Heron Therapeutics, Inc.

Patent Trials and Appeals Board

Mar 19, 2021

2020004086 (P.T.A.B. Mar. 19, 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.
15/702,697 09/12/2017 Thomas B. Ottoboni 092459-0217/8026.US08 6151
108547 7590 03/19/2021
McDermott Will & Emery LLP
500 North Capitol Street NW
Washington, DC 20001
EXAMINER
LIU, TRACY
ART UNIT PAPER NUMBER
1612
NOTIFICATION DATE DELIVERY MODE
03/19/2021 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):
mweipdocket@mwe.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte THOMAS B. OTTOBONI and
LEE ANN LYNN GIROTTI1
________________

Appeal 2020-004086
Application 15/702,697
Technology Center 1600
________________

Before ERIC B. GRIMES, JOHN G. NEW, and
MICHAEL A. VALEK, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the term “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant identifies Heron Therapeutics, Inc. as the
real party-in-interest. App. Br. 1.
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Application 15/702,697

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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1–20. Specifically, claims 1–3, 5, 6,
13, 14, and 16–18 stand rejected as unpatentable under 35 U.S.C. § 103 as
being obvious over Ng et al. (US 2012/0283253 A1, November 8, 2012)
(“Ng”).
Claim 4 stands rejected as unpatentable under 35 U.S.C. § 103 as
being obvious over the combination of Ng and Campbell et al. (US
2010/0041765 A1, February 18, 2010) (“Campbell”).
Claims 7–12 stand rejected as unpatentable under 35 U.S.C. § 103 as
being obvious over the combination of Ng and Dadey et al. (US
2008/0299168 A1, December 4, 2008) (“Dadey”).
Claims 15, 19, and 20 stand rejected as unpatentable under 35 U.S.C.
§ 103 as being obvious over the combination of Ng and Wohabrebbi (US
2010/0015049 A1, January 21, 2010) (“Wohabrebbi”).
We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to compositions comprising
a delivery vehicle or delivery system and an active agent dispersed within
the delivery vehicle or system, wherein the delivery vehicle or system
contains a polyorthoester polymer and a polar aprotic solvent. Spec. Abstr.

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REPRESENTATIVE CLAIM
Independent claim 1 is the sole independent claim and recites:
1. A composition, consisting essentially of: a delivery
vehicle, an amide local anesthetic, and a non-steroidal anti-
inflammatory drug (NSAID), wherein the ratio of the amide local
anesthetic to the NSAID ranges from about 15:1 to 50:1, wherein
the NSAID is present in the composition in an amount between
about 0.005-0.75 wt%, wherein the NSAID is not diclofenac
and/or ketoprofen, and wherein the composition contains no
additional active agents.

App. Br. 13.

ISSUES AND ANALYSES
We decline to adopt the Examiner’s findings, reasoning, and
conclusion that the claims on appeal are prima facie obvious over the
combined cited prior art. We address the arguments raised by Appellant
below.

1. Rejection of claims 1–3, 5, 6, 13, 14, and 16–18 over Ng
Issue

Appellant argues that the Examiner erred because the teachings and
suggestions of Ng would not have motivated a skilled artisan to arrive at the
invention recited by claim 1. App. Br. 5.

