Ex Parte McElroy et al

Board of Patent Appeals and Interferences

Aug 29, 2003

09532806 (B.P.A.I. Aug. 29, 2003)

1 Application for patent filed March 21, 2000.
The opinion in support of the decision being entered today was not written for
publication and is not binding precedent of the Board.
Paper No. 21
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte DAVID McELROY,
EMIL OROZCO, and LUCILLE LACCETTI
____________
Appeal No. 2003-0936
Application No. 09/532,8061

ON BRIEF
____________
Before WINTERS, GRON, and GREEN, Administrative Patent Judges.
GRON, Administrative Patent Judge.
DECISION ON APPEAL UNDER 35 U.S.C. § 134
Introduction
This is an appeal under 35 U.S.C. § 134 of an examiner’s final
rejections of Claims 1, 4-54, and 85-131, all claims pending in
Application 09/532,806, under 35 U.S.C. § 112, first paragraph.
Claims 1, 4-54, and 85-113 stand finally rejected for noncompliance
with the written description requirement of 35 U.S.C. § 112, first
Appeal No. 2003-0936
Application No. 09/532,806
2
paragraph. Claims 1, 4-54, and 85-131 stand finally rejected for
noncompliance with the enablement requirement of 35 U.S.C. § 112,
first paragraph (Brief on Appeal, p. 3 (AB 3); Examiner’s Answer,
p. 3 (EA 3)). Claims 1, 4-20, 33, 34, 45, 46, 48, 49, 51, 52, 85,
96, and 114, reproduced below, are representative of the full scope
of the subject matter claimed.
1. An isolated nucleic acid comprising a maize GRP
promoter comprising at least 95 contiguous bases of
SEQ ID NO:1.
4. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 110 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
5. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 125 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
6. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 250 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
7. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 400 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
8. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 750 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
9. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 1000 to about
Appeal No. 2003-0936
Application No. 09/532,806
3
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
10. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 1500 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
11. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 2000 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
12. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 2500 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
13. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises from about 3000 to about
3536 contiguous nucleotides of the nucleic acid
sequence of SEQ ID NO:1.
14. The isolated nucleic acid of claim 1, wherein said
GRP promoter comprises the nucleic acid sequence of
SEQ ID NO:1.
15. The isolated nucleic acid of claim 1, further
comprising an enhancer.
16. The isolated nucleic acid of claim 15, wherein said
enhancer comprises an intron.
17. The isolated nucleic acid of claim 15, wherein said
intron is selected from the group consisting of the
rice actin 1 intron and the rice actin 2 intron.
18. The isolated nucleic acid of claim 1, further
comprising a terminator.
19. The isolated nucleic acid of claim 18, wherein said
terminator comprises an rbcS terminator.
Appeal No. 2003-0936
Application No. 09/532,806
2 We note here that the Markush grouping of
dicotyledonous plants twice recites cotton. Counsel should
edit all of appellants’ claims for typographical errors.
4
20. A transgenic plant stably transformed with a selected
DNA comprising a maize GRP promoter comprising at
least 95 contiguous bases of SEQ ID NO:1.
33. The transgenic plant of claim 20, wherein said
selected DNA further comprises a selected heterologous
coding region operably linked to said GRP promoter.
34. The transgenic plant of claim 33, wherein said
selected heterologous coding region encodes a protein
imparting insect resistance, bacterial disease
resistance, fungal disease resistance, viral disease
resistance, nematode disease resistance, herbicide
resistance, enhanced grain composition or quality,
enhanced nutrient utilization, enhanced environment
or stress resistance, reduced mycotoxin contamination,
male sterility, a selectable marker phenotype, a
screenable marker phenotype, a negative selectable
marker phenotype, or altered plant agronomic
characteristics.
45. The transgenic plant of claim 20, further defined
as a monocotyledonous plant.
46. The transgenic plant of claim 45, wherein said
monocotyledonous plant is selected from the group
consisting of wheat, maize, rye, rice, oat, barley,
turfgrass, sorghum, millet and sugarcane.
48. The transgenic plant of claim 20, further defined
as a dicotyledonous plant.
49. The transgenic plant of claim 48, wherein said
dicotyledonous plant is selected from the group
consisting of tobacco, tomato, potato, soybean,
cotton, canola, alfalfa, sunflower, and cotton.2
Appeal No. 2003-0936
Application No. 09/532,806
3 Note that claims dependent upon Claim 85 refer to
“[t]he transgenic plant cell of claim 85" (emphasis added).
5
51. The transgenic plant of claim 20, further defined
as a fertile R0 transgenic plant.
52. A seed of the fertile R0 transgenic plant of claim 51,
wherein said seed comprises said selected DNA.
