Ex Parte Lukyanov et al

Patent Trial and Appeal Board

May 23, 2017

11607828 (P.T.A.B. May. 23, 2017)

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.
11/607,828 11/30/2006 Sergey A. Lukyanov CLON-035CIPCIP 8977
24353 7590 05/25/2017
BOZICEVIC, FIELD & FRANCIS LLP
Bozicevic, Field & Francis
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
EXAMINER
ROBINSON, HOPE A
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
05/25/2017 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):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SERGEY A. LUKYANOV,
ARCADY F. FRADKOV, YULII A. LABAS,
MIKHAIL V. MATZ, and ALEXEY TERSKIKH1
Appeal 2015-007204
Application 11/607,828
Technology Center 1600
Before CHRISTOPHER G. PAULRAJ, TAWEN CHANG, and
RYAN H. FLAX, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to certain
nucleic acids, nucleic acid constructs, and expression cassettes, which have
been rejected as lacking in written description and/or as directed to patent
ineligible subject matter. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm in part.
1 Appellants identify the Real Party in Interest as Clontech Laboratories, Inc.
(Appeal Br. 3.)
Appeal 2015-007204
Application 11/607,828
STATEMENT OF THE CASE
According to the Specification, “[ljabeling is a tool for marking a
protein, cell, or organism of interest and plays a prominent role in many
biochemistry, molecular biology and medical diagnostic applications. . . .
Of particular interest is the development of new protein labels, including
chromo- and/or fluorescent protein labels.” (Spec. 1:30-2:2.) Further
according to the Specification, the present invention relates to “proteins that
are colored and/or fluorescent, where this feature arises from the interaction
of two or more residues of the protein,” as well as the nucleic acids encoding
these proteins. {Id. at 2:20—23.) The Specification states that the proteins of
the invention are “either obtained from non-bioluminescent Cnidarian, e.g.,
Anthozoan, species or . . . Anthozoan non-Pennatulacean (sea pen) species.”
{Id. at 2:23-26.)
Claims 71—107 and 109-115 are on appeal. Claim 71 is illustrative
and reproduced below:
71. A nucleic acid construct, the construct comprising:
a vector; and
a continuous open reading frame coding sequence that encodes
a nonbioluminescent Anthozoan chromo- or fluorescent polypeptide
or chromo- or fluorescent mutant thereof, wherein the polypeptide or
mutant thereof has an average molecular weight of 17.5 to 32.5 kDa,
comprises a P-can fold and a chromophore or fluorophore, and has an
absorbance maximum in the range of 300—700 nm and an emission
maximum in the range of 400—800 nm.
(Appeal Br. 119 (Claims App’x).)
The Examiner rejects claims 71—107 and 109-115 under 35 U.S.C.
§ 112(a) or 35 U.S.C. § 112 (pre-AIA), first paragraph, as failing to comply
with the written description requirement. (Ans. 4.)
2
Appeal 2015-007204
Application 11/607,828
The Examiner rejects claims 71—74, 76—82, 88, 91, 93, 95, 97, 99,
103, 109—111 and 114 under 35 U.S.C. § 101 as directed to patent ineligible
subject matter. (Ans. 9.)
I.
Issue
The Examiner has rejected claims 71—107 and 109—115 under 35
U.S.C. § 112(a)or35U.S.C. § 112 (pre-AIA), first paragraph, as failing to
comply with the written description requirement.
The Examiner finds that claim 71 can be construed as “any nucleic
acid that encodes any [non-bioluminescent Anthozoan] chromo or
fluorescent protein or a mutant thereof, wherein the polypeptide has three
characteristics (P-can fold, average molecular weight of 17.5—32.5kDa and a
chromophore/fhiorophore).” (Ans. 5, 7.) The Examiner finds that claim 71
and similar claims (e.g., claims 85 and 88), are “overly broad and encompass
a genus of structures not adequately described,” and that the Specification
“fails to provide a representative number of species for the claimed genus to
show that applicant was in possession of the claimed genus.” {Id. at 5—6, 7.)
In particular, the Examiner finds that “[t]he recited molecular weight
is not accompanied by a specific method used to derive[] said molecular
weight” and that, in any event, molecular weight does not sufficiently define
the protein recited in the claim. {Id. at 5.) The Examiner finds that the
recited P-can fold and absorbance information also do not provide structural
information sufficient to satisfy the written description requirement. {Id. at
6.) The Examiner further finds that the dependent claims that recite
reference polypeptide sequences, such as claims 72 and 109-115,
3
Appeal 2015-007204
Application 11/607,828
nevertheless fail to satisfy the written description requirement. (Id.) The
Examiner argues that these claims still encompass “an enormous amount of
variability,” because they claim sequences with just at least 40% or 70%
identity to the reference sequences. (Id.)
Likewise, with respect to dependent claims reciting specific types and
species of mutation (e.g., claims 89 and 90), the Examiner finds the claims
lack written description because the claims do not sufficiently identify the
claimed sequence(s) that contain the recited mutation(s) so as to correlate
structure and function. (Id. at 7.) With respect to claims 104 and 105, the
Examiner finds that the Specification additionally lacks description of the
recited “humanized” nucleic acid. (Id. at 8.) With respect to claims 106 and
107, the Examiner finds that the Specification further does not sufficiently
describe the “large genus of [recited] nucleic acid primers of 15 to 100
nucleotides that could hybridize under stringent conditions to a nucleic acid
or the complement thereof’ that encodes a polypeptide recited in the claims.
