Ex Parte Hale et al

Board of Patent Appeals and Interferences

Aug 15, 2011

11347307 (B.P.A.I. Aug. 15, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/347,307 02/06/2006 Laura P. Hale 01579-1079 3602
23117 7590 08/15/2011
NIXON & VANDERHYE, PC
901 NORTH GLEBE ROAD, 11TH FLOOR
ARLINGTON, VA 22203
EXAMINER
REDDIG, PETER J
ART UNIT PAPER NUMBER
1642
MAIL DATE DELIVERY MODE
08/15/2011 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte LAURA P. HALE and DAVID PRICE
__________

Appeal 2010-010589
Application 11/347,307
Technology Center 1600
__________

Before TONI R. SCHEINER, LORA M. GREEN, and
FRANCISCO C. PRATS, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 1-13 and 24. We have jurisdiction under 35
U.S.C. § 6(b).
Appeal 2010-010589
Application 11/347,307

2
STATEMENT OF THE CASE
Claims 1 and 8 are the independent claims on appeal, and read as
follows:
1. A method of diagnosing cancer in a test mammal comprising assaying
for the level of zinc α-2-glycoprotein (ZAG) present in a biological sample
from said test mammal and comparing that level to the level of ZAG present
in a biological sample from a control, non-tumor bearing mammal, an
elevated level of ZAG in the biological sample from said test mammal
relative to the level of ZAG in the biological sample from said control
indicating the presence of cancer in said test mammal.

8. A method of diagnosing an inflammatory disease or disorder in a test
mammal comprising assaying for the level of zinc α-2-glycoprotein (ZAG)
present in a biological sample from said test mammal and comparing that
level to the level of ZAG present in a biological sample from a control
mammal, an elevated level of ZAG in the biological sample from said test
mammal relative to the level of ZAG in the biological sample from said
control indicating the presence of an inflammatory disease or disorder in
said test mammal.

The following grounds of rejection are before us for review:
I. Claims 8-13 and 24 stand rejected under 35 U.S.C. § 112, first
paragraph, on the grounds that the Specification fails to enable the
full scope of the claimed subject matter.
II. Claims 1-13 and 24 stand rejected under 35 U.S.C. § 102(b) as
being anticipated by Frenette.1
III. Claims 1-4, 6, 8, 9, 11, and 13 stand rejected under 35 U.S.C.
§ 102(b) as being anticipated by Todorov.2

1 Frenette et al., The Major 40-kDa Glycoprotein in Human Prostatic Fluid
is Identical to Zn-α2-Glycoprotein, 11 THE PROSTATE 257-270 (1987).
Appeal 2010-010589
Application 11/347,307

3
IV. Claims 1-4, 6-11, 13, and 24 stand rejected under 35 U.S.C.
§ 102(b) as being anticipated by Bundred.3

We affirm Rejection I, reverse Rejections II-IV, but enter new
grounds of rejection for independent claims 1 and 8.
ISSUE (Rejection I)
Has the Examiner established by a preponderance of the evidence that
the Specification fails to enable the full scope of the claimed subject matter?

FINDINGS OF FACT
FF1. The Specification teaches:
The present invention relates, in general, to methods of
diagnosing and monitoring cancer and inflammatory
diseases/disorders and, in particular, to methods of diagnosing
and monitoring cancer and inflammatory diseases/disorders that
comprise assaying for elevated levels of zinc alpha-2-
glycoprotein (ZAG) in serum and other body fluids. The
invention also relates to methods of inhibiting thymic atrophy,
including tumor-associated atrophy.

(Spec. 1.)
FF2. The Specification teaches further:
The method of the invention can be used in the diagnosis
of a variety of tumor types that either produce ZAG or that
occur in organs in which ZAG is normally produced. Examples
include prostate tumors, breast tumors, colon tumors, squamous

2 Todorov et al., Purification and Characterization of a Tumor Lipid-
mobilizing Factor, 58 CANCER RESEARCH 2353-2358 (1998).
3 Bundred et al., 27 EUROPEAN J. OF CANCER 549-552 (1991).
Appeal 2010-010589
Application 11/347,307

4
cell carcinomas and pancreatic tumors. The samples used can
be solid (e.g., stool) or liquid. Advantageously, the sample
used is a serum or plasma sample, however, other bodily fluids,
such as urine, cerebrospinal fluid, seminal fluid, sweat and
nipple aspirates, can also be used. In the case of serum,
untreated serum can be used as can treated serum, e.g.,
fractionated serum in which certain components (for example,
albumin) have been removed, or serum in which certain
materials have been added.

