Ex Parte Hiller et al

Patent Trial and Appeal Board

Aug 13, 2018

10398266 (P.T.A.B. Aug. 13, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
10/398,266 04/03/2003
23570 7590 08/15/2018
PORTER WRIGHT MORRIS & ARTHUR, LLP
INTELLECTUAL PROPERTY GROUP
41 SOUTH HIGH STREET
29THFLOOR
COLUMBUS, OH 43215
Reinhard Hiller
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.
4007652-175259 3206
EXAMINER
MARCSISIN, ELLEN JEAN
ART UNIT PAPER NUMBER
1677
NOTIFICATION DATE DELIVERY MODE
08/15/2018 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):
ipdocket@porterwright.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte REINHARD HILLER, CHRISTIAN HARWANEGG, and
MANFRED MULLER1
Appeal2016-008154
Application 10/398,2662
Technology Center 1600
Before RICHARD M. LEBOVITZ, RYAN H. FLAX, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to methods of screening for
allergen-specific immunoglobulin E (IgE) in a serum sample comprising a
providing a microarray chip. The Examiner finally rejected the claims as
obvious under 35 U.S.C. § 103(a). Appellants appeal the rejections pursuant
to 35 U.S.C. § 134. We have jurisdiction for the appeal under 35 U.S.C.
§ 6(b) and affirm the rejections.
1 The Appeal Brief ("Appeal Br.") at page 1 lists Assignee, VBC Genomics
Bioscience Research GmbH, now Phadia Multiplexing Diagnostics GmbH,
by change of name, and Phadia AB, a Thermo Fisher Scientific company,
owner of the Assignee, as the real parties in interest.
2 The appealed Application's written disclosure is referenced as "the '266
Specification" or "the '266 Spec."
Appeal 2016-008154
Application 10/398,266
STATEMENT OF THE CASE
The claims are directed to methods of screening for allergen-specific
immunoglobulin E (IgE) in a serum sample. The methods comprise
providing a microarray chip comprising a solid support. The support
comprises at least 64 spots consisting essentially of single allergens
("discrete features"). The chip is incubated with serum and IgE bound to the
allergen spots is detected, if any is present.
Claims 93, 96, 97, 99--101, 104, 106-108, 110-120, 123, 124, 126-
128, 131, 133-135, and 137-167 stand rejected by the Examiner as follows:
1. Claims 93, 96, 97, 99--101, 104, 106-108, 110-115, 117-120, 123,
124, 126-128, 131, 133-135, 137-142, and 144--167 under 35 U.S.C.
§ I03(a) as obvious in view ofCalenoff et al., U.S. Patent. No. 4,845,027
(issued July 4, 1989) ("Calenoff'), Wagner et al., U.S. Publication Patent
Appl. No. 2002/0106702 Al (published Aug. 8, 2002) ("Wagner"), and
Simons et al., WO 99/25826 Al (published May 27, 1999) ("Simons").
2. Claims 116 and 143 under 35 U.S.C. § I03(a) as obvious in view
of Calenoff, Wagner, Simons, and Aalberse, U.S. Patent No. 4,468,470
(issued Aug. 28, 1984) ("Aalberse").
The following evidence is also cited in this Decision:
Fodor et al., US Patent 6,379,895 B 1 (issued Apr. 30, 2002)
("Fodor").
Lars Yman, The New Generation of Allergy Testing - Pharmacia CAP
System, 2 DIAGNOSTICA SPECIAL, 1-11 (1990) (English Translation) ("Yman
(1990")).
Lars Yman, Standardization of IgE Antibody Assays, 3 JIFCC, 198-
203 (Dec. 1991) ("Y man ( 1991 ") ).
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Application 10/398,266
Yman (1990) and Yman (1991) are collectively referred to as
"Y man."
Reinhard Hiller et al., Microarrayed allergen molecules: diagnostic
gatekeepers for allergy treatment, 16 THE FASEB JOURNAL, 414--16 (2002)
("Hiller"),
Second Declaration of Dr. Rudolph Valenta under 37 C.F.R. § 1.132
("Second Valenta Deel.").
An oral hearing was held on June 21, 2018. A transcript will be
entered into the record in due course.
