Ex Parte Savitski et al

Patent Trial and Appeal Board

Jun 14, 2017

13846666 (P.T.A.B. Jun. 14, 2017)

United States Patent and Trademark Office
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/846,666 03/18/2013 Mikhail M. SAVITSKI 3108US2/NAT 8672
44064 7590 06/16/2017
THERMO FINNIGAN LLC
ATTN: IP DEPT.
355 RIVER OAKS PARKWAY
SAN JOSE, CA 95134
EXAMINER
IPPOLITO, NICOLE MARIE
ART UNIT PAPER NUMBER
2881
NOTIFICATION DATE DELIVERY MODE
06/16/2017 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):
ussjo.ip@thermofisher.com
pair_thermofisher @ firsttofile. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE
THE PATENT TRIAL AND APPEAL BOARD
Ex parte MIKHAIL M. SAVITSKI1
and ROMAN ZUBAREV
Appeal 2016-006733
Application 13/846,666
Technology Center 2800
Before MARKNAGUMO, MONTE T. SQUIRE, and JANE E. INGLESE,
Administrative Patent Judges.
NAGUMO, Administrative Patent Judge.
DECISION ON APPEAL
Mikhail M. Savitski and Roman Zubarev (“Savitski”) timely appeal
under 35 U.S.C. § 134(a) from the Final Rejection2 of claims 1—7, which are
all of the pending claims. We have jurisdiction. 35 U.S.C. § 6. We reverse.
1 The real party in interest is identified as Thermo Fisher Scientific
(Bremen) GmbH. (Appeal Brief, filed 22 December 2014 (“Br.”), 3.)
2 Office Action mailed 29 January 2014 (“Final Rejection”; cited as “FR”).
Appeal 2016-006733
Application 13/846,666
OPINION
A. Introduction3
The subject matter on appeal relates to multiplexed multiple stage
mass spectroscopy. The ’666 Specification discloses that so-called
MS/MS—more generally, “MSn”—techniques are especially useful for
analyzing mixtures of large molecules such as partially digested proteins
(Spec. 3 [0007]) or a cell lysate (id. at [0008]) that contain “many different
molecules having closely similar mass to charge ratios” (id. at 1 [0003]).
Prior art methods are said to involve creating and mass-selecting a precursor
ion of interest, fragmenting it, mass analyzing the resultant ions sequentially,
and analyzing the peak list against a database of proteins to obtain a “score-
sorted list of the protein or peptide candidates along with their scores”
(id. at 5 [0012]), which is then interpreted by the user. The process is
repeated for the next precursor ion of interest, and is said to be costly,
because “instrument time is expensive,” as well as wasteful because
“relatively large proportions of the sample (which may only exist in very
small quantities) are consumed during the process.” (Id. at 6 [0017].) The
Specification cites a prior art multiplexing method in which “[fragment ions
from more than one precursor are intentionally measured in a single mass
spectrum taken with very high mass accuracy.” (Id. at [0018].) However,
the complexity of the fragment ion spectra is said to lead to less accurate
3 Application 13/846,666, MS/MS data processing, filed 18 March 2013, as
a continuation of 12/992,839, filed 14 January 2011 (now U.S. Patent
No. 8,481,924), which was filed as the national stage under 35 U.S.C. § 371
of PCT/EP2009/003175, filed 4 May 2009. We refer to the
“’666 Specification,” which we cite as “Spec.”
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Application 13/846,666
scores, but also to large numbers of false-positive identifications.
(Id. at 7 [0019].)
The inventors disclose methods of mass spectroscopy and data
analysis that are said to overcome these difficulties. The claims of the
present application are directed to methods of conducting the mass
spectroscopy.
Claim 1 is representative and reads:
A method of conducting mass spectrometric analysis,
comprising steps of:
sequentially isolating ions of a first and a second precursor
ion species,
the first and second precursor ion species having
different mass-to-charge ratios;
combining and storing the isolated ions of the first and
second precursor ion species;
fragmenting the combined ions to yield product ions; and
mass analyzing the product ions.
(Claims App., Br. 10; some indentation, paragraphing, and emphasis added.)
The Specification describes a particular embodiment of the claimed
method in reference to Figure 6, which is reproduced on the following page.
A sample, e.g., a protein, is prepared at 54, purified by chromatography at 6,
and supplied to ion source 20 for ionization. (Spec. 28 [0077].) Precursor
ions are selected sequentially in linear ion trap 26 and transferred to
intermediate ion store 31, “followed by fragmentation of all ions together in
4 Throughout this Opinion, for clarity, labels to elements are presented in
bold font, regardless of their presentation in the original document.
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Appeal 2016-006733
Application 13/846,666
the ion fragmentation means 50[5].” {Id. at 29 [0081].) The fragment ions
are then collected again in intermediate ion store 31 and mass analyzed
in 70, a high accuracy mass analyzer. {Id.)
(Figure 6 is reproduced (annotation added) below}
(Fig. 6 provides a block diagram of the method of claim 1}
The Examiner maintains the following grounds of rejection6,7:
A. Claims 1—3, 5, and 6 stand rejected under 35 U.S.C. § 102(b)
in view of Verentchikov.5 6 7 8
5 Fragmentation device 50 may be a collision cell. {Id. at 28 [0077].)
6 Examiner’s Answer mailed 13 March 2015 (“Ans.”).
7 Because this application claims the benefit of an application filed before
