Ex Parte Finn et al

Patent Trial and Appeal Board

Apr 4, 2016

12531214 (P.T.A.B. Apr. 4, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/531,214 11/17/2009
5514 7590 04/05/2016
FITZPATRICK CELLA HARPER & SCINTO
1290 A venue of the Americas
NEW YORK, NY 10104-3800
FIRST NAMED INVENTOR
MyhrenFinn
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.
01702.404400. 7703
EXAMINER
BAD IO, BARBARA P
ART UNIT PAPER NUMBER
1628
MAILDATE DELIVERY MODE
04/05/2016 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 PATENT TRIAL AND APPEAL BOARD
Ex parte MYHREN FINN, MARIT LILAND SANDVOLD,
OLE HENRIK ERIKSEN, and STEINER HAGEN
Appeal2014-000338
Application 12/531,214
Technology Center 1600
Before ERIC B. GRIMES, LORA M. GREEN, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1under35 U.S.C. § 134 involving a claim to a steroid
derivative. The claim stands rejected as obvious. We have jurisdiction
under 35 U.S.C. § 6(b).
We reverse.
1 Appellants identify the Real Party in Interest as Clavis Pharma ASA.
(Appeal Br. 1 ).
Appeal2014-000338
Application 12/531,214
STATEMENT OF THE CASE
The invention "relates to certain unsaturated fatty acid derivatives of
therapeutically active glucocorticoides [sic] and pharmaceutical
formulations containing them." (Spec. 1, 11. 5-7.)
Claim 7 is on appeal and is reproduced below:
7. A compound defined as:
(Appeal Br. 9 (Claims App'x.).) The compound having the chemical
structure depicted in claim 7 is a glucocorticoid derivative known as
budesonide elaidate. (Appeal Br. 3.)
Claim 7 stands rejected as obvious under 35 U.S.C. § 103(a) based on
the combination of Axelsson and Myhren.2
DISCUSSION
The Examiner finds that claim 7 is directed to the compound
budesonide elaidate - the trans isomer ofbudesonide oleate, which is
disclosed in Axelsson. (Ans. 4-5.) According to the Examiner, it would
have been prima facie obvious based on the teaching of Myhren to modify
2 Axelsson et al., EP 0 170 642, published Feb. 05, 1986 ("Axelsson");
Myhren et al., US 6,762,175, issued July 13, 2004 ("Myhren").
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Application 12/531,214
"the compound of Axelsson by derivatising with elaidic acid" to produce
budesonide elaidate. (Id.) In support, the Examiner cites Myhren's teaching
that lipophilic derivatives may be prepared by reacting a parent drug with
oleic acid or elaidic acid for improved effect:
the properties of numerous different biologically active
compounds may be favourably modified by derivatisation
with an co-9 C 18 or C20 monounsaturated fatty acid. The
present invention thus provides a widely utilisable but
simple technique for enhancing the value of many drugs
and agricultural chemicals, for instance.
***
The lipophilic derivatives of the present invention may be
prepared by reacting the parent drug or other biologically
active compound molecule with a cis- or trans-n-9
monounsaturated fatty acid, fatty acid alcohol, or fatty
amine having a chain length of 18 or 20 carbon atoms, or
with a reactive derivative of such a fatty acid, fatty alcohol
or fatty amine, for example acid chlorides, reactive esters,
halogenides, or the like. The notation n-9 indicates that the
unsaturation is between the 9 and 10 positions counted from
the C-terminal of the lipidic moiety. Thus, the fatty acids
(and alcohols and amines derived therefrom) which may be
used are cis-9-octadecenoic acid (oleic acid), trans-9-
octadecenoic acid ( elaidic acid), cis-11-eicosenoic acid and
trans-11-eicosenoic acid.
(See, e.g., Myhren col. 2, 11. 43-63; col. 4:31--44 (emphasis added).)
We agree with the Examiner that claim 7 would have been prima facie
obvious over Axelsson and Myhren. Where the prior art and the claimed
subject matter are close structural relatives, such as isomers, a presumption
of obviousness may arise. In re Dillon, 919 F.2d 688, 696 (Fed. Cir. 1990)
(en bane) ("if an examiner considers that he has found prior art close enough
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Application 12/531,214
to the claimed invention to give one skilled in the relevant chemical art the
motivation to make close relatives (homo logs, analogs, isomers, etc.) of the
prior art compound(s), then there arises what has been called a presumption
of obviousness or a primafacie case of obviousness."). Notwithstanding the
close structural relationship between prior art budesonide oleate and the
claimed isomer, budesonide elaidate, the Examiner here does more than rely
on a presumption of obviousness. Indeed, the Examiner provides an express
reason to combine Axelsson and Myhren drawn directly from the teachings
of Myhren, which expresses the desirability of creating therapeutic
derivatives with either oleic acid or elaidic acid. (Ans. 4-5, 7.)
Appellants' argument that the "applied art teaches away" from
budesonide elaidate is not persuasive. (Appeal Br. 3.) Appellants point to
nothing in the art itself showing any inferior or "negative" properties of
budesonide or budesonide oleate. (Appeal Br. 4-5.) Appellants instead rely
on the declaration of Marit Liland Sandvold, Ph.D.,3 but this appears to
reflect testing of budesonide and budesonide oleate performed years after the
present application was filed, and thus fails to show any "negative"
properties of the compounds in Axelsson that would have been known to
3 Appellants submitted a declaration dated October 5, 2012 from one of the
inventors, Marit Liland Sandvold, Ph.D., describing experiments comparing
the effect of the closest-identified prior art (budesonide oleate) to
budesonide elaidate. The objective of the experiment was to study the
effects of budesonide, budesonide oleate, and budesonide elaidate on lung
inflammation in rats (such inflammation induced by exposure to
lipopolysaccharide) by measuring the extent to which each compound
reduced neutrophil influx within the rats' lungs. (Deel. ,-i,-i 1-6.)
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Appeal2014-000338
Application 12/531,214
