Ex Parte Beetham et al

Patent Trial and Appeal Board

Jan 11, 2018

11941666 (P.T.A.B. Jan. 11, 2018)

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.
11/941,666 11/16/2007 PETER R. BEETHAM CIBUS-005-CT 1087
35938 7590
Acuity Law Group, P.C.
12707 High Bluff Drive
Suite 200
San Diego, CA 92130-2037
01/16/2018 EXAMINER
KRUSE, DAVID H
ART UNIT PAPER NUMBER
1663
NOTIFICATION DATE DELIVERY MODE
01/16/2018 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
docketing @ acuitylg.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PETER R. BEETHAM,
PATRICIA L. AVISSAR, KEITH A. WALKER, and RICHARD A. METZ
Appeal 2016-002654
Application 11/941,666 1
Technology Center 1600
Before RICHARD J. SMITH, TAWEN CHANG, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a non-transgenic
herbicide resistant plant. The Examiner entered final rejections for
obviousness, indefiniteness, and that the claims are directed to non-
patentable subject matter.
We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE.
1 Appellants identify the real party in interest as Cibus US LLC. App. Br. 4.
Appeal 2016-02654
Application 11/941,666
STATEMENT OF THE CASE
Background
Herbicide-tolerant plants may reduce the need for tillage
to control weeds thereby effectively reducing soil erosion. One
herbicide which is the subject of much investigation in this
regard is N-phosphonomethylglycine, commonly referred to as
glyphosate. Glyphosate inhibits the shikimic acid pathway
which leads to the biosynthesis of aromatic compounds
including amino acids, hormones and vitamins. . . . For
purposes of the present invention, the term “glyphosate”
includes any herbicidally effective form of N-
phosphonomethylglycine (including any salt thereof), other
forms which result in the production of the glyphosate anion in
plants and any other herbicides of the phosphonomethlyglycine
family.
Spec. 1:25—36.
Tolerance of plants to glyphosate can be increased by
introducing a mutant EPSPS gene having an alteration in the
EPSPS amino acid coding sequence into the genome of the
plant. . . . These proposed mutations typically have a higher IQ
for glyphosate than the wild-type EPSPS enzyme which confers
the glyphosate-tolerant phenotype, but these variants are also
characterized by a high Km for PEP which makes the enzyme
kinetically less efficient.... Many mutations of the EPSPS
gene are chosen so as to produce an EPSPS enzyme that is
resistant to herbicides, but unfortunately, the EPSPS enzyme
produced by the mutated EPSPS gene has a significantly lower
enzymatic activity than the wild-type EPSPS.
Id. at 2:1—14.
“While such variants in the EPSP synthases have proved useful in
obtaining transgenic plants tolerant to glyphosate, it would be increasingly
beneficial to obtain a variant EPSPS gene product that is highly glyphosate-
tolerant but still kinetically efficient, such that improved tolerance can be
obtained with a wild-type expression level.” Id. at 3:4—7.
2
Appeal 2016-02654
Application 11/941,666
The Claims
Claims 1—7 and 9-35 are on appeal. Claim 1 is illustrative and reads
as follows:
1. A non-transgenic herbicide resistant plant which comprises a
plant that expresses a mutant EPSPS gene product instead of a
wild-type EPSPS gene product instead of a wild-type EPSPS
gene product [sic, repeated phrase] wherein the wild-type
EPSPS gene product has been mutated at one or more amino
acid positions, said positions selected from the group
consisting of Leui73, Alans), Metiso, Argisi, Ser98, Ser255 and
Leui98 in SEQ ID NO:2 or at an analogous amino acid residue
in an EPSPS paralog and said plant has substantially normal
growth as compared to a plant expressing the wild-type EPSPS
gene product;
wherein the plant is selected from the group consisting of
com wheat, rice, barley, soybean, cotton, sugarbeet, oilseed
rape, canola, flax, sunflower, potato, tobacco, tomato, alfalfa,
poplar, pine, eucalyptus, apple, lettuce, peas, lentils and grape.
The Issues
The claims stand rejected as follows:
I. Claims 1—7 and 9-35 stand rejected under 35 U.S.C. § 101
because the claimed invention is directed to non-statutory
subject matter. Ans. 2.