85. A transgenic plant3 stably transformed with
a selected DNA comprising a maize GRP promoter
comprising at least 95 contiguous bases of
SEQ ID NO:1.
96. The transgenic plant cell of claim 85, wherein said
selected DNA further comprises a selected coding
region operably linked to said maize GRP promoter.
114. A method of preparing a transgenic plant comprising
the steps of:
(i) obtaining a construct comprising a maize GRP
promoter comprising at least 95 contiguous bases
of SEQ ID NO:1;
(ii) transforming a recipient plant cell with said
construct; and
(iii) regenerating said recipient plant cell to
obtain a transgenic plant transformed with said
construct.
According to the examiner, (1) appellants’ claims are drawn
to “subject matter which was not described in the specification in
such a way as to reasonably convey to one skilled in the relevant
art that the inventor(s), at the time the application was filed,
had possession of the claimed invention” (EA 3); and
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Application No. 09/532,806
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(2) “the specification, while being enabling for the isolated
nucleic acid that is the maize GRP promoter described in Example 1,
transgenic plants and cells comprising said promoter, and method of
preparing said transgenic plant, does not reasonably provide
enablement for other isolated nucleic acids that are a maize GRP
promoter, or transgenic plant, seeds and cells comprising other
isolated nucleic acids” (EA 3). In support of the final
rejections, the examiner cites Kim, Y., et al., “A 20 nucleotide
upstream element is essential for the nopaline synthase (nos)
promoter activity,” Plant Molecular Biology, Vol. 24, pp. 105-117
(1994), and Benfey, P., et al., “The Cauliflower Mosaic Virus 35S
Promoter: Combinatorial Regulation of Transcription in Plants,”
Science,” Vol. 250, pp. 959-966 (1990).
Discussion
1. Rejection for inadequate written description
Figure 4 describes SEQ ID NO:1 by naming its 3536 contiguous
nucleotides. In so doing, appellants’ specification, as originally
filed, prima facie described each and every isolated 95, 110, 125,
250, 400, 750, 1000, 1500, 2000, 2500, and 3000 contiguous
nucleotide segment of the 3536 contiguous nucleotides of SEQ ID
NO:1 comprising a functional maize GRP promoter. Nevertheless, the
examiner is concerned that appellants’ specification does not
Appeal No. 2003-0936
Application No. 09/532,806
7
identify which of all the possible at least 95 contiguous
nucleotide segments of the 3536 contiguous nucleotides of SEQ ID
NO:1 described are required to promote expression of the various
coding regions to be linked thereto. More specifically, the
examiner argues (EA 4-5):
35 U.S.C. § 112 requires that Appellants describe in some
manner the structure of the nucleic acid sequences that
would have promoter function. Showing how or why the
claimed promoter sequences function, in particular showing
which structural features are necessary for the function
of the maize GRP promoter, is one way in which Appellants
may describe the structure of subfragments of SEQ ID NO:1
that would have promoter function. Appellants might also
describe the structure of subfragments of SEQ ID NO:1 that
would have promoter function by describing a representative
number of species of subfragments having promoter function,
so that one skilled in the art would have a basis for
recognizing the characteristics of SEQ ID NO:1 subfragments
that retain promoter function. Here Appellants have done
neither. Appellants describe only a single element that
has promoter function. However, this element has only
been shown to have promoter activity when linked to the
rice act 2 intron 1 deletion derivative. This element
appears to be a 639 base pair subfragment of the 3536
base pair sequence of SEQ ID NO:1 (examples 2 and 3
pages 112-114 of the specification, and figures 1 and 2),
though it is unclear exactly which nucleotides of SEQ ID
NO:1 provided this promoter function, as the specification
describes the construction of the promoter containing
construct only in terms of the restriction enzymes used
to subclone the subfragment of SEQ ID NO:1 into the
reporter construct. . . . If a nucleotide required for
promoter function is not present in a given sequence,
that sequence will no longer exhibit promoter function.
Unlike the specification which describes every subfragment of SEQ
ID NO:1 that is between 95 and 3536 contiguous bases long, the
Appeal No. 2003-0936
Application No. 09/532,806
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examiner argues that “Claim 1 encompasses every subfragment of SEQ
ID NO:1 that is between 95 and 3536 contiguous bases long and that
has promoter function” (EA 5; emphasis added). According to the
examiner, “the description must allow those skilled in the art to
recognize what regions of SEQ ID NO:1 would need to be retained in
its subfragments such that the subfragments could reasonably be
expected to retain promoter function” (EA 6).
As we understand the rejection, the examiner concedes that
appellants’ specification describes every subfragment claimed which
can function as a promoter. However, that description does not
satisfy the written description requirement of 35 U.S.C. § 112,
first paragraph, because the subfragments of SEQ ID NO:1 between
95 and 3536 contiguous bases in length that can function as a
promoter are not distinguished from the subfragments of SEQ ID NO:1
between 95 and 3536 contiguous bases in length that cannot function
as a promoter. The problem with the examiner’s position is that it
confuses the written description requirement of 35 U.S.C. § 112,
first paragraph, with the enablement requirement of 35 U.S.C.
