Ex Parte Weiner et al

Patent Trial and Appeal Board

Jun 11, 2013

11517192 (P.T.A.B. Jun. 11, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte GEORGE WEINER and BERND JAHRSDORFER
__________

Appeal 2012-002789
Application 11/517,192
Technology Center 1600
__________

Before TONI R. SCHEINER, JEFFREY N. FREDMAN, and
ERICA A. FRANKLIN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal
1
under 35 U.S.C. § 134 involving claims to a method
of generating a cytotoxic Granzyme B producing B cell. The Examiner
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1
Appellants identify the Real Party in Interest as the University of
Iowa Research Foundation (see App. Br. 1).
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Statement of the Case
Background
“Ig production is not always beneficial. It has become more and more
evident during recent years that members of the . . . B1 cell subset, are
involved in the initiation and perpetuation of various autoimmune processes
by contributing to the production of self-reactive antibodies” (Spec. 3, ll. 11-
14). The Specification teaches that the “ability to eliminate B1 cells could
impact on each of these disease states” (Spec. 45, ll. 14-15). The
Specification teaches a “method of generating a cytotoxic Granzyme B-
producing B cell comprising contacting a B cell with a cytokine, such as IL-
2I or IL-10 and one or more of a second agent” (Spec. 4, ll. 8-10).
The Claims
Claims 1, 2, and 7-10 are on appeal. The claims have not been argued
separately and therefore stand or fall together with claim 1. 37 C.F.R. §
41.37(c)(l)(vii). Claim 1 reads as follows:
1. A method of generating a cytotoxic Granzyme B-producing B
cell comprising contacting a B cell with IL-21 and one or more second
agent selected from the group consisting of a TLR agonist, an antigen,
anti-idiotype antibody, or an agent that cross-links surface
immunoglobulin, wherein the B cell expresses Granzyme B.

The issue
The Examiner rejected claims 1, 2, and 7-10 under 35 U.S.C. § 103(a)
as obvious over Novak
2
and Brown
3
(Ans. 4-6).

2
Novak et al., US 6,307,024 B1, issued Oct. 23, 2001.
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The Examiner finds that “Novak discloses a cytokine polypeptide,
zalpha11, which amino acid sequence of SEQ ID NO:2 is 100% identical the
present SEQ ID NO:2, and is now known as IL-2l” (Ans. 4). The Examiner
finds that “human B-cell lines (lymphomas and myelomas, for example)
treated with zalpha11 Ligand grew much more slowly than untreated cells
when re-plated in cell culture dishes by inducing B-cell neoplasms to
differentiate to a less proliferative and or more FAS ligand sensitive state”
(id. at 4-5). The Examiner finds that “Novak teaches that the zalpha11
ligand could be administered in combination with other agents already in use
including both conventional chemotherapeutic agents as well as immune
modulators” (id. at 5).
The Examiner finds that “Novak does not specifically teach to use
zalpha11 (IL-21) in combination with a second agent of an anti-idiotype
antibody for the treatment of B-cell malignancy” (id.). The Examiner finds
that “Brown teaches a method of treating B-cell lymphomas with anti-
idiotype antibodies alone or in combination with alpha interferon” (id.).
The Examiner finds it obvious to “treat a B cell cancer with IL-21 and
an anti-idiotype antibody following the teachings by Novak and Brown
(both can be used for treating B-cell malignancy)” (id.). The Examiner finds
that the ordinary artisan would have been “motivated to do so for cancer
treatment and for the potential additive effect as the two agents target
different molecules and work through different mechanisms” (id. at 5-6).

3
Brown et al., Treatment of B-Cell Lymphomas With Anti-idiotype
Antibodies Alone and in Combination With Alpha Interferon, 73
BLOOD 651-661 (1989).
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The issue with respect to this rejection is: Does the evidence of
record support the Examiner‟s conclusion that Novak and Brown render
claim 1 obvious?
Findings of Fact
1. The Examiner finds that “Novak discloses a cytokine
polypeptide, zalpha11, which amino acid sequence of SEQ ID NO:2 is 100%
identical the present SEQ ID NO:2, and is now known as IL-2l” (Ans. 4; see
Novak, col. 122, SEQ ID NO: 2).
2. Novak teaches that “[h]uman B-cell lines treated with zalpha11
Ligand grew much more slowly than untreated cells when re-plated in cell
culture dishes” (Novak, col. 115, ll. 20-22).
3. Novak teaches that “zalpha11 Ligand could control some types
of B-cell neoplasms by inducing them to differentiate to a less proliferative
and or more FAS ligand sensitive state. Moreover, zalpha11 receptor is
expressed on the surface of several of these cell lines” (Novak, col. 115, ll.
27-31).
4. Novak teaches that “zalpha11 Ligand and the human zalpha11
Ligand-saporin immunotoxin conjugate . . . or other zalpha11 Ligand-toxin
fusion could be therapeutically used in B-cell leukemias and lymphomas”
(Novak, col. 115, ll. 31-35).
5. Novak teaches that:
Zalpha11 Ligand-treated IM-9 cells grew to only 27%
the density of the untreated cells in the absence of anti-FAS
antibody. In the presence of 0.33 µg/ml anti-FAS antibody,
the zalpha11 Ligand-treated cells were inhibited an
additional 52% while the untreated cells were inhibited by
only 30%. The overall inhibition of cell growth with both
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zalpha11 Ligand and 0.33 µg/ml anti-FAS antibody
treatment was 86%.

