Ex Parte Fisher et al

Board of Patent Appeals and Interferences

Jul 20, 2010

09293670 (B.P.A.I. Jul. 20, 2010)

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.
09/293,670 04/16/1999 JOSEPH FISHER RIGL-036CIP 5176
83092 7590 07/21/2010
Rigel Pharmaceuticals, Inc.
Bozicevic, Field & Francis LLP
1900 University Ave, Suite 200
East Palo Alto, CA 94303
EXAMINER
WESSENDORF, TERESA D
ART UNIT PAPER NUMBER
1639
MAIL DATE DELIVERY MODE
07/21/2010 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JOSEPH FISHER, JAMES LORENS,
DONALD PAYAN, and ALEXANDER ROSSI
__________

Appeal 2009-015210
Application 09/293,670
Technology Center 1600
__________

Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL1
This appeal under 35 U.S.C. § 134 involves claims to methods of
screening cells. The Examiner rejected the claims as obvious.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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2
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

STATEMENT OF THE CASE
Claims 17-26, 30, and 32 stand rejected and are on appeal (App. Br.
3).2 Claim 17, the only independent claim, is representative and reads as
follows:
17. A method of screening for an alteration in cellular
phenotype, said method comprising:
a) providing a population of cells comprising a library of
retroviral vectors encoding different candidate bioactive agents;
b) sorting said population of cells based on at least five
parameters using fluorescence activated cell sorting (FACS);
and
c) detecting at least one cell of said population having
said alteration in said cellular phenotype;
wherein said cellular phenotype is selected from a group
of cellular phenotypes consisting of cell cycle, apoptosis,
exocytosis, expression of a cell surface receptor, and expression
of a receptor protein.

The Examiner cites the following documents as evidence of
unpatentability:
Uhr US 5,612,185 Mar. 18, 1997
Nolan WO 97/27212 Jul. 31, 1997

Tao Jia-ping et al., Multi-parameter sorting technique in flow
cytometry, 17 CHINESE JOURNAL OF PHYSICAL MEDICINE 168-171 (1995).

E. Conneally et al., Rapid and Efficient Selection of Human
Hematopoietic Cells Expressing Murine Heat-Stable Antigen as an Indicator
of Retroviral-Mediated Gene Transfer, 87 BLOOD 456-464 (1996).

2 Appeal Brief filed May 7, 2008.
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Izumi Hide et al., Degranulation of Individual Mast Cells in Response
to Ca2+ and Guanine Nucleotides: An All-or-None Event, 123 THE JOURNAL
OF CELL BIOLOGY 585-593 (1993).

