DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Drawings
The drawings were received on 17 November 2025. These drawings are acceptable.
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Attention is directed to MPEP 2173.04 [R-10.2019]. As stated therein:
Breadth of a claim is not to be equated with indefiniteness. In re Miller, 441 F.2d 689, 169 USPQ 597 (CCPA 1971); In re Gardner, 427 F.2d 786, 788, 166 USPQ 138, 140 (CCPA 1970) ("Breadth is not indefiniteness."). A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
Claim Rejections - 35 USC § 112. Fourth paragraph / (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 22 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 22 depends from claim 21; however, claim 21 was cancelled via the amendment of August 19, 2025. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 2, 4, 5, 10-12, 14, 22-26, 28, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over EP 1892304 A1 (Takahashi et al.) in view of US 2017/0198340 A1 (Joe et al.), US 2015/0045369 A1 (Lambrechts), applicant’s admissions and US 2006/0088871 A1 (Finkelstein et al.) and US 2001/0053519 A1 (Fodor et al.).
Takahashi et al., teach of a “method and kit for detection of microsatellite instability-positive cell”. As disclosed at page 2, paragraph [0005]:
The genetic understanding of hereditary non-polyposis colorectal cancer (HNPCC) has dramatically progressed as a result of discovery of various types of genes associated with mismatch repair. Such a mismatch repair mechanism is a mechanism for recognizing an abnormal base pairing (mismatch base pairs) generated during DNA replication or genetic recombination, and eliminating and repairing the mismatched base pairs. With regard to HNPCC, one of the most typical diseases among familial neoplastic diseases, it has been known that the microsatellite instability (MSI) in the DNA of tumor tissues, which reflects deficiency in a mismatch repair system, is positive in 90% or more of the cases thereof (see, Non-Patent Document 4). The term "microsatellite" is used to mean a repetitive sequence formed by repeating several to several tens of repeat units each consisting of 2 to 5 bases. The term "instability" is used herein to mean a phenomenon in which repeat numbers of microsatellites are abnormally increased or decreased. MSI can be typically detected by assaying microsatellite markers (BAT25, BAT26, D2S123, D5S346, D17S250, etc.) using PCR method. Thus, detection of MSI contributes to HNPCC diagnosis (see, Non-Patent Document 5).
Takahashi et al., teach of a kit that comprises primers to be used in determining MSI. As disclosed at page 4:
[3] A kit for analyzing a gene expression level to detect a cell positive for microsatellite instability, comprising the following primer pairs (a) and (b):
a primer pair, which is a combination of a primer comprising a nucleotide sequence consisting of 15 to 50 contiguous nucleotides comprising a portion of an exon 1 sequence spanning from positions 1 to 183 from the nucleotide sequence as shown in SEQ ID NO: 1, with a primer comprising a nucleotide sequence complementary to a nucleotide sequence consisting of 15 to 50 contiguous nucleotides from an exon 2 sequence as shown in SEQ ID NO: 5; and
(b) a primer pair, which is a combination of a primer comprising a nucleotide sequence consisting of 15 to 50 contiguous nucleotides comprising a portion of exon 1 and 2 spanning from positions 1 to 132 from the nucleotide sequence as shown in SEQ ID NO: 2, with a primer comprising a nucleotide sequence complementary to a nucleotide sequence consisting of 15 to 50 contiguous nucleotides from an exon 2 sequence as shown in SEQ ID NO: 5.
Takahashi et al., at page 5, paragraph [0022], teach using capillary electrophoresis to evaluate the PCR product. As disclosed therein:
Examples of the method of measuring an expression level may include, but not limited to, the real-time PCR method, the semi-quantitative RT-PCR method, the competitive PCR method using a capillary electrophoresis apparatus, a gene expression level measurement method using a DNA chip or microarray, differential display method, and the Northern blot method. Using such methods, the abundance of each transcript contained in a nucleic acid sample (e.g. RNA or cDNA) prepared from a biological sample can be measured. Such a nucleic acid sample may be prepared from a biological sample according to a routine method, and it may also be purified before analysis. In the present invention, genomic DNA or RNA may be prepared in accordance with standard experimental instructions used in the molecular biological field, such as J. Sambrook et al. (Eds.), Molecular Cloning, 3rd ed. Cold Spring Harbor Laboratory Press (2001). (Emphasis added)
While Takahashi et al., teach of performing PCR and capillary electrophoresis, they have not been found to teach performing “real-time PCR” and using an automated system, such as “the Modaplex device” (claim 28), nor have they been found to teach performing real time PCR on multiple MSI targets in a simultaneous manner.
