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 .
The amended claims dated 11/14/2025 are under consideration.
The amendments and arguments presented in the papers filed 11/14/2025 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 7/14/2025 listed below have been reconsidered as indicated.
a) The amendments to the specification addressing trade names or marks usage are acknowledged.
b) The objection to the specification because of a reference to “Example 10” is withdrawn.
c) Any objections or rejections of claim 14 are rendered moot by the cancellation of the claim and are withdrawn as such.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
Claim Interpretation
Claim 1 states “a plurality of nucleic acid fragments corresponding to at least one chromosomal target region”. The term “corresponding” is broadly interpreted as nucleic acid fragments with sequences that are specific for the sequence of a chromosomal target region as well as nucleic acid fragments with sequences that are “associated” with a chromosomal target region, e.g. a “barcode” that is linked with or assigned to a chromosomal target region but itself does not hybridize with a chromosomal target region.
In claim 2, the term “microarray” is broadly interpreted in view of paragraph 127 of the instant specification.
Claim Objections
Claims 13 and 20 are objected to because of the following informalities: the claims were amended to recite “quantify allelic difference between” rather than “quantify allelic differences between” as was done in claim 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-13 and 15-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The following are new rejections necessitated by the amendments to the claims.
Regarding claim 1, as amended the claim states the “instructions” are for genotyping and detecting polymorphic site “by determining relative allele-specific differences from the major subpopulation and minor subpopulation”. It is unclear whether any additional structural limitations are imposed on the claim kit in order be able to carry out this intended use as set forth in the description of the “instructions”.
Claims 2-12 and 21 depend from claim 1 and are rejected for the same reason as claim 1.
Regarding claim 13, the claim as amended states the “system is configured to quantify allelic difference between the major and minor subpopulations”. It is unclear what additional structural elements are required, if any, in order to “configure” the system for this purpose.
Claims 15-19 depend from claim 13 and are rejected for the same reason as claim 13.
Regarding claim 20, the claim as amended states the “system is configured to quantify allelic difference between the major and minor subpopulations”. It is unclear what additional structural elements are required, if any, in order to “configure” the system for this purpose.
Regarding claim 21, the claim as amended states the “system is configured to quantify allelic imbalance between the major and minor subpopulations. It is unclear what additional structural elements are required, if any, in order to “configure” the system of claim 21 for this purpose.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-13 and 15-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Foster (BMC Medical Genomics. 2015. 8:5, 13 pages; previously cited).
The following are new rejections addressing the amendments to the claims.
Claim 1 is drawn to a kit. The term “kit” is not defined in the instant specification. The term is broadly interpreted as any collection of reagents used together.
Regarding claim 1, Foster teaches a “kit” or “system” used as part of a larger analysis that included an assay sold as the OncoScan® assay (p. 3, left column).
The kit includes a “capture device” in the form of the OncoScan® assay array (p. 3, right column), which has a plurality of nucleic acid fragments “corresponding” to at least one chromosomal target region to which samples are hybridized (p. 3, right column).
The kit further includes “a plurality of molecular probes” in the form of MIP probes for genotyping SNPs (p. 2, left column; and p. 3, left column). These probes are “capable” of “hybridizing to a mixed nucleic acid population comprising a major subpopulation and a minor subpopulation, wherein the major and minor subpopulations are from different biological sources and each include a target sequence located in a first chromosomal region and contain a polymorphic site, wherein the polymorphic site includes combinations of a first nucleotide variant and a second nucleotide variant” because they have all the structural features recited in the claim for detecting a SNP. The recitation in the claim also goes to the intended use of the product as it depends whether or not a sample includes a “mixed nucleic acid population”.
It is noted that “a mixed nucleic acid population”, “a major subpopulation” and “a minor subpopulation” are not structural elements of the claimed kit and do not impose any meaningful limitation on the structure of the “plurality of molecular probes”.
Furthermore, the instant specification used the OncoScan® assay and is described by the specification as having structural elements that supports the claimed functionality (para. 213-215). See also, para. 146 of the instant specification.
The kit includes instructions in the form of the OncoScan® assay manual. The claim states the “instructions” are for “genotyping and detecting the polymorphic site by determining relative allele-specific differences from the major subpopulation and minor subpopulation”. This use of the instructions broadly encompasses nonfunctional description material and does not further limit the scope of the claims because they are not related to the particular structural elements of the claimed kit. See MPEP 211.05.
Regarding claim 2, Foster teaches the “capture device” comprises an array (p. 3, right column), which is encompassed by the broad scope of a “microarray” as claimed.