There are four independent claims, claims 93, 120, 148, and 149. The
independent claims have not been argued separately and, thus, stand or fall
together. Appeal Br. 9. Claim 93, reproduced below, is representative:
93. A method of screening for allergen-specific
immunoglobulin E (IgE) in a serum sample comprising:
providing a microarray chip comprising a solid support
and an array of discrete features having a density of at least 64
discrete features per cm2 on the solid support, at least a portion
of the discrete features each being in the form of a spot having a
diameter of about 50-500 µm and consisting essentially of an
immobilized, single allergen having the capacity to induce and
combine with IgE antibody, or an immobilized, single
allergenic determinant or allergenic domain of an allergen, the
allergenic determinant or allergenic domain having the capacity
to induce and combine with IgE antibody, wherein the
respective discrete features are from more than one allergen
source;
incubating a serum sample containing immunoglobulin G
(IgG) with the microarray chip such that IgE which are specific
for respective allergens, if any such IgE are present, bind to the
respective allergens; and
detecting any IgE which are bound to the respective
allergens.
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RELATED APPEAL
This appeal is related to the appeal in Application No. 11/929,498
(Appeal No. 2017-001790), which has been concurrently decided.
REJECTION 1
Claim 93 is directed to a method of screening for allergen specific
immunoglobulin E (IgE) in a serum sample that comprises providing a
"microarray chip" have "an array of discrete features" which "consist[
]essentially" of single allergens, single allergen determinants, or single
allergen domains which have "the capacity to induce and combine with IgE
antibody." Each discrete feature is in the form of a spot with a specifically
recited diameter and density (per cm2).
The chip is incubated with a serum sample containing
immunoglobulin G (IgG) such that IgE, if present, binds to the allergens. In
the last step of the recited method, any IgE bound to the allergen is detected.
The Examiner found that Calenoff describes a method of detecting
IgE in a serum sample containing IgG using allergens immobilized on a
solid support. Final Act. 3--4. The Examiner also found that Calenoff
describes immobilizing the allergen on various solid supports, including a
microtiter well. Id. at 4; see also Calenoff 3: 15--4:29.
The Examiner further found that Calenoff teaches that the IgE is
detected using a labeled anti-IgE antibody. Final Act. 14.
The Examiner acknowledged that Calenoff does not describe the solid
support as a microarray chip with single allergens arrayed in the recited
density with the recited diameter as required by claim 93, but found that
Wagner describes a protein array with such features. Final Act. 4--5. The
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Examiner cited the disclosure in Wagner as teaching that its miniaturized
protein microarrays are an improvement over protein screening systems
using microarray plates. Id. at 6. Based on this teaching, the Examiner
determined it would have been obvious to one of ordinary skill in the art to
have utilized Wagner's microarrays to detect IgE as described in Calenoff to
obtain the known advantages of microarrays as described in Wagner. Id. at
8-9.
The Examiner recognized that Wagner does not teach using single
allergens in its microarray as required by the claims. Final Act. 4.
However, the Examiner determined that Simons teaches that isolated and
purified single allergens, including recombinant protein allergens, improve
diagnosis, providing a reason for a skilled artisan to have used single
allergens in Wagner's microarray. Id. at 7-9.
Large Capacity Substrate
Appellants argue:
DISCUSSION
it was customary prior to the present invention, when using
blood or plasma samples to conduct IgE screening for in vitro
allergy diagnosis, to measure IgE using a large capacity
substrate, i.e., a high surface area substrate that can hold an
excess of allergen relative to the amount of IgG and IgE in a
sample.
Appeal Br. 11.
Appellants explain that a large capacity substrate was used "in order
to minimize the risk of underestimating the amount of IgE in the sample
owing to IgG reaction with the allergen and/or IgG blocking of IgE reaction
with the allergen." Id. To support this argument, Appellants cited Yman
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(1990), Yman (1991), and a second Declaration by Valenta. Id. at 11-12.