§ 112, first paragraph. For example, in support of the written
description requirement of 35 U.S.C. § 112, first paragraph, the
examiner states (EA 5-6)(emphasis added):
Appeal No. 2003-0936
Application No. 09/532,806
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While it is not required that Appellant describe exactly
the subject matter claimed, the description must allow
those skilled in the art to recognize what regions of
SEQ ID NO:1 would need to be retained in its subfragments
such that the subfragments could reasonably be expected
to retain promoter function. The Examiner maintains that
the instant disclosure does not allow those skilled in
the art to recognize what regions of SEQ ID NO:1 would
need to be retained in its subfragments such that the
subfragments could reasonably be expected to retain
promoter function . . . .
The examiner’s criticism that the specification would not have
allowed persons skilled in the art to recognize what nucleotide
subfragments of SEQ ID NO:1 function as promoters is indistinct
from the concomitant criticism that the specification would not
have allowed persons skilled in the art to make and use the
nucleotide subfragments of SEQ ID NO:1 as promoters without undue
experimentation. However, Vas-Cath, Inc. v. Mahurkar, 935 F.2d
1555, 19 USPQ2d 1111 (Fed. Cir. 1991), instructs at 1562, 19 USPQ2d
at 1117:
This court in [In re ]Wilder[, 736 F.2d 1516, 1520,
222 USPQ 369, 372 (Fed. Cir. 1994), cert. denied,
469 U.S. 1209 (1985),] ( and the CCPA before it)
clearly recognized, and we hereby reaffirm, that
35 USC 112, first paragraph, requires a “written
description of the invention” which is separate and
distinct from the enablement requirement. The purpose
of the “written description” requirement is broader
than to merely explain how to “make and use”; the
applicant must also convey with reasonable clarity to
those skilled in the art that, as of the filing date
sought, he or she was in possession of the invention.
Appeal No. 2003-0936
Application No. 09/532,806
10
The invention is, for purposes of the “written
description” inquiry, whatever is now claimed.
More recently, the Federal Circuit discussed both the Vas-Cath
and Eli Lilly decisions (Vas-Cath, Inc. v. Mahurkar, supra; and
Regents of the University of California v. Eli Lilly & Co., 119
F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997)), in Enzo Biochem Inc.
v. Gen-Probe Inc., 296 F.3d. 1316, 63 USPQ2d 1609 (Fed. Cir. 2002).
The court stated in Enzo Biochem Inc. v. Gen-Probe Inc., 296 F.3d.
at 1324, 63 USPQ2d at 1613:
In Eli Lilly, we concluded that a claim to a microorganism
containing human insulin cDNA was not adequately described
by a statement that the invention included human insulin
cDNA. Id. at 1557, 43 USPQ2d at 1405. The recitation
of the term human insulin cDNA conveyed no distinguishing
information about the identity of the claimed DNA sequence,
such as its relevant structural or physical characteristics.
Id. We stated that an adequate written description of
genetic material “‘requires a precise definition, such
as by structure, formula, chemical name, or physical
properties,’ not a mere wish or plan for obtaining the
claimed chemical invention,” and that none of those
descriptions appeared in that patent. Id. at 1566,
43 USPQ2d at 1404 . . . . The specification in the
Eli Lilly case did not show that the inventors had
possession of human insulin cDNA.
However, the court in Enzo Biochem Inc. v. Gen-Probe Inc.,
296 F.3d. at 1329, 63 USPQ2d at 1616-17, clarified:
It is true that in Vas-Cath, we stated: “The purpose of
the ‘written description’ requirement is broader than to
merely explain how to ‘make and use’; the applicant must
also convey with reasonable clarity to those skilled in
the art that, as of the filing date sought, he or she
Appeal No. 2003-0936
Application No. 09/532,806
11
was in possession of the invention.” Vas-Cath, 935 F.2d
at 1563-64, 19 USPQ2d at 1117. That portion of the
opinion in Vas-Cath, however, merely states a purpose
of the written description requirement, viz., to ensure
that the applicant had possession of the invention as
of the desired filing date. It does not state that
possession alone is always sufficient to meet that
requirement. Furthermore, in Lockwood v. American
Airlines, Inc., we rejected Lockwood’s argument that
“all that is necessary to satisfy the description
requirement is to show that one is “in possession”
of the invention. 107 F.3d 1565, 1572, 41 USPQ2d 1961,
1966 (Fed. Cir. 1997). Rather, we clarified that the
written description requirement is satisfied by the
patentee’s disclosure of “such descriptive means as
words, structures, figures, diagrams, formulas, etc.,
that fully set forth the claimed invention.” Id.
