Ex Parte Fisher et al

Patent Trial and Appeal Board

Sep 28, 2012

09293670 (P.T.A.B. Sep. 28, 2012)

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 09/28/2012
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
1636
MAIL DATE DELIVERY MODE
09/28/2012 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 JOSEPH FISHER, JAMES LORENS,
DONALD PAYAN, and ALEXANDER ROSSI

__________

Appeal 2012-008150
Application 09/293,670
1

Technology Center 1600
__________

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

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a method for
screening cells. The Examiner entered rejections for new matter, lack of
written description, lack of enablement, and obviousness.

1
This application has been before us on appeal previously, as Appeal No.
2009-015210. A decision affirming rejections for obviousness was entered
on July 21, 2010.
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Application 09/293,670

2
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
STATEMENT OF THE CASE
Claims 37-44 stand rejected and appealed (App. Br. 3).
2
Claim 37,
the only independent claim, illustrates the appealed subject matter and reads
as follows:
37. A method, comprising:
introducing a library of at least 10
3
vectors encoding different
candidate agents into a population of mammalian cells grown in vitro;
subjecting the population of cells to a physiological signal,
wherein said physiological signal stimulates a phenotype in said cells
in the absence of the candidate bioactive agents;
sorting the individual cells in the population on the basis of at
least three optical properties by fluorescent activated cell sorting
(FACS),
identifying a cell having a phenotype that is altered relative to
other cells in the population; and
sequencing the nucleic acid encoding said candidate agent in
said cell that has an altered phenotype, thereby identifying said
candidate agent in said cell.

The following rejections are before us for review:
(1) Claims 37-44, under 35 U.S.C. § 112, first paragraph, as reciting
new matter (Ans. 6-12);
(2) Claims 37-44, under 35 U.S.C. § 112, first paragraph, as failing to
comply with the written description requirement (Ans. 12-14);
(3) Claims 37-44, under 35 U.S.C. § 112, first paragraph, as lacking
enablement for the full scope of the subject matter claimed (Ans. 14-17);
(4) Claims 37 and 40-44, under 35 U.S.C. § 103(a) as obvious over
Nolan,
3
Jia-ping,
4
and Uhr
5
(Ans. 18-22); and

2
Appeal Brief entered November 22, 2011.
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Application 09/293,670

3
(5) Claims 38 and 39, under 35 U.S.C. § 103(a) as obvious over
Nolan, Jia-ping, Uhr, and Hide
6
(Ans. 22-23).
NEW MATTER
In rejecting claims 37-44 as containing new matter, the Examiner
found that, “[c]laim 37 in its entirety is not supported in the as-filed
specification” (Ans. 6). The Examiner found that the portions of the
Specification cited by Appellants as describing the claimed process did not
adequately support claim 37 (id. at 6-12), reasoning in particular that “the
disparate sections cited by applicants do not lend support for the present
[amended] claims” (id. at 12).
Instead, the Examiner contended, claim 37 “in its entirety should
appear in the specification as in the claim. Picking and choosing disparate
sections in the specification to support the individual element of the claims
leads to a claim that is loosely connected and as the elements themselves do
not find support in the as-filed specification” (id.).
As our reviewing court explained in In re Oetiker, 977 F.2d 1443,
1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the

3
WO 97/27212 A1 (published July 31, 1997).
4
Tao Jia-ping et al., Multi-parameter sorting technique in flow cytometry,
17 CHINESE JOURNAL OF PHYSICAL MEDICINE 168-171 (1995).
5
U.S. Patent No. 5,612,185 (issued March 18, 1997).
6
Izumi Hide et al., Degranulation of Individual Mast Cells in Response to
Ca
2+
and Guanine Nucleotides: An All-or-None Event, 123 J. CELL BIOL.
585-593 (1993).
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4
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

As the Federal Circuit also explained in TurboCare Div. of Demag
Delaval Turbomachinery Corp. v. General Elec. Co., 264 F.3d 1111, 1118
(Fed. Cir. 2001):
The written description requirement and its corollary, the new
matter prohibition of 35 U.S.C. § 132, both serve to ensure that
the patent applicant was in full possession of the claimed
subject matter on the application filing date. When the applicant
adds a claim or otherwise amends his specification after the
original filing date . . ., the new claims or other added material
must find support in the original specification.

