Ex Parte Chen

Board of Patent Appeals and Interferences

Mar 27, 2003

09273835 (B.P.A.I. Mar. 27, 2003)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.
Paper No. 13
UNITED STATES PATENT AND TRADEMARK OFFICE
__________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________
Ex parte XIAN CHEN
__________
Appeal No. 2001-1880
Application No. 09/273,835
__________
ON BRIEF
__________
Before WINTERS, SCHEINER and MILLS, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. §134 from the examiner's final
rejection of claims 1-26, which are all of the claims pending in this application.
Claim 1, 4, 5, 8, 14 and 21 are illustrative of the claims on appeal and read as
follows:
1. A method for determining the nucleotide composition of an oligonucleotide
which comprises the steps of:
(a) incorporating a stable, isotope-labeled form of one of the four nucleotide units
of an oligonucleotide into the oligonucleotide under investigation in place of the ordinary
nucleotide therein, the other three types of nucleotides in the oligonucleotide being
unlabeled;
(b) measuring the mass peak of the unlabeled oligonucleotide using mass
spectrometry;
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Application No. 09/273,835
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(c) measuring the mass peak of the labeled oligonucleotide using mass
spectrometry;
(d) obtaining the magnitude of the mass shift between the labeled
oligonucleotide and the unlabeled oligonucleotide, whereby the number of isotope-
labeled nucleotides in the oligonucleotide under investigation is determined; and
(e) comparing the number of isotope-labeled nucleotides with the number of that
type of nucleotide in a reference oligonucleotide.
4. The method for determining the nucleotide composition of an oligonucleotide
as described in claim 3, wherein the chosen primers contain a sequence for the type IIS
restriction enzyme.
5. The method for determining the nucleotide composition of an oligonucleotide
as described in claim 1, wherein said step of incorporating a stable, isotope-labeled
form of one of the four nucleotide units of an oligonucleotide into the oligonucleotide
under investigation in place of the ordinary nucleotide therein is achieved using
isothermal rolling-circle amplification.
8. A method for determining the nucleotide composition of an oligonucleotide
which comprises the steps of:
(a) incorporating a stable, isotope-labeled form of two of the four nucleotide units
of an oligonucleotide into the oligonucleotide under investigation in place of the ordinary
nucleotide therein, the other three types of nucleotides in the oligonucleotide being
unlabeled;
(b) measuring the mass peak of the unlabeled oligonucleotide using mass
spectrometry;
(c) measuring the mass peak of the labeled oligonucleotide using mass
spectrometry;
(d) obtaining the magnitude of the mass shift between the labeled
oligonucleotide and the unlabeled oligonucleotide, whereby the number of isotope-
labeled nucleotides in the oligonucleotide under investigation is determined; and
(e) comparing the number of isotope-labeled nucleotides with the number of that
type of nucleotide in a reference oligonucleotide.
14. A method for detecting polymorphisms in oligonucleotides which comprises
the steps of:
(a) incorporating a stable, isotope-labeled form of one of the four nucleotide units
of an oligonucleotide into the oligonucleotide under investigation in place of the ordinary
nucleotide therein, the other three types of nucleotides in the oligonucleotide being
unlabeled;
(b) measuring the mass peak of the unlabeled oligonucleotide using mass
spectrometry;
Appeal No. 2001-1880
Application No. 09/273,835
1 Although claims 7 and 20 do not appear in the statement of the statutory basis
of any rejection, they are discussed in the body of the statement of rejection, for
example, Answer, pages 5 and 8. In addition, the appellant has understood these
claims to be included in the rejections. Brief, pages 3 and 5. We note a prior objection
to claims 7 and 20 was withdrawn by the examiner (Paper No. 8, page 2), however, as
claims 7 and 20 appear to remain rejected in the answer, we treat the rejection of these
claims as still pending. The examiner is reminded that all rejected claims should
appear in the listing of the statutory basis of the rejection.
3
(c) measuring the mass peak of the labeled oligonucleotide using mass
spectrometry;
(d) obtaining the magnitude of the mass shift between the labeled
oligonucleotide and the unlabeled oligonucleotide, whereby the number of isotope-
labeled nucleotides in the oligonucleotide under investigation is determined.
