Ex Parte Leonard

Board of Patent Appeals and Interferences

Sep 14, 2011

10821278 (B.P.A.I. Sep. 14, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/821,278 04/08/2004 Thomas W. Leonard 9448-51 1153
20792 7590 09/14/2011
MYERS BIGEL SIBLEY & SAJOVEC
PO BOX 37428
RALEIGH, NC 27627
EXAMINER
JAVANMARD, SAHAR
ART UNIT PAPER NUMBER
1627
MAIL DATE DELIVERY MODE
09/14/2011 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte THOMAS W. LEONARD
__________

Appeal 2010-009295
Application 10/821,278
Technology Center 1600
__________

Before TONI R. SCHEINER, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of treating vasomotor symptoms. The Examiner rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

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Statement of the Case
Background
The Specification teaches that “vasomotor hot flashes are a common
symptom in women during menopause. . . . Various studies have suggested
that megestrol acetate, a progestational agent, can decrease the frequency of
hot flashes” (Spec. 2 ¶ 0008). The Specification teaches that “a progestin
administered in large doses, together with large amounts of a synthetic
estrogen, induces changes in blood lipids which . . . have been implicated in
the appearance of strokes and myocardial infarction . . . it may be desirable
to relieve vasomotor symptoms through alternative methods of therapy”
(Spec 2 ¶ 0008).
The Claims
Claims 10-16, 19-23, and 29 are on appeal. Claim 10 is representative
of the rejected claims. See 37 C.F.R. § 41.37(c)(1)(vii).
Claim 10 reads as follows:
10. A method of treating vasomotor symptoms
comprising:
administering a first dose of a therapeutic
amount of an estrogenic compound to a subject;
administering a second dose of a therapeutic
amount of an estrogenic compound at a later time
period to the subject, said second dose comprising
a lower dosage of said therapeutic amount of an
estrogenic compound than said first dose; and
administering a therapeutic amount of a
progestational agent of less than 20 mg.

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The issue
The Examiner rejected claims 10-16, 19-23, and 29 under 35 U.S.C. §
103(a) as obvious over Pickar,
1
Labrie,
2
Coulson,
3
Prestwood,
4
and Utian
5

(Ans. 6-10).
The Examiner finds that “Pickar teaches a composition comprising
preferably conjugated estrogens such as PREMARIN (conjugated equine
estrogens, USP) and CENESTIN (synthetic conjugated estrogens, A), and
medroxyprogesterone acetate (androgen and progestin) as an estrogen
replacement therapy” (Ans. 6). The Examiner finds that “for the treatment
of vasomotor symptoms, it is preferred that the treatment may last from one
month to several years, depending on the severity and duration of the
symptoms” (Ans. 8).
The Examiner finds that Prestwood teaches “that breast tenderness,
bleeding, and endometrial changes were significantly less frequent in the
0.25 mg/day and placebo groups compared with the higher dose groups”
(Ans. 9). The Examiner finds that Utian teaches that “the main reason for

1
Pickar, James H., US 2001/0034340 A1, published Oct. 25, 2001.
2
Labrie, Fernand, US 5,798,347, issued Aug. 25, 1998.
3
Coulson, Patricia B., US 4,381,298, issued Apr. 26, 1983.
4
Prestwood et al., The effect of low dose micronized 17-estradiol
on bone turnover, sex hormone levels, and side effects in older
women: a randomized, double blind, placebo-controlled study, 85
J. CLINICAL ENDOCRINOLOGY AND METABOLISM 4462-4469
(2000).
5
Utian et al., Efficacy and safety of low, standard, and high
dosages of an estradiol transdermal system (Esclim) compared
with placebo on vasomotor symptoms in highly symptomatic
menopausal patients, 181 AM. J. OBSTET. GYNECOL. 71-79 (1999).
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changing to a lower dosage in ERT is to reduce estrogen side effects,
especially genital bleeding and breast pain. It is therefore necessary to obtain
a balance between relief of symptoms and the risk of adverse effects” (Ans.
9).
The Examiner finds it obvious
to administer the dosage in a first and lower second dosage
or even a lower third dosage is because (1) Prestwood et al.
teaches it was found that breast tenderness, bleeding, and
endometrial changes were significantly less frequent in the
0.25 mg/day and placebo groups compared with the higher
dose groups (2) Utian et al. teaches the main reason for
changing to a lower dosage in ERT is to reduce estrogen
side effects, especially genital bleeding and breast pain. It is
therefore necessary to obtain a balance between relief of
symptoms and the risk of adverse effects and (3) Pickar
teaches the dosage of a patient may need to be adjusted
(either up or down), to achieve the desired effect during the
middle of a treatment period.

