Ex Parte Meuleman et al

Patent Trial and Appeal Board

May 31, 2017

13627134 (P.T.A.B. May. 31, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/627,134 09/26/2012 Wouter Meuleman IP-0610-US 1933
759020583
Jones Day
250 Vesey Street
New York, NY 10281-1047
06/01/2017 EXAMINER
KAUP, SAHANA S
ART UNIT PAPER NUMBER
1639
MAIL DATE DELIVERY MODE
06/01/2017 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 WOUTER MEULEMAN, ELENA CRESSINA, GEOFFREY
PAUL SMITH, ROSAMOND JACKSON, and XIAOHAI LIU
Appeal 2015-004372
Application 13/627,1341
Technology Center 1600
Before RACHEL H. TOWNSEND, DEVON ZASTROW NEWMAN and
DAVID COTTA, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a method
of synthesizing a polynucleotide, which have been rejected as anticipated
and obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
“The most prevalent method for reading the sequence of nucleotides
in a genome is sequencing-by-synthesis (SBS).” (Spec. 1.) “In a typical
SBS protocol, millions of genome fragments are attached to individual
1 Appellants identify the Real Party in Interest as Illumina Cambridge
Limited. (Appeal Br. 3.)
Appeal 2015-004372
Application 13/627,134
locations on the surface of a chip or microscope slide. The surface-attached
fragments are subjected to repeated cycles of reagent delivery and detection
such that the nucleotides in each fragment are ‘read’ one by one.” (Id.) In
SBS, blocking groups are used to “prevent[] more than one nucleotide from
being added [by a polymerase] to the growing complementary
polynucleotide during each cycle.” (Id. at 2.) “[A] subsequent nucleotide
cannot be added [by a polymerase] until [a] deblocking agent removes it.”
(Id.) Appellants’ invention is directed to a method of synthesizing a
polynucleotide where a collection of different nucleotide analogs, a
polymerase, and a deblocking agent are present together in the synthesis
mixture.
Claims 1—28 and 30-42 are on appeal. Claims 1 and 28 are
representative and read as follows:
1. A method of synthesizing a polynucleotide, comprising
(a) providing a mixture comprising a nucleic acid, a
collection of different nucleotide analogs, a polymerase and a
deblocking agent, and
(b) allowing sequential addition of a plurality of the
different nucleotide analogs to the nucleic acid to proceed via
several reaction cycles in the mixture, wherein the polymerase
and the deblocking agent are simultaneously present in the
mixture to carry out the reaction cycles,
wherein each reaction cycle comprises
(i) the polymerase adding a nucleotide analog to
the nucleic acid to form a transient nucleic acid species
comprising a blocking moiety, and
(ii) the deblocking agent modifying the transient
nucleic acid species to remove the blocking moiety.
(Appeal Br. 23.)
28. A method of synthesizing a polynucleotide, comprising
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Application 13/627,134
(a) providing a mixture comprising a nucleic acid, a
collection of different nucleotide analogs, a polymerase, a
phosphodiesterase and a phosphodiesterase,
wherein the different nucleotide analogs each comprise a
phosphotriester blocking moiety, and
(b) sequentially adding a plurality of the different
nucleotides analogs to the nucleic acid by several reaction
cycles in the mixture, wherein the polymerase,
phosphotriesterase and phosphodiesterase are simultaneously
present in the mixture to carry out the reaction cycles,
wherein each reaction cycle comprises:
(i) the polymerase adding a nucleotide analog to
the nucleic acid to form a transient nucleic acid species
comprising a phosphotriester blocking moiety,
(ii) the phosphotriesterase converting the
phosphotriester blocking moiety to a phosphodiester
blocking moiety, and
(iii) the phosphodiesterase removing the
phosphodiester blocking moiety from the nucleic acid.
(Appeal Br. 26.)