The following rejections are before us for review:
(1) Claims 17-24 and 30, rejected under 35 U.S.C. § 103(a) as obvious
over Uhr and Conneally (Ans. 4-7);
(2) Claims 17-25, 30, and 32, rejected under 35 U.S.C. § 103(a) as
obvious over Nolan, Jia-ping, and Uhr (Ans. 7-10); and
(3) Claim 26, rejected under 35 U.S.C. § 103(a) as being unpatentable
over Nolan, Jia-ping, Uhr, Hide, and Appellants’ admitted prior art (Ans. 10-
11).
OBVIOUSNESS -- UHR AND CONNEALLY
ISSUE
The Examiner finds that “Uhr, alone, discloses or teaches all the
elements of the claim[ed] method. Uhr does not positively teach [a] library
of retroviral vectors albeit, at least suggests said library of retroviral vectors”
(Ans. 6).
To supplement the asserted suggestion in Uhr of using a library of
retroviral vectors, however, the Examiner cites Conneally as teaching “the
advantages in the use of recombinant retroviuses [sic] for the genetic
modification of cells,” the advantages including “the ability to assess gene
transfer to specific subpopulations of cells immediately after infection. The
detectable level is sorted by FACS” (id. at 6-7).
Based on these advantages, the Examiner concludes that the “use of
recombinant retroviral vectors to transfect cells would have been obvious to
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one having ordinary skill in the art at the time the invention was made as
taught by Conneally and at least contemplated by Uhr” (id. at 7).
“In a nutshell, the Appellants submit that the claims are not obvious in
view of the cited references because neither of the cited references provide a
library of retroviral vectors” (App. Br. 5). Specifically, Appellants argue,
the portion of Uhr cited by the Examiner to meet that feature, column 22,
lines 14-20, only teaches inducing cell cycle arrest in tumor cells using gene
therapy (id. at 6), and Conneally fails to remedy that shortcoming (id. at 7).
The Examiner responds that column 22 of Uhr teaches that the gene
therapy may be effected using retroviruses (Ans. 11), and also teaches that
cells may be transfected with at least two genes, c-fos and c-jun (id. at 13).
Thus, the Examiner reasons, because the Specification defines “‘library of
cells’” as meaning “at least two cells”, the claims encompass the process
suggested by Uhr (id. at 13-14).
In view of the positions advanced by Appellants and the Examiner,
the issue with respect to this rejection is whether the evidence of record
supports the Examiner’s finding that the cited references suggest a process
that includes a step of “providing a population of cells comprising a library
of retroviral vectors encoding different candidate bioactive agents” as recited
in claim 17.
FINDINGS OF FACT (“FF”)
Claims and Specification
1. Claim 17 recites a method of screening for an alteration in cellular
phenotype. The method’s first step is “(a) providing a population of cells
comprising a library of retroviral vectors encoding different candidate
bioactive agents.”
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2. The Specification states that, “[b]y a ‘population of cells’ or ‘library
of cells’ or ‘plurality of cells’ herein is meant at least two cells, with at least
about 103 being preferred, at least about 106 being particularly preferred, and
at least about 108 to 109 being especially preferred” (Spec. 9).3
The Prior Art
3. Uhr discloses “strategies for the treatment of cancer, including
methods to induce or maintain a state of arrest to prevent tumor growth or
metastasis” (Uhr, col. 2, ll. 62-65).
4. In one embodiment Uhr discloses that “it is contemplated that tumor
cell cycle arrest may be induced by gene therapy. DNA encoding key genes
in this process, such as, for example, c-fos or c-jun, may be applied directly
to cells, in the form of oligonucleotides, or other genetic constructs” (id. at
col. 22, ll. 6-10).
5. Uhr further discloses that the “preparation of vectors which
incorporate nucleic acid sequences capable of encoding the desired genes,
once introduced into the cells to be treated, is also contemplated. In this
regard, replication defective retrovirus, such as LNSX, LN or N2A, may be
used” (id. at col. 22, ll. 14-19).
6. Uhr further discloses that “[s]everal studies are contemplated to assay
the effects of fos expression, and a variety of other protooncogenes, on
malignant growth and cell cycle arrest, both in in vivo and in vitro” (id. at
col. 22, ll. 43-45).
7. Uhr discloses, for example, that “[t]ransfected clones will be
introduced into normal Balb/c and Id-immune mice, in controlled

3 Substitute Specification filed June 3, 2002.
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experiments, and malignant growth [will] be evaluated” (id. at col. 22, ll. 48-
50).
8. Uhr discloses that “it will be important to demonstrate the presence of
cell cycle arrested tumor cells. Spleen from mice >60 days after tumor cell
transplant will be analyzed for arrested BCL1 cells by FACS, employing the
methods of the present invention” (id. at col. 22, ll. 56-60).
9. Uhr discloses that, using its FACS cell sorting methods, “cells can be
sperated [sic] on the basis of 6 parameters” (id. at col 3, ll. 64-65).
10. Conneally discloses studies of retroviral transfection of “primary
human hematopoietic cell targets using an amphotropic vector encoding
heat-stable antigen (HSA) . . . as a selectable marker” (Conneally 457).
11. Conneally discloses:
These studies highlight the potential of using retroviral
constructs encoding cell surface markers not normally
expressed on the target cells of interest to facilitate the selection
immediately after infection of those to which gene transfer has
been achieved. For many gene therapy applications, the
capacity to control the number or proportion of transduced stem
cells could be of considerable significance . . . .

