Ex Parte DeLuca et al

Patent Trial and Appeal Board

Jun 26, 2017

12955567 (P.T.A.B. Jun. 26, 2017)

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.
12/955,567 11/29/2010 Hector F. DeLuca 032026-1212 7723
81079 7590 06/28/2017
Wisconsin Alumni Research Foundation (WARF)
C/O Foley & Lardner LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
EXAMINER
BADIO, BARBARA P
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
06/28/2017 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):
ipdocketing @ foley. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HECTOR F. DELUCA, PAWEL GRZYWACZ, LORI A. PLUM,
and MARGARET CLAGETT-DAME
Appeal 2016-005782
Application 12/955,567
Technology Center 1600
Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134. The Examiner has rejected
the claims for obviousness and obviousness-type double patenting. We have
jurisdiction under 35 U.S.C. § 6(b).
We Affirm.
Appeal 2016-005782
Application 12/955,567
STATEMENT OF CASE
The following claim is representative.
1. A compound of formula I
t
I
wherein X1 and X2 are independently selected from H and hydroxy
protecting groups.
Cited References
DeLuca et al.
DeLuca et al.
Clagett-Dame et al.
DeLuca et al.
US 5,843,928
US 7,244,719 B2
US 8,188,064 B2
WO 2006/057886 A2
Dec. 1, 1998
(“DeLuca ’928”)
July 17, 2007
(“DeLuca ’719”)
May 29, 2012
(“Clagett-Dame”)
June 1,2006
(“DeLuca ’886”)
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Application 12/955,567
Grounds of Rejection
1. Claims 1—19 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over DeLuca ’886 in view of Clagett-Dame.
2. Claims 1—19 are rejected on the ground of nonstatutory
obviousness-type double patenting as being unpatentable over
claims of U.S. Patent No. 7,244,719 in view of DeLuca ’928.
FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Answer at pages
2—13. The following facts are highlighted.
1. The claimed generic compound includes compound 26N, 2-
methylene-19,26,27-trinor-(20S)-la-hydroxyvitamin D3, which
has the following structure:
i
wherein XI and X2 are independently selected from H and
hydroxy protecting groups.
2. The compound 2-methylene-19,26,27-trinor-(20S)-la-
hydroxyvitamin D3 of DeLuca ’886 has the following structure:
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Appeal 2016-005782
Application 12/955,567
where X1 and X2, which may be the same or different, are each
selected from hydrogen or a hydroxy-protecting group.
3. The first Declaration of Hector F. DeLuca dated October 2, 2013,
includes the following Exhibit A.
Titbits. Iiutfcstfotsti CalciSMW Transport Activity «f Cnnspottuds
I; Compound i Dtss>«: 0/M | Isierea&e in O/M. ahuve |
1 i in (Satosal OtSdsoa | mrsiHed oosstto? sues |
S i pntoi ] .'Mswwssi CalcRsnil i §
A**«y I
None (utssfSKed cox*wt4) & s; 4,5 -
; 9,26,27-
hvdro'KyvifsrtssR Rj
fOM")
702» -s A 5,0
1 o.,25-^fevdfoxvYss.a!Tii«
I'h eU5(OH)sRs") 7020 as119.5 =S A 6,0
Assay 2
Mcme Runu-tatied control) 0 «S-2 -
S-fEietliyfsaie' 1-
2 US' l ti-hy siraxy vitamin
R>s
7020 12,4 -A 7.2
Exhibit A shows the ratio of the serosal calcium concentration to the
mucosal calcium concentration (“S/M”) measured in untreated control
rats and in rats dosed at 7020 pmol with the compounds OM (DeLuca
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Appeal 2016-005782
Application 12/955,567
’886 compound), l,25(OH)2D3, and 26N (compound of claimed
invention).” Declaration of DeLuca dated Oct. 2, 2013,15.