According to Appellants, the Pharmacia CAP (ImmunoCAP) System
described in Yman (1990) and (1991) "was and remains a widely used
device which has a large capacity substrate and uses an excess of allergen
sufficient to react with both the IgG and IgE in a sample." Id. at 11. In
contrast, Appellants contend that the claimed methods "do not use a large
capacity substrate having an excess of allergen as compared with the amount
of IgG and IgE in a sample" and, thus, are contrary to "conventional practice
in the art of IgE screening and in vitro allergy diagnosis" and surprisingly,
"a small capacity substrate, can successfully screen for IgE in a serum
sample to allow in vitro allergy diagnosis from the serum sample." Id. at 12.
In support of their arguments and as rebuttal evidence, Appellants
provided a second Declaration by Dr. Valenta. 3 Dr. Valenta stated that he
has "spent over 25 years working and researching in the fields of allergy and
immunology, including diagnostics thereof by IgE detection" and has
"authored or co-authored more than 300 peer-reviewed articles in the fields
of allergy and immunology." Second Valenta Deel. ,r 1.
Dr. Valenta stated in his Declaration that there would have been no
reasonable expectation of success4 that microarray chips could be used
successfully to measure IgE in a sample because:
3 A "first" declaration by Dr. Valenta is also of record, but not cited by
Appellants in this appeal.
4 An obviousness determination requires finding both that a skilled artisan
would have been motivated to combine the teachings of the prior art and that
the skilled artisan would have had a reasonable expectation of success in
doing so. Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d
1359, 1367 (Fed. Cir. 2016).
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Interference of allergen-specific IgG with allergen-specific IgE
in a blood or plasma sample would have been anticipated in a
microarray chip test, in particular when allergen extracts would
be used, whereas single allergens would represent only a small
percentage of the extract proteins, leaving them even less
represented on a microarray chip, preventing accurate IgE
detection.
Id. ,r 5; see also id. ,r 9.
With respect to this argument, Dr. Valenta focused on an allergen
extract. However, the Examiner specifically cited Simons' teaching of using
isolated and purified recombinant allergens to improve the diagnosis of an
allergy by detection of IgE. As found by the Examiner, Simons teaches:
Purification or isolation of each of the saliva proteins is
required to improve studies of the diagnosis and
immunotherapy of mosquito allergy, and studies of mechanisms
of mosquito-transmitted diseases.
Simons 2:35-38.
The present invention also provides an immunoassay for
measurement of mosquito salivary allergen-specific IgE and
IgG using recombinant mosquito salivary allergen as the
substrate to which the allergen-specific IgE and IgG binds.
Id. at 4:24--28.
Thus, even if Dr. Valenta is correct that an allergen extract might not
have reasonably been expected to accurately detect IgE on a microarray, he
did not address the disclosure in Simons, as applied by the Examiner, which
teaches one of ordinary skill in the art that single isolated allergens improve
IgE detection in samples. Based on Simons, one of ordinary skill in the art
would have known that an extract having multiple proteins would have
considerably less of each antigen than a single protein spot described in
Wagner. Simon 2: 13-28. Consequently, while we have considered Dr.
Valenta's testimony in paragraphs 5 and 9 of his Declaration, we do not find
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it persuasive because he did not provide adequate evidence or reasoning as
to why the single recombinant allergens described in Simons would have the
same alleged detection problem, when used in Wagner's microarray, as
compared to an allergen extract comprised of a plurality of different
allergens.
Dr. Valenta also testified in his Declaration that there was a lack of a
reasonable expectation of success because allergen testing for IgE was
performed using large capacity surfaces such as the Pharmacia CAP System,
while Wagner does not have the large capacity to detect IgE. Second
Valenta Deel. ,r,r 6, 9. To support this position, Dr. Valenta cites the Yman
(1990) and Yman (1991) publications. Id. ,r 7. Dr. Valenta states:
Figure 1 (page 198) of Y man 1991 shows a substrate with
increased capacity binds greater IgE. Specifically, the highest
capacity substrate, ImmunoCAP, had better IgE binding than an
activated paper disk (a RAST test), and the RAST had higher
capacity and better IgE binding than a passive coated tube,
which is similar to a microtiter plate. Y man 1991 concludes
that a high capacity solid phase minimizes the risk of
underestimation of the IgE antibody as a result of IgG and IgE
competition for the same binding sites (pages 201-202). Figure
8 (page 202) of Yman 1991 shows that the low capacity
substrates employed in tests x and z bound 45-90% less IgE as
compared with the high capacity substrates.
