Ex Parte Peyman

Board of Patent Appeals and Interferences

Aug 21, 2003

09265532 (B.P.A.I. Aug. 21, 2003)

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for publication and is not binding precedent of the Board.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. 20
UNITED STATES PATENT AND TRADEMARK OFFICE
__________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________
Ex parte RAGAB EL-RASHIDY
Appeal No. 2002-0783
Application No. 09/268,957
__________
ON BRIEF
__________
WINTERS, SCHEINER, and LORIN, Administrative Patent Judges.
WINTERS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal was taken from the examiner's decision rejecting claims 1 and 3
through 23, which are all of the claims remaining in the application.
The Invention
The invention relates to a controlled release composition containing sildenafil for
delivery by the sublingual mode of administration. In addition to sildenafil, the
composition includes an osmotic agent, a swellable hydrophilic carrier, and a water
dispersible polymer. Claim 1, which is illustrative of the subject matter on appeal, reads
as follows:
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Application No. 09/268,957
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1. A composition providing a controlled release of sildenafil by sublingual route
and consisting essentially of:
about 10 to about 75 milligrams of sildenafil;
an osmotic agent;
a swellable hydrophilic carrier; and
a water dispersible polymer;
the ratio of the amount by weight of the osmotic agent to the amount by weight of the
swellable hydrophilic carrier being the range of about 0.3 to about 4; and
the composition having a T90 value in the range of more than about 25 to about
300.
The Prior Art References
The examiner relies on the following prior art references:
Bell et al. (Bell '534) 5,250,534 Oct. 5, 1993
Bell et al. (Bell '901) 5,346,901 Sep. 13, 1994
El-Rashidy et al. (El-Rashidy) 5,624,677 Apr. 29, 1997
Bell et al. (Bell '283) 5,719,283 Feb. 17, 1998
The Issue
The issue presented for review is whether the examiner erred in rejecting claims
1 and 3 through 23 under 35 U.S.C. § 103(a) as unpatentable over the combined
disclosures of El-Rashidy and the above-cited Bell patents.
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Application No. 09/268,957
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Deliberations
Our deliberations in this matter have included evaluation and review of the
following materials: (1) the instant specification, including all of the claims on appeal;
(2) applicant's Appeal Brief (Paper No. 10); (3) the Examiner's Answer (Paper No. 11);
(4) the Reply Brief (Paper No. 12) excluding Exhibits A-E attached thereto; and (5) the
above-cited prior art references.
On consideration of the record, including the above-listed materials, we affirm
the examiner's rejection under 35 U.S.C. § 103(a).
Procedure
Applicant filed a Reply Brief received at the USPTO February 23, 2001 (Paper
No. 12). As stated in 37 CFR § 1.193(b)(1), "The primary examiner must either
acknowledge receipt and entry of the reply brief or withdraw the final rejection and
reopen prosecution to respond to the reply brief." Here, the examiner did not withdraw
the final rejection and reopen prosecution. It follows that the Reply Brief has been
entered and made part of the administrative record (id.); this is consistent with the
Office communication mailed May 7, 1991 (Paper No. 14), stating that the Reply Brief
has been entered.
In his Reply Brief, applicant argues that the examiner's proposed combination of
references is improper. Applicant relies on Exhibits A-E, attached to the Reply Brief, to
support that argument. However, as stated in 37 CFR § 1.195, "Affidavits, declarations,
or exhibits submitted afer the case has been appealed will not be admitted without a
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Application No. 09/268,957
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showing of good and sufficient reasons why they were not earlier presented." In Paper
No. 16, mailed February 13, 2003, the examiner determined that Exhibits A-E would not
be admitted because applicant has not provided a showing of good and sufficient
reasons why they were not earlier presented. Accordingly, those exhibits are not part of
the administrative record.
In other words, applicant's Reply Brief is technically of record. But applicant's
argument in the Reply Brief, with respect to the propriety of combining references, is
unavailing because that argument is based on Exhibits A-E which are not of record.
