhibitor inhibits Oct-
1 mRNA function.

The Examiner rejected the claims as follows:
• Claims 9 and 11 are rejected under 35 U.S.C. § 112, first
paragraph, for failure to comply with the written description
requirement;
• Claims 9 and 11-13 are rejected under 35 U.S.C. § 112, first
paragraph, for failure to comply with the enablement
requirement.

1 Claims 4-8 are also pending but withdrawn from consideration as a result
of an earlier restriction requirement and election. (Office action mailed
2/2/2006.)
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WRITTEN DESCRIPTION
The Examiner rejected claims 9 and 11 under 35 U.S.C. § 112, first
paragraph, as lacking written description support. The Examiner’s position
is that the claims encompass the use of inhibitors of Oct-1 mRNA function
“of any type,” including both nucleic acid-based inhibitors and “non-nucleic
acid inhibitors such as proteins, antibodies, small organic molecules and
inorganic molecules.” (Ans. 4.) The Specification disclosed using an
antisense oligonucleotide, but the Examiner found that antisense inhibitors
are not representative of non-nucleic acid inhibitors. (Ans. 5.) The
Examiner found no description for non-nucleic acid inhibitors of Oct-1
mRNA function. Although the Examiner found that two non-nucleic acid
inhibitors of Oct-1 were known in the art, the Examiner stated that the
skilled artisan “cannot envision the detailed structure of the encompassed
modulating agents that inhibit Oct-1 mRNA function.” (Ans. 6.)
Appellants contend that the absence of a working example is not fatal
to compliance with the written description requirement when the
Specification otherwise conveys possession of the invention. (App. Br. 10.)
A Specification may contain a written description of a broadly claimed
invention without describing all the species that the claim encompasses. Id.
“[T]he mere fact that the specification fails to describe the full genus of
encompassed compounds that have the function of inhibiting OCT-1 does
not mean that the application fails to meet the written description
requirement.” Id.
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The issue with respect to this rejection is whether those of skill in the
art would have credited Appellants with possession of the genus of Oct-1
inhibitors that inhibit Oct-1 mRNA function.
Findings of Fact Relating to the Written Description Issue
1. Oct-1 is a protein transcription factor. (Spec. ¶ 9.)
2. Oct-1 mRNA is the messenger RNA that codes for the Oct-1 protein.
3. The claimed method requires administration of “an Oct-1 inhibitor
that inhibits Oct-1 mRNA function.” (App. Br. 16.)
4. One full-length antisense molecule that inhibits Oct-1 mRNA function
is disclosed. (Spec. ¶ 24.)
5. The Specification does not identify or provide structural information
about non-nucleic acid inhibitors of Oct-1 mRNA function.
6. Heparan sulfate and interferon α are known inhibitors of Oct-1. (Ans.
5.)
7. Appellants do not assert that heparan sulfate or interferon α inhibits
Oct-1 mRNA function.
8. Appellants do not identify evidence that pre-existing knowledge in the
art supplements the Specification with a description for non-nucleic
acid inhibitors of Oct-1 mRNA function.
Principles of Law Relating to Written Description
When an Applicant claims a class, the Applicant “must describe that
class in order to meet the description requirement of the statute.” In re
Lukach, 442 F.2d 967, 968 (CCPA 1971). In assessing whether the written
description requirement is satisfied, “[t]he primary consideration is factual
and depends on the nature of the invention and the amount of knowledge
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imparted to those skilled in the art by the disclosure.” Vas-Cath, Inc. v.
Mahurkar, 935 F.2d 1555, 1562 (Fed. Cir. 1991) (citation omitted, emphasis
in original). The amount of description needed to meet the requirement can
vary with the scientific and technologic knowledge already in existence.
Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005).
Analysis of the Written Description Issue
We construe the claim phrase “[a]n Oct-1 inhibitor that inhibits Oct-1
mRNA function” to name a genus by naming a function. The genus
includes molecules or agents that function as an Oct-1 mRNA inhibitor. We
agree with the Examiner’s undisputed finding that the named inhibitor genus
includes both agents that have a nucleic acid structure and agents that have a
non-nucleic acid structure. (Ans. 4.) The genus is “highly variant” (Ans. 6),
potentially including “non-nucleic acid inhibitors such as proteins,
antibodies, small organic molecules and inorganic molecules.” (Ans. 4.)
The Specification does not name or provide a structural description for non-
nucleic acid inhibitors of Oct-1 mRNA function (FF5), and the Examiner
found that their identity and structure is not readily predictable. Appellants
do not dispute those findings. We accordingly find that the burden was
properly shifted to Appellants rebut the Examiner’s finding with evidence or
argument. Hyatt v. Dudas, 492 F.3d 1365, 1370 (Fed. Cir. 2007). Rather
than cite where the missing information could be found, or make an
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amendment to address the deficiency, Appellants present arguments.2 We
address each in turn.
First, Appellants correctly observe that the absence of a working
example is not fatal where the Specification otherwise conveys that the
Applicants possessed the claimed invention at the time of filing. (App. Br.
10.) The Examiner acknowledged the disclosure of one working example
using a nucleic acid-based Oct-1 mRNA function inhibitor, a full-length
antisense molecule. The Examiner withdrew the rejections of claims using
inhibitors that have a nucleic acid structure, i.e., Claim 12 (“an Oct-1
antisense sequence”) and Claim 13 (“an RNA inhibitor molecule”). (Ans.
3.)
Appellants do not indicate or explain how an inhibitor that has a
nucleic acid structure is representative of non-nucleic acid structures such as
proteins, antibodies, small organic molecules and inorganic molecules.
There is no working example of a non-nucleic acid based Oct-1 mRNA
function inhibitor, and the question is whether some other form of disclosure
identifies or describes that kind of inhibitor. Appellants do not point to any
evidence in the record that those of skill in the art would know of any such
inhibitors. Unlike the disclosure of a single antisense molecule, which may
be representative of other nucleic acid molecules such as those in Claims 12
and 13, we find no disclosure of anything representative of non-nucleic acid
Oct-1 mRNA function inhibitors such as proteins, antibodies, small organic

