Ex Parte Wentland

Patent Trial and Appeal Board

Jun 23, 2016

12506354 (P.T.A.B. Jun. 23, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/506,354 07/21/2009
23405 7590 06/23/2016
HESLIN ROTHENBERG FARLEY & MESITI PC
5 COLUMBIA CIRCLE
ALBANY, NY 12203
Mark P. Wentland
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
0094.141A 3947
EXAMINER
DESAI, RITA J
ART UNIT PAPER NUMBER
1625
MAILDATE DELIVERY MODE
06/23/2016 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 MARK P. WENTLAND 1
Appeal2014-005603
Application 12/506,354
Technology Center 1600
Before JOHN G. NEW, JACQUELINE T. HARLOW and
TA WEN CHANG, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1Appellant states the real party-in-interest is Rensselaer Polytechnic
Institute. App. Br. 1.
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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 1-27 and 30.2 Specifically, claims 1-
27 and 30 stand rejected as unpatentable under 35 U.S.C. §102(b) as being
anticipated by Melissa VanAlstine, Design, Synthesis and Evaluation of
Novel N-substituted derivatives of 8-carboxamidocyclazocine, Ph.D.
dissertation, Rensselaer Polytechnic Institute, available online July 9, 2009
(the "VanAlstine dissertation").
Claims 1-27 and 30 also stand rejected as unpatentable under 35
U.S.C. §102(±) because the Examiner concludes Appellant did not invent the
claimed subject matter.
Claims 1-27 and 30 also stand rejected as unpatentable under 35
U.S.C. § 103(a) as being obvious over the combination of Wentland (WO
2007/014137 A3, February 1, 2007) ("Wentland '137") and Mark P.
Wetland et al., Redefining the Structure-Activity Relationships of 2, 6-
Methano-3-benzazocines. 4. Opioid Receptor Binding Properties of 8-[N-
(4 '-phenyl)-phenethyl)carboxamido} Analogues of Cyclazocine and
Ethylketocycalzocine, 49 J. MED. CHEM. 5635-39 (2006) ("Wentland
'099"). 3,4
2 Claims 28, 29, and 31-34 have been withdrawn. App. Br. 2.
3 Appellant states claims 1-27 and 29 were rejected as unpatentable under
35 U.S.C. §§ 102 and 103. App. Br. 4. However, this appears to be a
typographical error; claim 29 is withdrawn and claim 30 rejected in the Final
Office Action. See Ans. 8.
4 Claims 1-27 and 30 were also rejected as unpatentable under the
judicially-created doctrine of constituting an improper Markush group and
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We have jurisdiction under 35 U.S.C. § 6(b)
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellant's invention is directed to 8-Substituted-2, 6-methano-3-
benzazocines useful as analgesics, anti-diarrheal agents, anticonvulsants,
antitussives and anti-addiction medications. Abstract.
REPRESENTATIVE CLAIM
Appellant argues all of the claims together. Claim 1 is representative
of the claims on appeal, and recites:
1. (Original) A compound of formula I:
wherein
R1 and R2 are each independently chosen from hydrogen,
optionally substituted lower alkyl, optionally substituted alkenyl,
optionally substituted alkynyl, optionally substituted aryl,
-COR10 -S02R10, -CONR10R11 , -C(=S)R10, -C(=NOR11)R10,
[-]C(=NR10)R11 , and -S02NR10R11 ; or, taken together with the
nitrogen to which they are attached, R1 and R2 may form from
under 35 U.S.C. § 112, first paragraph, for lack of enablement. Final Act. 2-
3. These rejections are withdrawn by the Examiner. Ans. 8.
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one to three rmgs, said rmgs having optional additional
substitution;
R3 is chosen from hydrogen, C1-Cs hydrocarbon, heterocyclyl,
aryl and hydroxyalkyl;
R4 is chosen from hydrogen, hydroxyl, amino, lower alkoxy, C1-
C20 alkyl and C1-C20 alkyl substituted with hydroxyl or carbonyl;
Rs is lower alkyl;
R 6 is lower alkyl;
R7 is chosen from NR10R 11 and-OR10· or together R4 Rs R6 and
' ' ' '
R 7 may form from one to three rings, said rings having optional
additional substitution;
Rs and R sa are both hydrogen or taken together Rs and R sa are
=O·
'
R9 is chosen from hydrogen and lower alkyl;
R 10 and R11 are each independently hydrogen, optionally
substituted lower alkyl, optionally substituted alkenyl, optionally
substituted alkynyl, optionally substituted aryl, hydroxyl,
amino or optionally substituted lower alkoxy;
y is -(C(R10)(R11))p- or a direct bond, wherein pis 0 1, 2, 3, 4, 5,
6, or 7:
Y2 is a direct bond or -(C(R10)(R11))q-, wherein q is 0, 1, 2, 3, 4,
or 5·
'
Lis a direct bond or or-(C(R10)(R11))q-; and
Cy is Ar1-B-Ar2, wherein
Ar1 is absent, or an aryl or heteroaryl radical having from
1to4 N, 0 and/or S atoms, which may be unsubstituted or
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mono-, di- or trisubstituted by halogen, lower alkyl,
alkenyl, alkynyl, cycloalkyl, -OR10, -NR10R11 , -CN, -
COR10 or -COOR10·
' '
B is a direct bond, -0-, -NR10, -S02, or -(C(R10)(R11)[)]s-,
wherein sis 0, 1, 2, 3, 4 or 5; and
Ar2 is aryl or heteroaryl radical having from 1 to 4 N, 0
and/or S atoms, which may be unsubstituted or mono-, di-
or trisubstituted by halogen, lower alkyl, alkenyl, alkynyl,
cycloalkyl -OR10 -NR10R11 -CN -COR10 or
' ' ' '
-COOR10.
App. Br. 27-28.
ISSUES AND ANALYSIS
With respect to the Examiner's findings and conclusions concerning
the rejections of the claims under 35 U.S.C. §§ 102(b) and 102(±), we
decline to adopt the Examiner's findings and conclusions. We agree with,
and adopt, the Examiner's findings and conclusion with respect to the
rejection under 35 U.S.C. §103(a). We address the arguments raised by
Appellant on appeal below.
A. The Rejection of claims 1-27 and 30 under 35 U.S.C. §102(b)
Issue
Appellant contends the Examiner erred in finding VanAlstine is prior
art under 35 U.S.C. §102(b) to Appellant's application. App. Br. 15.
Analysis
Appellant admits Melissa VanAlstine orally presented her dissertation
to her graduate committee. App. Br. 15. However, Appellant points to In re
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Cronyn, 890 F.2d 1158, 1160 (Fed. Cir. 1989), which, Appellant contends,
held that the oral presentation of a dissertation, even with dissemination of a
printed publication to the members of the dissertation committee, was not
found to be patent-defeating prior art. Id. at 16 (citing In re Bayer, 568 F.2d
1357, 1362 (C.C.P.A. 1978)).
Appellant also adduces as evidence a screenshot taken from the
Rensselaer Polytechnic Institute Library Catalog obtained on April 26, 2012.
App. Br. 16 (citing App'x C). Appellant argues Field 583 of the screenshot
shows the issue date is "2007-11-01," which, Appellant asserts is the date
when the electronic dissertation record was created in the digital collections
software. Id. However, Appellant contends the dissertation was not actually
available to the public on that date; according to Appellant, the "CAT
DATE" field of the screenshot shows that the VanAlstine dissertation was
not available to the public until the catalog date of July 10, 2009. Id.
Appellant argues the instant application claims priority to US provisional
application 61/082,255, which was filed on July 21, 2008. Id.
Consequently, Appellant argues, Appellant's application antedates the date
the VanAlstine dissertation became available to the public, and the
VanAlstine dissertation is not available as prior art under § 102(b ). Id.
Appellant argues further that the Examiner relies upon Bayer in
finding that a reference constitutes a printed publication as long as a
presumption is raised that the portion of the public concerned with the art,
such as the inventor who was also an advisor and had access to the
dissertation, would know of the invention. App. Br. 16-17 (citing Final Act.
