Ex Parte Neerven

Board of Patent Appeals and Interferences

May 22, 2007

09467901 (B.P.A.I. May. 22, 2007)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JOOST VAN NEERVEN
__________

Appeal 2007-1070
Application 09/467,901
Technology Center 1600
__________

Decided: May 22, 2007
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and RICHARD M.
LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal from the final rejection of claims 1-6, 8-
14, and 16-23. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

STATEMENT OF CASE
CD23 and FcεRI were known in the prior art to be the biological
receptors for IgE antibody (Specification 4: 16 to 5: 15). The claimed
invention relates to methods of using these known biological receptors to
detect IgE antibody in a sample.
Appeal 2007-1070
Application 09/467,901

Claims 1-6 and 8-23 are pending (Br. 2). Claim 15 is stated to be
allowable (Answer 2). Claims 1-6, 8-14, and 16-23 are appealed. The
Examiner cites the following patents as evidence of unpatentability:
Arnold US 6,004,745 Dec. 21, 1999
Johnson US 6,034,066 Mar. 7, 2000
Frank US 6,060,326 May 9, 2000
Johansen US 6,087,188 Jul. 11, 2000
Claims 1-5, 8-14, 16, and 21-23 stand rejected under 35 U.S.C. § 103
as obvious over Johansen in view of Johnson and Frank (Answer 3).
Claims 6 and 17-20 stand rejected under 35 U.S.C. § 103 as obvious
over Johansen in view of Johnson and Frank, and further in view of Arnold
(Answer 7).
Within the first rejection, Claims 1-5, 8-14, 16, 21, and 22 stand or
fall together; we select claim 1 as representative. However, separate
arguments were provided for the patentability of claim 23;1 thus, we
consider it separately. In the second rejection, claims 6 and 17-20 stand or
fall together because Appellant has not provided separate reasons for the
patentability of any individual claim in this grouping; we select claim 6 as
representative. See 37 C.F.R. § 41.37(c)(1)(vii). Claims 1, 6, and 23 read as
follows:

1 On pages 16-18 and 25-26 of their Brief, Appellant recites the claimed
features of dependent claims 2-5, 8, 9, 17-19, 20, and 21, but do not provide
arguments for their patentability apart from referring to the arguments set
forth for independent claims 1 and 6. “A statement which merely points out
what a claim recites will not be considered an argument for separate
patentability of the claim.” 37 C.F.R. § 41.37(c)(1)(vii).
2
Appeal 2007-1070
Application 09/467,901

1. A method of detecting and/or quantifying an IgE
antibody specific to a ligand in the form of an antigen, an
antibody, or a hapten in a liquid sample suspected to contain the
IgE antibody comprising the steps of:

(a) contacting (i) the sample with (ii) a free dissolved
ligand in the form of an antigen, an antibody, or a hapten to
form a mixture I comprising complexes that comprise the IgE
antibody and the ligand (IgE-containing complexes),
(b) mixing the mixture I with a carrier to which is
bound (iii) an IgE receptor, wherein said IgE receptor is CD23
(FсεRII) and/or FсεRI, to form a mixture II comprising carrier-
bound IgE-containing complexes,
(c) separating the carrier-bound IgE-containing
complexes from the mixture II, and
(d) determining the amount of the carrier-bound IgE-
containing complexes formed by detecting a label present in the
carrier-bound IgE-containing complexes,
wherein the label to be detected is associated with the
ligand or the IgE antibody and wherein the label to be detected
is added to the complexes present in steps (a), (b), or (c) and
does not form part of the carrier.
6. A method of detecting and/or quantifying an IgE
antibody specific to a ligand in the form of an antigen, an
antibody, or a hapten in a liquid sample suspected to contain the
IgE antibody comprising the steps of:
(a) contacting (i) the sample with (ii) a free dissolved
ligand in the form of an antigen, an antibody, or a hapten to
form a mixture I comprising complexes that comprise the IgE
antibody and the ligand (IgE-containing complexes),
3
Appeal 2007-1070
Application 09/467,901