Nonetheless, “[i]n order to satisfy the written description requirement,
the disclosure as originally filed does not have to provide in haec verba
support for the claimed subject matter at issue.” Purdue Pharma L.P. v.
Faulding, Inc., 230 F.3d 1320, 1323 (Fed. Cir. 2000).
Rather, the “test for sufficiency is whether the disclosure of the
application relied upon reasonably conveys to those skilled in the art that the
inventor had possession of the claimed subject matter as of the filing date.”
Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010).
Beyond simple possession, however, the “test requires an objective
inquiry into the four corners of the specification from the perspective of a
person of ordinary skill in the art. Based on that inquiry, the specification
must describe an invention understandable to that skilled artisan and show
that the inventor actually invented the invention claimed.” Id.
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In this instance, we agree with Appellants that the preponderance of
the evidence does not support the Examiner‟s finding that the Specification
fails to adequately describe the process recited in claim 37.
As Appellants point out, the general method recited in claim 37 is
initially described at page 4 of the Specification:
7

The methods generally comprise combining at least one
candidate bioactive agent and a population of cells, sorting the
cells in a FACS machine by separating the cells on the basis of
at least three, four or five cellular parameters. The candidate
agents can be part of a molecular library comprising fusion
nucleic acids encoding the candidate bioactive agents.

(Spec. 4.)
The Specification also discloses that a “population of cells” means at
least 10
3
cells (id. at 10), and that, when nucleic acid vectors such as
retroviral vectors are used as the candidate bioactive agents, each cell in the
population receives a distinct construct (see id. at 19-21; App. Br. 9). We
acknowledge that preferred embodiments of the described process use a
library of vectors with at least 10
6
different sequences (see id. at 19).
However, given the disclosure of using cell populations of at least 10
3
cells,
each of which receives a distinct construct, i.e., one cell receives at least one
vector, we agree with Appellants that the Specification adequately describes
introducing a library of at least 10
3
vectors to those cells, as recited in claim
37.

7
Appellants and the Examiner both appear to cite to pages of the
Specification as originally filed on April 16, 1999. We do the same for
consistency.
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6
Similarly, given the Specification‟s express disclosure that the
described method may include evaluation of the cells‟ reaction to the
bioactive agents in the presence of a physiological signal such as a hormone,
antibody peptide, cytokine, growth factor, etc. (Spec. 9-10), we agree with
Appellants that the Specification necessarily describes claim 37‟s step of
subjecting the cells to a physiological signal. Also, because the FACS
technique sorts on the basis of optical properties, we agree with Appellants
that an ordinary would understand that sorting cells based on at least three,
four, or five cellular parameters (see Spec. 4) would in effect describe
sorting on the basis of at least three optical parameters, as recited in claim
37.
We acknowledge that the Specification does not explicitly state that
the nucleic acid sequence of the vector encoding the bioactive agent is
determined, as required by claim 37. However, we agree with Appellants
that a disclosure of analyzing the structure of the bioactive agent in a manner
“appreciated by those in the art” (Spec. 43) would lead an ordinary artisan to
understand that the sequence would be determined when the agent is
encoded by a nucleic acid. Cf. Purdue Pharma v. Faulding, 230 F.3d at
1323 (“Put another way, one skilled in the art, reading the original
disclosure, must immediately discern the limitation at issue in the claims.”).
Thus, the Specification initially describes a general process as recited
in claim 37, and subsequently describes the steps of claim 37‟s process as
being preferred features of that general process. We therefore agree with
Appellants that a preponderance of the evidence does not support the
Examiner‟s finding that the overall process recited in claim 37 lacks
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adequate descriptive support. Accordingly, we reverse the Examiner‟s new
matter rejection of claim 37 and its dependent claims.

WRITTEN DESCRIPTION
In rejecting claims 37-44 for lack of written description, the Examiner
found that, “[s]ince there is no description of a library of [10
3
] vectors hence,
there is no description of a candidate agent that has been isolated or
identified by the encoded diverse library of [10
3
] vectors where the
candidate agents alter a phenotypic change to a population of mammalian
cells” (Ans. 13). The Examiner also found that the Specification does not
exemplify a process as claimed, since the “working example in the
specification describes the effect of a single known candidate agent p21 and
its phenotypic effect to a population of [10
3
] cells. There is no description of
whether the single known p21 has been selected, purified and identified
from the [10
3
] library of vectors” (id. at 13-14).
The Examiner further found:
Nor is there a description of an isolated and identified candidate
agent that alters any or all kind(s) of phenotypes in a population
of cell. Since no identification of a candidate peptide agent has
been made and the single protein (not peptide) is known hence,
it is not readily apparent how sequencing can be done to an
already known protein.

