Ex Parte Latham

Patent Trial and Appeal Board

Aug 30, 2016

13548358 (P.T.A.B. Aug. 30, 2016)

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.
13/548,358 07/13/2012 Keith R. Latham 250-004 2375
37468 7590 08/30/2016
STOCKWELL & SMEDLEY, PSC
861 CORPORATE DRIVE, SUITE 200
LEXINGTON, KY 40503
EXAMINER
HEYER, DENNIS
ART UNIT PAPER NUMBER
1628
MAIL DATE DELIVERY MODE
08/30/2016 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 KEITH R. LATHAM1
____________________

Appeal 2015-001468
Application 13/548,358
Technology Center 1600
____________________

Before JEFFREY N. FREDMAN, JOHN G. NEW, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.

NEWMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) from a final rejection of
claims 1, 7, 8, 13, 14, 16, 17, 20–24, 92, 93, 102, and 104–107, which are all
of the claims pending in the application.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Background
The Specification discloses compositions for targeted delivery and
release of compounds such as dopamine at sites of inflammation and/or
disease within the body of an individual. Spec. 1. The claimed

1 According to Appellant, the real party in interest is IPE, Inc. Br. 2.
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compositions2 are designed for targeted delivery at sites of elevated levels of
free radicals and/or oxidative species (“high FROS sites”) in tissues and
cells within individuals whose disease or other condition is associated with
affected cells and tissues becoming hypermetabolic. Id. at 13–14.

Representative Claims
Claims 1, 7, 8, 13, 14, 16, 17, 20–24, 92, 93, 102, and 104–107 are on
appeal. Claims 7, 8, 13, 14, 16, 17, 20, 22–24, 92, 93, 102, and 104–107
have not been argued separately and therefore stand or fall with claims 1 and
21. 37 C.F.R. § 41.37(c)(1)(vii). Claims 1 and 21 are representative and
reproduced below:
1. A composition comprising a starting compound having
the following chemical structure:

2 The Examiner issued a Restriction requiring election of species for claim 1
and Appellant responded “Applicant elects the species of claim 21
encompassed by claims 1 and 6–24. Applicant further elects a species of
claim 21 in which R2, R3 and R4 are each hydrogen, X is iodine, and the
ether linkage between the halogenated phenol ring and the core structure of
the drug compound is in the para-position relative to the hydroxyl group of
the phenol ring, encompassed by claims 21–24.” Response to Election
(Aug. 9, 2013). Accordingly, we limit our consideration of this record to
Appellant’s elected species, and we take no position respecting the
patentability of Appellant’s claimed composition as it may relate to the
remaining, non-elected species. Cf. Ex parte Ohsaka, 2 USPQ2d 1460
(BPAI 1987).

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wherein R2, R3 and R4 are each a hydrogen, a hydroxyl, a
sulfhydryl, an alkyl, a halogen, an amino, or a nitro group,

wherein Y is oxygen,

wherein X is a halogen, and

wherein R1 is a core structure of a drug compound,
and

wherein the drug compound is dopamine.

21. A composition comprising a starting compound having
the following chemical structure:

wherein R2, R3 and R4 are each a hydrogen, a
hydroxyl, a sulfhydryl, an alkyl, a halogen, an
amino, or a nitro group,

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wherein X is a halogen, and

wherein the starting compound produces dopamine
via a dehalogenation and ether cleavage reaction
involving the starting compound.

Rejections
The Examiner rejected claims 1, 7, 8, 13, 14, 16, 17, 20–24, 92, 93,
102, and 104–107, under 35 U.S.C. § 103 as being unpatentable over
Stenzel-Poore.3 Final Act. 4.
The Examiner finds that Stenzel-Poore teaches a method of protecting
a subject against cell injury caused by an excitotoxic, ischemic and/or
hypoxic event comprising administering thyronamine and 3-
iodothyronamine, which are derivatives of thyroid hormone that have been
found to rapidly induce hypothermia independent of gene transcription
mechanisms. Stenzel-Poore ¶ 4. Thyronamines are agonists for trace amine
associated receptor 1 (TAAR1), a G-protein-coupled receptor found on the
plasma membrane. Id. at ¶ 4. Selective hypothermia induction is desirable
“a profoundly neuroprotective treatment for stroke.” Id. at ¶ 6.
The Examiner finds Stenzel-Poore discloses a thyronamine compound
of the formula shown below, for administration in advance of an excitotoxic,
ischemic and/or hypoxic event:

