DETAILED CORRESPONDENCE
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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 5, 2025 has been entered.
This action is in response to the papers filed November 5, 2025. Currently, claims 31-39, 41-48, 50-52 are pending. Claims 41-44, 48, have been withdrawn as drawn to non-elected subject matter.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow.
Any objections and rejections not reiterated below are hereby withdrawn.
The 112B rejections have been withdrawn in view of the amendments to the claims.
Election/Restrictions
Applicant's election without traverse of PTPN22 gene in the paper filed December 3, 2024 is acknowledged. Claims 40-44, 48-49, 51 have been withdrawn as drawn to non-elected subject matter.
Applicant further elected PTPN22 and PLK2 on November 5, 2025 as the combination for the newly amended claims.
The examiner has required restriction between subcombinations usable together. Where applicant elects a subcombination and claims thereto are subsequently found allowable, any claim(s) depending from or otherwise requiring all the limitations of the allowable subcombination will be examined for patentability in accordance with 37 CFR 1.104. See MPEP § 821.04(a). 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.
The requirement is still deemed proper and is therefore made FINAL.
Response to Arguments
The response provides election of PTPN22 and PLK2 on November 5, 2025. The response argues the withdrawal of Claims 40-44, 48-49 and 51 is improper because the claim encompasses the elected species of a method that uses at least PTPN22. This argument has been considered but is not convincing because the examiner has required restriction between subcombinations usable together. Applicant elected PTPN22 which is a subcombination of genes. The subcombination of methods requiring PTPN22 alone is not allowable. Where applicant elects a subcombination and claims thereto are subsequently found allowable, any claim(s) depending from or otherwise requiring all the limitations of the allowable subcombination will be examined for patentability in accordance with 37 CFR 1.104. See MPEP § 821.04(a). 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.
Thus, for the reasons above and those already of record, the rejection is maintained.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
Information Disclosure Statement
Applicant filed a 41 page Information Disclosure Statements (IDS) with 866 citations on April 21, 2025. The IDS has been reviewed to the extent reasonably possible.
Applicant is reminded that "burying" relevant references ina lengthy IDS is discouraged. See, e.g., Molins PLC v. Textron Inc., 48 F.3d 1172, 33USPQ2d 1823, 1831 (Fed. Cir. 1995) The court concluded that, by “burying” Wagenseil in a multitude of other references, Hirsh and Smith intentionally withheld it from the PTO because this manner of disclosure was tantamount to a failure to disclose. Citing PennYan Boats, Inc. v. Sea Lark Boats, Inc., 359 F.Supp. 948, 175 USPQ 260(S.D. Fla. 1972), aff'd, 479 F.2d 1328, 178 USPQ 577 (5th Cir.), cert.denied, 414 U.S. 874 (1973), the court stated that Hirsh's and Smith's failureto highlight Wagenseil in light of their knowledge of Whitson's actions in theforeign prosecutions violated their duty of candor to the PTO. Citing ourprecedent, Textron asserts that Smith's and Hirsh's conduct is “inexcusable,fraudulent, and cannot operate to cure Whitson's inequitable conduct.” See
Rohm & Haas Co. v. Crystal Chem. Co., 722 F.2d 1556, 220 USPQ 289(Fed.Cir. 1983), cert. denied, 469 U.S. 851 (1984) (where intentionalmaterial misrepresentations have been made, a “cure” through voluntaryefforts during prosecution must be demonstrated by clear, unequivocal, andconvincing evidence).
Claim Rejections - 35 USC § 112-Description
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.
Claims 31-39, 45-47, 50-52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a likelihood score. Neither the specification nor the art describes how the likelihood score is calculated. The elected invention is directed to a PTPN22 and an additional gene.
The specification teaches expression measurements for RNA transcripts or combinations of RNA transcript levels are formulated into linear or non-linear-models or algorithms (eg., an “expression signature”) and converted into a likelihood score. The likelihood score may indicate the probability that a biological sample is from a patient who will benefit from radiation therapy (para 126). The specification provides no guidance how expression signatures are converted into likelihood scores and how to know whether the likelihood scores are greater than or less than 0.
The specification teaches a PORTOS score is the resulting score of a 24 gene model. The specification states a 24-gene model was developed using ridge-penalized Cox regression to model the interactions of the genes and radiation therapy to generate the PORTOS (Table 2).
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The specification provides a pairwise comparison of PTEN22 and the claimed genes in Table 4 and 5. Table 4 is directed to univariate and multivariate analysis of each of the genes individually. PTPN22 demonstrates a significant p-value. Each of the other genes are also individually significant.
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Table 5 provides pairwise combination of PTPN22 and the other genes. When analyzed in pairwise comparison, numerous combinations of the PTPN22 expression and the additional gene were not significantly associated. Thus, adding additional genes does not render the additional combinations described.
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The specification does not describe a likelihood score or a PORTOS score with combination of three, four, five, six, etc genes and levels of expression. Instead, the specification provides single gene analysis, pairwise analysis and a PORTOS score in a 24-gene model score.
The art does not describe how to obtain or calculate a likelihood score with PTPN22 gene expression and 2, 3, 4, 5 6,…. additional genes. In particular, Zhao teaches development and validation of a 24-gene predictor or response to postoperative radiotherapy in prostate cancer, PORTOS (see Lancet Oncol. Vol. 17, No. 11, pages 1612-1620, November 2016). The art further defines PORTOS as an expression signature of 24 DNA damage repair and immune pathway genes (see ASTRO 2022, Dr. Dal Pra). The art does not provide any description of a PORTOS score relying on a subcombination of 3 or more genes.
