Ex Parte Saeki et al

Board of Patent Appeals and Interferences

Oct 30, 2009

10508150 (B.P.A.I. Oct. 30, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte YUKIHIKO SAEKI, HIDEYUKI KOBAYASHI,
and YUICHIRO TABUNOKI

__________

Appeal 2009-0034561
Application 10/508,150
Technology Center 1600
__________

Decided: October 30, 2009

__________

Before TONI R. SCHEINER, RICHARD M. LEBOVITZ, and
FRANCISCO C. PRATS, Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the final rejection of
claims 8-19, directed to a method for identifying a compound that reduces

1 Heard October 21, 2009.
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the severity of myeloma, and a method of diagnosing myeloma. We have
jurisdiction under 35 U.S.C. § 6(b).
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STATEMENT OF THE CASE
Multiple myeloma is “a malignant, uncontrolled proliferation of
plasma cells derived from a single clone. In most cases of this
disease, patients develop significant osteoclastic bone-resorbing
lesion[s] accompanied by intractable acute pain and risk of easy
osteoclastic bone loss . . . [and] histopathological research of
bone slices has revealed significant activation of osteoclastic
cells at bone-resorbing lesions neighboring myeloma cells.

(Spec. 2.)
The present invention is directed to “preventive or therapeutic agents
(drugs) for myeloma tumors, a screening method therefor, and a diagnostic
method for myeloma tumors” (Spec. 1).
Claims 8 and 18 are representative of the subject matter on appeal:
8. A method for identifying a compound that reduces the severity of
myeloma comprising:
contacting cells which produce osteopontin with a test compound and
determining the amount of osteopontin produced in the presence of said test
compound compared to the amount of osteopontin produced by the cells in
the absence of said test compound,
selecting a test compound which reduces the amount of osteopontin
produced by said cells, and
contacting said test compound, which reduces the amount of
osteopontin produced, with myeloma tumor cells, and
selecting a test compound which reduces the severity of myeloma.

18. A method for diagnosing myeloma, comprising:
measuring the blood osteopontin level of a subject and comparing the
measured level with the osteopontin level in a reference sample,
wherein an elevated osteopontin level in said subject compared to the
level in the reference sample correlates with the presence of myeloma in a
subject.

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The Examiner relies on the following evidence:
Chabas et al. US 2005/0119204 A1 Jun. 2, 2005

J. McPhaden et al., Plasma Osteopontin Levels in Multiple Myeloma, 84
BLOOD 172a, Abstract 674 (1994).

Diosdado S. Bautista et al., Quantification of Osteopontin in Human Plasma
with an ELISA: Basal Levels in Pre- and Postmenopausal Women, 29
CLINICAL BIOCHEMISTRY 231-239 (1996).

Hirokazu Okada et al., Osteopontin Expressed by Renal Tubular Epithelium
Mediates Interstitial Monocyte Infiltration in Rats, 278 AM. J. PHYSIOL.
RENAL PHYSIOL. F110-F-121 (2000).

Rafael Fonseca et al., Prognostic Value of Serum Markers of Bone
Metabolism in Untreated Multiple Myeloma Patients, 109 BRITISH JOURNAL
OF HAEMATOLOGY 24-29 (2000).

Appellants rely on the following additional evidence:

Phillip R. Greipp and Robert A. Kyle, Clinical, Morphological, and Cell
Kinetic Differences Among Multiple Myeloma, Monoclonal Gammopathy of
Undetermined Significance, and Smoldering Multiple Myeloma, 62 BLOOD
166-171 (1983).

M.A. Frassanito et al., Deregulated Cytokine Network and Defective Th1
Immune Response in Multiple Myeloma, 125 CLIN. EXP. IMMUNOL. 190-197
(2001).

The Examiner rejected the claims as follows:
(A) Claims 18 and 19 under 35 U.S.C. § 103(a) as unpatentable over
Bautista and McPhaden.

