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 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 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. This judicial exception is not integrated into a practical application and the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because for the reasons set forth below. See MPEP § 2106 for analysis parameters.
The instant claims are drawn to a method of diagnosing high grade squamous intraepithelial lesions (HSIL) in a subject and in some embodiments treating subjects diagnosed with HSIL, which is a statutory category of invention (Step 1: YES).
The instant claims are directed to the natural correlation of a set of miRNA levels to matching the signature of HSIL biomarker positive or negative and then classifying the subject as biomarker positive or biomarker negative based on the natural correlation followed deciding by VGX-3100 administration if biomarker positive. As such the instant claims recite judicial exceptions (JE) in the form of a law of nature and abstract idea (STEP 2A, Prong One: YES).
While in some embodiments, a VGX-3100 treatment is given to a subject who is identified as positive for HSIL biomarkers, in other embodiment the subject is identified as negative for HSIL biomarkers and no treatment is given. In such embodiments, the claimed method is limited to appreciation of the natural correlation to make a decision, i.e., do not administer VGX-3100 to a subject, based on gathered biomarker data. As such, these embodiments do not integrate the JE into a practical application (STEP 2A, Prong Two: NO).
As discussed in detail below, it was well-understood, routine, and conventional at the time of filing to identify an altered miRNA profile in a subject’s biological sample, including those recited in claim 1, and correlate the expression profiles to diagnose HSIL. In the instance claims where no treatment is given after identifying a subject’s negative biomarker status, the claims are limited to only recite WURC data-gathering steps, which does not reasonably provide an inventive concept. As such the instant claims do not recite significantly more than JE (STEP2B: NO).
In view of the foregoing, the instant claims do not constitute patent eligible subject matter under 35 U.S.C 101.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 3, and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tell et al. (WO 2021/168143) and Kowalik et al. (US 2011/0151430 to hereinafter, "Kowalik")
For claim 1, Tell et al. teaches detecting oncogenic HPV (the method further identifies which strain of the oncogenic pathogen the subject has been afflicted with. For example oncogenic virus For instance member of the papillomavirus family the strain of the member of the papillomavirus family is HPV16, HPV18, Para. [00161]) and teaches treating human papillomavirus (HPV) type 16- or HPV type 18-related high grade cervical intraepithelial lesion (HSIL) (the classifier is trained for determining the HPV status of a test subject having an HPV-associated cancer selected from cervical cancer, head and neck squamous cell carcinoma, ovarian cancer, Para. [00219]; methods for treating cancer patients based on whether their cancer is associated with an oncogenic pathogen infection, Para. [0007]; the strain of the member of the papillomavirus family is HPV16, HPV18, Para. [00161]); evaluating one or more biological samples from a subject who has HPV type 16- or HPV type 18-related HSIL (The method includes obtaining a dataset for the subject, the dataset including a plurality of abundance values, where each respective abundance value in the plurality of abundance values quantifies a level of expression of a corresponding gene in a cancerous tissue from the subject, Para. [00166]); and a therapcutically effective amount of VGX-3100 (the first therapy tailored for treatment of cervical cancer associated with an HPV infection is a therapeutic vaccine the therapeutic vaccine is selected from VGX-3100, Para. [00242]; the subject is administered a therapeutically effective dosing regimen, Para. [00210]).
For claims 3 and 4, Tell et al. teaches wherein the plasma sample (para 43 and 161) is isolated from the subject prior to administration of VGX-3100 (the first therapy tailored for treatment of cervical cancer associated with an HPV infection is a therapeutic vaccine the therapeutic vaccine is selected from VGX-3100, Para. [00242]; upon a determination that the subject has a phase 3 cervical cancer associated with an HPV infection, the subject is assigned and/or administered a therapeutically effective dosing regimen, Para. [00210]). It would have been obvious to one of ordinary skill in the art before the priority date to modify Kowalik with the teaching of Tell et al. to provide the method of claim 3, wherein the plasma sample is isolated from the subject prior to administration of VGX-3100. The motivation for doing SO would have been treating the HPV infection after the diagnostic method determining the presence of HPV infection, and thereby using the effective treatment for the corresponding virus.
