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 .
2. This action is in response to the papers filed December 29, 2025. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicant's amendments. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
Claims 1, 5-15, and 18 are currently pending.
Claims 9-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 11, 2023.
Priority
3. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
Regarding Claims 1, 5-8, and 14-15, the disclosure of the prior-filed application, Application No. 62685410 filed on June 15, 2018, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In particular the provisional application does not provide support for the criteria (i-v) and (vi-vii) that are set forth in claim 1.
Therefore Claims 1, 5-8, and 14-15 only get priority back to PCT/US2019/036953 which was filed on June 13, 2019.
Regarding Claim 18, the disclosure of the prior-filed application, Application No. 62685410 filed on June 15, 2018, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In particular the provisional application does not provide support for using the combination of SEQ ID NOs: 1-3 OR SEQ ID NOs: 4-7 to identify a patient who will benefit from adjuvant chemotherapy. The method disclosed in the provisional requires the combination of SEQ ID NOs: 1-7. Further the provisional does not provide support for the criteria (i-v) and (vi-vii) that are set forth in claim 18.
Therefore Claim 18 only gets priority back to PCT/US2019/036953 which was filed on June 13, 2019.
Response To Arguments- Priority
4. In the response the Applicants argue that they have amended Claim 1 to recite “quantifying mRNA expression of at least three genes comprising SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3, and at least four genes comprising SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, and SEQ ID NO:7”. Applicant argue that this limitation is fully supported by U.S. provisional application No. 62/685,410.
The amendment has been fully considered and the Examiner agrees there is support for the combination of SEQ ID NOs: 1-7. However it is noted that newly added claim 18 recites “quantifying mRNA expression of at least three genes comprising SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3, or at least four genes comprising SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, and SEQ ID NO:7” and this is not supported in the provisional application. Therefore Claim 18 only gets priority back to PCT/US2019/036953 which was filed on June 13, 2019.
Additionally the Applicants argue that the predictive model recited in instant Claim 1 is sufficiently described throughout the provisional application to support the claimed invention. For example, at page 4 of the provisional application, the legend for Supplementary Figure 1 explicitly states "The 7- gene prognostic and predictive NSCLC model. A. The 7-gene model in decision-tree format. B. The 7-gene prognostic and predictive model in rule-base format."
This argument has been fully considered but is not persuasive. While page 4 refers to Supplementary Figure 1, the figure was not filed with the provisional application. In the absence of the figure, any information that may have been provided in the figure cannot be relied upon. Therefore Claims 1, 5-8, and 14-15 only get priority back to only gets priority back to PCT/US2019/036953 which was filed on June 13, 2019.
Claim Rejections - 35 USC § 112(a)
5. 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.
Claims 6-7 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 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.
Scope of the Claims/Nature of the Invention
Claim 6 is drawn to a method wherein an increased mRNA expression of SEQ ID NO:5 is used to determine that said patient will show chemoresistance to adjuvant chemotherapy of carboplatin.
Claim 7 is drawn to a method wherein an increased mRNA expression of SEQ ID NO:6 is used to determine that said patient will show chemoresistance to adjuvant chemotherapy of one or more of
(a) carboplatin and Taxol (paclitaxel),
(b) carboplatin and Taxotere (docetaxel),
(c) cisplatin and Taxotere (docetaxel), and
(d) cisplatin and Taxol (paclitaxel).
The nature of the invention requires reliable correlation between the mRNA level of the markers and the benefit of the recited specific adjuvant chemotherapies.
Teachings in the Specification and Examples
The specification teaches the following:
[0079] Another method of this invention provides for the high expression of FUT7 (SEQ ID NO:5) predicted chemosensitivity to carboplatin.
[0080] Another method of this invention provides for the high expression of ZNF71 (SEQ ID NO:6) predicted chemosensitivity to carboplatin and Taxol (paclitaxel), carboplatin and Taxotere (docetaxel), cisplatin and Taxotere (docetaxol), and cisplatin and Taxol (paclitaxel).
State of the Art and the Unpredictability of the Art
While methods of measuring mRNA levels are known in the art, methods of correlating mRNA levels with a phenotype (such as responsiveness to specific adjuvant chemotherapies) are highly unpredictable. The unpredictability will be discussed below.
Claim 6 broadly encompass a method wherein an increased level of SEQ ID NO: 5 is associated with chemoresistance to the following adjuvant chemotherapy: carboplatin. However this directly contradicts the teachings in the specification. The specification only provides enablement for a correlation between high expression of SEQ ID NO: 5 and chemosensitivity to carboplatin. Any other correlation would be highly unpredictable.
