AGILENT TECHNOLOGIES, INC.

Patent Trials and Appeals Board

Dec 10, 2021

2021001708 (P.T.A.B. Dec. 10, 2021)

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.
14/772,063 09/01/2015 Michael RUVOLO 20130026-02
(027644.8223)
5441
22878 7590 12/10/2021
Agilent Technologies, Inc.
Global IP Operations
5301 Stevens Creek Blvd
Santa Clara, CA 95051
EXAMINER
SISSON, BRADLEY L
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
12/10/2021 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):
Agilentdocketing@cpaglobal.com
ipopsadmin@agilent.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MICHAEL RUVOLO and EMILY MARINE LEPROUST1
Appeal 2021-001708
Application 14/772,063
Technology Center 1600
Before ERIC B.GRIMES, TINA E. HULSE, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to an
oligonucleotide-containing composition and a related kit, which have been
rejected as ineligible for patenting and anticipated. We have jurisdiction
under 35 U.S.C. § 6(b).
We REVERSE.

1 Appellant identifies the real party in interest as Agilent Technologies, Inc.
Appeal Br. 2. “Appellant” refers to “applicant” as defined in 37 C.F.R.
§ 1.42.
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Application 14/772,063

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STATEMENT OF THE CASE
“Chromosomal rearrangements, deletions, and other aberrations have
long been associated with genetic diseases.” Spec. 1:5–6. “There is an
ongoing need to develop efficient ways to make probes for use in genomics,
particular in the detection and analysis of chromosomal abnormalities.” Id.
at 1:11–12.
The Specification discloses “a method of making a pool of probes by
primer extension,” using two populations of oligonucleotides having the
formulas V1-B-3' and V2'-B'-3' (where V1, V2', B, and B' are defined in claim
12, below) that hybridize to each other and can be “extended to produce a
population of double stranded products comprising a top strand sequence
having the following formula V1-B-V2, where V2 is complementary to V2'.”
Id. at 1:15–28.
The Specification discloses that the V1-B-V2 oligonucleotides can be
used in an assay for chromosomal abnormalities:
In certain cases, the test genome may have a chromosomal
rearrangement relative to the reference genome that effectively
moves a V1-complemenary [sic] sequence to a site that is both
proximal to and on the same strand as V2-complemenary [sic]
sequence. In these cases, if a first oligonucleotide contains V1
and V2 sequences that are complementary to the sequences
moved into proximity by the rearrangement, [a] complex . . .
that comprises a single genomic fragment that is hybridized to
both ends of a first oligonucleotide is produced.
Id. at 19:14–20. Following steps of ligation and amplification, a product
indicating chromosomal rearrangement can be detected. See id. at 19:28 to
20:17.
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Claims 12–20 are on appeal.2 Claim 12, reproduced below, is
illustrative:
12. A composition of matter comprising:
a first population of oligonucleotides comprising a top
strand sequence having the following formula:
V1-B-3'; and
a second population of oligonucleotides comprising a
bottom strand sequence having the following formula:
V2'-B'-3';
wherein:
the nucleotide sequences of B and B' are
complementary and are at least 15 nucleotides in length;
the nucleotide sequence of B is the same for each
oligonucleotide of said first population;
the nucleotide sequence of B' is the same for each
oligonucleotide of said second population;
the nucleotide sequence of V1 is variable between
the oligonucleotides of the first population;
the nucleotide sequence of V2' is variable between
the oligonucleotides of the second population;
the first and second population of oligonucleotides
are capable of hybridizing to each other to produce a
population of duplexes, and
V1 and V2' hybridize to different sites in a
reference genome.
Appeal Br. 15 (Claims App.).
Claim 16 is the other independent claim and is directed to a kit
comprising the oligonucleotides defined by claim 12.