Accordingly, we espouse the view expressed in Evans v. Eaton,
20 U.S. (7 Wheat.) 356 (1822), as did the court in Vas-Cath, Inc.
v. Mahurkar, 935 F.2d at 1561, 19 USPQ2d at 1114-15, that:
[T]he Court concluded that the specification of a
patent had two objects, the first of which was “to
enable artizans to make and use [the invention]. . . .”
[Evans v. Eaton,] . . . at 433. The second object of
the specification was
to put the public in possession of what the
party claims as his own invention, so as to
ascertain if he claims anything that is in
common use, or is already known, and to guard
against prejudice or injury from the use of
an invention which the party may otherwise
innocently suppose not to be patented. It
is, therefore, for the purpose of warning an
innocent purchaser, or other person using . . .
[the invention], of his infringement of the
patent; and at the same time, of taking from
the inventor the means of practicing upon the
credulity or the fears of other persons, by
Appeal No. 2003-0936
Application No. 09/532,806
4 The examiner has not adequately explained why
appellant’s Claims 14, 32, and 95 stand rejected under 35 U.S.C.
§ 112, first paragraph, for inadequate written description. As
per those claims, the GRP promoter comprises the complete nucleic
acid sequence of SEQ ID NO:1.
12
pretending that his invention is more than what
it really is, or different from its ostensible
objects, that the patentee is required to
distinguish his invention in his specification.
Id. at 434.
In that light, we find that here the isolated nucleic acid
maize GRP promoter appellants claim comprising at least 95, 110,
125, 250, 400, 750, 1000, 1500, 2000, 2500, 3000, and 3536
contiguous nucleotide fragments of the 3536 contiguous nucleotides
of SEQ ID NO:1 of Figure 4 is so precisely defined in terms of
structure, formula, chemical name, and function, including
Figures 1-4 and examples, that persons skilled in the art
immediately would have understood what appellants claim as their
invention and could readily distinguish what appellants claim from
anything that is in common use, all that is known, and anything
proposed for production and use in the art. If an isolated
nucleotide sequence comprises at least 95 contiguous nucleotides of
the 3536 contiguous nucleotides of SEQ ID NO:1 and functions as a
GRP promoter when operably linked to a coding region, appellants
claim it.4 Whether the inventors “had possession of the claimed
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Application No. 09/532,806
13
invention” (EA 3), the test the examiner used to determine
compliance with the written description requirement of the first
paragraph of Section 112, is not the gauge for compliance. As the
court instructs in Enzo Biochem Inc. v. Gen-Probe Inc., 296 F.3d.
at 1330, 63 USPQ2d at 1617:
A showing of “possession” is ancillary to the statutory
mandate that “[t]he specification shall contain a written
description of the invention,” and that requirement is
not met if, despite a showing of possession, the
specification does not adequately describe the claimed
invention.
Accordingly, the examiner erred in rejecting Claims 1, 4-54,
and 85-113 for noncompliance with the written description
requirement of 35 U.S.C. § 112, first paragraph.
2. Rejection for nonenablement
The examiner’s rejection of Claims 1, 4-54, and 85-131, all
claims pending in this application, for noncompliance with the
enablement requirement of 35 U.S.C. § 112, first paragraph,
is an entirely distinct issue. At the onset, appellants’ own
specification teaches that: (1) the art is unpredictable, and
(2) a considerable amount of experimentation may be required to
enable persons skilled in the art to make and use the full scope
of the subject matter claimed; yet the kind and amount of
experimentation required to enable one skilled in the art to make
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Application No. 09/532,806
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and use the full scope of the subject matter claimed is well within
the knowledge and skill of a person with the ordinary level of
knowledge and skill in this art to perform without undue
experimentation. For example, appellants’ specification teaches
(Spec., pp. 12-13; emphasis added)):
[T]he current invention includes sequences which have
been derived from the maize GRP promoter disclosed
herein. One efficient means for preparing such
derivatives comprises introducing mutations into the
sequences of the invention, for example, the sequence
given in SEQ ID NO:1. Such mutants may potentially
have enhanced or altered function relative to the
native sequence or alternatively, may be silent with
regard to function.
Mutagenesis may be carried out at random and the
mutagenized sequences screened for function in a trial-
by-error procedure. Alternatively, particular sequences
which provide the ZMGRP promoter with desirable expression
characteristics could be identified and these or similar
sequences introduced into other related or non-related
sequences via mutation. Similarly, non-essential elements
may be deleted without significantly altering the function
of the elements. It further is contemplated that one
could mutagenize these sequences in order to enhance
their utility in expressing transgenes in a particular
species, for example, maize.
