Ex Parte Gordon et al

Patent Trials and Appeals Board

Jan 10, 2019

13898064 - (D) (P.T.A.B. Jan. 10, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/898,064 05/20/2013
115138 7590 01/14/2019
Medlen & Carroll, LLP
1440 Broadway
SUITE 1010
Oakland, CA 94612
FIRST NAMED INVENTOR
Steven Gordon
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.
INTELLI-17532 3857
EXAMINER
CHUNDURU, SURYAPRABHA
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
01/14/2019 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):
rldalton@medlencarroll.com
cjcollins@medlencarroll.com
docketing@medlencarroll.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte STEVEN GORDON and PHILLIP A. VEATCH
Appeal2017-007859
Application 13/898,064
Technology Center 1600
Before ULRIKE W. JENKS, RYAN H. FLAX, and DAVID COTTA,
Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims directed to a method of enriching a template using PCR. Examiner
rejected the claims as anticipated. We have jurisdiction under 35 U.S.C.
§ 6(b).
We REVERSE.
STATEMENT OF THE CASE
Claims 7, 8, 11-17, and 20-23 are on appeal, and can be found in the
Claims Appendix of the Appeal Brief. Claim 7 is representative of the
claims on appeal, and reads as follows:
1 Appellant, is the Applicant, Intelligent Bio-Systems, Inc., of Waltham,
MA, which according to the Brief, is the real party in interest. Br. 3
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Application 13/898,064
7. A method of enriching, comprising:
a) providing i) an aqueous mix comprising PCR reagents, ii)
template, iii) first and second PCR primers, said first PCR
primers immobilized on emulsion beads for emulsion PCR, said
second PCR primers comprising biotin, iv) an oil/detergent mix,
and v) enrichment beads, wherein said enrichment beads
comprise streptavidin;
b) adding said template, said first and second primers, said
aqueous mix and said oil/detergent mix together so as to create
one or more microemulsions, said one or more microemulsions
comprising an aqueous compartment, each compartment
comprising on average less than one template molecule;
c) temperature cycling said one or more microemulsions so
as to amplify at least some of said template on at least some of
said emulsion beads so as to create amplified product comprising
biotin; and
d) enriching for beads with amplified template among said
emulsion beads by contacting with said enrichment beads,
wherein said emulsion beads with amplified template bind to said
enrichment beads.
Appellant requests review of Examiner's rejection of claims 7, 8, 11-
17, and 20-23 under 35 U.S.C. § I02(a)(l) as being anticipated by
Shimkets. 2
The issue is: Does the preponderance of evidence of record support
Examiner's finding that Shimkets teaches the creation of amplified product
comprising biotin within the microemulsion environment as claimed?
Findings of Fact
FF 1. Shimkets teaches sequence amplification using microreactors. One
method uses beads coated with oligonucleotides to capture and
2 Shimkets et al., US 2005/0221341 Al, published Oct. 6, 2005
("Shimkets").
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Application 13/898,064
amplify nucleic acids in a microemulsion. The method has the
following steps:
First, magnetic beads are covalently coated with streptavidin and
then bound to biotinylated oligonucleotides designed to capture
two or more genes of interest from a single cell .... Second, an
aqueous mixture comprising hundreds of thousands to millions
of microreactors are generated by mixing together the
components for PCR, primer-bound beads, the cell population of
interest, and an oil/ detergent mixture to create a microemulsion.
The aqueous compartments ... include an average of less than
one cell and less than one bead. Third, the microemulsion is
temperature-cycled, e.g., in a conventional PCR machine, such
that the bead bound oligonucleotides can act as primers for
amplification for cells having the target genes .... Fourth, the
emulsion is broken and the beads comprising the amplified genes
of interest are isolated, e.g., by magnet. Fifth, after denaturation,
the bead are incubated with oligonucleotides that serve as
primers for the genes of interest, while at least one primer is
added in a de-activated form. Sixth, sequencing is performed on
the beads to determine the first sequence of interest. Seventh, the
next primer is activated and sequencing is performed on the next
gene, e.g., a member of a gene pair. ... Primers can be added
sequentially to sequence additional genes captured by this
method (i.e., three or more genes).
Shimkets ,r 97; see Ans. 2.
FF2. Shimkets teaches that "[a]n amplicon is defined as any nucleic acid
molecule[] produced by an in vitro nucleic amplification technique."
Id. ,I 168.
FF3. Shimkets teaches bead emulsion PCR amplification that creates an
amplicon bound bead. See id. ,r,r 134--140. "'[B]ead emulsion
amplification' is performed by attaching a template nucleic acid ( e.g.,
DNA) to be amplified to a solid support, preferably in the form of a
generally spherical bead." Id. ,r 136. In this amplification, primer Bis
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Application 13/898,064
linked to the bead. Id. ,r 137. The beads linked with primer Bare then
annealed to template DNA, and these beads are then mixed with a
solution based PCR primer pair (primer A and primer B) to form an
aqueous reaction mixture. Id. This mixture is then encapsulated into a
water-and-oil emulsion and thermocycled in an asymmetric PCR
reaction. Id. "Thermostable polymerases then utilize the A strand as a
template to synthesize an immobilized, bead bound B strand of the
amplicon." Id. ,r 139. After completion of the PCR reaction the
emulsion is broken and the immobilized product is rendered single-
stranded by denaturing (by heat, pH etc.) which removes the
complementary A strand and leaves the single strand B attached to the
bead. Id. ,r 140.
FF4. Shimkets teaches an enrichment process that starts with an amplicon
bound bead. Shimkets ,r 172; see Ans. 5. The process starts with (1) an
amplicon bound bead mixed with a biotinylated primer
complementary to the amplicon (Shimkets ,r 172); (2) this is followed
by adding DNA polymerase and the four natural deoxynucleotides