(Id. at 6—7.)
Appellants contend that claim 71 recites six characteristics of peptides
encoded by the claimed genus of nucleic acid, including the structural
characteristics of (1) molecular weight, (2) a P-can fold, and (3) the presence
of a chromophore/fluorophore, as well as the functional characteristics of (4)
color/fluorescence, (5) absorbance maximum, and (6) emission maximum.
4
Appeal 2015-007204
Application 11/607,828
(Appeal Br. 19.) Citing Yang,2 Ormo,3 Lehninger,4 and Friedberg,5
Appellants contend that these characteristics in combination “provide a
sufficient number of properties of the polypeptides encoded by the claimed
nucleic acids to describe the claimed genus of nucleic acids sufficiently so as
to demonstrate that Appellants are in possession of the pending claimed
genus.” {Id. at 20.)
Appellants further contend that the Specification discloses “48
examples of continuous open reading frame coding sequences encompassed
by the pending claimed genus of nucleic acid constructs,” including 9 wild-
type nucleic acid sequences obtained from 8 different wild-type Anthozoan
species as well as 39 mutant nucleic acid sequences. {Id. at 20—21, 23.)
Citing Daly6 and the McFadden Declaration,7 Appellants argue that these
exemplary sequences provide “a representative number of species of
continuous open reading frame nucleic acids encompassed by the pending
2 Fan Yang et al., The Molecular Structure of Green Fluorescent Protein, 14
Nature Biotechnology 1246 (1996).
3 Mats Ormo et al., Crystal Structure of the Aequorea victoria Green
Fluorescent Protein, 273 Science 1392 (1996).
4 1 Albert L. Lehninger et al., Principles of Biochemistry 87 (4th ed. 2005).
We note that no copy of Lehninger was provided in the record.
5 Iddo Friedberg & Hanah Margalit, Persistently Conserved Positions in
Structurally Similar, Sequence Dissimilar Proteins: Roles in Preserving
Protein Fold and Function, 11 Protein Science 350 (2002).
6 Mary Megan Daly et al., The Phylum Cnidaria: A Review of Phylogenetic
Patterns and Diversity 300 Years After Linnaeus, 1668 Zootaxa 127
(2007).
7 Declaration of Catherine McFadden, Ph.D. under 37 C.F.R. § 1.132 (Mar.
30, 2010).
5
Appeal 2015-007204
Application 11/607,828
claims.” (Id. at 22—24.)
With respect to claim 72 and other claims reciting reference
polypeptide sequences, Appellants argue that, in light of the disclosure of the
reference sequences, the teaching in the Specification of “homologs [that]
may have at least about 40% sequence identity with the disclosed fluorescent
polypeptides,” and the fact that certain of the reference polypeptide
sequences are highly conserved, a skilled artisan would reasonably conclude
that the inventors had possession of the claimed inventions. (See, e.g., id. at
28-29, 31, 32-33, 34—35, 44, 46, 47-52.)
With respect to claims 104 and 105, which contain a limitation
relating to humanized nucleic acid, Appellants argue that it is well known in
the art that “humanization of nucleic acids involves the creation of a
synthetic nucleic acid through the replacement of endogenous codons with
human preferred codons coding for the same amino acid as the endogenous
codon.” (Id. at 45.) Appellants argue that, given the “well-understood
nature of the humanization of nucleic acids within the art of molecular
biology” and the specific examples of humanized nucleic acids encoding for
fluorescent proteins, the Specification has sufficiently described the
limitation. (Id.)
With respect to claims 106 and 107, which contain limitations relating
to certain nucleic acid primers, Appellants argue that “[t]he [Specification
describes small DNA fragments of the subject nucleic acids [to be] useful as
PCR primers” and that use of such primers is well-understood in the art. (Id.
at 47.) Accordingly, Appellants argue that the Specification satisfies the
written description requirements with respect to these limitations. (Id.)
The issue with respect to this rejection is whether the evidence of
6
Appeal 2015-007204
Application 11/607,828
record supports the Examiner’s conclusion that claims 71—107 and 109—115
fail to comply with the written description requirement.
Analysis
Claim 71
Regarding claim 71, we find Appellants to have the better argument.
Claim 71 is directed to a nucleic acid construct comprising a vector and a
continuous open reading frame coding sequence encoding a wild type or
mutant Anthozoan polypeptide defined by the following properties: (1) it is
a chromo- or fluorescent polypeptide; (2) it has an average molecular weight
of 17.5 to 32.5 kDa; it comprises (3) a P-can fold and (4) a chromophore or
fluorophore; (5) it has an absorbance maximum in the range of 300—700 nm;
and (6) it has an emission maximum in the range of 400—800 nm.
The Federal Circuit has stated that
[t]he written description requirement can be met by “showing] that an
invention is complete by disclosure of sufficiently detailed, relevant
identifying characteristics ... i.e., complete or partial structure, other
physical and/or chemical properties, functional characteristics when
coupled with a known or disclosed correlation between function and
structure, or some combination of such characteristics.”
Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002)
(citation omitted). Furthermore, description of a genus is sufficient where
there is “disclosure of either a representative number of species falling
within the scope of the genus or structural features common to the members
of the genus so that one of skill in the art can ‘visualize or recognize’ the
members of the genus.” Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co.,
598 F.3d 1336, 1350 (Fed. Cir. 2010) (citation omitted).
In this case, we find that the evidence submitted fry Appellants
7
Appeal 2015-007204
Application 11/607,828
satisfies many of the factors cited by Enzo and Ariad for the written
description requirement. The Specification discloses a structural feature
common to the polypeptides encoded by the claimed nucleotide sequence,
i.e., the (3-can fold with a chromophore or fluorophore, which is known to
correlate with the claimed functional characteristics of color / fluorescence
(See generally Yang and Ormo.) The Specification also provides the amino
acid sequences of the encoded polypeptides from eight Anthozoan species
and the corresponding cDNA sequences, including an alignment of the
amino acid sequences of these polypeptides showing specific amino acids
that are conserved across the species. (Spec. Figs. 1—9, 23, Table 1.) The
Specification further describes different amino acid changes that can be
made in the wild-type sequences without eliminating the protein’s color
and/or fluorescence. (See, e.g., Spec. Table 2.) Finally, Appellants have
submitted an expert declaration from Dr. Catherine McFadden stating that
the eight Anthozoan species discussed in the Specification are representative
both of “the two subclasses that make up the Class Anthozoa” and of “the
diversity of polyps between and within these two subclasses.” (McFadden
Deck Iff 10—12.) Dr. McFadden further opines that, “in view of the number
and diversity of nonbioluminescent Anthozoans identified by [Appellants] as
organisms that expressed fluorescent proteins,” a skilled artisan would
reasonably expect that the fluorescent proteins recited in the claims “were
conserved in species across the Class Anthozoa.” (Id. at If8)] 9-13.)
The Examiner finds the above disclosure and evidence lacking
because “[n]o specific nucleotide sequence with a corresponding expression
product is claimed” in claim 71, (Ans. 15—16.) There is no requirement,
ho wever, that a darn must recite a reference sequence in order to satisfy
8
Appeal 2015-007204
Application 11/607,828
written description, Cf. Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)
(holding that even specifications need not recite structure or formula or
chemical name for nucleotide sequences of claimed chimeric genes where
such sequences are known in the art).
The Examiner further questions how it is possible that “48 examples,
as stated by appellants could be considered representative of what the
appellants] consider to be ‘a multitude of nucleic acids' encompassed in th
claimed invention,” and argues that the claims are overly broad because
“[they] are not limited to the 9 species of wild-type ... or the 39 species of
mutant nucleic acid sequences” discussed in the Appeal Brief. (Ans. 16,
19.) We are not persuaded. Compliance with the written description
requirement does not require each species of a claimed genus to be
disclosed. Instead, what is requi red is “a representati ve number of species . .
. or structural features common to the members of the genus” so as to allow1'
a skilled artisan to “‘visualize or recognize’ the members of the genus.”
Ariad, 598 F.3d at 1350 (citation omitted). The Examiner neither addresses
the statements in Dr. McFadden’s declaration regarding why the Anthozoan
species disclosed in the Specification might be considered representative,
nor explains why the disclosure in the Specification regarding conserved
amino acids in the encoded polypeptides of the eight species does not
The Examiner argues that the recited P~can fold with a chromophore
and fluorophore also does not suffice as “a structural feature to describe
specific embodiments of the claimed invention.” (Ans. 17—18.) In
particular, the Examiner argues that “there are no indicia in the instant
specification of a specific structure possessing a P-can fold,” that “a
9
Appeal 2015-007204
Application 11/607,828
structure including a | BI - can fold does not define the composition of the
amino acids in said structure,” and that “possession of a chromophore,”
likewise, “does not define the entire structure of a protein,” (Id.)
We are not persuaded. Appellant has represented that “all of the
exemplary ami no acid sequences of the disclosed Anthozoan polypeptides
contain a p-can fold,” and this statement appears supported by the
Specification. (Reply Br. 7—8; Spec. 29:30—32 (“In many embodiments, the
subject homologues have structural features found in the above provided
specific sequences, where such structural features include the fi-can fold,”)
(emphasis added).) Similarly, while different amino acid sequences can
form a p-can fold, and a p-can fold secondary or tertiary structure thus may
not have a one-to-one correspondence with the primary structure of a
protein, the Specification has also provided multiple examples of non-
bioluminescent Anthozoan proteins having a P-can fold, together with
indications of amino acids that are conserved across these proteins and
mutations that do not appear to affect the P-c-an fold structure. (See, e.g.,
Spec. Figs. 1—9, 23, Tables 1, 2.)
With respect to the Examiner’s argument that a chromophore does not
define the entire structure of the protein, we n ote that to sati sfy the written
description requirement it is not necessary that the Specification discloses
the entire structure of each species within a genus. Rather, as already
discussed above, it is only necessary that there be disclosure of “structural
features common to the members of the genus so that one of skill in the art
can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at
1350 (citation omitted) (emphasis added).
