Ex Parte McDonough et al

Patent Trial and Appeal Board

Aug 18, 2017

12697512 (P.T.A.B. Aug. 18, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/697,512 02/01/2010 Joseph McDonough UTX-10604/3 8 2163
13173 7590 08/22/2017
Rlne Filament T aw EXAMINER
700 E. Maple Road
Suite 450
FRAZIER, BARBARA S
Birmingham, MI 48009 ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
08/22/2017 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOSEPH A. MCDONOUGH and
STANTON FURST MCHARDY1
Appeal 2016-004137
Application 12/697,512
Technology Center 1600
Before ERIC B. GRIMES, JOHN G. NEW, and RICHARD J. SMITH,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants state the real party-in-interest is Southwest Research Institute
of San Antonio, Texas. App. Br. 2.
Appeal 2016-004137
Application 12/697,512
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1—3, 7, 20, and 21 as unpatentable
under 35 U.S.C. § 103(a) as being obvious over Tattersall (WO 97/02824
Al, January 30, 1997) (“Tattersall”), either alone or in combination with
G.W. Ponder et al., Resolution of Promethazine, Ethopropazine,
Trimeprazine and Trimipramine Enantiomers on Selected Chiral Stationary
Phases Using High-Performance Liquid Chromatography, 692 J.
Chromatogr. A. 173—182 (1995) (“Ponder”) and/or Appellants’ admission
of the prior art in their Specification (“APA”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
Appellants’ invention is directed to enantomerically-purified
phenothiazines that are provided as active ingredients of medicaments to
limit activity of bone resorbing cells so as to reduce bone loss. Abstract.
NATURE OF THE CFAIMED INVENTION
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A compound having the structure:
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Application 12/697,512
where
R1 and R3 are both H and R2 is one of F, Cl, Br, I, C1-C6
alkyl, C1-C6 fluoro-alkyl, C1-C6 perfluoro-alkyl, O-C1-C4 alkyl,
(C0-C6 linear alkyl or C3-C6 branched alkyl)-R6-OH, (C0-C6,
linear alkyl or C3-C6 branched alkyl)-C(0)0R6,
(CVC* alkyl)
-C(0)-R6, ■ x......... , C6-aryl, a substituted C6-
aryl where the substituent is at least one of hydroxyl radicals,
halogens, alkyl radicals having a total of from 1 to 6 carbon
atoms, cyclic alkylene groups and heterocyclic alkylene groups
having a heterocyclic element of nitrogen and sulfur where Co
alkyl denotes a nullity;
X is 2-propyl;
R4 is a tertiary amine radical structure of N-(R5)2 wherein
R5 in each occurrence is independently hydrogen, C1-C4 alkyl
radicals and C1-C4 alkenyl radical having cyclic alkylene
groups, or heterocyclic alkylene groups having a heterocyclic
element of nitrogen or sulfur;
R6 is independently in each occurrence H, C1-C4 alkyl or
N-(R5)2; and
Q is independently in each occurrence an sp2-hybridized
C-R6 or a nitrogen.
App. Br. 14.
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Appeal 2016-004137
Application 12/697,512
ISSUE AND ANALYSIS
We agree with, and adopt, the Examiner’s reasoning and conclusion
that the claims are obvious over the cited prior art references. We address
Appellants’ arguments below.
Issue 1
Appellants argue that the Examiner erred because a person of
ordinary skill in the art would not be motivated to modify the chemical
structures taught by the prior art cited by the Examiner to obtain the
claimed composition. App. Br. 8.
Analysis
Appellants have chosen, as their elected species (R)-l-(2-methoxy-
10H-phenothiazin-10-yl)-N,N-dimethylpropan-2-amine, a composition with
the following structure:
*isC.\ /
£}■
CM,
See Resp. to Restr. Req. 2 (Applicant Arguments/Remarks) (dated Apr. 23,
2012); see also Spec. 39 (Table 3, entry 2); Ans. 8.
The Examiner points to two species, taught by Tattersall and well
known in the art as antihistamines: methotrimeprazine:
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Application 12/697,512
and promethazine:
See Final Act. 5.
The Examiner finds that methotrimeprazine differs from Appellants’
elected species by only the presence of an additional methylene group
between the tertiary amine (at the top of the formula) and the chiral carbon
in the chain between the nitrogens, as indicated by a comparison of the two
compounds. Final Act. 5—6. The Examiner also finds promethazine differs
from the elected species only in lacking a methoxy moiety at the 2-carbon
position. Id. at 5.
The Examiner concludes that it would have been obvious to a person
of ordinary skill in the art to add a methoxy group to promethazine, thus,
arriving at the elected species. Final Act. 6. The Examiner finds that,
because other phenothiazines having amine-alkyl groups similar to
promethazine (i.e., differing only in the presence of a 2-methoxy moiety)
also have antihistaminic activity (i.e., methotrimeprazine), it would have
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Application 12/697,512
been within the ability of a skilled artisan to add a methoxy group to
promethazine at the 2-position, with a reasonable expectation of the
resultant compound would also have antihistaminic activity. Id.
