Ex Parte Benito Collado et al

Patent Trial and Appeal Board

Dec 16, 2016

13504176 (P.T.A.B. Dec. 16, 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.
13/504,176 04/26/2012 Ana Belen Benito Collado X18680 6041
25885 7590 12/20/2016
FT T T TT T Y fr TOMPANY
EXAMINER
PATENT DIVISION DESAI, RITA J
P.O. BOX 6288
INDIANAPOLIS, IN 46206-6288 ART UNIT PAPER NUMBER
1625
NOTIFICATION DATE DELIVERY MODE
12/20/2016 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):
patents @ lilly.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANA BELEN BENITO COLLADO, NURIA DIAZ BUEZO,
ALMA MARIE JIMENEZ-AGUADO, CELIA LAFUENTE BLANCO,
MARIA ANGELES MARTINEZ-GRAU,
CONCEPCION PEDREGAL TERCERO, and
MIGUEL ANGEL TOLEDO ESCRIBANO* 1
Appeal 2015-007891
Application 13/504,176
Technology Center 1600
Before, JEFFREY N. FREDMAN, JOHN G. NEW, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to ORL-1
receptor antagonists which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify the real party in interest as Eli Lilly and Company. Br.
1.
Appeal 2014-003262
Application 12/515,165
STATEMENT OF THE CASE
The present invention is ORL-1 antagonists having the general
formula:
Spec. 2. The compounds are useful in the treatment of various disorders
including depression and eating disorders. Spec 1.
Claims 1—17 are on appeal. Claim 1 is illustrative below and reads as
follows:
1. A compound of the formula:
Wherein
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R1 is fluoro or chloro;
R2a and R2b are each hydrogen or are each fluoro;
R3 is hydrogen, methyl, hydroxymethyl, or (C1-C3)
alkoxymethyl;
R4 is selected from the group consisting of fluoro, chloro,
cyano, cyanomethyl, (C1-C3) alkyl, cyclopropyl,
hydroxymethyl, methoxy, methoxymethyl,
aminocarbonyloxymethyl, methylaminocarbonyloxymethyl,
dimethylaminocarbonyloxymethyl, methylcarbonyl,
aminocarbonyl, thylaminocarbonyl,_dimethylaminocarbonyl, -
NR5R6, -CH2-NR5R6, morpholin-4-yl, morpholin-4-ylmethyl,
Ar1, -CH2Ar1, 3,3-difluoroazetidin-l-ylmethyl, pyrrolidin-1-
ylmethyl, 1-aminocyclopropyl, 1-methylaminocyclopropyl,
and 1- dimethylaminocyclopropyl;
R5 is hydrogen, C1-C4 alkyl, cyclopropyl, hydroxy ethyl,
methoxyethyl, -C(0)CH3, or -C(0)0(Ci-C3) alkyl;
R6 is hydrogen or methyl;
R7 is hydrogen, fluoro, chloro, methyl, hydroxymethyl, or
methoxy; and
Ar1 is a moiety selected from the group consisting of imidizol-
1-yl, imidizol-2-yl, 2-methylimidizol-l-yl, 1-methylimidizol-2-
yl, and l,2,4-triazol-3-yl; or
a pharmaceutically acceptable salt thereof.
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Application 12/515,165
Claims 1—17 stand rejected on the grounds of non-statutory
obviousness-type double patenting over Benito Collado,2 in view of
Wermuth.3
DISCUSSION
Issue
In rejecting the present claims under obviousness-type double
patenting the examiner finds that Benito Collado discloses compounds with
the general formula:
which differs from the claimed compound in that the claimed compounds
have a phenyl group in place of the pyridyl group as the terminal ring. Ans.
4—5. The Examiner finds that Wermuth teaches that phenyl and pyridyl are
bioisoteres. Ans. 4—5. The Examiner concludes that since pyridyl and
2 Benito Collado et al., US 8,232,289 B2, issued July 31, 2012 (“Benito
Collado”).
