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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/25/2025 has been entered.
Status of the Claims
2. Claims 1-19 are the original claims filed on 10/31/2022. In the Preliminary Amendment of 5/8/2023, Claims 1-19 are canceled and new Claims 20-39 are added. Claims 20-39 are all the claims. In the Response of 5/6/2025, Claims 20, 25-29, and 35-39 are amended. Claims 20-39 are all the claims. In the Response of 9/25/2025, claim 20 is amended. Claims 20-39 are all the claims.
This Office Action contains new grounds for rejection.
Priority
3. USAN 18/051,307, filed 10/31/2022 and having 1 RCE-type filing therein, is a Continuation of 16/362,940, filed 03/25/2019, now U.S. Patent # 11513122, 16/362,940 is a Continuation of PCT/EP2017/074150, filed 09/25/2017, and claims foreign priority to EP 17166789.2, filed 04/18/2017, and claims foreign priority to EP 16190591.4, filed 09/26/2016.
Information Disclosure Statement
4. As of 10/22/2025, a total of one (1) IDS is filed: 10/31/2022. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Claim Objections
5. The objection to Claims 20-39 because of informalities is withdrawn.
Applicants have amended Claim 20 to recite: (iii) when the DC-related gene signature expression level is above the reference DC-related gene signature expression level.”
Specification
6. The objection to the abstract of the disclosure because it contains indefinite language, “e.g.,” is withdrawn. The phrase is deleted in the Response of 9/25/2025.
Rejections 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 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.
7. The rejection of Claims 20-39 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11513122 is maintained.
Applicants allege the species of RCC and NSCLC being restricted under speciation in the Office Action of 2/19/2021 (sec. 4) in Application no. 16/362,940 (USPN 11513122) renders the methods “per se” patentably distinct and nonobvious.
Response to Arguments
Applicants are invited to file a change in the status of the application from a continuation to a divisional pursuant to the rules for updating an application data sheet. MPEP 37 CFR 1.76(c) allows for updating an application data sheet until the payment of the issue fee.
The rejection is maintained.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
8. Claims 20-39 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim interpretation
A Claims 20-23 and 25-39 are drawn to a method of determining the abundance of dendritic cells (DCs) in a RCC tumor tissue sample to predict response to treatment with the PD-1 axis inhibitor, atezolizumab, in a patient. The abundance of DCs characterized by enhanced expressions of at least one of XCR1, IRF8, BATF3 and FLT3 is used to predict a clinical response to the PD-L1 blockade treatment.
The claims are examined based on whether enhanced expression of less than all four markers can reliably predict response to treatment of RCC in a patient with the PD-1 axis inhibitor, atezolizumab. The claims are examined whether the specification and data support the use of single DC-related gene or less than all four DC-related genes based on the interpretation of the claims.
Disclosure in the Specification
The abstract of disclosure specifically teaches that all four markers are used in the evaluation of the signature level in order to advance the method to the administration of atezolizumab: “Methods of determining the abundance of dendritic cells (DCs) in a tumor tissue sample are used to predict response to treatment with a PD-1 axis inhibitor. The abundance of DCs characterized by enhanced expressions of XCR1, IRF8, BATF3 and FLT3 predicts clinical response to the PD-L1 blockade treatment.”
Figure 10 shows “the Kaplan-Meier survival cures based on the expression of a cumulative DC gene signature including genes: IRF8, FLT3, BATF3 and XCRL. A higher DC signature score correlates with clinical benefit to a PD-1 axis inhibitor atezolizumab in patients with RCC.” Those data are not obtained from a signature assessment for just any one but for all four markers. Example 3 teaches:
[0166] As several genes linked to human dendritic cell development were associated with the survival advantages, we investigated the impact of multiple genes involved in human DC development and function by defining a cumulative DC gene score (DC score) reflecting the cumulative expression of these marker genes.
[0169] We also investigated the impact of multiple genes involved in human DC development and function (XCR1, BATF3, FLT3, and IRF8) by defining a cumulative DC gene score (DC score) reflecting the cumulative expression of these marker genes.
[0171] DC-related gene signature correlates with survival in patients treated with atezolizumab as shown in the Kaplan-Meier survival curves based on the expression of a cumulative DC gene signature including genes: XCR1, IRF8, FLT3, and BATF3 (FIG. 11).
While specification demonstrates the correlation of each marker in its correlation to survivability in RCC (Figure 8A-8B), the specification does not suggest nor practice the use of single gene marker expression as a diagnostic in being correlated to responsiveness to atezolizumab but repeatedly describes cumulative DC scoring for the combination of markers.
The POSA could reasonably conclude from those data shown in the application as filed that the cumulative expression of the markers is what comprises the DC gene score (DC score) in the RCC patient population in the assessment whether to treat the patient with atezolizumab.
B Claims 20-39 are drawn to a method of treating a RCC patient with a therapeutically effective amount atezolizumab.
“treatment”: the specification is unequivocal in teaching the phrase encompasses both therapeutic and prophylactic endpoints.
[0097] As used herein, “treatment” (and grammatical variations thereof such as “treat” or “treating”) refers to clinical intervention in an attempt to alter the natural course of the individual being treated, and can be performed either for prophylaxis or during the course of clinical pathology. Desirable effects of treatment include, but are not limited to, preventing occurrence or recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis. In some embodiments, antibodies are used to delay development of a disease or to slow the progression of a disease.
“therapeutically effective amount”: the specification is unequivocal in teaching the phrase encompasses both therapeutic and prophylactic endpoints.
[0093] A “therapeutically effective amount” refers to an amount of a therapeutic agent to treat or prevent a disease or disorder in a mammal. In the case of cancers, the therapeutically effective amount of the therapeutic agent may reduce the number of cancer cells; reduce the primary tumor size; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and/or relieve to some extent one or more of the symptoms associated with the disorder. To the extent the drug may prevent growth and/or kill existing cancer cells, it may be cytostatic and/or cytotoxic. For cancer therapy, efficacy in vivo can, for example, be measured by assessing the duration of survival, time to disease progression (TTP), the response rates (RR), duration of response, and/or quality of life.
Disclosure in the Specification
Example 3 shows DC biomarker data obtained tumor specimens from PD-L1+ RCC patients in a clinical trial receiving atezolizumab (NCT01375842) with cumulative XCR1, IRF8, FLT3, and BATF3 levels correlating with survival advantages in the patients.
Example 4 shows DC biomarker data obtained tumor specimens from PD-L1+ NSCLC patients in a clinical trial receiving atezolizumab (NCT01903993) with cumulative XCR1, IRF8, FLT3, and BATF3 levels correlating with survival advantages in the patients.
The specification does not demonstrate a single example of the method being associated with the prevention of RCC in a PD-L1+ patient where the prevention is correlated with the panel of DC gene markers.
Conclusion
9. No claims are allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached on Mon-Fri 9 AM-5 PM.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643