Regarding claims 3 and 4, Foster teaches the MIP probes are designed to genotype at least one chromosomal target region, including within chromosome 1 and/or 5, as demonstrated in the results of Fig. 3.
Regarding claim 5, the MIP probes taught by Foster are “linear molecular inversion probes” as demonstrated by the instant specifications description of the OncoScan® assay.
Regarding claims 6 and 7, Foster teaches the kit includes a “first set of nucleotides” in the form of dATP (A) and dTTP (T) (A/T) and a “second set of nucleotides” in the form of dGTP (G) and dCTP (C) (G/C) (p. 3, left column).
Claim 6 further states “for mixing with respective first and second channels of a nucleic acid sample following addition of the linear molecular inversion probes to the nucleic acid sample”, which is a recitation of an intended use of the sets of nucleotides and does not limit their structural features or any other features of the claimed kit.
Regarding claim 8, Foster teaches the MIP probes are circularized (p. 3, left column). The ordinary artisan would recognize the MIP probes are linear until circularized through the use of a ligase. The instant specification’s use of the OncoScan® assay supports this conclusion.
Regarding claim 9, Foster teaches the kit includes an exonuclease (p. 3, left column).
Regarding claim 10, Foster teaches the kit includes a “restriction enzyme” in the form of a cleavage enzyme (p. 3, left column).
Regarding claim 11, Foster teaches the kit includes reagents for a PCR amplification (p. 3, left column), which is known to includes primers and a polymerase.
Regarding claim 12, Foster teaches the “kit” includes a scanner as a “detector” (p. 3, right column).
Regarding claims 13 and 15, Foster teaches a “kit” or “system” used as part of a larger analysis that included an assay sold as the OncoScan® assay (p. 3, left column).
The kit of Foster further includes “a plurality of linear molecular inversion probes” in the form of MIP probes for genotyping SNPs (p. 2, left column; and p. 3, left column). These probes are “capable” of “hybridizing to a mixed nucleic acid population that includes a major subpopulation and a minor subpopulation, wherein the major and minor subpopulations are from different biological sources and each include a target sequence located in a first chromosomal region and containing a polymorphic site, wherein the polymorphic site includes combinations of a first nucleotide variant and a second nucleotide variant” because they have all the structural features recited in the claim for detecting a SNP. The recitation in the claim also goes to the intended use of the product as it depends whether or not a sample includes a “mixed nucleic acid population”.
It is noted that “a mixed nucleic acid population”, “a major subpopulation” and “a minor subpopulation” are not structural elements of the claimed kit and do not impose any meaningful limitation on the structure of the “plurality of molecular probes”.
Furthermore, the instant specification used the OncoScan assay and is described as having the structural elements that supports the claimed functionality (para. 213-215). See also, para. 146 of the instant specification.
Foster teaches the MIP probes are circularized (p. 3, left column). The ordinary artisan would recognize the MIP probes are linear until circularized through the use of a ligase. The instant specification’s use of the OncoScan® assay supports this conclusion.
Foster teaches the kit includes a “first set of nucleotides” in the form of dATP (A) and dTTP (T) (A/T) and a “second set of nucleotides” in the form of dGTP (G) and dCTP (C) (G/C) (p. 3, left column).
The claim recites “the system is configured to quantify allelic differences between the major and minor subpopulations”. The clause sets forth an intended use of the “system” and does not further limit any of the structural elements set forth by the claim.
Regarding claim 16, Foster teaches the kit includes an exonuclease (p. 3, left column).
Regarding claim 17, Foster teaches the kit includes a “restriction enzyme” in the form of a cleavage enzyme (p. 3, left column).
Regarding claim 18, Foster teaches the kit includes reagents for a PCR amplification (p. 3, left column), which is known to includes primers and a polymerase.
Regarding claim 19, Foster teaches the “kit” includes a scanner as a “detector” (p. 3, right column).
Regarding claim 20, Foster teaches a “kit” or “system” used as part of a larger analysis that included an assay sold as the OncoScan® assay (p. 3, left column).
The kit further includes “a plurality of molecular probes” in the form of MIP probes for genotyping SNPs (p. 2, left column; and p. 3, left column). These probes are “capable” of “hybridizing to a mixed nucleic acid population that includes a major subpopulation and a minor subpopulation, wherein the major and minor subpopulations are from different biological sources and each include a target sequence located in a first chromosomal region and containing a polymorphic site, wherein the polymorphic site includes combinations of a first nucleotide variant and a second nucleotide variant” because they have all the structural features recited in the claim for detecting a SNP. The recitation in the claim also goes to the intended use of the product as it depends whether or not a sample includes a “mixed nucleic acid population”.