3 Camille G. Wermuth, Molecular Variations Based on Isosteric
Replacements, The Practice of Medicinal Chemistry, 203—237 (1996)
(“Wermuth”).
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Application 12/515,165
phenyl are equivalents, “one [] skilled in the art would have been motivated
to modify the pyridyl ring with a phenyl ring and have a reasonable
expectation [of success] that the properties of the compounds will be
maintained.” Ans. 5.
Appellants contend that the Examiner mischaracterizes the difference
between the compounds disclosed in Benito Collado and the present
invention. Appeal Br. 3. Appellants argue that the present invention does
not involve simply substituting phenyl for pyridyl as the present invention
calls for a particularly substituted phenyl to replace a differentially
substituted pyridyl group. Id. Appellants also argue that a skilled medicinal
chemist would not consider phenyl and pyridyl to be the same and that the
Examiner impermissibly used hindsight to make the proposed substitution.
Id. Appellant does on to argue that the Examiner has failed to point to a
reason why one skilled in the art would make the propose substitution.
Appeal Br. 5. Appellants point out that the references teach that such
substitutions often do not work. Appeal Br. 5—6.
The issue with respect to this rejection is whether the Examiner has
established by a preponderance of the evidence that claims 1—17 are not
patentably distinct from the claims of Benito Collado.
Findings of Fact
We adopt as our own the Examiner’s findings and analysis. The
following findings are included for emphasis and reference convenience.
FF1. Benito Collado claims a compound having the general formula:
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Application 12/515,165
wherein
R1 is fluoro or chloro;
R2a and R2b are each hydrogen or are each fluoro;
R3 is hydrogen, methyl, hydroxymethyl, or (C1-C3) alkoxymethyl;
R4 is selected from the group consisting of fluoro, chloro, cyano,
cyanomethyl, (C1-C3) alkyl, cyclopropyl, hydroxymethyl, methoxy,
cyclopropylmethoxy, aminocarbonylmethoxy, (Ci -C3) alkoxymethyl,
cyclopropyloxymethyl, cyclopropylmethoxymethyl, 1-hydroxy-1-
methylethyl, aminocarbonyloxymethyl, methylaminocarbonyloxymethyl,
dimethylaminocarbonyloxymethyl, aminocarbonyl, aminocarbonylmethyl, -
CH2-NR5R6, hydroxyimine, methoxyimine, morpholin-4-yl, morpholin-4-
ylmethyl, Ar1,—CH2Ar1, tetrahydrofuran-2-yl, 3-oxomorpholin-4-ylmethyl,
2-oxopyrrolidin-l-ylmethyl, and 2-oxopiperidin-l-ylmethyl;
R5 is hydrogen, C1-C3 alkyl, cyanomethyl, -C(0)CH3,
aminocarbonylmethyl;
R6 is hydrogen or methyl;
R7 is hydrogen, fluoro, chloro, methyl, hydroxymethyl, or methoxy; and
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Ar1 is a moiety selected from the group consisting of imidizol- 1 -yl,
imidizol-2-yl, 2-methylimidizol-l-yl, pyrazol-l-yl, 1,2,3-triazol-l-yl; 1,2,3-
triazol-2-yl; 1,2,4-triazol-l-yl, isoxazol-3-yl, oxazol-5-yl, and 3-methyl-
l,2,4-oxadiazol-5-yl; or a pharmaceutically acceptable salt thereof. Benito
Callado, col. 100,11. 25^col. 101,1. 6.
FF2. Wermuth teaches that “the isoterism concept, taken in its
broadest sense, has proven to be a research tool of the utmost importance.
The main reason for this is that isoteres are often much more alike in their
biological than in their physical and chemical properties.” Wermuth 207.
FF3. Wermuth teaches that “[t]he substitution of —C= by —N= or —
CH=CH— by —S— in aromatic rings has been one of the most successful
applications of classical isoterism.” Wermuth 211.