Cf., In re Mehta, 347 F.2d 859, 866, 146 USPQ 284, 289 (CCPA 1965) (Unsworn
"Exhibit" can be taken merely as argument and not to establish facts).
The Merits
El-Rashidy discloses a composition comprising an osmotic agent; a swellable
hydrophilic carrier; and a water dispersible polymer in combination with an effective
amount of water soluble drug (active ingredient) for providing controlled release of the
drug by sublingual route. Additionally, El-Rashidy discloses a T90 value and a ratio of
the amount by weight of osmotic agent to the amount by weight of swellable hydrophilic
carrier which meet the terms of claim 1 on appeal.
El-Rashidy discloses a composition for the controlled release of water soluble
drugs by sublingual mode of administration, focusing attention on the specific drug
apomorphine hydrochloride. As best seen in Example 19, El-Rashidy discloses
apomorphine hydrochloride for treating male erectile dysfunction. According to El-
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Application No. 09/268,957
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Rashidy,
the apomorphine dose required to achieve a significant erectile response
is usually accompanied by nausea or other serious undesirable side
effects such as hypertension, flushing and diaphoresis. [El-Rashidy,
Background of the Invention, column 2, lines 24-27]
and
The present invention provides compositions that release water-
soluble drugs relatively slowly over an extended time period. The
composition is suitable for dosage forms that deliver drugs by the
sublingual or buccal routes. In the practice of this invention with its
application to the pharmacological agent, apomorphine, a sublingual
tablet formulation that includes particular constituents permits the drug to
achieve its effective therapeutic plasma concentration which is below a
plasma concentration where undesirable side effects such as nausea and
vomiting occur. In addition to this major improvement arising from the
present invention, the added benefit of drug release over a longer period
of time from the tablet can increase the duration of the therapeutic activity
for the drug.
The composition, in the form of a tablet, delivers the
pharmacological agent, such as apomorphine, at a controlled rate to
produce the desired physiological effect of the drug while preventing or
diminishing the side effects such as hypotension, nausea and vomiting
that have been associated with apomorphine. Such a composition thus
provides the therapeutic benefits of apomorphine, as for example, in the
treatment of Male Erectile Dysfunction . . . with minimal side effects.
[El-Rashidy, Summary of the Invention, column 3, lines 17-40].
We agree with the examiner that it would have been well within the skill of the art
and obvious to a person having ordinary skill to apply the teachings of El-Rashidy to the
active ingredient sildenafil. In his specification, page 6, lines 15 and 16, applicant
describes sildenafil as water soluble. Further, at the time the invention was made, the
oral use of the citrate salt of sildenafil had been approved by the U.S. Food and Drug
Administration (FDA) for treating male erectile dysfunction (specification, page 2, lines
30-33). In dose-response studies, increasing doses of sildenafil (25 to 100 mg)
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reportedly increased the erectogenic efficacy of sildenafil (specification, page 3, lines
21-23). However, the oral administration of sildenafil is also accompanied by dose-
responsive undesirable side effects. Consequently, at doses higher than 50 milligrams,
the incidence of such side effects as abnormal vision problems ranging from blue or
green halo effects to blurring, dyspepsia, nasal congestion, blinding headaches,
flushing redness, diarrhea, dizziness, rash, and urinary tract infection increases (id.,
lines 23-31). Other more serious side effects have also been reported (specification,
paragraph bridging pages 3 and 4). Thus, at the time the invention was made, there
was a need and desire for oral administration forms that promote the bioavailability of
sildenafil at lower doses while minimizing side effects (specification, page 4, lines 9-11).
