Ex Parte Namavari et al

Patent Trial and Appeal Board

Jun 18, 2018

14590538 (P.T.A.B. Jun. 18, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/590,538 01/06/2015
24504 7590 06/20/2018
THOMAS I HORSTEMEYER, LLP
3200 WINDY HILL ROAD, SE
SUITE 1600E
ATLANTA, GA 30339
FIRST NAMED INVENTOR
Mohammad Namavari
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.
221907-1531 9616
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
06/20/2018 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):
uspatents@tkhr.com
ozzie. liggins@tkhr.com
docketing@thomashorstemeyer.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MOHAMMAD NAMA VARI, SANJIV SAM GAMBHIR,
and BEYERL Y S. MITCHELL 1
Appeal2017-006107
Application 14/590,538
Technology Center 1600
Before FRANCISCO C. PRATS, JOHN G. NEW, and
RICHARD J. SMITH, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants identify The Board of Trustees of the Leland Stanford Junior
University as the real party-in-interest. App. Br. 3.
Appeal2017-006107
Application 14/590,53 8
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 1, 2, 4, and 5 as unpatentable under
35 U.S.C. § 103(a) as being obvious over the combination of J.A.
Montgomery et al., 9-(2-Deoxy-2-jluoro-/J-D-arabinofuranosyl)guanine: A
Metabolically Stable Cytotoxic Analogue of 2 '-Deoxyguanosine, 29 J. MED.
CHEM. 2389--92 (1986) ("Montgomery"), C.U. Lambe et al., 2-Amino-6-
methoxypurine Arabinoside: An Agent for T-Cell Malignancies, 55 CANCER
REs. 3352-56 (1995) ("Lambe"), S.L. Berg et al., Phase II Study of
Nelarabine (compound 506U78) in Children and Young Adults With
Refractory T-Cell Malignancies: A Report From the Children's Oncology
Group, 23:15 J. CLIN. ONCOL. 3376-82 (2005) ("Berg"), Price (US
4,489,052, December 18, 1984) ("Price"), and Lopez et al. (US 4,211,773,
July 8, 1980) ("Lopez").
We have jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to the method of imaging a T -Cell,
among others, including administering to the subject one of the disclosed
compounds, and imaging the subject, wherein detecting the presence of the
compound corresponds to the presence of the T-cell. Spec. 1.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method of imaging a T Cell comprising:
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administering to the subject a compound having formula
3;and
imaging the subject, wherein detecting the presence of the
compound corresponds to the presence of the T cell, wherein
formula 3 is represented by the following structure,
wherein Ist is 18F, wherein R' is a compound having a
formula selected from the group consisting ofR'l, R'2, R'3, R'4,
and R'S:
App. Br. 12.
ISSUES AND ANALYSES
Issue 1
Appellants argue that the Examiner erred because a person of ordinary
skill in the art, comprehending the cited prior art references, would have had
no expectation of success in performing the claimed methods. App. Br. 5.
Analysis
The Examiner finds that Montgomery teaches cytotoxicity and
inhibitory effects of 9-(2-deoxy-2-fluoro-B-D-arabinofuranosyl) guanine
3
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Application 14/590,53 8
toward T-cell malignancies. Final Act. 3. The Examiner finds that Lambe
teaches that teach that the water-soluble prodrug 2-Amino-6-methoxypurine
arabinoside ("506U") is converted to guanine arabinoside ("ara-G") by
adenosine deaminase and demonstrates in vitro and in vivo antitumor
activity against a GEM/human T-lymphoblastoid cell line. Id. The
Examiner further finds that Berg teaches that nelarabine (506U78), another
water soluble prodrug of ara-G demonstrated activity against T-cell
lymphoblastic malignancies in human patients. Id. at 4. The Examiner also
finds that Price teaches that 1-(2'-deoxy-2'-substituted-D-arabinofuranosyl)
pyrimidine nucleoside can be radiolabeled with 18F. Id.
