VIB VZW et al.

Patent Trials and Appeals Board

Mar 10, 2021

2020006186 (P.T.A.B. Mar. 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.
15/555,752 09/05/2017 Diether LAMBRECHTS 1781-0017US01 2251
137713 7590 03/10/2021
Potomac Law Group, PLLC
8229 Boone Boulevard
Suite 430
Vienna, VA 22182
EXAMINER
HANEY, AMANDA MARIE
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
03/10/2021 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):
eofficeaction@appcoll.com
patents@potomaclaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte DIETHER LAMBRECHTS and BERNARD THIENPONT
____________

Appeal 2020-006186
Application 15/555,752
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and
DAVID COTTA, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134(a) involving claims to a
method of determining tumor hypoxia in a human breast cancer patient. The
examiner rejected the claims as containing an improper Markush group and

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a). Appellant identifies the real parties in interest as VZW,
Katholieke Universiteit Leuven, and Life Sciences Research Partners VZW
(Appeal Br. 2). We have considered the Specification of Sept. 5, 2017
(“Spec.”); Final Office action of Sept. 23, 2019 (“Final Act.”); Appeal Brief
of Feb. 13, 2020 (“Appeal Br.”); Examiner’s Answer of July 1, 2020
(“Ans.”); and Reply Brief of Aug. 31, 2020 (“Reply Br.”). An oral hearing
was held March 4, 2021, a transcript from which will be entered into the
record.
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as reciting non-statutory subject matter. We have jurisdiction under
35 U.S.C. § 6(b). We affirm-in-part.
Statement of the Case
Background
“Most cancers originate from a single cell that starts to behave
abnormally due to the acquisition of somatic mutations” (Spec. 1:11–12).
“[T]umors are also epigenetically distinct from their tissue of origin. The
most established epigenetic alterations are at the level of DNA methylation”
(id. at 13–14).
Although DNA hypermethylation and hypoxia are widely
recognized as cancer hallmarks, the impact of hypoxia on TET
hydroxylase activity and subsequent DNA (de)methylation has
not been assessed. We here unravel a new mechanism in which
hypoxia decreases TET hydroxylase activity, leading to an
accumulation of 5mC and the acquisition of tumor
epimutations.
(id. at 2:29–32). “[T]reatment of various tumor models . . . can cause a
persistent switch to ‘vasoinvasion’, leading to increased metastasis. Tumor
hypoxia generally has been considered as a driver of this increased escape
behavior” (id. at 26:24–26). “The invention described here by which
hypermethylation accumulates under hypoxia could thus also be underlying
these escape mechanisms” (id. at 26:26–29).
The Claims
Claims 8–13, 16, 22, and 23 are on appeal. Independent claim 8 is
representative and reads as follows:
8. A method of determining tumor hypoxia in a human
breast cancer patient, comprising:
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obtaining a sample comprising tumor DNA from the
human breast cancer patient, wherein the tumor DNA
comprises one or more promoters of tumor suppressor genes;
assaying the sample to determine the methylation status
of the promoter of a tumor suppressor gene selected from the
group consisting of the genes KDM6A, NF2, KDM5C,
IGFBP2, ARNT2, PTEN, ATM, MLH1, BRCA1, SEMA3B,
THBD, and CLDN3; and
detecting hypoxia in the breast tumor of the human breast
cancer patient when the promoter of the tumor suppressor gene
is hypermethylated in the sample in comparison to the
methylation level of the promoter of the same tumor suppressor
gene in a normoxic control sample matched or unmatched to the
sample comprising tumor DNA from the human breast cancer
patient.

The Issues
A. The Examiner rejected claims 8–13 and 16 as unpatentable under
35 U.S.C. § 101 as directed to non-statutory subject matter (Final Act. 3–5).
B. The Examiner rejected claims 8–13, 16, 22, and 23 as containing an
improper Markush grouping of alternatives (Final Act. 8–10).