Id. ,r 7 ( emphasis added).
Dr. Valenta also cited evidence that "ImmunoCAP employs about
10,000,000 times more allergen than a microarray spot" and stated that the
"increased concentration of a pure allergen as compared with an extract does
not compensate for the significant decrease in the amount of allergen in a
microarray spot as compared with the amount of allergen in the
ImmunoCAP. Id. ,r 13. Dr. Valenta also cited Yman (1990):
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Y man 1990 teaches that while allergen concentration and
composition, anti-IgE, labeling and detector parameters are
factors determining the signal to noise ratio of an immunoassay
for IgE detection, "the critical factor is the solid phase which
serves as a support of a double immune reaction (allergen-IgE
and IgE-anti-IgE)" and "irrespective of where the solid phase is
involved during the test, only a solid phase with a high specific
binding capacity and low unspecific interference provides the
basis for a sensitive assay with a broad measuring range"
(English translation, page 2).
Second Valenta Deel. ,r 13.
Dr. Valenta places importance on Yman's teachings regarding its high
capacity ImmunoCAP system. However, while the Pharmacia ImmunoCAP
system is described as "a sensitive and specific quantitative assay for
allergen-specific IgE antibodies" (Yman (1990) 11), it was not the only
system known in the prior art that was capable of detecting IgE antibodies in
the presence ofigG. Yman (1990) compared its new ImmunoCAP system
to a lower capacity system, Phadebas RAST, which had been a "routine test
system" for IgE antibodies. Yman (1990) 1. Pharmacia's ImmunoCAP
system was designed to provide increased and enhanced sensitivity as
compared to Phadebas RAST. Id. Yman lists himself as an employee of
Pharmacia and, thus, it is reasonable to expect that his publications were
aimed at least in part at showing the advances of the new Pharmacia IgE
assay, not necessarily as addressing the IgE detection prior art. Id.
Consistently, Y man (1990) states: "Based on many years of experience in
the development and preparation of immunoassays, Pharmacia has
developed a new generation after Phadebas RAST with a new solid phase."
Id. at 2.
Moreover, as acknowledged by Dr. Valenta (Second Valenta Deel.
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Application 10/398,266
,r 7), Yman (1991) expressly teaches that "low-capacity" tests were available
to "catch specific IgE antibodies." Yman (1991) 202 (Fig. 8). Figure 8 of
Yman (1991) is reproduced below:
'a
120 ~
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Figure 8 Analy1;is of re/a/foe allergr.m excess in four
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ference by lgG antibodieE;~ com:peti'ng far thf: same aller~
gen. Tests x ,md z utilize low-capacity supports to
c(J/th sp!!-cific IgE antibodies or complexes.
Figure 8 ofYman (1991) shows a percentage ofigE antibody bound
in the CAP System, Phadebas RAST, Test x, and Testy. Tests x and y are
characterized by Y man ( 1991) as "low-capacity supports to catch specific
IgE antibodies or complexes." With respect to Figure 8, Yman (1991) states
that the "Pharmacia CAP System is much less sensitive" to IgG interference
"than tests utilizing low-capacity solid phases as carrier of allergen or for the
catching of soluble allergen-IgE complexes (Figure 8)." Yman (1991) 202.
Thus, while the high capacity CAP system is stated to be more sensitive and
specific (id. at 203), Y man (1991) did not conclude that the "low-capacity
supports" for allergen did not work in detecting IgE. Rather, Figure 8 of
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Y man ( 1991) confirms IgE detection in antiserum comprising IgG using
"low-capacity" supports, which are characterized as "commercial tests."
Despite the express disclosure in Y man ( 1991) of the ability of low
capacity supports to detect IgE, Dr. Valenta states there was no reasonable
expectation of success that a microarray chip could be used to successfully
measure IgE in a sample. Second Valenta Deel. ,r 6. Dr. Valenta states that,
"Wagner's microarray does not have the large capacity substrate Y man
taught, and was understood in the allergy art, as necessary for accurate IgE
detection." Id. ,r 9.
