Ex Parte SNUTCH et al

Board of Patent Appeals and Interferences

Nov 22, 2006

09346794 (B.P.A.I. Nov. 22, 2006)

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for publication and is not binding precedent of the Board.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 TERRY P. SNUTCH and DAVID L. BAILLIE
__________

Appeal No. 2006-2389
Application No. 09/346,794
__________

HEARD October 19, 2006
__________

Before GRIMES, MILLS, and SCHEINER, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL

This appeal involves claims to a method of identifying calcium channel
antagonists, which the examiner has rejected for lack of utility. We have jurisdiction
under 35 U.S.C. § 134. We reverse.
Background
“Calcium channels are a heterogeneous class of molecules that respond to
depolarization by opening a calcium-selective pore through the plasma membrane. The
entry of calcium into cells mediates a wide variety of cellular and physiological
responses.” Specification, page 1. Calcium channels “are also implicated in a number
of human disorders.” Page 2, first full paragraph.
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“Native calcium channels have been classified by their electrophysiological and
pharmacological properties as T, L, N, P and Q types. . . . T-type (or low voltage-
activated) channels describe a broad class of molecules that activate at negative
potentials and are highly sensitive to changes in resting potential.” Page 2, last
paragraph.
The specification discloses
sequences for . . . mammalian calcium channel subunits of T-type calcium
channels, . . . labeled as α1G, α1H and α1I subunits. . . . [T]hese subunits,
either alone or assembled with other proteins, can produce functional
calcium channels, which can be evaluated in model cell lines to determine
the properties of the channels containing the subunits of the invention.
These cell lines can be used to evaluate[ ] the [e]ffects of pharmaceuticals
and/or toxic substances on calcium channels incorporating α1G, α1H and α1I
subunits.

Page 7. “The complete cDNA sequences of the rat α1G, α1H and α1I subunits are given
by Sequence ID Nos. 23, 25 and 27, respectively.” Page 16, first paragraph.
Discussion
1. Claims
Claims 28-31, 37, and 40 are pending and on appeal. Claim 28 is representative
and reads as follows:
28. A method to identify an antagonist of a T-type calcium channel which
method comprises:

a) contacting a recombinant cell expressing the α1 subunit of a
heterologous T-type calcium channel with a known agonist of said T-type calcium
channel;

b) contacting said cell with a compound to be tested; and

c) determining the ability of said compound to diminish the activation of
said α1 subunit by said agonist;

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wherein said α1 subunit is functional as a T-type calcium ion channel and
is encoded by a nucleotide sequence which hybridizes under conditions of stringency
corresponding to washing at 62o C in 0.2 x SSPE/0.1% SDS to a nucleic acid
comprising SEQ ID NO: 23 and

wherein said activating comprises enhancing the flow of calcium ions into
said cell in the presence as compared to the absence of said agonist;

whereby a compound which diminishes the activation of said α1 subunit by
said agonist is identified as an antagonist.

Claim 28 is directed to a method of identifying compounds as T-type calcium
channel antagonists, by contacting compounds with a recombinant cell expressing an α1
subunit of a T-type calcium channel (encoded by a nucleic acid that hybridizes to SEQ
ID NO:23 under specified conditions) and determining the ability of the compound to
diminish the activation of the α1 subunit by an agonist.
2. Utility
The examiner has rejected claims 28-31, 37, and 40 under 35 U.S.C. §§ 101 and
112, first paragraph, for lack of patentable utility. The examiner reasons that “[t]he
T-type calcium channel of SEQ ID NO:23 has no known utility. There is no disclosure in
the specification of any . . . antagonists of pharmacological significance that have been
shown to specifically bind and modulate calcium flux through the T-type calcium
channel of SEQ ID NO:23. . . . There is no disclosure that . . . an antagonist will be
beneficial.” Examiner’s Answer, page 4.
The examiner notes that “[t]he specification discloses conditions associated with
calcium channels . . . [but] the question is what specific disease state is associated with
dysfunction of the ion channel of SEQ ID NO:23. . . . Determining which compounds
interact with T-type ion channel of SEQ ID NO:23 do not provide a utility for the ion