(Novak, col. 115, ll. 47-54.)
6. Novak teaches that the “ligand could be administered in
combination with other agents already in use including both conventional
chemotherapeutic agents as well as immune modulators such as interferon
alpha” (Novak, col. 41, ll. 7-11).
7. Novak teaches that:
Zalpha11 Ligand will be useful in treating
tumorgenesis, and therefore would be useful in the treatment
of cancer. Zalpha11 Ligand inhibits IL-4 stimulated
proliferation of anti-IgM stimulated normal B-cells and a
similar effect is observed in B-cell tumor lines suggesting
that there may be therapeutic benefit in treating patients with
the zalpha11 Ligand in order to induce the B cell tumor cells
into a less proliferative state.

(Novak, col. 41, ll. 1-8.)
8. Brown teaches that “in recent animal experiments the addition
of interferon or interleukin-2 (IL-2) to MoAb therapy has enhanced the
action of antibody against idiotype-positive disease, resulting in more
efficient selection for antigen-negative variant tumor cells” (Brown, 659,
col. 1).
9. Brown teaches “an update of the previous trial of anti-idiotype
antibodies alone and report the results of the trial combining anti-idiotype
antibodies and interferon. Both studies confirm the antitumor effect of anti-
idiotype antibodies” (Brown, 651, col. 2).
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10. Brown teaches that “[a]nti-idiotype antibodies have
reproducible objective antitumor activity in B-cell lymphoma” (Brown,
abstract).
11. The Examiner finds that “[w]hile B cell malignancy is being
treated with the methods taught by Novak and Brown, a cytotoxic Granzyme
B-producing B cell would be inherently generated in the patient being
treated because the active ingredient, the method steps and the patient
population in the prior art teachings would be the same” (Ans. 6).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
Analysis
Novak teaches that zalpha11 Ligand, now known as interleukin 21
(FF 1), “could be therapeutically used in B-cell leukemias and lymphomas”
(Novak, col. 115, ll. 31-35; FF 4; see FF 7). Novak teaches that interleukin
21 “could be administered in combination with other agents already in use
including both conventional chemotherapeutic agents as well as immune
modulators such as interferon alpha” (Novak, col. 41, ll. 7-11; FF 6).
Brown teaches that “[a]nti-idiotype antibodies have reproducible
objective antitumor activity in B-cell lymphoma” (Brown, abstract; FF 10).
Brown teaches that “addition of interferon or interleukin-2 (IL-2) to MoAb
therapy has enhanced the action of antibody against idiotype-positive
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disease, resulting in more efficient selection for antigen-negative variant
tumor cells” (Brown, 659, col. 1; FF 8).
Applying the KSR standard of obviousness to the findings of fact, we
agree with the Examiner that the person of ordinary skill would have
reasonably combined Novak‟s B-cell lymphoma treating interleukin-21 with
other known chemotherapeutic agents for B-cell lymphoma such as Brown‟s
anti-idiotype antibodies (FF 1-10) since both Novak and Brown teach
administering chemotherapeutic agents in combination (FF 6, 8; see Ans. 5-
6). Such a combination is merely a “predictable use of prior art elements
according to their established functions.” KSR, 550 U.S. at 417.
Appellants contend that “the cited section (col. 115, lines 30-35)
addresses 1L-21 fusions to toxins. Thus, IL-21 is merely acting as a
targeting agent, and not in its role as a cytokine” (App. Br. 4).
We find that the evidence does not support Appellants‟ contention. At
Appellants‟ citation to Novak, Novak teaches treatment with both zalpha11
Ligand (i.e. IL-21) and treatments with zalpha11 Ligand-immunotoxin
conjugates (FF 4). This is borne out by the next example, which refers to the
effect of human zalpha11 Ligand alone on B-cell lines, and where Novak
teaches that treatment with human zalpha11 Ligand (IL-21) results in a
reduction of the growth of cells to only 27% of the density when compared
to untreated cells (FF 5). Thus, the human zalpha11 Ligand reduced cell
growth by 73% relative to the untreated control (FF 5). The combination
therapy with an anti-FAS antibody resulted in a further inhibition of 52%,
better than the 30% inhibition caused by the anti-FAS antibody alone (FF 5).
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Appellants contend that “if it was indeed obvious to combine 1L,-21
with anti-idiotype antibodies for the treatment of a B cell malignancy, why
would the „024 patent, which was initially filed 10 years after the
publication of Brown et al., fail to mention this possibility?” (App. Br. 4-5).
We are not persuaded. “The mere age of the references is not
persuasive of the unobviousness of the combination of their teachings,