(Id. at 14.)
We agree with Appellants that the preponderance of the evidence does
not support the Examiner‟s finding that the claims lack descriptive support.
As the Federal Circuit has noted:
A claim will not be invalidated on section 112 grounds
simply because the embodiments of the specification do not
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contain examples explicitly covering the full scope of the claim
language. That is because the patent specification is written for
a person of skill in the art, and such a person comes to the
patent with the knowledge of what has come before. Placed in
that context, it is unnecessary to spell out every detail of the
invention in the specification; only enough must be included to
convince a person of skill in the art that the inventor possessed
the invention and to enable such a person to make and use the
invention without undue experimentation.

Falkner v. Inglis, 448 F.3d 1357, 1366 (Fed. Cir. 2006) (quoting LizardTech,
Inc. v. Earth Resource Mapping, PTY, Inc., 424 F.3d 1336, 1345
(Fed.Cir.2005)).
In the instant case, in contrast to claims requiring a specific
therapeutic compound unknown in the prior art and structurally undefined in
the Specification, as was the case for example in Univ. of Rochester v. G.D.
Searle & Co., 358 F.3d 916, 922 (Fed. Cir. 2004), the process of claim 37 is
a screening method which, by its nature, seeks to identify a phenotype-
altering agent from the library of candidate agents encoded by nucleic acid
vectors.
While the Examiner urges that the library of vectors has not been
described, as noted above in Falkner, exemplification is not necessary where
an ordinary artisan would understand that Appellants possessed the process
as claimed. As Appellants point out, the Specification explains, with
significant specificity, the nature of nucleic acid vector libraries useful in the
disclosed process, including a focus on retroviral libraries (see Spec. 19-21).
In contrast, the Examiner has not advanced any persuasive evidence
specifically suggesting that an ordinary artisan would have failed to be
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9
convinced, based on that disclosure, that Appellants invented a screening
process that included the use of such libraries.
We are therefore not persuaded that a preponderance of the evidence
supports the Examiner‟s finding that Appellants did not possess the
screening method recited in claim 37. Accordingly, we reverse the
Examiner‟s written description rejection of that claim, and its dependents.
ENABLEMENT
The Examiner rejected claims 37-44 under 35 U.S.C. § 112, first
paragraph, because the Specification, “while being enabling for a method
using a single protein, does not reasonably provide enablement for claim 37
method using a library of [10
3
] vectors and the other claim parameters (as
given in the new matter rejection above)” (Ans. 14).
The Examiner reasoned that, because the Specification provided “only
broad generalized statements,” an ordinary artisan would have to undertake
an “undue amount of experimentation to determine the [10
3
] library of
vectors encoding different candidate agents that alters any type of phenotype
in a cell(s) population. This is made more complex since the specification
does not provide support for the claim[ed] general method. (Please see the
new matter rejection above.)” (Id. at 15.) As evidence of unpredictability in
the art, the Examiner cited Polyak,
8
Nakanishi,
9
and Tournier
10
(id. at 16-
17).

8
Kornelia Polyak et al., Genetic determinants of p53-induced apoptosis and
growth arrest, 10 GENES & DEVELOPMENT 1945-52 (1996).
9
Makoto Nakanishi et al., Identification of the active region of the DNA
synthesis inhibitory gene p21
Sdil/CIP1/WAF1
, 14 THE EMBO JOURNAL 555-563
(1995).
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We conclude that a preponderance of the evidence does not support
the enablement rejection.
As noted in Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d
1313, 1334 (Fed. Cir. 2003):
The enablement requirement is often more indulgent
than the written description requirement. The specification
need not explicitly teach those in the art to make and use the
invention; the requirement is satisfied if, given what they
already know, the specification teaches those in the art enough
that they can make and use the invention without “undue
experimentation.”