6). However, Appellant contends, mere "knowledge of' the invention is not
enough to support a 35 U.S.C. § 102(b) rejection. Id. at 17. Rather,
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Appellant argues, the predecessor to our reviewing court has distinguished
between "technical accessibility" of knowledge versus "dissemination" of
knowledge. Id. "Knowledge is not in the possession of the public where
there has been no dissemination, as distinguished from technical
accessibility .... " Id. (quoting In re Tenney, 254 F.2d 619, 629 (C.C.P.A.
1958) (Rich, J., concurring) (internal quotation marks and emphasis
omitted); see also MPEP § 2128.01). Appellant argues that, in the instant
case, no dissemination occurred. Furthermore, Appellant argues, Judge
Rich, in Tenney, stated that a printed publication implies the probability of
wide circulation and the presumption that those concerned with the art
would know of the invention. Id. (citing Tenney, 254 F.2d at 629).
Consequently, argues Appellant, although the electronic dissertation
of VanAlstine may have been technically accessible prior to cataloguing and
shelving at the university library, knowledge contained in the electronic
dissertation was not disseminated to, or in possession of, the public, and
there was no probability of wide circulation of said knowledge. App. Br. 17.
The Examiner finds: (1) the VanAlstine dissertation was signed by the
named inventor of this application: indicating that he knew of the disclosures
within it, at that time; and (2) a copy of the dissertation was required to be
given to all the committee members for the defense/dissertation. Ans. 9.
The Examiner points to the relevant portion of the requirements of
Rensselaer Polytechnic Institute, which states:
2.1.3 Doctoral Dissertation
Doctoral candidates must submit a copy of the dissertation
in its final form along with a copy of the abstract to the thesis
advisor at least one month before the end of the term in which it
is expected that the degree will be awarded. You must furnish
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each doctoral committee member with an individual copy of the
dissertation and the abstract at least one week before the
dissertation defense. For due dates specific to your intended
semester of graduation, check the academic calendar.
Id. (citing Graduate School Guidelines retrieved from the University
website). Therefore, the Examiner finds, Appellant's arguments that the
dissertation was not distributed does not match the stated requirements of the
Graduate school guidelines. Id.
The Examiner points next to Mass. Inst. of Tech. v. AB Fortia, 774
F.2d 1104 (Fed. Cir. 1985), in which the court held that a presentation could
be a printed publication. Ans. 10. In that case, the cited art was an oral
presentation to 50-500 scientists at a conference, and copies of the paper
were distributed on request afterward to as many as six people. Id. The
court held that the presentation was a printed publication because (a) 50-500
interested persons were actually told of the existence of the paper and
informed of its contents by the oral presentation, and (b) the document itself
was actually disseminated without restriction to at least six persons. Id.
The Examiner further cites Bayer and In re Hall, 781 F.2d 897 (Fed.
Cir. 1986), in support of finding that the VanAlstine dissertation, the
contents of which were known by the dissertation committee, and which
were deposited in the library, is a prior publication of valid prior art.
We are persuaded by Appellant's arguments. It is undisputed by
Appellant and the Examiner that copies of the V anAlstine dissertation were
provided to members of the dissertation committee (typically 3-6 members)
for purposes of review prior to then-Ms. VanAlstine's defense of her
dissertation. Moreover, it is similarly undisputed that the dissertation was,
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in due course, submitted to, and catalogued in, the lnstitute's library
holdings.
However, we are not persuaded that then-Ms. VanAlstine's provision
of her dissertation to the members of her committee (in conformance with
Institute guidelines), prior to her defense of her dissertation before the
committee, is sufficient to qualify her dissertation as a "printed publication"
under 25 U.S.C. § 112. As the Institute guidelines make clear, these copies
are disseminated for the purpose of review by the committee members prior
to the defense and are not generally made available to the public. The
Examiner quotes Bayer, which has a similar set of facts, in which the Board,
upon request for reconsideration stated:
[T]he crucial fact leading to our decision is that the members of
appellant's graduate committee could have located his thesis in
the library where it was available to them on request.
Furthermore, in the absence of any indication of a continued
obligation of confidentiality, the members of the graduate
committee could have transmitted the information necessaf'J for
obtaining the thesis to any number of other people having an
interest in its subject matter.