2 We do not agree with Appellants’ characterization “nor does the
Examiner dispute the existence of numerous other Oct-1 inhibitors.” (App.
Br. 9.) The Examiner does dispute it. (Ans. 9.)
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molecules and inorganic molecules. Not only is a working example for non-
nucleic acid based inhibitors absent, the Specification does not otherwise
convey possession of that kind of inhibitor.
Appellants correctly observe that a specification may contain a written
description of a broadly claimed invention without describing all the species
that the claim encompasses, citing Utter v. Hiraga, 845 F.2d 993, 998 (Fed.
Cir. 1988). (App. Br. 10.) In Utter, specific references to knowledge in the
prior art supplemented the specification’s limited disclosure. There, the
disputed application disclosed the geometry of an internal pivot embodiment
and cited prior art patents that were directed to external pivot embodiments.
Utter, 845 F.2d at 998-99. In other words, the Specification “otherwise”
conveyed possession of external pivot embodiments. The court found the
disclosure that included citations to known external pivots supported a
generic interference count covering both internal and external pivot
embodiments. Utter, 845 F.2d at 999.
Unlike the party in Utter, Appellants have not provided citations to
prior art disclosures of inhibitors that inhibit Oct-1 mRNA function. Nor did
Appellants cite evidence that the two known Oct-1 inhibitors the Examiner
identified (heparan sulfate and interferon α) would be recognized by those of
skill in the art as inhibitors of Oct-1 mRNA function. The amount of
description needed to meet the written description requirement can vary with
the scientific and technologic knowledge already in existence. Capon, 418
F.3d at 1357. In this case, however, Appellants have not shown evidence of
pre-existing knowledge relating to non-nucleic acid Oct-1 inhibiting
molecules that inhibit Oct-1 mRNA function. The written description
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requirement may alternatively be satisfied if in the knowledge of the art the
disclosed function is sufficiently correlated to a known structure. Amgen,
Inc. v. Hoecsht Marion Roussel, Inc., 314 F.3d 1313, 1332 (Fed. Cir. 2003).
However, Appellants have not shown there was a known correlation of non-
nucleic acid inhibitor structure to the function of inhibiting Oct-1 mRNA
function, nor have Appellants pointed to such a correlation disclosed in their
Specification.
On this record, the only known or disclosed inhibitors of Oct-1
mRNA function have a nucleic acid structure, e.g., an antisense molecule.
Appellants have not shown that those of skill in the art would recognize non-
nucleic acid inhibitors from that disclosure, or think that Appellants were in
possession of non-nucleic acid inhibitors. Nor have Appellants shown that
those of skill in the art would accept that the disclosure of nucleic acid
molecules that inhibit Oct-1 mRNA function is a disclosure of non-nucleic
acid molecules that inhibit Oct-1 mRNA function. “[A] patentee of a
biotechnological invention cannot necessarily claim a genus after only
describing a limited number of species because there may be
unpredictability in the results obtained from species other than those
specifically enumerated.” Noelle v. Lederman, 355 F.3d 1343, 1350 (Fed.
Cir. 2004). Appellants have not shown reversible error in the Examiner’s
finding that non-nucleic acid inhibitors of Oct-1 mRNA function lack
written description.