(Conneally 462.)
12. Thus, Conneally discloses, “[o]ne of the major advantages of the
HSA/CD24 family of vectors is the ability to assess gene transfer to specific
subpopulations of cells immediately after infection” (id.)
PRINCIPLES OF LAW
In KSR Int' l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme
Court advised that, in determining whether the prior art supplied a reason for
practicing the claimed subject matter, the analysis “need not seek out precise
teachings directed to the specific subject matter of the challenged claim, for
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a court can take account of the inferences and creative steps that a person of
ordinary skill in the art would employ.” Id. at 418; see also id. at 421 (“A
person of ordinary skill is . . . a person of ordinary creativity, not an
automaton.”).
The Court also reasoned that “[i]n determining whether the subject
matter of a patent claim is obvious, neither the particular motivation nor the
avowed purpose of the patentee controls. What matters is the objective
reach of the claim. If the claim extends to what is obvious, it is invalid
under § 103.” Id. at 419.
Lastly, during examination, the PTO must interpret terms in a claim
using “the broadest reasonable meaning of the words in their ordinary usage
as they would be understood by one of ordinary skill in the art, taking into
account whatever enlightenment by way of definitions or otherwise that may
be afforded by the written description contained in the applicant’s
specification.” In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997).
ANALYSIS
We agree with the Examiner that the evidence of record supports a
finding that the cited references suggest a process that includes a step of
“providing a population of cells comprising a library of retroviral vectors
encoding different candidate bioactive agents” as recited in claim 17.
The Specification defines a “population of cells” or “library of cells”
or “plurality of cells” as meaning “at least two cells” (Spec. 9 (FF 2)).
Given this definition, we further agree with the Examiner that the population
of retroviral-transfected cells suggested by Uhr, which would include at least
two retroviral vectors (one encoding c-fos, the other encoding c-jun), would
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be encompassed by the “population of cells comprising a library of retroviral
vectors” recited in claim 17.
Turning to the prior art, Uhr discloses processes of treating cancer by
arresting tumor cells’ growth cycle (FF 3-4). Uhr discloses that cell cycle-
arresting genes, such as c-fos and c-jun can be introduced into cells using
retroviruses (FF 4-5). Uhr further discloses that the effect of the genes
encoded by the retroviruses can be studied by implanting the gene-carrying
cells into mice, and then removing presumed cycle-arrested cells from the
mice and sorting them by FACS, using as many as 6 parameters, to evaluate
the presence of the altered cell cycle phenotype (FF 6-9).
In view of these teachings, we agree with the Examiner that Uhr
would have suggested to an ordinary artisan that it would be desirable to
transfect a population of cells with retroviral vectors encoding at least two
potential cell cycle-arresting genes, c-fos and c-jun. As pointed out by the
Examiner, Conneally also discloses the desirability of using retroviral
vectors having detectable cell surface markers as vehicles for nucleic acids
of interest (FF 10-12).
We acknowledge, as Appellants argue, that Uhr refers to its methods
as “gene therapy” (FF 4). Regardless of terminology, however, given Uhr’s
teachings, we find that Uhr would have prompted an ordinary artisan to
provide a population of cells including at least two different retroviral
vectors encoding tumor cell cycle-arresting agents, one encoding c-fos, the
other encoding c-jun.
In sum, we agree with the Examiner that an ordinary artisan viewing
the teachings of the cited references have been prompted to transfect a
population of cells with retroviral vectors encoding at least two potential cell
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cycle-arresting genes, c-fos and c-jun. As claim 17 encompasses a library of
this size, we conclude that the evidence of record supports the Examiner’s
position that the cited references suggest performing claim 17’s step of
“providing a population of cells comprising a library of retroviral vectors
encoding different candidate bioactive agents.”
Accordingly, we affirm the Examiner’s obviousness rejection of claim
17 over Uhr and Conneally, as well as the rejection of claims 18-24 and 30,
which were not argued separately. See 37 C.F.R. § 41.37(c)(1)(vii).
OBVIOUSNESS -- NOLAN, JAI-PING AND UHR
ISSUE
Claims 17-25, 30, and 32 stand rejected under 35 U.S.C. § 103(a) as
obvious over Nolan, Jia-ping, and Uhr (Ans. 7-10).
In traversing this rejection, Appellants do not dispute the Examiner’s
fact findings regarding the references’ teachings or the conclusions drawn
from them. Rather, Appellants argue only that the Nolan reference is not
prior art with respect to the instant application as evidenced by the Fisher
Declaration (App. Br. 7-9).
Specifically, Appellants argue, the instant application claims priority
to an application (09/062,330) filed less than one year after the publication
date of the Nolan reference, and the Nolan reference is therefore available as
prior art to the instant application only under 35 U.S.C. § 102(a) (id. at 8).
Thus, Appellants urge, because the Fisher Declaration filed under 37 C.F.R.
§ 1.131 establishes invention of the subject matter in the rejected claims
prior to the publication date of Nolan, Nolan is not available as prior art
against the rejected claims (id.). Appellants further urge that the Examiner
has failed to properly consider the Fisher Declaration (id.)
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The Examiner responds that “Nolan was published more than one year
[before] applicants’ earliest filing date (please note appellants’ statement that
the instant application is a continuation-in-part (CIP) of the 09/062,330
application)” (Ans. 17). See also Final Rejection 13 (entered August 10,
2007) (“[T]he 35 USC 1.131 declaration does not overcome the 103
rejection based on 102(b) rejection over the Nolan reference as Nolan (WO
97/27212) is a bar against the instant application.”) (Emphasis added).
Specifically, the Examiner urges, Appellants “are not entitled to the
priority date of the ‘330 application” because the ‘330 application does not
provide support for screening for “‘at least five parameters,’” and also does
not provide support for screening for all of the phenotypes recited in the
rejected claims (Ans. 17).
In view of the positions advanced by Appellants and the Examiner,
the issue with respect to this rejection is whether Appellants are entitled to
priority to parent application serial no 09/062,330, which issued as U.S.
Patent 6,897,031.
PRINCIPLES OF LAW
37 C.F.R. § 1.131 states, in relevant part (emphasis added):
(a) When any claim of an application or a patent under
reexamination is rejected, the inventor of the subject matter of
the rejected claim, the owner of the patent under reexamination,
or the party qualified under §§ 1.42, 1.43, or 1.47, may submit
an appropriate oath or declaration to establish invention of
the subject matter of the rejected claim prior to the effective
date of the reference or activity on which the rejection is based.
. . . Prior invention may not be established under this section if
. . .
(2) The rejection is based on a statutory bar.

