Ex Parte DeLuca et al

Patent Trial and Appeal Board

Nov 15, 2018

14710744 (P.T.A.B. Nov. 15, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/710,744 05/13/2015
26753 7590 11/19/2018
Andrus Intellectual Property Law, LLP
100 EAST WISCONSIN A VENUE, SUITE 1100
MILWAUKEE, WI 53202
Hector F. DeLuca
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
1256-01915 5655
EXAMINER
PODGORSKI, DANIEL MICHAEL
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
11/19/2018 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
patentdocketing@andruslaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HECTOR F. DELUCA,
LORI A. PLUM, and MARGARET CLAGETT-DAME
Appeal2017-010188
Application 14/710,744
Technology Center 1600
Before RICHARD M. LEBOVITZ, JEFFREY N. FRED MAN, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1, 2 under 35 U.S.C. § 134 involving claims to a
method of reducing serum parathyroid hormone levels in a subject having
primary hyperparathyroidism and exhibiting elevated serum parathyroid
hormone levels. The Examiner rejected the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.
1 Appellants identify the Real Party in Interest as the Wisconsin Alumni
Research Foundation (see App. Br. 1 ).
2 We have considered and herein refer to the Specification of May 13, 2015
("Spec."); Final Office Action of May 13, 2016 ("Final Act."); Appeal Brief
of Jan. 1, 2017 ("App. Br."); Examiner's Answer of May 23, 2017 ("Ans.");
and Reply Brief of July 24, 2017 ("Reply Br.").
Appeal2017-010188
Application 14/710, 7 44
Statement of the Case
Background
"'Hyperparathyroidism' refers to a disorder of the parathyroid glands
in which the parathyroid glands exhibit overactivity. 'Primary'
hyperparathyroidism means the disorder originates in the parathyroid glands
themselves in contrast to 'secondary' hyperparathyroidism which means the
disorder results subsequent to another underlying disease" (Spec. ,r 3). "In
primary hyperparathyroidism, the parathyroid glands become overactive and
release excessive parathyroid hormone (PTH) into the blood stream. One of
the primary functions of PTH is to increase serum calcium levels" (id. ,r 4).
"[E]xcessive serum PTH results in excessive serum calcium levels or
'hypercalcemia,' which presents a number of health risks" (id. ,r 5).
"In order to reduce PTH secretion directly, a calcimimetic also may be
administered to treat primary hyperparathyroidism. A calcimimetic is an
agent that mimics the effect of calcium on the calcium receptors (CaRs) in
the parathyroid gland" (id. ,r 9). "[N]ew vitamin D analogs that can be used
to treat primary hyperparathyroidism are highly desirable" (id. ,r 11 ). The
Specification teaches that "a highly potent active vitamin D analog (A VD),
namely, 2-methylene-19-nor-(20S)-1 a,25-dihydroxyvitamin D3, otherwise
referred to as '2MD' is shown to suppress PTH production in patients
having primary hyperparathyroidism without increasing serum calcium or
serum phosphate" (id. ,r 11 ).
The Claims
Claims 1, 3, 4, and 6-9 are on appeal. Independent claim 1 is
representative and reads as follows:
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Appeal2017-010188
Application 14/710, 7 44
1. A method of reducing serum parathyroid hormone levels
in a subject having primary hyperparathyroidism and exhibiting
elevated serum parathyroid hormone levels, the method
comprising administering a therapeutically effective amount of
2-methylene-19-nor-(20S)-1 a,25-dihydroxyvitamin D3 or a
pharmaceutically acceptable salt thereof to the subject wherein
the serum parathyroid hormone levels in the subject are reduced
without inducing hypercalcemia in the subject.
The Issues
A. The Examiner rejected claims 1, 3, 4, 6, and 9 under 35 U.S.C.
§ 103(a) as obvious over Shevde, 3 Khan, 4 and Taniegra5 (Final Act. 4--7).
B. The Examiner rejected claims 7 and 8 under 35 U.S.C. § 103(a) as
obvious over Shevde, Khan, Taniegra, and Michis-Troussard6 (Final Act. 7-
9).
A. 35 USC§ 103(a) over Shevde, Khan, and Taniegra
The Examiner finds Shevde teaches "2MD is a potent bone-selective
analog of [1, 25-dihydroxy-vitamin D3] effective in treating bone loss
diseases" but acknowledges that Shevde "does not teach treatment of
primary hyperparathyroidism" (Final Act. 5).
The Examiner finds Khan teaches "primary hyperparathyroidism is
associated with bone loss" and that the "calcium receptor allows calcium to
act with parathyroid hormone (PTH) and 1,25-dihydroxy-vitamin D3 in
3 Shevde et al., A potent analog of 1 a,25-dihydroxyvitamin D3selectively
induces bone formation, 99 PROC. NAT'LACAD. SCI. USA 13487-91 (2002).
4 Khan et al., Primary hyperparathyroidism: pathophysiology and impact on
bone, 163 CMAJ 184--7 (2000).