2 The Examiner has indicated that claims 1–11 are allowable. Office Action
mailed Apr. 8, 2020, page 14.
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Application 14/772,063

4
The claims stand rejected as follows:
Claims 12–20 under 35 U.S.C. § 101 as being directed to patent-
ineligible subject matter (Non-Final Action3 7) and
Claims 12–20 under 35 U.S.C. § 102(a)(2) as anticipated by Koroulis4
(Non-Final Action 11).
OPINION
Eligibility
The Examiner has rejected claims 12–20 on the basis that “the
claimed invention is directed to a judicial exception (i.e., a law of nature, a
natural phenomenon, or an abstract idea) without significantly more.” Non-
Final Action 7. The Examiner finds that “the claims are to oligonucleotides,
the nucleotide sequence of which can occur in nature,” and therefore “are
directed to a natural phenomenon.” Id.
The Examiner also finds that the claims do not recite additional
elements that integrate the judicial exception into a practical application,
because “the claims simply define the types of sequences that can be
present.” Id. at 8. Finally, the Examiner finds that the claims “do not include
additional elements that are sufficient to amount to significantly more than
the judicial exception because the oligonucleotides can be that which occurs
in nature.” Id.
Appellant argues that, in Ass’n for Molecular Pathology v. Myriad
Genetics, Inc., 569 U.S. 576 (2013),
claims to an isolated DNA having the same sequence as
naturally occurring genes were found to be ineligible products