The Examiner concludes that it would have been obvious to a person
ordinary skill in the art to substitute the fluorine of Montgomery with the
radio labeled 18F of Price to obtain the advantage of PET imaging of a
subject, because Price teaches substituting fluorine on an arabinofuranosyl
moiety, such as those of Lopez with the 18F isotope. Final Act. 4. The
Examiner further concludes that it would also have been obvious to a person
of ordinary skill to use the 18F-labelled 9-(2-deoxy-2-fluoro-B-D-
arabinofuranosyl)guanine for in vivo imaging of T-Cells or T-lymphoblasts,
because Lambe and Berg teach 9-(2-deoxy-2-fluoro-B-Darabinofuranosyl)
guanine exhibits cytotoxicity and inhibitory effects upon T-cell and T-
lymphoblast malignancies, respectively, in vivo.
The Examiner further points out that it was well known in the prior art
that one could prepare the composition of Formula 3, in which Ist is F (but
not 18F) and R' is R'l at temperatures of from 25°C to 200°C in a period
from one hour to 10 days followed by saponification with an alkali metal
alkoxide over an interval from 5 minutes to three days. Final Act. 4--5
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Application 14/590,53 8
(citing Watanabe et al. (US 4,751,221, June 14, 1988) ("Watanabe"), cols.
2-3).
The Examiner also finds that it was well-known in the art that Klecker
et al. (US 6,753,309 B2, June 22, 2004) ("Klecker") teaches methods of
preparing 18F fluorinated nucleosides at Ri (corresponding Ist of Formula 3).
Final Act. 5. The Examiner finds Klecker teaches that the half-life of 18F is
110 minutes and that the fluorinated molecule must be prepared on the day
of its clinical use. Id. The Examiner finds Klecker teaches that the reaction
steps are consequently optimized for short synthesis times, with yield as a
secondary consideration. Id. (citing Klecker col. 16, 11. 18-36; col. 17, 11.
14--20).
Appellants first argue that none of the cited references teach or
suggest an actual reduction to practice of a method falling within the scope
of claims 1 or 4. Appellants point to our reviewing court's holding that:
"there is no absolute predictability of success until the invention is reduced
to practice." App. Br. 6. ( citing In re O 'Farrell, 853 F .2d 894, 903 (Fed.
Cir. 1988)). However, neither an "actual reduction to practice" nor an
"absolute predictability of success" are requisites for a prima facie
conclusion of obviousness. Id. Rather, the proper test for obviousness is
what the combined teachings would have suggested to a person of ordinary
skill in the art. In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000).
Moreover, "[ o ]nly a reasonable expectation of success, not absolute
predictability, is necessary for a conclusion of obviousness." In re Langi,
759 F.2d 887, 897 (Fed. Cir. 1985). We therefore direct our analysis to
whether a person of ordinary skill in the art would have had a reasonable
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Application 14/590,53 8
expectation of success in combining the references to arrive at Appellants'
claimed invention.
According to Appellants, claims 1 and 4 recite imaging a compound
according to Formula 3 where Ist is 18F. App. Br. 6. Appellants agree with
the Examiner that the half-life of 18F is 110 min and, to be a viable probe for
imaging according to the methods of claims 1 and 4, the 18F labeled probe
molecule must therefore be synthesized within an interval such that it
remains viable as a probe, as determined by the half-life of 18F. Id. (citing
Klecker col. 17, 11. 14--16).
Appellants argue that Montgomery teaches the synthesis of 2-amino-
9-(2-deoxy-2-fluoro-B-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one ( a
claimed composition), however, it is not 18F-labeled at the Ist position. App.
Br. 7. Appellants contend that, to reach the claimed compound with 18F, a
person of ordinary skill would have to either: ( 1) start with 18F-labeled
reagents and synthesize the finished composition; or (2) label the
composition taught by Montgomery with 18F after synthesis. Id. Appellants
assert that Montgomery teaches that the method of making 2-Amino-9-(2-
deoxy- 2-fluoro-B-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one requires
6 steps, where the first step alone requires 16 hours and the overall method
requires about 80 hours to produce the final product. Id. Appellants
therefore argue that the first method suggested above is not feasible for the
claimed method, given the short half-life of 18F. Id.