Claim 7 broadly encompass a method wherein an increased level of SEQ ID NO: 6 is associated with chemoresistance to the following adjuvant chemotherapies:
(a) carboplatin and Taxol (paclitaxel),
(b) carboplatin and Taxotere (docetaxel),
(c) cisplatin and Taxotere (docetaxel), and
(d) cisplatin and Taxol (paclitaxel).
However this directly contradicts the teachings in the specification. The specification only provides enablement for a correlation between high expression of SEQ ID NO: 6 and chemosensitivity to these adjuvant chemotherapies. Any other correlation would be highly unpredictable.
Quantity of Experimentation:
For the reasons discussed above, it would have required undue, unpredictableexperimentation of a trial- and-error nature to practice the recited methods in the full,broad scope encompassed by the rejected claims. The type of experimentation requiredis not routine and the subsequent data analysis is sophisticated. Furthermore, theoutcome of the tasks is entirely unpredictable based on the limited data and analysisprovided in the instant specification.Conclusions:
Herein, although the level of skill in the art is high, given the lack of disclosure in the specification and in the prior art and the unpredictability of the art, it would require undue experimentation for one of skill in the art to make and use the invention as broadly claimed.
Response To Arguments- 35 USC 112(a)
6. In the response the Applicants traversed the rejection under 35 USC 112(a). The Applicants argue that they have amended instant Claims 5-8 to recite "wherein an increased mRNA expression of SEQ ID NO:... is used to determine that said patient will show chemoresistance to adjuvant chemotherapy..."
The amendments have been fully considered. While they overcome the rejections over claims 5 and 8, they are insufficient to overcome the rejections over claims 6-7 for the reasons set forth above.
Claim Rejections - 35 USC § 102
7. 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.
Claims 1, 5, 8, 14-15, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guo (EbioMedicine 32 (2018) 102-110 Available online 1 June 2018).
It is noted for the record that the 102(b)(1) exception does NOT apply to the prior art of Guo (EbioMedicine 32 (2018) 102-110 Available online 1 June 2018) because the reference was published more than 1 year before the filing date of PCT/US2019/036953 6/13/2019.
Regarding Claims 1 and 18 Gu teaches a method comprising: extracting total RNA from a tumor of non-small cell lung cancer of a patient after the surgical resection; generating complementary DNA (cDNA) of the extracted total RNA from said patient tumor; quantifying of mRNA expression of 7 genes of ABCC4 (SEQ ID NO:1), CCL19 (SEQ ID NO:2), SLC39A8 (SEQ ID NO:3), CD27 (SEQ ID NO:4), FUT7 (SEQ ID NO:5), ZNF71 (SEQ ID NO:6); and DAG1 (SEQ ID NO:7); normalizing of the quantification of said 7 genes with the quantification of a control gene UBC (SEQ ID NO:8) by subtracting from the mRNA expression, mRNA expression of SEQ ID NO: 8 (page 103, col 2 to page 104, col 1, col 2). Guo teaches that the 7-gene assay predicted chemotherapy benefit (high risk) patients (page 105, col 2). Guo discloses the 7 gene model in decision tree format and rule based format (Supplemental Figures 1A and 1B). Guo teaches that treating patients with adjuvant chemotherapy (Table 1).
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Regarding Claim 5 Guo teaches increased expression level of ABCC4 is correlated with chemoresistance in patients treated with (a) cisplatin and Taxol (paclitaxel), (b) cisplatin and Taxotere (docetaxel), (d) carboplatin and Taxol (paclitaxel), (e) carboplatin and Taxotere (docetaxel), and (f) Taxol (paclitaxel) (page 106, col 1, Table 2).
Regarding Claim 8 Guo teaches increased expression of SLC39A8 is correlated with chemoresistance in patient treated with (a) Taxol (paclitaxel), and (b) Alimta (pemetrexed) (page 106, col 2 Table 2).
Regarding Claim 14 Guo teaches a method wherein the one or more adjuvant chemotherapies are selected from a group consisting of: (a) cisplatin and Taxol (paclitaxel),(b) cisplatin and Taxotere (docetaxel), (c) carboplatin, (d) carboplatin and Taxol (paclitaxel), (e) carboplatin and Taxotere (docetaxel), (f) Taxol (paclitaxel), and (g) Alimta (pemetrexed) (page 106, col 2 Table 2).
Regarding Claim 15 Guo teaches a method further comprising validating protein expression of ZNF71 (SEQ ID NO: 6) (page 104 col 2 and 106, col 2).