We also note, but are not persuaded by, the Examiner’s additional
10
Appeal 2015-007204
Application 11/607,828
arguments that the claim limitations regarding molecular weight, absorbance
maximum, and emission maximum do not sufficiently disclose the claimed
genus of nucleic acid constructs because none of these limitations, by itself,
defines the structure of the encoded protein, (Ans. 16—17, 18, 19.) While
the Examiner’s arguments may be factually accurate, the written description
requirement is met for the reasons discussed above.
Claims 104 and 105
Claims 104 recites a humanized nucleic acid encoding the non-
bioluminescent Anthozoan chromo- or fluorescent polypeptide or mutant
that is also described in claim 71, while claim 105, which depends from
claim 104, recites additional narrowing limitations relating to 40% sequence
identity with certain reference sequences.
As discussed above, the Examiner finds that “the claimed invention
. . . directed to a humanized nucleic acid encoding a fluorescent polypeptide
. . . is not adequately described.” (Ans. 8.) The Examiner does not dispute
Appellant’s explanation that “the humanized element refers to changes made
to the nucleic acid sequence to optimize the codons for expression of the
protein in human cells” and acknowledges that “[t]he art appears to
recognize humanized proteins.” {Id. at 8, 25; see also Spec. 24:9-14.)
However, the Examiner argues that “[a] skilled artisan cannot envision the
detailed chemical structure of the encompassed genus of nucleic acids and
the encoding polypeptides based on the limitations found in claim 104”
because understanding of the humanization process “does not provide the
missing structural elements in the claim.” (Ans. 25.)
In light of the above, the Examiner’s rejection of claims 104 and 105
also appear to be based on the Examiner’s finding that the claimed genus of
11
Appeal 2015-007204
Application 11/607,828
nucleic acid and/or amino acid sequences relating to the recited chromo- or
fluorescent polypeptide or mutants is insufficiently described. We find the
rejection lacking for the same reasons described above regarding claim 71.
Claims 106 and 107
Claim 106 and 107 claims nucleic acid primers of 15 to 100
nucleotides in length that hybridize under stringent conditions of 50°C and
0.1 xSSC to a nucleic acid, or the complement or complement thereof, that
encodes a polypeptide recited in claim 71. The Examiner argues that “the
recitation of a nucleic acid primer of 15 to 100 nucleotides that hybridizes
under stringent conditions to a nucleic acid or complement thereof without
providing a reference structure lacks adequate written description.” (Ans.
25.)
As noted with approval in Enzo, the USPTO’s Written Description
Examination Guidelines suggests that “genus claims to nucleic acids based
on their hybridization properties . . . may be adequately described if they
hybridize under highly stringent conditions to known sequences because
such conditions dictate that all species within the genus will be structurally
similar.” Enzo, 323 F.3d at 967. In light of our finding that the encoding
sequence of claim 71 is sufficiently described, we find that Appellants have
the better argument as to these claims as well.8
8 We note that claims 106 and 107 differ from the scenario described in Enzo
in that the claims recite “stringent” hybridization conditions rather than
“highly stringent” conditions. However, the Examiner has provided no
argument or evidence that a skilled artisan would not expect primers that
hybridize to target polynucleotides under stringent, rather than highly
stringent, conditions, to be similar in sequence.
12
Appeal 2015-007204
Application 11/607,828
Accordingly, we reverse the Examiner’s rejection of claims 71 and
104—107. Having found the nucleotide acid constructs of claim 71 to be
described, we are also not persuaded by the Examiner’s similar arguments
with respect to claims 79, 81, 83, 85, and 88. (Ans. 19.) Likewise, we find
that dependent claims 72, 80, 82, 84, 89—103, and 109—115, which recite
narrowing limitations regarding 40% or 70% identity to specific reference
sequences and/or specific mutations or types of mutations, axe also described
for at least the same reasons discussed above for claim 71. Finally, the
Examiner made no additional specific arguments regarding claims 73—78,
86, and 87. We therefore also reverse the Examiner’s rejection of those
claims for lack of written description, for the reasons already discussed.
II.
Issue
The Examiner has rejected claims 71—74, 76—82, 88, 91, 93, 95, 97,
99, 103, 109—111, and 114 under 35 U.S.C. § 101 as directed to non-
statutory subject matter.
The Examiner finds that “[t]he claimed invention encompasses a
coding sequence that is naturally occurring,” including for instance naturally
occurring mutants. (Ans. 9.) While claim 71 recites a nucleic acid construct
that also comprises a vector, the Examiner points out that the Specification
defines a vector as “a replicon, such as plasmid, phage or cosmid, to which
another DNA segment may be attached so as to bring about the replication
of the attached segment.” {Id. at 10 (internal quotation marks omitted).)
The Examiner finds that the broadest reasonable interpretation of vector thus
encompasses “a chromosome segment comprising a coding region.” {Id.)
As to claim 76, which recites a nucleic acid construct prepared by inserting a
13
Appeal 2015-007204
Application 11/607,828
coding sequence into a vector, the Examiner further finds the claim to be a
product by process claim that does not alter the structure of the coding
sequence. {Id. at 11—12.) Likewise, the Examiner finds that the Kozak
sequence and multiple cloning sites recited respectively in, e.g., claims 81
and 79, to be naturally present in a coding sequence. {Id. at 12.)