3 WO 2007/059039 A1, published May 24, 2007.
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Ans. 2.
The Examiner finds Stenzel-Poore teaches pharmaceutical
compositions comprising thyronamine agents for administration to humans
to precondition tissues against a later excitotoxic, ischemic and/or hypoxic
event (“[p]reconditioning [a]gent[s]”). Id. at 3. The Examiner finds Table 2
discloses fifteen such preconditioning compounds (as determined by their
EC50 value against the TAAR1 receptor), including the compound
reproduced below and listed on the fourth line of Table 2:

Id.
The Examiner finds the above compound is identical to the elected
compound except for the variable “R”: in Stenzel-Poore, R=H, while R=OH
in the claimed compounds. Id. The Examiner further finds “Stenzel-Poore
also teaches the variable ‘R’ in Figure 1 above, (taught as as R4 and R5 by
Stenzel-Poore) may be independently selected from an at once envisaged
genus encompassed by H, cyano, halo, alkyl, fluoroalkyl or OR11, wherein
R11 is H, acyl or lower alkyl” so that OR11 expressly encompasses OH. Id. at
7.
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The Examiner finds
It would have been prima facie obvious . . . to select the
compound of Stenzel-Poore wherein R = H as a lead compound
for further modification . . . because said compound is explicitly
disclosed as an exemplary compound that activates the
rTAAR1 receptor in vitro and is thus characterized as having
the ability to induce hypothermia in vivo . . . .
Moreover, it would have been prima facie obvious . . . to
modify the compound of Stenzel-Poore, wherein R = H, with an
OH group, to provide the elected compound . . . because
Stenzel-Poore teaches an OH group as one specie from an at
once envisaged genus of alternative “R” groups (i.e. R4 and R5
substituents). Accordingly, one of ordinary skill in the art
would have reasonably expected that modification of the
compound wherein R = H with an OH group would provide a
compound that activates the rTAAR1 receptor in vitro and have
the ability to induce hypothermia in vivo.

Id. at 3–4.

The Examiner further finds that although Stenzel-Poore does not teach
that “the starting compound produces dopamine via a dehalogenation and
ether cleavage reaction involving the starting compound” that the functional
properties accruing from the starting compound “are considered
characteristic features” (id. at 4), are inherent (id. at 5), and/or represent
recognition of “additional advantages or latent properties present in the
claimed compounds.” Id. at 8. The Examiner further finds that prior art of
record, Piccariello,4 discloses a “spontaneous dehalogenation and cleavage
reaction resulting in the release of a phenol compound (a thyroxine
compound)” and that Piccariello establishes that “it would have been

4 US 2004/0116391 A1, published June 17, 2004.
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expected that the elected compound . . . would under[go] a cleavage reaction
to release a phenol compound.” Id. at 9–10.
ISSUE
The issue with respect to this rejection is whether a preponderance of
the evidence of record supports the Examiner’s conclusion that Stenzel-
Poore teaches or suggests the compositions required by claims 1 and 21.
FINDINGS OF FACT
The following findings of fact (“FF”) are supported by a
preponderance of the evidence of record.
1. The Specification teaches that the claimed compounds contain a
halogenated phenol ring to which drug compounds, including dopamine, can
be linked. Spec. ¶ 93.
2. Figure 8A of the Specification discloses a dehalogenation and
cleavage reaction of the claimed compounds in which dopamine is a product
of the reaction.
3. Stenzel-Poore teaches thyronamines and thyronamine analogs
for use as preconditioning agents, including for use in preconditioning by
exerting a hypothermic effect through activation of TAAR. Id. at ¶ 72.
4. Stenzel-Poore teaches preconditioning agents of the formula

where R4 and R5 independently are H, cyano, halo, lower alkyl, fluoroalkyl,
or -OR11; and R11 is H, acyl or lower alkyl. Id. at ¶¶ 80, 81.
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5. Table 2 of Stenzel-Poore discloses fifteen compounds of the
formula

that were synthesized and tested for efficacy as preconditioning agents as
determined by their EC50 value against the TAAR1 receptor. Id. at ¶ 89.
6. Stenzel-Poore discloses a preconditioning agent with the
formula shown below and an EC50 range of 41 (rTAAR1) to ~1000
(mTAAR1) in Table 2. Id.

