Ex parte Pishevar

Board of Patent Appeals and Interferences

Nov 23, 2001

08831993 (B.P.A.I. Nov. 23, 2001)

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publication and is not binding precedent of the Board.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. 16

UNITED STATES PATENT AND TRADEMARK OFFICE

__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte SHERVIN K. PISHEVAR
__________

Appeal No. 2000-1919
Application No. 08/831,993
__________

ON BRIEF
__________

Before ROBINSON, MILLS, 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, 2, 4-12, and 14-20, all of the claims remaining. Claim
1 is representative and reads as follows:
1. A method for inhibiting the development of a parasite in a
erythrocyte, said method comprising the step of contacting the erythrocyte,
infected with an intracellular parasite, with a magainin, PGLa or XPF peptide
under conditions whereby the development of said parasite in said erythrocyte is
inhibited.
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Application No. 08/831,993

2
The examiner relies on the following references:
Pasvol et al. (Pasvol), “Separation of viable schizont-infected red cells of
Plasmodium falciparum from human blood,” Annals of Tropical Medicine and
Parasitology, Vol. 72, No. 1, pp. 87-88 (1978)

Gwadz et al. (Gwadz), “Effects of Magainins and Cecropins on the Sporogonic
Development of Malaria Parasites in Mosquitoes,” Infection and Immunity, Vol.
57, No. 9, pp. 2628-2633 (1989)

Cabantchik, “Properties of Permeation Pathways Induced in the Human Red Cell
Membrane by Malaria Parasites,” Blood Cells , Vol. 16, pp. 421-432 (1990)

Magowan et al. (Magowan), “Role of the Plasmodium falciparum Mature-
Parasite-Infected Erythrocyte Surface Antigen (MESA/PfEMP-2) in Malarial
Infection of Erythrocytes,” Blood, Vol. 86, No. 8, pp. 3196-3204 (1995)

Matsuzaki et al. (Matsuzaki 1), “Molecular Basis for Membrane Selectivity of an
Antimicrobial Peptide, Magainin 2,” Biochemistry, Vol. 34, pp. 3423-3429 (1995)

Matsuzaki et al. (Matsuzaki 2), “Translocation of a Channel-Forming
Antimicrobial Peptide, Magainin 2, across Lipid Bilayers by Forming a Pore,”
Biochemistry, Vol. 34, pp. 6521-6526 (1995)

Matsuzaki et al. (Matsuzaki 3), “Kinetics of Pore Formation by an Antimicrobial
Peptide, Magainin 2, in Phospholipid Bilayers,” Biochemistry, Vol. 34, pp. 12553-
12559 (1995)

Claims 1, 2, 4-12, and 14-20 stand rejected under 35 U.S.C. § 112, first
paragraph, as unsupported by an enabling disclosure.
We reverse.
Background
“Magainins, PGLa and XPF comprise a class of linear, amphipathic
cationic peptides originally found in the skin of Xenopus laevis and shown to
have broad-spectrum antimicrobial activity. . . . [M]againins have been reported
to disrupt extracellular stages of Plasmodia parasites. Unfortunately, the life
cycles of the Plasmodia, like many intracellular pathogens, comprise only brief
Appeal No. 2000-1919
Application No. 08/831,993

3
extracellular stages and the magainins were reported to have no effect on their
intracellular development.” Specification, page 1.
The specification discloses “methods and compositions for inhibiting the
development of intracellular parasites by treating [infected] cells with an effective
concentration of a magainin, PGLa or XPF peptide under conditions whereby the
development of the parasite in said cell is inhibited. The targeted parasites have
been found to increase in [sic] the accessibility of the plasma membrane of the
cell to the peptide and effect an increase in the cytopathic, especially lytic,
sensitivity of the cell to the peptide.” Page 2.
The specification provides two working examples. In the first example,
human red blood cells infected with Plasmodium falciparum parasites were
treated with increasing doses of a magainin peptide (“magainin 2”) and
parasitemia was assayed daily for four days. The results showed >50%
reduction in parasitemia in the highest-dosage sample as compared to the
untreated control cells by the fourth day. See Table 1 (page 5). Appellant
concluded that “[t]he data demonstrate dose and time dependent inhibitions of
parasitemia by the magainin peptide.” Page 6.
The second example discloses an immunofluorescent assay to determine
the location of the magainin peptide within treated erythrocytes. Plasmodium-
infected cells treated with magainin 2 as in the first example were assayed using
an antibody against magainin 2 at different times and different magainin
concentrations. Appellant found that “[a]t each time point at each magainin
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concentration, the antibody was visualized exclusively within the parasite inside
infected erythrocytes.” Page 6.
Discussion
The examiner rejected all of the claims as nonenabled because the
claimed effect on intracellular parasites is contrary to what would be expected
based on the prior art. See the Examiner’s Answer, pages 3-4 (emphasis in
original):
Gwadz et al. teach that the magainin peptide could disrupt
extracellular stages of the parasites but had no effect on
intracellular development. . . . [T]he question is whether there is a
predictability in the prior art that, despite the cited teaching of
Gwadz et al., magainins can [a]ffect intracellular development of
malaria parasites. . . . The prior art, however, does not indicate that
magainins, instead of being either bound to plasma membrane of a
cell or lysing a cell altogether, are capable of permeating into
intracellular space of a live cell.