Accordingly, the Examiner finds:
[T]he instant specification discloses that a new fluorescent protein
was discovered by applicant^] however, there is no indication in the
specification as to how the claimed subject matter markedly differs
from a wild-type fluorescent protein. Further, there is no distinction
made between the fluorescent protein or mutant thereof claimed and
the natural form[;] thus, the claim language is not patent eligible ....
(Id. at 13.)
Appellants contend that the rejected claims recite a continuous open
reading frame coding sequence, which is not naturally occurring. (Appeal
Br. 96—99.) With respect to claim 71 and dependent claims, Appellants
further argue that, in any event, “the . . . claimed nucleic acid construct that
comprises the continuous open reading frame coding sequence together with
a vector would rise to the level of marked difference.” {Id. at 101—104,
113.) With respect to claims 72, 80, 82, 103, 109—111, and 114, which
recite certain reference sequences, Appellants argue that the additional
limitations in the claims further narrow the claims so as to render them
patent eligible. {Id. at 102—103, 106, 107—108, 112—116.) With respect to
claims 73, 74, 76—82, 110, and 111, which further define the claimed vector
and/or the nucleic acid construct, Appellants argue that the additional
limitations “will inherently result in the nucleic acid construct having a
different structure and sequence than any naturally occurring nucleic acids,
14
Appeal 2015-007204
Application 11/607,828
e.g., through inclusion of heterologous nucleic acid sequence from the
vector.” (Id. at 103, 105—108, 114—115.) With respect to claims 88, 91, 93,
95, 97, 99, 103, and 114, which recite additional limitations relating to a
mutant polypeptide, Appellants contend that the claimed polypeptide “will
have different structural characteristics than any naturally occurring nucleic
acid, which rises to the level of marked difference.” (Id. at 109—113, 116.)
The issue with respect to this rejection is whether the evidence of
record supports the Examiner’s conclusion that claims 71—74, 76—82, 88, 91,
93, 95, 97, 99, 103, 109—111, and 114 are directed to patent ineligible
subject matter.
Analysis
We analyze this issue under the Supreme Court’s controlling
precedent, Assoc, for Molecular Pathology v. Myriad Genetics, Inc., 133
S.Ct. 2107 (2013); see also Alice Corp. Pty. Ltd. v. CLS Bank Int’l., 124
S.Ct. 2347, 2355 (2014) (instructing to first consider whether the claims are
directed to an ineligible concept and, if so, then consider whether the claims
individually and as an ordered combination recite sufficiently more to
transform the claimed invention into patent-eligible subject matter). In
Myriad, the Supreme Court found that claims directed to isolated DNA
encoding the BRCA1 polypeptide and certain fragments thereof, to be
directed to patent ineligible subject matter. /J. at 2113, 2117—2119. In
particular, the Court found that, unlike the Chakrabarty bacterium that was
“new ‘with markedly different characteristics from any found in nature’,”
“separating the gene from its surrounding genetic material is not an act of
invention.” Id. at 2117. However, the Court found that:
15
Appeal 2015-007204
Application 11/607,828
cDNA does not present the same obstacles to patentability as naturally
occurring, isolated DNA segments. . . . [CJreation of a cDNA
sequence from mRNA results in an exons-only molecule that is not
naturally occurring. Petitioners concede that cDNA differs from
natural DNA in that “the non-coding regions have been removed.”
They nevertheless argue that cDNA is not patent eligible because
“[t]he nucleotide sequence of cDNA is dictated by nature, not by the
lab technician.” That may be so, but the lab technician
unquestionably creates something new when cDNA is made. cDNA
retains the naturally occurring exons of DNA, but it is distinct from
the DNA from which it was derived. As a result, cDNA is not a
“product of nature” and is patent eligible under § 101, except insofar
as very short series of DNA may have no intervening introns to
remove when creating cDNA. In that situation, a short strand of
cDNA may be indistinguishable from natural DNA.
Id. at 2119.
Claims 71-74. 76-78. 109
Claim 71 claims a nucleic acid construct comprising a vector and a
continuous open frame coding sequence that encodes the recited non-
bioluminescent Anthozoan chromo- or fluorescent polypeptide or mutant.
Claims 72—74, 76—78, and 109 all depend directly or indirectly from claim
71. Claim 72 and 109 include narrowing limitations requiring the
polypeptide or mutant to have 40% or 70% sequence identity with certain
identified sequences. Claims 73, 74, 77, and 78 further characterize the
structure of the nucleic acid construct by requiring certain sequences or
types of vectors. Claim 76 recites that the construct is prepared by inserting
the coding sequence into the vector.
Appellants first contend that the recited “continuous open reading
frame coding sequence” is not naturally occurring because, like the cDNA
found to be patent eligible in Myriad, it retains the exons and excludes the
16
Appeal 2015-007204
Application 11/607,828
introns, if any, of the genomic locus from which the sequence is derived.
(Appeal Br. 96—99.)