R4 and R5 are shown above in the compound at issue.
7. In the compounds of claims 1 and 21, shown below, R2 is in the
position of R4 of Stenzel-Poore (directly above) and R3 is in the position of
R5 of Stenzel-Poore.
R4
R5
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In light of the teaching of FF 4 above, both R4 and R5 of Stenzel-
Poore can be a hydroxyl group (-OH).
8. Figure 1 of Piccariello discloses a spontaneous dehalogenation
and cleavage reaction resulting in the release of a phenol compound (a
thyroxine compound). The thyroxine compound disclosed has an iodine in
the R position to both sides of the ether linkage as indicated in Figure 1.

PRINCIPLES OF LAW
This court, in reconsidering this case in banc, reaffirms that
structural similarity between claimed and prior art subject
matter, proved by combining references or otherwise, where the
prior art gives reason or motivation to make the claimed
compositions, creates a prima facie case of obviousness, and
that the burden (and opportunity) then falls on an applicant to
rebut that prima facie case.

In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990).
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
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ANALYSIS
Stenzel-Poore teaches thyroxine derivatives that are highly
structurally similar to the claimed compounds and directly suggests that the
claimed compounds may be synthesized through substitution of either R4 or
R5 (FF 4). Stenzel-Poore discloses fifteen compounds that were synthesized
and tested for efficacy as preconditioning agents as determined by their EC50
value against the TAAR1 receptor. (FF 5).
We find the Examiner’s selected compound from Stenzel-Poore (e.g.,
the “lead compound”) (FF 6) is “‘a compound in the prior art that would be
most promising to modify in order to improve upon its ... activity and obtain
a compound with better activity.’” Otsuka Pharm. Co., Ltd. v. Sandoz, Inc.,
678 F.3d 1280, 1291 (Fed. Cir. 2012) (citing Takeda Chem. Indus., Ltd. v.
Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007)). Stated
another way, “a lead compound is ‘a natural choice for further development
efforts.’” Id. (citing Altana Pharma AG v. Teva Pharm. USA, Inc., 566 F.3d
999, 1008 (Fed. Cir. 2009)). The lead compound determination “must, in
keeping with KSR, not rigidly focus on the selection of a single, best lead
compound.” Daiichi Sankyo Co., Ltd. v. Matrix Laboratories, Ltd., 619 F.3d
1346, 1354 (Fed. Cir. 2010). The analysis of whether a chemist of ordinary
skill would have chosen the prior art compound as a lead compound “is
guided by evidence of the compound’s pertinent properties” including
“positive attributes such as activity and potency,” “adverse effects such as
toxicity,” “and other relevant characteristics in evidence.” Otsuka, 678 F.3d
at 1292.
We agree with the Examiner that because of the structural similarity
and similar use of the lead compound, “it would have been prima facie
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obvious . . . to select the compound of Stenzel-Poore wherein R = H as a
lead compound for further modification . . . [and] to modify the compound . .
. to provide the elected compound . . . because Stenzel-Poore teaches an OH
group as one specie from an at once envisaged genus of alternative ‘R’
groups.” Ans. 3–4. See Dillon, 919 F.2d at 696 (“[T]he cases establish that
if an examiner considers that he has found prior art close enough to the
claimed invention to give one skilled in the relevant chemical art the
motivation to make close relatives (homologs, analogs, isomers, etc.) of the
prior art compound(s), then there arises what has been called a presumption
of obviousness or a prima facie case of obviousness . . . . The cases of Hass
and Henze established the rule that, unless an applicant showed that the prior
art compound lacked the property or advantage asserted for the claimed
compound, the presumption of unpatentability was not overcome”). In
addition, the lead compound is a “natural choice for further development
efforts” because it is effective at a low EC50 and is disclosed for use in
preconditioning tissues against the same types of injuries that the claimed
compounds seek to address. Otsuka, 678 F.3d at 1292.
Appellant argues the Examiner erred in rejecting the claimed
compounds over Stenzel-Poore because the claimed compounds are
“directed to the targeted release of the drug dopamine” while “Stenzel-Poore
describes the use of thyronamine derivatives to protect cells from subsequent
damage by acting as an agonist for a TAARl receptor.” Br. 7. Appellant
argues the rejection should be reversed because that reference does not
“contemplate a dehalogenation and cleavage reaction, which may lead to the
selection of a particular compound to provide masking and targeted release
of a drug.” Id.
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We do not agree that the issue is one of analogous art where the prior
art compounds must have analogous utility to those claimed, but rather one
of structural obviousness. Indeed, Dillon expressly overrules Appellant’s
line of reasoning, stating that
it is not necessary in order to establish a prima facie case of
obviousness . . . that there be a suggestion in or expectation
from the prior art that the claimed compound or composition
will have the same or a similar utility as one newly discovered
by applicant. To the extent that Wright suggests or holds to the
contrary, it is hereby overruled.