II. Claims 24—35 stand rejected under 35 U.S.C. § 112(b) or
35 U.S.C. § 112 (pre-AIA), second paragraph, as indefinite. Id.
at 3.
3
Appeal 2016-02654
Application 11/941,666
III. Claims 1—7 and 9-35 stand rejected under pre-AIA 35 U.S.C.
§ 103(a) as obvious over Meyer2 or Kmiec3 in view of Barry,4
Padgette,5 and Shah.6 Id. at 4.
I - INELIGIBLE SUBJECT MATTER
Section 101 of the Patent Act provides that “[wjhoever invents or
discovers any new and useful process, machine, manufacture, or
composition of matter, or any new and useful improvement thereof, may
obtain a patent therefor, subject to the conditions and requirements of this
title.” 35 U.S.C. § 101. There are, however, “three specific exceptions to
§ 101 ’s broad patent-eligibility principles: Taws of nature, physical
phenomena, and abstract ideas.’” Bilski v. Kappos, 561 U.S. 593, 601
(2010) (quoting Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980)).
Claims directed to such “building blocks of human ingenuity” are not
subject to patent protection because monopolizing the building block itself
would tend to impede rather than promote innovation — “thwarting the
primary object of the patent laws.” Alice Corp. Pty. Ltd. v. CLS Banklnt’l,
134 S. Ct. 2347, 2354 (2014). Nevertheless, “an invention is not rendered
ineligible for patent simply because it involves [for example] an abstract
2 U.S. 6,136,601, issued Oct. 24, 2000 (“Meyer”).
3 WO 97/48714, published Dec. 24, 1997 (“Kmiec”).
4 U.S. 5,627,061, issued May 6, 1997 (“Barry”).
5 Stephen R. Padgette, et al., Site-directed Mutagenesis of a
Conserved Region of the 5-Enolpyruvylshikimate-3-phosphate
Synthase Active Site, 266(33) J. Biol. Chem. 22364—69 (1991)
(“Padgette”).
6 U.S. 4,940,835, issued July 10, 1990 (“Shah”).
4
Appeal 2016-02654
Application 11/941,666
concept.” Id. To the contrary, claims that integrate such building blocks
into something more may be patentable. Id.
The Supreme Court has set forth a “framework for distinguishing
patents that claim laws of nature, natural phenomena, and abstract ideas
from those that claim patent-eligible applications of those concepts.” Id.
According to that framework, first “we determine whether the claims at
issue are directed to one of those patent-ineligible concepts.” Id. “If so, we
then ask, ‘[w]hat else is there in the claims before us?’” Id. (quoting Mayo
Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 78 (2012)). To
answer this second question,
we consider the elements of each claim both individually and as
an ordered combination to determine whether the additional
elements transform the nature of the claim into a patent-eligible
application. [The Supreme Court has] described step two of
this analysis as a search for an inventive concept — i.e., an
element or combination of elements that is sufficient to ensure
that the patent in practice amounts to significantly more than a
patent upon the [ineligible concept] itself.
Id. (internal citations and quotation marks omitted).
The Examiner rejected claims 1—7 and 9—35 under 35 U.S.C. § 101 as
directed to non-statutory subject matter. Ans. 2—3. The Examiner finds the
claims “read on a naturally occurring mutant plant comprising a mutant
EPSPS gene product.” Id. at 2. The Examiner finds the Specification and
prior art lack evidence that the claimed mutations “would not occur in
nature” and finds that glyphosate resistance by mutation of an EPSPS gene
“can and does occur in nature, the EPSPS gene naturally occurs in all
plants.” Id.
5
Appeal 2016-02654
Application 11/941,666
The Examiner cites Neve7 as “a rigid ryegrass having naturally
occurring resistance to both glyphosate and to an ALS inhibitor” and Heck8
as disclosing “a Helianthus salicifolius (willow leaf sunflower) having a
‘mutated’ amino acid at position Ala^ relative to instant SEQ ID NO: 2,
said sunflower having a Serine at such a position,” which the Examiner finds
teaches “that at least one of the claimed structures occur in nature.” Id. at 2—
3. As such, the Examiner finds that the method of making “point mutations
in situ in a plant genome such that the hand of man is not evident in the end
product, such a point mutation being indistinguishable from what would
occur in nature” comprises nonstatutory subject matter. Id. at 3.
