Ex Parte Dykstra et al

Board of Patent Appeals and Interferences

Jan 27, 2004

08185079 (B.P.A.I. Jan. 27, 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for publication and is not binding precedent of the Board.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. 38

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CHRISTINE C. DYKSTRA, RONALD I. SWANSTROM,
and RICHARD R. TIDWELL
__________

Appeal No. 2001-1051
Application No. 08/185,079
__________

ON BRIEF
__________

Before ADAMS, MILLS, and GREEN, 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
final rejection of claims 12-31. Claim 12 is representative of the subject matter
on appeal, and is drawn to “[a] method of combating a retroviral infection in a
subject having a retroviral infection, comprising administering to said subject an
effective retroviral infection combatting [sic] amount of a compound according to
Formula I . . . or a pharmaceutically acceptable salt thereof.” Exemplary
compounds of Formula I include 1,2-bis[5-amidino-2-benzimidazolyl]ethane; 1,2-

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Application No. 08/185,079

bis[5-isopropylamidino-2-benzimidazolyl]ethane; bis[5-(2-imidazolyl)-2-
benzimidazolyl]methane and bis[5-amidino-2-benzimidazolyl]methane. See
claims 17 and 28. Claim 23, the only other dependent claim, is drawn
specifically to “[a] method of treating HIV infection in a subject having an HIV
infection, comprising administering to said subject an effective HIV infection
combatting [sic] amount of a compound according to Formula (I) . . . or a
pharmaceutically acceptable salt thereof.”
The examiner relies upon the following references:
Tidwell et al. (Tidwell I) 4,324,794 Apr. 13, 1982
Tidwell et al. (Tidwell II) 4,397,863 Aug. 09, 1983
Tidwell et al. (Tidwell III) 4,619,942 Oct. 28, 1986

Vonderfecht et al. (Vonderfecht) “Protease Inhibitors Suppress the In-Vitro and
In-Vivo replication of Rotavirus,” Journal of Clinical Investigation,
Vol. 82, pp. 2011-2016

Claims 12-31 stand rejected under 35 U.S.C. § 103(a) as being obvious
over the combination of Tidwell I, II or III as combined with Vonderfecht. After
careful review of the record and consideration of the issue before us, we reverse.
DISCUSSION
Claims 12-31 stand rejected under 35 U.S.C. § 103(a) as being obvious
over the combination of Tidwell I, Tidwell II or Tidwell III as combined with
Vonderfecht.
Tidwell I, II and III are cited for teaching that the claimed compounds are
known antiviral agents. The rejection acknowledges that the cited prior art
“differs from the claimed invention by failing to recite the claimed HIV etiological
agent.” Examiner’s Answer, page 3.
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According to the rejection:
This deficiency is cured by the similarity between the respiratory
syncytial virus (RSV) and the AIDS etiological agent. RSV and HIV
are both RNA viruses possessing a similar replicative schema in
their respective host cells. It is noted that Tidwell [ ] reported the
claimed compounds exhibiting antiviral activity to virus other that
[sic] the claimed RSV (([Tidwell III]), column 11, lines 43-45).
Vonderfecht [ ] further motivate[s] the skilled artisan to employ
these compounds therapeutically on retroviral infection. Attention
is directed to page 2015 wherein Vonderfecht [ ] suggest[s] these
compounds as useful for the claimed retroviral etiological agent.

Absent information to the contrary, the skilled artisan would
have been motivated by the data of Tidwell [ ] to employ the
claimed compounds against various RNA virus and enjoy a
reasonable expectation of success. Although Tidwell [ ] report[s]
that the claimed compounds are specific for the RSV etiologial
agent, the statement at column 11 and the presented data render
such averments moot.

Thus, two distinct and powerful motivations [exist] [sic] to
employ Applicants’ compounds in retroviral therapy. It would follow
therefore that the instant claims recite prima facie obvious subject
matter, and are properly rejected under 35 USC 103.

Id. at 3-4.
Appellants argue that the Tidwell references are all cumulative to one
another, and all deal with the RSV virus. According to Appellants, RSV is not a
retrovirus, but a paramyxovirus and that paramyxovirus and its replicative
scheme is not analogous to that of a retrovirus. Vonderfecht, Appellants argue,
relates to a rotavirus, which again, is not a retrovirus. Moreover, Appellants
contend that, contrary to the statement in the rejection that the claimed
compounds are useful against retroviruses, “Vonderfecht only states that a
number of viruses require host proteases for productive infection and that
therefore protease inhibitors MAY have a broad range of antiviral activity.”
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Application No. 08/185,079