(b) mixing the mixture I with a carrier to which is
bound (iii) an IgE receptor, wherein said IgE receptor is CD23
(FсεRII) and/or FсεRI, to form a mixture II comprising carrier-
bound IgE-containing complexes,
(c) separating the carrier-bound IgE-containing
complexes from the mixture II,
(d) adding a label compound to the carrier-bound IgE-
containing complexes resulting from the separation step (c) to
form a mixture II’,
(e) separating the labeled carrier-bound IgE-
containing complexes from the mixture II’, and
(f) determining the amount of the carrier-bound IgE-
containing complexes formed by detecting the label present in
the carrier-bound IgE-containing complexes,
wherein the label compound is associated with the ligand or the
IgE antibody.
23. A method of detecting and/or quantifying
physiologically active forms of an IgE antibody specific to a
ligand in the form of an antigen, an antibody, or a hapten in
liquid sample suspected to contain the IgE antibody by
simulating in vivo interactions between the IgE antibody, the
IgE antibody’s ligand and the IgE antibody’s receptor,
comprising the steps of:
(a) contacting (i) the sample with (ii) a free dissolved
ligand in the form of an antigen, an antibody, or a hapten to
form a mixture I comprising complexes that comprise the IgE
antibody and the ligand (IgE-containing complexes),
(b) mixing the mixture I with a carrier to which is
bound (iii) an IgE receptor, wherein said IgE receptor is CD23
(FсεRII) and/or FсεRI, to form a mixture II comprising carrier-
bound IgE-containing complexes, and wherein the complexes
that comprise the IgE antibody and the ligand are formed prior
4
Appeal 2007-1070
Application 09/467,901

to contact with the IgE receptor to simulate in vivo interactions
between the IgE antibody, the ligand, and the IgE receptor,
(c) separating the carrier-bound IgE-containing
complexes from the mixture II, and
(d) detecting and/or quantifying physiologically active
forms of ligand-specific IgE bound to said receptor by
determining the amount of the carrier-bound IgE-containing
complexes formed by detecting a label present in the carrier-
bound IgE-containing complexes,
wherein the label to be detected is associated with the ligand or
the IgE antibody and wherein the label to be detected is added
to the complexes present in steps (a), (b), or (c) and does not
form part of the carrier and wherein in vivo interactions
between the IgE antibody, the IgE antibody’s ligand and the
IgE antibody’s receptor are simulated to measure
physiologically active forms of IgE.

FINDINGS OF ACT
Johansen
1. Johansen describes an IgE assay which is specific for an IgE antibody;
the IgE antibody recognizes a specific antigen or hapten of interest
(Johansen, col. 4, ll. 50-62 and col. 5, ll. 50-60; Answer 4).
2. The assay contains: 1) specific IgE-antibody; 2) a specific allergen
(antigen or hapten) bound to biotin; 3) a monoclonal mouse anti-IgE bound
to magnetic particles; and 4) a chemiluminescent avidin-acridinium ester
label (Johansen, col. 5, ll. 50-60; Answer 4).
3. The specific IgE-antibody (present in a “sample”) is mixed with the
specific allergen bound to biotin (“ligand antigen”) and the anti-IgE bound
5
Appeal 2007-1070
Application 09/467,901

to magnetic particles (“antibody directed against the [IgE] antibody”) to
form a first complex (Johansen, col. 3, ll. 37-42; col. 5, ll. 50-60; Answer 4).
4. The label (“chemiluminescent acridinium compound”) is added to the
first complex to form a second complex (Johansen, col. 3, ll. 43-46; Answer
4).
5. The second complex is separated from the liquid phase and the label is
detected (Johansen, col. 3, ll. 47-51; Answer 4).
6. Example 2 describes detection and quantification of a specific IgE
according to this method (Johansen, cols. 8-9).
7. Johansen’s Fig. 1 illustrates the assay steps.
8. The correspondence between the steps recited in instant claim 1 and
Johansen’s specific IgE assay is shown below.

