Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 04 December, 2025. Claims 1, 2-11, and 13 are pending in the instant application.
35 U.S.C. § 112(b)
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.
Claims 1, 3-11, and 13 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. Two separate requirements are set forth under this statute: (1) the claims must set forth the subject matter that applicants regard as their invention; and (2) the claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant.
Claim 1 references a treatment method wherein the amount of CEACAM1 or PSTPIP2 is measured. However, it is not readily manifest if the claims are measuring mRNA or protein levels. Moreover, the claim also references “said RNA” in line five. However, there is insufficient antecedent basis for this limitation in the claim. Appropriate correction is required.
35 U.S.C. § 101
The following is a quotation of 35 U.S.C. § 101 which 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 therefore, subject to the conditions and requirements of this title.
The previous rejection of claim(s) 1-13 under 35 U.S.C. § 101 because the claimed invention is directed to a judicial exception [e.g., law of nature, natural phenomenon, product of nature, abstract idea] without significantly more, is hereby withdrawn in response to Applicant’s amendment.
35 U.S.C. § 112(a)
The following is a quotation of 35 U.S.C. § 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Enablement
Claims 1, 3-11, and 13 are rejected under 35 U.S.C. § 112(a), as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The claims of the instant application are directed toward a method of treating a viral infection comprising measuring the amount of CEACAM1 or PSTPIP2 levels in a subject, comparing said levels to an uninfected subject, and administering an antiviral to the subject if their levels exceed those of the uninfected subject.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
1) The disclosure fails to provide a direct correlation between CEACAM1 or PSTPIP2 levels and any given viral infection. The disclosure fails to provide any type of comparison involving the viral load of any given virus and CEACAM1/PSTPIP2 expression levels.
2) The disclosure fails to provide a direct correlation between additional biomarkers set forth in Tables 1-6A, 15A, or 15B. Table 1 encompasses the following biomarkers: AIM2, ANKRD2, BMX, C19ORF59, CD177, CEACAM1, CLEC4D, CMPK2, EIF1AY, EIF2AK2, EPSTI1, FFAR3, GALM, IFITM3, INCA, IRF7, JARID1D, JUP, MT1G, MT2A, OTOF, PLSCR1, PSTPIP2, RGS1, TREML4, UTY, PARP12, PNPT1, TRIB2, UC003HRL.1, USP41, ZCCHC2, and TCONS_00003184-XLOC_001966. However, the disclosure fails to identify which biomarkers correlate with any given viral infection.
As previously set forth, patients (HIV-1-, HBV-, and HCV-negative) underwent two multiplex-PCR diagnostic assays from nasal swab samples: (i) Seeplex® RV15, for detection of parainfluenza virus 1, 2, 3, and 4, coronavirus 229E/NL63, adenovirus A/B/C/D/E, bocavirus 1/2/3/4, influenza virus A and B, metapneumovirus, coronavirus OC43, rhinovirus A/B/C, respiratory syncytial virus A and B, and Enterovirus, and (ii) Seeplex® PB6 for detection of Streptococcus pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Legionella pneumophila, Bordetella pertussis, and Mycoplasma pneumoniae. A microarray experiment was also performed to assess gene expression in subjects. RNA samples were hybridized to a Human Gene 1.0 ST Array which examines transcription of over 28,000 human genes. Software was utilized to assess various statistical parameters (e.g., area under the receiver operating curve (AUC)) and the purported ability of any given RNA determinant to measure viral or bacterial infections was determined. Perusal of the data failed to provide a direct correlation between any given RNA determinant and any specific virus. The data fails to correlate CEACAM1/PSTPIP2 expression with any specific virus.
The claims recite additional biomarkers from Tables 2-6A, 15A, and 15B. These tables contain 27 (CYBRD1,…,TCONS_12_000023; Table 2), 22 (CCL2,…,PPM1K; Table 3), 64 (APOBEC3C,…,IFIT3; Table 4), 7 (RSAD2,…,IFIT3; Table 5A), 3 (BTN3A3, RNF213, and PARP9; Table 6A), ~900 (TC14000584.hg.1,…,TC02001333.hg.1; Table 15A), and ~250 (TC0X002125.hg.1,…,TC0X001784.hg.1; Table 15B), respectively. Once again, the disclosure fails to provide a direct correlation between RNA determinant expression and any given viral infection. For example, if a sample comes back with elevated levels of AIM, CYBRD1, and CCL2, what type of viral infection does this detect?
3) The disclosure fails to provide adequate guidance with respect to the establishment of predetermined biomarker levels for any given biomarker. As noted supra, an inordinate number of RNA determinants/biomarkers were screened using a chip array. However, the disclosure failed to provide adequate guidance with respect to the level of expression of any given determinant/biomarker and viral infection. If the skilled artisan detects a CEACAM1/PSTPIP2 transcript, what level would be predictive of any given viral infection? What constitutes a positive or negative sample? The disclosure is silent with respect to this issue.