Firstly, Dr. Valenta assumes, but does not provide evidence, that the
microarray of Wagner is low capacity when a single allergen as claimed is
utilized as the spot in a microarray chip.
Secondly, and more significantly, Dr. Valenta's statement ignores
Y man ( 1991) 's disclosure that low-capacity supports could detect IgE
antibody. Y man (1991) 202 (Fig. 8). While higher capacity systems may be
more accurate and sensitive, the evidence of record is that low capacity
systems could successfully detect an IgE antibody. Id. The rejected claims
do not require a specific degree of sensitivity. Moreover, Dr. Valenta did
not establish that Wagner's microarray is lower capacity than the low-
capacity supports shown in Figure 8 ofYman (1991) nor did Dr. Valenta
adequately distinguish the capacity of the array in Wagner from the capacity
of other tests in the prior art. For example, in addition to the commercial
tests described in Wagner's Figure 8, the '266 Specification acknowledges
that "there are various in vitro methods for diagnosing allergies which detect
the presence of IgE or IgG antibodies in the blood of a patient." '266 Spec.
4. The '266 Specification discloses ELISA, Western blots, and RAST tests
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Application 10/398,266
(id.) and four patent publications describing assays used to test for IgE (id. at
4--5). Thus, while ImmunoCAP may hold 10,000,000 times more allergen
than a microarray spot (Second Valenta Deel. ,r 13), such a difference is not
necessarily indicative of other prior art tests used to successfully detect IgE
mentioned by Yman (1991) (low-capacity and RAST) and disclosed in
Appellants' own Specification. Thus, Dr. Valenta's focus on the large
capacity of the ImmunoCap system ignores the low capacity supports of
Yman (1991), the RAST assays, and the inventor's own disclosure in the
'266 Specification of alternative IgE tests.
For the above-mentioned reasons, we do not agree that a
preponderance of the evidence supports Appellants' statement that "the state
of the art at the time of the invention understood that a large capacity
substrate was needed for IgE screening and allergy." Appeal Br. 20
(emphasis added). To the contrary, the evidence of record shows that
alternatives existed in the prior art to detect IgE, including low-capacity
supports that would have been known to one of ordinary skill in the art.
Dr. Valenta states that the Y man publications, rather than Calenoff,
show the state of the prior art. Second Valenta Deel. ,r 8. However, as
discussed above, it is admitted that other IgE tests existed in the prior art to
measure IgE (Spec. 4--5), and Yman (1991) expressly shows low-capacity
and RAST tests for IgE antibodies in antiserum, in addition to ImmunoCAP.
Thus, there is no dispute that Calenoff is not representative of the prior art at
the time of the invention for IgE testing. However, the Y man publications
are not representative of the prior art either, because they are largely directed
to a discussion of ImmunoCAP and its properties, rather than a review of the
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Application 10/398,266
prior art, which includes additional IgE tests, such as those described in the
'266 Specification.
Dr. Valenta further states that "[a]s one skilled in the allergy and IgE
detection art, I would not have had any reason to combine Calenoff and
Wagner or to try to use Calenoff' s allergen extracts in Wagner's microarray
to detect IgE in a blood sample." Id. ,r 9. Dr. Valenta also states that
"Simons provides nothing that would have caused one of ordinary skill in
the art to not follow Yman's direction to use a large capacity substrate for
IgE detection, or to use single purified allergens, rather than a standardized
extract, for IgE detection." Id. ,r 12.
Dr. Valenta's arguments do not persuade us that the Examiner erred.
The rejection does not involve using Calenoff's allergens, but rather the
recombinant allergens described in Simons. The Examiner provided a
logical reason to apply Simons' methods to Calenoff s allergens, namely, to
improve diagnosis and facilitate allergy studies. Final Act. 7. Dr. Valenta
does not identify a flaw in this reasoning.
Furthermore, while Yman (1991) teaches using high capacity
supports, Wagner describes microarray technology and discloses that it can
be used for antibody/antigen detection (Wagner ,r 125), and the additionally
cited Fodor patent specifically mentions using its arrays to detect IgE
antibodies (Fodor 64:40-41, 113:27-25). Thus, one of ordinary skill in the
art had reason to tum to Wagner's disclosed technology for IgE detection for
the advantages described by the Examiner, e.g., for high throughput
screening and for screening a plurality of proteins in parallel. Final Act. 5-
6, 8. Appellants did not identify a defect in this reasoning, but instead argue
that Wagner does not teach allergen arrays or assays for IgE. Appeal Br. 14.