(B) Claims 8-13 under 35 U.S.C. § 103(a) as unpatentable over Chabas,
McPhaden, and Bautista.

(C) Claims 8-15 under 35 U.S.C. § 103(a) as unpatentable over Chabas,
McPhaden, Bautista, and Okada.
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(D) Claims 8-15, 16, and 17 under 35 U.S.C. § 103(a) as unpatentable
over Chabas, McPhaden, Bautista, and Fonseca.

(E) Claims 8-17 under 35 U.S.C. § 112, first paragraph, as failing to
comply with the written description requirement (new matter).

We affirm rejection (A), and reverse rejections (B)-(E).
OBVIOUSNESS
Issue (A): claims 18 and 19
The Examiner rejected claims 18 and 19 as unpatentable over Bautista
and McPhaden. The issue raised by this rejection is whether Appellants
have established that the Examiner erred in concluding that it would have
been obvious to diagnose myeloma by determining an elevated level of
osteopontin in a subject’s blood, given the teachings of Bautista and
McPhaden.
Findings of Fact
FF1 “Osteopontin [OPN] is a secretory phosphorylated glycoprotein
. . . expressed in a diversity of cells such as osteoclastic cells, macrophages,
activated T cells, smooth muscle cells, and epithelial cells, and in some tissues
such as bones, kidneys, placenta, smooth muscles, and secretory epithelium”
(Spec. 3).
FF2 According to the Specification, “production of osteopontin
significantly increases in a myeloma tumor; in particular, multiple myeloma
. . . [and] blood osteopontin level is intimately correlated with the presence
of a myeloma tumor and the condition of the disease” (Spec. 4).
FF3 Bautista teaches that blood osteopontin levels are elevated in a
number of other human diseases including advanced metastatic carcinomas of
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the colon, breast, liver, prostate, stomach, and lung. In addition, high
expression of OPN is correlated with calcification of human breast tumors, and
with the severity of human astrocytomas (Bautista 231).
FF4 Bautista describes “a ‘capture’ ELISA that allows fast and
convenient measurement of OPN levels in the blood” (Bautista 237, col. 1).
FF5 McPhaden teaches that “[m]ultiple myeloma has a unique
propensity to localize to bone marrow and to produce generalized osteoporosis
as well as lytic bone lesions mediated at least in part by humoral mechanisms”
(McPhaden ¶ 1).
FF6 McPhaden teaches that osteopontin is believed to have a role in
bone metabolism and mineralization and resorption of bone matrix (McPhaden
¶ 1).
FF7 Given the generalized osteoporosis and the lytic bone lesions
associated with multiple myeloma, and osteopontin’s role in bone metabolism,
McPhaden “postulated that OPN may be a clinical marker of osteoblast and
osteoclast activity in multiple myeloma” (McPhaden ¶ 1).
FF8 McPhaden used “a ‘capture’ ELISA to measure plasma OPN
levels in patients with myeloma” (McPhaden ¶ 1), and “found a strong
correlation between clinical stage and OPN levels . . . as well as between bone
scale [score] and OPN levels” (id.). In other words, McPhaden found that
osteopontin elevation increased with increasing disease severity.
FF9 According to McPhaden, these “results suggest that plasma OPN
may be a useful clinical marker for disease severity in multiple myeloma”
(McPhaden ¶ 2).
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Principles of Law
Expectation of success is assessed from the perspective of a person of
ordinary skill in the art, at the time the invention was made. See Life Techs.
Inc. v. Clontech Labs. Inc., 224 F.3d 1320, 1326 (Fed. Cir. 2000).
“Obviousness does not require absolute predictability of success. . . .
For obviousness under § 103, all that is required is a reasonable expectation
of success.” In re O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988).
Analysis
Claim 18 is directed to a method for diagnosing myeloma, comprising
measuring the osteopontin level in a subject’s blood and comparing it with
the osteopontin level in a reference sample, wherein an elevated osteopontin
level in the subject’s blood compared to the level in the reference sample
correlates with the presence of myeloma in the subject. Claim 19 specifies
that the osteopontin level is measured immunologically.
The Examiner rejected claims 18 and 19 as unpatentable over Bautista
and McPhaden, concluding that it would have been obvious for one of
ordinary skill in the art “to use the assays taught by Bautista et al as a
diagnostic method for multiple myeloma” given McPhaden’s “teach[ing]
that there is a strong correlation between this disease and osteopontin levels”
(Ans. 13). The Examiner’s position is that “[o]ne of ordinary skill in the art
would have had a reasonable expectation of success since McPhaden et al
had shown specific results . . . that showed a strong correlation between
clinical stage and osteopontin levels” (id.).
Appellants concede that McPhaden “discusses a correlation between
clinical stage of myeloma and OPN levels” but contend that the reference
doesn’t “provide adequate motivation for combining the cited art or a
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reasonable expectation of success for the present invention” because
McPhaden’s study was “not properly controlled . . . . For example, McPhaden
does not compare OPN levels between normal subjects, patients with myeloma
and patients with monoclonal gammapathy of undetermined significance
(MGUS)” (App. Br. 14).2
Appellants’ argument is not persuasive. Claims 18 and 19 are directed
to diagnosing myeloma based on the presence of elevated levels of osteopontin,
but it’s important to note that at the time of the invention, elevated osteopontin
levels were known to be associated with a number of other conditions as well
(FF3). Thus, the claimed method can corroborate a diagnosis of myeloma, but
the method is not necessarily definitive on its own, and any differential
diagnosis could take a number of other factors into consideration, which the
claim is open to include. McPhaden teaches that osteopontin levels are
elevated in multiple myeloma, becoming increasingly elevated with increasing
severity (as measured by clinical stage and bone scale score) (FF8), and
suggests that plasma osteopontin levels may be a useful clinical marker for
disease severity in multiple myeloma (FF7, FF9).
The evidence of record supports the Examiner’s conclusion that one of
skill in the art would reasonably have expected osteopontin levels to be
relevant to a diagnosis of myeloma based on McPhaden’s teachings, even if not
definitive, and that it would have been obvious for one of ordinary skill in the
art to measure osteopontin levels in diagnosing myeloma.
Conclusions of Law