Analysis
The Examiner finds that Ng teaches a semi-solid delivery vehicle
containing a polyorthoester and an active agent. Final Act. 3 (citing Ng
Abstr.). The Examiner finds that the term “active agent,” as taught by Ng,
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includes any compound or mixture of compounds which produces a
beneficial or useful result, and can include anti-inflammatory agents such as
ibuprofen (a NSAID) and amide-type local anesthetics such as bupivacaine.
Id. (citing Ng ¶ 23). The Examiner finds that Ng further teaches that its
composition provides controlled delivery of active agents. Id. (citing Ng
¶ 9).
The Examiner finds that Ng teaches that the concentration of the
active agent in the semi-solid polyorthoester composition can vary over a
wide range (e.g., 0.1–80 wt. %, based on the composition as a whole),
depending on a variety of factors, such as the release profile of the
composition, the therapeutically effective dose of the active agent, and the
desired length of the time period during which the active agent is released.
Final Act. 3 (citing Ng ¶ 75). The Examiner also finds that the concentration
of the polyorthoester may range between 1–99 wt. %. Id. (citing Ng ¶ 76).
The Examiner finds, however, that Ng does not teach the claimed
ratio of amide local anesthetic to NSAID of about 15:1 to 50:1 or that
NSAID is present in an amount between about 0.005-0.75 wt%. Final Act.
4.
Nevertheless, the Examiner concludes, it would have been obvious to
a person of ordinary skill in the art to have incorporated, e.g., 0.125 wt%
NSAID and 5 wt% amide local anesthetic into the composition of Ng,
because that amount totals to 5.125 wt%, which is within Ng’s range of 0.1-
80 wt%, and the ratio of amide local anesthetic to NSAID is 40:1. Final Act.
4–5. The Examiner reasons that, in cases in which the claimed ranges
“overlap or lie inside ranges disclosed by the prior art,” a prima facie case of
obviousness exists. Id. at 5 (citing MPEP § 2144.05 (A)).
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Appellant acknowledges that Ng teaches a composition comprising an
active agent and a semi-solid delivery vehicle, and defines an active agent as
including any compound or mixture of compounds, which produces a
beneficial or useful result. App. Br. 5–6 (citing Ng ¶ 23). However,
Appellant argues, Ng teaches an extensive and varied list of potential active
agents, including anti-inflammatory agents and amide local anesthetics. Id.
at 6 (citing Ng ¶ 23). Appellant contends that Ng does not disclose or
exemplify any composition comprising a mixture of any particular
compounds. Id. Appellant asserts that the list of potential active agents
represents an untenable number of possible combinations of two, three, or
more constituent compounds. Id. at 6–7. Consequently, argues Appellant,
Ng alone cannot be said to render obvious the combination of anti-
inflammatory agent and amide-type local anesthetic, and excluding any
additional active agent. Id. at 7.
Furthermore, Appellant contends, Ng does not instruct the skilled
artisan that any combination of its listed active agents will produce an
effective formulation exhibiting any desirable therapeutic properties. App.
Br. 7 (citing, contra, Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804,
805–06 (Fed. Cir. 1989)). In contrast, Appellant asserts that it has found that
the addition of an NSAID to a local amide anesthetic, as recited in claim 1,
can synergistically extend the analgesic effect of the local amide anesthetic.
Id. (citing Spec. ¶¶ 183, 281).
Summarizing, Appellant argues that Ng teaches formulations of wide
varieties of one or more compounds with a delivery vehicle, and does not
teach specific formulations comprising an anti-inflammatory agent and local
anesthetic. App. Br. 8. Appellant points to Impax Labs., Inc. v. Lannett
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Holdings Inc., 893 F.3d 1372 (Fed. Cir. 2018), in support of its argument
that Ng is insufficient to render obvious the claimed composition comprising
anti-inflammatory agents and local anesthetics. Id. (citing Impax, 893 F.3d
at 1380–81).
We agree with Appellant that the Examiner has failed to establish a
prima facie case of obviousness over Ng. Ng is directed to: “A semi-solid
delivery vehicle contain[ing] a polyorthoester and an excipient, and a semi-
solid pharmaceutical composition contain[ing] an active agent and the
delivery vehicle.” Ng Abstr.; see also ¶¶ 8–9:
A first objective of the present invention is to provide a semi-
solid delivery vehicle which comprises a polyorthoester and an
excipient.… Another objective of the present invention is to
provide a controlled release semi-solid pharmaceutical
composition for local controlled delivery of an active agent. The
composition comprises an active agent and the semi-solid
delivery vehicle.