Response To Arguments- 35 USC 102
8. In the response the Applicants traversed the rejection under 35 USC 102. The Applicants state that they believe that the claimed invention is entitled to the priority date of June 15, 2018, and respectfully requests that the Office restore the priority claim of the present application to June 15, 2018, for this claim, then withdraw the rejection for alleged anticipation under 35 U.S.C. § 102.
This argument has been fully considered but is not persuasive for the reasons discussed above in paragraphs 3 and 4.
Double Patenting
9. 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.
10a. Claims 1, 5-8, 14, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 17/906,315. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claims 1 and 18 both sets of claims are drawn to a method of providing a treatment for non-small cell lung cancer to a patient in need thereof, the method comprising: extracting total RNA from a tumor of non-small cell lung cancer of a patient after a surgical resection; generating complementary DNA (cDNA) of the extracted total RNA from said patient tumor; quantifying the mRNA expression of SEQ ID NOs:1-7; normalizing said mRNA expression with the mRNA expression level of a control gene SEQ ID NO: 8 (UBC); determining whether a patient will benefit from adjuvant chemotherapy using the mRNA expression levels and administering to the patient one or more adjuvant chemotherapies (see clms 1-2 of the copending application).
Regarding Claim 5 both sets of claims state that SEQ ID NO: 1 is used to determine whether said patient will benefit from receiving adjuvant chemotherapy of one or more of (a) cisplatin and Taxol (paclitaxel), (b) cisplatin and Taxotere (docetaxel), (d) carboplatin and Taxol (paclitaxel), (e) carboplatin and Taxotere (docetaxel), and (f) Taxol (paclitaxel) (see clm 5 of the copending application). Regarding Claim 6 both sets of claims state that SEQ ID NO:5 is used to determine whether said patient will benefit from receiving adjuvant chemotherapy of carboplatin (see clm 6 of the copending application). Regarding Claim 7 both sets of claims state that SEQ ID NO: 6 is used to determine whether said patient will benefit from receiving adjuvant chemotherapy of one or more of (a) carboplatin and Taxol (paclitaxel), (b) carboplatin and Taxotere (docetaxel), (c) cisplatin and Taxotere (docetaxel), and (d) cisplatin and Taxol (paclitaxel) (see clm 7 of the copending application). Regarding Claim 8 both sets of claims state that SEQ ID NO: 3 is used to determine whether said patient will benefit from receiving adjuvant chemotherapy of one or more of (a) Taxol (paclitaxel) and (b) Alimta (pemetrexed) (see clm 8 of the copending application). Regarding Claim 14 both sets of claims state that the one or more adjuvant chemotherapies are selected from a group consisting of: (a) cisplatin and Taxol (paclitaxel), (b) cisplatin and Taxotere (docetaxel), (c) carboplatin, (d) carboplatin and Taxol (paclitaxel), (e) carboplatin and Taxotere (docetaxel), (f) Taxol (paclitaxel), and (g) Alimta (pemetrexed) (see clm 2 of the copending application). The instant claims are different from the copending claims because they set forth criteria for determining if the patient will benefit from the adjuvant chemotherapy (see clm 1). However it is noted that those portions of the specification which provide support for the copending claims may also be examined and considered when addressing the issue of whether a claim in an application defines an obvious variation of an invention claimed in a copending application. Herein it is noted that the limitations set forth in claim 1 of the instant application are disclosed in Figures 4A and 4B of the copending application. Accordingly, it would have been obvious to modify the method of the copending claims by reciting the specific criteria for making the determination that are recited in claim 1 of the instant application since this same information is present in Figures 4A and 4B of the copending application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
8b. Claim 15 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 17/906,315 in view of Guo (EbioMedicine 32 (2018) 102-110 Available online 1 June 2018). Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of the copending application have been discussed above. The instant claims are different because they require validating protein expression of SEQ ID NO: 6 (ZNF71). However as discussed in the 103 rejection the prior art of Guo teaches this. It would have been obvious to modify the method of the copending claims by detecting protein expression of SEQ ID No: 6 since Guo teaches mRNA expression and protein expression of ZNF71 are both prognostic of NSCLC outcome and predictive of the benefits to chemotherapy.
Response To Arguments
10. In the response to the double patenting rejection, the Applicants requested that this rejection be held in abeyance until such time that the claims are found to be otherwise allowable.
Applicants are reminded that only objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. Because a double patenting rejection is not “as to form”, such a rejection should not be held in abeyance. Because the rejection has not been specifically traversed, the rejection is maintained.
11. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 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 CFR 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached Monday-Friday, 8:15am-4:45pm EST.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682