Ans. 12 (quoting Bayer, 568 F.2d 1357, 1359). However, we find the
predecessor to our reviewing court reversed that decision of the Board,
holding:
[W]e are unconvinced that appellant's thesis defense before the
graduate committee in its official capacity as arbiter of
appellant's entitlement to a master's degree was somehow
transmuted into a patent-defeating publication merely by
depositing the thesis in the university library where it remained
uncatalogued and unshelved as of the critical date in question.
We believe that the board has attempted to draw too fine a line
of distinction here, and in so doing, has unjustifiably denied
appellant's claims.
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Bayer, 568 F.2d at 1362 (emphasis added).
Similarly, in Hall, the Federal Circuit held that a single copy of a
doctoral dissertation in the University of Freiburg "dissertation was
accessible" because it had been indexed, cataloged and shelved in the
University's library. Hall, 781 F.2d at 899.
Finally, in Cronyn, the Federal Circuit held that student theses:
[W]ere not accessible to the public because they had not been
either cataloged or indexed in a meaningful way. Although the
titles of the theses were listed on 3 out of 450 cards filed
alphabetically by author in a shoebox in the chemistry
department library, such "availability" was not sufficient to make
them reasonably accessible to the public. Here, the only research
aid was the student's name, which, of course, bears no
relationship to the subject of the student's thesis.
Cronyn, 890 F .2d at 1161.
Summarizing the holdings in Bayer, Hall, and Cronyn, and
considering the totality of the evidence presented by Appellant, we come to
the conclusion that the VanAlstine dissertation was not available to the
public as prior art until it had been catalogued by the Institute library and
thus made generally available to the public.
The VanAlstine dissertation was eventually catalogued by the Institute
library, but Appellant has adduced evidence, unrebutted by the Examiner,
that the dissertation was not catalogued until July 10, 2009, subsequent to
the priority date of July 21, 2008 claimed by Appellant's application. We
therefore conclude, that it was not until the dissertation was catalogued by
the Institute library that it became available to the public as a printed
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publication valid as prior art under 35 U.S.C. § 102(b). We therefore reverse
the Examiner's rejection upon this ground.
B. The Rejection of claims 1-27 and 30 under 35 U.S.C. §102(±)
Issue
Appellant argues the Examiner erred in rejecting the claims under 35
U.S.C. § 102(f) because the Examiner finds Appellant did not invent the
claimed invention. App. Br. 18.
Analysis
Appellant argues that, contrary to the Examiner's conclusion that "it
would be improper to assume that a Ph.D. thesis is not the authors own
work, especially if they obtained a Ph.D. degree because of it," Appellant is
in fact the inventor of the claimed invention. App. Br. 18 (quoting Final
Act. 8). Appellant points to MPEP § 2137.01, which states: "[T]he party or
parties executing an oath or declaration under [pre-A.I.A.] 37 C.F.R. § 1.63
are presumed to be the inventors." Id. (also citing Driscoll v. Cebalo, 5
USPQ2d 1477, 1481(BPAI,1982). Appellant asserts such a declaration
was signed by Appellant, Mark Wentland, on August 24, 2009, and was
uploaded to the Board's PAIR website on August 26, 2009. Id. Appellant
contends there is no reason to doubt the veracity of this declaration. Id.
According to Appellant, Professor Wentland was the graduate
dissertation director of then-Ms. VanAlstine and originally conceived of the
invention, which Ms. VanAlstine then utilized in her graduate research. Id.
Appellant contends that conception of the invention is the sine qua non of
inventorship. Id. at 18-19 (citing MPEP § 2137.01) ("The threshold
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question in determining inventorship is who conceived the invention. Unless
a person contributes to the conception of the invention, he is not an
inventor .... Insofar as defining an inventor is concerned, reduction to
practice, per se, is irrelevant").
Appellant also points to the Board's decision in Ex parte Cherepinsky,
Appeal No. 2009-009698, in which the inventorship of the filed patent
application differed from the authorship of the Ph.D. thesis. App. Br. 18.
According to Appellant, in Cherepinsky, the Board concluded that: "[A]
publication of a scientific work is not evidence of 'invention' as that term is
used in the patent statutes. Therefore, the Cherepinsky published Ph.D.
thesis does not provide adequate evidence on which to reject the claims
under section 102(f)." Id. (quoting Cherepinsky 15) (internal citation
omitted). Similarly, Appellant contends, the authorship of a graduate thesis
completed under the supervision of Professor Wentland is not evidence that
Dr. VanAlstine is the inventor of the claimed application. Id.
