Ex Parte QUAN et al

Board of Patent Appeals and Interferences

Feb 26, 2004

08993010 (B.P.A.I. Feb. 26, 2004)

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for publication and is not binding precedent of the Board.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. 35

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte STELLA QUAN,
PABLO VALENZUELA and ALAN POLITO
__________

Appeal No. 2003-1679
Application No. 08/993,010
__________

ON BRIEF
__________

Before WINTERS, SCHEINER, and ADAMS, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal under 35 U.S.C. § 134 from the
examiner’s final rejection of claims 1-3, 6-10, 13-17, 20-22 and 24. Claims 25-44
were withdrawn from consideration as a result of a restriction requirement.1
Claim 1 is illustrative of the subject matter on appeal and is reproduced
below:
1. A method of detecting Helicobacter pylori antibodies associated with
infection in a human subject comprising:
(a) reacting a biological sample from the subject with one or more
H. pylori type-common antigens provided in an H. pylori lysate
and with one or more purified type-specific H. pylori Type I

1 We note there is some degree of confusion regarding the status of claim 24. The examiner’s
statement of the status of the claims lists claim 24 as both involved in this appeal, and as
withdrawn from consideration. Answer, page 2. Similarly, appellants’ Brief (page 2), identifies
claim 24 as withdrawn. However, since the examiner has rejected claim 24 under 35 U.S.C. §
103, we have considered claim 24 in our deliberations.
Appeal No. 2003-1679 Page 2
Application No. 08/993,010

antigens, wherein the type-specific antigens are H. pylori
vacuolating cytotoxin (VacA) and cytotoxin associated antigen
(CagA), under conditions which allow H. pylori antibodies, when
present in the biological sample, to specifically bind with said
type-common antigens or said type-specific antigen(s),
(b) removing unbound antibodies;
(c) providing one or more moieties comprising a detectably labeled
anti-human immunoglobulin antibody which bind to said bound
antibodies;
(d) detecting the presence or absence of said one or more
moieties;
(e) correlating the presence of antibodies that specifically bind to
the type-specific antigens to infection with Type I H. pylori; and
(f) correlating the absence of antibodies that specifically bind to the
type-specific antigens and the presence of antibodies that
specifically bind to the type-common antigens to infection with
Type II H. pylori.

The references relied upon by the examiner are:
Crabtree et al. (Crabtree), “Mucosal Humoral Immune Response to Helicobacter
pylori in Patients with Duodenitis,” Digestive Diseases and Sciences, Vol. 36, No.
9, pp. 1266-1273 (1991)

Telford et al. (Telford), “Unraveling the pathogenic role of Helicobacter pylori in
peptic ulcer: potential new therapies and vaccines,” TIBTEC, Vol. 12, No. 10, pp.
420-436 (1994)

Figura, “Progress in defining the inflammatory cascade,” European Journal of
Gastroenterology & Hepatology, Vol. 7, No. 4, pp. 296-302 (1995)

Xiang et al. (Xiang), “Analysis of Expression of CagA and VacA Virulence Factors
in 43 Strains of Helicobacter pylori Reveals that Clinical Isolates Can Be Divided
into Two Major Types and that CagA Is Not Necessary for Expression of the
Vacuolating Cytotoxin,” Infection and Immunity, Vol. 63, No. 1, pp. 94-98 (1995)

GROUNDS OF REJECTION
Claims 1-3, 6-10 and 13-172 stand rejected under 35 U.S.C. § 103 as
being unpatentable over Figura in view of Xiang and Crabtree.

2 We note the following typographical error. In the statement of this rejection, the examiner
included claims 11 and 18. Since claims 11 and 18 are cancelled, we have not included these
claims in our deliberation.
Appeal No. 2003-1679 Page 3
Application No. 08/993,010

Claims 20-22 and 24 stand rejected under 35 U.S.C. § 103 as being
unpatentable over Figura in view of Xiang and Crabtree and further in view of
Telford.
We reverse.

DISCUSSION
Figura in view of Xiang and Crabtree:
The examiner finds (Answer, page 4), “Figura define Helicobacter pylori
strains by dividing them into two phenotypically distinct groups: Type I strains
express VacA and CagA; and Type II do not express VacA and CagA
proteins….” The examiner also finds (id.), Figura teach “[a] method of detecting
antibodies associated with Helicobacter pylori infection in humans….” According
to the examiner (Answer, page 5), Figura’s method of detecting antibodies
associated with Helicobacter infection comprises:
(a) reacting a biological sample from a subject with one or
more H.[ ]pylori type common antigens and one or more Type-I
specific antigens provided in an H.[ ]pylori whole cell preparation
(lysate) from a Type-I specific strain (see page 299, figure 5,
narrative, line 4). The common type antigens were shown to be
urease subunits A and B and H.[ ]pylori heat shock protein, and the
Type-I specific antigens shown were both VacA and CagA
antigens,

(b) removing unbound antibodies in light of the method being
incorporated by reference to Xiang who teaches the removal of
unbound antibodies (Xiang, page 95, col. 2, last paragraph, lines)
(see Figura reference, page 298, col. 2, paragraph 6, reference [1]
is Xiang et aI, 1995),
(c) providing a moiety to detect antibodies that specifically
bound to common and Type-I specific antigens were visualized
(see Figure 5 immunoreactive bands), and
(d) detecting the presence or absence detectably labeled
anti-human immunoglobulin antibody, thereby detecting the
presence or absence of H.[ ]pylori antibodies associated with
Appeal No. 2003-1679 Page 4
Application No. 08/993,010

infection in the subject.

