Aratana Therapeutics, Inc.

Patent Trials and Appeals Board

Mar 8, 2021

2020004014 (P.T.A.B. Mar. 8, 2021)

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.
14/039,114 09/27/2013 Bill ZOLLERS 064768-463265 2053
27148 7590 03/08/2021
POLSINELLI PC
900 WEST 48TH PLACE
SUITE 900
KANSAS CITY, MO 64112-1895
EXAMINER
THOMAS, TIMOTHY P
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
03/08/2021 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@polsinelli.com
rendsley@polsinelli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte BILL ZOLLERS, LINDA RHODES,
ERNST HEINEN, and GOPINATH DEVARAJ
__________

Appeal 2020-004014
Application 14/039,114
Technology Center 1600
__________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a method
of treating inappetence by administering a composition with capromorelin
the increased food intake by at least 50%. The Examiner rejected the claims
as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Real Party in Interest as Aratana
Therapeutics, Inc. (see App. Br. 4). We refer to the Specification of Sept.
27, 2013 (“Spec.”); Final Action of July 1, 2019 (“Final Act.”); Appeal Brief
of Dec. 31, 2019 (“Appeal Br.”); Examiner’s Answer of Mar. 4, 2020
(“Ans.”); and Reply Brief of May 4, 2020 (“Reply Br.”).
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Statement of the Case
Background
“[C]ompanion animals and livestock can suffer from inappetence and
other disorders that can result in loss of lean muscle, an inability to
participate in physical activity, and other undesirable outcomes for the
companion animal and the owner” (Spec. ¶ 3). “[A]lthough a general
increase in food consumption could be helpful to animals, it is important that
these animals do not experience a significant increase in deposition of
adipose tissue” (id. ¶ 4). “Increasing lean muscle mass is important for the
overall health of companion animals and livestock. A compound for
controlling inappetence while building lean muscle mass has not been
previous provided in the art” (id. ¶ 5).
The Claims
Claims 1, 3, 19, 22, 23, 27, 29–31, 33, 38, 44, 130–132, 138–140,
142, 144–146, 148, 152, 153, and 157. Independent claim 1 is
representative and reads as follows:
1. A method of treating inappetence in a companion
animal,
the method comprising the step of administering at
least once per day a therapeutically effective amount of a
capromorelin-containing composition to the companion
animal for at least five days, which therapeutically effective
amount comprises from 3 milligrams to 4.5 milligrams of
capromorelin per kilogram of body weight of the companion
animal, wherein after the administrating the companion
animal increases food intake by at least 50% relative to food
intake prior to the administrating, and wherein lean muscle
mass in the companion animal is increased by at least 5%
relative to the lean muscle mass of the companion
animal prior to the administrating;
wherein the companion animal is a cat or a dog.
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The Issue2
The Examiner rejected claims 1, 3, 19, 22, 23, 27, 29–31, 33, 38, 44,
130–132, 138–140, 142, 144–146, 148, 152, 153, and 157 under 35 U.S.C.
§ 103(a) as obvious over Pan3 and SciFinder4 (Final Act. 5–12).
The Examiner rejected claims 1, 3, 19, 22, 23, 27, 29–31, 33, 38, 44,
130–132, 138–140, 142, 144–146, 148, 152, 153, and 157 under 35 U.S.C.
§ 103(a) as obvious over Pan, Fraser,5 and SciFinder (Final Act. 15–23).
The Examiner rejects all the claims over Pan and SciFinder and then
separately writes an additional rejection over all the claims further including
Fraser. Because the same issues apply to both rejections, we will consider
them together.
The issues with respect to these rejections are:
(i) Does a preponderance of the evidence of record support the
Examiner’s finding that Pan, Fraser, and SciFinder render the rejected
claims obvious?
(ii) If so, has Appellant provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness?
Findings of Fact
1. Fraser claims a “method of treating a subject suffering from a