Joe et al., in paragraph [0068], teach:
[0068] In order to confirm whether simultaneous multiple detection of the 5 types of mutant genes included in the wild type gene is possible, SEQ ID Nos. 15˜19 in Table 1 as PNA detection probes, SEQ ID No. 22 as a PNA clamping probe, and SEQ ID No. 20 as an internal control (complementarily binding to wild type gene) were used. A reaction mixture solution of PNA probe and PCR primer was prepared by the method of Example 4-1, and real-time PCR reaction analysis and melting curve analysis were carried out for simultaneous analysis of multiple genotypes. (Emphasis added)
The aspect of detecting mutant genes is deemed to fairly suggest that one is analyzing the DNA, and not a transcript of a gene (RNA). The aspect of using real-time PCR is deemed to fairly suggest yet another limitation of claim 1.
Joe et al., at paragraph [0057], teach using fluorophore-labeled amplicons.
Lambrechts teaches performing multiplex PCR analysis so to determine microsatellite instability, and that the amplicons are from “tumor or normal DNA”. As disclosed in paragraph [0219]:
Microsatellite instability (MSI) status was analyzed at ten different loci containing mono- or dinucleotide repeat sequences (respectively, two and eight markers), using the panel recommended by the international guidelines for evaluation of MSI, i.e., the revised Bethesda panel (Boland et al., 1998; Dietmaier et al., 1997). PCR amplifications were performed in two pentaplexes: Multiplex A (BAT25, BAT26, D5S346, D17S250, D2S123) and multiplex B (BAT40, D17S787, D18S58, D18S69, TGF.beta.-RII). The forward primers were labeled with 6-FAM, HEX, VIC or TET. The amplicons from tumor and normal DNA of the same patient were analyzed on an ABI 3130 Genetic Analyzer (Applied Biosystems).
As a result of amendment claim 9 no longer specifies that the method is performed on “a Modaplex device”, but rather, is performed on a device that has the same properties. Applicant, at page 9, first full paragraph, teaches that just such a device was known in the art. As asserted to therein:
Modaplex detection system or Modaplex device (former also published as ICEplex or STAR technology; EP1601780B1; Hlousek et al. 2012) is an automated high multiplex real time qPCR platform technology which combines within an integrated system solution a PCR thermocycler and a capillary electrophoreses (CE) device (Biotype GmbH, Dresden, DE). The fluorescence detection unit of the CE comprises at least one, preferably at least two, fluorescence excitation source (gas laser, diode laser, light-emitting diode) and at least one appropriate fluorescence detection channel. (Emphasis added)
It is noted that EP 1601780 B1 (Slepnev) was published 07.12/2005 which is nearly 14 years prior to applicant’s priority date and, thusly, qualifies as available prior art.
Finkelstein et al., at paragraph [0213], teach using “fluorescent labeled oligonucleotide primers” and in paragraph they teach performing real-time PCR. It is recognized that by using “fluorescent labeled oligonucleotide primers”, one will produce “fluorophore-labeled amplicons” (claim 1).
Fodor et al., at paragraph [0101], teach providing and using an “n-mer array” which comprises all possible sequences of a length “n”. Such an array of oligonucleotides/primes would comprise every nucleotide sequence for each microsatellite.
In view of the well-developed state of the art, one of ordinary skill in the art would have been amply motivated to have employed the automated means for analysis of microsatellite instability which relies at least in part on the use of fluorescently labeled amplicons whereby the amplicons are produced via real time PCR in a multiplexed manner. Said ordinary artisan would have been amply motivated given the applicability of such a detection system to detection of cancers in patients. In view of the well-developed state of the art, said ordinary artisan would have been well motived to have used such known methods and automated systems.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1, 2, 4, 5, 10-12, 14, 22-26, 28, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over EP 1892304 A1 (Takahashi et al.) in view of US 2017/0198340 A1 (Joe et al.), US 2015/0045369 A1 (Lambrechts), applicant’s admissions and US 2006/0088871 A1 (Finkelstein et al.) and US 2001/0053519 A1 (Fodor et al.).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682