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channel or the method of its use, it is just a method to discover the functionality of the
ion channel.” Examiner’s Answer, pages 4-5.1 The examiner cites Ertel2 as evidence
that “[a] compound that acts as an . . . antagonist on the α1 T-type channel protein used
in the claimed method may not have the same effect on other α1 T-type channel
proteins” and that “compounds may have different effects depending on their
concentration.” Id., page 9.
Appellants argue that the evidence of record shows that “T-type calcium ion
channel modulators do have clinical function.” Appeal Brief, page 7. Appellants cite
references disclosing that mibefradil is a selective antagonist of T-type calcium
channels and has been used to treat hypertension and congestive heart failure, among
other things. Appeal Brief, pages 7-8. Appellants also cite the declaration of Terrance
Snutch (submitted March 26, 2004). Dr. Snutch declares that T-type calcium channels
were known to be associated with various cardiac and neurological conditions.
Declaration, pages 1-2; Appeal Brief, pages 8-9.
The examiner bears the initial burden of showing that a claimed invention lacks
patentable utility. See In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed.
Cir. 1995) (“Only after the PTO provides evidence showing that one of ordinary skill in
the art would reasonably doubt the asserted utility does the burden shift to the applicant
to provide rebuttal evidence.”).

1 The examiner also takes issue with the use of sequence homology to identify the protein encoded by
SEQ ID NO:23 as a calcium channel. See the Examiner’s Answer, pages 12-15. However, the examiner
later states: “In [the] instant case Examiner is not arguing that alpha 1 subunit of the SEQ ID NO:23 is
not a T-Type calcium channel.” Id., page 19. As we understand it, the examiner does not dispute that
SEQ ID NO:23 encodes a T-type calcium channel subunit.
2 Ertel et al., “Low-voltage-activated T-type Ca2+ channels,” TiPS, Vol. 18, pp. 37-42 (1997).

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The U.S. Court of Appeals for the Federal Circuit recently addressed the utility
requirement as it applies to DNA. See In re Fisher, 421 F.3d 1365, 76 USPQ2d 1225
(Fed. Cir. 2005). The Fisher court held that § 101 requires a utility that is both
substantial and specific. Id. at 1371, 76 USPQ2d at 1229. Disclosing a substantial
utility means “show[ing] that an invention is useful to the public as disclosed in its
current form, not that it may be useful at some future date after further research. Simply
put, to satisfy the ‘substantial’ utility requirement, an asserted use must show that that
claimed invention has a significant and presently available benefit to the public.” Id., at
76 USPQ2d at 1230.
A specific utility is “a use which is not so vague as to be meaningless.” Id. In
other words, “in addition to providing a ‘substantial’ utility, an asserted use must show
that th[e] claimed invention can be used to provide a well-defined and particular benefit
to the public.” Id.
In this case, we conclude that a preponderance of the evidence of record supports
Appellants’ position rather than the examiner’s. There is no dispute that SEQ ID NO:23
is a subunit of a T-type calcium channel. The specification provides working examples
that are said to show that the protein of SEQ ID NO:23 has the properties of a α1 subunit
of a T-type calcium channel (pages 24-26) and the examiner has not disputed the
accuracy of that conclusion. The examiner, in fact, has stated that the function of SEQ
ID NO:23 is not in dispute (“Examiner is not arguing that alpha 1 subunit of the SEQ ID
NO:23 is not a T-Type calcium channel,” Examiner’s Answer, page 19).
The utility asserted for the instantly claimed method is directly related to the
function of the protein of SEQ ID NO:23. That is, the compounds identified in the

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claimed assay are asserted to be useful because they have the property of antagonizing
the function of the T-type calcium channel that includes SEQ ID NO:23, the α1 subunit.
The evidence of record shows that at least some antagonists of T-type calcium
channels are clinically useful. For example, Ertel states that “promising new drugs are
being developed, which block T channels. Many are CNS drugs that target epilepsy,
where T channels are believed to trigger repetitive firing.” Page 37, left-hand column.
See also page 41, middle column (“anti-convulsants are probably the most prolific
therapeutic field for T-channel blockers”). Ertel also states that mibefradil is a
“antihypertensive, antianginal Ca2+ channel antagonist . . . which has the unique
property of blocking preferentially T channels.” Id.
Appellants have submitted abstracts from several research papers that describe
use of mibefradil in treating hypertension, congestive heart failure, and ischemic left
ventricular dysfunction; as a vasodilator; and for preventing neointima formation. See
Exhibits A-F attached to the Appeal Brief (references originally filed March 26, 2004).
Appellants have also submitted the abstract from a paper that describes “the effects of
zonisamide, a new antiepileptic drug, on voltage-dependent T-type calcium current . . .
in cultured neuroblastoma cells. . . . The blockage of T-type calcium channels by
zonisamide could . . . inhibit[ ] the spread of seizure activity.” Exhibit G attached to the
Appeal Brief.
The evidence of record therefore shows that antagonists of T-type calcium
channels are known in the art for treating specific conditions. Based on the known utility
of other T-type calcium channel antagonists, those skilled in the art would reasonably

