Ex Parte Rabbani et al

Patent Trial and Appeal Board

Jul 1, 2016

10902586 (P.T.A.B. Jul. 1, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/902,586 0712912004
28171 7590 07/01/2016
ENZO BIOCHEM, INC
Donna M. Tirella
527 MADISON A VENUE (9TH FLOOR)
NEW YORK, NY 10022
FIRST NAMED INVENTOR
Elazar Rabbani
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.
Enz-60(D7) 1448
EXAMINER
TUNG, JOYCE
ART UNIT PAPER NUMBER
1637
MAILDATE DELIVERY MODE
07/01/2016 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 ELAZAR RABBANI, JANNIS G. STA VRIANOPOULOS,
JAMES J. DONEGAN, and JACK COLEMAN
Appeal2014-001223
Application 10/902,586
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and
TINA E. HULSE, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a
composition of matter comprising a library of linear double-stranded nucleic
acids. The Examiner rejected the claims as anticipated and as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We reverse and enter a New
Grounds of Rejection.
1 Appellants identify the Real Party in Interest as Enzo Life
Sciences, Inc. (See Br. 2.)
Appeal2014-001223
Application 10/902,586
Statement of the Case
Background
"The quantification of RNA expression provides major insights into
analysis of cellular metabolism, function, growth and interactions" (Spec. 1 ).
"[I]nterest is currently being shown in analysis of the patterns of the
simultaneous expression of multiple RNA species of both known and
unknown function. This approach allows comparative studies on the patterns
of expression between different populations of cells" (id.).
The Claims2
Claims 401--403, 408, 418--424, 427--434, and 437 are on appeal.
Independent claim 401 is representative. Independent claim 401 was
amended in the After-Final Arndt. filed Mar. 20, 2013, the amendment was
entered in the Advisory Action mailed Apr. 11, 2013, and claim 401 as
amended reads as follows:
401. A composition of matter comprising a library of linear
double-stranded nucleic acids, said nucleic acids comprising
sequences complementary or identical in part or whole to
inherent sequences of a library obtained from a sample,
wherein said double-stranded nucleic acids comprise at
least one inherent universal detection target (UDT) proximate to
one end of said double strand and at least one non-inherent
production center comprising a bacteriophage RNA promoter
proximate to the other end of said double strand,
wherein said inherent UDT allows detection of the
presence of sequences of interest, said sequences of interest
being located between said inherent UDT proximate to one end
2 The Appeal Brief identifies claims 1--400, 404--417, 425--427,
435, 436, and 438-952 were cancelled (Br. 4), but claim 408
remains pending (see Br. 20; cf Ans. 3).
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Application 10/902,586
and said bacteriophage promoter proximate to the other end of
said double strand,
wherein said at least one inherent UDT comprises (i) a 3'
poly A segment, (ii) a consensus sequence, or both (i) and (ii),
wherein said consensus sequence (ii) comprises a signal
sequence for poly A addition, a splicing element, a multicopy
repeat, or any combination thereof; and
wherein said double-stranded nucleic acids do not
comprise a non-inherent homopolymeric sequence.
The Issues
A. The Examiner rejected claims 401--403 and 408 under 35 U.S.C.
§ 102(e) as anticipated by Serafini3 (Final Act. 3--4).
B. The Examiner rejected claims 401--403 and 408 under 35 U.S.C.
§ 103(a) as obvious over Serafini and Umovitz4 (Final Act. 4--5).
C. The Examiner rejected claims 418, 419, 421--423, 427--429, 431--434,
and 437 under 35 U.S.C. § 103(a) as obvious over Serafini and Church5
(Final 1A .. ct. 5).
D. The Examiner rejected claims 420 and 430 under 35 U.S.C. § 103(a)
as obvious over Serafini, Church, and Yu6 (Final Act. 5-6).
E. The Examiner rejected claims 424 and 434 under 35 U.S.C. § 103(a)
as obvious over Serafini, Church, and Umovitz (Final Act. 6).
Because all of these rejections rely upon the Serafini reference, we
will consider them together.