Bell '534, Bell '901, and Bell '283 disclose that sildenafil and a suitable
pharmaceutically acceptable vehicle or carrier may be prepared for sublingual
administration. We are persuaded that a person having ordinary skill, armed with the
disclosure of the Bell patents and the acknowledged state of the prior art described in
applicant's specification, would have found it obvious to apply the teachings of El-
Rashidy to the water soluble drug sildenafil. In this manner, a person having ordinary
skill would have arrived at a composition providing a controlled release of sildenafil by
sublingual route containing (1) from 25 to 100 milligrams of sildenafil; (2) an osmotic
agent; (3) a swellable hydrophilic carrier; and (4) a water dispersible polymer. As
disclosed by El-Rashidy, that composition would have a T90 value in the range of more
than about 25 to about 300 and a ratio of the amount by weight percent of the osmotic
agent to the amount by weight percent of the swellable hydrophilic carrier less than
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Application No. 09/268,957
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1 As pointed out in the Background of the Invention section of applicant's
specification, page 4, lines 13-15, "[t]he main reason for sublingual route of drug
administration is to provide a rapid onset of action of potent drugs."
2 In independent claim 1, applicant recites a composition containing "about 10
to about 75 milligrams of sildenafil." Claims 4 through 22 depend from claim 1, "and
then specify a further limitation of the subject matter claimed." 35 U.S.C. § 112, fourth
paragraph. In each instance, that further limitation does not relate to or further restrict
the amount of sildenafil.
about 4.
It is our judgment, therefore, that a person having ordinary skill would have
arrived at the composition sought to be patented in claim 1 with a reasonable
expectation of providing a rapid onset of action1 and a controlled release of sildenafil;
and promoting the bioavailability of sildenafil while minimizing adverse side effects. We
therefore affirm the examiner's decision rejecting claim 1 under 35 U.S.C. § 103(a).
In Section D of his Appeal Brief, applicant emphasizes the amount of sildenafil
recited in claims 3 through 22. Applicant argues that the cited references would not
have suggested "from about 15 milligrams to about 50 milligrams of sildenafil" recited in
dependent claim 3; or "about 10 to about 75 milligrams of sildenafil" recited in
dependent claims 4 through 22.2 Again, we find it sufficient to note that the oral use of
the citrate salt of sildenafil had been approved by the U.S. Food and Drug
Administration (FDA) for treating male erectile dysfunction at the time applicant's
invention was made. (Specification, page 2, lines 30-33). In dose-response studies,
increasing doses of sildenafil (25 to 100 mg) reportedly increased the erectogenic
efficacy of sildenafil (Background of the Invention, applicant's specification, page 3,
lines 21 through 23). In our judgment, therefore, the amount of sildenafil recited in
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claims 3 through 22 "reads on" an effective amount of this water soluble drug known in
the art at the time the invention was made.
In section E of his Appeal Brief, applicant argues claim 23 separately. It is not
entirely clear to us, however, what limitation in claim 23 applicant would rely on to
patentably distinguish over the prior art. It may be that applicant would predicate
patentability on the recitation "suitable for the treatment of psychogenic impotence"
which appears in claim 23 but not claim 1. See the Appeal Brief, paragraph bridging
pages 11 and 12 ("Here, even if the Bell et al. Patents are deemed to be properly
combinable, arguendo, with the El-Rashidy et al. Patent, there is no indication
whatsoever that out of the myriad of disclosed compounds one of ordinary skill would
turn to sildenafil in the specific controlled release, sublingual composition for the
successful treatment of psychogenic impotence" (emphasis added)). If this is so, the
argument lacks merit. Again, at the time the invention was made, the oral use of the
citrate salt of sildenafil had been approved by the U.S. Food and Drug Administration
(FDA) for the treatment of male erectile dysfunction (Background of the Invention
portion of applicant's specification, page 2, lines 30 through 33).
Conclusion
In conclusion, for reasons set forth in the body of this opinion, we affirm the
rejection of claims 1 and 3 through 23 under 35 U.S.C. § 103(a) as unpatentable over
the combined disclosures of El-Rashidy and the above-cited Bell patents.
The examiner's decision is affirmed.
No time period for taking any subsequent action in connection with this appeal
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may be extended under 37 CFR § 1.136(a).
AFFIRMED
)
Sherman D. Winters )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Toni R. Scheiner )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
Hubert C. Lorin )
Administrative Patent Judge )
Appeal No. 2002-0783
Application No. 09/268,957
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