Moreover, “[working] examples are not required to satisfy section
112, first paragraph.” In re Strahilevitz, 668 F.2d 1229, 1232 (CCPA 1982).
For example, in Falkner v. Inglis, the court affirmed the conclusion of the
Board of Patent Appeals and Interferences, that claims to a modified pox
virus vaccine were enabled, despite the fact that the specification focused on
viruses other than pox virus, provided no examples directed to pox virus,
and discussed pox virus only in general terms relating to the inventive
disclosure. Falkner, 448 F.3d at 1365.
Also, significant experimentation does not preclude enablement:
Enablement is not precluded by the necessity for some
experimentation such as routine screening. However,
experimentation needed to practice the invention must not be
undue experimentation. . . . The test is not merely quantitative,
since a considerable amount of experimentation is permissible,
if it is merely routine, or if the specification in question

10
Sylvie Tournier, Heterologous Expression of the Human Cyclin-dependent
Kinase Inhibitor p21
Cip1
in the Fission Yeast, Schizosaccharomyces pombe
Reveals a Role for PCNA in the chkl+ Cell Cycle Checkpoint Pathway, 7
MOLECULAR BIOLOGY OF THE CELL 651-662 (1996).
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provides a reasonable amount of guidance with respect to the
direction in which the experimentation should proceed.

In re Wands, 858 F.2d 731, 736-37 (Fed. Cir. 1988) (citations omitted).
In this case, the process recited in claim 37 is a screening method,
which by its nature includes a substantial degree of unpredictability, since
the outcome of the screening procedure is not assured. Similarly, an
ordinary artisan would understand that screening methods, because of their
nature, involve significant amounts of experimentation. Thus, while it may
be true that Polyak, Nakanishi, and Tournier suggest that understanding cell
cycle regulation can present significant problems, the point of the claimed
method is to study such processes by ascertaining molecules that can affect
them.
We acknowledge that the claimed screening method may require a
significant number of repetitions to obtain any useful result. However, as
noted above, the claim is limited to screening a population of cells using a
library of nucleic acid vectors, a known class of molecules, and the
Specification describes, with reference to the prior art, techniques by which
those molecules can be obtained (see Spec. 19-20). In contrast, the
Examiner has not advanced any specific evidence clearly suggesting that an
ordinary artisan, equipped with what was already known about generating
libraries of nucleic acid vectors, would have been unable to practice the
claimed invention based on the teachings provided in the Specification.
Thus, as we are not persuaded that a preponderance of the evidence
supports the Examiner‟s conclusion that practicing the full scope of claim 37
would necessitate undue experimentation, we reverse the Examiner‟s
rejection of claim 37 and its dependents for lack of enablement.
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OBVIOUSNESS
In concluding that the process recited claims 37 and 40-44 would have
been obvious to an ordinary artisan viewing Nolan, Jia-ping, and Uhr, the
Examiner reasoned that the artisan would have been prompted to “determine
the changes in the exocytosis phenotype of a cell by at least 3 optical
parameters in the method of Nolan in the manner as taught by Jia-ping and
Uhr . . . for the advantages taught by Jia-ping and Uhr” (Ans. 21-22).
In concluding that the processes recited in dependent claims 38 and 39
would have been obvious over Nolan, Jia-ping, Uhr, and Hide, the Examiner
further reasoned that an ordinary artisan would have been prompted to “use
stimulus as Ca++ or ionomycin to differentiate one cell from another by the
effect of the stimulus. One would have a reasonable expectation of success
since exocytosis phenotype has been used to differentiate cells in a
population using FACS” (id. at 23).
Appellants do not allege error in either the Examiner‟s fact findings or
the ultimate conclusions of obviousness drawn from them. Instead,
Appellants argue only that the Nolan reference is not prior art with respect to
the instant application as evidenced by the Fisher Declaration
11
(App. Br.
23-25).
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 24).
Thus, Appellants urge, because the Fisher Declaration filed under 37 C.F.R.

