Luis Rafael. Herrera-Estrella et al.

Patent Trials and Appeals Board

Aug 14, 2019

13560680 - (D) (P.T.A.B. Aug. 14, 2019)

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.
13/560,680 07/27/2012 Luis Rafael Herrera-Estrella LIP 301USCON2 8986
23581 7590 08/14/2019
KOLISCH HARTWELL, P.C.
520 SW YAMHILL STREET, SUITE 300
PORTLAND, OR 97204
EXAMINER
BURAN, ASHLEY KATE
ART UNIT PAPER NUMBER
1662
NOTIFICATION DATE DELIVERY MODE
08/14/2019 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
docketing@khpatent.com
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte LUIS RAFAEL HERRERA-ESTRELLA, DAMAR LIZBETH
LÓPEZ-ARREDONDO, and ALFREDO HERIBERTO HERRERA-
ESTRELLA1
____________

Appeal 2019-002835
Application 13/560,680
Technology Center 1600
____________

Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and
MICHAEL A. VALEK, Administrative Patent Judges.

VALEK, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellants submit this appeal under
35 U.S.C. § 134(a) involving claims to a method of propagating a transgenic
fungus. Examiner rejected claims 18, 20, and 26–37 as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 Appellants identify the real party in interest as Centro de lnvestigación y de
Estudios Avanzados del lnstituto Politécnico Nacional (CINVESTAV).
App. Br. 4.
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STATEMENT OF THE CASE
Claims 18, 20, and 26–37 are on appeal and can be found in the
Claims Appendix of the Appeal Brief. App. Br. 35–37. Claim 18 is the
only independent claim and representative of the claims on appeal. It reads
as follows:
18. A method of propagating a fungus, comprising:
obtaining a fungus transgenically adapted to express a
phosphite dehydrogenase enzyme that catalyzes oxidation of
phosphite to phosphate; and
growing the fungus in a medium containing phosphite as
a source of phosphorus.
App. Br. 35 (Claims Appendix).
Appellants seek review of Examiner’s rejection of claims 18, 20, and
26–37 under 35 U.S.C. § 103 as unpatentable over Metcalf,2 in view of
Herrera-Estrella,3 Wong,4 Metcalf 98,5 and McDonald.6 App. Br. 9.
Because Appellants do not argue the dependent claims 20 and 26–37

2 William W. Metcalf et al., US 2004/0091985 A1; published May 13, 2004
(“Metcalf”).
3 Alfredo H. Herrera-Estrella et al., US 5,922,603; issued July 13, 1999
(“Herrera-Estrella”).
4 Mee-Hua Wong, Phosphite Induces Morphological and Molecular
Changes in Phytophthora Species (2006) (Masters thesis, Murdoch
University) (“Wong”).
5 William W. Metcalf et al., Molecular Genetic Analysis of Phosphite and
Hypophosphite Oxidation by Pseudomanas Stutzeri WM88, J. Bacteriology,
Vol. 180, 5547–5558 (1998) (“Metcalf 98”).
6 Allison E. McDonald et al., Phosphite (Phosphorous Acid): Its Relevance
in the Environment and Agriculutre and Influence on Plant Phosphate
Starvation Response, J. Plant Nutrition, Vol. 24, 1505-1519 (2001)
(“McDonald”).
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separately, we focus our analysis on independent claim 18 and Appellants’
other claims stand or fall with claim 18. 37 C.F.R. § 41.37 (c)(1)(iv).
The issue is: Has Examiner established a prima facie case of
obviousness, and if so have Appellants provided evidence of secondary
considerations that, upon reweighing the entire merits of the case,
demonstrates Examiner’s determination of obviousness is not supported by
the preponderance of the evidence of record?
Findings of Fact
FF1. Metcalf teaches the amino acid sequence for a phosphite
dehydrogenase enzyme designated PtxD, which “was cloned from
Pseudomonas and also found in other bacteria.”7 Metcalf Abst. According to
Metcalf, PtxD catalyzes the oxidation of phosphite to phosphate. Id. Abst.,
¶ 65. Metcalf further teaches E. coli can be transformed “by use of a
recombinant system” to overproduce PtxD and then grown on a media with
phosphite as the sole source of phosphorus. Metcalf ¶¶ 65, 68, ¶¶ 135–136.
FF2. Herrera-Estrella teaches methods for transforming a fungus,
Trichoderma spp., to express the proteinase PrB1 in order to improve its
“capacity as biological control agents for phytopathogenic fungi and
nematodes.” Herrera-Estrella Abst. In particular, Herrera-Estrella teaches
the cotransformation of Trichoderma cells with a first vector comprising the
PrB1 gene and a second vector comprising a selectable maker that codes for
resistance to antibiotics, an herbicide, or a fungicide. Id. at col. 4, l. 61– col.
5, l. 10; col. 11, ll. 21–52. The selectable marker allows for the selection of