For claims 3 and 4, Tell et al. teaches wherein the plasma sample (para 43 and 161) is isolated from the subject prior to administration of VGX-3100 (the first therapy tailored for treatment of cervical cancer associated with an HPV infection is a therapeutic vaccine the therapeutic vaccine is selected from VGX-3100, Para. [00242]; upon a determination that the subject has a phase 3 cervical cancer associated with an HPV infection, the subject is assigned and/or administered a therapeutically effective dosing regimen, Para. [00210]). It would have been obvious to one of ordinary skill in the art before the priority date to modify Kowalik with the teaching of Tell et al. to provide the method of claim 3, wherein the plasma sample is isolated from the subject prior to administration of VGX-3100. The motivation for doing SO would have been treating the HPV infection after the diagnostic method determining the presence of HPV infection, and thereby using the effective treatment for the corresponding virus.
Tell et al. do not teach the miRNA to diagnose with.
For claim 1, Kowalik discloses a method of treating human papillomavirus (HPV) (agents and compositions can be administered in an effective dose to an organism or subject in methods for attenuating and/or treating a viral infection, Para. [0030]; the virus is Human Papilloma virus (HPV), Para. [0025]) said method comprising: (a) evaluating one or more biological samples from a subject who has HPV (a method of identifying a virus-specific signature, involving (a) generating a miRNA profile from a test sample obtained from a cell infected with a virus, Para, [0032]; the cell is obtained from a sample obtained from a subject, e.g., a biopsy sample, a blood sample, or another fluid sample, Para. [0043]) and use plasma for test samples (para 161) for the presence of miRNAs (the miRNAs may include miRNAs selected from those listed in Table 1, and Para. [0029]) hsa.miR.375.3p, hsa.miR.425.5p, hsa.miR.193a.5p, hsa.miR.199b.5p, hsa.miR.365a.3p, hsa.miR.223.5p (see Table 1, hsa-miR-223, corresponding miRbase accession number MIMAT0000280 that has the same sequence as hsa.miR.223.5p), hsa.miR.148b.3p, hsa.miR.143,3p, hsa.miR.941, hsa.miR.340.5p, hsa.miR.151a.3p, and hsa-miR-23a, corresponding miRbase accession number MIMAT0000078 that has the same sequence as hsa.miR.23a.3p); (b) calculating normalized levels for the miRNAs (miRNA and miRNA* sequences known at the time of the experiment were probed on microarray chips Data was normalized, Para. [0157]); (c) determining a miRNA signature based on normalized levels of the miRNAs (a method of identifying a virus-specific signature, involving (a) generating a miRNA profile from a test sample obtained from a cell infected with a virus; and (b) comparing the test sample a miRNA profile to an appropriate control sample miRNA profile; wherein one or more alterations between the test sample miRNA profile and the control sample miRNA profile defines the virus-specific miRNA signature, Para. [0032]); (d) categorizing the subject as biomarker positive or biomarker negative based on the miRNA signature (methods of identifying an miRNA signature associated with a specific disease or pathological state of a subject infected with a virus detecting the discase or pathological state of a subject infected with a virus using an miRNA signature associated with a specific disease or pathological state, Para. [0008]); and (e) administering a therapeutically effective amount of a treatment to said subject if the subject is categorized as biomarker positive (methods of treating or attenuating a viral infection in an organism by administering compositions that include an antiviral agent, Para. [0128]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Tell et al. with the teaching of Kowalik et al. The motivation for doing so would have been choosing a detection method that is very accurate in detecting HPV. It is routine in the art to screen for conditions and one of ordinary skill in the art would have been able to choose from art known markers and have the expectation of success knowing that they have been used to detect HPV.
