Ex Parte Hogrefe et al

Patent Trial and Appeal Board

Jun 30, 2016

10208508 (P.T.A.B. Jun. 30, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/208,508 07/30/2002
22878 7590 07/05/2016
Agilent Technologies, Inc, in care of:
CPA Global
P. 0. Box 52050
Minneapolis, MN 55402
FIRST NAMED INVENTOR
Holly Hogrefe
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
10070544-01 3960
EXAMINER
HUTSON, RICHARD G
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
07/05/2016 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):
IPOPS.LEGAL@agilent.com
Agilentdocketing@cpaglobal.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HOLLY HOGREFE, MICHAEL BORNS, and JOSEPH SORGE
Appeal2013-008687
Application 10/208,508
Technology Center 1600
Before ERIC B. GRIMES, MELANIE L. McCOLLUM, and TA WEN
CHANG, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to isolated
polynucleotide encoding a mutant DNA polymerase, which have been
rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
STATEMENT OF THE CASE
"DNA polymerases catalyze the synthesis of DNA." (Spec. 1: 11.)
Although all DNA polymerase possess 5'-3' DNA polymerization activity,
only some DNA polymerases also possess 3 '-5' endonuclease activity,
sometimes referred to as the "proofreading" activity. (Id. at 1: 12-17, 2:4.)
Appeal2013-008687
Application 10/208,508
The Specification states that, while such "high fidelity" polymerases
increase the accuracy of DNA synthesis, they usually do not amplify long
DNA fragments as efficiently as a DNA polymerase lacking a 3'-5'
exonuclease activity. (Id. 2:7-15.) The Specification further states that,
while combining a standard polymerase with a small amount of proofreading
polymerase may provide a balance between fidelity and yield, "the high
polymerization activity result[ing] from combining [] two DNA polymerases
may [also] inhibit the efficiency and therefore the yield of the amplification
reaction." (Id. at 2:27-29.)
According to the Specification, therefore, there is a need for "new
methods and compositions which improve polymerization fidelity [while]
reduc[ing] the side effects result[ing] from having high polymerization
activity in the reaction." (Id. at 3: 5-7.) Further according to the
Specification, this goal may be accomplished by providing an enzyme
mixture for DNA synthesis where the first enzyme has DNA polymerization
activity and the second enzyme has 3 '-5' exonuclease activity and a reduced
DNA polymerization activity. (Id. at 3:9-12.)
Claims 20-22, 25, 27--47 are on appeal. Claim 20 is illustrative and
read as follows:
20. An isolated polynucleotide encoding a mutant DNA
polymerase, wherein said mutant DNA polymerase is a mutated
version of a wild type DNA polymerase, said wild type DNA
polymerase comprising the partitioning domain sequence
YXGG (SEQ ID N0:6), the polymerase domain sequence
DXXSL YP (SEQ ID NO: 1) or DFRAL YP (SEQ ID NO: 13),
the polymerase domain sequence YXDTDS (SEQ ID N0:4),
YIDTDG (SEQ ID NO: 15), Y ADTDG (SEQ ID NO: 16), or
YSDTDG (SEQ ID NO: 17), and the polymerase domain
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Appeal2013-008687
Application 10/208,508
sequence KXY, and wherein said mutant DNA polymerase
comprises two or more amino acid substitutions at an amino
acid position selected from the group consisting of amino acid
positions corresponding to: T542, D543, K593, Y595, Y385,
G387, G388 and Y410 of the Pfu DNA polymerase comprising
the amino acid sequence of SEQ ID NO: 19, wherein said
mutant DNA polymerase possesses 3 '-5' exonuclease activity
and a 5 '-3' DNA polymerization activity that is less than 10%
as compared to the wild type DNA polymerase,
wherein if the amino acid position corresponds to Y3 85
of SEQ ID NO: 19, the substitution is selected from Y385N,
Y385L, Y385H, Y385Q, and Y385S,
wherein if the amino acid position corresponds to G387
of SEQ ID NO: 19, the substitution is selected from G387S and
G387P, and
wherein if the amino acid position corresponds to G388
of SEQ ID NO: 19, the substitution is selected from G388A and
G388P.