3 Office Action mailed Apr. 8, 2020.
4 Koroulis et al., US 2002/0187476 A1, published Dec. 12, 2002.
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5
of nature. However, claims to cDNA prepared from RNA
transcribed from those same genes was eligible for patenting,
since the sequence only contained exons of the gene. Because
the recited sequence had “markedly different characteristics”
than naturally occurring sequences, it was not “directed to” a
product of nature.
Appeal Br. 7.
Appellant argues that the Examiner “did not identify any naturally
occurring counterpart for comparison to the claimed composition, and . . .
did not consider whether it had markedly different characteristics.” Id. “The
Office Action does not make any attempt to identify a naturally occurring
counterpart which has first and second populations of oligonucleotides,” as
recited in claim 12. Id. at 8. Appellant argues that, contrary to the
Examiner’s conclusion, “[t]he claimed composition is not directed to a
product of nature or any other natural phenomenon, but is man-made and not
found in nature.” Id. at 9.
Principles of Law
Section 101
Patent-eligible subject matter is defined in 35 U.S.C. § 101. An
invention is patent-eligible if it claims a “new and useful process, machine,
manufacture, or composition of matter.” 35 U.S.C. § 101. The Supreme
Court, however, has carved out exceptions to what would otherwise appear
to be within the literal scope of § 101, e.g., “[l]aws of nature [and] natural
phenomena” such as products of nature that are considered “building blocks
of human ingenuity.” Alice Corp. v. CLS Bank Int’l, 573 U.S. 208, 216
(2014) (citing Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569
U.S. 576 (2013) and Mayo Collaborative Servs. v. Prometheus Labs, Inc.,
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566 U.S. 66 (2012)). “[T]he ‘manifestations of laws of nature’ are ‘part of
the storehouse of knowledge,’ ‘free to all men and reserved exclusively to
none.’” Manual of Patent Examiner Procedure (“MPEP”) § 2106.04(b)(I)
(quoting Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130
(1948)). “When a law of nature or natural phenomenon is claimed as a
physical product, the courts have often referred to the exception as a
‘product of nature.’” MPEP § 2106.04(b)(II).
The Supreme Court has established a two-step framework for
“distinguishing patents that claim laws of nature, natural phenomena, and
abstract ideas from those that claim patent-eligible applications of those
concepts.” Alice, 573 U.S. at 217. “First, we determine whether the claims at
issue are directed to . . . [a] patent-ineligible concept[].” Id. “If so, . . . 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.” Id. (quoting Mayo,
566 U.S. at 78–79).
The United States Patent and Trademark Office (“PTO”) issued the
2019 Revised Patent Subject Matter Eligibility Guidance (“Revised
Guidance”), indicating how the PTO would analyze patent eligibility under
the Supreme Court’s two-step framework. 84 Fed. Reg. 50 (January 7,
2019). In response to received public comments, the Office issued further
guidance on October 17, 2019, clarifying the 2019 Revised Guidance.
USPTO, October 2019 Update: Subject Matter Eligibility (the “October
2019 Update”) (available at https://www.uspto.gov/sites/default/files/
documents/peg_oct_2019_update.pdf).
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Under the Revised Guidance, in determining what concept the claim
is “directed to,” we first look to whether the claim recites any judicial
exceptions, including laws of nature, natural phenomena, and/or abstract
ideas. 84 Fed. Reg. at 53–54 (“Step 2A, Prong One”). If it does, then we
look to whether the claim recites additional elements that integrate the
recited judicial exception into a practical application. Id. at 54–55 (citing
MPEP § 2106.05(a)–(c), (e)–(h)) (“Step 2A, Prong Two”).
Only if a claim (1) recites a judicial exception and (2) does not
integrate that exception into a practical application, i.e., it is found to be
“directed to” a judicial exception, do we then look to whether the claim
contains an “‘inventive concept’ sufficient to ‘transform’” the claimed
judicial exception into a patent-eligible application of the judicial exception.
84 Fed. Reg. at 56; see also Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S.
at 82).
Claims alleged to be patent-ineligible because they recite products of
nature are properly analyzed under the framework of the Revised Guidance.
See 84 Fed. Reg. at 54 n.20 (“This notice does not change the type of claim
limitations that are considered to recite a law of nature or natural
phenomenon. For more information about laws of nature and natural
phenomena, including products of nature, see MPEP 2106.04(b) and (c).”).
Revised Guidance Step 2(A), Prong 1
Following the Revised Guidance, we first consider whether the claims
recite a judicial exception; i.e., whether they set forth or describe a product
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of nature in accordance with the guidance in MPEP § 2106.04(b) and (c).
Revised Guidance, 84 Fed. Reg. at 54; October 2019 Update, at 1.
Each of independent claims 12 and 16 recites a first population of
oligonucleotides V1-B-3' having a common B sequence and a variable V1
sequence, and a second population of oligonucleotides V2'-B'-3' having a
common B' sequence and a variable V2' sequence, where B and B' are
complementary and at least 15 nucleotides long, and where V1 and V2'
hybridize to different sites in a reference genome.
As Appellant pointed out (Appeal Br. 7), the Examiner has not
identified any naturally occurring populations of oligonucleotides that meet
the structural requirements recited in Appellant’s claims. The fact that some
