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 .
Claim Status
Currently, claims 181-196 are pending in the instant application. Claims 1-180 have been canceled and claims 193-196 have been added. This action is written in response to applicant' s correspondence submitted 06/09/2026. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is FINAL.
Election/Restrictions
Applicant’s election of TP53 species in the reply filed on 12/1/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 181-196 are under examination with respect to TP53.
Withdrawn Rejections
The rejection of claims 181-190 under 35 USC 102(a)(1) as anticipated by Ginkel (2016) is withdrawn in view of the amendment to the claims.
The rejection of claims 181-185, 187-188, 190-192 under 35 USC 102(a)(1) as anticipated by Vogelstein (US20180171413A1) is withdrawn in view of the amendment to the claims.
The rejection of claims 181-185, 187-188, 190-192 under 35 USC 102(a)(1) and 102(a)(2) as anticipated by Vogelstein (US20220220563A1) is withdrawn in view of the amendment to the claims.
New Grounds of Rejection – Necessitated by Amendment to the Claims
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 181-196 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract idea and a law of nature without significantly more. This rejection was previously presented and has been rewritten to address the amendment to the claims.
Claim 181 recite a method for screening for head and neck cancer or precancer and detecting mutations in two or more genes in a nucleic acid sample, the genes comprising TP53 and FAT1 or CASP8. This encompasses a law of nature/natural phenomenon and an abstract idea. The abstract idea is a mental process of screening for head and neck cancer or precancer, this encompasses evaluating data and critical thinking wherein one mentally reads information or report and screens for head and neck cancer or precancer. The step of detecting mutations with the recitation of a method for screening head and neck cancer or precancer is law of nature, the relationship is a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of a natural process.
Thes judicial exception is not integrated into a practical application because the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps in addition to the judicial exception are data gathering steps recited at a high level of generality employing techniques that were well-established, routine and conventional at the time of the invention. For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
While claim 181 recites obtaining nucleic acids from a sample and detecting mutations in two or more genes of at least FAT1 or CASP8 and elected gene TP53, he claims generically recites any method for detecting mutations in TP53 and FAT1 or CASP8. Additionally detecting mutations in TP53, FAT1, and CASP8 were well known routine and conventional in the art taught by Lawrence (Nature, 2015, vol 517, pp 576-582)
Claims 182 recite exonic regions of DNA. These claims only limit the judicial exceptions. However, it was routine in the art to determine exonic regions of TP53, FAT1, and CASP8 as taught by Lawrence (Nature, 2015, vol 517, pp 576-582)
Claims 183-184 and 192,further limit the sample, this is a field of use limitation which does not amount to significantly more.
Claims 185-189 further limit the detection step to include next generation sequencing and enriching target sequence. These steps were well known, routine and conventional in the art as taught by Lawrence (Nature, 2015, vol 517, pp 576-582).
Claim 190 further limit the head or neck cancer or precancer which further limits the judicial exception and does not amount to significantly more.
Claim 191 further limits the detecting step and recites absence of mutation is indicative of a benign oral lesion which is an additional judicial exception reciting a natural correlation and thus is a law of nature.
Response to Arguments
The response traverses the rejection on pages 4-8 of the remarks mailed 06/09/2026. The response asserts the claims are not directed to a judicial exception and even arguendo the claims integrate any such exception into a practical application and recite additional elements that mount to significantly more constituent with MPEP 2106.
The response asserts the claims do not merely recite a biological correlation and the claims define multi-gene screening workflow that requires obtaining nucleic acid from a biological sample and detecting mutations across two or more genes including FAT1 or CASP8 from a defined panel. The response asserts that the specification teaches that oral rinse and saliva specimens provide rich substrates that achieve concordance rates of mutations exception 90% with primary tumor biopsy. The response further asserts that FAT1 or CASP8 reflect inventors specific contribution to the art, these genes identified as two of the three most frequently mutated genes in OCSCC and are not part of any conventional screening panel for head and neck cancer. This response has been thoroughly reviewed but not found persuasive. The claims are not limited to obtaining nucleic acid from saliva specimens or oral rinse samples. While claim 192 recites a swab, saliva, or oral rinse sample, this recitation was routine and conventional in the art for detecting mutations in head and neck cancer as taught by Vogelstein (US20180171413A1, see para 14, for example). As such, while not all the claims are limited to oral rinse and saliva specimens, even with this limitation this would not be significantly more than the natural correlation of mutations in TP53 and FAT1 or CASP8 and head and neck cancer. The association of mutations in TP53 and FAT1 or CASP8 with head and neck cancer is a natural correlation and the claim does not recite any additional elements that integrate the natural correlation into a practical application. While the response asserts that FAT1 and CASP8 reflect inventors contribution to the art, the association of mutations in FAT1 and CASP8 in head and neck cancer was known in the art as taught by Lawrence (Nature, 2015, vol 517, pp 576-582). Even arguendo if the art did not teach mutations in FAT1 and CASP8, the association of mutations in FAT1 and CASP8 with head and neck cancer is judicial exception and can not integrate the natural correlation into a practical application.