A. 35 U.S.C. § 101
Appellant does not provide any arguments regarding the rejection of
claims 8–13 and 16 under 35 U.S.C. § 101 as being directed to patent-
ineligible subject matter (see Appeal Br. 4 “The present appeal is not
directed to the final rejection of claims 8–13 and 16 under Section 101.”) If
a ground of rejection stated by the Examiner is not addressed in the
Appellant’s Appeal Brief, Appellant has waived any challenge to that
ground of rejection and the Board may summarily sustain it. See Manual of
Patent Examining Procedure (MPEP) § 1205.02. See also Hyatt v. Dudas,
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551 F.3d 1307, 1314 (Fed. Cir. 2008) (“When the appellant fails to contest a
ground of rejection to the Board . . . the Board may treat any argument with
respect to that ground of rejection as waived.”)
B. Improper Markush grouping
The Examiner finds:
The Markush grouping of “a tumor suppressor gene selected
from the group consisting of the genes KDM6A, NF2,
KDM5C, IGFBP2, ARNT2, PTEN, ATM, MLH1, BRCA1,
SEMA3B, THBD, or CLDN3” is improper because the
alternatives defined by the Markush grouping do not share both
a single structural similarity and a common use.
(Final Act. 9). The Examiner finds the tumor suppressor genes recited in the
claims were not a “recognized class because the prior art does not teach that
it was well known that each of the recited genes could be substituted for
each other with the expectation that the intended result of being able to
detect tumor hypoxia in a human breast cancer patient would occur” (id. at
10). The Examiner also finds the “recited genes do not share both a
substantial structural feature and a common use that flows from the
substantial structural feature” (id.). The Examiner finds “the shared
structure of nucleotides is not essential to the common use of detecting
tumor hypoxia since not all genes made up of nucleotides could be used to
detect tumor hypoxia” (id.).
Appellant contends the “improper Markush rejection should be
reversed because (1) the alternative genes are all members of the same
chemical class, and (2) the alternative genes share a substantial structural
feature and a common use that flows from the substantial structural feature”
(Appeal Br. 4).
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Appellant contends, regarding structural similarity, that “genes belong
to the same chemical class, because they are chains of the same 4 repeating
units that simply occur in a different order” (Appeal Br. 5). Appellant
further contends the “chemical moieties do not vary between the 12
alternative genes. While the information content of the 12 alternative genes
(i.e., the protein coded by each) varies, it is self-evident that the gene
structures are strikingly similar” (id.).
Appellant contends
the 12 alternative genes share a common use. In fact, there are
two shared common uses:
• First, the 12 alternative genes share the use of tumor
suppression.
• Second, as discovered by the inventors, the genes share
the use of assaying the methylation status of promoters of the
12 genes to determine tumor hypoxia.

(Appeal Br. 6). Appellant also contends, as to common use, that the prior art
“refers to the common use as tumor suppressor genes” and the “common use
of assaying the methylation status of promoters of the 12 genes as an
alternative way for determining tumor hypoxia is disclosed in the
specification” (id.). Appellant contends “the present specification makes the
relevant disclosure. As such, it is irrelevant whether or not the prior art
makes the relevant disclosure” (id. at 7).
Principles of Law
A Markush claim contains an “improper Markush
grouping” if: (1) the species of the Markush group do not share
a “single structural similarity,” or (2) the species do not share a
common use. Members of a Markush group share a “single
structural similarity” when they belong to the same recognized
physical or chemical class or to the same art-recognized class.
Members of a Markush group share a common use when they
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are disclosed in the specification or known in the art to be
functionally equivalent.
Supplementary Examination Guidelines for Determining Compliance With
35 U.S.C. 112 and for Treatment of Related Issues In Patent Applications,
76 Fed. Reg. 7162, 7166 (2011) (“Guidelines”).
Thus, a Markush grouping is ordinarily proper if all the
members of the group belong to a recognized class (whether
physical, chemical, or art recognized) and are disclosed in the
specification to possess at least one property in common which
is mainly responsible for their function in the claimed
invention, and it is clear from their very nature or from the prior
art that all members possess this property.
(MPEP § 2117 (II)(A)).
Analysis
We begin with claim interpretation because before a claim is properly
interpreted, its scope cannot be analyzed. In particular, we are concerned
with interpretation of what are the components of the Markush group at
issue in the claims. Claim 8 recites the step of “assaying the sample to
determine the methylation status of the promoter of a tumor suppressor gene
selected from the group consisting of the genes KDM6A, NF2, KDM5C,
IGFBP2, ARNT2, PTEN, ATM, MLH1, BRCA1, SEMA3B, THBD, and
CLDN3.”
The Examiner understands the Markush group to be the recited genes
while Appellant contends the Markush group is the “promotors of the recited
tumor suppressor genes” (Final Act. 9; Reply Br. 5).
We agree with Appellant that the claims are drawn to promoter
regions and not to the genes themselves. The recited promoter regions do
share common structure, not only because they necessarily comprise a CpG
region that may be methylated, but because human core promoter regions
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comprise at least an RNA polymerase binding site, and a transcription start
site. Thus, promoters of genes such as those recited in the instant claims
share not only the common function of methylation control of gene
expression but also share structural similarities including specific sequence
similarities. The Examiner provides no evidence that any of these promoters
lacks the physical structures of either CpG, an RNA polymerase binding
region, or a transcription start site. Thus, this is not a situation where the
genes themselves are at issue.2
Consequently, because in this particular fact situation the claimed
promoters share both a common function and common structure, including
common sequences necessarily present in these promoters such as a RNA
polymerase binding region, transcription start sites, and CpG, we conclude
that this Markush group is proper.

2 We do agree with the Examiner that Ex Parte Chettier, 2016 WL 4487978
(PTAB 2016) persuasively explains that genes,
like all DNA sequences, are made up of the same four bases,
they do not share any significant similarity in the order in which
those bases are arranged. Thus, the structures of the DNA
molecules represented by the sequences are different. We
therefore agree with the Examiner that the 133 DNA sequences
shown in the Specification’s Table 1 do not make up a proper
Markush group.
(Chettier at 3). We do not agree with Appellant that claims drawn solely to
different coding sequences or arbitrary different DNA sequences with no
structural similarity would necessarily form a proper Markush group solely
based on the shared deoxyribose-phosphate backbone (see, e.g., Appeal Br.
5).
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DECISION SUMMARY

In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
8–13, 16 101 Eligibility 8–13, 16
8–13, 16,
22, 23
101 Improper Markush 8–13, 16,
22, 23
Overall
Outcome
8–13, 16 22, 23

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