2 The provisional obviousness-type double patenting rejection was
withdrawn by the Examiner in view of a terminal disclaimer filed Nov. 8,
2019 (see Ans. 3).
3 Pan et al., Preclinical Pharmacology of CP-424,391, an Orally Active
Pyrazolinone-Piperidine Growth Hormone Secretagogue, 14 Endocrine
121–32 (2001).
4 SciFinder, Capromorelin, CAS Registry Number: 193273-66-4 (accessed
Mar. 7, 2016) (see Final Act. 5).
5 Fraser et al., US 2009/0170747 A1, published July 2, 2009.
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lack of appetite, suppressed appetite, or a disease or disorder that results in
decreased food intake comprising administering to a subject in need thereof
an effective amount of a compound” “comprising administering a growth
hormone secretagogue” “wherein the growth hormone secretagogue is . . .
capromorelin” (Fraser, claims 1, 7, 8).
2. Fraser teaches “[s]ubjects suitable to be treated according to the
present invention include . . . canines, felines, bovines, caprines, equines,
ovines, porcines, rodents” (Fraser ¶ 382).
3. Fraser teaches the “dosage can be from about 0.1 to about 100
mg/kg, administered orally 1-4 times per day. . . . Treatment could continue
for weeks, months or longer. Determination of optimal dosages for a
particular situation is within the capabilities of those skilled in the art”
(Fraser ¶ 385).
4. Pan teaches that capromorelin “is the most extensively
characterized compound from this series and has been selected for clinical
evaluation based on its potent activity and excellent oral bioavailability in
preclinical species” (Pan 122, col. 1).
5. Pan teaches:
The chronic efficacy of 391 was evaluated by its effect on body
weight in subadult and middle-aged female rats. To assess its
effect in growing animals, 391 at 3.9 mg/kg or vehicle (water)
was administered daily for 28 days to 7-wk-old female rats by
oral gavage. Vehicle-treated rats at this age grew rapidly;
however, 391 further augmented weight gain. The difference
between average body weight in the two groups first reached
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significance (p < 0.05) after 15 d of treatment.
(Pan 124, col. 2 to 125, col. 2).

6. Figure 10 is reproduced below:

Fig. 10. Body weight changes during a 4-wk oral study of 391
in subadult female rats. Seven-week-old female Sprague-
Dawley rats were dosed daily by oral gavage with 3.9 mg/kg of
391 (●) or vehicle (water, ○) and weighed. Data are mean ±
SEM for 10 rats per treatment group. *p < 0.01 vs vehicle by
unpaired student’s t-test.
(Pan 128).
7. Pan teaches:
Plasma GH and IGF-I levels were measured in a 5-d study of
once daily oral dosing at 1 mg/kg to beagle dogs. Chronic
dosing produced attenuation of the GH response in conjunction
with elevation of plasma IGF-1 levels . . . Chronic treatment for
12 mo with doses as low as 0.3 mg/kg showed a trend toward
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increased body weight.
(Pan 126, col. 2).
8. Pan teaches “some GHRPs are known to stimulate food intake.
In our studies, food intake was neither controlled nor measured” (Pan 130,
col. 1; citation omitted).
9. Pan teaches, regarding a different growth hormone
secretagogue, that “[i]n dogs, MK-0677 accelerated recovery of muscle mass
and strength during rehabilitation following 10 wk of hindlimb
immobilization” (Pan 130, col. 1).
10. Figure 1 of Pan is reproduced below:

“Fig. 1. Structure of CP-424,391” (Pan 122, col. 2).
11. SciFinder shows that the structure of Fig. 1 of Pan above is
identical to the structure of capromorelin reproduced below:

The figure shows 2-amino-N-[(1R)-2-[(3aR)-2,3,3a,4,6,7-hexahydro-2-
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methyl-3-oxo-3a-(phenylmethyl)-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-oxo-1-
[(phenylmethoxy)methyl]ethyl]-2-methyl-propanamide (SciFinder 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).
Prima facie obviousness can be rebutted by presenting evidence of
secondary considerations and when such evidence is submitted, all of the
evidence must be considered anew. In re Piasecki, 745 F.2d 1468, 1472-
1473 (Fed. Cir. 1984).
Analysis
Prima facie obviousness
We agree with the Examiner that Fraser teaches treating inappetence
using capromorelin (FF 1) in cats and dogs (FF 2) for at least five days in
doses overlapping the range recited in claim 1 (FF 3). We also agree that
Pan teaches treating inappetence using capromorelin in beagles for five days
with 0.3 and 1 mg/kg dosages (FF 7). Pan also teaches treatment of
inappetence in rats using 3.9 mg/kg for more than five days (FF 6).
We recognize Appellant’s argument that Fraser and Pan would not
have a reasonable expectation of success (see Appeal Br. 12) but both
references teach treatment of dogs with capromorelin in similar doses and
“[o]bviousness does not require absolute predictability of success . . . all that
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is required is a reasonable expectation of success.” In re Kubin, 561 F.3d
1351, 1360 (Fed. Cir. 2009)(emphasis omitted).
As to prima facie obviousness, we are not persuaded by Appellant’s
reliance on the functional food intake and lean muscle mass limitations
because the Examiner reasonably takes the initial position that these are
inherent. See In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (“[T]he PTO
can require an applicant to prove that the prior art products do not
necessarily or inherently possess the characteristics of his claimed product.”)
We therefore agree with the Examiner that the claims are prima facie
obvious.
Secondary Considerations
However, prima facie obviousness does not end our inquiry. We then
address Appellant’s evidence of secondary considerations, here unexpected
results regarding precise dosages that increase food intake, and determine if
these results, when weighed with the prima facie case of obviousness,
supports a finding of obviousness or nonobviousness of the claims at issue.
Appellant contends the Specification “demonstrate[s] unexpected and
surprising results” (Appeal Br. 15). Appellant contends a study in dogs
“using Formulation 2 [of capromorelin], the 0.33 mg/kg and 2.0 mg/kg did
not consume at least 50% greater the amount of food as compared to placebo
(no administration). The 3.0 mg/kg dosage rate also did not achieve the at
least 50% increase in food intake using Formulation 2” (Appeal Br. 16,
citing Spec. ¶¶ 234–237, 241). Appellant also relies on a study in beagles
using Formulation 9 of capromorelin showing “that Group 2 [3mg/kg]
consumed 58.7% more food than the placebo group and Group 3 [4.5
mg/kg] consumed 50.5% more food than the placebo group. Group 4,
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getting an effective dosage of 6 mg/kg of bodyweight, only consumed 48.5%
more food than the placebo group” (Appeal Br. 16–17, citing Spec. ¶¶ 225–
233). The Heinen Declaration III6 states that Zollers,7 a post filing date
article, shows “that after administration of a dose of 3.0 mg/kg bodyweight
capromorelin, a dog would consume greater than 50% more food as
disclosed in the specification” (Heinen Decl. III ¶ 4).
The Examiner “agrees that [in Pan] the dosing range from 3.0-4.5
mg/kg of capromorelin is not explicitly taught for dogs, but a range
overlapping, including the specific example 3.9 mg/kg, are clearly taught for
rats” (Ans. 7). The Examiner finds “Zollers is evidentiary that at 3.0 mg/kg,
on average, 60% increase in food consumption occurs with dogs. For the
obvious[ness] basis, reliant on an amount in the instant claimed range, such
as 3.9 mg/kg, at least this level of food consumption is also reasonably
expected” (id. at 8). The Examiner also finds that for the “2, 3, & 4 mg/kg,
there is clearly no statistically significant difference” and therefore “3–4.5
mg/kg, as in the current claims, cannot be considered to have criticality,
because the 2 mg/kg dose (outside the range claimed) is statistically
identical” (id. at 12). The Examiner finds “claimed properties or functions
are presumed to be inherent . . . Thus, the difference between Pan and the
instant claims is only a difference between 1 mg/kg and the claimed range,
3.0–4.5 mg/kg” (id. at 18–19).

6 Third Declaration of Dr. Ernst Heinen, dated Feb. 22, 2019.
7 Zollers et al., Capromorelin oral solution (ENTYCE®) increases food
consumption and body weight when administered for 4 consecutive days to
healthy adult Beagle dogs in a randomized, masked, placebo controlled
study, 13 BMC Veterinary Res. 1–5 (2017).
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We agree with Appellant that the results are unexpected. We note that
the claims are narrowly tailored to these unexpected results, with the claims
limited to treatment of a single condition, inappetence, using a single drug,
capromorelin, in an narrow therapeutically effective amount of 3 to 4.5
mg/kg, in only two species, cats and dogs, and requires the functional effect
of increasing food intake by at least 50% relative to placebo. The results of
Example 5 shows that both 3 and 4.5 mg/kg result in a 50% increase in food
intake while 6 mg/kg does not. The results of Example 7 show that lower
amounts of 0.33, 2, and 3 mg/kg amounts also did not result in a 50%
increase in food intake (Spec. ¶ 241; Appeal Br. 16). This demonstrates
uncertainty of 50% food intake increase at a point around 3 mg/kg of
capromorelin administration. We also agree with Appellant that it would
have been unexpected for a more capromorelin to cause less food intake.
That this is unexpected is supported by Appellant’s expert Dr. Heinen8 who
states “the fact that the administration of 3 to 4.5 mg/kg to a companion
animal of capromorelin resulted in a 50% increase in food intake compared
to the control was surprising and unexpected” (Heinen Decl. II ¶ 5).
We appreciate that Fraser provides suggests a broad overlapping
range of capromorelin dosages (FF 3) and Pan teaches that treatment of rats
with 3.9 mg/kg of capromorelin (FF 6).
But, as the Examiner acknowledges, neither Fraser nor Pan teach or
suggest that relative changes in feed intake result from particular
capromorelin dosages (Ans. 7), so feed intake was not recognized as an