Claim 22 is similar to claim 20 but requires only a single substitution
at a position selected from Y410, T542, D543, K593, Y595, and G388,
"wherein if the amino acid position corresponds to G388 of SEQ ID NO: 19,
the substitution is selected from G388A and G388P."
3
Appeal2013-008687
Application 10/208,508
The claims stand rejected as follows: 1
Claims 20-22, 25, and 27--47 are rejected under 35 U.S.C. § 103(a) as
being unpatentable over Truniger. 2
DISCUSSION
Issue
The Examiner has rejected claims 20-22, 25, and 27--47 under
35 U.S.C. 103(a) as being unpatentable over Truniger. (Ans. 5.)
The Examiner finds that Truniger teaches
a polynucleotide ... encod[ing] a mutant DNA polymerase,
wherein said ... polymerase is a mutated version of a wild-type
DNA polymerase having the domains SEQ ID N0:6, SEQ ID
NO: 1 or 13, SEQ ID N0:4, 15, 16 or 17 and the polymerase
domain KXY, wherein the mutant DNA polymerase comprises
a substitution at an amino acid position Y385, G387 and G388
of the Pfu DNA polymerase of SEQ ID NO: 19 and wherein
said polymerase has 3 '-5' exonuclease activity and altered 5'-
3' DNA polymerization activity as compared to the wild-type
DNA polymerase ....
1 Appellants state in the Reply Brief that claim 26 stands as allowed in light
of the Examiner's withdrawal of the anticipation rejection and request the
Board to so indicate. (Reply Br. 2.) We decline to do so and note that there
appears to be some confusion as to whether claim 26 is subject to the
35 U.S.C. § 103 rejection: Appellants indicated in the Appeal Briefthat
with respect to that rejection claim 26 stands or falls with independent claim
20. (Appeal Br. 24.) In any event, claim 26 currently depends from a
rejected claim. Thus, we leave it to the Examiner to determine the
appropriate course of action with respect to claim 26.
2 Veronica Truniger et al., A DNA binding motif coordinating synthesis and
degradation in proofreading DNA polymerases, 15 The EMBO J. 3430-
3441 (1996).
4
Appeal2013-008687
Application 10/208,508
(Id. at 6.)
The Examiner did not find Truniger to teach a mutant DNA
polymerase comprising multiple amino acid substitutions. However, the
Examiner concludes that a skilled artisan would have been motivated to
create a cp29 DNA polymerase comprising multiple substitutions at amino
acid positions corresponding to G388, G387, and Y385 of the Pfu DNA
polymerase, in order to further characterize the role of the "Y xGG/ A" motif
in coordinating DNA polymerase synthetic and degradative activities. (Id. at
7.) For the same reason, the Examiner concluded that a skilled artisan also
would have been motivated to mutate residues at these positions to all
possible amino acid substitutions, thus making obvious claims reciting
particular mutations. (Id.) The Examiner concludes that there would have
been a high expectation of success in generating the claimed mutant DNAs
in light of the high degree of knowledge in the art and Truniger' s teachings
regarding the methods of mutagenesis. (Id.) The Examiner further
concludes that the claimed level of polymerase activity would be inherent.
(Id. at 10.)
Appellants contend that, in light of Truniger' s teachings, a skilled
artisan would have no reasonable expectation of achieving a mutant
polymerase having the claimed level of polymerization activity. (Appeal Br.
24--29.) Appellants also contend that inherency of a claimed property does
not render a claim obvious unless the inherent property was known at the
time of the filing of the patent application. (Reply Br. 3--4.)
5
Appeal2013-008687
Application I 0/208,508
Claims 20 and 22 are representative. 3 Thus, the issue with respect to
this rejection is whether the evidence of record supports the conclusion that
a skilled artisan would have had a reasonable expectation of success in
creating the mutant DNA polymerase recited in claims 20 and 22.