(Id. at 8.)
FF3. As to inflammatory diseases/disorders, the Specification teaches:
In another embodiment, the present invention relates to a
method of diagnosing or monitoring an inflammatory disease or
disorder that is associated with injury to the ZAG-producing
epithelium of the involved tissue or organ. The method
comprises assaying for the level of ZAG present in a biological
test sample and comparing that level to a control sample, an
elevated level of ZAG in the test sample being indicative of the
presence of an inflammatory disease or disorder.
Diseases/disorders that can be detected in accordance with this
embodiment include inflammation of the breast, prostate, liver
or salivary, bronchial, gastrointestinal or sweat glands.
Inflammatory bowel disease is a specific example of a disease
detectable in accordance with this embodiment. In a preferred
aspect of this embodiment, the biological sample used is a
serum sample, however, other biological samples can also be
used, including saliva samples. The level of ZAG present can
be determined using techniques described above.

(Id. at 10-11.)
FF4. Example 1 of the Specification is drawn to ZAG expression by
malignant prostatic epithelium (see id. at 12), and Example 2 is drawn to
looking at the role of ZAG in tumor-associated thymic atrophy (see id. at
26).
Appeal 2010-010589
Application 11/347,307

5
FF5. In looking at serum ZAG levels in patients with ZAG-positive
prostate cancers, the Specification notes that “[w]hile larger studies with
long-term follow-up are needed, it appears that elevated serum ZAG levels
occur early in prostate cancer progression, prior to its detectability by digital
rectal exam or elevated PSA” (id. at 24).
FF6. The Examiner’s statement of the rejection may be found at pages 3-7
of the Answer.
FF7. Specifically, the Examiner finds that while the claims enable a method
of diagnosing cancer by assaying for ZAG levels, the Specification “does
not reasonably provide enablement for a method of diagnosing an
inflammatory disease or disorder” using ZAG levels (Ans. 3-4).
FF8. The Examiner notes that “inflammatory diseases and disorders are
broad group of maladies with distinct etiologies and pathologies and neither
the specification nor the art of record has provided sufficient guidance or
direction to establish a nexus between any inflammatory disease or disorder,
other than cancer, and elevated levels of ZAG” (id. at 6).
FF9. The Examiner relies on Van Noort4 as evidence that inflammatory
diseases such as autoimmune diseases encompass a broad range of maladies,
such as diabetes mellitus, rheumatoid arthritis, multiple sclerosis, etc., and
that the “precise role of the immune system in the initiation and perpetuation
of autoimmune diseases can only be speculated on and the self-antigens
trigger disease in human cannot be definitively answered” (id. at 7 (citing
Van Noort, p. 129)).

4 Johannes M. Van Noort and Sandra Amor, Cell Biology of Autoimmune
Diseases, 178 INTERNATIONAL REVIEW OF CYTOLOGY 127-206 (1998).
Appeal 2010-010589
Application 11/347,307

6
FF10. The Examiner thus concludes:
Given that neither the specification nor the art of record has
demonstrated any nexus between the broadly claimed
inflammatory diseases and disorders, other than cancer, and
elevated levels of ZAG, given the breadth of diseases
encompassed by the claims, and given the unpredictable and
undefined nature of the etiology of many inflammatory diseases
or disorders, undue experimentation would be required to use
the method as broadly claimed.

(Ans. 7.)

PRINCIPLES OF LAW
As the court stated in In re ’318 Patent Infringement Litigation, 583
F.3d 1317, 1327 (Fed. Cir. 2009):
“If mere plausibility were the test for enablement under section
112, applicants could obtain patent rights to ‘inventions’
consisting of little more than respectable guesses as to the
likelihood of their success. When one of the guesses later
proved true, the ‘inventor’ would be rewarded the spoils instead
of the party who demonstrated that the method actually worked.
That scenario is not consistent with the statutory requirement
that the inventor enable an invention rather than merely
proposing an unproved hypothesis.”

Id. (quoting Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1325
(Fed. Cir. 2005)).

