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 Claims
Claims 1-20 are pending.
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a CIP of a national stage entry of and claims priority to Application Serial No. PCT/US2020/060808, filed 11/16/2020. The application also claims priority to provisional application number 62/935,763, filed on 11/15/2019.
Information Disclosure Statement
All references from IDS(s) received 3/01/2023 have been considered unless marked with a strikethrough.
Response to Arguments
Applicant's arguments filed 10/22/2025 have been fully considered but they are not fully persuasive.
In a non-final dated 07/22/2025, Claims 1-20 were examined upon their merits.
In a non-final dated 07/22/2025, Claims 1-20 were rejected under 35 U.S.C. 103. In response, Applicant amended claim 1 to include “where in the modulation of EGFR reduces EGFR copy number heterogeneity.”
With respect to the 103 rejection for claims 1-13, the Examiner finds the applicant’s argument persuasive. The applicant argues that the primary reference provided by the Examiner (“Moroni”) fails to teach treating a subject that is resistant to an EGFR inhibitor (referred to as EGFRi). Moroni teaches the treatment of cancer cells that are resistant to chemotherapy. The Examiner agrees that EGFRi resistance would not explicitly fall under this category. The Examiner agrees with the Applicant that the other two references (“Kurmasheva” and “Mishra”) do not remedy this deficiency. Since this is a crucial part of the independent claim, the Examiner finds the rejection for claims 1-13 moot and withdraws the 103 rejection for these claims.
With respect to the 103 rejection for claims 14-20, the Examiner finds the applicant’s argument not persuasive. The Applicant argues that the primary reference provided by the Examiner (“Black”) fails to teach any KDM4A treatment of its use in reducing heterogeneity of EGFR copy numbers. Along the same line, the Applicant argues that Black primarily focuses on drug resistance of oncogene CKS1B and although Black identifies KDM4A as a key enzymatic regulator of hypoxia related site-specific copy gains. It fails to suggest that inhibiting this pathway would result in sensitizing a tumor to EGFRi treatment. Finally, the Applicant argues that Black teaches that KDM4A is unlikely to be the only regulator of hypoxia related site-specific copy gains. The Examiner maintains the argument that since Black teaches that “Hypoxia-driven copy gains … are dependent on the KDM4A histone demethylase and are blocked by inhibition of KDM4A with a small molecule or the natural metabolite succinate” and the results are implicated in understanding copy number heterogeneity that Black does indeed teach a suggestion of using “treatment” of KDM4A to reduce heterogeneity of EGFR copy numbers. Further, the additional references (“Moroni” and “Kurmasheva”) teach the treatment of a tumor sensitized to EGFRi therapy through the administration of an EGFRi. Therefore, the Examiner maintains the argument that it would be obvious in view of the art to sensitize the tumor through KDM4 inhibition and apply it to the methods of treatment taught by Moroni and Kurmasheva. The Examiner also points out that the argument above for claims 1-13 does not apply here because claims 14-20 do not specific that the tumor has to be resistant to EGFRi. Therefore, the 103 rejection is maintained for claims 14-20.
MAINTAINED REJECTIONS
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 14-20 are rejected under 35 U.S.C. 103 as being unpatentable over Black, J. et al. (Genes Dev. 2015 May 15;29(10):1018–1031.; cited in the IDS filed 3/01/2023; “Black”) in view of Moroni, M. et al. (Lancet Oncol. 2005 May;6(5):279-86; cited in the IDS filed 3/01/2023; “Moroni”)and Kurmasheva, R. et al. (Pediatr Blood Cancer. 2017 Mar;64(3):10.1002/pbc.26218; cited in the IDS filed 3/01/2023; “Kurmasheva”).
Black teaches hypoxia-driven copy gains are dependent on the KDM4A histone demethylase and are blocked by inhibition of KDM4A (Abstract). Black also teaches that hypoxia contributes to tumor heterogeneity and suggests that KDM4A inhibitors may be useful cotherapeutics to suppress copy gains (Discussion, para. 1), as required by instant claim 14, 17, and 19.
