Ex parte Egidio et al.

Board of Patent Appeals and Interferences

Oct 21, 1999

08181259 (B.P.A.I. Oct. 21, 1999)

Application for patent filed January 13, 1994. According to appellants, this application is a divisional of1
Application 07/899,421, filed June 16, 1992, now U.S. Patent No. 5,314,904, which issued May 24, 1994.
THIS OPINION WAS NOT WRITTEN FOR PUBLICATION
The opinion in support of the decision being entered today (1) was not written for publication in a law journal and (2) is
not binding precedent of the Board.
Paper No. 22
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte MARCHI EGIDIO, ROTINI L. GABRIELE, DESAI SUBHASH and GRILLI MASSIMO
____________
Appeal No. 1996-0944
Application No. 08/181,2591
____________
HEARD: October 6, 1999
____________
Before JOHN D. SMITH, WALTZ, and SPIEGEL, Administrative Patent Judges.
SPIEGEL, Administrative Patent Judge.
Appeal No. 1996-0944
Application No. 08/181,259
The amendment filed April 7, 1995 (Paper No. 8), amending claims 24 and 30 and canceling claims 31 and 32,2
was entered by the examiner in the advisory action mailed April 20, 1995 (Paper No. 9).
Exhibit G from the brief and all the references from the reply brief except for Martindale The Extra3
Pharmacopoeia have not been considered because of incomplete documentation.
Exhibits A-G were first submitted by appellants in the amendment filed July 21, 1994 (Paper No. 5).4
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DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the decision of the examiner finally
rejecting claims 25 through 29 and refusing to allow claims 24 and 30, which are all of the claims
pending in this application. Claim 24 is illustrative:2
24. A pharmaceutical composition for topical application on the vagina, the
composition being effective against the vaginal infection which is bacterial vaginosis due
to at least one of the following anaerobic bacteria Gardnerella vaginalis, Bacteroides
bivius-disiens, the species Mobiluncus and Lactobacillus and to the aerobic bacteria
Neisseria gonorrhoeae, Haemophilus ducreyi, and Chlamydia trachomatis, which
contains between 50 and 500 mg of Rifaximin and vaginal compatible carriers, said
composition being in the form of a foam or a cream.
The examiner relies upon the following references in rejecting the appealed claims:
Parenti et al. (Parenti) 5,141,953 Aug. 25, 1992
(filed Mar. 22, 1990)
The Merck Index (Merck), “An Encyclopedia Of Chemicals, Drugs, and Biologicals,”
Eleventh Edition, page 1309:8218 (1989).
Remington’s Pharmaceutical Sciences (Remington), 18th edition, pages 1694-1710 (1990).
Appellants rely upon the following references in their brief (pages 10-17) and reply brief (page
2) :3, 4
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Application No. 08/181,259
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Marchi et al. (Marchi) 4,341,785 Jul. 27, 1982
Swedberg et al. (Exhibit A), “Comparison of Single-Dose vs One-Week Course of
Metronidazole for Symptomatic Bacterial Vaginosis,” 254 Journal of the American Medical
Association 8, 1046-1049 (Aug. 23/30, 1985).
J. McCue (Exhibit B), “Evaluation and Management of Vaginitis: An Update for Primary Care
Practitioners,” 149 Archives of Internal Medicine, 565-568 (March 1989).
Durfee et al. (Exhibit C), “Ineffectiveness of Erythromycin for Treatment of Haemophilus
vaginalis-Associated Vaginitis: Possible Relationship to Acidity of Vaginal Secretions,” 16
Antimicrobial Agents and Chemotherapy 5, 635-637 (November 1979).
B. Majeroni (Exhibit D), “New Concepts in Bacterial Vaginosis,” 44 AFP 4, 1215-1218
(October 1991).
Physicians’ Desk Reference (Exhibit E), 47th ed., pages 927-928:METROGEL-VAGINAL
(1993).
Treherne et al. (Exhibit F), “In Vitro Studies of Chlamydia trachomatis Susceptibility and
Resistance to Rifampin and Rifabutin,” 33 Antimicrobial Agents and Chemotherapy 8, 1393-1394
(August 1989).
Martindale The Extra Pharmacopoeia, Thirteenth Edition, page 200:Rifaximin (1993).
The references relied upon by this Merits Panel are:
Curtis-Prior et al. (Curtis-Prior) 4,804,674 Feb. 14, 1989
Egidio et al. (Egidio) 5,314,904 May 24, 1994
(filed Jun. 16, 1992)
ISSUES
Claims 24-30 stand rejected under 35 U.S.C. § 103 as being unpatentable over Parenti in view
of Merck and Remington. We reverse.