ANALYSIS
Appellants argue that the fact that the phrase “‘inflammatory disease
or disorder’” “may encompass a number of diseases/disorders does not
negate the fact that a patent applicant enjoys the presumption that the
Appeal 2010-010589
Application 11/347,307

7
invention can be practiced as claimed” (App. Br. 9). Appellants assert it is
the Examiner’s burden to provide evidence of non-enablement, which the
Examiner has not done (id.). Appellants thus contend that the rejection
should be reversed.
As to claim 24, Appellants argue that the claim is limited to
inflammatory bowel disease, with the sample being a serum sample, which
is supported by the Specification (see FF3) (App. Br. 9). Appellants argue
there is no requirement for a working example, and that the “Examiner
offers nothing by way of explanation/evidence to support the rejection of
this claim as non-enabled” (id.)
We agree with the Examiner that the Specification fails to enable the
use of assaying for increased levels of ZAG as a diagnostic for an
inflammatory disease or disorder, such as inflammatory bowel disease.
First, the Examiner cites Van Noort as evidence that inflammatory diseases
covers a broad range of diseases, including diseases such as multiple
sclerosis, diabetes mellitus, and rheumatoid arthritis, and that it is unclear
what role the immune system plays or which autoantigens are implicated in
those diseases. Thus, Van Noort is evidence that inflammatory disorders
cover a broad range of diseases and disorders whose etiologies, symptoms,
and treatments can greatly differ. The Specification has presented no
evidence how, for example, ZAG expression may be correlated with
diseases such as diabetes mellitus, multiple sclerosis, or inflammatory bowel
disease, other than noting that it is present in plasma, and the cytoplasm of
normal secretory epithelial cells, including those of the breast, prostate, and
liver (Spec. 1-2).
Appeal 2010-010589
Application 11/347,307

8
While we agree that there is no requirement for a working example, in
the diagnostic art, there need be some evidence correlating a potential
diagnostic marker to a disease or disorder. The Specification only provides
evidence for cancers, such as prostate cancer, which is not sufficient support
for the genus of inflammatory diseases and disorders, for the reasons set
forth above.

CONCLUSION OF LAW
We conclude that the Examiner has established by a preponderance of
the evidence that the Specification fails to enable the full scope of the
claimed subject matter. We thus affirm the rejection of claims 8-13 and 25
under 35 U.S.C. § 112, first paragraph, on the grounds that the Specification
fails to enable the full scope of the claimed subject matter.

ISSUES (Rejections II-IV)
Has the Examiner established by a preponderance of the evidence that
each of Frenette, Todorov, and Bundred anticipates the claimed methods?

FINDINGS OF FACT
FF11. The Examiner’s statement of the anticipation rejections may be found
at pages 7-12 of the Answer.
FF12. As to the each of the anticipation rejections, the Examiner finds that
each reference teaches all of the method steps as required by the independent
claims, that is, assaying for the level of ZAG present in a biological sample
from said test mammal and comparing that level to the level of ZAG present
Appeal 2010-010589
Application 11/347,307

9
in a biological sample from a control, nontumor bearing mammal (see Ans.
8, 9, and 11).
FF13. Thus, according to the Examiner:
[T]he claimed methods are anticipated because the method of
the prior art will inherently be a method of diagnosing
cancer/prostate cancer or a method of screening a test mammal
to determine whether said test mammal is at an increased risk
for cancer. See Ex parte Novitski 26 USPQ[2d] 1389 (BPAI
1993). Although the reference does not specifically state that it
is a method of diagnosing cancer, prostate cancer, or an
inflammatory disease or disorder or a method of screening a test
mammal to determine whether said test mammal is at an
increased risk for cancer, the claimed method appears to be the
same as the prior art method, absent a showing of unobvious
differences.

(Id. at 8; see also id. at 9-11.)

PRINCIPLES OF LAW
If the claim preamble, when read in the context of the entire
claim, recites limitations of the claim, or, if the preamble is
“necessary to give life, meaning, and vitality” to the claim, then
the claim preamble should be construed as if in the balance of
the claim. . . . If, however, the body of the claim fully and
intrinsically sets forth the complete invention, including all of
the limitations, and the preamble offers no distinct definition of
any of the claimed invention’s limitations, but rather merely
states, for example, the purpose or intended use of the
invention, then the preamble is of no significance to claim
construction because it cannot be said to constitute or explain a
claim limitation.

Pitney Bowes, Inc. v. Hewlett Packard Co., 182 F.3d 1298, 1305 (Fed. Cir.
1999) (citations omitted).
Appeal 2010-010589
Application 11/347,307

10
In order to serve as an anticipatory reference, “the reference must
disclose each and every element of the claimed invention, whether it does so
explicitly or inherently.” In re Gleave, 560 F.3d 1331, 1334 (Fed. Cir.
2009).