Ng expressly teaches that an “active agent” is defined as “any
compound or mixture of compounds which produces a beneficial or useful
result,” and distinguishes active agents from “such components as vehicles,
carriers, diluents, lubricants, binders and other formulating aids, and
encapsulating or otherwise protective components.” Ng ¶ 23. Ng
subsequently provides a list of possible examples of active agents:
Examples of active agents and their pharmaceutically acceptable
salts, are pharmaceutical, agricultural or cosmetic agents.
Suitable pharmaceutical agents include locally or systemically
acting pharmaceutically active agents which may be
administered to a subject by topical or intralesional application
(including, for example, applying to abraded skin, lacerations,
puncture wounds, etc., as well as into surgical incisions) or by
injection, such as subcutaneous, intradermal, intramuscular,
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intraocular, or intra-articular injection. Examples of these agents
include, but not limited to, anti-infectives (including antibiotics,
antivirals, fungicides, scabicides or pediculicides), antiseptics
(e.g., benzalkonium chloride, benzethonium chloride,
chlorhexidine gluconate, mafenide acetate, methylbenzethonium
chloride, nitrofurazone, nitromersol and the like), steroids (e.g.,
estrogens, progestins, androgens, adrenocorticoids, and the like),
therapeutic polypeptides (e.g. insulin, erythropoietin,
morphogenic proteins such as bone morphogenic protein, and the
like), analgesics and anti-inflammatory agents (e.g., aspirin,
ibuprofen,2 naproxen, ketorolac, COX-1 inhibitors, COX-2
inhibitors, and the like), cancer chemotherapeutic agents (e.g.,
mechlorethamine, cyclophosphamide, fluorouracil, thioguanine,
carmustine, lomustine, melphalan, chlorambucil, streptozocin,
methotrexate, vincristine, bleomycin, vinblastine, vindesine,
dactinomycin, daunorubicin, doxorubicin, tamoxifen, and the
like), narcotics (e.g., morphine, meperidine, codeine, and the
like), local anesthetics (e.g., the amide- or anilide-type local
anesthetics such as bupivacaine, dibucaine, mepivacaine,
procaine, lidocaine, tetracaine, and the like), antiemetic agents
such as ondansetron, granisetron, tropisetron, metoclopramide,
domperidone, scopolamine, and the like, antiangiogenic agents
(e.g., combrestatin, contortrostatin, anti-VEGF, and the like),
polysaccharides, vaccines, antigens, DNA and other
polynucleotides, antisense oligonucleotides, and the like. The
present invention may also be applied to other locally acting
active agents, such as astringents, antiperspirants, irritants,
rubefacients, vesicants, sclerosing agents, caustics, escharotics,
keratolytic agents, sunscreens and a variety of dermatologics
including hypopigmenting and antipruritic agents. The term
“active agents” further includes biocides such as fungicides,
pesticides, and herbicides, plant growth promoters or inhibitors,
preservatives, disinfectants, air purifiers and nutrients. Prodrugs

2 Ibuprofen and naproxen are NSAIDs. See, e.g., Cleveland Clinic, Non-
Steroidal Anti-Inflammatory Drugs (NSAIDs), available at:
https://my.clevelandclinic.org/health/drugs/11086-non-steroidal-anti-
inflammatory-medicines-nsaids (last visited March 5, 2021).
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of the active agents are included within the scope of the present
invention.

Id. (emphases added). We quote this passage at length to demonstrate that
the genus of “active agents” contemplated by Ng is exceedingly capacious
and diverse, including, at least, agents as disparate as narcotics, antiviral
drugs, fungicides, nucleic acids, and sunscreens, in addition to amide local
anesthetics and NSAIDs.
Ng also provides several exemplary combinations of active agents that
can be incorporated into its compositions:
Exemplary compositions of this invention, and their uses,
include:

(1) compositions containing local anesthetics, optionally in
combination with glucocorticosteroids … for the prolonged
relief of local pain or a prolonged nerve blockade [see also ¶ 101]
.…

(6) compositions containing anti-inflammatory agents such as
the NSAIDs, e.g. ibuprofen, naproxen, COX-1 or COX-2
inhibitors, and the like, or glucocorticosteroids, for intra-articular
application or injection;
….