Appeal No. 1996-0944
Application No. 08/181,259
We note that no restriction requirement between method claims and composition claims was made in the5
record of parent Application 07/899,421. Thus, appellants apparently cancelled the composition claims in ‘421
voluntarily.
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Pursuant to the provisions of 37 C.F.R. § 1.196(b), we make the following new rejections:
Claim 24 is rejected under the judicially created doctrine of obviousness-type double patenting
as being unpatentable over claims 1-7 of U.S. Patent No. 5,314,904. Claim 30 is rejected under the
judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-7
of U.S. Patent No. 5,314,904 in view of Curtis-Prior. Claims 25-29 are rejected under the judicially
created doctrine of obviousness-type double patenting as being unpatentable over claims 1-7 of U.S.
Patent No. 5,314,904 in view of Parenti, Remington and Curtis-Prior. 5
In reaching our decision in this appeal, we have given careful consideration to the appellants’
specification and claims, to the applied prior art references and to the respective positions articulated by
the appellants and the examiner. We make reference to the examiner’s answer (Paper No. 14, mailed
September 21, 1995) for the examiner’s reasoning in support of the rejection, and to the appellants’
brief (Paper No. 12, filed June 30, 1995) and to the appellants’ reply brief (Paper No. 14, filed
October 6, 1995) for the appellants’ arguments thereagainst.
THE INVENTION
Appellants’ invention is directed to a pharmaceutical foam or cream composition for topical
treatment of bacterial vaginosis, caused by at least one of Gardnerella vaginalis, Bacteroides bivius-
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Application No. 08/181,259
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disiens, the species Mobiluncus and Lactobacillus, Neisseria gonorrhoeae, Haemophilus ducreyi,
and Chlamydia trachomatis, wherein the antibacterial agent Rifaximin is the active ingredient in a
vaginal compatible carrier (claim 24).
OPINION
1. Rejection under 35 U.S.C. § 103
To establish a prima facie case of obviousness, there must be both some suggestion or
motivation to modify the reference or combine reference teachings and a reasonable expectation of
success. Furthermore, the prior art must teach or suggest all the claim limitations. In re Vaeck, 947
F.2d 488, 493, 20 USPQ2d 1438, 1442 (Fed. Cir. 1991).
Parenti discloses that vaginal infections may be caused by yeasts (e.g., Candida albicans),
protozoans (e.g., Trichomonas vaginalis) and/or bacteria (e.g., Bacteroides spp. and especially
Gardnerella vaginalis) (col. 1, lines 22-50). Parenti describes a pharmaceutical composition for
topical treatment of infectious vaginitis wherein the antimicrobial purpurmycin is the active ingredient
because purpurmycin is effective against all three types of microorganisms, i.e., Trichomonas,
Candida and Gardnerella (col. 2, lines 16-32). The topical composition may be provided as a cream
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or foam (col. 5, lines 48-52) in suitable dosage preparations as found in Remington’s Pharmaceutical
Sciences, 17th Edition, 1985 (col. 5, line 67 - col. 6, line 2).
Merck describes Rifaximin as a nonabsorbable antibacterial agent useful as an intestinal
disinfectant, in infectious diarrhea, in hepatic encephalopathy and in intestinal infections.
Remington describes typical foam system topical pharmaceutical formulations.
According to the examiner, since Parenti uses an “antibacterial” agent in a vaginal composition,
it would have been obvious to modify the topical, vaginal antibacterial composition of Parenti by using
rifaximin as the active ingredient because Merck discloses that rifaximin is an antibacterial agent
(answer, pages 3-4). According to the examiner, both the target microorganisms and the target body
area(s) treated by the antibacterial composition are “irrelevant” (answer, page 5), i.e., since “rifaximin is
known as a pharmaceutical ... it would be obvious to place it in a pharmaceutical composition”
(answer, page 4). We disagree.
First, the examiner’s proposed modification of Parenti would destroy a fundamental
characteristic of Parenti, i.e., the ability to effectively treat each of the three types of infectious vaginitis
simultaneously. The examiner has failed to explain what would have motivated one of ordinary skill in
the art to destroy such a fundamental characteristic of Parenti.