triphosphates ( dNTPs) to create a mixture (id.); (3) introducing
streptavidin coated beads susceptible to attraction by a magnetic field
("magnetic streptavidin beads") to the mixtures created in step 2 in
order to arrive at a biotin-streptavidin bead mixture (id.); (4) placing a
magnet in proximity to the biotin-streptavidin bead mixture (id., see
also id. at Fig. 17); (5) applying a magnetic field (id. ,r 173); and (6)
separating the extended biotinylated primer strand from the amplicon
strand by "melting" (id. ,r 173).
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Principle of Law
To anticipate, every element and limitation of the claimed invention
must be found in a single prior art reference, arranged as in the claim.
Karsten Mfg. Corp. v. Cleveland Golf Co., 242 F.3d 1376, 1383 (Fed. Cir.
2001).
Analysis
Appellant contends that the claims require two types of beads
( emulsion beads and enrichment beads) and these beads are not found in the
amplification disclosed in paragraph 97 of Shimkets. Br. 7. Appellant also
contends that the claims require that the amplicon containing biotin be
created in the microemulsion (see claim 7 step ( c ), see claim 16 step ( c)) and
this is not taught in paragraphs 172-17 6 of Shimkets. Br. 6.
Examiner's position is that "[t]he cited paragraphs 0097, 0172-0176
clearly teach separate emulsion beads ( capture beads) and enrichment beads
(streptavidin coated magnetic beads) as required by the claims." Ans. 5. In
the Answer, Examiner finds that Shimkets "also teach[ es] said capture bead
bound primers in other parts of the document." Id.
On this record, we find that Appellant has the better position. Here,
Examiner is relying on multiple parts of the disclosure other than that of
cited paragraphs 0097 and 0172---0176 to teach either a second type of bead,
or a particular capture bead structure. See Ans. 5. Relying on multiple
different disclosures to cobble together the various elements as recited in the
claim in order to arrive at the finding that these multiple disclosures
anticipate the claim is not permissible.
As stated inArkley, an anticipatory reference under 35 U.S.C. § 102
must clearly and unequivocally disclose the claimed compound
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or direct those skilled in the art to the compound without any
need for picking, choosing, and combining various disclosures
not directly related to each other by the teachings of the cited
reference. Such picking and choosing may be entirely proper in
the making of a 103, obviousness rejection, where the applicant
must be afforded an opportunity to rebut with objective evidence
any inference of obviousness which may arise from the similarity
of the subject matter which he claims to the prior art, but it has
no place in the making of a 102, anticipation rejection.
In re Arkley, 455 F.2d 586, 587-588 (CCP A 1972).
Because the method of claim 7 requires both emulsion beads and
enrichment beads, we agree with Appellant that the method taught in
paragraph 97 of Shimkets disclosing only a single type of bead does not
anticipate. See FF 1. Specifically, Shimkets' s method takes magnetic beads
coated with streptavidin and binds biotinylated oligonucleotides to these
beads to create the primer-bound beads. Id. It is these beads that are then
used in a PCR microemulsion mixture. Id. Based on these disclosures in
Shimkets, we agree with Appellant that this particular method, relied on by
Examiner, does not anticipate the presently claimed enrichment method
because it only uses one type of bead.
Examiner relies on a different portion of Shimkets to establish that the
reference teaches two types of beads. See Ans. 5. We do not disagree with
Examiner's assessment that Shimkets teaches two types of beads. See FF 1-
FF 4. Specifically, Shimkets teaches amplicons attached to a bead that are
enriched with another bead containing streptavidin. See FF4. The problem is,
as pointed out by Appellant, that the disclosure Examiner relies on in
Shimkets does not "amplify ... said emulsion beads so as to create
amplified product comprising biotin" as recited in claim 7 ( c) because the
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beads in Shimkets are not incubated in the presence of a biotinylated primer
within the microemulsion. Br. 5---6.
The production of the amplicon-bound bead in Shimkets does utilize a
microemulsion. But this process, as pointed out by Appellant, does not use a
primer that contains biotin. See Br. 6; FF3. Shimkets teaches that after PCR
amplification is complete the amplicon-bound bead product is denatured in
order to create a single-stranded product attached to the bead. FF3. It is this
single-stranded-amplicon-bead product that is used in the bead purification
method of Shimkets. Here, the purification as set out in paragraphs 172-17 6
of Shimkets, found by Examiner to be anticipating, does not create another
microemulsion that introduces the biotinylated primer with the amplicon
bead product "to create amplified product comprising biotin" as required by
the claim. FF4; see also Shimkets Fig. 17. Because the addition of the
biotinylated primer and primer extension does not occur within a
microemulsion, we agree with Appellant's contention that these disclosures
do not anticipate the claim.
Examiner's position that Shimkets teaches various types of capture
beads and bound primers within the reference does not persuade us that the
reference anticipates. It is not enough to find every limitation recited in the
claim within a single prior art reference but these limitations must also be
taught to be arranged as they are in the claim. See Karsten Mfg. Corp., 242
F.3d at 1383. For the reasons discussed above, we agree with Appellant that
the prior art features are not arranged as are the limitations presented in the
claim.
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Application 13/898,064
On the record before us, we reverse Examiner's decision rejecting all
claims as anticipated by Shimkets under 35 U.S.C. § 102. Whether the
recited reference renders the claims obvious is not a question before us.
SUMMARY
We reverse the anticipation rejection of all claims.
REVERSED
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