The examiner relies on Xiang to teach a method using Western blot to distinguish
between Type I and Type II H. pylori clinical isolates based upon VacA and CagA
expression. Answer, page 7. The examiner relies on Crabtree (Answer, page 7),
to teach “the use of a detectably labeled anti-human immunoglobulin antibodies
in an analogous art for the purpose of detecting human antibodies associated
with Helicobacter pylori infection … in subject serum samples.”
According to the examiner (id.), Figure 5, lanes 3-6 of Figura demonstrate
that Figura distinguished Type I and Type II antibodies present in human serum
samples “through specific binding of common Type II and Type I specific
antigens,” wherein lane 6 illustrates “[a]ntibodies to Type II antigens were
detected, no binding to VacA or CagA,” and lanes 3-5 illustrate “antibodies to one
or more Type I specific antigens were detected.”
Based on this evidence, the examiner finds (Answer, bridging sentence,
pages 7-8), “it would have been prima facie obvious to a person of ordinary skill
in the arat [sic] the time the invention was made … to utilize detectably labeled
anti-human immunoglobulin to detect the presence or absence of human
antibodies that specifically bound to Helicobacter common and Type-I specific
antigens….”
Appellants, however, point out (Brief, page 11) that Figura “fails to
establish a definitive correlation between expression of VacA and CagA antigens
and infectivity.” In addition, appellants emphasize (id., emphasis removed),
Figura admits “that CagA and VacA expression does not necessarily correlate
Appeal No. 2003-1679 Page 5
Application No. 08/993,010

with infectivity. (Figura, page 298, right column; Figure 5 and accompanying
legend).”
Figura characterizes H. pylori Type I strains as expressing VacA and
CagA, and Type II strains as being VacA- and CagA-negative. See Figura,
Abstract. Consistent with appellants’ analysis (Brief, page 11), Figura teaches
(page 298, second column, last paragraph, endnotes omitted), Western blots
are not quantitative and sometimes difficult to interpret. In Fig. 5,
for example, disparate immune responses to CagA and VacA can
be observed (lanes 3 to 5). These proteins are expressed together
in more than 70% of H. pylori isolates. Surprisingly, out of the
hundreds of Western blots we have performed, VacA immune
recognition was observed in only about 15% of cases in which
serum samples reacted with CagA, and in about 5% of cases which
were seronegative for CagA. Although the results of Xiang et al.
explain the existence of strains expressing only VacA (in about 10%
of isolates), the examples shown in Fig. 5 indicate that more
studies are needed to clarify the situation in vivo.

We remind the examiner, that in order to establish a prima facie case of
obviousness, there must be both some suggestion or motivation to modify the
references or combine reference teachings and a reasonable expectation of
success. In re Vaeck, 947 F.2d 488, 493, 20 USPQ2d 1438, 1442 (Fed. Cir.
1991). On this record, while Figura refers to Xiang to “explain the existence of
strains expressing only VacA,” Figura expressly states that “more studies are
needed to clarify the situation in vivo.” In this regard, notwithstanding the
examiner’s position to the contrary (Answer, page 16, paragraph 15), appellants’
claimed invention is directed to a method of detecting Helicobacter pylori
antibodies associated with infection in a human subject comprising, inter alia,
correlating the presence of antibodies that bind to specific antibodies to either
Appeal No. 2003-1679 Page 6
Application No. 08/993,010

infection with Type I or Type II H. pylori. As appellants’ point out (Brief, page 11),
Figura makes no such correlation, but instead, expressly states that more studies
are necessary. Furthermore, while both Figura and the examiner direct our
attention to Xiang, Xiang classifies some CagA- and VacA-negative H. pylori
strains as Type I, and others as Type II. See Xiang, page 95, Table 1, strains 32,
33, and 36-43. Accordingly, we agree with appellants’ (Brief, page 13), Xiang
does not provide a clear “correlation between anti-CagA and anti-VacA
antibodies and [T]ype I infection.”
In this regard, we note the examiner’s reference to Xiang, page 97,
second column, third paragraph. Answer, page 19. This portion of Xiang notes
only that “Type II bacteria do not have the gene coding for CagA and do not
produce CagA…,” there is no discussion or recognition that the VacA antigen is
also associated with Type I strains, as is required by appellants’ claimed
invention. With regard to VacA, Xiang discusses the possibility of “intermediate
phenotypes.” See Xiang, page 97, column 2, paragraphs 5 and 6; Answer, page
19. However, Xiang expressly states (first sentence, bridging paragraph, pages
97-98), “[f]rom these observations, we conclude that an understanding of the
linked expression of CagA and VacA must await characterization of the genetic
differences between [T]ype I and [T]ype II bacteria….” Based on this evidence, it
is our opinion that Xiang failed to recognize that CagA and VacA were associated
with Type I H. pylori. We remind the examiner, in determining whether the
claimed invention is obvious, a prior art reference must be read as a whole and
consideration must be given where the reference teaches away from the claimed
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Application No. 08/993,010