3 Serafini et al., US 6,114,152, issued Sept. 5, 2000 ("Serafini").
4 Umovitz, US 6,344,317 B2, issued Feb. 5, 2002.
5 Church et al., US 6,326,489 Bl, issued Dec. 4, 2001 ("Church").
6 Yu et al., US 6,376,191 Bl, issued Apr. 23, 2002 ("Yu").
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Application 10/902,586
The Examiner finds that:
Serafini et al. disclose a method and composition for
making nucleic acids (see column 1, lines 65-66). The method
is used to make cDNA libraries from a single cell (see column
4, lines 4-6). During the method, double stranded DNA
sequences are produced (see fig. 1, step (e)) in which a T7
promoter sequence is proximate to one end and a poly A
segment is proximate to another end (see column 4, lines 54-
59).
(Final Act. 3.) The Examiner finds that "the language 'allow' relates to
'intended use', which does not confer patentable weight, and the term
'sequences of interest' can refer to any possible sequences" (Final Act. 3--4 ).
The issue with respect to these rejections is: Does the evidence of
record support the Examiner's conclusion that Serafini teaches a nucleic acid
library "wherein said double-stranded nucleic acids do not comprise a non-
inherent homopolymeric sequence"?
Findings of Fact
1. Serafini teaches a method comprising the steps:
(a) An oligonucleotide primer, consisting of 5'-T7-RNA
polymerase promoter-oligo (dT)24-3 ',is annealed to the poly(A)
tract present at the 3' end of mature mRNAs, and first-strand
cDNA is synthesized using reverse transcriptase, yielding an
RNA-DNA hybrid ... ;
(b) The hybrid is treated with RNase H, DNA
polymerase, and DNA ligase to convert the single-stranded
cDNA into double-stranded cDNA;
( c) T 7 RNA polymerase is used to synthesize large
amounts of amplified RNA (aRNA) from this cDNA. The
incorporation of a modified T 7 polymerase promoter sequence
into our primer, ...
(d) The aRNA is tailed with poly(A) using a poly(A)
polymerase. This modification, generates much longer first-
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Application 10/902,586
strand cDNA in the next step as compared to the original
protocol;
( e) After denaturation and elimination of the aRNA, a T 7-
RNA polymerase promoter-oligo ( dT) primer is annealed to this
newly synthesized poly(A) sequence, and reverse transcriptase
is used to synthesize first-strand cDNA. Second-strand cDNA
and the complementary strand of the polymerase promoter are
synthesized as in (b ); and
(f) T7 RNA polymerase is then used to generate aRNA
from this cDNA template.
(Serafini 4: 3 5---61.)
2. The Specification teaches "a composition of matter comprising
a library of double-stranded nucleic acids substantially incapable of in vivo
replication and free of non-inherent homopolymeric sequences" (Spec. 19).
3. The Specification teaches that "[n]on-inherent homopolymeric
or unique sequences that can be used for primer binding may be introduced
into RNA templates by means that can include but not be limited to poly A
polymerase or RNA ligase" (Spec. 66).
Principles of Law
"The protocol of giving claims their broadest reasonable interpretation
during examination does not include giving claims a legally incorrect
interpretation." In re Skvorecz, 580 F.3d 1262, 1267 (Fed. Cir. 2009).
Analysis
Appellants contend that "Serafini does not disclose a double stranded
nucleic acid free of non-inherent homopolymeric sequences" (Br. 12).
The Examiner finds that "since the nucleic acids themselves cannot be
structurally distinguished from those of the instant claims, it is submitted
that the rejection is proper" (Ans. 8).
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Application 10/902,586
We find that Appellants are correct. Claim 401, as amended, includes
the limitation "wherein said double-stranded nucleic acids do not comprise a
non-inherent homopolymeric sequence." The Specification explains that
"non-inherent homopolymeric" sequences include those introduced by
poly A polymerase (FF 3).
The "wherein" clause is reasonably assigned patentable weight
consistent with Griffin v. Bertina, a case where the Federal Circuit addressed
a claim to a "method for diagnosing an increased risk for thrombosis"
comprising two steps of "obtaining" nucleic acids and "assaying" for point
mutations and a final clause "wherein the presence of said point mutation in
said test nucleic acid indicates an increased risk for thrombosis." Griffin v.
Bertina, 285 F.3d 1029, 1031 (Fed. Cir. 2002). Griffin found that "the
Board did not err in giving limiting effect to the 'wherein' clauses because
they relate back to and clarify what is required by the count." Id. at 1033.