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However, as indicated above, the disclosures of Wagner and Fodor would
have reasonably suggested using a microarray chip to achieve high
throughput and parallel screening of a plurality of allergens for IgE.
Dr. Valenta acknowledges the disclosure in Fodor of
screening allergic reactions or susceptibilities and a simple IgE
specificity test useful in determining a spectrum of allergies and
at column 113 to an immobilized set of antigens attached to a
solid substrate on which a blood sample may be assayed to
determine the presence of antibodies, e.g., IgE or other type
antibodies.
Second Valenta Deel. ,r 11. Dr. Valenta disparages this teaching by stating
that it "only show[ s] a desire by one not knowledgeable in IgE detection to
be able to use array technology for IgE detection" and one of ordinary skill
in the art would not have followed Fodor in view of Yman's teaching of
high capacity substrates as "required for accurate IgE detection." Id.
The claimed method does not require a level of sensitivity or
accuracy. Thus, Dr. Valenta's argument regarding these properties is not
persuasive since these features are not limitations of the claims.
In addition, as already discussed, particularly in view of Figure 8 of
Yman (1991), and the admitted prior art in the '266 Specification,
Appellants did not establish that the so-called high capacity substrates were
required for IgE detection. For this reason, we do not agree that the
evidence supports Dr. Valenta's testimony that one of ordinary skill in the
art would have ignored Fodor's teaching. Furthermore, as to the wish or
desire of Fodor to use its microarray for IgE detection, Dr. Valenta did not
provide evidence that the microarray technology, using a small volume of
serum as compared to protein on a spot, is low-capacity when compared to
the amount of IgE in a serum sample, i.e., when the ratio of single protein to
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Application 10/398,266
serum is taken into account. Dr. Valenta also did not explain or address the
fact that Y man ( 1991) provides evidence that low capacity supports could
detect IgE. Consequently, the Examiner's determination that there was a
reasonable expectation of success that Wagner's array could be used
successfully to detect IgE is not inconsistent with Y man ( 1991).
Appellants argue that the skilled worker would not have used
Wagner's microarray technology to detect IgE because
one of ordinary skill in the art of IgE screening and in vitro
allergy diagnosis, having familiarity both with the challenges of
conventional allergen-specific IgE screening of serum samples
due to the abundance of IgG, and with the large capacity (high
surface area) substrate devices used at the time of the invention,
would have recognized that Wagner's protein arrays do not
provide a high surface area substrate or the high immobilized
allergen capacity that was generally understood by those of
ordinary skill in the art as necessary for allergen-specific IgE
screening of serum samples and in vitro allergy diagnosis using
such samples.
Appeal Br. 15-16.
As already discussed, this argument disregards Dr. Valenta's own
statement that "Yman 1991 shows that the low capacity substrates employed
in tests x and z bound 45-90% less lgE as compared with the high capacity
substrates~' (Second Valenta DecL 17)- indicating that the low-capacity
supports 1oaded v1ith allergen detected JgE in sen1m. This argument a1so
does not address the admitted prior art in the Specification, which is part of
the scope and content of the prior art, prior art the inventors knew about and
disclosed. Indeed, Dr. Valenta stated he read and understood the patent
application, which included this admitted prior art, and would be expected to
be ::nvare of various methods of IgE detection given his 25 years of
experience. Id. ,r~ 1, 3,
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\Ve have given Dr. Vaknta's testimonv in his second Declaration full
~ J
consideration, including his statement that it was a surprise to him that "lgE
to microarray chip-bound allergens could be measured." Second Valenta
Dec L 1113. However; De Valenta did not address his own statements about
the teaching in Yman (1991) oflovv-capacity supports and the disclosure in
the ;266 Specification of alternative screens for IgE. Nor did Dr. Valenta
provide a persuasive scientific explanation for his statement that pure
allergen as compared to an extract would not have compensated for the
reduced protein in a microarray chip. Second Valenta Deel. ir 13.