The instant disclosure provides no evidence that the observed
effects of magainin on malaria parasites are due to inhibition of
parasite’s intracellular development, and is [sic] not due to effect of
magainins on parasites located outside erythrocytes (the latter
effect is well documented in prior art).

The examiner acknowledges the working examples in the specification but
disputes their probative value. The examiner characterized the first example as
providing “[n]o evidence” to support the claimed invention. See the Examiner’s
Answer, pages 4-5:
Example 1 offers Table 1 with some unidentifiable numbers and
informs that parasitemia assays were performed according to
Pasvol or Magovan. The cited references, however, teach a
number of assays and various ways of data analysis which make it
impossible to one skilled in art to identify the origin of the numbers
presented in the instant Table 1. Further, because the description
of Example 1 informs that magainin was added in extracellular
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Application No. 08/831,993

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medium, the numbers presented in the Table may equally reflect
extracellular effect of the peptide on the parasite (i.e. described in
the prior art), or inhibition of intracellular development of the
parasite (i.e. asserted in the application). No evidence for the latter
is provided.

The examiner was also unimpressed by the second working example.
See the Examiner’s Answer, page 5:
Turning to Example 2, the uniformly overexposed image of a cell
stained with antibody against magainin 2 . . .reflect[s] one of three
possibilities: 1) stained magainin is located outside the cell; 2)
stained magainin is bound to the plasma membrane (as suggested
by the prior art, see above), or 3) stained magainin is located inside
a cell. Again, no evidence for the latter is offered.

The examiner cited an additional basis of non-enablement for claims 1
and 11. These claims read on using any of three classes of peptides—
magainins, PGLa or XPF peptides—in the claimed method, but the working
examples in the specification are limited to magainins. The examiner concluded
that the specification does not enable the full scope of these claims because it
“does not provide guidance on how to use PGLa or XPF peptide, how to select
effective concentration for PGLa vs XPF peptide vs magainin. Therefore,
insufficient guidance exist[s] in the specification to enable a person of ordinary
skill in the art to practice the invention without the need for undue
experimentation.” Examiner’s Answer, page 5.
Appellant argues that “[t]he application provides all the teaching necessary
for one skilled in the art to practice the invention without undue experimentation.”
Revised Appeal Brief, page 3. In support, Appellant has submitted a declaration
under 37 CFR § 1.132 by Steve Ludtke. Dr. Ludtke states that, in his opinion,
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Application No. 08/831,993