Second, both the target microorganisms and the target body area(s) are relevant. A target
microorganism’s sensitivity to a particular antibacterial agent is a primary motivating factor in selecting
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that particular antibacterial agent. Here, purpurmycin and rifaximin are structurally unrelated. The
examiner has failed to establish why one of ordinary skill in the art would have reasonably expected
purpurmycin and rifaximin to be effective against at least one common microorganism. Neither Parenti
nor Merck disclose or suggest that rifaximin is effective against Gardnerella vaginalis, Bacteroides
bivius-disiens, the species Mobiluncus and Lactobacillus, Neisseria gonorrhoeae, Haemophilus
ducreyi or Chlamydia trachomatis. The only place we find such a teaching is in appellants’
specification. Furthermore, the particular target body area(s) is relevant both to the type of
microorganisms expected to be found there and to the pharmacokinetics of the active agent, e.g.,
delivery means, stability, clearance rate, etc. As noted by appellants, the prior art discloses using
rifaximin to treat intestinal infections caused by totally unrelated bacteria, e.g., Escherichia coli,
Salmonella, Enterococcus, etc. (brief, pages 10-11, 16). Thus, while the examiner is correct that only
a reasonable expectation of success, not absolute predictability, is required to establish a prima facie
case of obviousness, the examiner has failed to establish the requisite reasonable expectation of success
on this record. Moreover, the examiner has not rebutted appellants’ arguments that whether a known
antibiotic will be effective against bacterial vaginitis is unpredictable, even with related antibiotics such
as rifampin and rifabutin, (see e.g., Exhibits C and F) and that effective antibiotics may be
contraindicated because of the target body area (see e.g., Exhibits D and E) (brief, pages 12-14 and
reply brief, page 2).
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A discussion of Remington is not necessary to our decision since Remington does not remedy
the deficiencies noted above.
We find that the examiner has relied on impermissible hindsight in making the determination of
obviousness. In re Fritch, 972 F.2d 1260, 1266, 23 USPQ2d 1780, 1784 (Fed. Cir. 1992) (“It is
impermissible to engage in hindsight reconstruction of the claimed invention, using the applicant’s
structure as a template and selecting elements from references to fill the gaps.). Therefore, the
rejection of claims 24-30 under 35 U.S.C. § 103 as being unpatentable over Parenti in view of Merck
and Remington is reversed.
2. New grounds of rejection - 37 C.F.R. § 1.196(b)
We reject (a) claim 24, (b) claim 30 and (c) claims 25-29 under the judicially created doctrine
of obviousness-type double patenting over claims 1-7 of Egidio taken (a) alone, (b) in view of Curtis-
Prior and (c) in view of Parenti, Remington and Curtis-Prior.
Claims 1-7 of Egidio read as follows:
1. A method of treatment of a vaginal infection which consists of administering
topically to a subject in need of treatment a vaginal pharmaceutical composition
containing a therapeutically effective amount of Rifaximin in the form of a foam, a
cream, a gel, a vaginal ovule or a vaginal capsule.
2. The method according to claim 1 wherein said treatment is with said foam,
the flora of Gardnerella vaginalis, Mobiluncus spp., Bacteroides spp. and
Streptococcus pyogenes are eliminated and the vaginal bacterial flora is normalized
with the reappearance of the Doderlein’s bacillus.
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3. The method according to claim 1 wherein said vaginal infection consists of
bacterial vaginosis.
4. The method of treatment of a vaginal infection oaccording to claim 1 which
consists of applying by the topical route a pharmaceutically effective amount of
Rifaximin to a patient in need of said treatment.
5. The method according to claim 4 wherein said vaginal infection consists of
bacterial vaginosis.
6. The method according to claim 4 wherein said topical application is carried
out by means of a vaginal foam.
7. The method according to claim 4 wherein said topical application is carried
out by means of a cream.

Thus, the claimed pharmaceutical composition is obvious over the pharmaceutical composition
specifically required by the methods of Egidio.
Appealed claim 24 requires between 50 and 500 mg of rifaximin while claim 1 of Egidio recites
a “therapeutically effective amount” of rifaximin. In order to determine what constitutes a
“therapeutically effective amount” of rifaximin, one must consult the specification of Egidio. In re
Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970) (the specification of a patent may
be consulted under these circumstances not as prior art, but “to learn the meaning of terms in a claim”).
Turning to Egidio, col. 2, lines 24-26, we find that as in the present invention a “therapeutically effective
amount of rifaximin, [is] preferably between 50 mg and 500 mg.” Thus, it is apparent that claims 1-7 of
Egidio encompass the pharmaceutical composition of appealed claim 24.
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Appealed claim 30 requires a vaginal cream composition wherein the vaginal compatible carrier
is white vaseline, liquid paraffin, white wax, hydrogenated castor oil or methyl glucose dioleate.
Curtiss-Prior discloses usual excipients, e.g., carriers, for vaginal creams to include a hydrocarbon
base, e.g., white petroleum (i.e., white vaseline) and emulsifiers (col. 2, lines 14-17 and 35-39).
