Ex Parte Ohshiro

Board of Patent Appeals and Interferences

Jul 25, 2003

09133942 (B.P.A.I. Jul. 25, 2003)

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for publication and is not binding precedent of the Board.

Paper No. 25

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KYOUICHI OHSHIRO
__________

Appeal No. 2002-1360
Application No. 09/133,942
__________

ON BRIEF
__________

Before WILLIAM F. SMITH, SCHEINER, and GRIMES, Administrative Patent
Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL

This is a decision on appeal under 35 U.S.C. § 134 from the examiner’s
final rejection of claims 1-10, all of the claims in the application. Claim 1 is
representative and reads as follows:
1. A method for measuring in solution the concentration of urinary
trypsin inhibitor in a sample comprising:

adding antibodies against urinary trypsin inhibitor that are not
adhered to an insoluble support to the sample in a reaction
solution;

measuring the degree of the resulting agglutination in the reaction
solution; and

correlating the degree of agglutination to the inhibitor concentration.
Appeal No. 2002-1360 Page 2
Application No. 09/133,942

The examiner relies on the following references:
Craig et al. (Craig) 4,703,018 Oct. 27, 1987
Maehara et al. (Maehara), “Immunochemical Determination of the Serum Protein
Reacting with Antibody against Human Urinary Trypsin Inhibitor by Single Radial
Immunodiffusion: Use of Polyethylene Glycol,” Journal of Immunological
Methods, Vol. 80, pp. 117-123 (1985)

Claims 1-8 stand rejected under 35 U.S.C. § 102(b) as anticipated by
Maehara.
Claims 1-10 stand rejected under 35 U.S.C. § 103 as obvious in view of
Craig and Maehara.
We reverse.
Background
The specification discloses a “method for measuring the concentration or
activity of urinary trypsin inhibitor (UTI) contained in body fluids. The presence of
UTI was initially recognized in urine but its presence has been confirmed in body
fluids other than urine by subsequent studies.” Page 1. “[I]t has been reported
that the amount of UTI present in urine significantly increases in patients with
bacterial infections, malignant tumors . . ., renal diseases or myocardial
infarction, or patients having undergone surgical operations, pregnancy, or the
like.” Id.
Conventional methods of detecting UTI immunologically “include single
radial immunodiffusion (SRID), radioimmunoassay (RIA), enzyme immunoassay
(EIA), enzyme-linked immunosorbent assay (ELISA), latex agglutination
Appeal No. 2002-1360 Page 3
Application No. 09/133,942

immunoassay (LAIA), and the like.” Specification, page 2. Each of these assays
has various drawbacks. See id.
The specification discloses that “with respect to UTI, it was found that
agglutination reaction can be measured even if free anti-UTI antibodies that are
not adhered to an insoluble support such as latex particles etc. are used.” Page
3. Thus, the disclosed method “compris[es] preparing antibodies against UTI
that are not adhered to an insoluble support (free anti-UTI antibodies), adding the
antibodies to said sample, and measuring the degree of the resulting
agglutination. Examples of the insoluble support include latex particles, gold
colloid particles, and the like.” Id. According to the specification, this method “is
excellent in precision and reproducibility, . . . [and] can be carried out easily
without the need of special operations such as immobilization of antibodies, or
use of special equipment. Furthermore, compared to LAIA, it has an advantage
of causing less contamination in an automatic analyzer.” Id.
Discussion
Claim 1, the only independent claim, is directed to a method of measuring
the concentration of UTI in solution by adding, to a sample, anti-UTI antibodies
“that are not adhered to an insoluble support,” measuring the degree of
agglutination that results, and correlating the degree of agglutination to UTI
concentration. The examiner rejected most of the claims as anticipated by
Maehara, and rejected all of the claims as obvious in view of Craig and Maehara.
Appeal No. 2002-1360 Page 4
Application No. 09/133,942