Appellants argue that neither Lambe nor Berg teach or suggest
making 18F labeled probes, or making probes having a structure according to
Formula 3. App. Br. 8. Appellants acknowledge that Price teaches that 18F
is an isotope label that can be used for PET imaging ( citing Price col. 2, 11.
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27-29). Id. However, Appellants contend, Price neither teaches nor
suggests any methods for making 18F-labeled probes; rather, the examples of
Price are all directed to 14C-labeled probes. Id. Appellants assert that Price
does not teach or suggest any 18F-labeled probe, and does not teach or
suggest any probe according to Formula 3. Appellants argue further that
Lopez does not teach or suggest making 18F-labeled compounds and does
not teach or suggest making a compound according to Formula 3, as
required by instant claims 1 and 4. Id.
With respect to the Examiner's citations to Watanabe and Klecker,
Appellants argue that neither Watanabe nor Klecker correct the alleged
deficiencies of the other cited prior art references. App. Br. 8. Appellants
contend that Watanabe teaches methods of making compounds with the
following formula:
Formula I of Watanabe teaches 2'-Deoxy-2' -fluoro-B-D-
arabinofuranosyl nucleosides
Appellants assert that the compositions of Watanabe are not 18F-labeled and
do not have a structure according to Formula 3 as required by the claims. Id.
Appellants acknowledge Klecker teaches preparing 18F-fluorinated
nucleosides starting from compounds having the formula:
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Initial compound of Example 4 of Klecker
However, Appellants assert that this family of compounds are not
compounds according to Formula 3 and do not result in compounds
according to Formula 3 as required by instant claims 1 and 4. App. Br. 9.
We do not find Appellants' arguments persuasive. Montgomery
teaches that that the "enhanced toxicity of certain deoxynucleosides toward
T-cell lines relative to B-cell lines may result from the greater ability of
these cells to accumulate toxic concentrations of the corresponding
deoxynucleoside triphosphates." Montgomery 2389. As an example of such
a compound that preferentially accumulates in T-cells Montgomery teaches,
as Appellants acknowledge, a composition of Formula 1, in which the R
group is fluorine ("F"), as depicted below:
Formula 1 of Montgomery
The only element lacking in this compound of Montgomery is that the
fluorine molecule R ( corresponding to Ist in claim 1) is not the 18F isotope.
Similarly, Watanabe teaches methods of synthesizing closely-related 2'-
deoxy-2 '-fluoro-B-D-arabinofuranosyl nucleosides:
8
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Application 14/590,53 8
F onnula I of Watanabe
Lambe and Berg teach that such compounds are effective against the
growth of T-cell lines and isolated T-leukemic cells. Lambe Abstr.; Berg,
3378-79.
Klecker is directed to: "[m]ethods of diagnosing and/or of treating
tumors by administering a nucleoside analogue which is activated by
thymidylate synthase and/or thymidine kinase enzyme into a diagnostic or
toxic metabolite, and uridine analogue compounds," and: "diagnostic
applications, compounds containing a label and methods of use of such
compounds." Klecker, Abstr.
A most preferred embodiment of Klecker is illustrated below:
Preferred embodiment of Klecker col. 9, 11. 2-15
in which:
A=N C·
' '
B=H, hydroxy, halogen, acyl (C1---C6), alkyl (C1---C6),
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Application 14/590,53 8
E= H, alkly, substituted alkyl, alkenyl, substituted alkenyl,
alkoxy, substituted alkoxy, halogen, or any substituent
which is
W, X, Y, Z H, hydroxy, halogen, alkyl (C 1---C6), alkoxy
(C 1---C6), a label containing moiety or a label;
J=C S· and
' '
K=O,C.
In preferred embodiments for anti-tumor activity, E may be
H
Id. at col. 9, 11. 15-28. Klecker also teaches that:
In preferred embodiments for imaging applications, W may be a
label containing moiety or a label. The label may be any moiety
that permits the detection of the nucleoside analogue. In
preferred embodiments, the label includes a positron emitting
atom and in a most preferred embodiment, Wis 18F.
