Ex Parte Das

Board of Patent Appeals and Interferences

Feb 23, 2010

11500113 (B.P.A.I. Feb. 23, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte KIRON M. DAS
____________

Appeal 2009-001498
Application 11/500,113
Technology Center 1600
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Decided: February 23, 2010
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Before DONALD E. ADAMS, LORA M. GREEN, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal by the Patent Applicant from the Patent
Examiner’s rejection of claims 1 and 2 in U.S. Application Serial No.
11/500,113. The Board’s jurisdiction for this appeal is under 35 U.S.C.
§§ 6(b) and 134. We affirm.

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STATEMENT OF THE CASE
There are only two pending claims in the application involved in this
appeal. Claim 1 is drawn to a method of treating ulcerative colitis (“UC”)
with a compound that inhibits the interaction of colon epithelium-specific
protein (“CEP”) and human tropomyosin 5 (hTM5). Claim 2 is to a method
of inhibiting the externalization of hTM5 by contacting cells with an agent
that blocks secretion of hTM5 and CEP.
In response to a Restriction Requirement, Appellant elected the
compound phorbol-12-myristate-13-acetate (“PMA”) for the claimed
methods of treating UC (claim 1) and inhibiting the externalization of hTM5
(claim 2) (Reply to Restriction Requirement, Feb. 20, 2007). Therefore,
while the claims listed in the Claim Appendices (App. Br. 14) do not recite a
particular compound, the claims were examined as if they were limited to
PMA (Ans. 4).
The Specification discloses that hTM5 is externalized from colon cells
and that CEP, a protein found in colon cells, is “important for the release
[externalization] of hTM outside the cell.” (Id. at 4:15-17). The
Specification teaches that the externalized hTM5 stimulates an immune
response in subjects with UC and may responsible for a deleterious
autoimmune response (id. at 4:1-20; 12:17 to 13:11). The Specification
characterizes the invention as treating UC subjects with agents that inhibit
hTM5 externalization and the interaction of hTM5 and CEP to reduce the
presence of hTM in the treated subject (id. at 14:8-24). PMA is identified in
the Specification as such an effective agent (id. at 11:26 to 12:6).
The claims are rejected by the Examiner under two grounds:
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Claims 1 and 2 under 35 U.S.C. § 112, first paragraph, as failing to
comply with the enablement requirement (Ans. 4); and
Claim 2 under 35 U.S.C. § 102(b) as anticipated by Dumont (U.S. Pat.
No. 4,914,188, issued Apr. 3, 1990) (Ans. 10).
In support of the enablement rejection, the Examiner cited the Han
publication (Han et al., 95 PROC. NATL. ACAD. SCI. 5357-5361, Apr. 1998).
Claims 1 and 2 are reproduced below:
1. A method for treating ulcerative colitis, comprising
administering a compound to a human subject, wherein said
compound inhibits interaction between colon epithelium-
specific protein and human tropomyosin 5 thereby treating
ulcerative colitis.

2. A method for inhibiting the externalization of human
tropomyosin 5 (hTM5) comprising contacting a cell with an
agent which blocks the secretion of a hTM5 and colon
epithelium-specific protein complex thereby inhibiting the
externalization of hTM5.