Findings of Fact
FFI. Fig. IA of Truniger is excerpted below:
f~ ... ~:~-:rinin~~~ d(~:ff~~~~n
~""""'-·-·-·-·-·-···--· ................................................................... ) ~............................................................ .-.-.-. .-................................................................ . . . . . . . . . . . . . . . . . . . . .................. -~
~:~'.'.~!;:~~~~:'.~:~~~~w~~;:~0~~~::1~rl~~:~~~~~:~~~~~~~~I~~~~:=~~?~~~;~~~~~cL~
J -~- .~r" ~:):{:.-.~-::~$;~( ~~~{~~{(' {}/VA p{~(~:~-=~~:~-~~~j.:$8~\:~.~~
Fig. IA of Truniger depicts the "modular organization of enzymatic
activities in cp29 DNA polymerase." (Truniger Fig. IA.)
FF2. Truniger teaches that the "'YxGG/ A' motif, located in the
connecting region between the N-terminal and C-terminal domains, has a
primary role in DNA binding, playing a critical role in the coordination or
cross-talk between synthesis and degradation." (Id. at Abstract.)
FF3. Truniger teaches studying "the functional significance of the
conserved motif 'YxGG/A' located between the 3 '-5' exonuclease and
3 "With respect to the rejection under 35 U.S.C. § I03, independent claim 20
and its dependent claims 2I, 25, 26, 28, 30, 4I, and 42 stand or fall together,
and independent claims 22 and 32 and their dependent claims 27, 29, 3 I,
33--40, and 43--47 stand or fall together." (Appeal Br. 24.)
6
Appeal2013-008687
Application 10/208,508
polymerization domains of eukaryotic-type DNA polymerases ... by site-
directed mutagenesis in cp29 DNA polymerase." (Id.)
FF4. Truniger teaches single amino acid substitutions at the
"YxGG/ A" motif of cp29 DNA polymerase, which produced
(Id.)
mutants [that] showed an altered polymerase/3 '-5' exonuclease
balance on a template/primer DNA structure, giving rise to
three different mutant phenotypes: (i) favored polymerization
(high pol/exo ratio); (ii) favored exonucleolysis (low pol/exo
ratio); and (iii) favored exonucleolysis and null polymerization.
FF5. Table I of Truniger is excerpted below:
........................................................................................................................................................................................................................................................................................................................................................... ..-.-.-----.---.---.---.---.---.---.---.---.---.---.---.---.---.---.---.---.---.---.---.---.---.----------------------------------------""----------~------··~ ~-
t~:i:'.rnu-d~~·di.i.:- P>.)Ve-~n:.. P rnt~v:.:
~·~k"!··t)''P~~ WO Eli() ~00 IW ~~*) ;
!?2130 148 'ii!O "' 73 ·;:;,~·~ 1).2 Y21t1t: 141 :t ·no .; w 1m
Y·?:.?6S II S 3HO -;::1 Wll ,1_2
1~217~ t:lJ .:~~~ ~ ~6 ~I 700 O,t
G2:~~A 1;.~ !l H~l ;O 9~
et2:::9A l26 >% "'~ Gl29D Ml .~()2 <)(fY 95 -:i-S {)'.~ 85 !IX.I 0.t'}
~,.,w; 141 s~~- c!O -~5 m' Ol
Ft~HA w, .t~ 'HO 6 !Jl 12)
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______________________ ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.,,,,. ........... .,,.,,.,,.,,.,,.,,.,,.,,.,,.,,.,,.,,.,,.,,.,,.,,.,,
~n\!ta rnh-:n fr.nm f~m:<:i~,ir.: f'.:-:*f:tit.~F::i ~)fl :r n;x·~-:~::;iv1: -t"~t1l.J:x . . ·. . _ _
~r:h:)-': -1..\":.'11.:.~~~~f.~~11)~ (~~· dNTf.-::o ~t't:~~~~y t'-} \.~f)~n~~~·ot~ t'-.'li.OUfJd~i:::.~y,,~s. ;1.;Jnwm~ l:::ffa.-i-t!m t.:t.pHi.::~£:t-1)n ·Of fat:· \i:-r:~p·l:f)~e :DNA ~>.plf;if~.;;+aiJ:t. h ~ndl.;,:~te