5 Taniegra, Hyperparathyroidism, 69 AM.FAMILY PHYSICIAN 333-9 (2004).
6 Mischis-Troussard et al., Primary hyperparathyroidism with normal serum
intact parathyroid hormone levels, 93 QJ MED. 365-7 (2000).
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Appeal2017-010188
Application 14/710, 7 44
maintaining calcium homeostasis" (Final Act. 5-6). The Examiner finds
Khan teaches "when extracellular calcium binds to the calcium receptor in
the parathyroid cell, PTH secretion and parathyroid cell growth are
inhibited" (id. at 6). The Examiner acknowledges that "[ n ]either Shevde nor
Khan teach serum parathyroid hormone levels in primary
hyperparathyroidism patients" (id. at 6).
The Examiner finds Taniegra teaches "that persistent hypercalcemia
and an elevated serum parathyroid hormone level are the diagnostic criteria
for primary hyperparathyroidism" and that "in the diagnosis and treatment of
hyperparathyroidism that one should check for signs and symptoms of
hypercalcemia and manage crisis if present" (Final Act. 6).
The Examiner finds it obvious
to have administered 2MD to patients with primary
hyperparathyroidism with elevated parathyroid hormone levels.
One would have been motivated to do so because 1) Shevde
teaches that 2MD is a potent bone-selective analog of [1, 25-
dihydroxy-vitamin D3] effective in treating bone loss diseases
by inducing substantial bone growth both in vitro and in vivo,
2) Khan teaches that primary hyperparathyroidism is associated
with bone loss, and 3) Taniegra teaches that patients with
primary hyperparathyroidism have elevated parathyroid
hormone levels and persistent hypercalcemia that should be
managed and monitored.
(Final Act. 6-7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Shevde, Khan, and Taniegra
renders treatment of patients "having primary hyperparathyroidism and
exhibiting elevated serum parathyroid hormone levels" with 2MD obvious
as required by claim 1?
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Application 14/710, 7 44
Findings of Fact
1. Shevde teaches:
We report here on the properties of 2-methylene-19-nor-(20S)-
1 a,25-(0H)2D3 (2MD), a highly potent analog of 1,25(0H)2D3
that induces bone formation both in vitro and in vivo.
Selectivity for bone was first demonstrated through the
observation that 2MD is at least 30-fold more effective than
1,25(0H)2D3 in stimulating osteoblast-mediated bone calcium
mobilization while being only slightly more potent in
supporting intestinal calcium transport. 2MD is also highly
potent in promoting osteoblast- mediated osteoclast formation
in vitro, a process essential to both bone resorption and
formation.
(Shevde 13487, abstract).
2. Figure la of Shevde is reproduced below:
a Bone Gak~luff1 MooHi;,ahon 12--------------------"""
• 1,2~)(0H}zD:t
*Veh
()..,_ ___________________ ~
~· ~
iO 100 ·1000 10000
Figure 1 a shows animals were treated with "the indicated doses of either
1,25(0H)2D3 or 2MD" and "(a) Twenty-four hours after the final dose ...
blood was taken to determine serum calcium levels (mg/dl)" (Shevde 13488,
col. 2).
3. Khan teaches "[p ]rimary hyperparathyroidism has been
associated with bone loss, especially at cortical skeletal sites" (Khan 184,
abstract).
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Application 14/710, 7 44
4. Khan teaches "discovery of the calcium receptor that allows
calcium to act with PTH and 1,25-dihydroxy-vitamin D3 in maintaining
calcium homeostasis" (Khan 184).
5. Khan teaches"[ w ]hen extracellular calcium binds to the
calcium receptor in the parathyroid cell, PTH secretion and parathyroid cell
growth are inhibited" (Khan 184 ).
6. Taniegra teaches "[p ]ersistent hypercalcemia and an elevated
serum parathyroid hormone level are the diagnostic criteria for primary
hyperparathyroidism. Other causes of hypercalcemia are rare" (Taniegra
333, abstract).
7. Taniegra teaches "[ c ]onfirmed hypercalcemia: check for signs
and symptoms of hypercalcemia; manage crisis if present" (Taniegra 3 3 6,
Figure 2).
8. Taniegra teaches "no medical therapies are available to
effectively cure primary hyperparathyroidism. In postmenopausal women,
estrogen may reduce PTH-stimulated bone resorption. The effects of newer
oral bisphosphonates, calcimimetics, and raloxifene are being studied.
Medications may be tried in symptomatic patients who have severe
concurrent illness but are poor surgical candidates" (Taniegra 339, col. 1 ).
Principles of Law
A prima facie case for obviousness "requires a suggestion of all
limitations in a claim," CFMT, Inc. v. Yieldup Int 'l Corp., 349 F.3d 1333,
1342 (Fed. Cir. 2003) and "a reason that would have prompted a person of
ordinary skill in the relevant field to combine the elements in the way the
claimed new invention does." KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
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Application 14/710, 7 44
Analysis
Appellants contend "claim 1 was amended to recite a method of
administering 2MD to a specific class of subjects, which are subjects having
primary hyperparathyroidism and exhibiting elevated serum PTH levels"
(App. Br. 5). Appellants contend "a patient group having primary
hyperparathyroidism and exhibiting elevated serum parathyroid hormone
levels is a distinct patient group and is not the same as a patient group
having primary hyperparathyroidism and exhibiting bone loss" (id. at 9).