ENABLEMENT REJECTION
Claims 1 and 2 stand rejected under 35 U.S.C. § 112, first paragraph,
as failing to comply with the enablement requirement (Ans. 4).
Statement of the Issue
The issue in this rejection is whether Appellant showed an error in the
Examiner’s conclusion that it was unpredictable at the time of the invention
that PMA could be utilized to treat ulcerative colitis in human subjects (Ans.
9; App. Br. 7). The Examiner’s position as to the lack of predictability is
based on three key findings:
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• PMA is a pro-inflammatory agent and therefore would not have
reasonably been expected to treat UC which is known to be an inflammatory
condition (id. at 5-6);
• As demonstrated by Han, PMA has adverse effects on humans and
therefore it was unpredictable that PMA would be useful to treat UC (id. at
6-7); and
• There is inadequate basis on which to extrapolate from the in vitro
result that PMA inhibits secretion of hTM5 in colon tumor cells to treating
UC in a human subject (id. at 8).
We therefore focus our analysis on whether the Examiner erred in
making these findings.
Principles of Law
When rejecting a claim under the enablement
requirement of section 112, the PTO bears an initial burden of
setting forth a reasonable explanation as to why it believes that
the scope of protection provided by that claim is not adequately
enabled by the description of the invention provided in the
specification of the application; this includes, of course,
providing sufficient reasons for doubting any assertions in the
specification as to the scope of enablement. If the PTO meets
this burden, the burden then shifts to the applicant to provide
suitable proofs indicating that the specification is indeed
enabling. ... Marzocchi, 439 F.2d at 223-24.
In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993).
It may be difficult to predict, however, whether a novel
compound will exhibit pharmacological activity, even when the
behavior of analogous compounds is known to those skilled in
the art. Consequently, testing is often required to establish
practical utility. See, e.g., Blicke, 241 F.2d at 720. . . . But the
test results need not absolutely prove that the compound is
pharmacologically active. All that is required is that the tests be
“reasonably indicative of the desired [pharmacological]
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response.” Nelson, 626 F.2d at 856 . . . (emphasis added). In
other words, there must be a sufficient correlation between the
tests and an asserted pharmacological activity so as to convince
those skilled in the art, to a reasonable probability, that the
novel compound will exhibit the asserted pharmacological
behavior. See Cross, 753 F.2d at 1050.
Fujikawa v. Wattanasin, 93 F.3d 1559, 1564 (Fed. Cir. 1996).

Findings of Fact
1. The Specification discloses that the “physical interaction of hTM with
CEP” is “important for the release of hTM outside the cell.” (Spec. 4: 15-
17.)
2. “Since an autoantibody response to hTM is associated with ulcerative
colitis, the condition can be treated by decreasing the externalization of hTM
in the colon.” (Id. at 4: 16-20.)
3. The Specification teaches that PMA prevents secretion and
externalization of the CEP-hTM complex from colon cells (id. at 4:20 to
5:12; 11:29-30).
4. The Specification describes an in vitro system in which the effect of PMA
on secretion of hTM5 from LS-180 colon cancer cells was studied (id. at
31:19-32:7; 21:1-4).
5. The Specification reports that PMA “almost totally inhibited the
secretion” of hTM5 from the LS-180 cells, which was “a surprising result”
(id. at 33:5-9).
6. Based on its ability to decrease externalization of hTM5 in LS-180 cells,
the Specification teaches that PMA can be used to treat UC (id. at 4:20 to
5:12; 14:8-24).
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Analysis
The Examiner has the initial burden of establishing a reasonable basis
to question the enablement provided for the claimed invention. Wright, 999
F.2d at 1561. To meet this burden, the Examiner argued, and provided
factual evidence to support the argument, that it would have been
unpredictable that PMA would treat UC because (1) PMA induces
inflammation and UC is an inflammatory condition; (2) PMA has adverse
effects on human subjects; and (3) there was inadequate basis on which to
extrapolate from the in vitro results described in the Specification to the
claimed method of treating. As to points (1) and (2), Appellant provided
sufficient evidence to rebut the Examiner’s position (Reply Br. 3-4) and
therefore we do not address these points further. This leaves us with point
(3) which is discussed in more detail below.
When an in vitro test is relied upon to establish a pharmacological
activity, it must be shown that there is a reasonable correlation between the
test and the asserted activity. Fujikawa, 93 F.3d at 1564. Here, Appellant
based the asserted use of PMA to treat ulcerative colitis on an in vitro test.
Namely, the ability of PMA to inhibit secretion of hTM5 from LS-180 colon
cancer cells (FF2-FF6). The Examiner found that the Specification did not
provide any evidence that inhibiting secretion of hTM5 in the cancer cell
line would reasonably predict the activity of PMA in patients with UC, and
properly rejected the claim for lack of enablement.
Appellant did not identify a defect in the Examiner’s reasoning or
provide rebuttal evidence establishing that persons of ordinary skill in the
art, based on the in vitro result, would have reasonably believed that PMA
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would exhibit a therapeutic effect in patients with ulcerative colitis.
Therefore, Appellant did not rebut the Examiner’s determination.
Instead, Appellant argued that the PTO had granted U.S. Pat. No.
6,605,276 (“the ‘276 patent”) to Appellant in which “teaches and claims the
use of an antibody that binds to hTM5 for treating ulcerative colitis in a
human,” establishing that the “PTO and the skilled artisan [would] have
accepted that the externalization of hTM5 via CEP is linked to ulcerative
colitis.” (App. Br. 7-8.)
Claim 1 in the ‘276 patent is drawn to a method of treating ulcerative
colitis in a human comprising administering to the human an antibody to a
tropomyosin isoform. It therefore involves administration of a tropomyosin
antibody. Appellant has not established that PMA has the same activity as a
tropomyosin antibody (Ans. 12). For instance, an antibody could act by
binding to the tropomyosin. PMA, on the other hand, is taught in the
Specification to inhibit tropomyosin secretion (FF5). Consequently, the
Examiner had adequate basis to conclude that persons of ordinary skill in the
art would have doubted that the activity of an antibody in treating UC would
reasonably predict the therapeutic effect of PMA, an unrelated agent with a
different mechanism of action.