21. A method for detecting polymorphisms in oligonucleotides which comprises
the steps of:
(a) incorporating a stable, isotope-labeled form of two of the four nucleotide units
of an oligonucleotide into the oligonucleotide under investigation in place of the ordinary
nucleotide therein, the other three types of nucleotides in the oligonucleotide being
unlabeled;
(b) measuring the mass peak of the unlabeled oligonucleotide using mass
spectrometry;
(c) measuring the mass peak of the labeled oligonucleotide using mass
spectrometry;
(d) obtaining the magnitude of the mass shift between the labeled
oligonucleotide and the unlabeled oligonucleotide, whereby the number of isotope-
labeled nucleotides in the oligonucleotide under investigation is determined.
The prior art references relied upon by the examiner are:
Arlinghaus et al (Arlinghaus) 5,780,232 July 14, 1998
Rothberg et al. (Rothberg) 5,972,693 Oct. 26, 1999
Lizardi (Lizardi) 5,854,033 Dec. 29, 1998
Grounds of Rejection 1
Claims 1-3, 6-10 and 13 stand rejected under 35 U.S.C. 102 as anticipated by
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Arlinghaus.
Claims 1-4, 6-11 and 13 stand rejected under 35 U.S.C. 103 as obvious over
Arlinghaus in view of Rothberg.
Claims 1-26 stand rejected under 35 U.S.C. 103 as obvious over Arlinghaus and
Rothberg in view of Lizardi.
DISCUSSION
In reaching our decision in this appeal, we have given consideration to the
appellant's specification and claims, to the applied references, and to the respective
positions articulated by the appellant and the examiner.
Rather than reiterate the conflicting viewpoints advanced by the examiner and
the appellant regarding the noted rejections, we make reference to the examiner’s
Answer for the examiner’s reasoning in support of the rejection, and to the appellant's
Brief and Reply Brief for the appellant's arguments thereagainst. As a consequence of
our review, we make the determinations which follow.
Background
According to the specification (page 6, lines 14-18) the invention includes “the
generation of nucleotide specific, stable isotope 13C/15N/2H-labeled DNA coupled with
analysis of the resulting mass shifts using mass spectroscopy (MS) to determine the
number of each type of the labeled nucleotide.” The claimed invention (claim 1) is
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directed to a method for determining the nucleotide composition of an oligonucleotide
which comprises the steps of:
(a) incorporating a stable, isotope labeled form of one of the four nucleotide units
of an oligonucleotide into the oligonucleotide under investigation in place of the ordinary
nucleotide therein, the other three types of nucleotides in the oligonucleotide being
unlabeled;
(b) measuring the mass peak of the unlabeled oligonucleotide using mass
spectrometry;
(c) measuring the mass peak of the labeled oligonucleotide using mass
spectrometry;
(d) obtaining the magnitude of the mass shift between the labeled
oligonucleotide and the unlabeled oligonucleotide, whereby the number of isotope-
labeled nucleotides in the oligonucleotide under investigation is determined; and
(e) comparing the number of isotope labeled nucleotides with the number of that
type of nucleotide in a reference oligonucleotide.
“By incorporating stable, isotope-labeled nucleotides into oligonucleotides, 'mass
tags' are introduced into PCR products, that is, the substitution of any or all of 13C for
12C, 15N for 14N, and 2H for 1H leads to a mass change of the oligomer.” Specification,
page 6. With the presence of only one type (A,T, C or G) of labeled nucleotide in an
oligomer, the overall mass change of the oligomer corresponds to the number of the
labeled nucleotides in the oligomer, the other three types of nucleotides remaining
unlabeled with their masses unchanged. Specification, pages 6-7. The specification
indicates that “stable isotope labeling requires cells to be grown on a minimal medium
containing 99% (15NH4)2SO4 or 15NH4Cl as the sole source of nitrogen for 15N labeling,
and/or 99% 13CH3OH or sodium [1,2-13C2 99%] acetate as the sole carbon source for
13C labeling, and/or 99% 2H2O as the sole source of deuterium for 2H labeling of DNA.”
Specification, page 8.
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Claim Interpretation
Our appellate reviewing court stated in Panduit Corp. v. Dennison Mfg. Co.,
810 F.2d 1561, 1567-1568, 1 USPQ2d 1593, 1597 (Fed. Cir.), cert denied, 481 U.S.
1052 (1987):
Analysis begins with a key legal question -- what is the invention claimed?
Courts are required to view the claimed invention as a whole. 35 U.S.C.
103. Claim interpretation, in light of the specification, claim language,
other claims and prosecution history, is a matter of law and will normally
control the remainder of the decisional process. [Footnote omitted.]
