Ex Parte Danenberg

Patent Trial and Appeal Board

Dec 10, 2012

10426836 (P.T.A.B. Dec. 10, 2012)

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.
10/426,836 05/01/2003 Kathleen D. Danenberg 11220/169 9906
23838 7590 12/11/2012
KENYON & KENYON LLP
1500 K STREET N.W.
SUITE 700
WASHINGTON, DC 20005
EXAMINER
MUMMERT, STEPHANIE KANE
ART UNIT PAPER NUMBER
1637
MAIL DATE DELIVERY MODE
12/11/2012 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte KATHLEEN D. DANENBERG
__________

Appeal 2012-002357
Application 10/426,836
Technology Center 1600
__________

Before TONI R. SCHEINER, STEPHEN WALSH, and
JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) from the rejection of
claims directed to a method for determining the level of epidermal growth
factor receptor expression in a tissue sample. The Patent Examiner rejected
the claims on non-statutory obviousness-type double patenting grounds. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm.
Appeal 2012-002357
Application 10/426,836

2
STATEMENT OF THE CASE
Claims 13 and 25 are on appeal. The claims read:
13. A method for determining the level of EGFR expression in a fixed
paraffin-embedded tissue sample comprising:
(a) deparaffinizing the tissue sample to obtain a deparaffinized
sample;
(b) isolating mRNA from the deparaffinized sample by first heating
the tissue sample in a solution comprising an effective concentration
of a chaotropic compound to a temperature in the range of 75 to about
100°C for a time period of 5 to 120 minutes and recovering the
mRNA from the chaotropic solution;
(c) subjecting the mRNA to reverse transcriptase-polymerase chain
reaction (RTPCR) amplification using a pair of oligonucleotide
primers that are capable of amplifying a region of the EGFR gene to
obtain an amplified sample, wherein the pair of oligonucleotide
primers have the sequences represented by SEQ ID NO:1 and SEQ ID
NO:2; and
(d) determining the quantity of EGFR mRNA relative to the
quantity of mRNA of an internal control gene.

25. The method of claim 13, wherein the internal control gene is the
β-actin gene.

The Examiner rejected the claims as follows:
I. claims l3 and 25 on the ground of nonstatutory obviousness-type
double patenting as unpatentable over claims 1 and 22 of US
6,610,488 B21 in view of Shum,2 Ullrich (abstract only),3 and Buck;4
and

1 Kathleen Danenberg et al., US 6,610,488 B2, Aug. 26, 2003.
2 Lillian Shum et al., EGF abrogation induced fusilli-form
dysmorphogenesis of Meckel’s cartilage during embryonic mouse
mandibular morphogenesis in vitro, 118 DEVELOPMENT 903-917 (1993).
Appeal 2012-002357
Application 10/426,836

3
II. claims 13 and 25 on the ground of nonstatutory obviousness-type
double patenting as unpatentable over claims 1, 2, and 26 of US
6,428,963 B25 in view of Shum, Ullrich, and Buck.

DISCUSSION
Findings of Fact
1. We adopt the Examiner’s findings concerning the scope and content
of the prior art. The following facts are repeated for reference
convenience.
2. Claim 22 in the Danenberg ‘488 patent reads:
22. A method for recovering RNA from a formalin-fixed paraffin-
embedded biological tissue sample comprising:
deparaffinizing the sample;
heating the sample in a chaotropic solution comprising an
effective concentration of a guanidinium compound to a temperature
in the range of about 50 to about 100° C. for a time period of about 5
to about 120 minutes; and
recovering said RNA from said chaotropic solution, wherein the
RNA recovered from the chaotropic solution is suitable to determine
the level of gene expression by reverse transcription, polymerase
chain reaction (RT-PCR) amplification.