Appellants argue the Examiner has not met the initial burden of
demonstrating unpatentability because the Examiner “offers no evidence of
record that the claimed plants are naturally occurring.” App. Br. 7.
Appellants further contend, citing guidance provided by the PTO in the
March 2014 Procedure For Subject Matter Eligibility Analysis Of Claims
Reciting Or Involving Laws Of Nature/Natural Principles, Natural
Phenomena, And/Or Natural Products in support, that the Examiner must
show the claimed element exists in nature, and not merely that it is possible
the element may exist in nature. Id. at 7—8.
Appellants further argue in their Reply Brief that Neve does not
“establish[] any of the specific mutations recited in the present claims,” that
7 Paul Neve, et al., Multiple herbicide resistance in a glyphosate-resistant
rigid ryegrass (Lolium risidum) population, 52(6) Weed Science 920—928
(2004) (abstract only) (“Neve”).
8 Heck, G.R., et al, Investigations into glyphosate resistant horseweed
(Conyza Canadensis): EPSPS gene family (unpublished) (2004, GenBank
Accession No. AAT45238.1) (“Heck”).
6
Appeal 2016-02654
Application 11/941,666
“rigid ryegrass” is not within the scope of the claims, and that the resistance
disclosed is not a natural process but rather “due to exposure to glyphosate
applied by farmers.” Reply Br. 3. Appellants argue that the Examiner has
not established that the sequence of Heck, which “is described as a partial
nucleic acid sequence . . ., is even expressed as a protein” and that the
Examiner thus has not established that the sequence is a naturally occurring
sequence with a mutated amino acid at position ALAi79. Id. at 3^4. Without
such evidence and with only the “assertion of possibility,” Appellants
contend, the burden to establish unpatentability has not been met. Id. at 4.
On the record before us, we are not persuaded the Examiner met the
burden to show the claims are directed to patent-ineligible subject matter.
The Examiner has not persuasively shown that the claims, considered in
their entirety, are limited to subject matter that is known in nature. We agree
with Appellants that the Examiner’s rejection — based on the hypothesis of
the claimed subject matter existing in nature without man’s intervention as
shown by the Neve and Heck references — fails to establish by a
preponderance of the evidence that the subject matter in fact occurs in
nature. In particular, Heck discloses only a partial sequence with no
identifying information to establish that the sequence encodes a protein
found in nature.
For the reasons above, we conclude the Examiner did not establish by
a preponderance of the evidence that claims 1—7 and 9-35 are unpatentable
under 35 U.S.C. § 101.
II - INDEFINITENESS
The Examiner has rejected claims 24—35 as indefinite under 35 U.S.C.
§112, second paragraph, because
7
Appeal 2016-02654
Application 11/941,666
the amino acid positions recited appear to be relative, for
example in instant claim 24 being to SEQ ID NO: 2, an
Arabidopsis thaliana EPSPS coding sequence, and would not
necessarily occur at the recited positions in an EPSPS paralog
from a different Arabidopsis species. Hence, the metes and
bounds of the claims are unclear.
Ans. 3.
Independent claim 24 recites:
24. A non-transgenic herbicide resistant plant which
comprises a plant that expresses a mutant EPSPS gene product
instead of a wild-type EPSPS gene product instead of a wild-
type EPSPS gene product [sic] wherein the wild-type EPSPS
gene product has been mutated at one or more amino acid
positions, said positions selected from the group consisting of
Leui73, Alan9, Meti80, Argisi, Ser98, Ser255 and Leui98 in
Arabidopsis or at an analogous amino acid residue in an EPSPS
paralog and said plant has substantially normal growth as
compared to a plant expressing the wild-type EPSPS gene
product;
wherein said non-transgenic herbicide resistant plant is selected
from the group consisting of com, wheat, and sugarbeet and
wherein said herbicide is glyphosate.
App. Br. 20 (Claims Appendix). Independent claim 32 is identical to claim
24, but recites that the plant has “substantially the same catalytic activity” as
the wild-type plant rather than “substantially normal growth.” Id. at 21.