Teaching Away
Appellants contend that "by teaching a need for a large capacity
substrate to accurately screen for IgE, Y man teaches away from the use of a
small capacity substrate." Appeal Br. 23 (discussing Yman (1991)).
Furthermore, Appellants state:
Since a microarray is a small capacity substrate, smaller even
than the small capacity substrates tested by Y man, Y man
teaches one of ordinary skill in the art away from the ... [use]
of a microarray ... to accurately screen for IgE [in a serum
sample].
Id. ( also discussing Y man ( 1991)).
As discussed above, Appellants did not provide evidence that the
microarray of Wagner is smaller in capacity that the low capacity substrates
ofYman (1991). Dr. Valenta did not provide testimony on this issue. An
argument made by counsel in a brief does not substitute for evidence lacking
in the record. Estee Lauder, Inc. v. L 'Orea!, S.A., 129 F.3d 588, 595 (Fed.
Cir. 1997).
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Application 10/398,266
We agree with Appellants that Yman (1990) and Yman (1991) would
have led one of ordinary skill in the art to choose a solid support with a high
and stable binding capacity. However, as discussed by the Examiner, one of
ordinary skill in the art would also have had reason to pursue the microarray
technology described in Wagner to achieve a high throughput screen of a
plurality of allergens in parallel using smaller volumes of serum. Ans. 21.
As acknowledged by Appellants, Fodor provides an explicit suggestion to
carry out IgE screening using microarray technology. Ans. 25-26; Appeal
Br. 23. Appellants' argument that Wagner/Fodor should be ignored because
the latter were not experts in the relevant technology of IgE screening and
Y man teaches using high capacity supports overlooks the fact that there are
other goals to be fulfilled in the field of allergen screening. One such goal is
reflected in the teaching of Calenoff, which describes testing for IgE in
microtiter plates having a plurality of test wells (Calenoff 3 :59---68), enabling
parallel and high throughput processing of multiple different allergens at the
same time. Wagner's microarrays are an advancement over the previously
used microtiter format of Calenoff. Final Act. 6. Thus, one of ordinary skill
in the art seeking to implement high throughput testing for IgE would have
had reason to utilize Wagner's technology. Simply because one goal in IgE
testing is to increase accuracy and sensitivity by using high capacity
supports does not mean that other goals would be ignored, such as
implementing high throughput and parallel screening of a plurality of single
allergens for IgE binding.
We emphasize that a preponderance of the evidence does not support
Appellants' argument that Wagner's teaching is undermined because it
allegedly is not high capacity ( a fact that has not been established in this
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record). Namely, while Yman (1991) refers to a solid phase with high
biding capacity as providing "the basis for a sensitive, wide-range assay"
(Y man (1991) 198), low capacity supports also worked (id. at 202, Fig. 8).
Driven by the goal to implement high throughput allergen screening, it
would have been obvious to the skilled artisan to have used the solid support
array described in Wagner for IgE antibody testing. As held by the U.S.
Supreme Court in KSR Int 'l Co. v. Teleflex Inc., 550 US 398, 421 (2007):
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under § 103.
Expanding on this analysis, the Court of Appeals of the Federal
Circuit in Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352, 1361 (Fed. Cir.
2011) held:
To render a claim obvious, prior art cannot be "vague" and
must collectively, although not explicitly, guide an artisan of
ordinary skill towards a particular solution. Bayer Schering,
575 F.3d at 1347. Indeed, "most inventions that are obvious
were also obvious to try," id., and a combination is only
obvious to try if a person of ordinary skill has "a good reason to
pursue the known options." KSR, 550 U.S. at 421. ... When a
field is "unreduced by direction of the prior art," and when prior
art gives "no indication of which parameters were critical or no
direction as to which of many possible choices is likely to be
successful," an invention is not obvious to try. Bayer Schering,
575 F.3d at 1347 ( citing In re O 'Farrell, 853 F.2d 894, 903
(Fed. Cir. 1988)); see also Ortho-McNeil, 520 F.3d at 1364
( stating the number of options must be "small or easily
traversed").