(Danenberg ‘488, col. 16.)
3. Claim 26 in the Danenberg ‘963 patent reads:

3 A. Ullrich et al., Human epidermal growth factor receptor cDNA sequence
and aberrant expression of the amplified gene in A431 epidermoid
carcinoma cells, 309 NATURE 418-425 (1984).
4 G.A. Buck et al., Design Strategies and Performance of Custom DNA
Sequencing Primers, 27 BIOTECHNIQUE 528-536 (1999).
5 Kathleen Danenberg et al., US 6,428,963 B2, Aug. 6, 2002.
Appeal 2012-002357
Application 10/426,836

4
26. A method for recovering RNA from a biological tissue sample
wherein the sample is not an aqueous sample of a bodily fluid,
comprising:
heating the sample in a chaotropic solution comprising an
effective concentration of a guanidinium compound to a temperature
in the range of about 75 to about 100° C. for a time period of about 5
to about 120 minutes; and
recovering said RNA from said chaotropic solution, wherein the
RNA recovered from the chaotropic solution is suitable to determine
the level of gene expression by reverse transcription, polymerase
chain reaction (RT-PCR) amplification.

(Danenberg ‘963, col. 16.)
4. The legend for Shum’s Figure 2 states in part:
Adult mouse salivary gland EGF, EGFr and beta-actin RT-PCR
products were used as positive controls, and RT-PCR amplification of
DEPC water for EGF and E10 mandibles for insulin were used as
negative controls (data not shown).

(Shum 908.)
5. The legend for Shum’s Figure 3 states in part:
The relative level of EGF precursor mRNA per mandible cell (see
Slavkin et al., 1989) is shown in B and D and is based on a
comparison with internal EGF precursor mRNA standards obtained
from adult male mouse submaxillary gland. Comparable data were
also obtained using relative units EGF transcripts to beta-actin
transcripts.

(Id.)
6. Buck disclosed: “The results of the empirical sequencing analysis
were surprising in that nearly all of the primers yielded data of
extremely high quality.” (Buck 535.)

Appeal 2012-002357
Application 10/426,836

5

Analysis
The Examiner and Appellant agree that Danenberg ‘488 claims 1 and
22 differ from appealed claims 13 and 25 by

(1) not reciting subjecting the mRNA to RT-PCR amplification using
a primer pair of SEQ ID NOs: 1 and 2 as recited in step (c) of the
pending claim 13; and
(2) not reciting determining the quantity of EGFR mRNA relative to
the quantity of mRNA of an internal control gene as recited in step (d)
of the pending claim 13.

(App. Br. 9; Ans. 5-6.)
The Examiner found that (i) Shum described extracting mRNA from
tissue and determining the level of EGFR expression by RT-PCR using β-
actin as a control, (ii) Ullrich provided the full sequence of human EGFR
cDNA, comprising SEQ ID NOs:1 and 2 (via GenBank Accession No.
X00588), and (iii) Buck evidenced that any primer selected according to
ordinary criteria from a known sequence would be expected to function.
The Examiner concluded: “Considering the teachings of Shum, it would
have been prima facie obvious at the time the invention was made to have
extended the broad and generic method claimed in the ‘488 patent to arrive
at the claims of the instant application.” (Ans. 6.) Danenberg ‘488 claim 22
explicitly states that the RNA produced in its method “is suitable to
determine the level of gene expression by reverse transcription, polymerase
chain reaction (RT-PCR) amplification.” (FF 2.) It was therefore
reasonable to conclude that applying the RT-PCR method to EGFR gene
expression determination would be a reasonable extension in view of Shum.
Appeal 2012-002357
Application 10/426,836