1. Claim construction
“[N]ot unlike a determination of infringement, a determination of
anticipation, as well as obviousness, involves two steps. First is construing the
claim, . . . followed by, in the case of anticipation or obviousness, a comparison
of the construed claim to the prior art.” Key Pharms. Inc. v. Hercon Labs. Corp.,
161 F.3d 709, 714, 48 USPQ2d 1911, 1915 (Fed. Cir. 1998).
“It is axiomatic that, in proceedings before the PTO, claims in an
application are to be given their broadest reasonable interpretation consistent
with the specification and that claim language should be read in light of the
specification as it would be interpreted by one of ordinary skill in the art.” In re
Sneed, 710 F.2d 1544,1548, 218 USPQ 385, 388 (Fed. Cir. 1983) (citation
omitted). “Although words in a claim are generally given their ordinary and
customary meaning, a patentee may choose to be his own lexicographer and use
terms in a manner other than their ordinary meaning, as long as the special
definition of the term is clearly stated in the patent specification or file history.”
Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582, 39 USPQ2d 1573,
1576 (Fed. Cir. 1996).
In this case, the claims are directed to a method of measuring UTI
concentration comprising adding to the sample anti-UTI antibodies “that are not
adhered to an insoluble support,” and “measuring the degree of the resulting
agglutination.” Claim 1. The specification discloses that “it was found that
agglutination reaction can be measured even if free anti-UTI antibodies that are
not adhered to an insoluble support such as latex particles etc. are used.” Page
Appeal No. 2002-1360 Page 5
Application No. 09/133,942

3. In the first working example (pages 8-11), solutions containing varying
concentrations of UTI were prepared and mixed with buffer. The absorbance of
the mixture was measured, then anti-UTI antibody solution was added and the
absorbance was measured again. The change in absorbance indicated the UTI
concentration.
As used in immunology, “agglutination” means “[c]lumping of particulate
antigens, e.g. red cells, bacteria, etc. by reaction with specific antibody which
forms bridges between antigenic determinants on contiguous particles.” See
Herbert,1 page 6. Precipitation, by contrast, means “the formation of a visible
complex on the addition of soluble antibody to soluble antigen.” Id., page 179.
See also Leffell,2 page 120: “Precipitation and agglutination were the first
methods employed for demonstrating autoantibodies in human sera.
Precipitation of cardiolipin has long served as a method for supporting the
diagnosis of syphilis. . . . Agglutination reactions are highly sensitive methods for
demonstrating antibody. Indirect, or conditioned, hemagglutination requires that
a soluble antigen be attached to a particle, such as a red blood cell or latex.”
The difference between an assay based on precipitation and one based
on agglutination is discussed in detail by Tizard.3 Tizard states that the
difference between precipitation and agglutination is “determined by the physical
state of the reactants. If antibodies combine with soluble antigens in solution

1 Herbert et al. (eds.), “Dictionary of Immunology,” 3rd edition, Blackwell Scientific Publications
(1985), copy attached.
2 Leffell et al. (eds.), “Handbook of Human Immunology,” CRC Press (1997), copy attached.
3 Tizard, “Immunology: An Introduction,” Saunders College Publishing (1988), copy attached.
Appeal No. 2002-1360 Page 6
Application No. 09/133,942

under appropriate conditions, the resulting complexes may precipitate. If,
however, the antigens are particulate (for example, bacteria or red blood cells),
they will agglutinate (clump).” Page 122.
Tizard describes a precipitation reaction as follows: “If a suitable amount
of a clear solution of soluble antigen is mixed with its antisera and incubated at
37°C, the mixture becomes cloudy within a few minutes, then flocculent, and
within an hour or so a precipitate settles to the bottom of the tube.” Id.
Agglutination is similar, but results from “mixing a suspension of antigenic
particles, such as bacteria, with antiserum. Antibody combines rapidly with the
particles, the primary interaction, but agglutination is a much slower process,
since adherence between particles occurs only when they touch each other.”
Page 131.
The instant specification describes assays in which “UTI solutions having
various concentrations of” UTI (page 8) were mixed with “Antibody Solution”
(page 9). After addition of antibody, the mixtures were allowed to react only five
minutes before the change in absorbance was measured. See page 10. Thus,
in the assays described in the specification, the reaction takes place between
soluble antigen and soluble antibody, and results can be measured in a few
minutes. Based on these characteristics, the assays described in the
specification appear to be what would normally be called “precipitation”, rather
than “agglutination”. However, an applicant is allowed to be his own
lexicographer. Since the meaning of the claim is reasonably definite when read
in light of the specification, we do not consider the claims indefinite. We will
Appeal No. 2002-1360 Page 7
Application No. 09/133,942

