Ex Parte Marmsater et al

Patent Trial and Appeal Board

Feb 12, 2015

12593041 (P.T.A.B. Feb. 12, 2015)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte FREDRIK P. MARMSATER, MARC C. MUNSON,
JAMES P. RIZZI, JOHN E. ROBINSON, STEPHEN T. SCHLACTER,
GEORGE T. TOPALOV, and JOSEPH P. LYSSIKATOS1
__________

Appeal 2012-008613
Application 12/593,041
Technology Center 1600
__________

Before ERIC. B. GRIMES, JEFFREY N. FREDMAN, and CHRISTOPHER
G. PAULRAJ, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to inhibitors
of tyrosine kinase, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 According to Appellants, the Real Party in Interest is Array BioPharma
Inc. (Appeal Br. 2).
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STATEMENT OF THE CASE
The Specification describes “certain imidazopyridine compounds
useful in the treatment and prevention of diseases mediated by class 3 and
class 5 receptor tyrosine kinases” (Spec. 1 ¶ 1). “[S]uch kinases are
frequently aberrantly expressed in common human cancers” (id. at 1 ¶ 2).
Claims 1–15 and 21 are on appeal. Claim 1 is the only independent
claim and is directed to a genus of imidazopyridine compounds (Appeal Br.
24–26 (Claims Appendix)). As the result of a restriction requirement,
Appellants elected the following species for initial examination:

(Response to Restriction Requirement, Sept. 9, 2010, page 5.) Appellants
identify the above compound as 1-(2-(7-(2-methoxyethoxy)imidazo[1,2-
a]pyridin-3-yl)quinolin-8-yl)-4-methylpiperidin-4-amine (Spec. 42 ¶ 289).
DISCUSSION
Issue
The Examiner has rejected all of the claims on appeal under 35 U.S.C.
§ 103(a) as obvious based on Barth2 and Bilodeau3 (Ans. 5). The Examiner
finds that Barth discloses a compound that inhibits tyrosine kinase and
differs from the elected species only in the identity of the left-most bicyclic

2 Barth et al., WO 01/40217 A1, June 7, 2001.
3 Bilodeau et al., WO 03/092595 A2, November 13, 2003.
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ring in the above formula: the claimed compound has an imidazopyridine
moiety, whereas the prior art compound has a benzimidazole moiety (Ans.
6–7). The Examiner concludes that the elected species would have been
obvious in view of Barth’s compound for either of two reasons: (1) the
claimed and prior art compounds are related as position isomers and the
structural similarity itself supports a prima facie case of obviousness (id. at
7–8), or (2) Bilodeau teaches substituted imidazopyridine compounds that
inhibit tyrosine kinase and, based on this teaching, substituting an
imidazopyridine moiety for Barth’s benzimidazole moiety would have been
expected to produce a compound that also inhibits tyrosine kinase (id. at 8).
Appellants contend that all of Barth’s compounds include a
benzimidazole moiety and “the exclusive utilization of this core suggests
that the core is optimized regarding the structure-activity relationship (SAR)
of this series of compounds for receptor tyrosine kinase inhibitory activity”
(Br. 17–18). Appellants also contend that Bilodeau’s compounds differ
from Barth’s not only in the identity of the left bicyclic ring but also in the
point of attachment, in that Bilodeau’s compounds have a carbon-to-carbon
bond while Barth’s have a carbon-to-nitrogen bond (id. at 18). Finally,
Appellants contend that all of Bilodeau’s specifically disclosed compounds
have a monocyclic ring where Barth’s compound has a bicyclic quinoline
ring (id. at 19). Appellants conclude that these structural differences would
not provide a reasonable expectation of success in modifying Barth’s
compound as required to produce the elected species (id.).
The issues with respect to this rejection are whether a person of
ordinary skill in the art would have considered it obvious to modify Barth’s
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compound in a manner that results in the elected species, and whether the
prior art would have supported a reasonable expectation that the resulting
compound would retain activity as a tyrosine kinase inhibitor.
Findings of Fact
1. Barth states that the “compounds of [its] invention, which are
selective inhibitors of certain receptor tyrosine kinases, in particular PDGFr,
are useful in the treatment of abnormal cell growth, in particular cancer, in
mammals” (Barth 1:33–35).
2. Barth exemplifies the following compound:

(Id. at 104:15–16.) Barth states that the above compound is 1-{2-[5-(2-
Methoxy-ethoxy)-benzoimidazol-1-yl]-quinolin-8-yl}-4-methyl-piperidin-4-
ylamine (id. at 104:14).
3. Barth’s exemplified compound differs from the elected species in
two respects: (1) the left-most bicyclic ring in Barth’s compound is a
benzimidazole moiety in the position where the elected species has a
imidazopyridine moiety, and (2) the two bicyclic rings in Barth’s compound
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are connected by a carbon-to-nitrogen bond, whereas the bicyclic rings in
the elected species are connected by a carbon-to-carbon bond.
4. Bilodeau discloses “imidazopyridine compounds which inhibit,
regulate and/or modulate tyrosine kinase signal transduction” (Bilodeau 1:5–
6).
5. Bilodeau states that the “compounds of [its] invention are useful in
the inhibition of kinases and are illustrated by a compound of Formula I:”

in which R1 is selected from, among other things, heteroaryl and can be
substituted with certain R3 substituents (id. at 2:33 to 4:4). Bilodeau’s
Formula I is an imidazopyridine compound substituted with R1 and R2
moieties.
6. Bilodeau states that “heteroaryl, as used [t]herein, represents a
stable monocyclic or bicyclic ring of up to 7 atoms in each ring, wherein at
least one ring is aromatic and contains from 1 to 4 heteroatoms selected from
the group consisting of O, N and S” (id. at 12:7–9), and that heteroaryl
groups include a quinolinyl group (id. at 12:12).
7. The right-most bicyclic ring in Barth’s exemplified compound is a
quinolinyl group (see Br. 17 (“[T]he genus compounds described by Barth
have a benzimidazole core wherein one of the ring nitrogen atoms is coupled
to a quinolinyl ring.”)).