oligonucleotides are naturally occurring is not sufficient to show that the
combination of specific oligonucleotides of Appellant’s claims are naturally
occurring.
In Myriad, for example, the Supreme Court distinguished between
naturally occurring and non-naturally occurring DNAs. Myriad “assert[ed] a
patent on ‘[a]n isolated DNA coding for a BRCA1 polypeptide,’ which has
‘the amino acid sequence set forth in SEQ ID NO:2.’” 569 U.S. at 584. The
Court held that the DNA recited in this claim was not eligible for patenting
because “Myriad did not create anything. To be sure, it found an important
and useful gene, but separating that gene from its surrounding genetic
material is not an act of invention.” Id. at 591.
The Myriad Court also held, however, that “cDNA does not present
the same obstacles to patentability as naturally occurring, isolated DNA
segments” because a cDNA is “an exons-only molecule that is not naturally
occurring.” Id. at 594. The Court reasoned that “the lab technician
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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.” Id. at 595.
The same reasoning applies here: the V1 and V2' segments recited in
Appellant’s claims might have the same sequence of nucleotides as found in
a naturally occurring genome (since they hybridize to a reference genome)
but the Examiner has not shown that a population of such segments—having
variable sequences—are naturally found next to a common B or B' sequence
in their natural state. Thus, on this record, the Examiner has not shown that
either the first or second population of oligonucleotides V1-B-3' or V2'-B'-3',
having a common B or B' sequence and a variable V1 or V2' sequence, is a
product of nature, much less the combination of those oligonucleotides, as
recited in Appellant’s claim 12.
“If the claim does not recite a judicial exception, it is not directed to a
judicial exception . . . and is eligible. This concludes the eligibility analysis.”
Revised Guidance, 84 Fed. Reg. at 54. We reverse the rejection of claims
12–20 under 35 U.S.C. § 101.
Anticipation
The Examiner has rejected claims 12–20 as anticipated by Koroulis.
The Examiner finds that Koroulis discloses arrays containing
oligonucleotides, and also states that its “array can contain all possible
oligonucleotides of a given length n.” Non-Final Action 11–12. The
Examiner reasons that, “[g]iven that the composition/array of Koroulis et al.,
encompasses all possible oligonucleotides of a length n, such must
encompass the very oligonucleotides present in the claimed composition and
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kit, including that represented by the formulae of V1-B-3' and V2'-B'-3'.” Id.
at 12.
Appellant argues that the Examiner “relies on Koroulis’ single,
generic sentence that ‘an array can contain all possible oligonucleotides of a
given length n.’ However, . . . [t]he Office Action makes no attempt to
identify where Koroulis discloses the particular claim elements recited by
the rejected claims.” Appeal Br. 12. Appellant argues that, in fact, “Koroulis
does not disclose a composition of matter or a kit having a first and second
population of oligonucleotides” having the structural characteristics recited
in Appellant’s claims 12 and 16. Id. at 12–13.
We agree with Appellant that the Examiner has not persuasively
shown that Koroulis discloses the composition or kit of Appellant’s claims.
“[T]he examiner bears the initial burden, on review of the prior art or on any
other ground, of presenting a prima facie case of unpatentability.” In re
Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
[U]nless a reference discloses within the four corners of the
document not only all of the limitations claimed but also all of
the limitations arranged or combined in the same way as recited
in the claim, it cannot be said to prove prior invention of the
thing claimed and, thus, cannot anticipate under 35 U.S.C.
§ 102.
Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008).
In this case, the Examiner relies solely on the following disclosure:
An array can contain a chosen collection of oligonucleotides,
e.g., probes specific for all known clinically important
pathogens or specific for all known clinically important
pathogens or specific for all known sequence markers of
genetic diseases. Such an array can satisfy the needs of a
diagnostic laboratory. Alternatively, an array can contain all
possible oligonucleotides of a given length n.
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Koroulis ¶ 6. The Examiner reasons that “[g]iven that the composition/array
of Koroulis et al., encompasses all possible oligonucleotides of a length n,
such must encompass the very oligonucleotides present in the claimed
composition and kit.” Non-Final Action 12.
We do not agree with the Examiner’s reasoning. The bare statement
that an array can include all possible nucleotides having an undefined length
is not a disclosure of the two populations of oligonucleotides—having
segments meeting specified structural requirements, arranged in a specified
way—that are recited in Appellant’s claims. Thus, the cited disclosure
“cannot be said to prove prior invention of the thing claimed and, thus,
cannot anticipate under 35 U.S.C. § 102.” Net MoneyIN, 454 F.3d at 1371.
We conclude that the Examiner has not met the initial burden of
showing that Koroulis discloses “all of the limitations arranged or combined
in the same way as recited in the claim[s],” id., and has not made out a prima
facie case of anticipation. The rejection of claims 12–20 under 35 U.S.C.
§ 102(a)(2) is reversed.
DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
12–20 101 Eligibility 12–20
12–20 102(a)(2) Koroulis 12–20
Overall
Outcome
12–20

REVERSED