“Although words in a claim are generally given their ordinary and customary meaning, a
patentee may choose to be his own lexicographer and use terms in a manner other
than their ordinary meaning, as long as the special definition of the term is clearly
stated in the patent specification or file history.” Vitronics Corp. v. Conceptronic, Inc.,
90 F.3d 1576, 1582, 39 USPQ2d 1573, 1576 (Fed. Cir. 1996). To that end, we also
note that during ex parte prosecution, claims are to be given their broadest reasonable
interpretation consistent with the description of the invention in the specification. In re
Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
Appellant urges that step (a) as claimed, “incorporating a stable, isotope labeled
form of one of the four nucleotide units of an oligonucleotide into the oligonucleotide
under investigation in place of the ordinary nucleotide therein, the other three types of
nucleotides in the oligonucleotide being unlabeled”, when read in view of the
specification, “requires the isotopic labeling of all of one type of atom in a chosen
nucleotide unit, for example, all of the carbon atoms. No atoms are introduced that do
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not normally occur, and not atoms are attached to a nucleotide.” Brief, pages 7-8.
We are mindful that it is “improper to add extraneous limitations to a claim, that is
limitations added wholly apart from any need to interpret what the patentee meant by
particular words or phrases in a claim.” Amgen v. Hoechst Marion Roussel, Inc., 314
F3d 1313, 1393, 65 USPQ2d 1385 (Fed. Cir. 2003). Courts must take extreme care
when ascertaining the proper scope of the claims, lest they simultaneously import into
the claims limitations that were unintended by the patentee. See, e.g., Hoganas AB v.
Dresser Indus., Inc., 9 F.3d 948, 950, 28 USPQ2d 1936, 1938 (Fed. Cir. 1993).
However, it is also well settled that the claims are best understood in light of the
specification of which they are a part. In the present case, appellant urges that, when
the claims are read in view of the specification, the term “stable isotope-labeled form”
takes on a specific meaning. In our view, when the claims are read in view of the
specification as elucidated by the prosecution history, they require that all of one type of
atom in a chosen nucleotide unit, for example, all of the carbon atoms, be labeled with
an isotope, consistent with appellant’s interpretation. Appellant argues (Brief, page 8)
that a “measurement according to the present invention involving less than all of a
chosen element having been replaced by its isotopic form would not yield results that
could be readily analyzed to yield the number of particular nucleotides present in an
oligonucleotide.” Because the claimed invention would not yield results that could be
readily analyzed if appellant's claim interpretation is not accepted, we find it reasonable
to interpret that the claimed invention as supported by the specification, requires all of
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the carbon, nitrogen, or hydrogen atoms, be labeled with an isotope. We also find that
appellant's stable isotope labeled nucleotides, as claimed, are limited to those
nucleotides labeled with 13C, 15N and/or 2H. Specification, page 6.
With this claim interpretation in mind, we review the prior art rejections made of
the application.
35 U.S.C. § 102
Claims 1-4, 6-10 and 13 stand rejected under 35 U.S.C. 102 as anticipated by
Arlinghaus.
A claim is anticipated only if each and every element as set forth in the claim is
found, either expressly or inherently described, in a single prior art reference.”
Verdegaal Bros., Inc. v. Union Oil Co., 814 F.2d 628, 631, 2 USPQ2d 1051, 1053 (Fed.
Cir. 1987). “It is also an elementary principle of patent law that when, as by a recitation
of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if
one of them is in the prior art.” Titanium Metals Corp. of America v. Banner, 778 F.2d
775, 782, 227 USPQ 773, 779 (Fed. Cir. 1985).
The examiner, in the Answer at pages 3-5, has indicated where each of the
claimed steps is disclosed in the Arlinghaus reference. Arlinghaus (abstract) teaches a
“DNA sequencing, mapping, and diagnostic process which includes the steps of
labeling nucleotide segments or peptide nucleic acids (PNAs) with one or more atoms
of specific stable or long-lived radioactive isotopes of a selected element that do not
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normally occur in DNAs, [oligodeoxynucleotides] ODNs or PNA's such that the
nucleotide segment or PNS has specific, stable, or long lived radioactive isotope of a
specified selected element at a terminal or interior position; hybridizing the labeled
nucleotide segment or PNA to complementary nucleic acid segments or PNAs which
are fixed on a hybridization surface; and, using mass spectrometric techniques,
including RIS, to analyze the presence and position of the labeled hybridized nucleotide
segments or PNAs which are bound to the fixed nucleotide segments or PNAs.”