The means for mutagenizing a DNA segment encoding a
ZMGRP promoter sequence of the current invention are well-
known to those of skill in the art. Mutagenesis may be
performed in accordance with any of the techniques known
in the art, such as, but not limited to, synthesizing an
oligonucleotide having one or more mutations within the
sequence of a particular regulatory region. In particular,
site-specific mutagenesis is a technique useful in
the preparation of promoter mutants, through specific
mutagenesis of the underlying DNA. The technique further
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Application No. 09/532,806
15
provides a ready ability to prepare and test sequence
variants, for example, incorporating one or more of the
foregoing considerations, by introducing one or more
nucleotide sequence changes into the DNA. . . . .
The specification teaches that “the technique of site-specific
mutagenesis is well known in the art, as exemplified by various
publications” (Spec., p. 14). “The preparation of sequence
variants of the selected promoter DNA segments using site-directed
mutagenesis is provided as a means of producing potentially useful
species and is not meant to be limiting as there are other ways in
which sequence variants of DNA sequences may be obtained” (Spec.,
p. 15)(emphasis added). According to the specification (Spec.,
pp. 15-16)(emphasis added):
Examples of such methodologies are provided by U.S.
Patent No. 4,237,224, specifically incorporated herein by
reference in its entirety. A number of template dependent
processes are available to amplify the target sequences of
interest present in a sample, such methods being well
known in the art and specifically disclosed herein below.
One efficient, targeted means for preparing
mutagenized promoters or enhancers relies upon the
identification of putative regulatory elements within
the target sequence. This can be initiated by comparison
with, for example, promoter sequences known to be
expressed in a similar manner. Sequences which are
shared among elements with similar functions or
expression patterns are likely candidates for the
binding of transcription factors and are thus likely
elements which confer expression patterns. Confirmation
of these putative regulatory elements can be achieved
by deletion analysis of each putative regulatory region
followed by function analysis of each deletion construct
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Application No. 09/532,806
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by assay of a reporter gene which is functionally attached
to each construct. As such, once a starting promoter or
intron sequence is provided, any of a number of different
functional deletion mutants of the starting sequence
could be readily prepared.
As indicated above, deletion mutants of the ZMGRP
promoter also could be randomly prepared and then assayed.
With this strategy, a series of constructs are prepared,
each containing a different portion of the clone (a
subclone), and these constructs are then screened for
activity. A suitable means for screening for activity
is to attach a deleted promoter construct to a selectable
or screenable marker, and to isolate only those cells
expressing the marker protein. In this way, a number
of different, deleted promoter constructs are identified
which still retain the desired, or even enhanced, activity.
The smallest segment which is required for activity is
thereby identified through comparison of the selected
constructs. This segment may then be used for the
construction of vectors for the expression of exogenous
protein.
The specification also generally describes various regulatory
elements (Spec., pp. 18-21), terminators (Spec., p. 21), transit
or signal peptides (Spec., pp. 21-23), marker genes (Spec.,
pp. 23-27), and exogenous genes for herbicide resistance, insect
resistance, environment or stress resistance, disease resistance,
mycotoxin reduction, grain quality, etc. (Spec., pp. 27-61), which
are suitable for use in modifying plant characteristics, and
include citations to prior art and summaries of the state of the
art. The specification thereafter discusses assays which may be
employed to determine levels of expression of new transgenic DNA
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constructs (Spec., pp. 61-108) and various art recognized methods
suitable for plant transformation, growth, stabilization,
regeneration, seed production, and breeding (Spec., pp. 69-74),
including liberal citation of the prior art and discussion of the
state of the art. Following the aforementioned teachings, the
specification introduces the examples presented as follows (Spec.,
pp. 110-111)(emphasis added):
The following examples are included to demonstrate
preferred embodiments of the invention. It should
be appreciated by those of skill in the art that the
techniques disclosed in the examples which follow
represent techniques discovered by the inventor to
function well in the practice of the invention, and
thus can be considered to constitute preferred modes
for its practice. However, those of skill in the art
should, in light of the present disclosure, appreciate
that many changes can be made in the specific embodiments
which are disclosed and still obtain a like or similar
result without departing from the concept, spirit and
scope of the invention. . . . .
. . . . .
The current inventors have demonstrated the utility
of a novel maize promoter, designated Zea Mays Glycine
Rich Protein (ZMGRP) promoter, in conjunction with an intron
in transgenic maize. The ZMGRP promoter comes from a gene
(Genbank Acc# GI/22312) that is induced in response to
water stress and wounding. The ZMGRP mRNA has been shown
to accumulate in epidermal cells upon induction (Gomez
et al., 1988). The ZMGRP promoter was isolated from a
maize B73 genomic library and fused to the gus reporter
gene, both with and without a modified intron from the rice
Act2 gene (see Example 5).