11
Declaration of Joseph Fisher under 37 C.F.R. § 1.131 (executed June 25,
2006).
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§ 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. at 24-25).
The Examiner does not dispute that the Fisher Declaration is adequate
to support invention of the claimed subject matter prior to the July 31, 1997
publication date of the Nolan reference. Rather, the Examiner argues that
the „330 application
12
fails to provide adequate descriptive support for the
process recited in the rejected claims.
In particular, the Examiner notes that the „330 application‟s disclosure
is limited to “screening for alterations in exocytosis of a population of cells
(not the now presently broad claimed physiological signal)” (Ans. 45).
As to the specific features of the claimed process, the Examiner states that
“the responses above under the new matter rejection are incorporated herein
in its entirety. The cited section as support, for example, for library of [10
3
]
vectors in the parent application is no different from the instant application”
(id. at 46).
We agree with Appellants that the preponderance of the evidence does
not support the Examiner‟s finding that the „330 application fails to provide
adequate descriptive support for the claimed process.
We initially note, as the Examiner contends, that the disclosure of the
„330 application is very similar to that of the instant application. Thus, the
„330 application initially describes a general method of screening cells by

12
This application is a continuation in part of 09/157,748, filed September
21 (now U.S. Patent No. 6,461,813), which is in turn a continuation in part
of 09/062,330, filed April 17, 1998 (now U.S. Patent No. 6,897,031).
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14
FACS to select introduced agents that alter phenotypic traits characteristic of
exocytosis:
In accordance with the objects outlined above, the
present invention provides a method for screening for
alterations in exocytosis of a population of cells or in single
cells under different conditions or combined with different
bioactive agents. The methods comprise sorting the cells in 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.

(„330 Spec. 3.) Like the instant application, the „330 application discloses
that a “population of cells” means at least 10
3
cells (id. at 24), and that, when
nucleic acid vectors such as retroviral vectors are used as the candidate
bioactive agents, each cell in the population receives a distinct construct (see
id. at 24-26).
We acknowledge that preferred embodiments of the process described
in the „330 application use a library of vectors with at least 10
6
different
sequences (see id. at 24). However, given the disclosure of using cell
populations of at least 10
3
cells, each of which receives a distinct construct,
just as described in the instant application, we agree with Appellants that the
„330 application adequately describes introducing a library of at least 10
3

vectors to that population of cells, as recited in claim 37.
Similarly, given the „330 application‟s express disclosure that the
described method may include evaluation of the cells‟ reaction to the
bioactive agents in the presence of a physiological signal such as a hormone,
antibody peptide, cytokine, growth factor, etc. („330 Spec. 8), we agree with
Appellants that the „330 application necessarily describes claim 37‟s step of
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subjecting the cells to a physiological signal that stimulates a phenotype in
the cells. Also, because the „330 application describes FACS sorting on the
basis of “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” (id. at 3), we agree with Appellants that the sorting step in
claim 37 is adequately described in the „330 application.
We also acknowledge that the „330 application does not explicitly
state that the nucleic acid sequence of the vector encoding the bioactive
agent is determined, as required by the final step of claim 37. However, we
agree with Appellants that a disclosure of analyzing the structure of the
bioactive agent as “appreciated by those in the art” („330 Spec. 40) would
lead an ordinary artisan to understand that the sequence would be
determined when the agent is encoded by a nucleic acid.
Thus, like the instant Specification, the „330 application initially
describes a general process as recited in claim 37, and subsequently
describes the steps of claim 37‟s process as being preferred features of that
general process. We therefore agree with Appellants that a preponderance
of the evidence does not support the Examiner‟s finding that the processes
recited in claim 37 and its dependents lack adequate descriptive support in
the „330 application.
Accordingly, as a preponderance of the evidence does not support the
Examiner‟s finding that the claimed process is not entitled to priority to the
„330 application, and as the Examiner does not dispute that the Fisher
Declaration adequately demonstrates invention of the claimed process prior
to the Nolan reference, we reverse the Examiner‟s obviousness rejection of
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16
claims 37 and 40-44 over Nolan, Jia-ping, and Uhr, as well as the
Examiner‟s rejection of claims 38 and 39 over Nolan, Jia-ping, Uhr, and
Hide.

SUMMARY
We reverse the Examiner‟s rejection of claims 37-44, under 35 U.S.C.
§ 112, first paragraph, as reciting new matter.
We also reverse the Examiner‟s rejection of claims 37-44, under 35
U.S.C. § 112, first paragraph, as failing to comply with the written
description requirement.
We also reverse the Examiner‟s enablement rejection of claims 37-44.
We also reverse the Examiner‟s obviousness rejection of claims 37
and 40-44 over Nolan, Jia-ping, and Uhr.
We also reverse the Examiner‟s obviousness rejection of claims 38
and 39 over Nolan, Jia-ping, Uhr, and Hide.

REVERSED

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