Principles of Law
“Obviousness-type double patenting is a judge-made doctrine that
prevents an extension of the patent right beyond the statutory time limit. It
requires rejection of an application claim when the claimed subject matter is
not patentably distinct from the subject matter claimed in a commonly
owned patent. Its purpose is to prevent an unjustified extension of the term
of the right to exclude granted by a patent by allowing a second patent
claiming an obvious variant of the same invention to issue to the same owner
later.” In re Berg, 140 F.3d 1428, 1431—32 (Fed. Cir. 1998) (citation
omitted).
“[T]he law of obviousness-type double patenting looks to the law of
obviousness generally. As . . . explained in Amgen, ‘[tjhis part of the
obviousness-type double patenting analysis is analogous to an obviousness
analysis under 35 U.S.C. § 103.’” AbbVielnc. v. The Mathilda and
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Terrence Kennedy Inst, of Rheumatology Trust, 764 F.3d 1366,1378 (Fed.
Cir. 2014).
“Obviousness does not require absolute predictability of success. . . .
For obviousness under § 103, all that is required is a reasonable expectation
of success.” In re O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988).
Analysis
Claim 1 is representative of the pending claims and is recited above.
We agree with the Examiner that claim 1 is not patentably distinct
from the claim 1 in Benito Collado. The compound of claim 1 in the instant
claims is essentially the same as that recited in claim 1 of Benito Collado.
FF1. The only significant difference is that the claim 1 calls for a phenyl
group at the terminal end whereas the compound claimed in Benito Collado
has a pyridyl group. Ans. 12. As shown by the teachings of Wermuth, one
skilled in the art would recognized that phenyl and pyridyl are bioisoteres
and would consider substituting one for the other in the course of developing
new drug compounds. FF2and3. We therefore agree with the Examiner
that the pending claims are not patentably distinct from the claims of Benito
Collado.
Appellants argue that the present invention does not simply involve a
substitution of a phenyl group for a pyridyl group, but is the substitution of a
“particularly substituted phenyl group for a differentially (though to an
extent overlapping)-substituted pyridyl group of the reference. The group of
substituted phenyls of the presently claimed invention required a great deal
of experimentation to find and was not obvious from the substituted pyridyl
compounds claimed in the ‘289 patent.” Appeal Br. 3. We are unpersuaded.
As Appellants admit and as noted by the Examiner, there is significant
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overlap between the substitutions in claim 1 and those in the claims of
Benito Collado. Ans. 6—9. We agree with the Examiner that the only
significant difference in the compounds is the substitution of phenyl for
pyridyl. Ans. 9.
Appellants next argue that one skilled in the art would not view
pyridyl and phenyl as the same and would not be motivated to substitute one
for the other. Appeal Br. 3—7. Again, we are unpersuaded. Wermuth
teaches that “[t]he substitution of —C= by —N= or —CH=CH— by —S— in
aromatic rings has been one of the most successful applications of classical
isoterism.” FF5. One skilled in the art would be motivated to make the
substitution as isoteres have similar biological effects even though there are
chemical and physical differences. FF4. See In re Dillon, 919 F.2d 688, 696
(Fed. Cir. 1990). (“[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”). Appellants provide no such
secondary consideration evidence.
Appellants argue that one skilled in the art would not expect the
substitution to be successful as Wermuth teaches that some isoteres are not
effective. Appeal Br. 4. We remain unpersuaded. While Wermuth teaches
that substitution sometimes fails, Wermuth also states that the proposed
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substitution of phenyl for pyridyl in one of the most successful applications
of classical isoterism. Wermuth 211. Based on this teaching, one skilled in
the art would have a reasonable expectation of success in making the
claimed substitution.
Conclusion of Law
We conclude that the Examiner has established by a preponderance of
the evidence that claim 1 is not patentably distinct from claim 1 of Benito
Collado.
Claims 2—17 have not been argued separately and therefore fall with
claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm the rejection based on non-statutory obviousness-type
double patenting.
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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