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Transient expression assays in microparticle
bombarded maize suspension cells and in excised maize
root and leaf tissue were carried out in order to
determine the activity of the ZMGRP promoter. The
promoter was shown to be functionally active in
conjunction with a modified actin 2 (Act2) intron 1.
Furthermore, the ZMGRP promoter - Act2 intron combination
yielded transient expression levels that were at least
70% the level observed from the rice actin 1 (Act1)
promoter - intron combination (Zhang, W., McElroy, D.,
Wu, R., 1991). Finally, the ZMGRP promoter - intron - gus
construct was shown to express high levels of GUS protein
in the leaves, stems and meristematic regions of the
roots of RO maize plants regenerated from transformed
maize callus.
Accordingly, appellants argue that the broad teachings of the
specification and claims are supported by a number of specific
examples of isolated DNA comprising at least 95 contiguous bases of
SEQ ID NO:1 which comprise a functional maize GRP promoter. We
examine those examples below.
Example 1 teaches that the inventors serendipitously isolated
the ZMGRP promoter “from a maize B73 size-selected lambda genomic
DNA (gDNA) library while attempting to isolate a second maize
promoter, designated A3” (Spec., p. 111). Example 1 reports
(Spec., p. 112):
The analysis revealed that the restriction map and
hybridization pattern of the putative clone was highly
similar to, but not identical to, the expected A3
pattern. Partial sequencing of the clone revealed that
the 5' sequence was highly homologous, but not identical
to that of the A3 5' region. A GenBank search revealed
that the 4000 base pair cloned sequence shared homology in
Appeal No. 2003-0936
Application No. 09/532,806
5 SEQ ID NO:2 includes 8076 nucleotides (Raw Sequence
Listing (Paper No. 4)).
6 SEQ ID NO:3 includes 9002 nucleotides (Raw Sequence
Listing (Paper No. 4)).
19
about the 400 most 3' based pairs with an ABA-inducible
genomic clone reported by Gomez et al. (1988)(GenBank
Accession Number X12564).
Example 2 characterizes the ZMGRP promoter constructs used
in subsequent examples of transient expression analyses and
transformations therewith. Example 2 in its entirety reads
(Spec., pp. 112-113)(emphasis added):
Sequence characterization of the ZMGRP promoter-
containing plasmid revealed that the ~ 4.0 kb SacI insert
contained a HindIII site 97 bp from the 5' end of the
insert and approximately 360 bp of ZMGRP coding sequence
3' of the ATG start codon. Restriction enzyme analysis
determined that there was a unique XhoI site approximately
400bp 5' of the ATG start site. The sequence around the
XhoI site was determined and used to design a 5' PCR
primer. A 3' PCR primer was designed to change the
sequence around the ATG start site to create an NcoI site
and to introduce a SmaI site 4 bp 5' of the ATG start
codon. These primers were used to PCR amplify the DNA
at the 3' end of the promoter from the XhoI site to the
newly created NcoI site. The PCR fragment was used in a
three way ligation, employing a HindIII to XhoI fragment
containing the 5' ~3.2kbp part of the ZMGRP promoter
region, the XhoI to NcoI fragment containing the 3' 0.4 kbp
part of the ZMGRP promoter region, and the gus-nos sequence
containing vector pGN73, which had been digested with
HindIII and NcoI. The resulting construct was designated
pZMGRP-GN73 (Fig. 2, SEQ ID NO:2)5. A construct designated
pZMGRP-Act2-int-GN73 was made by replacing the SmaI - NcoI
region of the ZMGRP promoter with a PvuII - NcoI restriction
fragment from pDPG836 containing a rice Act2 intron 1
deletion derivative (Act2-int)(Fig. 1, SEQ ID NO:3)6.
Appeal No. 2003-0936
Application No. 09/532,806
20
Example 3 (Transient Expression Analysis of ZMGRP Promoter
Function) describes the transient expression assays used for
analysis of (Spec., p. 113):
. . . expression of the gus reporter gene (E. coli
beta-glucuronidase) fused to the ZMGRP promoter
with an actin 2 intron (U.S. Serial No. 09/312,304)
(ZMGRP (639) act 2 pGN73, FIG. 1) or without any
intron (ZMGRP (639) pGN73, FIG. 2) . . . .
Having considered the teaching in appellants’ specification,
we now focus on the examiner’s reasons to doubt the objective truth
of the statements contained therein. In re Marzocchi, 439 F.2d
220, 223-24, 169 USPQ 367, 369-70 (CCPA 1971), instructs (footnote
omitted):
As a matter of Patent Office practice . . . a
specification disclosure which contains a teaching of
the manner and process of making and using the invention
in terms which correspond in scope to those used in
describing and defining the subject matter sought to
be patented must be taken as in compliance with the
enabling requirement of the first paragraph of § 112
unless there is reason to doubt the objective truth of
the statements contained therein which must be relied
on for enabling support. . . . .