Id. at col. 10, 11. 14--19 (emphasis added). We further note that Klecker also
teaches a moiety at Appellants' position R':
General formula of tumor inhibiting and/ or diagnosing
compound from Klecker col. 8, 11. 36-45
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Application 14/590,53 8
in which:
A=N C·
' '
B=H, hydroxy, alkoxy (C1---C6);
E=H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy,
substituted alkoxy, halogen, or any substituent which is readily
cleaved in the body to generate any one of the before listed
groups;
G=substituted or unsubstituted cyclic sugar, substituted or
unsubstituted acyclic sugar, substituted or unsubstituted mono, di,
or tri-phospho-cyclic-sugar phosphate; substituted or
unsubstituted mono, di, or tri-phospho-acyclic-sugar phosphate;
substituted or unsubstituted mono, di, or triphospho-cyclic sugar
analogues, substituted or unsubstituted mono, di, or tri-phospho-
acyclic sugar analogues wherein the substituents are alkyl (C1 to
C6), alkoxy (C1 to C6), halogen.
Id. at col. 8, 11. 46-63 (emphasis added). We observe that that this general
formula of column 8 of Klecker corresponds to groups R'3 and R' 4 of claim
1:
Furthermore, Klecker teaches that G of its general formula in column
8 can be a substituted cyclic sugar, which corresponds to the substituted
ribose moiety if Appellants' Formula 3. We consequently disagree with
Appellants' argument that Klecker fails to teach or suggest the claimed
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compound. See Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807
(Fed. Cir. 1989) (holding that all disclosures of the prior art, including
unpreferred embodiments, must be considered).
Klecker expressly teaches, in Example 4, that Appellants' position Ist
can be labeled with 18F, as recited in the claims. Klecker col. 10, 11. 14--19.
Furthermore, Klecker acknowledges that: "Because of the short half-life of
18F (110 minutes), the fluorinated nucleoside must prepared on the day of its
clinical use. In these circumstances, the reactions steps are optimized for
short times, with yield as a secondary consideration." Id. at col. 17, 11. 14--
18. Klecker teaches methods by which labeling with 18F at position W (i.e.,
position Ist of the claims, can be accomplished to achieve this end. Id. at
cols. 17-18, 11. 19-42. Klecker's synthetic method of Example 4 is,
therefore directed to a method designed expressly for the purpose of using
18F as a diagnostic marker, providing explicitly for the short half-life of the
isotope. We therefore agree with the Examiner that a person of ordinary
skill would have had a reasonable expectation of success in applying the
method of Klecker to label the compounds of Montgomery and similar
compounds, such as those recited in Formula 3 of the claims, with 18F at the
Ist location, despite the short half-life of the isotope in question. We are
consequently not persuaded by Appellants' arguments.
Issue 2
Appellants argue, with respect to independent claims 1 and 5 and,
separately, dependent claims 2 and 4, that the references teach away from
the claimed invention. App. Br. 10-11. Appellants rely upon their
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arguments presented supra, reasoning that a person of ordinary skill would
be dissuaded from pursuing the claimed invention. Id.
We do not agree. A reference "teaches away" when: "a person of
ordinary skill, upon reading the reference, would be discouraged from
following the path set out in the reference, or would be led in a direction
divergent from the path that was taken by the applicant." In re Gurley, 27
F.3d 551, 553 (Fed. Cir. 1994). As we have explained, Klecker expressly
teaches a method of labeling compositions, including the compositions of
Formula 3 and analogs, with 18F in Appellants' Ist position, with the specific
aim of providing a diagnostic label in view of the short half-life of the
isotope. Appellants point to no teaching or suggestion in any of the cited
prior art references that would expressly divert or discourage a person of
ordinary skill in the art from applying the methods taught by Klecker to
Montgomery's composition. We consequently do not find Appellants'
arguments persuasive, and we affirm the Examiner's rejection of the claims.
DECISION
The Examiner's rejection of claims 1, 2, 4, and 5 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. § 1.136(a)(l). See 37 C.F.R.
§ 1.136(a)(l )(iv).
AFFIRMED
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