Conclusion of Law and Summary
The Examiner did not err in rejecting claim 1 for lack of enablement
since it would not have been reasonably predicted at the time of the
invention that PMA could be utilized to treat ulcerative colitis in human
subjects. The rejection of claim 1 is affirmed. Claim 2 was not separately
argued and therefore falls with claim 1. 37 CFR § 41.37(c)(1)(vii).
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ANTICIPATION REJECTION
Claim 2 stands rejected under 35 U.S.C. § 102(b) as anticipated by
Dumont (Ans. 10).
Statement of the Issue
The issue in this rejection is whether the Examiner had sound basis to
believe that Dumont’s administration of PMA to T-cells inhibited the
externalization of hTM5 as required by claim 2.

Principles of Law
“To anticipate a claim, a prior art reference must disclose every
limitation of the claimed invention, either explicitly or inherently.” In re
Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
Once “the PTO shows sound basis for believing that the products of
the applicant and the prior art are the same, the applicant has the burden of
showing that they are not.” In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990).

Claim interpretation
Claim 2 is a drawn to a “method for inhibiting the externalization of
human tropomyosin 5” comprising contacting cells with “an agent which
blocks the secretion of a hTM5 and colon epithelium-specific protein
complex thereby inhibiting the externalization of hTM5.” Because of a
restriction requirement, the claim has only been examined to the extent that
the agent is PMA.
Since the claimed method is “for inhibiting the externalization” of
hTM5, we interpret the claim to require that hTM5 externalization is
inhibited by PMA. However, we do not interpret the claim to require that the
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method be practiced with the intent to inhibit hTM5 externalization because
intent or recognition that a process achieves a stated result does not change
how the method is carried out. The method steps are the same, whether or
not it is recognized that hTM5 is not externalized upon treatment with PMA.

Findings of Fact (FF)
Specification
7. The Specification teaches that in “the gastrointestinal tract, CEP is
expressed only in colon epithelial cells,” and not in the small intestine (Spec.
13:13-18).
8. “However, at extracolonic sites, CEP is expressed in skin and biliary
epithelium, ciliary epithelium in eye, and also in chondrocytes. These are
organs and tissues commonly involved in inflammatory bowel disease.” (Id.
at 13:18-22.)
Dumont
9. Dumont describes treating T-cells with PMA (Dumont, at col. 11, ll. 20-
26).
Analysis
The Examiner contends that claim 2 is anticipated by Dumont because
Dumont’s method of treating T-cells with PMA would have inherently
inhibited externalization of hTM5 and CEP as required by the claim (Ans.
10).
The Examiner did not provide a sound basis upon which to believe
that hTM5 externalization would be inhibited in T-cells upon PMA
administration by Dumont (FF9). According to the Specification, PMA
prevents secretion and externalization of the CEP-hTM complex from colon
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cells (FF3-5). However, there is no evidence that T-cells express CEP (FF7-
8) or that hTM5 is externalized from T-cells. Consequently, the Examiner
has not met the burden of establishing that Dumont’s method would inhibit
hTM5 externalization as required by claim 2 because there is no sound basis
to believe that T-cell’s express hTM5 or CEP. The rejection of claim 2
under 35 U.S.C. § 102(b) is reversed.

TIME PERIOD FOR RESPONSE
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

dm

Appeal 2009-001498
Application 11/500,113

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JANE MASSEY LICATA
LICATA & TYRRELL P.C.
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