The response traverses the claims contain concrete actions performed don patients and physical samples. The response asserts that these steps cannot be interpreted as abstract mental steps and require physical sample collection, nucleic acid isolation and laboratory based mutational analysis. This response has been reviewed but not found persuasive. The additional concrete steps recited in the claim are well-known, routine and conventional in the art. The claims do not include any additional elements that integrate the judicial exceptions.
The response asserts the claims are not directed to single biomarkers but to a multi-gene panel that includes FAT1 or CASP8. The response asserts that these genes are inventors specific contribution of the art. This response has been reviewed but not found persuasive. the detection of mutations in FAT1 and CASP8 in head and neck cancer was known in the art as taught by Lawrence (Nature, 2015, vol 517, pp 576-582). Additionally, even arguendo that mutations in FAT1 and CASP8 were not identified this association is the natural correlation, the judicial exception. While the claims recite more than one gene, the recitation of additional genes that comprise the judicial exception does not integrate the judicial exception into a practical application and the recitation of a gene panel merely recites and is directed to the law of nature, the presence of mutations in CASP8 and FAT1 and associated with head and neck cancer.
The response asserts that the claims integrate the relationship of the natural correlation into a practical application by requiring specific laboratory steps that obtain nucleic acid and detect mutations across multiples biomarkers. This response has been reviewed but not found persuasive. Obtaining nucleic acids and detecting mutations across multiple biomarkers is routine, conventional and well-known in the art, as demonstrated by Lawrence (Nature, 2015, vol 517, pp 576-582) and Vogelstein (US20180171413A1, see para 14, for example). The claims do not recite additional elements that are significantly more than the recited judicial exception. For these reasons and reasons of record this rejection has been applied to the amended claims and is maintained.
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.
Claims 181-190, 194 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lawrence (Nature, 2015, vol 517, pp 576-582). This is a new grounds of rejection, necessitated by the amendment to the claims.
With regard to claim 181-185, 190, and 194-196, Lawrence teaches a method of
identifying mutations in head and neck squamous cell carcinomas. Lawrence teaches obtaining samples from oral cavity (see samples and clinical data). Lawrence teaches whole exome sequencing of identified somatically mutated genes (see somatic mutations) (mutations are detected in exonic regions) (claim 182-185). Lawrence teaches mutations were enriched in 11 genes, including TP53, CASP8, FAT1, CDKN2A, NOTCH1, PIK3CA and HRAS (see somatic mutations and fig 2) (claim 194-196). Lawrence teaches anatomic site includes oral cavity (See fig 2) and must CASP9 mutations were in oral cavity tumors (see pg. 580, 1st column) (claim 190).
With regard to claims 186-189, Lawrence teaches a method of isolating nucleic acid samples from tumor samples and sequencing by RNA-Seq (see S3.1 RNA sequencing). RNA-Seq encompasses next generation sequencing and comprises enriches for target nucleic acid. Lawrence teaches targeted resequencing of selected mutations using PCR primers (See S4.2) (primer or probe hybridize to the nucleic acid for targeted enrichment).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 191-193 are rejected under 35 U.S.C. 103 as being unpatentable over Lawrence (Nature, 2015, vol 517, pp 576-582) in view of Vogelstein (US20180171413 A1). This is a new ground of rejection, necessitated by the amendment to the claims.
Lawrence teaches a method of identifying mutations in head and neck squamous cell
carcinomas. Lawrence teaches whole exome sequencing of identified somatically mutated genes, including TP53, CASP8, FAT1, CDKN2A, NOTCH1, PIK3CA and HRAS (see somatic mutations and fig 2). Lawrence teaches anatomic site includes oral cavity (See fig 2) and must CASP9 mutations were in oral cavity tumors (see pg. 580, 1st column) (claim 190). Lawrence does not teach absence of mutations is indicative of a benign oral lesion or a sample that is a swab, saliva, or oral rinse sample. Lawrence does not teach a sample that is not tumor tissue sample.