2 Appellants cite Griepp and Frassanito as evidence that “such comparisons
are conventionally used in the art” (App. Br. 11).
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Appellants have not established that the Examiner erred in concluding
that it would have been obvious to diagnose myeloma by determining an
elevated level of osteopontin in a subject’s blood, given the teachings of
Bautista and McPhaden.
The rejection of claims 18 and 19 as unpatentable over Bautista and
McPhaden is affirmed.
OBVIOUSNESS
Issues (B), (C), and (D): claims 8-17
The Examiner rejected claims 8-13 as unpatentable over Chabas,
McPhaden, and Bautista; claims 8-15 as unpatentable over Chabas,
McPhaden, Bautista, and Okada; and claims 8-13, 16, and 17 as
unpatentable over Chabas, McPhaden, Bautista, and Fonseca.
The issue raised by all three of these rejections is whether the
Examiner has established that it would have been obvious to identify
compounds that reduce the severity of myeloma based on their ability to
reduce osteopontin production by myeloma tumor cells, given the teachings
of Chabas, McPhaden, and Bautista.
Findings of Fact
FF10 Independent claim 8 is directed in pertinent part to a method for
identifying compounds that reduce the severity of myeloma, by identifying
compounds that reduce osteopontin production in myeloma tumor cells.
Claims 9-17 all depend from claim 8, and therefore include all the
limitations of claim 8.
FF11 Chabas describes an assay for identifying agents “for treating
a subject afflicted with an osteopontin-related disorder” (Chabas ¶ 23) by
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“determining whether an agent reduces the amount of osteopontin in an
osteopontin-expressing cell” (id. at ¶ 30).