Appellants contend "[ a ]dministering a therapeutically effective amount of
2MD to this specific class of patients without inducing hypercalcemia is not
taught or suggested in the art, explicitly or inherently" (id. at 8). Appellants
contend regarding the primary prior art reference cited, Shevde, that:
Even if Shevde discloses the use of 2MD for bone formation,
Shevde does not disclose that 2MD can be administered at a
therapeutically effective dose such that serum PTH levels are
reduced without inducing hypercalcemia in a subject having
primary hyperparathyroidism. Rather, Shevde discloses that
2MD can be administered to increase bone mass in
ovariectomized rats in vivo at a dose that resulted only in a
slight increase in serum calcium levels.
(App. Br. 10).
The Examiner finds "the combination of references teaches the instant
patient population of subjects having both 1) primary hyperparathyroidism,
and 2) elevated parathyroid hormone levels" (Ans. 9). The Examiner finds
"while the two patient populations are not entirely the same, the rejection is
maintained as it reads on the instant patient population as Appellant admits
the patient populations overlap in scope" (id. at 10). The Examiner finds "a
reduction in serum parathyroid hormones and avoidance of hypercalcemia
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Application 14/710, 7 44
would naturally flow from practicing the prior art method of the above
aforementioned references, which render obvious administration of 2MD"
(id. at 11 ).
We agree with Appellants that the patient populations disclosed in
Shevde, Khan, and Taniegra differ from the patient population recited in
claim 1 who must have "primary hyperthyroidism and exhibiting elevated
serum parathyroid levels" and where effective treatment with 2MD reduces
parathyroid levels without inducing hypercalcemia.
In Perricone, the Federal Circuit distinguished between the topical
application of a lotion to skin generally to prevent sunburn, and the topical
application of a lotion to treat sunburned skin, finding that the "issue is not
... whether [the prior art] lotion if applied to skin sunburn would inherently
treat that damage, but whether Pereira discloses the application of its
composition to skin sunburn. It does not." Perricone v. Medicis Pharm.
Corp., 432 F.3d 1368, 1378 (Fed. Cir. 2005).
Similar to Perricone, claim 1 does not require administration of 2MD
to patients with hyperparathyroidism generally, but rather limits
administration to a specific subset of patients who not only meet the general
requirement of elevated serum parathyroid hormone levels disclosed by
Taniegra (FF 6) but further limits the patient population to those for whom
administration of 2MD will not induce hypercalcemia. As Appellants point
out, "Shevde discloses that 2MD can be administered to increase bone mass
in ovariectomized rats in vivo at a dose that resulted only in a slight increase
in serum calcium levels", and further note that Shevde does not show that
these 2MD levels necessarily result in reducing elevated parathyroid
hormone levels (see App. Br. 10; see, e.g., Figure IA of Shevde (FF 2)).
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Appeal2017-010188
Application 14/710, 7 44
Appellants argue that based on 2MD' s calcimetic properties, it would be
expected that it would induce hypercalcemia (see App. Br. 10-11; FF 2). In
response to these arguments, the Examiner has not established that the
ordinary artisan would have expected that 2MD not induce hypercalcemia,
and therefore has not established that the particular patient population at
issue would have been obvious based on the prior art.
We also note, regarding the Examiner's argument that the treatment
would "naturally flow from practicing the prior art method" (Ans. 11) that as
in Perricone, the issue is not whether 2MD would inherently treat the patient
population of claim 1, but rather whether the combination of Shevde, Khan,
and Taniegra suggest treatment of the particular patient subpopulation
required by claim 1. The claim is a method claim, not a product claim, and
therefore the intended patient population is not an "intended use" recitation
but rather is a limitation of the claim. We note that "every limitation
positively recited in a claim must be given effect in order to determine what
subject matter that claim defines." In re Wilder, 429 F.2d 447, 450 (CCPA
1970).
Conclusion of Law
The evidence of record does not support the Examiner's conclusion
that Shevde, Khan, and Taniegra renders treatment of patients "having
primary hyperparathyroidism and exhibiting elevated serum parathyroid
hormone levels" with 2MD obvious as required by claim 1.
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Application 14/710, 7 44
B. 35 US. C. § 103 (a) over Shevde, Khan, Taniegra, and Michis-
Troussard
Having reversed the obviousness rejection of claim 1 for failing to
render the patient population required by claim 1 obvious for the reasons
given above, we also find that the further combination with Michis-
Troussard does not address this issue and therefore does not render the
rejected claims obvious for the same reasons.
SUMMARY
In summary, we reverse the rejection of claims 1, 3, 4, 6, and 9 under
35 U.S.C. § 103(a) as obvious over Shevde, Khan, and Taniegra.
We reverse the rejection of claims 7 and 8 under 35 U.S.C. § 103(a)
as obvious over Shevde, Khan, Taniegra, and Michis-Troussard.
REVERSED
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