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There is inadequate evidence in this record to establish that there were
"numerous parameters" to try, that the "prior art teaches merely to pursue a
'general approach that seemed to be a promising field of experimentation' or
'gave only general guidance as to the particular form of the claimed
invention or how to achieve it,"' factors militating against a determination
that an invention which was "obvious to try" would have been obvious to
one of ordinary skill in art. Pfizer, Inc. v. Apotex Inc., 480 F.3d 1348, 1366
(Fed. Cir. 2007). To the contrary, Wagner and Fodor describe how to make
arrays and Calenoff teaches that IgE is detected using anti-IgE antibody
(Calenoff 4:43---65). Yman (1991) also teaches anti-IgE antibodies to detect
IgE. Y man ( 1991) 203 ("[ A] nti-IgE"). Appellants have not identified any
steps or additional direction or guidance not provided by the cited prior art,
and known to one of ordinary art at the time of invention, that were
necessary to carry out the claimed invention. Appellants' own publication
reported "that a single fluorescence-labeled monoclonal anti-human IgE
antibody allowed the detection of IgE reactivities to immobilized allergens
in serum samples containing high or low total IgE levels as well as allergen-
specific IgE levels" (Hiller (in "DISCUSSION" section), the same type of
antibody used in the prior art to achieve IgE detection.
Claims 99-101 and 126-128
Claims 99-101 and 126-128 depend from claims 93 and 120,
respectively, and recite that the array of discrete features has a density of at
least about 96 discrete features per cm2 ( claims 99 and 126), of at least about
500 discrete features per cm2 ( claims 100 and 127), or of at least about 1000
discrete features per cm2 ( claims 101 and 128).
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Appellants state that Fodor discloses "that a standard
radioallergosorbent test (RAST) may be used to check a 'much larger
population of antigens' ( column 113, lines 33-35)." Appeal Br. 30. For this
reason, Appellants contend that when a large set of antigens is to be tested,
"Fodor would lead one of ordinary skill in the art to use a RAST and away
from" the claimed array. Id.
Fodor states that RAST "may be used" (Fodor 113:33-35), but
doesn't require it. Rather, the term "may" indicates it is one possibility, but
not necessary. Consequently, Fodor's disclosure that a RAST test may be
used, does not mean that it must be used in place of a microarray.
Therefore, Appellants' argument is not persuasive.
Claims 117-119, 144-146, and 150-165
Dependent claims 117-119, 144--146, and 150-165 further recite
specific numbers of immobilized single antigens. Appellants contend that
"none of the Calenoff, Wagner and Simons disclose any IgE screening or in
vitro allergy diagnosis wherein a plurality of different single allergens, i.e.,
from a plurality of allergen sources, are employed as discrete features, as
required by the present claims." Appeal Br. 32. However, the Examiner
addressed these claims, finding that Wagner teaches 100 or more patches of
protein. Final Act. 14. As noted by the Examiner, Simon teaches that
allergen extracts can be replaced by single allergens, providing the reason to
use a plurality of single different allergens as required by the claim. Ans.
36-37. Appellants argue non-obviousness over Simons individually.
Appeal Br. 32. However, "Simons is not relied upon independently, but
rather it is the cited combination of references that is considered to address
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the claimed invention." Id. at 3 7. Appellants also repeat the same
unpersuasive regarding Fodor's teaching that RAST "may be used." Appeal
Br. 33. Therefore, Appellants' arguments are not persuasive.
SUMMARY
For the foregoing reasons, we affirm the obviousness rejection
(Rejection 1) of independent claim 93. Independent claims 120, 148, and
149 fall with claim 93 because separate reasons for their patentability were
not provided. The obviousness rejection of separately argued claims 99--
101, 117-119, 126-128, 144--146, and 150-165 is affirmed for the reasons
given above and those for claim 93. The same arguments were provided for
claims 96, 97, 104, 106-108, 110-115, 123, 124, 131, 133-135, 137-142,
147, 166, and 167. These claims, therefore, fall with the independent
claims. 37 C.F.R. § 4I.37(c)(l)(iv).
Appellants make the same arguments for the rejection of claims 116
and 143 (Rejection 2) as they do for Rejection 1. Appeal Br. 34--35. This
rejection is, therefore, affirmed for the same reasons.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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