FF12 According to Chabas,
“Osteopontin-related disorder” shall mean any disorder
(a) characterized by the over-expression of osteopontin in an
afflicted subject, (b) ameliorated by inhibiting osteopontin
expression in an afflicted subject, and/or (c) ameliorated by
inhibiting osteopontin activity in an afflicted subject, (d) in
which expression of osteopontin contributes to the
pathogenesis.

(Chabas ¶ 83.)
FF13 Chabas identifies graft versus host disease, epilepsy, herpes
simplex keratitis, granulomatous disorders, bacterial arthritis, multiple
sclerosis, rheumatoid arthritis, and type I diabetes as osteopontin-related
disorders, i.e., “disorder[s] in which expression of osteopontin contributes to
the pathogenesis” of the disorder (Chabas ¶ 13). Chabas does not identify
multiple myeloma as an osteopontin-related disorder.
Analysis
The Examiner concluded that
[O]ne of ordinary skill in the art would have been motivated to
practice the invention of Chabas et al as a screening method for
a preventive or therapeutic drug for a myeloma tumor . . . given
that multiple myeloma meets the criteria of an osteopontin-
related disorder as defined in Chabas et al specifically as
characterized by the overexpression of osteopontin in an
afflicted subject . . . and based on the disclosure of McPhaden
et al which shows increased osteopontin levels in Multiple
Myeloma patients . . . One of ordinary skill in the art would
have had a reasonable expectation of success since McPhaden
et al had shown . . . a strong correlation between clinical stages
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of Multiple Myeloma and osteopontin levels (p<.0002), as well
as between bone scale and osteopontin levels (p<.0006).

(Ans. 8-9.)
Appellants contend that none of the cited references “establish a
causal nexus between [reduction of] osteopontin levels and treatment of
myeloma” (App. Br. 11), and therefore “can’t provide any motivation for
performing the latter steps of Claim 8 which require evaluating the ability of
a test compound [to reduce osteopontin production] o[f] myeloma tumor
cells” (id.).
Appellants’ argument is persuasive on this point. As discussed above,
we agree with the Examiner that it would have been obvious to use
osteopontin as a diagnostic marker for multiple myeloma given McPhaden’s
teachings that osteopontin levels are increasingly elevated as the severity of
the disease increases. However, the Examiner has not provided any
evidence that osteopontin was thought to contribute to the pathogenesis of
the disease (as opposed to simply being elevated as a result of the disease),
or that those of skill in the art would have expected that reduction of
osteopontin levels would have a beneficial effect on the severity of multiple
myeloma or its associated osteoclastic bone loss.
Conclusions of Law
The Examiner has not established that it would have been obvious to
identify compounds that reduce the severity of myeloma based on their
ability to reduce osteopontin production by myeloma tumor cells, given the
teachings of Chabas, McPhaden, and Bautista.
The rejection of claims 8-13 as unpatentable over Chabas, McPhaden,
and Bautista; the rejection of claims 8-15 as unpatentable over Chabas,
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McPhaden, Bautista, and Okada; and the rejection of claims 8-13, 16, and 17
as unpatentable over Chabas, McPhaden, Bautista, and Fonseca are reversed.
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WRITTEN DESCRIPTION
Issue (E): claims 8-17
Independent claim 8, entered by amendment, is directed to a two-stage
method for identifying compounds that reduce the severity of myeloma,
where the method comprises contacting osteopontin-producing cells with a
test compound, selecting the compound for further screening based on its
ability to reduce osteopontin production in the cells, and further “contacting
said test compound, which reduces the amount of osteopontin produced,
with myeloma tumor cells, and selecting a test compound which reduces the
severity of myeloma.”
According to the Examiner, “[t]he disclosure as originally filed, only
supports a one step screening process . . . where the test compound is
determined to be effective as a therapeutic drug for myeloma after showing
the ability to reduce osteopontin produced by a cell” (Ans. 5-6), and the
“step of ‘contacting said test compound . . . with myeloma tumor cells, and
selecting a test compound which reduces the severity of myeloma’” is new
matter (id. at 5).
Appellants contend that the Specification clearly conveys the concept
of screening test compounds for their effects on osteopontin production by
myeloma tumor cells (App. Br. 9).
Thus, the issue raised by this rejection is whether the Examiner has
established that the Specification lacks adequate written descriptive support
for a two-stage method of screening compounds for the ability to reduce the
severity of myeloma, where the compounds are screened against two types
of cells, including myeloma tumor cells.