8 Second Declaration of Dr. Heinen, dated Feb. 28, 2018.
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optimizable parameter and therefore not reasonably subject to routine
optimization. See In re Antonie, 559 F.2d 618, 620 (CCPA 1977).
While we agree with the Examiner that a particular dosage of
capromorelin given to an animal would ordinarily have been expected to
inherently result in a particular food intake amount relative to placebo, that
expectation is based on complete identity in the treatment protocol.
Experiments with rats are not necessarily completely identical to
experiments with dogs. Therefore, simply because the range of 3 mg/kg to
4.5 mg/kg results in a 50% increase in dogs does not necessarily require that
treatment with 3.9 mg/kg in rats would yield the same result. And indeed
the Heinen Declaration I9 demonstrates that in this instance the rat model is
different from the dog model, specifically teaching the:
clinical data show that capromorelin administered to male and
female rats at dosages of 1 mg/ kg, 3 mg/kg, 15 mg/kg, and 75
mg/kg were incapable of stimulating a 50% increase in food
intake relative to the food intake prior to the administrating.
Because food intake did not increase by at least 50%,
capromorelin did not stimulate hunger in the rats in these
studies. A larger increase in food intake, such as an increase of
50% presently claimed for the method applied to cats and dogs,
relates to hunger stimulation in the treatment of inappetance.
(Heinen Decl. I ¶ 12).
That is, even at a point within the claimed range, where a greater than
50% increase in food intake occurred in dogs taking 3 mg/kg, no value for
rats, whether 1 mg/kg, 3 mg/kg, 15 mg/kg, or 75 mg/kg resulted in a 50 %
increase in food intake. This is sufficient to defeat an inherency argument
because “[i]nherency . . . may not be established by probabilities or

9 First Declaration of Dr. Heinen, dated Aug. 21, 2017.
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possibilities. The mere fact that a certain thing may result from a given set
of circumstances is not sufficient.” MEHL/Biophile Int’l. Corp. v.
Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999).
We therefore agree with Appellant that the specifically recited range
of 3 mg/kg to 4.5 mg/kg of capromorelin, demonstrated to result in a 50%
increase in food intake in dogs, where values including 0.33 mg/kg, 2 mg/kg
and 6 mg/kg did not result in a 50% increase in food intake in dogs, is
reasonably found to be an unexpected result that is commensurate in scope
with the claims.
Conclusion of Law
(i) A preponderance of the evidence of record supports the
Examiner’s finding that Pan, Fraser, and SciFinder render the rejected
claims obvious.
(ii) Appellant has provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness.

DECISION SUMMARY
In summary:
Claim(s)
Rejected
35
U.S.C. §
Reference(s)
/Basis
Affirmed Reversed
1, 3, 19, 22, 23, 27,
29–31, 33, 38, 44,
130–132, 138–140,
142, 144–146, 148,
152, 153, 157
103 Pan,
SciFinder
1, 3, 19, 22, 23, 27,
29–31, 33, 38, 44,
130–132, 138–140,
142, 144–146, 148,
152, 153, 157
1, 3, 19, 22, 23, 27,
29–31, 33, 38, 44,
130–132, 138–140,
103 Fraser, Pan,
SciFinder
1, 3, 19, 22, 23, 27,
29–31, 33, 38, 44,
130–132, 138–140,
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Claim(s)
Rejected
35
U.S.C. §
Reference(s)
/Basis
Affirmed Reversed
142, 144–146, 148,
152, 153, 157
142, 144–146, 148,
152, 153, 157
Overall Outcome 1, 3, 19, 22, 23, 27,
29–31, 33, 38, 44,
130–132, 138–140,
142, 144–146, 148,
152, 153, 157

REVERSED