(12) compositions comprising a combination of two or more of
the above active agents for concurrent therapeutic applications.

Ng ¶ 81.
With respect to local anesthetics, Ng teaches:
Conventionally, the soluble local anesthetics can be applied
topically and by injection, and the slightly soluble local
anesthetics are used only for surface application. The local
anesthetics conventionally administered by injection can also be
divided into two groups, esters and non-esters.… The non-esters
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are anilides (amides or nonesters) which include bupivacaine,
lidocaine, mepivacaine, pyrrocaine and priloca[i]ne
….

The semi-solid injectable form of a local anesthetic of the present
invention is prepared by incorporating the local anesthetic into
the delivery vehicle in a manner as described above. The
concentration of the local anesthetic may vary from about 0.1–
80 wt. %, preferably from about 1–60 wt. %, more preferably
from about 0.5–40 wt.%, most preferably from about 1–5 wt. %,
for example, about 2–3 wt. %.

Ng ¶¶ 97, 99.
However, nowhere does Ng either expressly teach or suggest
combining an NSAID with an amide local anesthetic, and excluding any
other active agents. Nor does Ng teach the range of ratios of NSAID to
amide local anesthetic recited in claim 1.
In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme
Court made clear that an obviousness analysis requires that we “determine
whether there was an apparent reason to combine the known elements in the
fashion claimed by the patent at issue.” 550 U.S. at 418 (quoting In re
Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006) (“[R]ejections on obviousness
grounds cannot be sustained by mere conclusory statements; instead, there
must be some articulated reasoning with some rational underpinning to
support the legal conclusion of obviousness”). The Examiner has failed to
make clear why a person of ordinary skill in the art would have been
motivated by the teachings of Ng and knowledge of the art at the time of
invention, to combine the two particular active agents (viz., “an amide local
anesthetic, and a non-steroidal anti-inflammatory drug (NSAID)”) in the
concentrations and ratios recited in claim 1. Simply put, the Examiner has
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not shown that Ng provides any reason why a skilled artisan might combine
these two active agents, and no others, from the extremely broad genus of
active agents taught by the reference.
Nor would one of skill in the art have found it obvious to try
combining the claimed active agents from those taught by Ng. In cases in
which the Examiner “merely throws metaphorical darts at a board filled with
combinatorial prior art possibilities, courts should not succumb to hindsight
claims of obviousness.” In re Kubin, 561 F.3d 1351, 1359 (Fed. Cir. 2009).
We do not so succumb here. In the absence of any teaching or suggestion of
Ng that would motivate a skilled artisan to combine an amide local
anesthetic and an NSAID in the concentrations and ratios recited in claim 1,
we do not sustain the Examiner’s rejection of the claims. And because this
issue is dispositive of the Examiner’s rejection of claim 1 upon this ground,
we do not reach Appellant’s additional arguments.

2. Claims 4, 7–12, 15, 19, and 20
Dependent claims 4, 7–12, 15, 19, and 20 all depend, directly or
indirectly, from independent claim 1. Because we reverse the Examiner’s
rejection of claim 1, we similarly, and for the same reasons, reverse the
Examiner’s rejection of claims 4, 7–12, 15, 19, and 20

CONCLUSION
The Examiner’s rejection of claims 1–20 under 35 U.S.C. § 103 is
reversed.
REVERSED

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Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–3, 5, 6, 13,
14, 16–18
103 Ng

1–3, 5, 6,
13, 14, 16–
18
4 103 Ng, Campbell 4
7–12 103 Ng, Dadey 7–12
15, 19, 20 103 Ng, Wohabrebbi 15, 19, 20
Overall
Outcome
1–20