The Examiner responds that the V anAlstine dissertation is marked
"Copyright 2007" and therefore how any compound or disclosure can be
obtained from the reference is not clear. Ans. 14. The Examiner also finds
the facts of the instant appeal are materially different from those of
Cherepinsky: (1) the abstract relied upon did not fully describe the invention;
(2) the abstract was not dated more than a year prior to the filing of the
application; and (3) the author of the thesis in question in Cherepinsky was
also listed as one of the inventors on the subsequent application. Id.
The Examiner finds the V anAlstine dissertation not only describes
making the compounds, but also discloses the activity of the compounds and
their selectivity, based on VanAlstine's research. Ans. 14. The Examiner
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finds Dr. VanAlstine thanks Professor Wentland for "giving her
independence and freedom to explore the many aspects of medicinal
chemistry," which the Examiner finds probative of inventorship. Id. The
Examiner finds these disclosures indicate that Dr. VanAlstine enabled and
reduced to practice the invention at the time the thesis was presented and is
therefore the "inventor" of the claimed invention. Id.
The Examiner also finds that Professor Wentland's inventorship
declaration does not remove the VanAlstine dissertation as prior art, since
the dissertation is dated more than a year before filing of the instant
application and thus creates a statutory bar under 35 U.S.C. § 102(b ). Ans.
15 (citing In re Katz, 687 F.2d 450, 454 (C.C.P.A. 1982)). The Examiner
also finds that, because Dr. VanAlstine has not filed a disclaiming affidavit,
Professor Wentland has not demonstrated that he is the sole inventor of the
work. Id. The Examiner finds that, if there is evidence that the co-author
has refused to disclaim inventorship and believes himself or herself to be an
inventor, Appellant's affidavit will not be enough to establish that applicant
is the sole inventor and the rejection will stand. Id.
We are persuaded by Appellant's arguments. The Examiner has the
burden of establishing that the claimed subject matter is unpatentable under
statute by providing a factual basis for the rejection. In re Oetiker, 977 F.2d
1443, 1445 (Fed. Cir. 1992).
"Mark P. Wentland" is named as the sole inventor of the application
on appeal on the Oath or Declaration of inventorship, filed, pursuant to [pre-
A.I.A.] 35 U.S.C. § 115, on August 26, 2009, thus establishing a rebuttable
presumption of inventorship. The Examiner adduces no persuasive evidence
that Professor Wentland did not conceive of the invention prior to the
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publication of the VanAlstine dissertation. Nor are we persuaded by the
Examiner's other findings. The fact that the VanAlstine dissertation is
marked with a copyright date is insufficient in itself to establish more than
that Dr. VanAlstine is the original author of the dissertation; it is not
sufficient, under the statutes governing patentability, to establish that Dr.
VanAlstine is the inventor of the claimed invention.
Furthermore, our reviewing court has held that: "authorship of an
article, by itself, does not raise a presumption of inventorship with respect to
the subject matter disclosed in the article." Katz, 687 F.2d at 454.
Moreover, the Examiner adduces no factual evidence that Professor
Wentland did not conceive of the claimed invention.
Nor are we persuaded by the Examiner's finding that Professor
Wentland's declaration is barred under 35 U.S.C. § 102(b). The Examiner
adduces no evidence of dissemination or publication of the claimed
invention more than a year prior to the filing of the application. And, as we
have related supra, the instant application was filed prior to the
"publication" of Dr. VanAlstine's dissertation, i.e., the date in which it was
catalogued by the Institute library and became publicly available.
Finally, the Examiner's finding that, because there were no
disclaiming affidavits filed by Dr. VanAlstine, Dr. VanAlstine is a co-
inventor, is inapposite and tautological, assuming ab initio that Dr.
VanAlstine is an inventor. However, the Examiner has adduced no evidence
that Dr. VanAlstine now claims inventorship of the claimed invention.
In the absence of factual evidence to the contrary, we conclude
Professor Wentland is properly named as inventor of the claimed subject
matter and we reverse the Examiner's rejection of the claims on this ground.