. . . Most often, additional factors, such as the
teachings in pertinent references, will be available
to substantiate any doubts that the asserted scope of
objective enablement is in fact commensurate with the
scope of protection sought and to support any demands
based thereon for proof. . . . [I]t is incumbent upon
the Patent Office, whenever a rejection on this basis
is made, to explain why it doubts the truth or accuracy
of any statement in a supporting disclosure and to back
up assertions of its own with acceptable evidence or
Appeal No. 2003-0936
Application No. 09/532,806
21
reasoning which is inconsistent with the contested
statement.
To satisfy the enablement requirement of 35 U.S.C. § 112,
first paragraph, for the full scope of contiguous nucleotide
sequences appellants claim,
. . . the specification [must] . . . enable any person
skilled in the art to which it pertains to make and use
the claimed invention. Although the statute does not
say so, enablement requires that the specification teach
those in the art to make and use the invention without
“undue experimentation.” In re Wands, 858 F.2d 731,
737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). That some
experimentation may be required is not fatal; the issue
is whether the amount of experimentation required is
“undue.” Id. at736-37, 8 USPQ2d at 1404.
In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir.
1991). As explained in In re Wands, 858 F.2d at 737, 8 USPQ2d
at 1404 (footnotes omitted), “Enablement is not precluded by the
necessity for some experimentation such as routine screening.”
In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404, amplified the
statement with a quote from Ex parte Jackson, 217 USPQ2d 804, 807
(Bd. App. 1982)(emphasis added):
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 provides
a reasonable amount of guidance with respect to the
direction in which the experimentation should proceed.
In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404, instructs (footnote
omitted):
Appeal No. 2003-0936
Application No. 09/532,806
22
Factors to be considered in determining whether a
disclosure would require undue experimentation have been
summarized by the board in Ex parte Forman[, 230 USPQ
546, 547 (Bd. Pat. App. & Int. 1986)]. They include
(1) the quantity of experimentation necessary,
(2) the amount of direction or guidance presented,
(3) the presence or absence of working examples,
(4) the nature of the invention, (5) the state of
the prior art, (6) the relative skill of those in
the art, (7) the predictability or unpredictability
of the art, and (8) the breadth of the claims.
There appears to be minimal differences in appellants’ and the
examiner’s respective views of the evidence relative to each of the
factors material to their respective determinations whether or not
appellants’ specification would have required persons skilled in
the art to make and use the full scope of the claimed invention
without undue experimentation. On balancing the weight of the
collective evidence relating to all the material factors, the
scales do not significantly sway one way or another. Appellants
and the examiner appear to agree that, for any person skilled in
the art to make and use the full scope of the claimed invention, a
considerable amount of trial and error experimentation would be
required. However, the specification provides a considerable
amount of direction and guidance in that effort and cites prior art
which suggests that the kind and amount of experimentation are
routine. Appellants point to their working examples, but the
examiner finds the whole and only one functionally effective 639 bp
Appeal No. 2003-0936
Application No. 09/532,806
23
fragment of the whole 3536 bp nucleotide appellants describe, and
the 639 bp fragment is defined solely in terms of its enzymatic
restriction sites. The number of promoters which have been used to
effect expression of phenotypic genetic codes appears to be small,
yet appellants serendipitously have discovered one which preferably
promotes expression of a gene to which it is fused only when a
plant transformed by the construct is stressed and disclosed its
sequence and functional properties in the application before us.
The claims are narrowly limited to promoters having 3536 contiguous
named nucleotides and functionally effective fragments thereof
having at least 95 contiguous nucleotides. The prior art cited by
the examiner relating to the activity and requisite functional
sequences of the cauliflower mosaic virus 35S and nopaline synthase
(nos) promoters does show that the nucleotide structure essential
for promoter activity is highly unpredictable. However, the same
prior art shows that the level of skill and knowledge in this art
is extremely high, that mutations and deletions to the basic
sequence more often than not lower rather than eliminate promoter
activity, and that it is well within the ordinary skill of the
artisan to determine those nucleotide sequences which are critical
for functional activity.
Appeal No. 2003-0936
Application No. 09/532,806
24
Having considered all the evidence, we are not convinced that
the examiner has satisfied her burden to show that, in light of the
guidance and direction provided by appellants’ specification, the
kind and amount of experimentation required of one skilled in the
art to make and use the full scope of the subject matter claimed is
more than routine.