We are not persuaded. As summarized in Myriad,
[c]reation of proteins from DNA involves two principal steps, known
as transcription and translation. In transcription, the bonds between
DNA nucleotides separate, and the DNA helix unwinds into two
single strands. A single strand is used as a template to create a
complementary ribonucleic acid (RNA) strand. The nucleotides on
the DNA strand pair naturally with their counterparts, with the
exception that RN A uses the nucleotide base uracil (U) instead of
thymine (T). Transcription results in a single strand RNA molecule,
known as pre-RNA, whose nucleotides form an inverse image of the
DNA strand from which it was created. Pre-RNA still contains
nucleotides corresponding to both the exons and introns in the DN A
molecule. The pre-RNA is then naturally “spliced” by the physical
removal of the introns. The resulting product is a strand of RNA that
contains nucleotides corresponding only to the exons from the original
DNA strand. The exons-only strand is known as messenger RNA
(mRNA), which creates amino acids through translation.
Myriad, 133 S.Ct. at 2111 (emphasis added). As further explained in
Myriad,
It is also possible to create DNA synthetically through processes
similarly well known in the field of genetics. One such method
begins with an mRN A molecule and uses the natural bonding
properties of nucleotides to create anew, synthetic DNA molecule.
The result is the inverse of the mRNA's inverse image of the original
DNA, with one important distinction: Because the natural creation of
mRNA involves splicing that removes introns, the synthetic DNA
created from mRNA also contains only the exon sequences. This
synthetic DNA created in the laboratory from mRNA is known as
complementary DNA (cDNA).
Id. at 2112. In short, although both cDNA and mRNA contain only exons,
mRNA exists in nature while cDNA does not.
Under the broadest reasonable construction, a continuous open
17
Appeal 2015-007204
Application 11/607,828
reading frame coding sequence includes mRNA coding sequences. Such a
construction is supported by the Specification, which states that “[njormally
mRNA species have contiguous exons, with the intervening introns, when
present, being removed by nuclear RNA splicing, to create a continuous
open reading frame encoding the protein.” (Spec. 17:1—5.) Accordingly,
contrary to Appellant’s argument, limitations in the claims relating to a
“continuous open reading frame” do not necessarily render the claims patent
eligible.
Our findings regarding “continuous open reading frame” does not end
our inquiry. Appellants next argue that, “even if the continuous open
reading frame coding sequence was considered to be naturally occurring, the
instantly claimed nucleic acid construct that comprises the continuous open
reading frame coding sequence together with a vector would rise to the level
of marked difference.” (Appeal Br. 101.)
The Examiner contends that “[t]he broadest reasonable interpretation
of [vector] is a chromosome segment comprising a coding region.” (Ans.
10.) The Examiner further contends that “[i]f the natural gene is taken out of
the organism and inserted into a vector, the gene remains the same,” and that
“[t]here is no evidence in the claim or instant specification that the gene is
altered.” {Id. at 12.)
Appellants respond that the Examiner’s construction of vector as
encompassing a chromosome is “plainly inconsistent with how the claim
term would be interpreted by one of ordinary skill in the art in view of the
specification”:
The specification is directed to the cloning and modification of
Anthozoan chromo- and fluorescent protein encoding nucleic acids.
The Specification provides specific examples where plasmid vectors
18
Appeal 2015-007204
Application 11/607,828
are utilized for cloning and expression of coding sequences. There is
no description in the specification of a construct comprising a
chromosome and a continuous open reading frame coding sequence
that are non-heterologous. In addition, the specification does not
describe a naturally occurring continuous open reading frame coding
sequence that encodes a chromo- or fluorescent Anthozoan
polypeptide that includes the limitations as set forth in Claim 71.
(Reply Br. 14.) Appellants also contend that the dependent claims, which
contain additional limitations with respect to the nucleic acid construct such
as multiple cloning sites (MCS), would lead a skilled artisan to interpret
vector as “not including] a chromosome that is non-heterologous to the
continuous open reading frame coding sequence.” (Id.)
We are not persuaded that Appellants’ narrow construction of vector
is correct in light of the broad and explicit definition of vector in the
Specification. Nevertheless, we find that the Examiner has not shown the
combination of a vector and the continuous open reading frame coding
sequence recited in claim 71 to be a patent-ineligible natural phenomenon.
We further explain our reasoning below.
The Specification defines a vector as “a replicon, such as plasmid,
phage or cosmid, to which another DNA segment may be attached so as to
bring about the replication of the attached segment.” (Spec. 4:28—29.)
Replicon is defined variously in dictionaries to be simply “a linear or
circular section of DNA or RNA which replicates sequentially as a unit,”9
“any genetic element that can regulate and effect its own replication from
9 “replicon.” Merriam-Webster Online Dictionary, https://www.merriam-
webster.com/dictionary/replicon (last visited April 28, 2017).