4) The disclosure fails to provide adequate guidance with respect to any given antiviral treatment. In order to practice the claimed invention, the skilled artisan would need to know how any give RNA determinant/biomarker correlates with a specific viral infection. The specification states that patient samples were subject to parainfluenza virus 1, 2, 3, and 4, coronavirus 229E/NL63, adenovirus A/B/C/D/E, bocavirus 1/2/3/4, influenza virus A and B, metapneumovirus, coronavirus OC43, rhinovirus A/B/C, respiratory syncytial virus A and B, and Enterovirus testing. The skilled artisan would utilize different antiviral agents depending upon the virus. A coronavirus-specific antibody would most likely be ineffective against an RSV infection. Thus, the skilled artisan would need to understand the correlation between any given determinant and the specific virus in order to practice the claimed invention.
5) The claim breadth is excessive and encompasses an inordinate number of biomarker combinations. As noted supra, the claims encompass an inordinate number of combinations of RNA determinants/biomarkers. Tables 1-6A, 15A, and 15B comprise the following number of markers: 33 (AIM2,…,TCONS_00003184-XLOC_001966; Table 1), 27 (CYBRD1,…,TCONS_12_000023; Table 2), 22 (CCL2,…,PPM1K; Table 3), 64 (APOBEC3C,…,IFIT3; Table 4), 7 (RSAD2,…,IFIT3; Table 5A), 3 (BTN3A3, RNF213, and PARP9; Table 6A), ~900 (TC14000584.hg.1,…,TC02001333.hg.1; Table 15A), and ~250 (TC0X002125.hg.1,…,TC0X001784.hg.1; Table 15B), respectively. The claims are not limited to a specific combination of RNA determinants/biomarkers.
The claims are also not limited to any particular viral infection. The claim breadth encompasses any viral infection including dsDNA viruses (e.g., Adenoviruses, Herpesviruses, and Poxviruses), ssDNA viruses (e.g., Parvoviruses), dsRNA viruses (e.g., Reoviruses), ssRNA(+) viruses (e.g., Coronaviruses, Picornaviruses, and Togaviruses), ssRNA(-) viruses (e.g., Orthomyxoviruses and Rhabdoviruses), ssRNA-RT viruses (e.g., Retroviruses), and dsDNA-RT viruses (e.g., Hepadnaviruses). Once again, however, the disclosure fails to provide a direct correlation between expression levels of any given RNA determinant/biomarker and any specific viral infection.
6) The identification and development of suitable RNA determinants /biomarkers for the identification of viral infection has been challenging. For example, AIM2 is expressed in response to some viral infections (e.g., vaccinia virus), certain bacterial infections (e.g., Aspergillus, Listeria, and Mycobacterium), and in inflammatory responses (e.g., psoriasis, dermatitis, and arthritis) (Man et al., 2016). However, simply measuring elevated levels of AIM2 does not demonstrate that any given subject has a viral infection. Biserni et al. (2021) examined the prior art with respect to the development of suitable biomarkers for human adenovirus (HAdV) infection. While some putative serum markers were identified, nevertheless, there usefulness in diagnosis and clinical management remain to be demonstrated. For example, CRP and IL-10 were elevated during early infection. However, these serum markers are also elevated during bacterial infections.
7) The disclosure fails to provide any working embodiments. As set forth in the preceding paragraph, the development of suitable RNA determinants/biomarkers for viral detection has been challenging. While the disclosure describes a microarray experiment to assess gene expression in subjects, nevertheless, perusal of the data failed to provide a direct correlation between any given RNA determinant and any specific virus. The data fails to correlate CEACAM1/PSTPIP2 expression with any specific virus. Moreover, statistical analyses utilizing AUC has potential limitations including the following: 1) Distorted calibration; patient characteristics and disease rates may vary greatly between sources (local clinics, regional health centers, different countries, etc.). AUC is not reliable for imbalanced datasets. If the case has a significant class imbalance (e.g., fraud detection where fraud cases are rare), AUC can be misleading. A high AUC score may still fail at predicting positive cases. 2) AUC does not consider decision thresholds. It evaluates model performance across all classification thresholds; however, certain applications may require a specific threshold for decision-making. 3) Statistical overfitting; high AUC scores (close to 1.0) might be indicative of overfitting if the model has used one dataset. Medical data may contain measurement error; biomarker expression results may vary with assay location and kits. Moreover, this type of statistical analysis does not provide any insight pertaining to the sensitivity and specificity of an assay.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that undue experimentation would be required to practice the claimed invention. Applicant’s arguments have been carefully considered but are not deemed to be persuasive for the reasons of record set forth supra. Additionally, the response failed to proffer any data demonstrating that CEACAm1/PSTPIP2 levels are reasonably predictive of viral infection.
Nonstatutory 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 obviousness-type 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 U.S.P.Q.2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 U.S.P.Q.2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 U.S.P.Q. 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 U.S.P.Q. 761 (C.C.P.A. 1982); In re Vogel, 422 F.2d 438, 164 U.S.P.Q. 619 (C.C.P.A. 1970); and In re Thorington, 418 F.2d 528, 163 U.S.P.Q. 644 (C.C.P.A. 1969).
A timely filed terminal disclaimer in compliance with 37 C.F.R. § 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 M.P.E.P. § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in M.P.E.P. § 2159. See M.P.E.P. §§ 706.02(l)(1)-706.02(l)(3) 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 C.F.R. § 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
The previous rejection of claims 1 and 5-11 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,466,331, is hereby withdrawn in response to Applicant’s amendment.
Action Is Final
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. § 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 extension fee pursuant to 37 C.F.R. § 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.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 21 March, 2026