4. Specification, Figs. 5A and B are reproduced below.
OTO. SA
tn&Mrttrutt Calcium
FIG, SB
ai Csteia® Tsars* $>£>??
Figures 5 A and 5B of the Specification are bar graphs comparing the
intestinal calcium transport activity of compound 26N with that of
l,25(OH)2D3 at differing dosages. Spec. 6115.
5. Clagett-Dame discloses that
2-MbisP, 2-MP (U.S. Pat. No. 6,579,861) 2-Mpregna (U.S. Pat. No.
6,566,352), have little, if any, activity in mobilizing calcium
from bone or in promoting intestinal calcium transport, whereas
the native hormone calcitriol (la,25-(OH)2D3) is quite potent in both
of these effects using a vitamin D deficient rat model. The above-cited
patents are all hereby incorporated by reference in their entireties and
for all purposes as if fully set forth herein. See also Plum L. A. et
al., Proc. Natl. Acad. Sci. USA 101(18), 6900-9004 (2004).
Likewise, 2a-methylP, (20R)2-MbisP, 2a-methylbisP,
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Appeal 2016-005782
Application 12/955,567
2-MtrisP, (20S)-OM, and VIT-I, have very little bone calcium
mobilization activity as compared to equimolar doses of the
native hormone, la,25-(OH)2D3. Furthermore, these compounds
have less activity as compared to that of l,25-(OH)2D3 in
stimulating intestinal calcium transport. In normal
vitamin D sufficient rats, very high oral doses of 2-MP
and 2-MbisP may be administered without producing an
increase in serum calcium whereas similar doses of the native
hormone produce frank hypercalcemia and even death.
Therefore, 2-MP, 2a-methylP, (20S) 2-MbisP, (20R)2-MbisP,
2a-methylbisP, 2MtrisP, OM and certain other vitamin D
analogs may be used at much higher does than can the native
hormone making them feasible for use in the treatment of
obesity in humans and other animal subjects.
... VD-03 exhibits a relatively low ability to mobilize calcium
from bone, yet retains approximately the same activity as the native
hormone, la,25-(OH)2D3 in promoting intestinal calcium transport.
Col. 133,1.35-Col. 134,1. 4.
6. Structures of compounds 2-MP, 2MbisP, and 2MtrisP (disclosed in
Clagett-Dame), and compound OM as reproduced from
Appellants’ Brief, page 8, are shown below:
2-MP, 2Mh!»P, ami 2MteisP shtwn alongside OM below"
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
PRINCIPLES OF LAW
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Appeal 2016-005782
Application 12/955,567
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
The predecessor court of the Court of Appeals for the Federal Circuit
has also held that members of a homologous series must possess unexpected
properties not possessed by the homologous compound disclosed by the
prior art to be considered unobvious. In re Hass, 141 F.2d 127, 129 (CCPA
1944).
The burden of demonstrating unexpected results rests on the party
asserting them, and “it is not enough to show that results are obtained which
differ from those obtained in the prior art: that difference must be shown to
be an unexpected difference.” In re Klosak, 455 F.2d 1077, 1080 (CCPA
1972). “Mere improvement in properties does not always suffice to show
unexpected results.” In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995).
Moreover, it has been long held that
even though applicant’s modification results in great
improvement and utility over the prior art, it may still not be
patentable if the modification was within the capabilities of one
skilled in the art, unless the claimed ranges “produce a new and
unexpected result which is different in kind and not merely in
degree from the results of the prior art.”
In re Huang, 100 F.3d 135, 139 (Fed. Cir. 1996) (quoting In re Aller, 220
F.2d 454, 456 (CCPA 1955), and citing In re Woodruff, 919 F.2d 1575, 1578
(Fed. Cir. 1990)).
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Application 12/955,567
“An assertion of what seems to follow from common experience is
just attorney argument and not the kind of factual evidence that is required to
rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470
(Fed. Cir. 1997).
Obviousness Rejection 1- DeLuca ’886 and Clagett-Dame
Appellants do not argue claims separately in the Appeal Brief.