Claim 1 Johansen’s Fig. 1

9. Johansen’s assay meets the limitations of steps (a)-(d) of claim 1, but
does not describe using an IgE receptor which is “CD23 (FcεRII) and/or
FcεR1” as recited in step (b). (Answer 5).
6
Appeal 2007-1070
Application 09/467,901

Frank
10. Frank describes “a method to detect canine IgE using a canine Fc
epsilon receptor (FcεR) to detect canine IgE antibodies in a biological
sample from a canid” (Frank, Abstract).
11. Frank states:
The present invention relates to the discovery that purified high
affinity canine Fc epsilon receptor (i.e., FcεRI; referred to
herein as FcεR) can be used in canine epsilon immunoglobulin
(referred to herein as IgE or IgE antibody)-based detection (e.g.,
diagnostic, screening) methods and kits.
(Frank, col. 2, ll. 13-17.)
12. Frank describes the advantage of using FcεR in an IgE detection assay
instead of anti-IgE.
[A]ntibodies that bind selectively to . . . (i.e., anti-IgE
antibodies) . . . have been used to detect IgE. These anti-IgE
antibodies, however, can cross-react with other antibody
idiotypes . . . . The discovery of the present invention includes
the use of . . . (FcεR) . . . to detect the presence of IgE in a
putative IgE-containing composition. . . . A canine FcεR
molecule provides an advantage over, for example anti-IgE
antibodies, to detect IgE because a canine FcεR molecule . . .
can bind to a canine IgE with more specificity . . . and more
sensitivity . . . than anti-IgE binding antibodies.
(Frank, col. 1, ll. 24-41.)

13.
The use of canine FcεR in diagnostic methods and kits is
unexpected because the use of canine FcεR avoids
complications presented by use of antibodies that bind to IgE
(i.e., anti-IgE antibodies). Such complications include, for
example, non-specific binding of anti-IgE antibodies to other
classes of immunoglobulin such as gamma immunoglobulin
(i.e., IgG).
7
Appeal 2007-1070
Application 09/467,901

(Frank, col. 2, ll. 17-25.)
Johnson
14. Johnson teaches that CD23 is a cellular receptor for IgE (Answer 6).
Obviousness over Johansen and Frank in view of Johnson
15. The Examiner contends:
It would have been obvious to one of ordinary skill in the art to
use the IgE receptors of Johnson et al. and Frank et al. to
measure IgE according to the method of Johansen et al. since
both of these receptors, CD23 and [FcεR], are specific to IgE
antibody and because [FcεR] and CD23 can bind to IgE with
less isotype cross-reactivity and more sensitivity than anti-IgE
binding antibodies. (See Frank et al. Col. 1, lines 19-34).
(Answer 6.)
Arnold
16. Arnold teaches
in the background section that a typical sandwich assay
involve[s] incubating an immobilized antibody (IgE receptor)
with a test medium (sample). Antigens, if in the medium, will
bind to the antibody. After incubation, unbound antigen is
removed in a separation step. After a second, or simultaneous
incubation with a solution of labeled antibody, the bound
antigen becomes sandwiched between the immobilized
antibody and the labeled antibody. After a second separation
step, the amount of labeled antibody can be determined as a
measure of the antigen in the medium. (see col. 1, lines 55-66).
(Answer 7.)
Obviousness over Arnold
17. The Examiner states that it would have been obvious to a person of
ordinary skill in the art to have utilized first and second separation steps as
taught by Arnold for their known advantages (Answer 7).
8
Appeal 2007-1070
Application 09/467,901