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C. The Rejection of claims 1-27 and 30 under 35 U.S.C. §103(a)
Issue
Appellant argues the Examiner erred in finding the cited prior art
references teach or suggest the limitations of claim 1. App. Br. 19.
Analysis
Appellant argues Wentland ' 13 7 and Wentland '099 do not provide
any guidance to make the particular substitution to arrive at compounds with
superior opiate receptor binding properties. App. Br. 19. Appellant points
to the Examiner's finding that Wentland '13 7 "teaches compounds similar to
compounds of the instant claims" and that Wentland '099 teaches "the
phenolic OH can be replaced by an amino and ... the Hof the amino group
can be replaced with biphenyl and its affinity increases." App. Br. 19-20
(quoting Non-Final Act. 14, January 7, 2013). According to Appellant, there
are no teachings in Wentland '099 that "the H of the amino group can be
replaced with biphenyl and its affinity increases," nor is there any data
displaying changes in activity under such conditions. Id. at 20. Appellant
asserts Wentland '099 discloses compounds in which the H of an amino
group can be replaced with a benzyl or phenyl derivative with increased
activity, but not with a biphenyl. Id. (citing Wentland '099, 5635).
Appellant also contends Wentland '099 teaches compounds wherein
the H of an amide group can be replaced with biphenyl, however, such
change results in a decrease in activity. Id. Appellant points to compounds
1 (R = H) and 13 (R = biphenyl) in Table 1, arguing that the compound
having the H of the amide group has a Ki of 0.31 +/-0.033 at the µopioid
receptor, whereas the compound in which the H of the amide is replaced by
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biphenyl has a Ki of 18 +/- 1.6 at theµ opioid receptor. Id. (citing Wentland
'099, 5636, Table 1 ). Appellant asserts similar decreases in activity are seen
at the other two opioid receptors 8 and K. Id.
Appellant argues that, although the phenolic OH may be replaced by
an amino, a person of ordinary skill in the art would not have been motivated
to replace this hydroxyl substituent with a primary amine. App. Br. 21.
Appellant argues that a brief review of the inventor's own work in the
relevant art demonstrates that this type of substitution on the skeleton of the
opioid compound has not led to particularly desirable outcomes. Id.
Appellant points to Wentland et al., 8-Aminocyclazocine analogues:
synthesis and structure-activity relationships 10(2) BIOORGANIC &
MEDICINAL CHEMISTRY LETTERS 183-87 (2000) ("Wentland et al."), which
is argued to show that when the 8-position hydroxyl group (Compound 1) is
substituted with -NH2 (Compound 4), -NHCH3 (Compound 7), or
-NH(CH3)2 (Compound 16), the activity at all three opioid receptors
decreases dramatically. Id. Similarly, Appellant points to Bidlack et al.
Selective protection and functionalization of morphine: synthesis and opioid
receptor binding properties of 3-amino-3-desoxymorphine derivatives, 43
JOURNAL OF MEDICINAL CHEMISTRY 3558-65 (2000) ("Bidlack") which,
Appellant argues, teaches that replacement of the -OH at the 3-position of
morphine (Compound 3) with -NH2 (Compound 16), -NHCH3 (Compound
17), or-NH(CH3)2 (Compound 18) again results in a significant decrease in
the activity at all three opioid receptors. Id. at 22-23. Therefore, Appellant
contends, there would have been no motivation for the person of skill to
replace a hydroxyl with an amine, as there would have been no expectation
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of comparability given the results of the hydroxyl to amine replacement at
the 3/8-position shown in the literature above. Id. at 22.
Appellant acknowledges the Examiner's findings that Wentland et al.
"is not the closest art for comparison" and that Wentland ' 13 7 teaches
compounds "that have a very similar replacement of the -OH group" As well
as "the amide linkage with a biphenyl ring at the 8 position." App. Br. 22
(quoting Final Act. 8). Appellant notes the Examiner continues by (1)
finding the Q group of Wentland ' 13 7 to be similar to the one in the instant
application, except for lacking an NR1R2 group, (2) finding that Wentland
'099 teaches the amino group has "some difference i[n] activity," and (3)
concluding that Wentland '099 would have motivated a person of ordinary
skill in the art to have an amine group on the cyclic ring of the compounds
taught in Wentland' 137. Id.