Thus, it would have been prima facie obvious before the effective filing date to modify Tell et al. with other art known biomarkers of Kowalik et al. and have the expectation of success.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tell et al. (WO 2021/168143) and Kowalik et al. (US 2011/0151430) as applied to claims 1, 3, and 4 above, and further in view of Halbert et al. (US 9,128,101, hereinafter, "Halbert")
Tell et al. and Kowalik et al. are discussed above.
Tell et al. and Kowalik et al. do not teach RNA sequencing.
Halbert is in the field of miRNA biomarkers for HPV (MicroRNAs comprise one class biomarkers assessed via methods of the invention, Col. 33, Lns. 58-59; The premalignant condition can be HPV, or other growth or lesion at risk of becoming malignant, Col. 7, Lns. 16-22) and teaches a set of miRNAs (Multiplexing of at least 12 different biomarkers may be performed, Pg. 139, Lns. 54-56) and isomiRs thereof (These biomarkers include a nucleic acid (e.g. miRNA) The biosignature can include any modification of a biomarker, Col. 77, Lns. 1-8).
For claim 2, Halbert teaches wherein the presence of the miRNA is determined by RNA sequencing (Other methods of conducting mutational analysis include miRNA sequencing. Applications for identifying and profiling miRNAs can be done by cloning techniques and the use of capillary DNA sequencing or "next-generation" sequencing technologies. The new sequencing technologies currently available allow the identification of low-abundance miRNAs or those exhibiting modest expression differences between samples, which may not be detected by hybridization-based methods, Col. 148, Lns. 42-50). It would have been obvious to one of ordinary skill in the art before the effective date to modify Tell et al. and Kowalik et al. with the teaching of Halbert to provide the method of claim 1, wherein the presence of the miRNA is determined by RNA sequencing. The motivation for doing so would have been detecting miRNA's that are present at small amounts, and thereby increasing the sensitivity of the diagnostic assay.
Thus, it would have been prima facie obvious before the effective filing date to modify Tell et al. and Kowalik et al. with miRNA sequencing and have the expectation of success.
Claim(s) 5-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tell et al. (WO 2021/168143) and Kowalik et al. (US 2011/0151430) as applied to claims 1, 3, and 4 above, and further in view of Trimble et al. (The Lancet, Volume 386, Issue 10008, 2015, Pages 2078-2088).
Tell et al. and Kowalik et al. are discussed above.
Tell et al. and Kowalik et al. do not teach the same method steps.
Trimble et al. teach the results of the clinical trial of VGX-3100.
For claim 5, the HPV type 16 of 18 is determined by biopsy (page 2080, col 2).
For claim 6, the administration is by intramuscular injection and electroporation (page 2080, col 1, Procedures).
For claim 7, the dose is 6 mg (page 2080, col 1, Procedures).
For claim 8, the administration is 3 times by 12 weeks (page 2078, Methods).
For claim 9, the specific buffer is disclosed but sodium/citrate buffers are well known in the art.
For claims 10-16 and 18, the results of regression, clearance, and non-progression are discussed. (page 2082, col 2). While the term non-progression is not specifically used, the art would have the same result as it is the same method steps treating the same population with the same product.
For claim 17, the immune response was improved compared to other therapeutics (page 2079, col 2, middle).
One of ordinary skill in the art before the effective filing date would have been motivated to use clinically successful method steps of Trimble et al. to use the VGX-3100 of Tell et al. and Kowalik et al. and have the expectation of success knowing that the results were shown using the same product and steps to treat the same population.
Thus, it would have been prima facie obvious before the effective date of filing to modify the method of Tell et al. and Kowalik et al. to use the VGX-3100 administration steps and have the expectation of success.
Conclusion
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/M.G.H/Examiner, Art Unit 1671
/Shanon A. Foley/Primary Examiner, Art Unit 1671
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