those of skill in the art at the time of invention. (Id.; Deel. passim.) The
testing does not, therefore, evidence any "teaching away" in the art.
Appellants' argument that Myhren does not provide adequate
motivation to combine the prior art is similarly unpersuasive. Appellants
point out that Myhren does not compare the effectiveness of elaidate and
oleate derivatives to each other (Appeal Br. 6.), and also that Myhren
"makes a comparative study only of derivitized prednisolone, not derivitized
budesonide." (Id.) Such head-to-head testing of elaidic acid versus oleic
acid derivatives is, however, not necessary to establish a prima facie case
here. Myhren teaches that elaidate and oleate derivatives are expected to
provide improved anti-inflammatory effect. (Myhren col. 3, 11. 12-32; col.
4:31--44.) And we agree with the Examiner that a person of ordinary skill in
the art would, therefore, combine the teachings of Axelsson and Myhren,
with the expectation that the "corresponding trans isomer of budesonide
oleate would also have improved anti-inflammatory property." (Ans. 7
(emphasis added). )4
4 We also reject Appellants' argument that the case law compels a finding in
their favor. (Appeal Br. 6-7.) Takeda Chem. Indus., Ltd. v. Alphapharm
Pty., Ltd., 492 F.3d 1350 (Fed. Cir. 2007) and Proctor & Gamble Co. v.
Teva Pharma USA Inc., 566 F.3d 989 (Fed. Cir. 2009) are distinguishable.
In both cases, the Federal Circuit affirmed a lower court's determination of
nonobviousness based on a unique record below that differs from the facts in
this appeal. For example, in Takeda, the evidence showed that the lead prior
art compound was known at the time of invention to be toxic and carry side
effects like weight gain - making that compound an undesirable starting
point to modify further and arrive at the claimed antidiabetic agent. Takeda,
492 F.3d at 1358.
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Appeal2014-000338
Application 12/531,214
Even if a prima facie case of obviousness exists, Appellants contend
the evidence provided in Dr. Sandvold' s declaration rebuts it. (Appeal Br.
4-5; Reply Br. 3--4.) According to Appellants, the data in Dr. Sandvold's
declaration "clearly show that budesonide oleate is ineffective in preventing
the influx of neutrophils to the lungs." (Appeal Br. 4-5.) Appellants argue
that the cited references "would not have provided a person of ordinary skill
with the reasonable expectation that budesonide elaidate would have
superior properties compared to its isomer budesonide oleate." (Id. at 5.)
Appellants argue that the Examiner erred in "ignoring [this] expert
testimony regarding the indicia of nonobviousness, namely the unexpected
results of the present invention." (Reply Br. 3--4.)
We agree with Appellants that Dr. Sandvold's declaration evidences
significantly superior performance of budesonide elaidate compared to the
closest prior art. More particularly, the experiments described in the
declaration demonstrated that the claimed budesonide elaidate exhibited a
roughly 2X (100%) improvement (measured by reduction of neutrophil
influx) over prior art budesonide oleate, and that the prior art failed to reach
statistically-significant effect. (Deel. ,-i7 (showing budesonide elaidate
"reduced the influx of neutrophiles to the lungs with 59.5% reduction versus
the LPS challenged control, significance level p<0.05" while "there was no
activity for budesonide at neutrophil influx and the effect ofbudesonide
oleate was only a 30.6% reduction ... [that] did not reach statistical
significance versus the vehicle treated animals simulated with LPS.").) And
Dr. Sandvold repeatedly describes these results as significant and surprising.
(Id. at ,-i,-i 5, 7, 8, 10.)
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Application 12/531,214
In response, the Examiner essentially rests on the merits of the prima
facie case. The Examiner does not, for example, challenge the methodology
of the experiments or the reliability of the results provided in the declaration.
The Examiner acknowledges that Dr. Sandvold' s declaration shows
"beneficial results of the elected compound" (Final Act. 4), but argues that
"evidence of unexpected results must be weighed against supporting prima
facie obviousness in making a final determination." (Ans. 7-8.)
We conclude that the results shown in Dr. Sandvold' s declaration
rebut the prima facie case here. The teachings of the prior art, for instance,
do not provide any suggestion that an elaidate derivative of budesonide
would perform in such a substantially improved manner compared to an
oleate derivative. On the other hand, the testing evidenced in Dr. Sandvold' s
declaration shows a "surprising" 2x improvement of the claimed compound
over the prior art compound (Deel. ,-i 7); in view of this unrebutted evidence,
we are unwilling to find that discovery ofbudesonide elaidate's extent of its
therapeutic activity would have been expected based on the prior art as
argued by the Examiner. (Ans. 10). In re Soni, 54 F.3d 746, 751 (Fed. Cir.
1995) ("when an applicant demonstrates substantially improved results ...
and states that the results were unexpected, this should suffice to establish
unexpected results in the absence of evidence to the contrary.")
We are persuaded on this record that the improvement observed with
budesonide elaidate is greater to an unobvious extent compared to the prior
art. Accordingly, we determine that Appellants have provided objective
indicia of non-obviousness in the form of unexpected results that rebuts the
Examiner's prima face case.
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Application 12/531,214
Conclusion of Law
For the reasons discussed above, the Examiner has not established by
a preponderance of the evidence that claim 7 would have been obvious.
SUMMARY
We reverse the rejection of claim 7 as obvious under 35 U.S.C.
§ 103(a) over Axelsson and Myhren.
REVERSED
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