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 6/29/2026 are under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 11, 20, 65, 66, 67, 68, 69, 70, 71, 72, 74, 77, 80, 81 and 82, in the reply filed on 6/29/2026 is acknowledged.
Upon further consideration of the elected invention, the restriction requirement between Groups I and III is withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim 135 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/29/2026.
Applicant’s election of the following species in the reply filed on 6/29/2026 is acknowledged:
Primer pairs SEQ ID NO: 1 and 2 (HPV16), SEQ ID NO: 3 and 4 (HPV18), SEQ ID NO: 5 and 6 (HPV33), SEQ ID NO: 7 and 8 (HPV35), SEQ ID NO: 9 and 10 (HPV45), and SEQ ID NO: 11 and 12 (HPV31).
Probe having SEQ ID NO: 29 (HPV16).
Primer pair SEQ ID NO: 27 and 28 (ERV-3).
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)).
Priority
The present application is a 371 national stage entry of PCT/US2022/023911 (filed 4/7/2022), which claims benefit of US provisional application 63/172,400 (filed 4/8/2021).
Priority is recognized.
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.
Specification
The amendments to the specification dated 10/6/2023 are acknowledged.
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.
Claim 81 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
The claims are drawn to methods, which are one of the four statutory categories.
The claim(s) recite(s):
“diagnosing…the subject with an HPV-associated cancer”.
The step broadly encompasses making a determination regarding the subject based on any criteria. This determination may be made in a purely mental manner and thus, encompasses an abstract idea.
The judicial exception is not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claimed limitations of “amplifying” and “detecting” as set forth in claim 1 add insignificant extra-solution activity to the judicial exceptions. The additional steps are data gathering. See MPEP 2106.05(g).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims encompass the use of PCR, which is known as described in paragraphs 102-105, 101 and 111 of the instant specification.
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.
Claim(s) 1, 2, 3, 69, 70, 71, 72, 74, 80, 81 and 82 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kurnit (US 2006/0160188 A1).
The following rejections are over the generic invention.
Regarding claim 1, Kurnit teaches amplifying HPV DNA with a set of primers specific for HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 in a sample (para. 68; and Table 1A).
Kurnit teaches detecting which HPV types are present in the sample using the PCR results (Fig. 1).
Regarding claim 2, Kurnit teaches the primers recognize the E6 region of HPV (para. 51).
Regarding claim 3, Kurnit teaches using probes for each of the HPV types (para. 21 and 23).
Regarding claim 69, Kurnit teaches the sample is blood or serum (para. 25 and 26).
Regarding claim 70, Kurnit teaches the HPV DNA is from a tumor (para. 21).
Regarding claim 71, Kurnit teaches that HPV in a serum is from cellular lysis (para. 27), making the HPV DNA in the serum cell-free DNA.
Regarding claim 72, Kurnit teaches the sample is a tissue (para. 34; and claim 2) or saliva (claim 19).
Regarding claim 74, Kurnit teaches detecting single copies of HPV DNA (para. 28, 93 and 105).
Regarding claim 80, Kurnit teaches quantifying the amount of HPV DNA in the sample (para. 50).
Regarding claim 81, Kurnit teaches the patient is treated for an HPV-associated cancer (para. 76 and 107).
Regarding claim 82, Kurnit teaches head and neck cancer is a known HPV-associated cancer (para. 4).
Claim(s) 171 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Higginson (WO 2020/055834 A2)
Regarding claim 171, Higginson teaches a step of treating a subject - for example with an anticancer therapeutic agent, with radiation therapy, with surgery, or any combination thereof (p. 10).
Higginson further teaches a sample from the subject was subjected to:
amplifying HPV DNA by performing a polymerase chain reaction to detect HPV circulating tumor DNA in a plasma sample, i.e., a sample with cell-free nucleic acids. The method uses primer pairs consisting of a forward primer and a reverse primer, wherein the forward and reverse primer: each bind to a target sequence that is within the E6 and/or E7 region of the HPV genome. See p. 4. Higginson further teaches the HPV circulating tumor DNA is DNA from HPV type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59. See p. 5.