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“the application teaches in detail everything one of ordinary skill in the art needs
to practice the invention (i.e. inhibit the development of intracellular parasites in
erythrocytes) without the need for any experimentation beyond routine screening
in simple, disclosed assays.” Ludtke declaration, paragraph 2.
“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.” In re Wright, 999 F.2d 1557, 1561-62, 27 USPQ2d 1510, 1513
(Fed. Cir. 1993). “[It] is incumbent upon the Patent Office, whenever a rejection
on this basis is made, to explain why it doubts the truth or accuracy of any
statement in a supporting disclosure and to back up assertions of its own with
acceptable evidence or reasoning which is inconsistent with the contested
statement. Otherwise, there would be no need for the applicant to go to the
trouble and expense of supporting his presumptively accurate disclosure.” In re
Marzocchi, 58 CCPA 1069, 1073, 439 F.2d 220, 224, 169 USPQ 367, 370
(1971).
In this case, the weight of the evidence in the record supports Appellant’s
position rather than the examiner’s. The examiner cited Gwadz and two papers
by Matsuzaki as “indicat[ing] that magainins do not have effect on the
intracellular parasite as they do not penetrate inside the cells.” Examiner’s
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Answer, page 6 (emphasis in original). We have reviewed the cited references,
however, and we do not find that they provide evidence to support the examiner’s
conclusion. Gwadz states that “[i]n vitro studies . . . showed that the magainin
peptide could disrupt extracellular stages of [plasmodial] parasites but that it had
no effect on intracellular development.” Page 2628, right-hand column.
However, Gwadz provides no evidence to support this conclusion, citing only
“unpublished data.” Id.
The Matsuzaki references cited by the examiner also do not support his
position. Matsuzaki investigated the molecular basis of the effect of magainins
on different membranes and the translocation of magainin peptides from one side
of a membrane to the other. The examiner has not adequately explained how
either Matsuzaki reference contradicts the data in the instant specification or
shows that magainins do not penetrate inside cells.
Appellant’s position, on the other hand, is supported by the working
examples in the specification. The examiner has complained that the
presentation of the data in the specification makes it difficult for him to
independently evaluate whether they support the specification’s conclusions.
However, “a specification disclosure which contains a teaching of the manner
and process of making and using the invention in terms which correspond in
scope to those used in describing and defining the subject matter sought to be
patented must be taken as in compliance with the enabling requirement of the
first paragraph of § 112 unless there is reason to doubt the objective truth of the
statements contained therein which must be relied on for enabling support.”
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Application No. 08/831,993

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Marzocchi, 439 F.2d at 223, 169 USPQ at 369, emphasis in original. The
examiner’s complaints about the data in this case do not provide a sufficient
basis “to doubt the objective truth of the statements” in the specification.
Appellant’s position is also supported by the Ludtke declaration. Dr.
Ludtke declares that “the application teaches in detail everything one of ordinary
skill in the art needs to practice the invention (i.e. inhibit the development of
intracellular parasites in erythrocytes) without the need for any experimentation
beyond routine screening.” Ludtke declaration, paragraph 2. The examiner has
cited no evidence that contradicts the Ludtke declaration. Rather, he dismissed it
as “not provid[ing] any further factual evidence and merely cit[ing] the
specification.” Examiner’s Answer, page 8. Therefore, as Appellant notes, the
Ludtke declaration remains uncontroverted as evidence that the claims are fully
enabled by the specification. Reply Brief, page 1.
With respect to the PGLa and XPF peptides encompassed by claims 1
and 11, Appellant argues that “[t]he use of PGLa and XPF peptides is the same
as the structurally analogous magainin peptides. . . . Substituting one taught
peptide for another taught peptide does not require undue experimentation.”
Revised Appeal Brief, page 4. The examiner provided no substantive response
(see the Examiner’s Answer, page 8) and no evidence or reasoning on which to
base a conclusion that using PGLa or XPF peptides in the claimed method would
require undue experimentation. We therefore conclude that the examiner has
not met his burden of showing nonenablement with respect to this limitation.
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Application No. 08/831,993

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We conclude that the examiner has not met his burden of “setting forth a
reasonable explanation,” Wright, 999 F.2d at 1561-62, 27 USPQ2d at 1513, as to
why he doubts the accuracy of the specification’s assertions. Even if it is true
that Appellant’s data could be better explained, or the photographic data could be
better reproduced, the examiner must do more than simply state that he cannot
interpret the data. The examiner’s burden is to “explain why [he] doubts the truth
or accuracy of any statement in a supporting disclosure and to back up
assertions of [his] own with acceptable evidence or reasoning which is
inconsistent with the contested statement.” Marzocchi, 439 F.2d at 224, 169
USPQ at 370. This burden has not been carried here. Therefore, the examiner
has not made out a prima facie case of non-enablement.
Summary
We reverse the rejection for non-enablement because the weight of the
evidence of record supports Appellant’s position rather than the examiner’s.
REVERSED

DOUGLAS W. ROBINSON )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
DEMETRA J. MILLS )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
ERIC GRIMES )
Administrative Patent Judge )
Appeal No. 2000-1919
Application No. 08/831,993

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RICHARD ARON OSMAN
SCIENCE AND ATECHNOLOGY LAW GROUP
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