Appeal Brief, page 5 (emphasis in original). Appellants conclude that
Vonderfecht does not motivate the ordinary artisan to use the presently claimed
compounds for combating a retroviral infection, such as an HIV infection. We
agree.
The burden is on the examiner to make a prima facie case of
obviousness, and the examiner may meet this burden by demonstrating that the
prior art would lead the ordinary artisan to combine the relevant teachings of the
references to arrive at the claimed invention. See In re Fine, 837 F.2d 1071,
1074, 5 USPQ2d 1596, 1598-99 (Fed. Cir. 1988). Obviousness is determined in
view of the sum of all of the relevant teachings in the art, not isolated teachings
in the art. See In re Kuderna, 426 F.2d 385, 389, 165 USPQ 575, 578
(CCPA 1970); see also In re Shuman, 361 F.2d 1008, 1012, 150 USPQ 54,
57 (CCPA 1966). In assessing the teachings of the prior art references, the
examiner should also consider those disclosures that may teach away from the
invention. See In re Geisler, 116 F.3d 1465, 1469, 43 USPQ2d 1362, 1365
(Fed. Cir. 1997).
In this case, each of the Tidwell references teaches that “[t]he suppressive
effect [of the compound taught by Tidwell] is virus specific, however, and does
not extend to cell fusion induced by P-3 virus or the MP mutant of herpes
simplex type I.” Tidwell I, Col. 2, ll. 64-67; Tidwell II, Cols. 2-3, ll. 66-1; Tidwell III,
Col. 3, ll. 1-4. Thus, Tidwell expressly teaches away from using the compounds
on viruses other than RSV. The examiner relies on Col. 11, lines 43-45, of
Tidwell III, finding that the teaching at Col. 11 renders the above teaching moot.
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Application No. 08/185,079

Tidwell III at Col. 11, ll. 43-45 teaches that “[t]he results in Table 5 also
reveal that the inhibitor produced a slight but consistent decrease in the yield of
P-3 virus.” That statement, however, relates to a single compound and a single
virus, and thus does not render the prior express teaching of Tidwell moot. In
addition, the decrease is only slight, thus the above statement, when read with
the statement that the suppressive effect of the compound is virus specific,
would not motivate one of ordinary skill to use the compounds on another,
completely different virus, i.e., a retrovirus.
Vonderfecht does not remedy the deficiencies of the Tidwell references.
Vonderfecht teaches that one compound, BABIM, which falls within the claimed
genus of compounds, is the most potent synthetic, reversible inhibitor of trypsin
yet identified. See Vonderfecht, page 2011, col. 2. The reference also teaches
that BABIM restricts the intestinal replication of the murine of rotavirus when the
compound and the virus were administered simultaneously to suckling mice.
See Vonderfecht, abstract. Finally, as relied upon by the examiner, Vonderfecht
also teaches:
In this instance, it was shown that BABIM delays viral penetration
into cells by its antiprotease action but does not interfere with viral
RNA replication. Protease inhibitors such as the ones described in
this report represent a new class of viral agents that functions at
the level of protein interactions and would not be expected to have
such potential for long-term untoward effects on mammalian
nucleic acids. In addition, many pathogenic viruses, including
myxoviruses, paramyxoviruses, retroviruses, coronaviruses, and
poxviruses, require viral or host proteases for productive infection.
Thus, chemotherapeutic agents which possess protease inhibitory
activity may have a broad range of antiviral activity. The availability
of antiviral agents capable of inhibiting a wide range of pathogenic
viruses without interfering with host nucleic acid replication may
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Application No. 08/185,079

represent a major advance in the prevention and treatment of viral
infections in humans and other animals.

Vonderfecht, page 2015, column 2.
Vonderfecht thus suggests that the BABIM may have a broad range of
antiviral activity. While the above teachings of Vonderfecht may have made it
obvious to try BABIM against retroviruses, in view of the statement in Tidwell that
the compounds are virus specific, and the fact that the data presented by the
Vonderfecht reference is limited to a murine rotavirus, the prior art as combined
does not provide a reasonable expectation of success that BABIM would be
effective against a retrovirus such as HIV. See In re Dow Chemical Co., 837
F.2d 469, 473, 5 USPQ2d 1529, 1531 (Fed. Cir. 1988) (noting that a
determination of obviousness not only requires that the prior art would have
suggested the claimed process to one of ordinary skill in the art, but also that the
process would have a reasonable likelihood of success when viewed in light of
the prior art).
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Application No. 08/185,079

CONCLUSION
Because the rejection fails to set forth a prima facie case obviousness for
the reasons as set forth above, it is reversed.
REVERSED

Donald E. Adams )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Demetra J. Mills )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Lora M. Green )
Administrative Patent Judge )

LG/dym

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Aries A. Taylor, Jr.
Jenkins & Wilson, P. A.
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