absent evidence that, notwithstanding knowledge of the references, the art
tried and failed to solve the problem.” In re Wright, 569 F.2d 1124, 1127
(CCPA 1977). Appellants have provided no evidence addressing this point.
Appellants contend that “the rejection is an improper hindsight
reconstruction of the invention based purely appellants‟ own specification,
and not any suggestion - explicit or more general in the relevant field” (App.
Br. 5).
While we are fully aware that hindsight bias often plagues
determinations of obviousness, Graham v. John Deere Co., 383 U.S. 1, 36
(1966), we are also mindful that the Supreme Court has clearly stated that “if
a technique has been used to improve one device, and a person of ordinary
skill in the art would recognize that it would improve similar devices in the
same way, using the technique is obvious unless its actual application is
beyond his or her skill.” KSR, 550 U.S. at 417. In this case, we conclude
that the person of ordinary skill would have recognized that Novak‟s
teaching to treat B-cell lymphoma with IL-21 (FF 1-5) in combination
therapy with antibodies (FF 6-7) along with Brown‟s teaching to treat B-cell
lymphoma with anti-idiotype antibodies, alone or in combination (FF 8-10)
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provides specific reasons to combine these two components for the treatment
of B-cell lymphoma.
Appellants contend that “surprisingly, the treatment of B cells with
IL-21 results in the production of Granzyme B, and further, that this
treatment can effect tumor cell killing” (App. Br. 5). Appellants contend
that “Inherency is a very limited doctrine almost exclusively applied to the
realm of anticipation” (id.). Appellants contend that “if it was permissible to
view the inherent outcome of any prima facie combination of references as
„spoiling‟ an unexpected result, then under no circumstance would an
unexpected result ever be sufficient” (id. at 6).
We are not persuaded. First, Appellants do not identify any teaching
in the Specification or other evidence which suggests that IL-21 induction of
Granzyme B is surprising or unexpected. See In re Soni, 54 F.3d 746, 750
(Fed. Cir. 1995) (“It is well settled that unexpected results must be
established by factual evidence. Mere argument or conclusory statements…
[do] not suffice.”) Also see In re Pearson, 494 F.2d 1399, 1405 (CCPA
1974) (“Attorney‟s argument in a brief cannot take the place of evidence.”).
Second, inherency may be relied upon in obviousness determinations.
See In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (“Whether the rejection is
based on „inherency‟ under 35 U.S.C. § 102, on „prima facie obviousness'
under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the
same, and its fairness is evidenced by the PTO‟s inability to manufacture
products or to obtain and compare prior art products.”)
In Wiseman, the CCPA rejected the argument of Appellants
that a structure suggested by the prior art, and, hence,
potentially in the possession of the public, is
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patentable to them because it also possesses an
Inherent, but hitherto unknown, function which they
claim to have discovered. This is not the law. A patent
on such a structure would remove from the public that
which is in the public domain by virtue of its
inclusion in, or obviousness from, the prior art.

In re Wiseman, 596 F.2d 1019, 1023 (CCPA 1979).
This is similar to the instant situation, where the prior art reason for
combining IL-21 and anti-idiotype antibodies is for combination therapy of
B-cell lymphoma (FF 1-10), not production of Granzyme B, but the
combination suggested by the prior art has the inherent property of
producing Granzyme B as well (FF 11). In Kubin, the Federal Circuit
reaffirmed that where the invention was obvious and inherently resulted in
composition with identical function, that inherent function does not
overcome the case of obviousness, teaching “[b]ecause this court sustains,
under substantial evidence review, the Board‟s finding that Valiante‟s p38 is
the same protein as appellant's NAIL, Valiante‟s teaching to obtain cDNA
encoding p38 also necessarily teaches one to obtain cDNA of NAIL that
exhibits the CD48 binding property.” In re Kubin, 561 F.3d 1351, 1357
(Fed. Cir. 2009).
Conclusion of Law
The evidence of record support the Examiner‟s conclusion that Novak
and Brown render claim 1 obvious.

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SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C. §
103(a) as obvious over Novak and Brown. Pursuant to 37 C.F.R. §
41.37(c)(1), we also affirm the rejection of claims 2, and 7-10, as these
claims were not argued separately.

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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