7 Examiner determines that the SEQ IDs taught in Metcalf share “100%
identity” with SEQ ID NO:1 of Appellants’ Specification. Non-Final Act. 4.
Appellants do not challenge that finding on appeal.
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transformed cells by means of the trait, e.g., resistance to a particular
antibiotic or fungicide, conferred by the selectable marker. See id.; see also
id. at col. 6, ll. 51–60 (describing transformation of a Trichoderma strain with
a plasmid that “contains all of the information that is necessary for the
expression of the gene prb1” and a second plasmid that “contains the
elements that are necessary for selecting the transgenic strains by means of
their resistance to the antibiotic hygromycin B”).
FF3. Wong teaches that “[p]hosphite is currently an effective chemical to
control Phytophthora species.” Wong 20. While acknowledging that
Phytophthora “are not true fungi,” Wong teaches that “they share many
characteristics with the true fungi such as an absorptive mode of nutrition,
growth by polarized hyphal extension and reproduction involving the
formation of spores.” Id. at 2. Wong describes experiments in which five
species of Phytophthora were grown in “a low phosphate defined medium”
and exposed to various concentrations of phosphite. Id. at Abst. Wong
reports that these Phytophthora showed decreased mycelial growth and
“[s]welling of hyphae with stunted side-branches and shrinking of cytoplasm
from hyphal tips and hyphal walls.” Id. According to Wong, “[p]hosphite
also retarded the development and caused distortion and lysis of
chlamydospores, sporangia and zoospores.” Id.
FF4. Metcalf 98 teaches that because “[a]ll organisms require P [i.e.,
phosphorus] in its most-oxidized form, phosphate, for growth . . . it is
possible to select for organisms capable of oxidizing reduced P compounds to
phosphate.” Metcalf 98 5550. According to Metcalf 98, “in media
containing reduced P compounds,” such as phosphite, “as the sole P source,
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only those organisms capable of oxidizing these reduced compounds to
phosphate are able to grow.” Id.
FF5. McDonald teaches that phosphite is “widely marketed . . . as an
agricultural fungicide” and that it is “an effective control agent for a number
of crop diseases caused by various species of pathogenic pseudo fungi
belonging to the genus Phytophthora.” McDonald Abst.; see also id. at 1516
(teaching phosphite is “an effective fungicide”). McDonald further teaches
that Saccharomyces cerevisiae, i.e., a yeast, “[l]ike plants . . . is clearly
unable to substitute the P in [phosphite] for the P in [phosphate]” and that
phosphate deprived “plants and yeast that have been treated with [phosphite]
suffer far greater deleterious consequences of [phosphate] starvation as
compared to those that had not been treated with [phosphite].” Id. at 1514.
Analysis
Examiner determines that Herrera-Estrella “teaches transforming
Trichoderma species with a selectable marker that provides fungicide
tolerance” and the other cited references teach that fungi “do not naturally
metabolize phosphite . . . and thus . . . phosphite is an effective selectable
marker for transgenic fungi.” Non-Final Act. 6. Accordingly, Examiner
finds that it would be obvious to use the PtxD gene taught in Metcalf “as a
selectable marker gene” to transform Trichoderma, according to the methods
taught in Herrera-Estrella, in order to “obtain successfully transformed
fungal species.” Id. at 6–7.
Appellants contend Examiner has not made out a prima facie case of
obviousness because none of the cited prior art teaches “that fungi cannot
grow on phosphite as a phosphorous source.” App. Br. 12. According to
Appellants, Wong and McDonald relate only “to Phytophthora species,
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which are water molds (Oomycetes), not true fungi.” Id. at 18. Thus,
Appellants urge, “there would have been no motivation for a skilled person
to obtain ‘a fungus transgenically adapted to express a phosphite
dehydrogenase enzyme that catalyzes oxidation of phosphite to phosphate,’
as recited in claim 18.” Id. at 18–19. Appellants additionally argue that
secondary considerations, including that the claimed invention unexpectedly
allows the use of phosphite as both a “fertilizer and contaminant
suppressant” and has garnered significant “professional and commercial
interest,” demonstrate that claim 18 is non-obvious. See id. at 29–33
(relying on Declaration of Luis Rafael Herrera-Estrella dated July 25, 2017
(“Herrera-Estrella Decl.”)).
We are not persuaded by Appellants’ arguments and agree with
Examiner’s statement of the rejection and responses to Appellants’
arguments in both the Answer and Non-Final Action, which we adopt and
incorporate by reference. In addition, we address Appellants’ arguments in
turn below.
We agree that Examiner has met the burden to establish a prima facie
showing of obviousness. The prior art teaches that PtxD can be used as a
selectable marker by transforming organisms and then growing them in an
environment where phosphite is the sole phosphorus source. See FF1; FF4.
McDonald teaches that both “pseudo fungi” like Phytophthora and yeast
(i.e., fungi) cannot effectively use phosphite as their sole phosphorus source
and that phosphite is a known fungicide. FF5. Thus, the record supports
Examiner’s finding that a skilled artisan would be motivated to use the PtxD
gene as a selectable marker (i.e., one that codes for resistance to a fungicide)
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in Herrera-Estrella’s method for transforming and selecting transgenic
Trichoderma fungi. FF2; Id. at 6–7.
We are not persuaded by Appellants’ argument that the cited prior art
fails to teach that fungi cannot utilize phosphite as a phosphorus source. See
App. Br. 12–19. Both Wong and McDonald teach that Phytophthora cannot
utilize phosphite and describe Phytophthora as “pseudo fungi” that share
many characteristics with fungi. FF3; FF5. In addition, we agree with
Examiner that McDonald also teaches that “true-fungi (exemplified by
Saccharomyces cerevisiae) have a similar response[] to phosphite as plants,
and it was known (and also explicitly taught by McDonald) that plants
cannot metabolize phosphite.” Ans. 15; see also FF5. Accordingly, the
record supports Examiner’s finding that a skilled artisan would reasonably
expect that the PtxD gene could be successfully used as a selectable marker
for transgenic fungi because only fungi with that gene would exhibit
sufficient resistance to phosphite to be grown in an environment where
phosphite is the sole source of phosphorus. See Par Pharm., Inc. v. TWI
Pharms., Inc., 773 F.3d 1186, 1198 (Fed. Cir. 2014) (citation omitted)
(“[T]he reasonable expectation of success requirement for obviousness does
not necessitate an absolute certainty for success.”).
We are also unpersuaded by Appellants’ objective indicia evidence,
which Appellants contend demonstrates that the claimed subject matter is
nonobvious. Appellants contend that the “use of phosphite as fertilizer and
contaminant suppressant is an unexpected product of modifying a fungus to
allow it to use phosphite instead of phosphate as a phosphorus source” as
recited in claim 18. See App. Br. 29–32. We, however, agree with
Examiner’s determination that a skilled artisan would expect such results
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from the prior art. See Non-Final Act. 10–13. Metcalf teaches that an
organism can be transformed with the PtxD gene, thereby allowing it to be
grown in a medium containing phosphite as the sole phosphorus source.
FF1. Thus, it would be expected that phosphite could be used as a fertilizer
on fungi transformed to express PtxD. In addition, McDonald teaches that
both plants and fungi cannot effectively metabolize phosphite and that
phosphite exacerbates the deleterious effects of phosphate starvation. FF5.
Thus, a skilled artisan would likewise expect phosphite to suppress
contaminants, e.g., other untransformed fungi and weeds, in fungi
transformed to express PtxD, particularly in a low-phosphate environment.
See In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991)
(“[W]hen unexpected results are used as evidence of nonobviousness, the
results must be shown to be unexpected compared with the closest prior
art.”); In re Skoner, 517 F.2d 947, 950 (CCPA 1975) (“Expected beneficial
results are evidence of obviousness of a claimed invention.”).
We are also unpersuaded by Appellants’ arguments pertaining to
commercial success and industry praise. See App. Br. 33. As we understand
the evidence in and attached to the Herrera-Estrella Declaration,8 the alleged
commercial interest and industry praise relates to engineering crops so that
such crops (not fungi) can be fertilized by phosphite as opposed phosphate.
Appellants have not clearly established a nexus between that evidence and
the “method of propagating a fungus” in claim 18. See In re GPAC Inc., 57
F.3d 1573, 1580 (Fed. Cir. 1995) (citation omitted) (“For objective evidence