19
Appeal 2015-007204
Application 11/607,828
initiation to completion,”10 “[a] genetic element that undergoes replication as
an autonomous unit,”11 “[a] segment of a chromosome (or of the DNA of a
chromosome or similar entity) that can replicate, with its own initiation and
termination codons, independently of the chromosome in which it may be
located,” 12 and “[t]he replication unit; several are found per DNA in
eukaryotic system.”13 The second portion of the Specification’s definition
of vector, i.e., that it permits “another DNA segment [to] be attached so as to
bring about the replication of the attached segment,” also contains no
requirement that the DNA segment attached to be heterologous. While
Appellants point to examples in the Specification where vectors comprise
heterologous nucleic acid sequences, we do not import limitations from the
Specification into the claims. See, e.g., Bayer AG v. Biovail Corp., 279 F.3d
1340, 1348 (Fed. Cir. 2002). Accordingly, we do not find that a skilled
artisan, in light of the Specification, would interpret a nucleic acid construct
comprising a vector and coding sequence to exclude a chromosomal
segment that is non-heterologous to the coding sequence.
Nevertheless, the definition of the vector in the Specification suggests
that the nucleic acid construct of claim 71 should be interpreted to require
the continuous open reading frame to be a DNA segment, rather than, e.g.,
10 “replicon.” http://www.dictionary.com/browse/replicon?s=t (last visited
April 28, 2017).
11 “replicon.” http://www.thefreedictionary.com/Replicon+(genetics) (last
visited April 28, 2017).
12 “replicon.” http://medical-
dictionary.theffeedictionary.com/Replicon+(genetics) (last visited April 28,
2017).
13 Id.
20
Appeal 2015-007204
Application 11/607,828
an mRNA sequence, because a vector is defined as a replicon “to which
another DNA segment may be attached so as to bring about the replication
of the attached segment.” (Spec. 4:28—29 (emphasis added).) We further
agree with Appellants that a continuous open reading frame DNA coding
sequences encoding the polypeptide recited in claim 71 does not fall within
the judicial exception of natural phenomena, because they are similar to the
cDNA sequences found to be patent eligible in Myriad. Myriad, 133 S.Ct.
2107 at 2119. We are not persuaded by the Examiner’s argument that claim
71 does not recite a cDNA (Ans. 27—28), because, regardless of the wording
used, the rationale the Supreme Court articulated in finding cDNA to be
patent eligible also applies to a “continuous open reading frame” DNA
sequence. We are likewise not persuaded by the Examiner’s argument that
“some genomic sequence can have a contiguous open reading frame and
there is no exclusion of these structures in the claim language.” {Id. at 28—
29.) The Examiner has not provided any persuasive evidence or explanation
suggesting that a genomic sequence coding for the polypeptide recited in
the claims naturally have a continuous open reading frame, while Appellants
have provided evidence that removal of introns is required to arrive at least
one such “continuous open reading frame.”14 (Appeal Br. 97.)
14 The Examiner suggests that the Specification’s description of certain
nucleotide sequences as “wild type” or as “found in, derived from, or are
mutants or homologues of nucleic acids found in Anthozoan organisms”
indicate that such sequences occur in nature. (Ans. 9, 28.) We are not
convinced. Derivation from a natural organism does not automatically result
in lack of patent eligibility: cDNA, which the Supreme Court has held to be
patent-eligible, may be said to be “derived from” a natural organism as well,
as it is generally created from mRNA. Myriad, 133 S.Ct. at 2119. Likewise,
21
Appeal 2015-007204
Application 11/607,828
Given the above, we find that the Examiner has not established that it
is more likely than not that claim 71 reads on a naturally occurring nucleic
acid construct, or one that is not markedly different from a naturally
occurring nucleic acid construct. Accordingly, we reverse the Examiner’s
rejection of claim 71 and dependent claims 72—74, 76—78, and 109.
Claims 79, 80, 110
Claim 79 recites a nucleic construct comprising (1) a continuous open
reading frame coding sequence that encodes a nonbioluminescent
Anthozoan chromo- or fluorescent polypeptide, or a chromo- or fluorescent
mutant thereof, that has the characteristics of the polypeptide recited in
claim 71 and (2) a multiple cloning site. Claims 80 and 110 depend from
claim 79 and further requires that the nucleic acid of claim 79 has a 40% or
70% sequence identity with a sequence selected from specified sequences.
The Examiner contends that
multiple cloning site ... is found in the naturally occurring coding
sequence as evidenced by the disclosure at paragraph [0189] which
discloses that, “[B]oth wild type (wt) and mutant zFP538 DNA were
amplified via PCR and reconstructed to EGFP-N1 backbone. This
vector has the same multiple cloning sites as EGFP-N1. Both
pYNFPwt and pYNFPW129V keep the same multiple cloning
sites as EGFP-N1.[”]
(Ans. 12 (emphasis added).) We are not persuaded. The portion of the
Specification cited by the Examiner shows that the Anthozoan DNA was
attached to a vector (i.e., the EGFP-N1 backbone) and that the resulting
we agree with Appellants that “wild type” in this context does not indicate
that the sequences necessarily occur in nature (Reply Br. 12—13), but rather
simply means non-mutant.
22
Appeal 2015-007204
Application 11/607,828
vector retained the multiple cloning sites present on the original vector. This
disclosure does not suggest that the Anthozoan DNA itself contains multiple
cloning sites. Accordingly, we find that the Examiner has not established a
prima facie case of patent ineligibility with respect to claim 79 and
dependent claims 80 and 110 and reverse the Examiner’s rejection of these
claims.