Therefore we select claim 1 as the representative claim.
Appellants appear not to take issue with the Examiner’s prima facie
case with respect to this rejection and rely solely on their evidence of
unexpected results. App. Br. 6—7.
The Examiner finds that
• the claimed compounds are higher homologs of the prior art
compounds [DeLuca ’866], i.e., the claimed compounds differ
from the prior art compounds by a single CH2 group;
• like the prior art compounds, the claimed compounds are
useful in treating diseases such as multiple sclerosis, psoriasis,
leukemia, Crohn’s disease, wrinkles, etc. and
• the prior art teaches vitamin D compounds differing only in a
single CH2 group have similar properties as evidenced by
Clagett-Dame.
Ans. 9. The Examiner further finds that the data of Declaration Exhibit A
(FF3) is not commensurate in scope with the claim, which encompasses a
range of dosages of the claimed compound, and that
a single data point is not evidence that said result occurs
irrespective of the dose, i.e., said higher intestinal calcium
transport activity occurs at every dose of the claimed compound
in comparison to the prior art compound at the same dose, over
the entire range. Thus, applicant’s showing is not considered
surprising or unexpected.
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Ans. 13.
Appellants contend that
the prior art and two declarations claimed compounds exhibit
surprising and unexpectedly higher intestinal calcium transport
activity .... This conclusion is supported by unrebutted
evidence from the art of record as well as two declarations from
the inventor. The Examiner ignores the foregoing evidence and,
contrary to law, requires additional evidence of surprising and
unexpected results.
App. Br. 6. Appellants further argue that
it is undisputed that Appellant’s claimed compound at 7020
pmol provides ICTA[‘] that significantly surpasses the art-
appreciated threshold for OM homologues. Based on Clagett
Dame a POSA[1 2] would expect Appellant’s claimed compounds
to exhibit similar ITCA as OM and its homologues - namely,
never exhibit an ITCA higher than the native hormone. See
FOA[3]at 4 (“the art teaches vitamin D compounds differing
only in a single CH2 would have similar properties as evidenced
by Clagett-Dame”). However, the evidence of record clearly
shows the presently claimed compounds surprisingly exhibit an
ITCA at 7020 pmol that is significantly higher than the native
hormone and OM. 1st DeLuca Decl.[4], 17; 2nd DeLuca
Decl.[5],H5-7.
App. Br. 12. Appellants argue that
1ICTA means intestinal calcium transport activity.
2 POSA means person of ordinary skill in the art.
3 FOA stand for Final Office Action.
4 Declaration of Hector F. DeFuca dated October 2, 2013.
5 Declaration of Hector F. DeFuca dated December 10, 2014.
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Application 12/955,567
The ITCA of Appellant’s [sic] compounds is surprising and
unexpected, especially in view of Clagett-Dame. A person of ordinary
skill in the art (“POSA”) would have expected Appellant's claimed
compounds to exhibit similar ITCA as OM and its homologues and,
therefore, never exhibit an ITCA higher than the native hormone. See
Examiner's Answer at 9 (“the art teaches vitamin D compounds
differing only in a single CH2 would have similar properties as
evidenced by Clagett-Dame”). The evidence of record clearly shows
the presently claimed compounds exhibit an ITCA at 7020 pmol that
is 1.2 SIM higher than the native hormone. 1st DeLuca Deck,
17 (explaining 26N “exhibits an increase in intestinal calcium
transport activity significantly greater than both the native hormone
l,25(OH)2D3 and the compound OM”; emphasis added). Further, this
ITCA is at least 2.2 S/M higher than OM at the same dosage, an
increase that is not only significantly larger {id.), but is also
therapeutically significant (2nd DeLuca Deck, H5-7).
Reply Br. 3.