construe the claim term “agglutination” as being equivalent to the art-accepted
term “precipitation”.
2. Anticipation
The examiner rejected claims 1-8 as anticipated by Maehara. The
examiner characterized Maehara as “teach[ing] an agglutination assay using
polyethylene glycol for immunodiffusion of urinary trypsin inhibitor.” Examiner’s
Answer, page 3. According to the examiner, “[t]he samples used in the assay
were human serum from males and females (page 119 para. 3). Antibody was
added to the reaction solution and distributed onto the plate (page 119 para. 2).”
Id., page 4. The examiner concluded that “Maehara et al., teaches a method for
measuring the concentration of UTI [i]n a serum sample containing antibodies
directed against UTI which are not attached to an insoluble support . . . and
measured [sic] the degree of agglutination on immunodiffusion plates.” Id.
Appellant argues that “Maehara, which uses a single radial diffusion
detection, does not anticipate claim 1. In the Maehara single radial diffusion, the
antibodies are fixed in the gel plate and thus are adhered to an insoluble
support.” Appeal Brief, page 5. Appellant notes that Maehara cites a reference
by Mancini4 for a detailed disclosure of the immunodiffusion method. Appellant
argues that Mancini makes clear that the antibody used in the immunodiffusion
assay is added to an agar solution that is then allowed to solidify before being
used in the assay. See the Appeal Brief, page 5.

4 Mancini et al., “Immunochemical quantitation of antigens by single radial immunodiffusion,”
Immunohistochemistry, Vol. 2, pp. 235-254 (1965).
Appeal No. 2002-1360 Page 8
Application No. 09/133,942

“A claim is anticipated only if each and every element as set forth in the
claim is found, either expressly or inherently described, in a single prior art
reference.” Verdegaal Bros., Inc. v. Union Oil Co., 814 F.2d 628, 631, 2
USPQ2d 1051, 1053 (Fed. Cir. 1987). “[E]very limitation of a claim must
identically appear in a single prior art reference for it to anticipate the claim.”
Gechter v. Davidson, 116 F.3d 1454, 1457, 43 USPQ2d 1030, 1032 (Fed. Cir.
1997).
We agree that Maehara does not anticipate claim 1. As Appellant points
out, in the immunodiffusion assay used by Maehara, the anti-UTI antibodies are
incorporated into a solidified agar matrix. See Mancini, page 235: “By definition
the single-diffusion type of precipitin reaction is performed by incorporating one
of the two partners of the reaction, usually the antibody, into the agar gel, at a
uniform concentration, whereas the other reactant, usually the antigen, is
introduced into a well from which it is allowed to diffuse into the gel.” Maehara’s
disclosure confirms that the anti-UTI antibodies used were incorporated into the
agar gel. See page 119, first full paragraph: “The concentration of agar in the
gel plate was adjusted to 0.9% in 7 ml of veronal buffer . . . containing . . . various
amounts of anti-UTIγG.” Anti-UTIγG is short for anti-UTI rabbit γ-globulin. See
page 118.
Thus, in the assay disclosed by Maehara, the anti-UTI antibodies are
attached to the insoluble agar gel support. Maehara therefore does not
anticipate claim 1.
Appeal No. 2002-1360 Page 9
Application No. 09/133,942