Dillon, 919 F.2d at 693.
Appellant argues that the presumption of obviousness is rebutted over
the claimed compounds because Stenzel-Poore “fails to teach or appreciate
the ‘criticality’ of the much narrower and distinguishable class of
compounds as presently claimed specifically for the inclusion of, and the
release of, dopamine.” Br. 7. According to Appellant, “Stenzel-Poore [does
not] teach or suggest modifications related to the cleavage of one of its
thyronamine TAARI agonists, nor the unmasking and release of any drug,
such as dopamine, by a dehalogenation and cleavage reaction.” Id. at 8.
Appellant argues the structure of the claimed compounds is a “new
and surprising ‘critical’ feature[]” that both permits the dehalogenation and
cleavage reaction to release dopamine and that confers “protection and
masking of the conjugated drug compound until its release at the target site.”
Id. at 8–9. Appellant argues this latter feature precludes recognition of the
claimed compounds by the DOPA-decarboxylase enzyme (which degrades
dopamine in vivo), allowing the compounds to be administered alone or with
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less of a companion drug (e.g., Carbidopa) that is designed to suppress
dopamine carboxylation. Id. at 9.
According to Appellant, Stenzel-Poore would not motivate the skilled
artisan to make the “claimed class of halogenated phenol compounds ether-
linked to the core structure of dopamine for the cleavage and release of
dopamine in FROS-containing environments” because “none of the example
compounds listed in Table 2 or elsewhere . . . would even produce the drug
dopamine” if cleaved. Id. at 8. Rather, “each of the examples listed in
Stenzel-Poore teach away from the present claims by including compounds
that would not produce dopamine even if they did undergo cleavage.” Id
We do not find these arguments persuasive. “Under the proper legal
standard, a reference will teach away when it suggests that the developments
flowing from its disclosures are unlikely to produce the objective of the
applicant’s invention. A statement that a particular combination is not a
preferred embodiment does not teach away absent clear discouragement of
that combination.” Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371,
1380 (Fed. Cir. 2005) (citations omitted). Rather than clearly discourage the
claimed combination, Stenzel-Poore teaches effective preconditioning agents
having a structurally similar formula and that R4 and R5 can comprise H, as
does the claimed compound. (FF 4, 7). In addition, Piccariello teaches the
dehalogenation and cleavage reaction that Appellant has argued is
unexpected. (FF 8). Piccariello further demonstrates that a dehalogenation
and cleavage reaction will occur if iodine is in the position on both sides of
an ether linkage, disproving Appellant’s argument that the claimed
compounds’ structure is critical to the reaction. Id. Appellant has not
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explained why the claimed compounds are not obvious in light of this
analysis.
Appellant has provided no evidence supporting Appellant’s claim of
criticality or unexpected results. Appellant’s arguments without more do not
rebut the Examiner’s finding of obviousness. See In re Geisler, 116 F.3d
1465, 1470 (Fed. Cir. 1997) (“[A]ttorney argument [is] not the kind of
factual evidence that is required to rebut a prima facie case of obviousness”).
Accordingly, we sustain the Examiner’s rejection of claims 1 and 21.

DECISION
For the reasons above, we affirm the Examiner’s decision rejecting
claims 1, 7, 8, 13, 14, 16, 17, 20–24, 92, 93, 102, and 104–107.

TIME TO RESPOND
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