ANALYSIS
Appellants assert that the Examiner’s statements regarding the
patentable weight of the preamble are not relevant to the analysis, as the last
clause of independent claims 1 and 8 links back to the preamble (App. Br.
10-12).
We agree with Appellants. Both of independent claims 1 and 8 have a
step of correlating an elevated level of ZAG in the biological sample back to
the recitation in the preamble. That is, claim 1 recites that “an elevated level
of ZAG in the biological sample from said test mammal relative to the level
of ZAG in the biological sample from said control indicating the presence of
cancer in said test mammal,” and claim 8 recites that “an elevated level of
ZAG in the biological sample from said test mammal relative to the level of
ZAG in the biological sample from said control indicating the presence of an
inflammatory disease or disorder in said test mammal.” Thus, the claims
require a step of diagnosing cancer or inflammatory disease in the test
mammal. As the Examiner has not addressed that limitation, we are
compelled to reverse Rejections II, III, and IV.
Ex parte Novitski, 26 USPQ2d 1389 (BPAI 1993) does not convince
us to the otherwise. The method at issue in that case was drawn to a
“method for protecting a plant from plant pathogenic nematodes which
Appeal 2010-010589
Application 11/347,307

11
comprises the step of inoculating said plant with a nematode-inhibiting
strain of P. cepacia which strain colonizes said plant.” Id. at 1390. The
Board found that the step of inoculating the plant inherently protected the
plant from pathogenic nematodes. Id. at 1391. In contrast, as discussed
above, the claims at issue require a step of correlating an elevated level of
ZAG to the diagnosis of cancer and/or inflammatory disease. Thus, a
finding that the method steps are taught by each of the references (see FF12)
is not sufficient to support a finding of anticipation.

CONCLUSION OF LAW
We conclude that the Examiner has not established by a
preponderance of the evidence that each of Frenette, Todorov, and Bundred
anticipates the claimed methods. We are thus compelled to reverse
Rejections II, III, and IV.

NEW GROUNDS OF REJECTION
We make the following new grounds of rejection pursuant to 37
C.F.R. § 41.50(b).
Claims 1 and 8 are rejected under 35 U.S.C. § 103(a) as being
rendered obvious by Todorov.
Claims 1 and 8 are rejected under 35 U.S.C. § 103(a) as being
rendered obvious by Bundred.

Appeal 2010-010589
Application 11/347,307

12
FINDINGS OF FACT
FF14. Todorov teaches that “[c]ancer patients with weight loss showed
urinary excretion of a lipid-mobilizing factor (LMF) . . . .” (Todorov,
Abstract.)
FF15. Todorov teaches further that the evidence supports that LMF is
identical to Zn-α2-glycoprotein, i.e., ZAG (id. at p. 2358, first column).
FF16. Todorov teaches that the LMF/ZAG was not detected in the urine of
cancer patients without weight loss, nor in normal subjects (id. at p. 2355,
first column).
FF17. Todorov teaches purification of LMF/ZAG from urine (id. at p. 2354,
first col.), and also teaches detection of LMF/ZAG by western blotting (id. at
2356, Figs. 1 and 2).
FF18. Bundred looks at the levels of ZnGP (ZAG) in breast fluid and serum
in woman with and without breast disease to determine its potential clinical
relevance (Bundred, p. 551, paragraph bridging cols. 1 and 2).
FF19. Bundred used radioimmunodiffusion to assay for ZnGP (id. at 550,
first col.).
FF20. Bundred teaches that “levels of ZnGP were significantly higher in
women with breast cancer compared to woman with ‘normal breast’ or
benign breast disease and the highest levels were seen in women with
positive axillary nodes or advanced disease suggesting ZnGP may be a
marker of disease ‘load’ in breast cancer” (id. at 551, second column).
FF21. According to Bundred, “ZnGP is a serum and breast marker of
apocrine activity and may prove to be a useful prognostic marker in breast
cancer” (id. at Abstract).
Appeal 2010-010589
Application 11/347,307

13
FF22. We find, as did the Examiner, that as the inflammatory response plays
a critical role in cancer, cancer is encompassed by inflammatory disease or
disorder (Ans. 5).

PRINCIPLES OF LAW
In KSR Int’l v. Teleflex Inc., 550 U.S. 398, 415 (2007), the Supreme
Court rejected a rigid application of a teaching-suggestion-motivation test in
the obviousness determination. The Court emphasized that “the
[obviousness] analysis need not seek out precise teachings directed to the
specific subject matter of the challenged claim, for a court can take account
of the inferences and creative steps that a person of ordinary skill in the art
would employ.” Id. at 418.
In determining whether obviousness is established by combining the
teachings of the prior art, “the test is what the combined teachings of the
references would have suggested to those of ordinary skill in the art.” In re
Keller, 642 F.2d 413, 425 (CCPA 1981). In addition, a reference disclosure
is not limited only to its preferred embodiments, but is available for all that it
discloses and suggests to one of ordinary skill in the art. In re Lamberti, 545
F.2d 747, 750 (CCPA 1976).