(Ans. 10).
Appellant contends that Pickar fails “to explicitly teach or suggest a
method of treating vasomotor symptoms wherein the second dose of an
estrogenic compound is lower than the first dose” (App. Br. 6). Appellant
contends that the “preferred amounts as indicated by Pickar et al. and by the
disclosures of Utian et al. suggest that treatment be initiated at low doses of
estrogenic compounds. The dose of estrogenic compounds discussed by
Pickar and Utian et al. is lower than those envisioned for the first dose in the
method of the present invention” (App. Br. 6). Appellant contends that “the
disclosures of Prestwood et al. do not explicitly disclose or suggest a method
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of treating vasomotor symptoms wherein the second dose of an estrogenic
compound is lower than the first dose” (App. Br. 6).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the prior art renders obvious
the method of claim 10?
Findings of Fact
1. Pickar teaches “methods and pharmaceutical compositions for
providing hormone replacement therapy in perimenopausal, menopausal,
and postmenopausal women through the continuous administration of
combinations of conjugated estrogens and medroxyprogesterone acetate”
(Pickar 1 ¶ 0002).
2. Pickar teaches that estrogen replacement therapy “has been
recognized as an advantageous treatment for relief of vasomotor symptoms”
(Pickar 1 ¶ 0005).
3. Pickar teaches that “it is desirable, and an objective to find the
lowest dose estrogen plus progestin HRT product, which also minimizes or
eliminates endometrial hyperplasia” (Pickar 3 ¶ 0007).
4. Pickar teaches a variety of dosages, noting that it “is preferred
that the dosage of PREMARIN is about 0.625 mg per day or less, and is
more preferred that the dosage of PREMARIN is either about 0.45 mg per
day or about 0.30 mg per day” (Pickar 3 ¶ 0016).
5. Pickar teaches that it “is preferred that the MPA is given in a
fixed daily dosage of about 1.5 mg, with an appropriate dose of conjugated
estrogens, preferably equivalent to about 0.45 mg or about 0.30
PREMARIN” (Pickar 4 ¶ 0022).
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6. Pickar teaches that “the dosage of a patient may need to be
adjusted (either up or down), to achieve the desired effect during the middle
of a treatment period” (Pickar 4 ¶ 0022).
7. Labrie teaches “administering a progestin (e.g.
medroxyprogesterone acetate”, thus teaching that medroxyprogesterone
acetate is a progestin (Labrie, col. 15, ll. 50-51).
8. Coulson teaches “an androgen (medroxyprogesterone acetate; 1
mg/kg b.w.)”, thus teaching that medroxyprogesterone acetate is an
androgen (Coulson, col. 3, ll. 42-43).
9. Prestwood teaches that “[b]reast tenderness, bleeding and
endometrial changes were significantly less frequent in the 0.25 mg/day and
placebo groups compared with the higher dose groups” (Prestwood abstract).
10. Utian teaches that in “2 previous studies in which dose titration
was allowed, clinical efficacy was maintained in patients who switched from
patches delivering 0.050 mg of estradiol in 24 hours to dosages of 0.025
mg/24 h. The main reason for changing to a lower dose was to reduce
estrogen side effects” (Utian 78, col. 2).
11. Utian teaches that “[w]omen frequently discontinue hormone
replacement therapy altogether because of unwanted side effects, especially
genital bleeding and breast pain. It is therefore necessary to obtain a balance
between relief of symptoms and the risk of adverse effects, particularly signs
of hyperestrogenism such as endometrial hyperplasia or mastorlynia” (Utian
78, col. 2).
12. Utian teaches that a “logical approach is to initiate treatment
with a low dose of estradiol, which is likely to provide an acceptable level of
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relief from vasomotor symptoms while minimizing the signs of
hyperestrogenism” (Utian 78, col. 2).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
Analysis
Pickar teaches a method of treating vasomotor symptoms (FF 2) by
administering a therapeutic amount of an estrogenic compound and a
progestational agent, medroxyprogesterone acetate (FF 1, 4) where the
progestational agent is less than 20 mg (FF 5). Pickar teaches that “the
dosage of a patient may need to be adjusted (either up or down), to achieve
the desired effect during the middle of a treatment period” (Pickar 4 ¶ 0022;
FF 6).
Labrie and Coulson teach that medroxyprogesterone acetate is a
progestin and androgen (FF 7-8).
Utian teaches that in “2 previous studies in which dose titration was
allowed, clinical efficacy was maintained in patients who switched from
patches delivering 0.050 mg of estradiol in 24 hours to dosages of 0.025
