filed pto response in biotech case

Attorney Docket No.: 1029.003

IN THE UNITED STATES PATENT AND TRADEMARK OFFICE

Inventor(s): Won Sun PARK Confirmation No.: 3931

Serial No.: 11/965,687 Examiner: Joyce TUNG

Filed: December 27, 2007 Group Art Unit: 1637

Title: PRIMER SET FOR DETECTING OVEREXPRESSION OF KATP CHANNEL AND MT COMPRISING SAID PRIMER SET

MAIL STOP APPEAL BRIEF - PATENTS Commissioner for Patents P.O. Box 1450 Alexandria, VA 22313-1450

REPLY BRIEF - PATENTS

Sir:

The Appellants respectfully submit this Reply Brief in response to the

Examiner's Answer mailed on July 8, 2010, and thus, this Reply Brief is timely filed within

two months of the Examiner's Answer.

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PATENT Atty Docket No.: 1029.003 App. Ser. No.: 11/965,687

TABLE OF CONTENTS

(1) Status of Claims ............................................................................................................. 3

(2) Grounds of Rejection to be reviewed on Appeal ...................................................... 4

(3) Arguments ....................................................................................................................... 5

A. The rejection of claims 1 and 2 under 35 U.S.C. §103(a) as being unpatentable

over Seino in view of Buck, Adelman and Gillim-Ross should be reversed. ............. 5

B. The rejection of claim 4 under 35 U.S.C. §103(a) as being unpatentable over

Seino in view of Buck, Gillim-Ross and Shyjan should be reversed. ........................ 11

(4) Conclusion .................................................................................................................... 13

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(1) Status of Claims

Claims 3 and 5 have been canceled without prejudice or disclaimer of the subject matter

contained therein.

Claims 1, 2 and 4 are pending and stand rejected.

Claims 1, 2 and 4 are appealed.

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(2) Grounds of Rejection to be reviewed on Appeal

A. Whether claims 1 and 2 were properly rejected under 35 U.S.C. §103(a) as being

unpatentable over U.S. Patent No. 7,115,797 to Seino et al. (hereinafter "Seino") in view of article

"Bio Techniques, 1999, 27(3), pg. 528-536," by Buck et al. (hereinafter "Buck"), and U.S. Patent

No. 5,744,594 to Adelman et al. (hereinafter "Adelman"), and U.S. Patent No. 7,129,042 to

Gillim-ross et al. (hereinafter "Gillim-ross").

B. Whether claim 4 was properly rejected under 35 U.S.C. §103(a) as being

unpatentable over Seino in view of Buck, Gillim-ross, and U.S. Patent No. 6,723,498 to Shyjan

et al. (hereinafter "Shyjan").

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(3) Arguments

A. The rejection of claims 1 and 2 under 35 U.S.C. §103(a) as being

unpatentable over Seino in view of Buck, Adelman and Gillim-ross should be reversed.

Claims 1 and 2 were rejected under 35 U.S.C. §103(a) as being unpatentable over

Seino in view of Buck, Adelman and Gillim-Ross. The rejection should be reversed for at least

the following reasons.

Independent claim 1 recites:

A primer set for detecting the overexpression of a mitochondrial KATP channel mRNA consisting of a forward primer having the sequence of SEQ ID NO: 1 and a reverse primer having the sequence of SEQ ID NO: 2.


A kit for detecting the overexpression of a mitochondrial KATP channel mRNA comprising a primer set for reverse transcriptase-polymerase chain reaction (RT-PCR) consisting of a forward primer having the sequence of SEQ ID NO: 1 and a reverse primer having the sequence of SEQ ID NO: 2.

Independent claims 1 and 2 thus recite, inter alia, a primer set consisting of a

forward primer having the sequence of SEQ ID NO: 1 and a reverse primer having the sequence

of SEQ ID NO: 2.

In setting forth the rejection of independent claims 1 and 2, the Examiner asserts that

Seino discloses a cDNA sequence (Sequence 2 from Seino, having a length of 1275 bases)

which includes SEQ ID NO:1 and SEQ ID NO:2. Please see Examiner's Answer, page 4, last

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paragraph. This rejection, however, fails to indicate why one of ordinary skill in the art would be

motivated to choose both SEQ ID NO:1 and SEQ ID NO:2, both being 20 bases in length, taken

from two specific sites within a sequence of 1275 bases to form a primer pair set. In fact, on

page 5, first paragraph, the Examiner indicates that Buck “discloses strategies to select a primer

from a known nucleic acid sequence and that all of the primers yielded data of extremely high

quality.” Appellants note that this is not an accurate representation of the disclosure in Buck.