Claims 81. 82. Ill
Claim 81 recites a nucleic construct comprising (1) a continuous open
reading frame coding sequence that encodes a nonbioluminescent
Anthozoan chromo- or fluorescent polypeptide, or a chromo- or fluorescent
mutant thereof, that has the characteristics of the polypeptide recited in
claim 71 and (2) a Kozak sequence. Claims 82 and 111 depend from claim
81 and further requires that the nucleic acid of claim 81 has a 40% or 70%
sequence identity with a sequence selected from specified sequences.
The Examiner contends that “it is well established in the art that a
Kozak sequence or Sine-Dalgamo sequence is an initiation sequence that is
naturally present in a coding sequence.” (Ans. 12.) The Examiner also
appears to argue, in the alternative, that the addition of a Kozak sequence
“do[es] not add significantly more to the judicial exception” of the coding
sequence. {Id. at 33.) Appellants contend that claim 81 “will inherently
result in the nucleic acid construct having a different structure and sequence
than any naturally occurring nucleic acids, e.g., through the inclusion of the
heterologous nucleic acid sequence of the Kozak sequence together with the
continuous open reading frame.” (Appeal Br. 107.)
The Examiner has not cited evidence showing that the Kozak
sequence is naturally present in a coding sequence encoding the recited
23
Appeal 2015-007204
Application 11/607,828
Anthozoan polypeptide or explained why its addition, to the extent it is not
naturally present, would not render the resulting nucleic acid construct
“markedly different” from a naturally occurring coding sequence. Because
“the Examiner bears the initial burden ... of presenting a prima facie case of
unpatentability,” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992), we
reverse the Examiner’s rejection of claim 81 and dependent claims 82 and
111.
Claims 88. 91. 93. 95. 97. 99. 103. 114
Claim 88 recites a continuous open reading frame nucleic acid
encoding chromo- or fluorescent mutant polypeptide of a non-
bioluminescent Anthozoan chromo- or fluorescent polypeptide, having the
characteristics of the polypeptide recited in claim 71. Claims 91, 93, 95, 97,
99, 103, and 114 all dependent from claim 88. Claims 91, 93, 95, and 97
further recites that mutant is a fluorescent protein from a particular species.
Claims 103 and 114 further requires that the nucleic acid of claim 88 has a
40% or 70% sequence identity with a sequence selected from specified
sequences.
Unlike claim 71, claim 88 does not require a nucleic acid construct
comprising a vector. As discussed above, a continuous open reading frame
nucleic acid encoding a wildtype non-bioluminescent Anthozoan chromo- or
fluorescent polypeptide encompasses natural phenomena, because it
encompasses mRNA sequences. Furthermore, none of the claims recited
above exclude naturally occurring mutants. Given that natural mutations are
well known (Spec. 6:17—19 (discussing “naturally-occurring mutational
events”), we agree with the Examiner that claims 88, 91, 93, 95, 97, 99, 103,
24
Appeal 2015-007204
Application 11/607,828
and 114 encompasses patent-ineligible subject matter.15
Appellants cite as support the USPTO’s 2014 Interim Guidance on
Patent Subject Matter Eligibility (“Interim Guidance”).16 In particular,
Appellants points to Claim 2 of Example 7 in the Interim Guidance’s
Nature-Based Product Examples—“Isolated nucleic acid comprising a
sequence that has at least 90% identity to SEQ ID No. 1 and contains at least
one substitution modification relative to SEQ ID No. 1”—which was found
in the Interim Guidance to be patent eligible. We are not persuaded. As an
initial matter, we are not bound by the Interim Guidance. Furthermore, we
find the instant claims distinguishable from the example in the Interim
Guidance, which requires a specific type of mutation (substitution) and
specifies that “[n]o substitution modifications of [the gene at issue] are
known to occur in nature.”
Accordingly, we affirm the Examiner’s rejection of claims 88, 91, 93,
95, 97, 99, 103, 114 as directed to patent-ineligible subject matter.
15 We note, but are not persuaded by, Appellants’ arguments that claims 103
and 114 are further patent eligible because they contain additional narrowing
limitations that “further ensures that the claim[s] . . . do[] not improperly tie
up the future use of any alleged judicial exception encompasse[d] by the
claimed nucleic acid construct.” (Appeal Br. 112—113, 116.) While these
claims are indeed narrower than claim 88, they are still more likely than not
to encompass patent-ineligible subject matter (i.e., a naturally occurring
mutant).
16 2014 Interim Guidance on Patent Subject Matter Eligibility, 79 Fed. Reg.
74,618 (Dec. 16, 2014), available at https://
www.federalregister.gov/ articles/2014/12/16/2014-29414/2014-interim-
guidance-on-patent-subject-matter-eligibility.
25
Appeal 2015-007204
Application 11/607,828
SUMMARY
We reverse the Examiner’s rejection of claims 71—107 and 109—115
as lacking in written description.
We reverse the Examiner’s rejection of claims 71—74, 76—82, and
109-111 as directed to patent ineligible subject matter.
We affirm the Examiner’s rejection of claims 88, 91, 93, 95, 97, 99,
103, 114 as directed to patent ineligible subject matter.
TIME PERIOD FOR RESPONSE
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-IN-PART
26