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Thus, a declaration under 37 C.F.R. § 1.131 cannot overcome a
rejection for anticipation or obviousness where the prior art antedates the
application’s effective filing date by more than one year, and is therefore
applicable against the claims under 35 U.S.C. § 102(b). See In re Foster,
343 F.2d 980, 989-90 (CCPA 1965).
Accordingly, for Appellants to overcome the statutory bar set by §
102(b), Appellants’ claimed subject matter must find support in Application
Serial No. 09/062,330, filed on April 17, 1998, which issued as U.S. Patent
No. 6,897,031 B1 (see FF 16, below).
“[T]he test to determine if an application is to receive the benefit of an
earlier filed application is whether a person of ordinary skill in the art would
recognize that the applicant possessed what is claimed in the later filed
application as of the filing date of the earlier filed application.” Noelle v.
Lederman, 355 F.3d 1343, 1348 (Fed. Cir. 2004).
Thus, to receive benefit of a previous application, every feature
recited in the claims at issue must be described in the prior application. See
In re van Langenhoven, 173 USPQ 426, 429 (CCPA 1972) (“The fact that
some of the elements of the breech claims have support of the parent and
foreign applications does not change the result. As to given claimed subject
matter, only one effective date is applicable.”) (Emphasis added); accord In
re Chu, 66 F.3d 292, 297 (Fed. Cir. 1995).
FINDINGS OF FACT (“FF”)
13. It is undisputed that the publication date of the Nolan reference is July
31, 1997.
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14. The filing date of the instant application is April 16, 1999 (see
Transmittal of New Application (entered April 16, 1999)), which is more
than one year after the publication date of the Nolan reference.
15. The Specification states that “[t]his application is a continuation-in-
part of U.S. Application Serial No. 09/062,330, filed on April 17, 1998 [now
U.S. Patent No. 6,897,031 B1], and U.S. Application Serial No. 09/157,748,
filed on September 21, 1998 (Specification 1 (as amended September 24,
2004)).
16. Thus, to remove the statutory bar set by 35 U.S.C. § 102(b) against
patenting claims anticipated or obviated by printed publications available
more than one year prior to an application’s filing date, Appellants’ claimed
subject matter must find support in Application Serial No. 09/062,330, filed
on April 17, 1998, which issued as U.S. Patent No. 6,897,031 B1.
17. The Examiner finds:
The 09/062330 (now US Patent 6,897,031) ('031 Patent) does
not provide support for the present broad claim “at least 5
parameters” as applied to the different claim cellular
phenotypes. The different claim phenotypes consist of cell
cycle, apoptosis, exocytosis, expression of a cell surface
receptor, and expression of a receptor protein. The '031 Patent
provides only four (4) parameters solely for exocytosis. It does
not provide support for the other claim cell phenotypes having
“at least five (5)” parameters being determined. See e.g.,
Example 9 of the '031 Patent.