Arlinghaus particularly mentions tin and rare earth isotopes, and isotopes attached to
DNA fragments or ODNs.. Columns 2, 5 and 6. Claim 1 of Arlinghaus indicates that
the isotopes are of an element that does not normally occur in DNAs or ODNs. Column
7, lines 57-59.
In response, appellant argues that the examiner fails to establish a prima facie
case of anticipation because the claimed invention requires “isotopic labeling of all of
one type of atom in a chosen nucleotide unit, for example, all of the carbon atoms.”
Brief, page 8. In addition, appellant argues the claimed invention differs from the
disclosure of Arlinghaus in that, “[n]o atoms are introduced that do not normally occur,
and no atoms are attached to a nucleotide.” Id. Appellant argues that this
interpretation of the claim language is supported by the meaning of “isotope labeled
form” in the specification at page 8, lines 2-12; page 9, lines 5-15 and Table 1 of the
specification. Id.
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Appellant urges that Arlinghaus teaches that its “process includes the step of
incorporating one or more atoms of a specific stable or long-lived radioactive isotope of
a selected element on the ODN primer or the DNA, or in one or more of the
deoxynucleotide triphosphates such that a DNA fragment has a specific stable or long-
lived radioactive isotope of a specified selected element at a terminal or interior
position.” Brief, page 8. Appellants also argues that Arlinghaus does not teach
radioactive isotopes of a selected element that normally occur in DNAs, ODNs or PNAs,
such as C-13, N-15 and H-2. Id.
The examiner responds arguing that “Arlinghaus teaches incorporating a stable,
isotope-labeled form of one of the four nucleotide units of an oligonucleotide into the
oligonucleotide under investigation, in place of the ordinary nucleotide therein, the other
three types of nucleotides in the oligonucleotide being unlabeled (column 6, lines 18-
51);[.]” Answer, page 9. The examiner suggests that, while appellant may argue that
isotopic labeling of all of one type of atom in a chosen nucleotide unit, for example, all
of the carbon atoms or nitrogen atoms or hydrogen atoms is not taught by Arlinghaus,
the examiner does not find such a feature to be recited in the pending claims. Id.
We have determined that when the claims are fairly read in view of the
prosecution history and specification, that appellant’s interpretation of the claims is
supported, and reasonable.
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In view of our claim interpretation, we find the examiner has not adequately
addressed appellant’s arguments concerning differences of the claimed method from
the disclosure of Arlinghaus. Thus, we cannot sustain the examiner’s rejection of the
claims in view of Arlinghaus.
35 U.S.C. 103
Claims 1-4, 6-11 and 13 stand rejected under 35 U.S.C. 103 as obvious over
Arlinghaus in view of Rothberg.
The disclosure of Arlinghaus is provided in the Examiner’s Answer, and
discussed above. Rothberg is relied on by the examiner only for the disclosure of the
use of chosen primers containing a sequence for type IIS restriction enzyme (Claim 4).
Answer, page 5. We do not find that Rothberg overcomes the noted deficiencies of
Arlinghaus. The rejection of the claims is reversed.
35 U.S.C. 103
Claims 1-26 stand rejected under 35 U.S.C. 103 as obvious over Arlinghaus and
Rothberg in further view of Lizardi.
The disclosure of Arlinghaus and Rothberg is provided in the Examiner’s
Answer, and discussed above. Lizardi is relied on by the examiner for the disclosure of
the use of isothermal rolling circle amplification. Answer, page 7. We do not find that
Lizardi overcomes the noted deficiencies of Arlinghaus and Rothberg. The rejection of
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the claims is reversed.
CONCLUSION
In view of the above, the rejections of claims 1-3, 6-10 and 13 under 35 U.S.C.
102 as anticipated by Arlinghaus; claims 1-4, 6-11 and 13 under 35 U.S.C. 103 as
obvious over Arlinghaus in view of Rothberg; and claims 1-26 under 35 U.S.C. 103 as
obvious over Arlinghaus and Rothberg in view of Lizardi are reversed.
REVERSED
)
SHERMAN D. WINTERS )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
TONI R. SCHEINER )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
DEMETRA J. MILLS )
Administrative Patent Judge )
Appeal No. 2001-1880
Application No. 09/273,835
13
Samuel Freund
Los Alamos National Laboratory
LC/BPL, MS D412
Los Alamos, NM 87545