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ENABLEMENT
The Examiner rejected claims 9 and 11-13 under 35 U.S.C. § 112,
first paragraph, for lack of an enabling disclosure. The Examiner’s position
is that delivering a therapeutically effective amount of nucleic acid to an in
vivo target cell is problematic, and would require more guidance than
provided in the Specification or the art of record. (Ans. 7-8.) The Examiner
relied on the Opalinska3 review article as evidence that using nucleic acid
molecules for in vivo therapy is wanting in reliability. (Ans. 7.) While “the
specification is enabling for inhibition of Oct-1 mRNA in cells in vitro, the
specification is not enabling for . . . treating tumors in a subject . . . as the art
of inhibiting gene expression by introducing oligonucleotides into an
organism is neither routine nor predictable.” (Ans. 8.)
Appellants contend that the Examiner relied on a per se rule rather
than giving case-specific reasons; that Appellants gave precise details about
the structural and chemical properties of the Oct-1 mechanism; that
inhibitors of Oct-1 are detailed by functional characteristics coupled with the
known correlation between Oct-1 function and structure; that numerous
inhibitors of Oct-1 are known; and that one could routinely apply
Appellants’ techniques to inhibit Oct-1 without undue experimentation.
(App. Br. 12.)

3 Joanna B. Opalinska and Alan M. Gewirtz, Nucleic-acid Therapeutics:
Basic Principles And Recent Applications, 1 NATURE REVIEWS DRUG
DISCOVERY 503-14, July 2002.
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The issue with respect to this rejection is whether inefficiency and
unreliability of oligonucleotide delivery to targeted cells mean that undue
experimentation would have been required to use the invention.
Further Findings of Fact Related to the Enablement Issue
9. The cell line 5637 was transfected in vitro with a full length, antisense
Oct-1 cDNA. (Spec. ¶¶ 24-28.)
10. Loss of oncogenic characteristics in the Oct-1 antisense transformants
suggests that Oct-1 is a candidate oncoprotein. (Spec. ¶ 31.) 11. The
Specification states: “It is within the scope of the present invention
that other modes of inhibiting or eliminating Oct-1 protein, DNA or
RNA expression, or DNA-binding capacity can be easily practiced by
one of ordinary skill in the art. . . . . Thus, it would be understood by
one of ordinary skill in the art that methods to prevent cellular
proliferation or tumorigenesis can be practiced by using Oct-1 RNA,
DNA, cDNA, or protein molecules in such applications.” (Spec. ¶
32.)
12. The Examiner relied on the Opalinska review article as evidence of the
state of the art. (Ans. 7.)
13. Opalinska “reviews different strategies for modulating gene
expression, and discusses the successes and problems that are
associated with this type of therapy.” (Opalinska, 503, abstract.)
14. According to Opalinska, the prospect of using nucleic acid molecules
for therapy “remains tantalizing but uncertain.” (Opalinska, 503, left
col.)
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15. Opalinska discusses methods that focus on destabilizing mRNA.
(Opalinska 504, right col. – 506, right col.)
16. Opalinska provides a summary of recent clinical trials with nucleic-
acid drugs. (Opalinska, 508, Table 1.)
17. Opalinska’s Table 1 reports on nine cancer trials targeting PKC-α,
BCL2, h-RAS, or c-RAF kinase, by administering an antisense
molecule. (Opalinska 508, Table 1.)
18. In trials targeting BCL2, there were two complete remissions, two
partial remissions, five minor responses, and two decreases in PSA,
among 61 patients treated. (Opalinska 508, Table 1.)
19. In trials targeting PKC, there were two complete remissions and 3
responses among 57 patients treated (Opalinska 508, Table 1), and
“antitumor effects were modest at best.” (Opalinska 509, right col.)