The following grounds of rejection by the Examiner are before us on
review:
1. Claims 1—5, 17—27, and 42 under 35 U.S.C. § 102(b) as
anticipated by Zhao.2
2. Claims 6—8 and 10-16 under 35 U.S.C. § 103(a) as
unpatentable over Zhao and Gelfand.3
2 Zhao et al., WO 2008/042067 A2, published Apr. 10, 2008.
3 Gelfand et al., WO 2007/075967 A2, published July 5, 2007.
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Application 13/627,134
3. Claim 9 under 35 U.S.C. § 103(a) as unpatentable over Zhao,
Gelfand, and Fiss.4
4. Claims 28—34 and 36-41 under 35 U.S.C. § 103(a) as
unpatentable over Gelfand, Zhao, and Kwiatkowski.5
5. Claim 35 under 35 U.S.C. § 103(a) as unpatentable over
Gelfand, Zhao, Kwiatkowski, and Fiss.
DISCUSSION
Claim 1 Is Not Anticipated by Zhao
The Examiner finds that Zhao teaches a method of synthesizing a
polynucleotide that includes (1) providing a mixture of nucleic acid, a
collection of different nucleotide analogs, a polymerase and a deblocking
agent and (2) allowing sequential addition via several reaction cycles in the
mixture, wherein the polymerase and the deblocking agent are
simultaneously present in the mixture to carry out the reaction cycles, and
where each of the reaction cycles includes the addition of a nucleotide
analog to the nucleic acid to form a transient nucleic acid species comprising
a blocking moiety with the polymerase and modifying the transient nucleic
acid species to remove the blocking moiety with the deblocking agent.
(Final Action 5.) According to the Examiner, Zhao teaches extension of the
nucleic acid primer using a polymerase and removal of a “label and the
blocking group” using “different enzymes contacted with the nucleotide in
the same or sequential reaction” and that there are successive cycles to grow
the polynucleotide. (Ans. 16—17.)
4 Fiss et al., WO 2010/017932 Al, published Feb. 18, 2010.
5 Kwiatkowski et al., US 2002/0051994 Al, published May 2, 2002.
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Application 13/627,134
Appellants argue that Zhao does not teach step b of claim 1 because it
does not “describe sequential addition of a plurality of [the] different
nucleotides [analogs] via several reaction cycles in the mixture, wherein
both the polymerase and deblocking agent are simultaneously presenf1 in
the mixture. (Appeal Br. 10-12.) We note, however, that step “b” recites
“(b) allowing sequential addition ... to proceed.” Allowing an action is
permissive, not a requisite action. A “process” requires action. See
Gottschalkv. Benson, 409 U.S. 63, 70 (1972) (“A process is a mode of
treatment of certain materials to produce a given result. It is an act, or
a series of acts, performed upon the subject-matter to be transformed and
reduced to a different state or thing.” (Emphasis added) (quoting Cochrane
v. Deener, 94 U.S. 780, 788 (1876))). We agree with the Examiner that step
“b” is akin to an intended use limitation and the manner in which sequential
addition is “allow[ed]” to occur as recited in step “b” need not be found in
the prior art reference for it to be anticipatory. Accord In re Collier, 397
F.2d 1003, 1006 (CCPA 1968) (limitations that refer to what may be done
with respect to structural elements, but are not required to be done “cannot
be regarded as structural limitations and therefore not as positive limitations
in a claim directed to structure.”)
However, Appellants further note that claim 1 recites in step (a) the
provision of a mixture in which a polymerase and a deblocking agent are
“simultaneously presenf’, and that Zhao does not teach provision of such a
mixture. (Appeal Br. 11—12, Reply Br. 4—5.) We agree. There is no dispute
that Zhao teaches sequential addition of nucleotides in a process that
involves addition of a nucleotide to the primer sequence with a polymerase
and that the nucleotide that is added includes a blocking agent that is then
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Application 13/627,134
removed with a deblocking agent. But, as Appellants point out, the passages
of Zhao that the Examiner contends teach the claimed mixture of deblocking
agent and polymerase being simultaneously present, i.e., p. 4,11. 18—23, pp.
5-6, p. 7,11. 1-3, p. 49,1. 27-p. 50,11. 1-7, p. 22,11. 1^1, p. 59 claims 20
and 21 (Final Action 5; Ans. 16—17), do not explicitly or inherently teach the
requisite mixture. As Appellants further note, the “description of repeating a
cyclic reaction does not distinguish a fluidic configuration where reagents
are sequentially added and removed (e.g. via automation) to separate the
polymerase and deblocking agent into separate mixtures during the cycles,
from a fluidic configuration where the polymerase and deblocking agent
instead remain simultaneously present for the duration of several cycles.”