ANALYSIS
We agree with the Examiner’s fact finding, statement of the rejection
and responses to Appellants’ arguments as set forth in the Answer. We find
that the Examiner has provided evidence to support a prima facie case of
obviousness. We provide the following additional comment to the
Examiner’s argument set forth in the Final Rejection and Answer.
Claim 1 is directed to a compound. Pending claims 6 and 7, which are
dependent upon claim 1, are directed to a pharmaceutical composition and
include a large “effective amount” range, e.g., 0.01 pg to about 1 mg (claim
6) and 0.01 pg to about 500 pg (claim 7). Claim 1 is broader than claims 6
and 7 not only in the fact that it is directed to a compound, but because it
encompasses any amount, including beyond the ranges recited in claims 6
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and 7. See Comark Commc ’ns, Inc. v. Harris Corp., 156 F.3d 1182, 1187
(Fed. Cir. 1998) (.
There is presumed to be a difference in meaning and scope
when different words or phrases are used in separate claims. To
the extent that the absence of such difference in meaning and
scope would make a claim superfluous, the doctrine of claim
differentiation states the presumption that the difference
between claims is significant.)
We agree with the Examiner that the data of record is not
commensurate in scope with the pending claims. In particular, Appellants’
Declaration evidence shows one dosage amount, 7020 pmol of claimed
compound 26N, provides a “therapeutically significant difference” in the
ratio of the serosal calcium concentration to the mucosal calcium
concentration (“S/M”). Declaration of Hector F. DeLuca dated December
10, 2014 | 6. By comparison the 260pmol dose of claimed compound 26N
did not provide improved intestinal calcium transport over naturally
occurring vitamin D. FF4 (Spec. Figs. 5A and B).
Moreover, nowhere in either Declaration does the Declarant state that
the results were unexpected or surprising. While the Declarant states that
compound 26N, provides a “therapeutically significant difference” in the
ratio of the serosal calcium concentration to the mucosal calcium
concentration, this is insufficient to establish “unexpected results” as “it is
not enough to show that results are obtained which differ from those
obtained in the prior art: that difference must be shown to be an unexpected
difference.” Klosak, 455 F.2d at 1080. “Mere improvement in properties
does not always suffice to show unexpected results.” Soni, 54 F.3d at 751.
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Application 12/955,567
Nor are Appellants’ arguments of counsel (App. Br. 6—7 and Reply
Br. 4—6), that the claimed invention provides unexpected results, persuasive.
“Attorney’s argument in a brief cannot take the place of evidence.” In re
Pearson, 494 F.2d 1399, 1405 (CCPA 1974); see also Gemtron Corp. v.
Saint-Gobain Corp., 572 F.3d 1371, 1380 (Fed. Cir. 2009) (“[UJnswom
attorney argument... is not evidence and cannot rebut [record evidence].”)
The obviousness rejection is affirmed for the reasons of record.
Obviousness-Type Double Patenting
Claims 1—19 are rejected on the ground of nonstatutory obviousness-
type double patenting as being unpatentable over claims of U.S. Patent No.
7,244,719 in view of 5,843,928.
Claim 1 of the ‘719 patent is reproduced below.
1. A compound having the formula:
where Xi and X2, which may be the same or different, are each
selected from hydrogen or a hydroxy-protecting group.
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Application 12/955,567
Appellants do not contest the Examiner’s prima facie case of
obviousness-type double patenting. Appellants rely on the same evidence of
unexpected results for the obviousness-type double patenting rejection (App.
Br. 7-10) as for the obviousness rejection (App. Br. 12) above. Having
found Appellants’ evidence of unexpected results insufficient, we also
affirm the obviousness-type double patenting rejection.
CONCLUSION OF LAW
The cited references support the Examiner’s obviousness rejection,
and obviousness-type double patenting rejection, which are affirmed for the
reasons of record. Appellants have not provided a preponderance of the
evidence to rebut the Examiner’s prima facie cases. All pending, rejected
claims fall with claim 1.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 41.50(f).
AFFIRMED
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