DISCUSSION
Obviousness of claims 1-5, 8-14, 16, and 21-23
Claims 1-5, 8-14, 16, and 21-23 stand rejected under 35 U.S.C. § 103
as obvious over Johansen in view of Johnson and Frank (Answer 3).
A claimed invention is obvious “if the differences between the subject
matter sought to be patented and the prior art are such that the subject matter
as a whole would have been obvious at the time the invention was made to a
person having ordinary skill in the art to which said subject matter pertains.”
35 U.S.C. § 103(a). To make this determination, we consider in the context
of the knowledge and level of skill possessed by a person of ordinary skill in
the art whether such a person would have had reason to combine the prior art
in the fashion claimed by the application at issue. See KSR Int’l Co. v.
Teleflex Inc., 550 U.S. __, 82 USPQ2d 1385, 1396 (2007).
In this case, we find that the Examiner has presented sufficient
evidence that a person of ordinary skill in the art would have had adequate
reason at the time the application was filed to have utilized Frank’s FcεR
molecule in Johansen’s method of detecting specific IgE antibodies. Frank
explicitly states that its FcεR molecule is an improvement over anti-IgE
antibody (i.e., the anti-IgE antibody utilized in Johansen’s method) “because
the use of canine FcεR avoids complications presented by the use of . . . anti-
IgE (i.e., anti-IgE antibodies),” such as non-specific binding (Frank, col. 2,
ll. 19-21; FF 12-13). Frank recognizes that this property is advantageous in
IgE antibody-based detection (e.g., diagnostic, screening) methods and kits
(Frank, col. 2, ll. 14-17; FF 11). The skilled worker would recognize this as
9
Appeal 2007-1070
Application 09/467,901

suggestion to utilize FcεR for IgE detection, including in methods such as the
one described by Johansen.
Appellant contends that “a general suggestion that an IgE receptor
might be used in the genus of detection assays does not suggest its use in the
particular method of the invention” (Br. 14). We do not agree. Precise
teachings directed to the specific subject matter of a claim are not required to
reach a conclusion of obviousness. KSR, 82 USPQ2d at 1396. “[T]he
teaching, motivation, or suggestion may be implicit from the prior art as a
whole, rather than expressly stated in the references. . . . The test for an
implicit showing is what the combined teachings, knowledge of one of
ordinary skill in the art, and the nature of the problem to be solved as a
whole would have suggested to those of ordinary skill in the art.” In re
Kahn, 441 F.3d 977, 987-988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). In
this case, Frank expressly teaches problems associated with anti-IgE
antibodies – the same antibodies used by Johansen – and suggests a solution:
substituting FcεR because it more specific and sensitive, providing “an
advantage over . . . anti-IgE antibodies . . . to detect IgE” (Frank, col. 1, ll.
36-38; FF 13).
Appellant also argues that “skilled [worker] would be encouraged to
use Frank’s . . . method in its entirety” which involves the use of not only
FcεR but also anti-IgE (Br. 13). Appellant asserts that Frank “describes
using FcεR with antibodies, not substituting antibodies for receptors” (Br.
13). We do not find this argument persuasive. The disclosure that Appellant
is apparently referring to is Frank’s teaching that anti-IgE antibodies can be
used to detect the FcεR molecule: IgE complex (Frank, col. 9, ll. 57-60).
10
Appeal 2007-1070
Application 09/467,901

However, Frank teaches different methods of detecting IgE using different
types of labeling reagents (col. 8, l. 50 to col. 9, l. 60), only one embodiment
which uses anti-IgE antibodies. In contrast, all Frank’s embodiments utilize
FcεR to detect IgE. FcεR as a detection reagent is characterized by Frank as
its “discovery” (Frank, col. 2, ll. 13-15; FF 11-13). This discovery is not
masked or denigrated by Frank’s teaching that FcεR can be used in different
assay formats (Br. 15-16), including formats which combine it with an anti-
IgE antibody. To the contrary, these teachings show the suitability of FcεR
in a wide range IgE detection methods, providing the reason to have
combined Frank’s disclosure with Johansen.
We also agree with the Examiner that Frank’s teaching that FcεR can
be used to detect IgE antibodies in a sample would have led a person of
ordinary skill in the art to reasonably expect that FcεR could be used
successfully in Johansen’s IgE detection method (Answer 9). Appellant
argues that the Examiner has not satisfied the initial burden of showing a
reasonable expectation of success (Br. 16), but has not explained why
Frank’s disclosure that FcεR works to detect IgE in a biological sample is
insufficient evidence to meet this burden.
Claim 23
It is stated by Appellant, especially with respect to claim 23 (Br. 19),
that
Prior systems that use, for example, anti-IgE antibodies to bind
to the IgE antibodies are artificial and useful for simply
measuring the concentration of specific immunoglobulins in a
sample. In fact, it can be said that prior systems are artificial
because they measure the total concentration of
immunoglobulin in a sample. See specification at page 1, lines
11
Appeal 2007-1070
Application 09/467,901