The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general guidance is what is needed. Since the disclosure fails to describe the calculation, how the calculation is performed or how a single gene can form a likelihood or PORTOS score, a likelihood or PORTOS score is insufficient to describe the genus. One of skill in the art would conclude that applicant was not in possession of the claimed score using a single PTPN22 or how to determine if the score was less than or equal to 0.
Response to Arguments
The response traverses the rejection. The response asserts the claims have been amended to require PTPN22 and one or more genes from the group recited in the claim. The response cites Tables 4 and 5 to support the claims. This argument has been considered but is not convincing because the claim encompasses PTPN22 and 2, 3, 4, or more additional genes. The specification teaches Table 4 and 5 that illustrate the significance of the single gene PTPN22 and the pairwise analysis of PTPN22 and the genes recited in the claim. The claims also encompass combinations of 3, 4, 5, 6, and more genes for determining a likelihood score based on expression levels to indicate the probability that a patient will benefit from radiation therapy. The response points to Tables 4 and 5 for performance of 24 genes. The specification does not provide any description of likelihood scores for PTPN22 and two or more genes. It is clear that not all combinations are suitable for determining whether a subject is likely to benefit from post-operative radiation therapy. The specification teaches 15 of the pairwise comparisons with PTPN22 were not associated. The specification does not describe which combinations of 3 genes, 4, 5, 6, etc would indicate the probability that a patient will benefit from radiation therapy.
The examiner notes the p-value for PTPN22 in Table 4 is less than 0.05. The examiner also notes numerous combinations of genes comprising PTPN22 is larger than 0.05 to signify no significant association. One of the combinations approaches 1 to signify no association at all. There is no description or discussion how p-values may be used to calculate a likelihood score to indicate whether a subject is likely to benefit from post-operative radiation therapy as required by the claims. The response is focused exclusively on the pairwise and single gene analysis and does not describe or discuss the breadth of the claims directed to 3, 4, 5, 6 or more genes in the likelihood score.
Thus, for the reasons above and those already of record, the rejection is maintained.
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 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.
Claims 31-39, 45-47, 50 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over Claims 1-9 of U.S. Patent No. 11,414,708.
The third sentence of 35 U.S.C. 121 prohibits the use of a patent issuing on an application in which a requirement for restriction has been made, or on an application filed as a result of such a requirement, as a reference against any divisional application in a nonstatutory double patenting rejection, if the divisional application is filed before the issuance of the patent. The 35 U.S.C. 121 prohibition applies only where the Office has made a requirement for restriction. The prohibition does not apply where the divisional application was voluntarily filed by the applicant and not in response to an Office requirement for restriction. The U.S. Court of Appeals for the Federal Circuit has concluded that the protection of 35 U.S.C. 121 does not extend to all types of continuing applications, stating that “the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353, 1362, 86 USPQ2d 1001, 1007-1008 (Fed. Cir. 2008). Here the instant application is a continuation, rather than a divisional of ‘933. In the event that applicant changed the status of the instant application to a divisional, this rejection would be reconsidered.
Although the conflicting claims are not identical, they are not patentable distinct from each other because Claims 31-39, 45-47, 50-52 of the instant application is generic to all that is recited in Claims 1-9 of U.S. Patent No. 11,414,708. That is, Claims 1-9 of U.S. Patent No. 11,414,708 falls entirely within the scope of Claims 31-39, 45-47, 50-52, or in other words, 31-39, 45-47, 50-52 are anticipated by Claims 1-9 of U.S. Patent No. 11,414,708. Here, Claim 1 of U.S. Patent No. 11,414,708 recites
1. A method for treating a subject having prostate cancer, comprising:
a) obtaining a post-operative radiation therapy outcome score (PORTOS) that has been calculated using a level of expression of a plurality of genes in the biological sample, wherein said plurality of genes comprises DRAM1, KRT14, PTPN22, ZMAT3, ARHGAP15, IL1B, ANLN, RPS27A, MUM1, TOP2A, GNG11, CDKN3, HCLS1, DTL, IL7R, UBA7, NEK1, CDKN2AIP, APEX2, KIF23, SULF2, PLK2, EME1, and BIN2;
b) determining whether or not the subject is likely to benefit from post-operative radiation therapy based on the PORTOS score, wherein a PORTOS greater than 0 indicates that the subject will benefit from the post-operative radiation therapy and a PORTOS less than or equal to 0 indicates that the subject will not benefit from the post-operative radiation therapy; and
c) if the PORTOS indicates that the subject will benefit from the radiation therapy, then administering the post-operative radiation therapy to the subject, and if the PORTOS does not indicate that the subject will benefit from the post-operative radiation therapy, then administering a cancer treatment other than the post-operative radiation therapy to the subject.
The instant claims and elected subject matter of analysis of one gene PTPN22 is generic to and anticipated by the issued claims.
Claims 32-39 of the instant claims are analogous to Claims 2-9 of ‘708.
Claims 45-47, 50 encompass the PTPN22 gene elected.
Response to Arguments
The Applicant requests that this rejection be held in abeyance until allowable subject matter is found in the pending application. This request has been noted and is denied. See 804(I)(b)(1) and 37 C.F.R. 1.111(b), which allows that some objections may be held in abeyance but includes no provision for holding rejections in abeyance. Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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 on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
December 4, 2025