3. Obviousness
The examiner also rejected all of the claims as obvious in view of the
disclosures of Craig and Maehara. According to the examiner, Craig discloses
an immunoassay that meets all of the limitations of claim 1 except that Craig
does not disclose the use of anti-UTI antibodies in the assay. See the
Examiner’s Answer, pages 4-6. Maehara teaches anti-UTI antibodies. The
examiner concluded that “it would have been obvious at the time of applicant[’]s
invention to use the method of agglutination where antibodies are not adhered to
an insoluble support as taught by Craig et al., with the antibodies of Maehara et
al., because Maehara et al., teach that it is well known i[n] the art to use UTI
antibodies to detect urinary trypsin inhibitor in agglutination assays.” Id., page 7.
Appellant argues that “Craig specifically teaches that the reactant (i.e.
antibody in the context of the present detection reaction) be bonded to the
polymer particles. Thus, Craig merely is teaching an insoluble support that is
considered to possess certain useful properties. As such, Craig also teaches
directly away from claim 1, which requires addition of antibody that is not
adhered to an insoluble support.” Appeal Brief, page 6. Appellant also argues
that “[e]ven if this combination is made . . . at best the combination would
suggest that an antibody against UTI could be bonded to the Craig shell-core
polymer particle. This still fails to suggest the addition of antibody not adhered to
an insoluble . . . support as required by claim 1.” Id.
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the initial
burden of presenting a prima facie case of obviousness.” In re Rijckaert, 9 F.3d
Appeal No. 2002-1360 Page 10
Application No. 09/133,942

1531, 1532, 28 USPQ2d 1955, 1956 (Fed. Cir. 1993). “The test for obviousness
is what the combined teachings of the references would have suggested to one
of ordinary skill in the art.” In re Young, 927 F.2d 588, 591, 18 USPQ2d 1089,
1091 (Fed. Cir. 1991). “The Patent and Trademark Office (PTO) must consider
all claim limitations when determining patentability of an invention over the prior
art.” In re Lowry, 32 F.3d 1579, 1582, 32 USPQ2d 1031, 1034 (Fed. Cir. 1994).
Here again, we agree with Appellant that the cited references do not
support the examiner’s rejection. The examiner characterizes Craig as teaching
a “method of agglutination where antibodies are not adhered to an insoluble
support.” See the Examiner’s Answer, page 7. The examiner, however, cites
nothing in the reference to support that interpretation.
We agree with Appellant’s interpretation of the reference: in Craig’s
assay, the antibodies are attached to an insoluble support, because the polymer
particles disclosed by Craig are insoluble. For example, in discussing the
process of binding antibody to the disclosed polymer particles, Craig teaches that
[a]fter sufficient time has elapsed to allow covalent attachment, a
separation of particle reagent from the suspending buffered
medium is effected, usually by centrifugation, although filtration,
gravitational settling, etc. would suffice to allow the removal of
unbound protein.

Column 10, lines 47-52.
Since Craig teaches that the particle-bound antibodies can be separated
from the medium by centrifugation, filtration or gravitational settling, it necessarily
follows that the particles are insoluble; soluble reagents cannot be taken out of
solution by centrifugation, filtration, or settling. Thus, neither Maehara nor Craig
Appeal No. 2002-1360 Page 11
Application No. 09/133,942

teach a method in which antibodies “are not adhered to an insoluble support,” as
required by claim 1. The rejection under 35 U.S.C. § 103 is reversed.
Other Issues
As discussed above (pages 3-6), the art-accepted meaning of the term
“agglutination” is an assay based on clumping of antibodies or antigens attached
to particulate antigens. “Precipitation”, on the other hand, means formation of
visible complex between soluble antigen and soluble antibody. Thus, the
claimed assay would conventionally be described as based on precipitation,
rather than agglutination. If the examiner’s initial search of the claimed assay
was directed toward art disclosing an “agglutination” assay involving only soluble
components, it probably did not produce the most relevant prior art.
Upon return of this case, the examiner should review the search that was
performed and, if necessary, re-search the relevant sources for assays based on
precipitation rather than agglutination. If a new search turns up prior art that
anticipates or renders obvious the instant claims, entry of new rejections under
35 U.S.C. § 102 and/or 35 U.S.C. § 103 would be appropriate.
We also note that Appellant has submitted two Information Disclosure
Statements since the Examiner’s Answer was filed. The examiner should act on
those IDSs as appropriate under 37 CFR § 1.97.
Appeal No. 2002-1360 Page 12
Application No. 09/133,942

Summary
The references cited by the examiner do not anticipate or render obvious
the claimed method. We therefore reverse the rejections on appeal.

REVERSED

William F. Smith )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Toni R. Scheiner )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Eric Grimes )
Administrative Patent Judge )
Appeal No. 2002-1360 Page 13
Application No. 09/133,942

Merchant & Gould PC
P.O. Box 2903
Minneapolis, MN 55402-0903

EG/jlb