Higginson further teaches detecting which HPV types are present by determining the quantity of a specific amplified PCR product. See p. 4.
Higginson further teaches the HPV-associated cancer is squamous cell carcinoma of the head and neck (p. 5).
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.
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.
Claim(s) 1, 2, 3, 11, 20, 69, 70, 71, 72, 74, 77, 80, 81 and 82 is/are rejected under 35 U.S.C. 103 as being unpatentable over Higginson (WO 2020/055834 A2) and Buck (Biotechniques. 1999. 27(3): 528-536).
Regarding claims 1, 2 and 69, Higginson teaches amplifying HPV DNA by performing a polymerase chain reaction to detect HPV circulating tumor DNA in a plasma sample. The method uses primer pairs consisting of a forward primer and a reverse primer, wherein the forward and reverse primer each bind to a target sequence that is within the E6 and/or E7 region of the HPV genome. See p. 4. Higginson further teaches the HPV circulating tumor DNA is DNA from HPV type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59. See p. 5.
Higginson further teaches detecting which HPV types are present by determining the quantity of a specific amplified PCR product. See p. 4.
Regarding claim 3, Higginson teaches a probe for each HPV type (p. 3).
Regarding claim 11, Higginson teaches design parameters for HPV specific primers were known and utilized known sequences (p. 3, 18 and 33).
Regarding claim 20, Higginson teaches design parameters for HPV specific probes were known and utilized known sequences (p. 3, 18 and 33).
Regarding claims 70 and 71, Higginson teaches the HPV DNA is circulating tumor DNA (p. 33), derived from a tumor cell.
Regarding claim 72, Higginson teaches the sample is blood, urine, cerebrospinal fluid, saliva, and cervical tissue samples (p. 31).
Regarding claim 74, Higginson teaches the HPV DNA was present at level of 8.1, 13.6 or 10.0 copies/mL (p. 40).
Regarding claim 77, Higginson teaches a droplet digital PR assay (p. 9) as encompassed by the claim.
Regarding claim 80, Higginson teaches quantifying the HPV DNA at levels of 8.1, 13.6 or 10.0 copies/mL (p. 40).
Regarding claim 81, Higginson teaches a step of treating the subject - for example with an anticancer therapeutic agent, with radiation therapy, with surgery, or any combination thereof (p. 10).
Regarding claim 82, Higginson further teaches the HPV-associated cancer is squamous cell carcinoma of the head and neck (p. 19).
While Higginson teaches the above methods, Higginson does not specifically teach PCR reactions for each of the high-risk HPV types.
However, it would have been prima facie obvious to ordinary artisan at the time of filing to have either run individual ddPCR reactions or a series of multiplex ddPCR reactions in order to evaluate each of the high-risk HPV types. One would be motivated to do so in order to assess the risk of a patient in terms of developing an HPV-associated cancer.
Regarding claims 11 and 20, as noted above, Higginson describes using known techniques to design primers and probes to known sequences. Higginson describes numerous primer and probes designed against HPV 16, 18 and 33 (see entire document).
The instant specification also acknowledges the state of the art regarding PCR and primer/probe design stating “Various methods for design and use of probes for detection of target nucleic acids are known to those skilled in the art” (para. 112) and “Various methods for use of primers for amplification of target nucleic acids are known to those skilled in the art” (para. 111).
Thus, the ability to design a variety of primers and probes against the known sequences of E6/E7 of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 is within the abilities of the ordinary artisan.