(Reply Br. 4—5.) For these reasons, we find that Zhao does not teach a
configuration where the polymerase and deblocking agent are
simultaneously together, nor is such a configuration the necessary and
inevitable result of Zhao’s “automated process” (Ans. 17).
Page 4 of Zhao simply teaches that in SBS, polymerases are used to
incorporate modified nucleotides and that blocking groups are removed after
the nucleotides are added. (Zhao 4:18—20, 5:3—6:32.) At page 6, Zhao
teaches a method that includes incorporation of a dye molecule in the
process so that an image can be taken to determine which base has been
incorporated based on a color code. (Id. at 6:26—32.) Zhao further teaches
that the dye and blocking group can be removed at the same time. (Id. at
6:26—7:3) Page 22 of Zhao further discusses the use of a label and a
blocking group and their subsequent removal from the nucleotide polymer.
(Id. at 22:1—4; see also Id. at 26:21—27:5; id. at 59 (claims 20 and 21).) This
teaching regarding removal of a label and blocking group in an SBS process
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Application 13/627,134
has nothing to do with whether the deblocking agent and the polymerase
were present in a mixture at the same time.
Pages 49-50 of Zhao describes carrying out “different reactions”
simultaneously in the same vessel or on the same substrate. As Appellants
explain, this does not require that the different reactions are necessarily
carried out with a mixture that includes the polymerase and deblocking
agent. (Reply Br. 9—10.) For example, even though reactions are carried out
in “the same vessel,” a wash step could occur prior to addition of a
deblocking agent. (See Reply Br. 5.) And in fact, the reagent choices
suggest that Zhao did not contemplate a mixture in which the deblocking
agent and polymerase would be together. (Id.) Consequently, because
Zhao’s language at pages 49-50 does not necessarily teach providing a
mixture that includes a deblocking agent and a polymerase as recited in
claim 1, Zhao cannot be said to explicitly or inherently teach this claim
limitation.
Thus, for the foregoing reasons we do not sustain the Examiner’s
rejection of claim 1 as being anticipated by Zhao.
The Claimed Invention Is Not Obvious
a. Claims 6—16
The Examiner relies on the additional references to teach dependent
limitations not taught by Zhao, but continues to rely on Zhao for the alleged
teaching of providing a mixture that includes a polymerase together with a
deblocking agent. (See Final Action 10-12.) Thus, for the same reasons set
forth above regarding claim 1, we do not sustain the Examiner’s rejections
of claims 6—16 for obviousness.
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Application 13/627,134
b. Claim 28
Claim 28, like claim 1, requires provision of a mixture that includes a
polymerase and a deblocking agent. In addition, unlike claim 1, claim 28
requires the active step of sequential addition of nucleotides in the presence
of both agents. The Examiner relies on Zhao for these claim requirements.
(Final Action 14, 16.) However, as discussed above, we find Zhao does not
teach provision of a mixture of a polymerase together with a deblocking
agent. Moreover, in light of this, we also find that Zhao does not teach
sequential addition of nucleotides in the presence of both the claimed
polymerase and deblocking agent.
Thus, we do not sustain the Examiner’s rejections of claims 28—34
and 36-41 for obviousness.
Regarding claim 35, the Examiner does not rely on Fiss to remedy the
deficiency of Zhao. (Final Action 17.) Consequently, we also do not sustain
the Examiner’s rejection of claim 35 for obviousness.
SUMMARY
We reverse the rejection of claims 1—5, 17—27, and 42 under 35
U.S.C. § 102(b) as anticipated by Zhao.
We reverse the rejection of claims 6—8 and 10-16 under 35 U.S.C. §
103(a) as unpatentable over Zhao and Gelfand.
We reverse the rejection of claim 9 under 35 U.S.C. § 103(a) as
unpatentable over Zhao, Gelfand, and Fiss.
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Application 13/627,134
We reverse the rejection of claims 28—34 and 36-41 under 35 U.S.C.
§ 103(a) as unpatentable over Gelfand, Zhao, and Kwiatkowski.
We reverse the rejection of claim 35 under 35 U.S.C. § 103(a) as
unpatentable over Gelfand, Zhao, Kwiatkowski, and Fiss.
REVERSED
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