6
Appellant contends that by “[u]sing beta-actin in two different roles:
as internal control and as positive control for EGFr without detailed
explanation, it is not clear how Shum used beta-actin in the two roles.”
(App. Br. 10, citing Shum’s Methods and Materials, and the legends to
Shum’s Figures 2 and 3.) Appellant argues that because Shum did not
disclose determining the quantity of EGFR mRNA relative to the quantity of
β-actin mRNA, “Shum does not cure the lack of recitation” in claims 1 and
22 of the ‘488 patent. (Id.) The Examiner found this argument
unpersuasive, responding: “Again, in the legend to [Shum’s] Figure 3 it is
noted that transcript levels were measured relative to beta actin transcript,
which fits the meaning of determining expression relative to an internal
control as claimed and as argued by Appellant.” (Ans. 13.) We conclude
that although Shum did not literally recite claim 13(d)’s phrasing
“determining the quantity of EGFR mRNA relative to the quantity of mRNA
of an internal control gene,” the Examiner’s reasoning is supported by what
Shum did recite. (See FF 4 and 5.)
Appellant next objects that the ‘488 patent claims do not recite
performing RT-PCR using the primer pair of SEQ ID NOs: 1 and 2. (App.
Br. 11.) According to Appellant, “Ullrich, Shum and Buck do not provide
any guidance to lead one of ordinary skill in the art to select, among the
5532 bp of [Ulrich’s] EGFR cDNA, an oligonucleotide sequence in
positions 1753 to 1770 of the human EGFR cDNA [SEQ ID NO:1] to be
paired with another oligonucleotide sequence in positions 1823 to 1804
[SEQ ID NO:2].” (Id. at 12.) Further, “the process of optimization and
routine experimentation by placing primers ‘throughout the region of
interest,’ i.e., the cDNA of human EFGR, ‘to arrive at the most robust and
Appeal 2012-002357
Application 10/426,836

7
consistent PCR product’ as put forth by the Final Office Action requires
testing an astronomical number of potential primer pairs” (id.), and the
references do not guide the selection of SEQ ID NOs: 1 and 2 from the
astronomical number that could be made (id. at 13).
The Examiner responds that Shum’s use of a different pair of primers
is a clear indication that other primers would be useful for amplifying EGFR
sequences. (Ans. 15.) According to the Examiner, a person of ordinary skill
in the art would understand how to design primers (id.), and “it is not
inventive to design a single pair of primers capable of amplifying a sequence
of [EGFR’s] length, even for the purposes of RT-PCR” (id. at 16). The
Examiner finds that number of potential primers is 5513, “not
insurmountable or ‘astronomical,’” and given Buck’s guidance, the pool of
potential primers would be smaller, and only routine experimentation would
be required. (Id. at 16-17.) The Examiner reiterates that “Buck provides
clear evidence of the equivalence of primers.” (Id. at 17.)
Buck investigated primer selection strategies, and reported that nearly
all primers chosen according to known strategies yielded high quality data.
(FF 6.) We find the Examiner’s evidence-based rebuttal of Appellant’s
attorney argument persuasive. The evidence demonstrates that a person of
ordinary skill in the art would not have required additional guidance to
choose a primer pair. Moreover, Appellant does not allege there is any
criticality or unexpected result associated with SEQ ID NOs:1 and 2. Based
on the rejection’s findings, we conclude that, contrary to Appellant’s
contentions, there would have been a reasonable expectation of success in
choosing primers from the known EGFR sequence. The selection of SEQ
ID NO:s 1 and 2 as primers would have followed from the routine
Appeal 2012-002357
Application 10/426,836

8
application of the prior art’s guidance. “Obviousness does not require
absolute predictability of success ... all that is required is a reasonable
expectation of success.” In re Droge, 695 F.3d 1334, 1338 (Fed. Cir. 2012)
(quoting In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re
O'Farrell, 853 F.2d 894, 903–04 (Fed.Cir.1988)).
In contesting the second rejection, Appellant relies on the same
arguments, which we have already concluded are unpersuasive against the
Examiner’s evidence. (See App. Br. 16.)

SUMMARY
We affirm the rejection of claims l3 and 25 on the ground of
nonstatutory obviousness-type double patenting as unpatentable over claims
1 and 22 of U.S. Patent No. 6,610,488 in view of Shum, Ullrich, and Buck;
and
We affirm the rejection of claims 13 and 25 on the ground of
nonstatutory obviousness-type double patenting as unpatentable over claims
1, 2, and 26 of U.S. Patent No. 6,428,963 in view of Shum, Ullrich, and
Buck.
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

lp