Similarly, concludes the Examiner, it would also have been obvious
to a person of ordinary skill in the art to remove a methylene group between
the chiral carbon atom and the tertiary amine of methotrimeprazine, thus,
arriving at the claimed invention. Final Act. 6. The Examiner finds that,
because other phenothiazines having similar amine-alkyl groups (i.e., not
having the methylene group between the chiral carbon atom and the tertiary
amine) also have antihistaminic activity (i.e., promethazine), and because
promethazine is a preferred phenothiazine (see, e.g., Tattersall 44
(“Promethazine is the archetypal phenothiazine”)), it would also have been
within the ability of a skilled artisan to remove the methylene group
between the chiral carbon atom and the tertiary amine, with the reasonable
expectation of the resultant compound also having antihistaminic activity.
Id.
Appellants argue the Examiner has resorted to mere speculation with
no support of record as to why a person of ordinary skill in the art would be
motivated to modify promethazine or methotrimeprazine in any way, let
alone to specifically select the elected species from among the thousands of
other compounds that could have been elected. App. Br. 8. Appellants
therefore allege the Examiner has impermissibly employed hindsight
analysis in making the obviousness rejection. Id. at 8—9.
According to Appellants, neither Tattersall nor Ponder provides any
support for the change in structure of the claimed invention. App. Br. 9.
Furthermore, Appellants assert, the teachings of the Admitted Prior Art
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Application 12/697,512
(APA) similarly fail to cure the deficiencies of Tattersall, alone or in
combination with Ponder. Id. at 9—10. Appellants contend that the
Examiner’s allegedly unsupported statement of such evidentiary support
found in the prior art, absent identification of where the support is found or
the nature of the support, is an improper basis for the Examiner’s prima
facie case of obviousness. Id. at 10.
Appellants further point to the teachings of Dahl and Strenkoski-Nix,
two additional art references that they submit as evidence of
unpredictability in the art.2 App. Br. 10. Appellants contend that these
references demonstrate that promethazine and methotrimeprazine have
different pharmokinetics despite differences in chemical structure that are
similar in scale to those of Appellants’ claims. Id. Appellants therefore
assert that changes of this scale to the structure of promethazine or
methotrimeprazine modify the activity of the resultant compound in a
manner that is unpredictable and therefore fail to sustain a prima facie case
of obviousness. Id.
The Examiner responds that, because the compounds in question
(i.e., the elected species versus methotrimeprazine and promethazine) are of
sufficient structural similarity, a person of ordinary skill in the art could
reasonably expect similar activity. Ans. 6. The Examiner finds the elected
species differs from methotrimeprazine only in that methotrimeprazine has
2 (1) S.G. Dahl, Pharmacokinetics of Methotrimeprazine after Single and
Multiple Doses, 19(4) Clin. Pharmacol. Ther. 435^42 (1976) (“Dahl”);
and (2) L.C. Strenkoski-Nix et al., Pharmacokinetics of Promethazine
Hydrochloride after Administration of Rectal Suppositories and Oral Syrup
to Healthy Subjects, 57(16) Am. J. Health Syst. Pharm. 1-6 (2000)
(“Strenkoski-Nix”).
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Application 12/697,512
an extra methylene group between the chiral carbon atom and the tertiary
amine group. Id. The Examiner points out that compounds which are
homologs (compounds differing regularly by the successive addition of the
same chemical group, e.g., by-CEE groups) are generally of sufficiently
close structural similarity that there is a presumed expectation that such
compounds possess similar properties. Id. at 6—7 (citing In re Wilder, 563
F.2d 457, 460-61 (C.C.P.A. 1977).
Furthermore, the Examiner finds, phenothiazine compounds having a
2-propyl group for the alkylene chain separating the phenothiazine ring
from the dialkyl amine group are already well known in the art (i.e.,
promethazine). Ans. 7. Therefore, the skilled artisan would be reasonably
guided to substitute the 2-butyl group in methotrimeprazine for a 2-propyl
group, with the reasonable expectation that the resulting compound would
have similar utility as that disclosed in Tattersall, i.e., as an antihistamine.
Id.
We are not persuaded by Appellants’ arguments. Both
methotrimeprazine and promethazine are expressly disclosed as
antihistaminic agents by Tattersall. Tattersall 44. Appellants’ elected
species differs from methotrimeprazine only in that the latter possesses an
additional methylene group between the chiral carbon and the tertiary
amine. Furthermore, promethazine has the same aryl-amino side chain as
Appellants’ elected species, but lacks the 2-carbon methoxy group.
Tattersall teaches that both methotrimeprazine and promethazine have
substantial antihistaminic activity, indeed, Tattersall refers to the latter
compound as “the archetypal phenothiazine.” Id.
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Because of the very close structural similarity of Appellants’ elected
species, which is essentially “in between” the phenothiazines taught by
Tattersall, and because those latter compounds exhibit similar functional
properties, we agree with the Examiner that Appellants’ elected species is
substantially identical to, and consequently obvious over, the teachings of
Tattersall.