Appellant counters that Wentland '099 teaches compounds in which
the H of an amino group attached to a cyclazocine core can be replaced with
a benzyl or phenyl derivative and show increased activity relative to the
unsubstituted NH2. App. Br. 22 (citing Wentland '099 5635). Appellant
argues these compounds are not relevant to the compounds of Appellant's
claimed invention, in which the H of an amide group attached to a
cyclazocine core is replaced. Id. at 22-23. Nor, Appellant contends, is there
any teaching or suggestion in Wentland '099 that an amine substitution of a
cyclic group as disclosed in the instant application would improve binding
activity. Id. at 23.
Appellant argues further that the results set forth in Appellant's
Specification are unexpected when compared to the teachings of Wentland
'13 7. App. Br. 23. According to Appellant, the Specification discloses
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compounds having a Q-type substitution of formula CONH(CH2)2(4-C6H4-
4-NH2C6H4) that provide greatly improvedµ opioid receptor binding activity
compared with compounds in Table 1, namely a Ki of 0.0014 +/- 0.00010
nM. Id. (citing Spec. 25, Table 1, compound SJJ-B-112g). Appellant
contends that the teachings of Wentland ' 13 7 and Wentland '099 would not
have been motivated a person of ordinary skill in the art to make the amino
substitution. Id.
The Examiner responds that both Wentland ' 13 7 and Wentland '099
teach compounds lacking the biphenyl groups. Ans. 17. The Examiner
finds Wentland' 137 discloses the closest compounds, with different
substituents at Rl5 on the phenyl, and that Rl5 can be various other groups.
Id. The Examiner finds VanAlstine et al., Redefining the structure-activity
relationships of 2, 6-methano-3-benzazocines. 5. Opioid receptor binding
properties of N-((4 '-phenyl)-phenethyl) analogues of 8-CAC, 17
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 6516-20 (2007) (submitted
by Appellant as App'x B of the Appeal Brief), teaches a comparative study
of these different substitutions at the Rl 5 locus. Id.
The Examiner also finds Wentland '099 also teaches the biphenyl
group without any substitutions, but teaches further that the biphenyl group
conforms to the hydrophobic portion of the receptor. Ans. 17. The
Examiner also finds the same reference teaches substitution at the 8 position,
especially the conversion of a phenolic -OH to a carboxamide or an amine.
Id. (citing Wentland '099, compound 3). The Examiner finds Wentland
'099 also teaches the substitutions on the opioid core recited by the claims
on appeal. Id. The Examiner further finds Wentland '099 teaches the
increased sensitivity following substitution with an amino group, a
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Application 12/506,354
dimethylamino group, a hydroxyl group, etc., by increasing the hydrophobic
nature of the group. Id. The Examiner concludes a person of skill in the art
would therefore substitute an amino group, which has the same valence as
the nitrogen, in the hope of probing the hydrophobic receptor pocket. Id. at
18. The Examiner therefore concludes it would have been prima facie
obvious to modify the compounds of Wentland '13 7, which discloses other
Rl5 substituents, so as to put an amino substituent, having the same valence
as the N, to study the activity/selectivity of the opioids with respect to the
phenyl alanine receptors. Id. at 18-19.
We are not persuaded by Appellant's arguments. As an initial matter,
the Wentland et al. and Bidlack references cited by Appellant are not entered
into the evidentiary record of this appeal and we therefore do not reach any
of the arguments made by Appellant with respect to those references. See 3 7
C.F.R. § 41.37(c)(iv).
The Examiner finds, and we agree, that both Wentland '13 7 and
Wentland '099 teach compositions possessing an opioid core that are very
similar to the composition recited in claim 1. The Examiner finds Wentland
'099 is cited to show that "the phenolic [-JOH can be replaced by an amino
and it also teaches that the H of the amino group can be replaced with
biphenyl and its affinity increases." Ans. 20 (quoting Non-Final Act. 14).
In short, the Examiner concludes it would be within the skill of a person of
ordinary skill to replace the phenol group of formula 2 in Figure 1 of
Wentland '099 with the carboxamide linkage of formula II in Figure 1 of
Wentland '099. The Examiner further concludes it would be within the skill
of a skilled artisan to replace the bi phenyl group of the latter composition
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Application 12/506,354
with the phenyl-N-phenyl group, with the N linking to the carboxamide
chain.