mg/24 h. The main reason for changing to a lower dose was to reduce
estrogen side effects” (Utian 78, col. 2; FF 10). Utian teaches that “[w]omen
frequently discontinue hormone replacement therapy altogether because of
unwanted side effects, especially genital bleeding and breast pain. It is
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therefore necessary to obtain a balance between relief of symptoms and the
risk of adverse effects, particularly signs of hyperestrogenism such as
endometrial hyperplasia or mastorlynia” (Utian 78, col. 2; FF 11).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that an ordinary artisan would have reasonably found it obvious to
administer lower dosage “second” doses of an estrogenic compound for
treating vasomotor symptoms since Utian teaches that clinical efficacy was
maintained when the dose was reduced to reduce the side effect (FF 10) and
that this would permit continuation of therapy and relieving symptoms while
reducing side effects (FF 11). Further, Pickar recognizes that such a dosage
adjustment may be necessary during treatment (FF 6). The ordinary artisan,
treating a patient with the composition of Pickar, would have recognized that
in patients with unwanted side effects, a dosage adjustment to a reduced
dosage would reduce the side effects, while Utian evidences that the reduced
dosage would maintain clinical efficacy (FF 10). “If a person of ordinary
skill can implement a predictable variation, § 103 likely bars its
patentability.” KSR, 550 U.S. at 417.
As noted by the Court in KSR, “[a] person of ordinary skill is also a
person of ordinary creativity, not an automaton.” 550 U.S. at 421.
Appellant contends that Pickar fails “to explicitly teach or suggest a
method of treating vasomotor symptoms wherein the second dose of an
estrogenic compound is lower than the first dose” (App. Br. 6).
We are not persuaded. Pickar expressly teaches that “the dosage of a
patient may need to be adjusted (either up or down), to achieve the desired
effect during the middle of a treatment period” (Pickar 4 ¶ 0022; FF 6). The
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express suggestion that dosage may be adjusted down when desired provides
a direct suggestion to reduce the dosage of the estrogenic compound.
Appellant contends that the “preferred amounts as indicated by Pickar
et al. and by the disclosures of Utian et al. suggest that treatment be initiated
at low doses of estrogenic compounds. The dose of estrogenic compounds
discussed by Pickar and Utian et al. is lower than those envisioned for the
first dose in the method of the present invention. As such, the disclosures of
Pickar et al. and Utian et al. teach away from a high first dose” (App. Br. 6).
We are not persuaded. Claim 10 does not require any specific amount
of a first dose, only that the first dose is higher than the second dose (see
Claim 10). While Pickar and Utian teach particular dosing regimens, Pickar
teaches a variety of dosages, noting that it “is preferred that the dosage of
PREMARIN is about 0.625 mg per day or less, and is more preferred that
the dosage of PREMARIN is either about 0.45 mg per day or about 0.30 mg
per day” (Pickar 3 ¶ 0016; FF 4). Similarly, Utian teaches that doses of 0.50
mg to 0.025 mg of estradiol can be administered (FF 10).
Thus, an ordinary artisan would recognize that a variety of different
dosages are taught, and that a higher initial dosage may be selected to relieve
symptoms, but that if that higher dosage results in unwanted side effects, the
dosage may be reduced, as expressly taught by Pickar and Utian (FF 6, 10).
The teachings in Pickar and Utian teach towards, not away from the
invention and do not criticize the idea of lowering the dosage where
appropriate. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) (The
court found that the “prior art’s mere disclosure of more than one alternative
does not constitute a teaching away from any of these alternatives because
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such disclosure does not criticize, discredit, or otherwise discourage the
solution claimed.”)
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
prior art renders obvious the method of claim 10.
SUMMARY
In summary, we affirm the rejection of claim 10 under 35 U.S.C. §
103(a) as obvious over Pickar, Labrie, Coulson, Prestwood, and Utian.
Pursuant to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we also affirm the rejection
of claims 11-16, 19-23, and 29, as these claims were not argued separately.

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED

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