invention. Akzo N.V., Aramide Maatschappij v.o.f. v. United States Int’l Trade
Comm’n, 808 F.2d 1471, 1481, 1 USPQ2d 1241, 1246 (Fed. Cir. 1986).
We note the examiner’s assertion (Answer, page 15), “[i]t is the position of
the examiner that Figura in view of Xiang clearly provides a reasonable
expectation of success in detecting the presence of humoral Type I and Type II
antibodies (see Figure 5) indicative of H.[ ]pyloir Type I or Type II strains infecting
the patient.” However, as discussed above, on this record, neither Figura nor
Xiang provide a correlation of the presence or absence of specific antibodies to
infection with Type I or Type II H. pylori. While the examiner has asserted that a
correlation exists, the evidence of record does not support this assertion. We
remind the examiner that “to imbue one of ordinary skill in the art with knowledge
of the invention in suit, when no prior art reference or references of record
convey or suggest that knowledge, is to fall victim to the insidious effect of a
hindsight syndrome wherein that which only the inventor taught is used against
its teacher.” W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 1553,
220 USPQ 303, 312-13 (Fed. Cir. 1983).
Crabtree, relied upon by the examiner (Answer, page 7) to teach “the use
of a detectably labeled anti-human immunoglobulin antibodies…,” fails to make
up for the deficiencies in the combination of Figura and Xiang. Accordingly, we
reverse the rejection of claims 1-3, 6-10 and 13-17 under 35 U.S.C. § 103 as
being unpatentable over Figura in view of Xiang and Crabtree.
Figura in view of Xiang and Crabtree and further in view of Telford:
Appeal No. 2003-1679 Page 8
Application No. 08/993,010

Claim 20 is drawn to a method of monitoring a human subject undergoing
therapy for Helicobacter pylori infection comprising, inter alia, the method of
detecting Helicobacter pylori antibodies as set forth in claim 1.
The combination of Figura in view of Xiang and Crabtree was discussed
above. While not clearly articulated by the examiner (see Answer, pages 9 and
28-29), it appears that the examiner relies on Telford to teach (bridging
paragraph, pages 421-422), “a simple scheme, in which all H. pylori strains could
be partitioned into two groups, which either express (Type I) or do not express
(Type II) the cytotoxin [VagA] and the CagA proteins.”
We note, however, that Telford published before either of the Figura or
Xiang references. As discussed above, with regard to Figura and Xiang, the later
published evidence on this record teaches away from the “simple scheme”
discussed by Telford. To establish a prima facie case of obviousness, the
examiner must show “some objective teaching in the prior art or that knowledge
generally available to one of ordinary skill in the art would lead that individual to
combine the relevant teachings of the references.” In re Fine, 837 F.2d 1071,
1074, 5 USPQ2d 1596, 1598 (Fed. Cir. 1988). There is no suggestion to
combine, however, if a reference teaches away from its combination with another
source. See id. at 1075, 5 USPQ2d at 1599. “A reference may be said to teach
away when a person of ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or would be led in a
direction divergent from the path that was taken by the applicant ... [or] if it
suggests that the line of development flowing from the reference’s disclosure is
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Application No. 08/993,010

unlikely to be productive of the result sought by the applicant.” In re Gurley, 27
F.3d 551, 553, 31 USPQ2d 1130, 1131 (Fed. Cir. 1994). In our opinion, for the
reasons discussed above, both Figura and Xiang would have led a person of
ordinary skill in the art at the time the invention was made away from the simple
scheme discussed by Telford, and accordingly, away from appellants’ claimed
invention.
Accordingly, we reverse the rejection of claims 20-22 and 24 under 35
U.S.C. § 103 as being unpatentable over Figura in view of Xiang and Crabtree
and further in view of Telford.
Appeal No. 2003-1679 Page 10
Application No. 08/993,010

Having determined that the examiner has not established a prima facie
case of obviousness, we find it unnecessary to discuss the del Giudice
Declaration, relied on by appellants (Brief, pages 20-23) to rebut any such prima
facie case.

REVERSED

)
Sherman D. Winters )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Toni R. Scheiner )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Donald E. Adams )
Administrative Patent Judge )
Appeal No. 2003-1679 Page 11
Application No. 08/993,010

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