Griffin concluded that "[t]he manipulative steps set forth in the count have
little meaning or utility unless they are placed within the context of the
diagnosis of an increased risk of developing thrombosis, recited in the
preamble and 'wherein' clauses." Id. at 1034.
Similarly here, the "wherein" clause imposes a specific structural
limitation on the library of nucleic acids, excluding nucleic acids with a
"non-inherent homopolymeric sequence," that is a homopolymeric sequence
added to the nucleic acids exogenously, rather than one found in the sample
itself.
Serafini teaches that the 5' sequence is generated "using a poly( A)
polymerase," the precise form of "non-inherent homopolymeric" sequence
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Application 10/902,586
excluded by claim 401 consistent with the reasonable interpretation of the
Specification.
Serafini therefore does not anticipate claim 401. In addition, the
additional references relied upon in the obviousness rejections do not cure
the failure of Serafini to teach sequences that lack "non-inherent
homopolymeric sequence" and fall for the same reason as Serafini.
Conclusion of Law
The evidence of record does not support the Examiner's conclusion
that Serafini teaches a nucleic acid library "wherein said double-stranded
nucleic acids do not comprise a non-inherent homopolymeric sequence."
NEW GROUND OF REJECTION
Under the provisions of 3 7 C.F .R. § 41. 50(b ), we enter the following
new ground of rejection.
Claims 401--403, 408, 418--424, 427--434, and 437 are rejected under
35 U.S.C. § 102(b) as anticipated by Wong7 as evidenced by Zhao. 8
Findings of Fact
4. Wong teaches that "[i]n one exemplary method, cDNA is made
from a sample of RNA with biotinylated oligo dT and converted to double
stranded cDNA by standard methods" (Wong, col. 6, 11. 37-39).
7 Wong, US 5,658,736, issued Aug. 19, 1997.
8 Zhao et al., Formation of mRNA 3 'Ends in Eukaryotes:
Mechanism, Regulation, and Interrelationships with Other Steps in
mRNA Synthesis, 63 Micro. Mol. Biol. Rev. 405--445 (1999)
("Zhao").
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Application 10/902,586
5. Wong teaches that the "cDNA is treated with 4 base pair cutter
NlaIII, that leaves a 4 base pair 3' overhang. The NlaIII cut cDNA is passed
over a streptavidin magnetic had [sic, bead] system to recover the 3' end of
cDNAs separate from the remaining cDNA population" (Wong, col. 6,
11. 39--43).
6. Wong teaches that the "uncovered 3' end cDNA is ligated to
the DNA shown below which contains the T7 promoter ... a type IIs
restriction site for BsmF 1 and a sticky end from a NlaIII site" (Wong, col. 6,
11. 43--47).
7. Wong teaches the promoter-linker cassette structure reproduced
below:
5' TAATACGACTACT1\TA OOOAC/\rG
3' AT'l''ATGCTOATG.AT.AT CCCT
I I Y
~ ~~ . ·1~~~ 'ff., ~.~ .. -.tt-..... JJ l1'.0illO[C.r J 1!"' ~ .;,,.~uv
forBsru'Fl
(Wong, col. 6, 11. 51-55).
8. Wong teaches that "the average cell has about 400,000 mRNA
molecules (sequences) .... One goal of the present invention is to be able to
uniquely identify and quantify each molecule within this population"
(Wong, col. 3, 11. 50-58).
9. Zhao teaches that three elements define the core
polyadenylation signal-the highly conserved hexanucleotide AAUAAA
found 10 to 30 nucleotides upstream of the cleavage site, a less highly
conserved U-rich or GU-rich element located downstream of the cleavage
site, and the cleavage site itself, which becomes the point of poly( A)
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Appeal2014-001223
Application 10/902,586
addition and is thus generally referred to as the poly( A) site. (Zhao 406, col.
2.)
Principles of Law
Anticipation under 35 U.S.C. § 102 requires that "'each and every
element as set forth in the claim is found, either expressly or inherently
described, in a single prior art reference."' In re Robertson, 169 F.3d 743,
745 (Fed. Cir. 1999).
Analysis
We begin with claim interpretation. Claim 401 requires a nucleic acid
composition with three positive structural elements in a particular
organization and one negative structural element. The positive elements
required are: (i) an "inherent universal detection target" which may
comprise "a 3' poly A segment" among several choices; (ii) "sequences of
interest"; and (iii) "a bacteriophage RNA promoter." The negative element
limits the nucleic acid composition to exclude "non-inherent homopolymeric
sequence."