8 Our review is limited by the fact that some of the exhibits attached to the
Herrera-Estrella Declaration are not in English. See Herrera-Estrella Decl.
Exs. B and D. Appellants have not provided translations of those exhibits.
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to be accorded substantial weight, its proponent must establish a nexus
between the evidence and the merits of the claimed invention.”). Even if
Appellants had established a sufficient nexus between their objective indicia
evidence and claim 18, that claim9 is broadly directed to the propagation of
any fungus species and does not require the use of the transformed fungi to
support phosphite metabolism in crops. Indeed, claim 18 encompasses the
use of the PtxD gene purely as a selectable marker in laboratory research to
select for fungi transformed to express another protein of interest (as taught
in Herrera-Estrella). Thus, Appellants’ evidence pertaining to a need for
alternatives to phosphate fertilizers as well as the alleged “professional and
commercial interest” that Appellants’ research has garnered is not
reasonably commensurate with the broader scope of claim 18. See In re
Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005) (Evidence of unexpected
results must also be “commensurate in scope with the degree of protection
sought by the claim[s]” on appeal to demonstrate non-obviousness).
Given these deficiencies and reweighing “the entire merits of the
matter” in light of Appellants’ unexpected results evidence, we determine
that Appellants’ evidence is insufficient to overcome Examiner’s prima facie
showing of obviousness. See In re Hedges, 783 F.2d 1038, 1039 (Fed. Cir.
1986). Accordingly, Examiner’s rejection of claim 18 is supported by the
preponderance of the evidence. As noted above, Appellants do not argue

9 As explained above, Appellants have not argued any of their other claims
separately on appeal. Thus, all of the claims presently before us stand or fall
with the validity of the broadest claim, independent claim 18. See 37 C.F.R.
§ 41.37 (c)(1)(iv).
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any of the other claims separately from claim 18. Thus, we affirm
Examiner’s rejection in full.

SUMMARY
We affirm the rejection of claims 18, 20, and 26–37 under 35 U.S.C.
§ 103 over Metcalf, Herrera-Estrella, Wong, Metcalf 98, and McDonald.
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