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Principles of Law
“In the chemical arts, we have long held 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.”
Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499 F.3d 1293, 1301
(Fed. Cir. 2007). “[I]t is sufficient to show that the claimed and prior art
compounds possess a ‘sufficiently close relationship . . . to create an
expectation,’ in light of the totality of the prior art, that the new compound
will have ‘similar properties’ to the old.” Id.
The “case law is clear that obviousness cannot be avoided simply by a
showing of some degree of unpredictability in the art so long as there was a
reasonable probability of success. . . . [T]he expectation of success need only
be reasonable, not absolute.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348,
1364 (Fed. Cir. 2007).
Analysis
Barth discloses tyrosine kinase inhibitors (FF1), including a
compound that differs from the elected species only (a) in the identity of the
left-most bicyclic ring (having a benzimidazole moiety in the position where
the elected species has an imidazopyridine moiety) and (b) in attaching the
bicyclic rings by a C–N bond rather than a C–C bond (FF2).
Bilodeau discloses tyrosine kinase inhibitors (FF4) having an
imidazopyridine moiety attached by a C–C bond to an R1 group that can be a
substituted heteroaryl group (FF5), including a quinolinyl group (FF6). We
agree with the Examiner that it would have been obvious to (1) replace the
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benzimidazole moiety in Barth’s compound with an imidazopyridine moiety
and (2) join the bicyclic rings together with a C–C bond, thereby producing
the elected species of compound.
The reason for making the above modifications to Barth’s compound
is Bilodeau’s teaching that compounds having an imidazopyridine moiety
coupled to, e.g., a quinolinyl group have tyrosine kinase inhibiting activity,
just like Barth’s compounds. Given that the compounds disclosed by Barth
and Bilodeau are structurally similar—in that both include two joined,
substituted bicyclic rings, one of which is a quinolinyl group—as well as
their disclosures that both sets of compounds inhibit tyrosine kinase, it
would have been reasonable to expect that modifying Barth’s compound to
include Bilodeau’s imidazopyridine moiety (rather than a benzimidazole
moiety) and joining the bicyclic rings with a C–C bond (rather than a C–N
bond) would also produce a compound having tyrosine kinase inhibiting
activity.
Appellants argue that, because all of Barth’s active compounds
include a benzimidazole core, “there is no motivation to explore other cores;
rather the exclusive utilization of this core suggests that the core is
optimized regarding the structure-activity relationship (SAR) of this series of
compounds for receptor tyrosine kinase inhibitory activity” (Br. 17).
This argument is not persuasive. As explained by the court in In re
Deuel, 51 F.3d 1552, 1558 (Fed. Cir. 1995):
Structural relationships may provide the requisite motivation or
suggestion to modify known compounds to obtain new
compounds. For example, a prior art compound may suggest
its homologs because homologs often have similar properties
and therefore chemists of ordinary skill would ordinarily
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contemplate making them to try to obtain compounds with
improved properties.
Here, a person of ordinary skill in the art would have had reason to
make the elected species compound based on the teachings of Barth and
Bilodeau in order to try to obtain compounds with improved properties. See
also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007):
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under § 103.
Appellants also argue that Bilodeau’s compounds differ in several
ways from Barth’s, which “would have made illogical any assumption that
one could simply exchange structural moieties between such compounds
without adversely impacting function” (Br. 18). The Specific differences
that Appellants point to are (1) an imidazopyridine ring instead of Barth’s
benzimidazole ring; (2) the C–C bond rather than Barth’s C–N bond; and
(3) Bilodeau’s use of monocyclic rings for R1 in all of the specific
compounds that it describes.
This argument is also unpersuasive. We have addressed above the
first two of the differences that Appellants point to. To repeat: Bilodeau’s
teaching that compounds having an imidazopyridine ring coupled via a C–C
bond to, e.g., a quinolinyl ring would have provided a reason for a skilled
artisan to make these changes to Barth’s compound with a reasonable
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expectation that the resulting compound would retain tyrosine kinase
inhibiting activity.
With regard to Bilodeau’s R1 group, Appellants argue that
[o]f the 27 compounds specifically disclosed by Bilodeau in
which R1 is either heteroaryl or aryl, all of the R1 groups are
monocyclic rings. . . . A person having ordinary skill in the art
would recognize that the bicyclic quinolinyl ring of Barth
would occupy a greater space in a receptor than the monocyclic
rings of Bilodeau. . . . Accordingly, there is no teaching in
Bilodeau that having a bicyclic R1 group coupled to the
imidazopyridine core would be tolerated and would provide a
compound having activity against a receptor tyrosine kinase.
(Br. 19.) Along the same line, Appellants argue that
the broadest disclosure of the R3 substituents for the
monocyclic R1 group are small groups, namely groups selected
from (C=O)aObalkyl, CO2H, halo, CN, OH, Ob(1-3C
perfluoroalkyl), Oa(C=O)bNH2, oxo, CHO, and (N=O)H2S. In
addition, the specifically disclosed compounds in Bilodeau
having monocyclic R1 groups are either unsubstituted or mono-
substituted with a small methoxy group, lending further
implication in Bilodeau that only small R1 moieties will provide
active compounds.
(Id.)
This argument is also unpersuasive, because Bilodeau expressly
discloses that the R1 group can be heteroaryl, including a substituted
quinolinyl group (FF6). Accordingly, Bilodeau supports a reasonable
expectation that including a quinolinyl group in the R1 position would result
in a compound that inhibits tyrosine kinase. See In re Antor Media Corp.,
689 F.3d 1282, 1288 (Fed. Cir. 2012) (“[A] prior art publication cited by an
examiner is presumptively enabling barring any showing to the contrary by a
patent applicant.”); Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d
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1313, 1355 (Fed. Cir. 2003) (“[T]he examiner is entitled to reject application
claims as anticipated by a prior art patent without conducting an inquiry into
whether or not that patent is enabled or whether or not it is the claimed
material (as opposed to the unclaimed disclosures) in that patent that are at
issue.”).
In addition, Barth provides evidence that a compound having joined,
substituted bicyclic rings, one of which is a quinolinyl group substituted
with the same moiety as the elected species, is capable of interacting with
and inhibiting tyrosine kinase. Appellants have not pointed to any evidence
of record that supports their position that a skilled worker would have
expected a compound having a quinolinyl ring in the position occupied by
Bilodeau’s R1 group to lack tyrosine kinase inhibiting activity.
Conclusion of Law
A person of ordinary skill in the art would have considered it obvious
to modify Barth’s compound in a manner that results in the elected species.
The prior art would have supported a reasonable expectation that the
resulting compound would retain activity as a tyrosine kinase inhibitor.
Claims 2–15 and 21 have not been argued separately and therefore fall
with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
SUMMARY
We affirm the rejection of claims 1–15 and 21 under 35 U.S.C.
§ 103(a) based on Barth and Bilodeau.
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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

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