20. In a trial targeting h-RAS, “[f]our [out of 23] patients had stabilized
disease for 6-10 cycles of treatment.” (Opalinska 509, right col.)
21. In trials targeting c-RAF kinase, “[n]o major tumour responses were
documented, but some patients had stabilization of their disease.”
(Opalinska 510, left col.)
22. According to Opalinska, the ability of nucleic acid molecules to
modify gene expression in vivo is quite variable and wanting in
reliability. (Opalinska 511, left col.)
23. According to Opalinska, one of the “root cause[s]” of the reliability
problem is “molecule delivery to targeted cells” (Opalinska 511, left
col.); “[a]nother problem in this field is the limited ability to deliver
nucleic acids into cells and have them reach their target. Without this
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ability, it is clear that even an appropriately targeted sequence is not
likely to be efficient.” (Opalinska, 511, right col.)
24. Opalinska’s Table 2 is entitled “Current and planned clinical trials with
antisense oligonucleotides and ribozymes,” and includes Phase II and
Phase III trials targeting tumors. (Opalinska, 511, Table 2.)
25. According to Opalinska, “[d]elivery technologies continue to improve,
so it is likely that present methods, and/or other evolving
technologies, will be used successfully to deliver optimized nucleic
acids to their cellular targets. Indeed, it is our hypothesis that
development of effectively targeted and efficiently delivered nucleic-
acid molecules will lead to important advances in the diagnosis and
treatment of human malignancies, and other diseases for which this
class of molecule has been proposed to be effective.” (Opalinska,
511-12.)
26. According to Opalinska, “clinical development of antisense
compounds has proceeded to the point at which several nucleic-acid
drugs have entered Phase I/II, and in a few cases, Phase III trials.”
(Opalinska, 512, right col.)
Principles of Law Relating to Enablement
The first paragraph of 35 U.S.C. § 112 requires that the specification
teach persons skilled in the art to use the invention without undue
experimentation. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). The
specification must teach more than a plan for those of skill in the art to
experiment at practicing the invention; it must provide sufficient guidance or
specificity as to how to execute the plan. Enzo Biochem, Inc. v. Calgene,
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Inc., 188 F.3d 1362, 1374 (Fed. Cir. 1999). The factors listed in the Wands
case may be taken into account but not all the factors need to be reviewed.4
Id. at 1374.
Analysis of the Enablement Issue
We first address the disputed claim construction. The claims recite
administering a “therapeutically effective amount of an Oct-1 inhibitor
[wherein the Oct-1 inhibitor inhibits mRNA function].” Appellants argue
that problems achieving a therapeutic effect need not be overcome because
administering an inhibitor is all that is required. (App. Br. 15.) That is, the
claims should be read as if the express limitation “therapeutically effective
amount of” were not there. We decline to read “therapeutically effective
amount” out of the claims and we hold the claims require that a
therapeutically effective amount be administered. See Texas Instruments
Inc. v. U.S. Int'l Trade Comm'n, 988 F.2d 1165, 1171 (Fed. Cir. 1993) (“[T]o
construe the claims in the manner suggested by TI would read an express
limitation out of the claims. This we will not do because courts can neither
broaden nor narrow claims to give the patentee something different than
what he has set forth.” (Internal quotation omitted)). Further, our reviewing
court rejected a similar argument concerning a count that read, in part,
“method of ‘treating a subject in cardiac arrest’ [comprising] . . . an oxygen-