The organization of the elements in claim 401 also requires placement
of the "sequences of interest" between the "bacteriophage RNA promoter" at
the 5' end of the nucleic acid and a "3 ' poly A segment" at the 3' end of the
nucleic acid.
Thus, a schematic of the double-stranded nucleic acid reasonably
interpreted as required by claim 401 is reproduced below:
5' 3'
Bacteriophage RNA Promoter Sequences of Interest 3' polyA segment
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Appeal2014-001223
Application 10/902,586
With regard to claim 401, Wong teaches a double nucleic acid, a
cDNA with a 3' poly A segment based on the use of biotinylated oligo dT,
the complement of poly A, for cDNA synthesis (FF 4). Wong teaches that
this cDNA is cleaved with Nla III, an enzyme leaving a 3' GTAC 5' sticky
end, and purified on a streptavidin magnetic system to obtain purified
nucleic acids comprising "sequences of interest" and a "3' poly A segment"
(FF 5). Wong teaches that this sequence is ligated by sticky end ligation to a
bacteriophage T 7 promoter sequence using a 5' CATG 3' sticky end that will
hybridize to the 3' GT AC 5' sticky end at the 5' end of the Nla III cut and
purified nucleic acids (FF 6-7).
The resulting intermediate product in Wong comprises a nucleic acid
library composition with a 5 ' bacteriophage T 7 promoter sequence, an
intervening set of sequences of interest, and a 3' poly A segment, and this
product does not comprise any "non-inherent homopolymeric sequence"
where the sequences of interest are located between the bacteriophage
promoter and the 3' poly A segment (FF 4--7). Therefore, Wong teaches a
composition that anticipates claim 401.
With regard to claims 402, 421, and 431, Wong teaches that the
biological source may comprise a cell (FF 8).
With regard to claims 403, 422, and 432, Wong teaches that the
library of nucleic acids may be derived from mRNA (FF 8).
With regard to claims 408, 427, and 437, Wong teaches the use of the
bacteriophage T7 RNA promoter (FF 6-7).
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Application 10/902,586
With regard to claims 418--420 and 428--430, Wong teaches that the
nucleic acids may be fixed by biotin to streptavidin magnetic bead solid
supports (FF 5).
With regard to claim 423 and 433, Wong teaches an inherent UDT
comprising a 3' poly A segment (FF 4--5).
With regard to claims 424 and 434, Wong teaches a 3' poly A segment
in a population cleaved by a 4-cutter enzyme (FF 5), that would inherently
result in cleavage about every 256 basepairs (e.g., 44 based on random
sequences for an enzyme cutting every time four particular bases appear
such as Nla III), and Zhao teaches that the polyadenylation signal is within
10 to 30 basepairs of the poly A sequence (FF 9), resulting in the inherent
presence of the polyadenylation signal within some of the intermediate
nucleic acids in the composition of Wong.
SUMMARY
In summary, we reverse the rejection of claims 401--403 and 408
under 35 U.S.C. § 102(e) as anticipated by Serafini.
We reverse the rejection of claims 401--403 and 408 under 35 U.S.C.
§ 103(a) as obvious over Serafini and Umovitz.
We reverse the rejection of claims 418, 419, 421--423, 427--429, 431-
434, and 437 under 35 U.S.C. § 103(a) as obvious over Serafini and Church.
We reverse the rejection of claims 420 and 430 under 35 U.S.C.
§ 103(a) as obvious over Serafini, Church, and Yu.
We reverse the rejection of claims 424 and 434 under 35 U.S.C.
§ 103(a) as obvious over Serafini, Church, and Umovitz.
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This decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b). Section 41.50(b) provides "[a] new ground of rejection
pursuant to this paragraph shall not be considered final for judicial review."
Section 41.50(b) also provides:
When the Board enters such a non-final decision, the
appellant, within two months from the date of the decision,
must exercise one of the following two options with respect to
the new ground of rejection to avoid termination of the appeal
as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the prosecution
will be remanded to the examiner. The new ground of rejection
is binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the
opinion of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the
claims, appellant may again appeal to the Board pursuant to this
subpart.
(2) Request rehearing. Request that the proceeding be
reheard under§ 41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.
Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure§ 1214.01.
REVERSED; 37 C.F.R. § 41.50(b)
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