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expect that at least some of the compounds identified using the instantly claimed
method would be useful as therapeutic agents.
The Snutch declaration supports this expectation. Dr. Snutch has stated that
compounds which are found to inhibit or stimulate the activity of nervous
T-type channels will also inhibit or stimulate the activity of T-type channels
found in other tissues. Thus any arbitrarily chosen T-type channel could
be expressed in a cell line for use in screening assays to identify agonists
or antagonists and the agonists or antagonists would be useful in treating
the conditions associated with any T-type channel.

¶ 3.
The examiner disputes this assertion, arguing that an antagonist of the protein of
SEQ ID NO:23 may not have the same effect on other T-type calcium channels.
Examiner’s Answer, pages 15-16. In support of this position, the examiner cites Ertel’s
disclosure that “Ni2+ blocks T channels but it is difficult to predict the actual potency of
Ni2+ block and it is risky to rely on it to classify an expressed channel as T-type.” Id.,
page 16.
We do not agree with the examiner’s interpretation of Ertel. Ertel summarizes
the presentations at a workshop devoted to T-type calcium channels. Ertel discloses
that “[t]he pharmacology of T channels was . . . heavily discussed as a means to
recognize them.” Page 37, middle column. In that context, Ertel reports that researcher
Gerald Zamponi “found that Ni2+ block [of T-type channels] is . . . a combination of four
actions: a reduction in the peak current, a slowing of activation, a slowing of
inactivation, and a shift of the voltage dependence of the channels towards more
positive values.” Page 37, right-hand column. Zamponi found that “[a]s each of these
actions appears to depend differently on the molecular composition of the expressed

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channels and on the experimental conditions, it is difficult to predict the actual potency
of Ni2+ block and it is risky to rely on it to classify an expressed channel as T-type.” Id.
The passage quoted by the examiner does not address the potential therapeutic
use of T-type calcium channel antagonists. Rather, the part of the reference cited by
the examiner focuses on identifying calcium channels as T-type channels based on their
interaction with different calcium channel antagonists. Therefore, we do not agree with
the examiner that Ertel’s discussion of the effect of Ni2+ in blocking T-type channels
would have led those skilled in the art to doubt the potential therapeutic utility of T-type
calcium channel antagonists.
The instant claims are directed to a screening assay, not to specific chemical
compounds. The claimed assay can be useful even if, as would undoubtedly be the
case, many of the compounds identified as T-type channel antagonists turn out not to
be therapeutically useful. The utility of the claimed method is in directing drug
screening research toward compounds that are more likely to have an activity that will
make them therapeutically useful.
The instant claims are different from, for example, the expressed sequence tags
(ESTs) at issue in In re Fisher, 421 F.3d 1365, 76 USPQ2d 1225 (Fed. Cir. 2005). The
ESTs claimed by Fisher were derived from genes of unknown function. See id. at 1373,
76 USPQ2d at 1231. Fisher argued that an EST is a research tool, like a microscope,
and therefore useful. Id. The court disagreed:
[A] microscope has the specific benefit of optically magnifying an object to
immediately reveal its structure. One of the claimed ESTs, by contrast,
can only be used to detect the presence of genetic material having the
same structure as the EST itself. It is unable to provide any information
about the overall structure let alone the function of the underlying gene.

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Id. The court concluded that
the claimed ESTs act as no more than research intermediates that may
help scientists to isolate the particular underlying protein-encoding genes
and conduct further experimentation on those genes. . . . Accordingly, the
claimed ESTs are . . . mere ‘object[s] of use-testing,’ to wit, objects upon
which scientific research could be performed with no assurance that
anything useful will be discovered in the end.