4 The Wands factors are (1) the quantity of experimentation necessary to
practice the invention, (2) the amount of direction or guidance presented, (3)
the presence or absence of working examples, (4) the nature of the
invention, (5) the state of the prior art, (6) the relative skill of those in the
art, (7) the predictability or unpredictability of the art, and (8) the breadth of
the claims. Wands, 858 F.2d at 737.
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carrying protective solution in an amount effective to deliver oxygen.” See
Manning v. Paradis, 296 F.3d 1098, 1102-03 (Fed. Cir. 2002) (affirming
Board’s construction requiring “oxygen sufficient to have a therapeutic
effect”) (original emphasis deleted). As in Manning, we will treat
“therapeutically effective” as a meaningful claim limitation. Appellants also
argue that the Examiner thinks “therapeutically effective amount” is
enabled. (App. Br. 15.) That is the opposite of what the Examiner said.
The Examiner concluded that no therapeutic response was enabled, without
quibbling about how an effective amount would be determined if,
hypothetically, the method were enabled. (Ans. 14-15.)
There is a second preliminary matter: Appellants focus several
arguments on inhibitors of the Oct-1 protein, rather than on inhibitors of
Oct-1 mRNA function, the subject matter elected for examination. The
misdirected contentions include: (1) that precise detail about the structural
and chemical properties of the Oct-1 mechanism was provided, (2) that
inhibitors of Oct-1 are detailed by their functional characteristics coupled
with the known correlation between Oct-1 function and structure, (3) that the
Examiner’s action argues that numerous inhibitors of Oct-1 are known,5 and
(4) that the references cited by the Examiner show that Oct-1 inhibiting
substances are sufficiently well-known that one could routinely apply
Appellants’ techniques to inhibit Oct-1 without undue experimentation.

5 The Examiner did not agree that numerous Oct-1 inhibitors are
known, but even if they were, the rejection is based on the unreliability and
unpredictability of achieving a therapeutic effect by administering nucleic
acid inhibitors of gene expression in vivo.

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(App. Br. 12.) These arguments about inhibiting protein functions are not
germane to delivering inhibitors of mRNA function to tumor cells, the issue
raised by the Examiner.
The Examiner identified delivery to targeted cells as the significant
unsolved problem for methods that administer nucleic acid molecules, citing
Opalinska as evidencing the state of the art. (FF12.) The state of the art is
that in vivo delivery to tumor cells is inefficient. (FF23.) The Specification
gives no guidance that addresses the delivery problem, and relies on the pre-
existing knowledge in the art. (FF11.) According to the Examiner, the
Specification leaves the person of skill in the art to carry out trial and error
experimentation. (Ans. 9.) Opalinska reported that “[d]elivery technologies
continue to improve, so it is likely that present methods, and/or other
evolving technologies, will be used successfully to deliver optimized nucleic
acids to their targets. Indeed, it is our hypothesis that development of
effectively targeted and efficiently delivered nucleic-acid molecules will
lead to . . . treatment of human malignancies.” (FF25.) In the trials
Opalinska reported on, the therapeutic effectiveness of methods treating
cancer with antisense molecules was statistically low. (FF17-21.) That is,
remissions were reported for all four of the cancer molecules targeted, but
the number of patients experiencing remission of any kind was low.
Based on the evidence of record, we conclude that those of skill in the
art would have expected similar results if they followed Appellants’
instruction to target Oct-1 mRNA using the methods available in the art as of
the filing date. A similar degree of “therapeutically effective” results would
likely have been expected. On this record, that kind and degree of result was
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relied on in the art to commence not only the Phase I and II trials reported in
Opalinska’s Table I, but also Phase III trials as listed by Opalinska in Table
2. (FF24 and 26.) The degree of experimentation that is considered “undue”
varies between different fields of endeavor and the evidence of record shows
that considerable experimentation is expected in the field of the present
invention.
We do not see evidence in the record that Oct-1 targeting would have
required trial and error experimentation to achieve the degree of
therapeutically effective results reported in Opalinska. Appellants were
apparently the first to show that targeting Oct-1 mRNA function with an
antisense molecule decreased cell proliferation in vitro. There is no Oct-1-
specific evidence in the record that leads us to expect results differing from
those achieved by targeting other cancer molecules in vivo.
CONCLUSIONS OF LAW
Those of skill in the art would not have credited Appellants with
possession of the genus “Oct-1 inhibitors that inhibit Oct-1 mRNA
function.”
Undue experimentation would not have been required to use in vivo
embodiments of the invention.
ORDER
The rejection of Claims 9 and 11 for lack of written description is
AFFIRMED; and
the rejection of Claims 9 and 11-13 for lack of an enabling disclosure
is
REVERSED.
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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-IN-PART

Ssc:
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