Therefore, it would have been obvious to use a conventional excipient such as white vaseline as a
carrier in the claimed vaginal cream as disclosed and suggested by Curtis-Prior.
Appealed claims 25-29 requires a vaginal foam composition having micronized rifaximin
particles in a vaginal compatible carrier including a thickening agent (i.e., emulsifier) and an oily
substance, wherein the foam is contained in an aluminum canister coated internally with an
epoxyphenolic resin, closed with a polyethylene valve and having a propellant gas. However, Parenti,
Remington and Curtiss-Prior suggest these added limitations as conventional in the art of foam aerosol
pharmaceutical compositions. Curtiss-Prior discloses vaginal foams containing a fluorinated
hydrocarbon propellant and a surfactant or emulsifier, as well as cetyl alcohol, stearyl alcohol and
sodium lauryl sulphate as emulsifiers (col. 2, lines 35-46). Remington discloses foam systems using a
blend of propane/isobutane or a hydrocarbon propellant (para. bridging pages 1697-98; page 1700,
col. 2, para. 1; page 1701, last para. - page 1702, col. 1, first 5 paras.); aluminum containers lined with
epoxy, vinyl or phenolic resins (page 1703, col. 2, first full para.; page 1707, col. 2, first full para.);
valves which may have dip tubes of polyethylene (page 1704, col. 2); use of lubricants, e.g., mineral oil,
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to prevent agglomeration and lubricate parts of the valve (page 1706, col. 2, pentultimate para.);
supplying antibacterial agents as dispersions or suspension, i.e., particulate aerosols (page 1706, col. 2,
para. 4); and, emulsifiers, including glycols and glycol derivatives (page 1707, col. 1, para. 5). Parenti
discloses the conventionality of micronized particulate antibacterial agents in pharmaceuticals (col. 6,
lines 3-10). Therefore, it would have been both obvious and within the ordinary skill in the art to
provide a vaginal foam composition in a conventional aluminum container lined with a conventional
epoxy/phenolic resin and having a conventional (fluorinated) hydrocarbon propellant to provide a
conventionally presented particulate (i.e., micronized) antibacterial agent in a conventional carrier
comprising emulsifiers and lubricants as suggested by Parenti, Remington and Curtis-Prior. Selection of
component amounts and particle sizes would have been a matter of routine optimization within the
ordinary skill in the art.
CONCLUSION
To summarize, the decision of the examiner to reject claims 24-30 under 35 U.S.C. § 103 as
unpatentable over Parenti in view of Merck and Remington is reversed. However, (a) claim 24, (b)
claim 30 and (c) claims 25-29 are rejected pursuant to the provisions of 37 C.F.R.
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Application No. 08/181,259
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§ 1.196(b) under the judicially created doctrine of obviousness-type double patenting over claims 1-7
of Egidio taken (a) alone, (b) in view of Curtis-Prior and (c) in view of Parenti, Remington and Curtis-
Prior.
This decision contains a new ground of rejection pursuant to 37 C.F.R. § 1.196(b) (amended
effective Dec. 1, 1997, by final rule notice, 62 Fed. Reg. 53, 131, 53, 197 (Oct. 10, 1997), 1203 off.
Gaz. Pat. & Trademark Office 63, 122 (Oct. 21, 1997)). 37 CFR § 1.196(b) provides that, “a new
ground of rejection shall not be considered final for purposes of judicial review.”
37 C.F.R. § 1.196(b) also provides that the appellant, WITHIN TWO MONTHS FROM
THE DATE OF THE DECISION, must exercise one of the two following options with respect to the
new ground of rejection to avoid termination of proceeedings (§ 1.197(c)) as to the rejectged claims:
(1) Submit an appropriate amendment of the claims so rejected or a showing
of facts relating to the claims so rejected, or both, and have the matter reconsidered by
the examiner, in which event the application will be remanded to the examiner ....
(2) Request that the application be reheard under § 1.197(b) by the Board of
Patent Appeals and Interferences upon the same record ...
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Application No. 08/181,259
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No time period for taking any subsequent action in connection with this appeal may be
extended under 37 CFR § 1.136(a).
REVERSED - 1.196(b)
JOHN D. SMITH )
Administrative Patent Judge )
)
)
)
) BOARD OF PATENT
THOMAS A. WALTZ ) APPEALS
Administrative Patent Judge ) AND
) INTERFERENCES
)
)
)
CAROL A. SPIEGEL )
Administrative Patent Judge )
CAS/dal
Appeal No. 1996-0944
Application No. 08/181,259
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