Buck shows that the state of the art was such that oligonucleotides (capable of being used as primers and probes) could be made for their intended purpose, i.e., to hybridize to and allow amplification and detection of a known target. Buck expressly provides evidence of the equivalence of oligonucleotides in analyzing known sequences. Specifically, Buck invited oligonucleotide submissions from a number of labs (39) (page 532, col. 3), with 69 different primers being submitted (see page 530, col. 1). Buck also tested 95 oligonucleotides spaced at 3 nucleotide intervals along the entire sequence at issue, thereby testing more than 1/3 of all possible 18 mers on the 300 base pair sequence (see page 530, col. 1). When Buck tested each of the oligonucleotides selected by the methods of the different labs, Buck found that every single oligonucleotide worked for its intended purpose (see page 533, col. 1). Further, every single control 18 mer functioned as well (see page 533, col. 1). Buck expressly states
The results of the empirical sequencing analysis were surprising in that nearly all of the primers yielded data of extremely high quality. (p. 535, col. 2.)
Buck teaches that all oligonucleotides selected according to the different criteria used by 39 different laboratories were functional. It is particularly striking that all 95 control primers functioned, which represent 1/3 of all possible oligonucleotides in the target region. Therefore, Buck provides direct evidence that there exists a reasonable expectation of success in designing oligonucleotides to known sequences that function in the analysis of a known sequence.
Designing primers and probes which are equivalents to those taught in the art is routine experimentation. The prior art teaches the parameters and objectives involved in the selection of oligonucleotides that function as primers, see Buck. Higginson and the instant specification further support this. Moreover, there are many internet web sites that provide free downloadable software to aid in the selection of primers and probes drawn from genetic data recorded in a spreadsheet or the parameter of Higginson may be employed. The prior art is replete with guidance and information necessary to permit the ordinary artisan in the field of nucleic acid detection to design primers and probes. As discussed above, the ordinary artisan would be motivated to have designed and tested new primers to obtain additional oligonucleotides that function to detect the E6 or E7 gene of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 and to identify oligonucleotides with improved properties. One having ordinary skill in the art would have a reasonable expectation of success of obtaining additional primers from within the known HPV sequences. Thus, for the reasons provided above, the ordinary artisan would have designed additional primers and probes using teachings known in the art at the time the invention was made.
Claim(s) 65, 67 and 68 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kurnit (US 2006/0160188 A1) in view of Lee (Journal of Neuroscience Methods. 2006. 157:225-229).
Regarding claims 65, 67 and 68, Kurnit teaches amplifying HPV DNA with a set of primers specific for HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 in a sample (para. 68; and Table 1A).
Kurnit teaches detecting which HPV types are present in the sample (Fig. 1).
Kurnit teaches the use of an internal standard but not the additional elements specific to claims 65, 67 and 68.
However, Lee teaches using HERV-3 primers and probes to detect human DNA from cells (p. 226, 2.4. ERV-3 real-time PCR method).
The primers are ERV-3-F and ERV-3-R and the probe is ERV-3-probe, which target the following regions of the sequence NM_001396062.1, respectively: 1625-1646, 1758-1737 and 1674-1702.
The present primers and probes of SEQ ID NOs: 27, 28 and 42 target the following regions of the sequence NM_001396062.1, respectively: 1653-1673, 1710-1691 and 1674-1690.
Thus, the primers and probes of Lee target the same region of the ERV-3 as presently claimed SEQ ID NOs: 27, 28 and 42.
It would have been prima facie obvious to the ordinary artisan to have included the PCR assay of Lee with the PCR assays of Kurnit to confirm the presence of human DNA, that the templates are amplifiable and to quantify the amount of DNA in the sample, for example, prior to running the PCR method of Kurnit. The modification has a reasonable expectation of success as it simply includes the addition of a known PCR method applied to the known source of DNA taught by Kurnit.
Regarding the primer sequences, the primers are obvious variants of those described by Lee as they target the same region of ERV-3 that is of interest to Lee. The probes and primers are functionally equivalent as they each detect the same region of ERV-3. In particular, the probes at issue overlap extensively to the region of ERV-3 with which they hybridize.
Conclusion
No claims allowed.
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.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
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