9-29. In contrast, however, by using IgE receptors, the
invention focuses on those antibodies that are biologically
active, thus measuring the relevant in vivo level of IgE. See
specification at page 6, lines 1-6.
(Br. 5-6). Claim 23 expressly recites that “in vivo interactions . . . are
simulated” in its method.
While the claimed method may facilitate the measurement of levels of
IgE “that are most likely to be active in vivo” (Br. 7), the method itself is
suggested by the prior art and these properties are inherent to carrying it out.
“Mere recognition of latent properties in the prior art does not render
nonobvious an otherwise known invention.” In re Baxter Travenol Labs.,
952 F.2d 388, 392, 21 USPQ2d 1281, 1285 (Fed. Cir. 1991).

Johnson
The IgE receptor in claim 1 is “CD23 (FcεRII) and/or FcεRI”; thus,
the receptor can be one of three different embodiments: 1) CD23 alone,
2) FcεRI, or 3) CD23 and FcεRI. Since we have concluded that the
combination of Johansen in view of Frank suggests the use of FcεRI in the
claimed assay, it is unnecessary for us to consider the other embodiments
which involve CD23. A claim covering a plurality of embodiments is
unpatentable under § 103 if the prior art demonstrates the obviousness of
any one of them. In re Klein, 987 F.2d 1569, 1570, 26 USPQ2d 1133, 1134
(Fed. Cir. 1993). For this reason, we do not address Appellant’s arguments
regarding Johnson which was cited for its teaching of CD23.
12
Appeal 2007-1070
Application 09/467,901

Conclusion
For the foregoing reasons, we affirm the rejection of claim 1 as
obvious over Johansen in view of Johnson and Frank (Answer 3). Claims
2-5, 8-14, 16, and 21-23 fall with claim 1 because separate arguments for
their patentability were not provided.

Obviousness of claims 6 and 17-20
Claims 6 and 17-20 stand rejected under 35 U.S.C. § 103 as obvious
over Johansen in view of Johnson and Frank, and further in view of Arnold
(Answer 7).
Claim 6 further requires adding a label after a first separation step
followed by a second separation step to separate non-complexed label from
the labeled complex (Br. 21; Answer 7).
The Examiner has provided evidence that a person of ordinary skill in
the art would have reason to have combined Arnold with Johansen and
Frank for Arnold’s known advantages (Answer 7; FF 17).
Appellant argues that Arnold does not “cure” the “defect” in the
combination of Johansen and Frank (Br. 22). They also argue that Arnold’s
assay differs from the claimed assay in teaching immobilized capture
antibody (Br. 22).
[T]hus the interaction between the antibody and the ligand does
not take place freely in solution . . . [as required by claim 6].
There is no teaching in Arnold suggesting that such an assay
could be adapted to detect antibodies let alone using an
antibody receptor that is not immobilized to do it.
(Br. 22.)
13
Appeal 2007-1070
Application 09/467,901

We concur with the Examiner’s finding that Arnold teaches that two-
step antibody separation methods are conventional in the art. Arnold states
that the label can be added in either a second step or “simultaneous” with the
first incubation step with antibody and antigen (Arnold, col. 1, l. 60; FF 16),
indicating the interchangeability of a one-step method (e.g., Johansen) with a
two-step method (e.g., Arnold). Appellant’s arguments address the
suitability of Arnold’s particular assay method when combined with
Johansen and Frank, not the use of the two-step assay format described in
Arnold’s background. Consequently, we do not find Appellant to have
rebutted the prima facie case of obviousness.
Conclusion
The rejection of claim 6 is affirmed. Claims 17-20 fall with claim 6
because different arguments for their patentability were not provided.

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).

AFFIRMED

lbg

FINNEGAN, HENDERSON, FARABOW,
GARRETT & DUNNER LLP
901 NEW YORK AVENUE, NW
WASHINGTON DC 20001-4413
14