In cases in which “the claimed and prior art products are identical or
substantially identical in structure or composition, or are produced by
identical or substantially identical processes, a prima facie case of either
anticipation or obviousness has been established.” MPEP § 2112.01(1)
(citing In re Best, 562 F.2d 1252, 1255 (C.C.P.A. 1977). Moreover, when
the Examiner “shows a sound basis for believing that the products of the
[Appellant] and the prior art are the same, the applicant has the burden of
showing that they are not.” Id. (citing In re Spada, 911 F.2d 705, 709 (Fed.
Cir. 1990). Therefore, the Examiner’s prima facie case of obviousness can
be rebutted by evidence showing that the prior art products do not
necessarily possess the characteristics of the claimed product. Id. (citing
Best, 562 F.2d at 1255).
Appellants point to their Dahl and Strenkoski-Nix references as
teaching that, because methotrimeprazine and promethazine allegedly
exhibit different pharmacokinetics, the art is unpredictable and a person of
ordinary skill would not be motivated to modify either to arrive at the
claimed compound. We are not persuaded.
As an initial matter, Tattersall expressly teaches that both compounds
are effective antihistamines with pronounced anti-muscarinic activity.
Tattersall teaches: “A further sub-class of compound with antihistamine and
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Application 12/697,512
pronounced anti-muscarinic activity are phenothiazines and related
compounds. Promethazine is the archetypal phenothiazine. Other examples
include chlorpromazine, methot[r]imeprazine, perphenazine,
prochlorperazine and trifluoperazine; and pharmaceutically acceptable salts
thereof.” Tattersall 44.
Furthermore, the teachings of Appellants’ proffered art do not permit
a direct comparison between the references. Dahl is presented merely as an
abstract and teaches that: “The highest plasma concentrations of
methotrimeprazine were found 30 to 90 min[.] after intramuscular injection,
and 1 to 3 hr[.] after oral administration.” Dahl, Abstr. Strenkoski-Nix
teaches that:
On average, absorption [of promethazine] was more rapid and
the maximum plasma concentration (Cmax) higher for the [orally
administered] syrup than for the suppositories. Cmax was
significantly lower for the 50-mg suppository (mean, 9.04
ng/mL) than for the syrup (19.3 ng/mL). The time to Cmax (tmax)
was significantly shorter for the syrup (mean, 4.4 hours) than for
the suppositories (6.7-8.6 hours).
Strenkoski-Nix 1. Appellants make no direct comparisons of the evidence
provided by the teachings of either reference, but merely assert that the
references teach that “have different pharmacokinetics,” without further
elaboration or citation to the record. We do not find this persuasive,
particularly in view of the absence of detailed data from Dahl, the different,
but overlapping, methods of administration of the drugs in the two
references, and the absence of explanation by Appellants as to why or how
the pharmacokinetics of the compounds are different.
Consequently, we agree with the Examiner that the species elected by
Appellants is obvious over the cited prior art references.
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Issue 2
Appellants argue that the Examiner erred because the cited prior art
references neither teach nor suggest that the claimed compounds have
osteoclastic or osteoporotic activity. App. Br. 11.
Argument
Appellants contend that, although Tattersall is cited for teaching
antihistaminic activity, there is no evidence of record as to how one of skill
in the art would extend these teachings to osteoclastic or osteoporotic
activity. App. Br. 11. Appellants argue that, whereas the subject matter of
their claims pertains to the treatment of bone loss, the record is devoid of a
reference that would inform one of ordinary skill in art how to predict the
bone loss activity based on antihistamine activity. Id.
We are not persuaded. We agree with Appellants that the cited prior
art references are silent with respect to the activity of the cited
phenothiazines in the treatment of bone loss. However, Appellants’ claims
on appeal are directed only to a composition of matter and not to any use of
the composition in the treatment of bone loss, or otherwise. Because
Appellants’ claims are directed only to compounds that are, as we have
explained, prima facie obvious over the cited prior art, and do not claim a
specific use for the claimed compounds, we affirm the Examiner’s rejection
of the claims.
Furthermore:
Where, as here, the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
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Application 12/697,512
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed product
.... Whether the rejection is based on “inherency” under 35
U.S.C. § 102, or “prima facie obviousness” under 35 U.S.C. §
103, jointly or alternatively, the burden of proof is the same, and
its fairness is evidenced by the PTO’s inability to manufacture
products or to obtain and compare prior art products.
Best, 562 F.2d at 1255 (emphasis added) (internal citations omitted).
Appellants adduce no evidence to show that the phenothiazines cited by the
Examiner, methotrimeprazine and promethazine, do not inherently have
osteoclastic or osteoporotic activity.
Consequently, we affirm the Examiner’s rejection of claims 1—3, 7,
20, and 21.
DECISION
The Examiner’s rejection of claims 1—3, 7, 20, and 21 under 35
U.S.C. § 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(l)(iv).
AFFIRMED
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