Id.
Thus, the ESTs claimed in Fisher were held to lack utility because they were not
useful for conducting research generally, but only for conducting research on the ESTs
themselves and the genes from which they were derived. Here, by contrast, the
evidence of record shows that the claimed assay method is useful for identifying
compounds that are likely to block T-type calcium channels generally, rather than only
the T-type calcium channel subunit of SEQ ID NO:23. The evidence of record also
shows that known T-type calcium channel antagonists are useful for treating a variety of
conditions. The evidence therefore provides a reasonable basis for expecting that the
claimed method would be useful for identifying other compounds useful for treating the
same conditions.
In summary, the evidence of record does not support the examiner’s position that
the claimed assay lacks patentable utility. The rejections under 35 U.S.C. §§ 101 and
112, first paragraph, are reversed.
Other Issue
The present application was filed July 2, 1999 and claims the benefit under
35 U.S.C. § 120 of application 09/030,482, filed February 25, 1998. Specification,
page 1.

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The claims in the present application require the use of “[an] α1 subunit . . .
functional as a T-type calcium channel and . . . encoded by a nucleotide sequence which
hybridizes under [specified] conditions of stringency . . . to a nucleic acid comprising
SEQ ID NO:23.” SEQ ID NO:23 is a full-length cDNA (7540 nucleotides long) encoding
the rat α1G subunit of a T-type calcium channel. Page 16, lines 1-11.
The parent ‘482 application states that it “provides partial sequences” for human
and rat calcium channel α1I subunits and a human calcium channel α1H subunit. Page 8,
lines 2-4. The ‘482 application does not appear to disclose nucleotide sequences
encoding an α1G subunit, and does not disclose any sequence that is 7540 nucleotides in
length.
Therefore, the claims on appeal do not appear to be supported by the earlier
application in the manner required by 35 U.S.C. § 112, first paragraph. Lacking such
support, the present claims would not be entitled to the benefit of priority under
35 U.S.C. § 120 based on the earlier-filed application; the effective filing date of the
claims appears to be July 2, 1999.
Perez-Reyes3 discloses “the amino acid sequences of full-length T-type
channels, and the sequences of suitable coding nucleic acids . . . at SEQ ID NOs:1-8
(α1G sequences).” Page 6, lines 5-7. Perez-Reyes indicates that SEQ ID NO:5 is
derived from rat (“Rattus sp.”). See page 37. Amino acids 33 to 2254 of the sequence
encoded by Perez-Reyes’ SEQ ID NO:5 appear to be virtually identical to amino acids
65 to 2287 of the sequence encoded by the present application’s SEQ ID NO:23.

3 Perez-Reyes et al., WO 99/29847, published June 17, 1999, submitted with the Information Disclosure
Statement filed March 15, 2001

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Perez-Reyes discloses a
method of identifying a drug which affects T-type calcium channels. The
method involves first expressing a T-type calcium channel in a cell to
produce an active channel. . . . The cell expressing the channel is then
exposed to a solution containing a putative drug for interfering with the
channel. Thereafter, the presence or absence of calcium flux in response
to a change in membrane potential is assayed.

Page 11, lines 7-12.
Perez-Reyes also includes a working example showing that “mibefradil almost
completely abolished T-type current in cells expressing α1G.” Page 18. The example is
said to “demonstrate[ ] that a cloned T-type calcium channel can be used for identifying
a drug which affects T-type calcium channels.” Id. Thus, Perez-Reyes reasonably
appears to disclose a method of identifying drugs that affect T-type calcium channels
using cells expressing a rat α1G calcium channel subunit.
However, Perez-Reyes does not reasonably appear to disclose the specific
methods defined by claims 28 and 31, the only independent claims remaining in the
present application. Claim 28 requires contacting a recombinant cell expressing an α1G
subunit “with a known agonist of [a] T-type calcium channel,” while claim 31 requires
determining binding of a test compound to a cell expressing an α1G subunit “by
observing competitive binding with a known agonist or antagonist of [a T-type calcium]
channel.”
Perez-Reyes does not disclose either of these limitations and therefore does not
appear to anticipate the presently pending claims. On return of this application,
however, we recommend that the examiner consider the differences between the
method disclosed by Perez-Reyes and the methods defined by the pending claims. If

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the examiner believes that the differences are such that the claimed methods would
have been obvious in view of the prior art method, a rejection based on 35 U.S.C. § 103
should be entered. If a new rejection is made, of course, Appellants must be given an
appropriate opportunity to respond.

REVERSED

Toni R. Scheiner )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Demetra J. Mills )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Eric Grimes )
Administrative Patent Judge )

EG/dm

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