Appellants argue that because the “EPSPS gene in the recited plant
species contains highly conserved regions which . . . are referred to in the
claims relative to Arabidopsis numbering,” the corresponding sites of
mutation in the claims “can be readily understood by those of skill in the art
and because they are unambiguously described in terms of the reference
Arabidopsis sequence.” Reply Br. 4. Appellants note the Examiner used the
conserved region as the basis for identification of the Heck reference {id. at
8
Appeal 2016-02654
Application 11/941,666
4—5) and that the Examiner does not explain why the skilled artisan would
be unable to recognize the claimed corresponding sites of mutation in the
Arabidopsis sequence or a paralog sequence. Id. at 5.
In response, the Examiner finds that “claim 24 makes no reference
[to] instant SEQ ID NO: 2 as being the sequence the recited amino acid
positions are relative to.” Ans. 8.
On balance, we find Appellants have the better position. The claimed
sequences of the EPSPS gene contain highly conserved regions as
acknowledged by Padgette, which the Examiner has relied upon in rejecting
Appellants’ claims. See Ans. 5, Padgett 22365. We find a preponderance of
the evidence does not support the Examiner’s finding that the ordinarily
skilled artisan would not have been able to identify the target amino acids
for mutation recited in the rejected claims.
For the reasons above, we conclude the Examiner did not establish by
a preponderance of the evidence that claims 24—35 are unpatentable under
35 U.S.C. § 112, second paragraph.
Ill-OBVIOUSNESS
The Examiner has rejected claims 1—7 and 9-35 as obvious over
Meyer or Kmiec in view of Barry, Padgette, and Shah. Ans. 4. The
Examiner finds Meyer teaches “a method for site-directed mutagenesis of a
nucleic acid molecule in a chromosomal gene of a plant.” Id. The Examiner
finds Kmiec teaches “introducing an alteration in a target sequence of the
genome of a plant cell” and that “if a desirable mutation has been identified
in one species, it can be introduced in the homologous genes of another
species.” Id. The Examiner finds that neither Meyer nor Kmiec teaches the
recited amino acid mutations. Id. The Examiner finds Barry teaches making
9
Appeal 2016-02654
Application 11/941,666
glyphosate tolerant plants using nucleic acids encoding an EPSPS,
“modifying the sequence GDKX3 at claim 1 which corresponds to GS^KS
of instant SEQ ID NO: 2,” and “modifying the sequence SAQX4K at claim 1
wherein X4 can be Y, corresponding to SS255QYL of instant SEQ ID. NO:
2.” Id.
The Examiner finds Padgette teaches “mutagenesis of a conserved
region of a plant EPSPS active site having the amino acid sequence of
LFL173GNAGi73Ti74A179M180R181 P178 (position numbers relative to instant
SEQ ID NO: 2)” and “mutating amino acids in a plant EPSPS corresponding
to amino acids in bacterial EPSPS genes that confer glyphosate resistance.”
Id. at 5. The Examiner finds Shah teaches “selecting mutant plant cells
resistant to glyphosate and determining the sequence of the EPSPS gene”
and “synthetic DNA probes for identifying mutations in a plant EPSPS.” Id.
The Examiner concludes it would have been obvious to the ordinary
artisan “to modify the teachings of either Meyer et al or Kmiec to make a
non-transgenic herbicide resistant plant which comprises a mutant EPSPS
gene product having mutations [at the claimed] one or more amino acid
positions” and in particular “to modify the teachings of Meyer et al or
Kmiec using the teachings of Barry et al given the teachings of Padgette et
al to modify Ser98 and/or Ser255 of a plant EPSPS gene.” Id.
Appellants argue that Meyer and Kmiec are “directed to general
mutagenesis methods in plants” and that neither establishes that the claimed
mutations are “‘desirable mutation[s]’” or that the skilled artisan “would
have a reasonable expectation of arriving at the claimed plants which are
both herbicide resistant and also exhibit substantially normal growth as
compared to plants having a wild-type EPSPS gene.” App. Br. 11—12.