Appellants further note that even if given the best reasonable interpretation of Buck, this

secondary reference fails to provide a motivation why one of ordinary skill in the art would be

motivated to choose both SEQ ID NO:1 and SEQ ID NO:2 from specific sites within the

sequence of 1275 bases disclosed in Seino to form a primer pair set. The Examiner, in the

argument section of the Examiner's Answer on page 8, last paragraph, attempts to overcome this

deficiency in the rejection by disregarding the issue and asserting “it is important to appreciate

how routine and ordinary the selection of a particular primer pair for amplification of a target

gene of interest is as taught by Buck” thus again inaccurately characterizing Buck to support the

unfounded assertion that any pair of primers is prima facie obvious when both are located in a

known sequence.

None of the other references are cited or contain any disclosure to overcome these

deficiencies in Seino and Buck. As such, it is clearly evident that the Examiner erred in asserting

that the combination of Seino and Buck render obvious a primer set consisting of a forward

primer having the sequence of SEQ ID NO: 1 and a reverse primer having the sequence of SEQ

ID NO: 2.

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Regarding Seino, Sequence 2 is 1275 bases in length. In Sequence 2 of Seino there are

1255 possible choices (i.e., 1275 less 20) presented for a choice of a first primer of 20 bases in

length and 1255 possible choices for a second choice of a primer of 20 bases in length. Thus,

Sequence 2 in Seino presents 1255 x 1255, which is 1,575,025 total possible choices for a pair of

primers, each being 20 bases in length. The number of variants increases four-fold if the forward

and reverse roles of the two different primers are also considered.

Regarding Buck, the article discloses survey results showing that the sequencing rules of

thumb incorporated into sequencing software at the time of the publication were being largely

disregarded by scientists engaged in primer selection for DNA sequencing. The article, in no

way, shape or form contains any blanket assertion that once a sequence is known, that

performing primer selection for replicating that sequence is simple or conventional. For

instance, Buck states at page 529, column 1, lines 8-14 “[i]n many sequencing projects, primer

design and synthesis represent the most significant costs and consume the bulk of effort and

time.”

Please also note that the test sequence, chosen in Buck for the survey, and illustrated in

figure 1 at page 530, is merely 300 bases in length. The survey participants were not asked to use

any specific parameters in choosing their primers, but were instead asked to use their best efforts

so these could be compared with what were then accepted as rules of thumb and which had been

incorporated into commercial software packages. The surprising result in Buck was the high

percentage of successful primers chosen from outside the established rules of thumb for primer

selection.

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Nevertheless, some selected primers were not successful and primer No. 8 failed

catastrophically as noted at page 533, column 2, at lines 5-10. It should also be noted that the

300 base length test sequence in Buck was chosen as it was optimal for being easily sequenced

as described at page 535, second column in the last 10 lines. Furthermore, Buck qualifies all the

findings in the disclosed survey noting that different results regarding successful primer selection

could result with a less favorable sequence under less optimal conditions as stated on page 536,

first column at lines 1-6: “Different results may be obtained using less carefully purified DNA

templates with unusual sequences or structures in less rigorously controlled sequencing

operations.”

The Court of Appeals for the Federal Circuit has approached the obviousness inquiry

regarding oligonucleotide primers in a known DNA sequence in two basic ways. One approach

is to analogize the different oligonucleotides to chemical analogues and apply chemical case law.

The second approach is to apply genus-species case law, under the assumption that small nucleic

acid pieces are “species” of a larger “genus” suggested by the full length sequence. Under either

approach, the Federal Circuit decisions would not support a prima facie finding of obviousness

regarding the combination of Seino and Buck rendering obvious a primer set consisting of a

forward primer having the sequence of SEQ ID NO: 1 and a reverse primer having the sequence of

SEQ ID NO: 2.

In the chemical approach, as demonstrated by In re Jones, 958 F.2d 347 (Fed. Cir. 1992), a

specific motivation to make the change in the chemical structure is required. The Federal Circuit

made the strong statement in Jones that “[c]onspicuously missing from this record is any

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evidence, other than the PTO's speculation (if it be called evidence) that one of ordinary skill in

the herbicidal art would have been motivated to make the modifications of the prior art salts

necessary to arrive at the claimed 2-(2'-aminoethoxy) ethanol salt.” See In re Jones, 958 F.2d

347, 351 (Fed. Cir. 1992).

Following Jones, a change of one chemical analog for another, in the absence of

particular motivation for the particular change in structure, leads to a conclusion of

non-obviousness. The motivational issue is central in this appeal because the Examiner has

provided no substantial reason or analysis why one of ordinary skill in the art would be motivated

to alter the particular nucleotide disclosed in Seino Sequence 2 at any particular position in that

1275 bases oligonucleotide to create the altered (i.e., substantially shortened) oligonucleotides in

the primer set consisting of a forward primer having the sequence of SEQ ID NO: 1 and a

reverse primer having the sequence of SEQ ID NO: 2.