Black fails to teach the administration of an EGFR inhibitor, such as gefitinib, as required by Claim 14(B).
Moroni teaches a method of using an EGFR inhibitor, cetuximab, for treating cancer cell lines with increased EGFR copy numbers, as measured by DNA FISH.
Moroni also teaches the method where the cells include diploid EGFR copies and have a copy number that can fall between 3-7 or of 8 or higher (Figure 5C).
Moroni also teaches the results are consistent with a response of about 10% in patients with non-small-cell lung cancer given the EGFR inhibitors gefitinib or erlotinib (Discussion, para. 2). Therefore, it would be obvious to a person skilled in the art that the method can be used with gefitinib.
Moroni fails to teach contacting the cells with an agent that modulates the amplification of EGFR.
Kurmasheva teaches EZH2 inhibitors, such as tazemetostat, sensitizes mutant NSCLC to topoisomerase II poisions and enhance the activity of EGFR inhibition (Discussion, last para.).
Kurmasheva also teaches a loss of heterozygosity, as required by instant claim 8, as it teaches results that suggest that there is heterogeneity in response to EZH2 inhibitors and that heterogeneity in response is unlikely to be the result of differential reduction (Page 6, Col. 2, para. 1).
Kurmasheva fails to teach a method of treating a tumor with altered EGFR copy numbers.
However, it would be obvious to a person skilled in the art at the time to incorporate an agent that would modulate EGFR amplification, as taught by Kurmasheva, to a level of sensitizing it to a method of treatment by EGFR inhibitors, as taught by Moroni.
The combined teachings of Kurmasheva and Moroni teach a method of sensitizing the tumor to EGFRi therapy by treating the tumor with an EGFR inhibitor.
Therefore, it would be obvious to a person skilled in the art at the time to sensitize the tumor through KDM4 inhibition, as taught by Black, and apply it to a method of treatment, as taught by Moroni and Kurmasheva.
With respect to claim 15, Moroni teaches a method of determining EGFR amplification levels before treatment (Page 283, Col. 1, para. 3). Moroni also teaches intravenous administration (methods, para. 2).
With respect to claims 16 and 20, Kurmasheva teaches measurement/determination of EZH2 mRNA expression (Figure 4B).
Since independent claims 1, 14, and 19 are obvious over the combined teachings of Black, Moroni, and Kurmasheva, with respect to claims 15, 16, and 20, it would be obvious to extract methods of measuring data from any of the prior arts and apply it to the method of sensitizing and treating a EGFRi-resistant tumor with modified copy numbers.
Applying KSR example rationale (A), it would have been prima facie obvious to extract the method of reducing tumor heterogeneity to sensitize a tumor to EGFR inhibitor therapy, as taught by Black, and apply methods of treating the tumor with an EGFR inhibitor, as taught by Moroni, as well as to further sensitize the tumor to EGFR inhibitor treatment, as taught by Kurmasheva. Therefore, claims 14-20 would have been obvious to a person who is skilled in the art prior to the effective filing date.
Allowable Subject Matter
Claim 1-13 are considered allowable subject matter.
The following is a statement of reasons for the indication of allowable subject matter:
The applicant argues that the primary reference provided by the Examiner (“Moroni”) fails to teach treating a subject that is resistant to an EGFR inhibitor (referred to as EGFRi). Moroni teaches the treatment of cancer cells that are resistant to chemotherapy. The Examiner agrees that EGFRi resistance would not explicitly fall under this category. The Examiner agrees with the Applicant that the other two references (“Kurmasheva” and “Mishra”) do not remedy this deficiency. Since this is a crucial part of the independent claim, the Examiner finds the rejection for claims 1-13 moot and withdraws the 103 rejection for these claims.
Conclusion
Claims 14-20 are rejected. Claims 1-13 are considered allowable subject matter.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621