10
Appeal 2016-02654
Application 11/941,666
Appellants argue that Padgette is “only interested in ‘ [understanding
the molecular basis of [glyphosate] tolerance’ in the active site of EPSPS
[and] discloses a single variant Gly%Ala [that] is not one of the mutational
sites referred to in the claims.” Id. at 12. Appellants also argue the
Examiner’s numbering of corresponding residues to the reference
Arabidposis sequence is incorrect, rendering the alleged mutation
comparison null. Id.
Appellants also argue the Examiner’s identified mutations in Barry
are “not one of the mutational sites referred to in the claims” and that Barry
does not teach changing the modifications the Examiner asserts, noting that
only “X4 is permitted to change” per Barry’s disclosure. Id.
Appellants also argue “there is nothing of record indicating that the
claimed residues in the EPSPS gene could be mutated and still result in
plants exhibiting substantially normal growth as compared to plants having a
wild-type EPSPS gene, as required by the present claims.” Id. at 13.
Specifically, Appellants argue that Padgette discloses the “mutated EPSPS
enzymes results in plants which exhibit diminished growth characteristics”9
and that, consequently, the skilled artisan would not have expected that the
claimed EPSPS sequences would grow normally, with any predictability. Id.
at 14.
9 During oral argument, Appellants clarified that the “diminished growth
characteristics” of plants containing the mutated EPSPS enzymes was a 70-
fold decrease in EPSPS activity, which Appellants argued would not
encourage the skilled artisan to pursue further similar mutations to achieve
plants having the claimed “normal growth.” Transcript of December 4, 2017
Hearing at 5:17—6:6; 9:9-18.
11
Appeal 2016-02654
Application 11/941,666
We agree with Appellants that the Examiner has not shown that the
claimed non-transgenic herbicide resistant plant would have been obvious
based on Meyer or Kmiec in view of Barry, Padgette, and Shah. Meyer and
Kmiec establish that methods for mutating plant genomes were known in the
art, which is not disputed. Ans. 4. However, we agree with Appellants that
neither reference establishes that the claimed mutations were desirable or
necessarily predictable.
Shah merely establishes that DNA probes for identifying mutations in
a plant EPSPS gene were known in the art, which is also not disputed. See,
e.g., Shah Figure 1.
Barry teaches plants transformed with EPSPS genes to create a
glyphosate resistance marker gene. Barry Abstract. Barry discloses that the
method can include production of an RNA sequence encoding an EPSPS
gene having claimed sequences including certain substituted amino acids.
Id. at 159:19—160:21 (claim 1). Barry does not disclose the claimed amino
acid mutations in those sequences.
Padgette teaches that there is a conserved region of EPSPS proteins
around Gly96 of the E. coli EPSPS sequence. Padgette 22365, Figure 1.
Padgette discloses that substituting glycine alanine at this position imparts
tolerance to additional EPSPS enzymes in other plant species. But Gly96 is
not one of the claimed mutations and the Examiner does not sufficiently
explain why the skilled artisan would select the claimed mutations as
obvious targets for mutation, or explain why normal growth would be
expected from a plant containing such mutation in light of the decreased
growth reported with mutation.
12
Appeal 2016-02654
Application 11/941,666
We agree with Appellants that the Examiner has not provided an
adequate basis for concluding that the skilled artisan would have been
motivated to use the methods of Meyer or Kmiec to make a non-transgenic
herbicide resistant plant which comprises a mutant EPSPS gene product
having mutations at the claimed amino acid positions, including to modify
Ser98 and/or Ser255 of a plant EPSPS gene. We agree with Appellants that
the modifications taught by Padgette indicated a substantial decrease in
EPSPS enzyme activity, which does not support the Examiner’s findings that
a claimed plant exhibiting “normal growth” would result from the proposed
modifications. Nor do we agree that Barry’s proposed mutations support the
Examiner’s proposed method of achieving the claimed substitutions.
“An examiner bears the initial burden of presenting a prima facie case
of obviousness.” In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir.
2011). Because that burden has not been carried here, we reverse the
rejection of claims 1—7 and 9—35 as obvious over Meyer or Kmiec in view of
Barry and Padgette under 35 U.S.C. § 103(a).
SUMMARY
We reverse all rejections on appeal.
REVERSED
13