Appellant argues that Wentland '099 teaches: "compounds wherein
the Hof an amino group can be replaced with a benzyl or phenyl derivative
with increased activity, but not with a biphenyl [but] discloses compounds
wherein the H of an amide group can be replaced with biphenyl, however,
such change results in a decrease in activity." App. Br. 20 (citing Wentland
'099 5635-36). Appellant appears to implicitly argue that Wentland '099
thus teaches away from a biphenyl substitution, but we are not persuaded
that Wentland '099 explicitly "criticize[s], discredit[s], or otherwise
discourage[s] the solution claimed." See In re Fulton, 391 F.3d 1195, 1201
(Fed. Cir. 2004). Moreover, in the context of an obviousness analysis, "'all
disclosures of the prior art, including unpreferred embodiments, must be
considered."' Merck & Co., Inc. v. Biocraft Laboratories, Inc., 874 F.2d
804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750
(C.C.P.A. 1976)).
Furthermore, inin re Dillon, 919 F.2d 688, 696 (Fed. Cir. 1990), the
Federal Circuit noted:
In brief, the 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.
In re Henze, 181 F.2d 196, 37 CCPA 1009, 85 USPQ 261,
(CCPA 1950);InreHass, 141F.2d122, 127, 130, 31CCPA895,
60 USPQ 544, 548, 552 (CCPA 1944). The burden then shifts to
the applicant, who then can present arguments and/or data to
show that what appears to be obvious, is not in fact that, when
the invention is looked at as a whole. In re Papesch, 315 F .2d
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Application 12/506,354
381, 50 CCPA 1084137 USPQ 43 (CCPA 1963). 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 re Dillon, 919 F.2d at 696. Appellant points to no disclosure of the
Specification that explains why the claimed compound is not obvious in its
properties or alleged advantages.
The Examiner further finds a person of ordinary skill would be
motivated to make this latter substitution because it would increase the
binding efficiency at the hydrophobic portion of the opioid receptor. The
Examiner points to page 5638 of Wentland '099 in support of this latter
finding.
We agree with the Examiner. Wentland '099 recites:
Since potency is much higher with the two methylene spacer than
with 0, 1, or 3 methylenes, conformation of the ligand also
appears to play an important role. It is interesting to speculate
what amino acid residues on the receptors are complementary to
the hydrophobic biphenylethyl group of 1. From the homology
model of the µ receptor bound to nor-BNI9, there are three
phenylalanine (Phe 152, Phe237, and Phe241) residues in the
region of the 8-position of benzomorphans which may create a
hydrophobic pocket complementary to the biphenylethyl group
ofl.
The putative hydrophobic binding pocket in the receptors that we
believe is complimentary to the N-( 4' -phenyl)-phenethyl) group
of 15 has not been previously explored to any great extent
because most opiate SAR studies lack the ability to probe this
receptor space due to the lower (than nitrogen) valence of the
oxygen of the phenolic-OH, the prototypic group of opiates.
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The SAR in this series appears to be additive in that the benefit
of the N-( 4 '-phenyl)-phenethyl group of 15 crosses over to
another core structure, namely the 8-carboxamido-EKC.
It is our belief that the knowledge gained from this study
will assist in the design of new high affinity opioid receptor-
interactive ligands modified at the phenolic-OH position of
opiates.
Wentland '099 5638. We therefore agree with the Examiner that a person of
ordinary skill in the art would be motivated to attempt substitutions designed
to explore variations of the compositions taught by Wentland '099 to space
the biphenyl groups such that interaction with hydrophobic portions of the
opioid receptors would be improved.
Consequently, we affirm the Examiner's rejection of the claims on
this ground.
DECISION
The Examiner's rejection of claims 1-27 and 30 as unpatentable under
35 U.S.C. § 102(b) is reversed.
The Examiner's rejection of claims 1-27 and 30 as unpatentable under
35 U.S.C. § 102(f) is reversed.
The Examiner's rejection of claims 1-27 and 30 as unpatentable
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. § l.136(a)(l). See 37 C.F.R.
§ l.136(a)(l )(iv).
AFFIRMED
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