More significantly, however, the examiner urges (EA 8-9)
(emphasis added):
Appellants need to provide sufficient guidance for one
skilled in the art to determine which of the claimed
subfragments of SEQ ID NO:1 would be likely to have
promoter function. In the absence of such guidance,
it would require undue experimentation for one skill[ed]
in the art to practice the claimed invention, because
the ability of a particular nucleic acid sequence to
function as a promoter is highly unpredictable on the
basis of nucleotide sequence information alone. . . . .
The examiner maintains that to provide sufficient guidance
for one skilled in the art to determine which sequences
have promoter function, the specification must provide
some indication of what specific nucleotides the sequences
must retain in order to retain promoter function. Appellants
need not describe why or how the invention works in order to
provide such guidance.
Also see the examiner’s rationale below (EA 11):
The examiner does not assert that one skilled
in the art would be without sufficient guidance in
obtaining the claimed contiguous subfragments because
the specification does not provide sufficient structural
and functional information to prepare the recited
sequences. The examiner asserts that one skilled
in the art would be without sufficient guidance in
recognizing the claimed contiguous subfragments that
Appeal No. 2003-0936
Application No. 09/532,806
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have promoter activity because the specification does
not provide sufficient structural and functional
information for one skilled in the art to recognize
which sequence has promoter function.
In the two quotations reproduced above, we find the origins of the
examiner’s reversible error in this case.
Even in an unpredictable art, this being one, it is legal
error for an examiner to require an applicant to disclose a common
chemical structure essential for functional activity, here the
nucleotide sequence of the maize GRP promoter of SEQ ID NO:1
critical for functional activity, to satisfy the enablement
requirement of 35 U.S.C. § 112, first paragraph. To enable persons
skilled in the art to make and use the full scope of the subject
matter claimed, here all the subfragments of SEQ ID NO:1 which are
in fact active as maize GRP promoters, (1) it may not be necessary
to disclose, or even know, the chemical structure essential for
functional activity in order to enable any person skilled in the
art to make and use the full scope of the subject matter claimed,
and (2) there may not be a common chemical structure essential for
functional activity of the full scope of the subject matter
claimed. While each case must be considered on its own facts, we
are directed to reverse the examiner’s rejection of appellants’
claims under 35 U.S.C. § 112, first paragraph, as explained in the
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Application No. 09/532,806
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examiner’s answer, by In re Angstadt, 537 F.2d 498, 503-04,
190 USPQ 214, 218-219 (CCPA 1976):
If . . . the disclosure must provide “guidance which
will enable one skilled in the art to determine,
with reasonable certainty before performing the
reaction, whether the claimed product will be
obtained” (emphasis in original), as the dissent
claims, then all “experimentation” is “undue,” since
the term “experimentation” implies that the success
of the particular activity is uncertain. Such a
proposition is contrary to the basic policy of the
Patent Act, which is to encourage disclosure of
inventions and thereby to promote progress in the
useful arts. To require disclosures in patent
applications to transcend the level of knowledge
of those skilled in the art would stifle the
disclosure of inventions in fields man understands
imperfectly, like catalytic chemistry. The Supreme
Court said it aptly in Minerals Separation, Ltd. v.
Hyde, 242 U.S. 261, 270-271 (1916) . . . :
. . . the certainty which the law requires
in patents is not greater than is reasonable,
having regard to their subject matter . . . .
Appellants have broadly disclosed a class of catalyst
complexes whose use they deem to be part of the
invention. But for this disclosure the public may
have been deprived of the knowledge . . . . In this
art, the performance of trial runs using different
catalysts is “reasonable,” even if the end result is
uncertain . . . .
We have considered the examiner’s explanations, appellants’
responses, and all the evidence for and against the patentability
of appellants’ claims under 35 U.S.C. § 112, first paragraph, in
light of the guidance our reviewing courts have provided.
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Application No. 09/532,806
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Accordingly, we reverse the examiner’s final rejections of
Claims 1, 4-54, and 85-131 for noncompliance with description and
enablement requirements of 35 U.S.C. § 112, first paragraph.
Conclusion
For the reasons stated herein above, it is
ORDERED that the examiner’s rejections of Claims 1, 4-54,
and 85-113 for noncompliance with the written description
requirement of 35 U.S.C. § 112, first paragraph, is REVERSED; and
FURTHER ORDERED that the examiner’s rejections of Claims 1,
4-54, and 85-131 for noncompliance with the enablement requirement
of 35 U.S.C. § 112, first paragraph, is REVERSED.
REVERSED
SHERMAN D. WINTERS )
Administrative Patent Judge )
)
)
)
) BOARD OF PATENT
TEDDY S. GRON ) APPEALS
Administrative Patent Judge ) AND
) INTERFERENCES
)
)
)
LORA M. GREEN )
Administrative Patent Judge )
Appeal No. 2003-0936
Application No. 09/532,806
28
Robert E. Hanson
FULBRIGHT & JAWORSKI LLP
600 Congress Avenue
Austin, TX 78701