(Ans. 17.)
18. Appellants do not dispute the Examiner’s characterization of the
disclosure of the ‘330 application/’031 patent.
19. The ‘031 patent states:
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Described is a method for screening for alterations in
exocytosis of a population of cells. The cells are sorted by a
FACS machine by assaying for alterations in at least three of
the properties selected from the group consisting of light
scattering, fluorescent dye uptake, fluorescent dye release,
annexin granule binding, surface granule enzyme activity, and
the quantity of granule specific proteins. Methods for screening
for bioactive agents capable of modulating exocytosis in a cell
are also described. The methods provide for reduced
background and increased specificity without increasing the
time or steps involved in assaying for exocytosis.

(‘031 patent, abstract).
20. Appellants do not point to any disclosure in the ‘031 patent regarding
sorting cells based on at least five parameters as recited in step (b) of claim
17. Nor do Appellants point to any disclosure of screening for alterations in
all of the cellular phenotypes recited in the “wherein” clause of claim 17.
ANALYSIS
We agree with the Examiner that Appellants have not shown that the
Nolan reference is unavailable as prior art against the rejected claims. As
noted above, Appellants cannot avail themselves of an antedating
declaration under 37 C.F.R. § 1.131 if the rejection is a statutory bar. See In
re Foster, 343 F.2d at 989-90.
Thus, to avoid the statutory bar set by 35 U.S.C. § 102(b), Appellants
must find descriptive support for the rejected claims in a priority application
filed less than one year after publication of the Nolan reference. In the
instant case, only the ‘330 application, which issued as the ‘031 patent, and
which is asserted as a continuation-in-part parent to this application, has
such a filing date (see FF 15).
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However, as the Examiner points out, and Appellants do not dispute,
the ‘330 application/’031 patent does not describe all of the features in the
rejected claims (FF 17-20). Thus, given the evidence of record, the earliest
effective filing date of the instant application is April 16, 1999, which is
more than one year after the Nolan reference’s publication date of July 31,
1997 (FF 13-14). Accordingly, the Fisher Declaration under 37 C.F.R. §
1.131 cannot be used to antedate the Nolan reference.
We therefore agree with the Examiner that Nolan is available prior art
against the rejected claims. As Appellants’ sole argument was on this basis,
and as we detect no other deficiency in the Examiner’s case of obviousness,
we affirm the Examiner’s obviousness rejection of claims 17-25, 30, and 32
over Nolan, Jia-ping, and Uhr.
The Examiner also rejected claim 26 as obvious over Nolan, Jia-ping,
Uhr, Hide, and Appellants’ admitted prior art (Ans. 10-11). Appellants’ sole
argument against this rejection is also the unavailability of Nolan as prior art
against the rejected claim (App. Br. 9). As discussed above, we do not find
this argument persuasive. We therefore also affirm this rejection.

SUMMARY
We affirm the Examiner’s obviousness rejection of claims 17-24 and
30 over Uhr and Conneally.
We also affirm the Examiner’s obviousness rejection of claims 17-25,
30, and 32, over Nolan, Jia-ping, and Uhr.
We also affirm the Examiner’s obviousness rejection of claim 26 over
Nolan, Jia-ping, Uhr, Hide, and Appellants’ admitted prior art.

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TIME PERIOD
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

alw

RIGEL PHARMACEUTICALS, INC.
BOZICEVIC, FIELD & FRANCIS LLP
1900 UNIVERSITY AVE, SUITE 200
EAST PALO ALTO, CA 94303