A different approach to the question of obviousness, as applied to Claims 1 and 2 and in

light of the prior art, is to view the question as the selection of a species from a larger genus.

The Federal Circuit applied this reasoning in Merck & Co. v. Biocraft Laboratories, Inc., where a

selection of a particular compound out of 1200 possible prior art compounds in the prior art

genus was determined to be obvious. See Merck & Co. v. Biocraft Laboratories, Inc., 874 F.2d

804, 807 (Fed. Cir. 1989). However, the obviousness in that case was based both on the

structural similarity of the different compounds and upon the record in that case that each and

every compound in the genus would have been expected to function. The Federal Circuit noted

that “any of the 1200 disclosed combinations will produce a diuretic formulation with desirable

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sodium and potassium eliminating properties.” See id. at 807. This is a clear point of distinction

to the facts in this case on appeal, as evidenced by Buck, because not all primer selections, even

when carefully selected, are successful for DNA replication.

The Federal Circuit, when given cases where the genus was substantially larger, has

stepped away from any bright line rule that species are prima facie obvious where the genus was

disclosed in the prior art. The genus at issue in the case of In re Baird was estimated to

encompass more than 100 million different compounds and selection of a single compound from

this genus was required for the rejection. See In re Baird, 16 F.3d 380, 382 (Fed. Cir. 1994).

The Federal Circuit found that given the large size of the genus, the reference did not render the

claimed invention obvious. See id. at 383. The Federal Circuit extended this reasoning into the

biotechnology domain in the case of In re Bell, where the court noted, Bell had argued without

contradiction that the amino acid sequences in that case could be coded for by more than 1036

different nucleotide sequences, only a few of which were the human sequences claimed in that

case. In re Bell, 991 F.2d 781 (Fed. Cir. 1993). Therefore, given the nearly infinite number of

possibilities suggested by the prior art, and the failure of the cited prior art to suggest which of

those possibilities was the human sequence, the claimed sequences would not have been obvious.

See id. at 784.

In this appeal, given the large number of choices (i.e., 1,575,025 possible choices for a

pair of primers, each being 20 bases in length) and the likelihood, as evidenced by Buck, that

many of the prospective primers other than SEQ ID NO: 1 and SEQ ID NO: 2 would not be

successful, Appellants, respectfully submit that the combination of Seino and Buck fail to render

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obvious a primer set consisting of a forward primer having the sequence of SEQ ID NO: 1 and a

reverse primer having the sequence of SEQ ID NO: 2. The Examiner therefore erred in rejecting

independent claims 1 and 2 as being unpatentable over Seino, Buck, Adelman, and Gillim-Ross.

Appellants therefore respectfully requests that the rejection of independent claims 1 and 2 be

reversed.

B. The rejection of claim 4 under 35 U.S.C. §103(a) as being unpatentable over

Seino in view of Buck Gillim-Ross and Shvjan should be reversed.


A method for utilizing a therapeutic agent for identifying a mitochondrial KATP

channel-related ischemic heart disease comprising: subjecting a cell in the presence of said agent or in the absence of said agent; amplifying the mRNA of mitochondrial KATP channel of the cell using a forward

primer of having the sequence of SEQ ID NO: 1 and a reverse primer having the sequence of SEQ ID NO: 2; and

comparing the expressed mRNA level of mitochondrial KATr channel in the presence of said agent with the expressed mRNA level in the absence of said agent.

Independent claim 4 recites one or more similar features to those described above as being

allowable over Seino in view of Buck, and Gillim-Ross, such as using a forward primer of having

the sequence of SEQ ID NO: 1 and a reverse primer having the sequence of SEQ ID NO: 2 to

amplify the mRNA.

At least for the reasons set forth above, it is respectfully submitted that the features of

independent claim 4, and discussed above with respect to independent claim 1 and 2, are not

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PATENT Any Docket No.: 1029.003 App. Ser. No.: 11/965,687

taught or suggested by Seino, Buck, Gillim-ross, and Shyjan, considered individually or in

combination, as proposed by the Examiner. The Examiner therefore erred in rejecting

independent claim 4 as being unpatentable over Seino, Buck, Gillim-Ross and Shyjan.

Appellants therefore respectfully request that the rejection of independent claim 4 be

reversed.

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(4) Conclusion

For at least the reasons given above, the rejection of claims 1, 2 and 4 described

above should be reversed and these claims allowed.

Please grant any required extensions of time and charge any fees due in connection with

this Appeal Brief to Deposit Account No. 503290.

Respectfully submitted,

Dated: September 8, 2010 By /Patrick R. Delaney/

Patrick R. Delaney Registration No. 45,338 (703) 865-7524

MANNAVA & KANG, P.C. 11240 Waples Mill Road Suite 300 Fairfax, VA 22030 (703) 865-5150 (facsimile)

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filed pto response in biotech case

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