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Findings of Fact
FF14 According to the Specification as originally filed,
[A] substance to be tested is added to cells having elevated
osteopontin-producing ability, such as myeloma cells, [and] the
osteopontin production may be measured through immunological
techniques . . . If the amount of osteopontin produced after
addition of the test substance is reduced as compared with the
amount determined for no addition of test substance, the
substance can be determined to be effective as a preventive or
therapeutic drug for myeloma tumors and osteoclastic bone loss
associat[ed] therewith.

(Spec. 8).
FF15 Original claims 4 and 5 (now canceled), were directed to a
screening method, and read as follows:
4. A screening method for a preventative or therapeutic
drug for a myeloma tumor, characterized by determining
osteopontin production regulatory or inhibitory effect.

5. The screening method as recited in claim 4, wherein the
osteopontin production regulatory or inhibitory effect is
determined by measuring osteopontin production in cells of the
B-cell line capable of producing osteopontin.

Principles of Law
“The purpose of the written description requirement is to prevent an
applicant from later asserting that he invented that which he did not.”
Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1330 (Fed. Cir.
2003).
“In order to satisfy the written description requirement, the disclosure
as originally filed does not have to provide in haec verba support for the
claimed subject matter at issue.” Purdue Pharma L.P. v. Faulding, Inc., 230
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F.3d 1320, 1323 (Fed. Cir. 2000). Rather, the disclosure must convey with
reasonable clarity to those skilled in the art that the inventor was in
possession of the invention. See id.
Analysis
The Specification teaches that an effective “preventive or therapeutic
drug for myeloma tumors and osteoclastic bone loss associat[ed] therewith”
can be identified by screening candidates against “cells having elevated
osteopontin-production ability, such as myeloma cells” (FF14). The original
claims recite that B-cells capable of producing osteopontin (not necessarily
myeloma tumor cells) can also be used to screen candidates (FF15). While
the Specification does not explicitly describe screening a candidate twice, it
clearly conveys the concept of screening candidates against different types
of osteopontin-producing cells, and one of skill in the art would have
recognized that Appellants were in possession of a method involving
screening a candidate against more than one type of osteopontin-producing
cell, including myeloma tumor cells. This is all that is required to satisfy the
written description requirement. The Specification need not provide in haec
verba support for the claimed subject matter.
Conclusions of Law
The Examiner has not established that the Specification lacks
adequate written descriptive support for a two-stage method of screening
compounds for the ability to reduce the severity of myeloma, where the
compounds are screened against two types of cells, including myeloma
tumor cells.
We reverse the rejection of claims 8-17 as failing to comply with the
written description requirement.
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SUMMARY
(A) The rejection of claims 18 and 19 under 35 U.S.C. § 103(a) as
unpatentable over Bautista and McPhaden is affirmed.

(B) The rejection of claims 8-13 under 35 U.S.C. § 103(a) as unpatentable
over Chabas, McPhaden, and Bautista is reversed.

(C) The rejection of claims 8-15 under 35 U.S.C. § 103(a) as unpatentable
over Chabas, McPhaden, Bautista, and Okada is reversed.

(D) The rejection of claims 8-15, 16, and 17 under 35 U.S.C. § 103(a) as
unpatentable over Chabas, McPhaden, Bautista, and Fonseca is
reversed.

(E) The rejection of claims 8-17 under 35 U.S.C. § 112, first paragraph, as
failing to comply with the written description requirement (new
matter) is reversed.

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)(1)(iv)(2006).

AFFIRMED-IN-PART
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