the 16 March 2013, effective date of the America Invents Act, we refer to
the pre-AIA version of the statute.
8 Anatoli N. Verentchikov, Tandem time of flight mass spectrometer and
method of use, U.S. Patent Application Publication 2005/0242279 A1
(2005).
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Application 13/846,666
Al. Claims 4 and 7 stand rejected under 35 U.S.C. § 103(a) in
view of the combined teachings of Verentchikov and
Bateman.9
B. Discussion
The Board’s findings of fact throughout this Opinion are supported by
a preponderance of the evidence of record.
Savitski urges the Examiner erred in finding that Verentchikov
describes an MS/MS analysis in which first and second precursor ions are
sequentially isolated. (Br. 6.) “Rather,” Savitski argues, “Verentchikov . . .
utilizes a method in which product ions derived from a single precursor ion
group are mass analyzed.” {Id. at 11. 21—22.) Savitski acknowledges that the
coarse resolution of the first time-of-flight (“TOF1”) stage is, in
Verentchikov’s words, “still sufficient to isolate a group of isotopes of
parent ions,” which can be considered first and second precursor ion species.
{Id. at para, bridging 6—7.) However, Savitski emphasizes, “the isolation of
the multiple ion species occurs in a single event in the Verentchikov
method” {id. at 7,11. 5—6), i.e., in the TOF1 stage. Claim 1, in Savitski’s
view, requires that the first and second precursor ion species be isolated
sequentially, in separate steps. Savitski also urges that “[m]ere spatial
separation along a continuous flight path . . . does not constitute ‘isolating’
precursor ion species.” {Id. at 11. 20-21.) Finally, Savitski argues that
Verentchikov fails to describe the subsequent steps of “combining and
9 Robert Harold Bateman et al., Mass spectrometer, U.S. Patent Application
Publication 2009/0173877 Al (July 9, 2009), based on an international
application filed 10 November 2005.
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Appeal 2016-006733
Application 13/846,666
storing the isolated ions of the first and second precursor ion species,” and of
“fragmenting the combined ions,” recited in claim 1. {Id. at 11. 24—25.)
Figures 1 and 2 of Verentchikov, reproduced below, and the
accompanying text, support Savitski’s arguments.
n 13 14 15 16
13
Fig. 1
(Figure 1 (top) shows the TOF-TOF mass spec in block form};
(Figure 2 (bottom) shows mass separations of ions at each stage}
Verentchikov provides pulses of ions from pulsed ion source 12
(Verentchikov, Fig. 1) every 10 ms {id., Fig. 2). The ions are separated
according to their m/e ratios in TOF1 13, “generating a train of ion packets
in a sequence of their masses.” {Id. at 3 [0049]; Fig. 2, 22.) The next step,
in CID [“collision induced dissociation”] cell 14 comprises “sequentially
fragmenting analyte ions without mixing said separated packets.”
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Application 13/846,666
(Id. at [0050] (emphasis added); Fig. 2, 23.) Each fragmented packet is then
mass-analyzed, in sequence, in TOF2 15, yielding mass spectra TOF2(Tl)
and TOF2(T2), etc. (Id. at [0051]—[0052]; Fig. 2, 24 and 25, respectively.)
In the words of Verentchikov, “Drastic difference in time scales of TOF1
and TOF2 allows data acquisition of multiple fragment spectra,
corresponding to different parent ions between source pulses. The
specialized data acquisition system (16) acquires multiple fragment spectra
in a time nested fashion, where individual spectra are not mixed together.'1'’
(Id. at [0058], emphasis added.)
In light of the weight of the evidence of record—in particular, both
Verentchikov and the ’666 Specification—the Examiner’s interpretation of
the claims is not in accord with the understanding of those having ordinary
skill in the art. It is from that point of view that the claims must be
interpreted. Cf. Nystrom v. Trex Co., Inc., 424 F.3d 1136, 1145 (Fed. Cir.
2005):
What Phillips[10] now counsels is that in the absence of
something in the written description and/or prosecution
history to provide explicit or implicit notice to the public—
i.e., those of ordinary skill in the art—that the inventor
intended a disputed term to cover more than the ordinary and
customary meaning revealed by the context of the intrinsic
record, it is improper to read the term to encompass a broader
definition simply because it may be found in a dictionary,
treatise, or other extrinsic source.
While it may be arguable that the term “sequentially isolating” is not
sufficiently well defined in the ’666 Specification to exclude the temporal
10 Phillips v. AWHCorp., 415 F.3d 1303, 1321 (Fed. Cir. 2005).
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Application 13/846,666
separation that occurs in a time-of-flight separator, reading the phrase
“combining and storing the isolated ions” on having them pass through
CID cell 14 is highly strained. Reading the step of “fragmenting the
combined ions” on the temporally sequential fragmentation illustrated in
step 23 (the ion packets are slightly broadened, but they remain distinct) is
strained beyond the breaking point.
The Examiner makes no findings regarding the additional reference
Bateman that cures the fundamental defects of Verentchikov.
We therefore reverse the rejections of record.
C. Order
It is ORDERED that the rejection of claims 1—7 is reversed.
REVERSED
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