It is noted that “a mixed nucleic acid population”, “a major subpopulation” and “a minor subpopulation” are not structural elements of the claims kit and do not impose any meaningful limitation on the structure of the “plurality of molecular probes”.
Furthermore, the instant specification used the OncoScan assay and is described as having the structure for that supports the claimed functionality (para. 213-215). See also, para. 146 of the instant specification.
Foster teaches the MIP probes are circularized (p. 3, left column). The ordinary artisan would recognize the MIP probes are linear until circularized through the use of a ligase. The instant specification’s use of the OncoScan® assay supports this conclusion.
Foster teaches the kit includes an exonuclease (p. 3, left column).
Foster teaches the kit includes a “restriction enzyme” in the form of a cleavage enzyme (p. 3, left column).
Foster teaches the kit includes reagents for a PCR amplification (p. 3, left column), which is known to includes primers and a polymerase.
Foster teaches the kit includes a “first set of nucleotides” in the form of dATP (A) and dTTP (T) (A/T) and a “second set of nucleotides” in the form of dGTP (G) and dCTP (C) (G/C) (p. 3, left column).
The claim recites “the system is configured to quantify allelic differences between the major and minor subpopulations”. The clause sets forth an intended use of the “system” and does not further limit any of the structural elements set forth by the claim.
Regarding claim 21, the claim further describes the “mixed nucleic acid population”. As noted previously, “a mixed nucleic acid population”, “a major subpopulation” and “a minor subpopulation” are not structural elements of the claims kit and do not impose any meaningful limitation on the structure of the “plurality of molecular probes”.
Foster anticipates claim 21 for the same reason it anticipates claim 1.
Response to the traversal of the 102 rejections
The Remarks argue claims 1, 13 and 20 have been amended to claim either a kit or system that includes, among other notable features, a plurality of molecular probes capable of hybridizing to a mixed nucleic acid population that comprises a major subpopulation and a minor subpopulation derived from different biological sources, and features that allow for genotyping and detecting polymorphic sites by determining relative allele-specific differences from the major subpopulation and minor subpopulation (p. 10).
The arguments have been fully considered but are not persuasive. The amendments further limit the “mixed nucleic acid population”, which is not a structural feature of the claimed “kits” or “systems”. The amended language imposes no additional structural limitation on the “plurality of molecular probes”.
The Remarks argue Foster's disclosure exclusively analyzes homogeneous FFPE tumor DNA from solid tissues and the Foster assay is validated using single-source tumor DNA. The Remarks argue no portion of Foster describes or suggests analyzing a mixture of two genetically distinct subpopulations within a single nucleic acid sample. The Remarks further argue Foster also does not disclose or inherently teach the claimed mixed-population structure or the claimed analytical capability to resolve major/minor allelic contributions because Foster merely determines copy-number and LOH determination across uniform tumor genomes and fails to provide any disclosure of quantitatively determining an allele-ratio measurement in a heterogeneous sample. The Remarks argue in conclusion Foster also does not perform nor suggest ratio-based genotyping between subpopulations. See p. 10-11.
The arguments have been fully considered but are not persuasive. The arguments do not identify any structural difference between probes of Foster and those encompassed by the claim. The arguments focus on a property or intended use of the “plurality of molecular probes”. This property does not need to be recognized by the prior art (MPEP 2112.II). The probes of Foster have all the structural features of a molecular probe described in the claim.
The arguments do not address any of the structural features of the claimed kit and/or how they differ from the structures of the prior art of Foster. As noted above, the kit and system of Foster have all the structural features required by the claims and are “capable” of performing the recited intended uses.
The claims are drawn not to a method, but to a product having the structural elements set forth in the claims. It is reiterated that “a mixed nucleic acid population”, “a major subpopulation” and “a minor subpopulation” are not structural elements of the claimed kit and system and do not impose any meaningful limitation on the structure of the “plurality of molecular probes”. The use of or type of “nucleic acid sample” does not impact the structural features of the claimed elements. The whole design of the product of Foster is to genotype a sample. There is no structural element lacking from the kit and system of Foster that prevents it from being used as intended in the claimed product. This is supported by the fact that the same kit of Foster was used in the instant specification for the purpose described in the claim.
Conclusion
No claims allowed.
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 JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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 Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682