ANALYSIS
Todorov teaches the steps of “assaying for the level of zinc α-2-
glycoprotein (ZAG) present in a biological sample from said test mammal
and comparing that level to the level of ZAG present in a biological sample
from a control, non-tumor bearing mammal” (see, e.g., FFs 14, 16, and 17).
Appeal 2010-010589
Application 11/347,307

14
While Todorov fails to specifically teach using the level of ZAG as a
diagnostic for an inflammatory disease/disorder, such as cancer, Todorov
does teach that cancer patients with weight loss show elevated levels of
LMF/ZAG in urine, while LMF/ZAG was not detected in the urine of cancer
patients without weight loss, nor in normal subjects (FF16). Thus, it would
have been obvious to the ordinary artisan to use LMF/ZAG as a diagnostic
marker for cancer patients who are at risk for weight loss.
Bundred also teaches the steps of “assaying for the level of zinc α-2-
glycoprotein (ZAG) present in a biological sample from said test mammal
and comparing that level to the level of ZAG present in a biological sample
from a control, non-tumor bearing mammal” (see, e.g., FFs18 and 19).
While Bundred fails to specifically teaching using the level of ZAG as a
diagnostic for an inflammatory disease/disorder, such as cancer, Bundred
does teach that levels of ZAG were significantly higher in women with
breast cancer compared to woman with normal breast or benign breast
disease and the highest levels were seen in women with positive axillary
nodes or advanced disease (FF20). Thus, it would have been obvious to the
ordinary artisan to use ZAG as a diagnostic marker for breast cancer.
As to Appellants assertion that Bundred teaches “that ZnGP may
prove to be useful as a prognostic marker in benign and malignant breast
disease” (App. Br. 12), the ordinary artisan recognizes that it is routine to
use qualifiers such as “may” in scholarly, peer-reviewed articles, such as that
of Bundred. In that regard, we note that Appellants’ Specification also uses
the qualifier “appears” in stating that “it appears that elevated serum ZAG
Appeal 2010-010589
Application 11/347,307

15
levels occur early in prostate cancer progression, prior to its detectability by
digital rectal exam or elevated PSA” (FF5).
In light of the above, we conclude that independent claims 1 and 8 are
unpatentable under 35 U.S.C. § 103(a) over either Todorov or Bundred.
With respect to claims 2-7, 9-13 and 24, although we decline to reject every
claim under our discretionary authority under 37 C.F.R. § 41.50(b), we
emphasize that our decision does not mean the remaining claims are
patentable. Rather, we merely leave the patentability determination of these
claims to the Examiner. See MPEP § 1213.02.

SUMMARY
We affirm the rejection of claims 8-13 and 24 under 35 U.S.C. § 112,
first paragraph, on the grounds that the Specification fails to enable the full
scope of the claimed subject matter.
The rejections of claims 1-13 and 24 under 35 U.S.C. § 102(b) as
being anticipated by Frenette; claims 1-4, 6, 8, 9, 11, and 13 under 35 U.S.C.
§ 102(b) as being anticipated by Todorov; and claims 1-4, 6-11, 13, and 24
under 35 U.S.C. § 102(b) as being anticipated by Bundred, are reversed.
We enter new grounds of rejection of independent claims 1 and 8
under 35 U.S.C. § 103(a) as being rendered obvious by either Todorov or
Bundred.

Regarding the affirmed rejection(s) that have not been denominated as
new grounds of rejection, 37 C.F.R. § 41.52(a)(1) provides “Appellants may
Appeal 2010-010589
Application 11/347,307

16
file a single request for rehearing within two months from the date of the
original decision of the Board.”
This decision contains new grounds of rejection pursuant to 37 C.F.R.
§ 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of rejection
pursuant to this paragraph shall not be considered final for judicial review.”
37 C.F.R. § 41.50(b) also provides that the Appellants, WITHIN
TWO MONTHS FROM THE DATE OF THE DECISION, must exercise
one of the following two options with respect to the new grounds of
rejection to avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of the claims so
rejected or new evidence relating to the claims so rejected, or both, and have
the matter reconsidered by the examiner, in which event the proceeding will
be remanded to the examiner….
(2) Request rehearing. Request that the proceeding be reheard under § 41.52
by the Board upon the same record….
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§1.136(a)(1)(iv)(2007).

AFFIRMED-IN-PART; 37 C.F.R. § 41.50(b)

cdc