However, Vogelstein teaches a method for assaying for tumor DNA in saliva from head and neck squamous cell carcinoma in a patient (claim 192). Vogelstein teaches samples from oral cavity cancer comprising HNSCC (see ex 4 and table 1) (oral potentially malignant disorder, oral cavity SCC) (claim 190). Vogelstein teaches extracting DNA from cells (See para 31) and Vogelstein teaches performing whole exomic sequences for mutations (see para 33). Vogelstein further teaches multiplex PCR and massively parallel sequencing for mutations in TP53 (see para 38, fig 5). Vogelstein teaches most commonly mutated gene was TP53. Vogelstein teaches no mutations were identified after surgery of five patients whose tumors did not recur (absence of mutation indicative of benign oral lesion) (para 25) (claim 191).
Given the prior art teaches analysis of mutations of TP53 in head and neck cancer, it would have been prima facie obvious to the ordinary artisan at the time the invention was made to modify the teaching of Lawrence to include saliva samples for analysis of mutations in head and neck cancer, as taught by Vogelstein to allow for a less invasive sample collection method in the method of Lawrence. The skilled artisan would have been motivated with a reasonable expectation of success to include analysis of samples that were not tumor tissue samples by obtaining saliva samples to allow for a safer, less invasive sample collection because Vogelstein teaches the use of saliva samples to analyze mutations in head and neck cancer. Additionally, Vogelstein teaches the absence of mutations is indicative of a benign oral lesion and ordinary artisan would have used a less invasive, safer sample collection to identify head and neck cancer by analysis of mutations, including saliva samples and the absences of mutation indicative of being oral lesion as taught by Vogelstein in the method of Lawrence.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 181-196 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim1-2, 7-9, 12, 18-20 of U.S. Patent No. 12275996 B2 in view of Lawrence (Nature, 2015, vol 517, pp 576-582).
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘996 in view of Lawrence renders obvious the instant claims. The claims recite assaying a sample to detect the presence of mutations in two or more genes in TP53 and CASP8 or FAT1. While claims achieve the same stated objected detecting the presence of HNSCC, ‘’996 does not teach CASP8 or FAT1 gene. However, mutations in CASP8 and FAT1 gene in HNSCC was known in the art as taught by Lawrence and it would have been obvious to include known mutations in known genes in the method of ‘996 to allow for a more robust detection of HNSCC. While claim ‘996 includes additional steps, as the practice of ‘996 results in performing the activities set forth in the instant claims, ‘996 in view of Lawrence renders obvious the instant claims and are not patentably distinct from the instant claims. ‘996 includes dependent claims that are analogous to the instant dependent claims – reciting the same preferred cancer types, amplification/sequencing, subjects such that instant claims 181-192 are not patentably distinct from ‘996 claims.
Claims 181-196 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-11, 13-19 of U.S. Patent No. 11268153B2 in view of Lawrence (Nature, 2015, vol 517, pp 576-582).
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘153 in view of Lawrence renders obvious the instant claims. The claims recite assaying a sample to detect the presence of mutations in two or more genes in TP53 and CASP8 or FAT1. While claims achieve the same stated objected detecting the presence of HNSCC, ‘’996 does not teach CASP8 or FAT1 gene. However, mutations in CASP8 and FAT1 gene in HNSCC was known in the art as taught by Lawrence and it would have been obvious to include known mutations in known genes in the method of ‘996 to allow for a more robust detection of HNSCC. While claim ‘996 includes additional steps, as the practice of ‘996 results in performing the activities set forth in the instant claims, ‘996 in view of Lawrence renders obvious the instant claims and are not patentably distinct from the instant claims. ‘996 includes dependent claims that are analogous to the instant dependent claims – reciting the same preferred cancer types, amplification/sequencing, subjects such that instant claims 181-192 are not patentably distinct from ‘996 claims.
Response to Arguments
The response traverses the rejection on page 9-10 of the remarks mailed 06/09/2026. The response asserts neither ‘152 or ‘226 mention FAT1 or CASP8 and the claims are therefore patentably distinct in view of the reference patents. This response has been reviewed but not found persuasive. While ‘152 and ‘226 does not teach CASP8 or FAT1 gene, the prior art demonstrate that CASP8 and FAT1 gene are known to be mutated in HNSSC, as taught by Lawrence (2015) and therefore in view of Lawrence, ‘152 and ‘226 are not patentably distinct from the instant claims.
Conclusion
No claims are 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 SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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