FINAL ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is responsive to the Amendments and Response filed 02 February 2026. Claims 20-21 have been amended, and claims 1-21 remain under consideration. Applicant’s amendments and arguments have been thoroughly reviewed, have overcome the following rejections set forth in the prior Office action:
the rejection of claims 20-21 under 35 USC 112(b), in view of Applicant’s amendments (as the manner in which the amended claims further limit claims 15/12/1 [from which they depend] is now sufficiently clear; and
the rejection of claim 20 under 35 USC 102(a)(1) in view of Applicant’s clarifying amendment.
Claims 1-21 remain rejected for the reasons given below, which include new grounds of rejection necessitated by Applicant’s amendments. Any rejections and/or objections not reiterated in this action have been withdrawn. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Interpretation
It is again noted that the specification states (see, e.g., paragraph 6 of the corresponding published application):
A covalent, irreversible inhibitor of KRas G12C is 2-[(2S)-4-[7-(8-chloro-1-naphthyl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1 -(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile, also known as MRTX849 and adagrasib.
Thus, the teachings of the specification establish that the terms “adagrasib” and “MRTX849” are each equivalent terms/synonyms for the inhibitor recited in the claims (see, e.g., independent claim 1).
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-8, 10-17, and 21 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hallin et al (Cancer Discovery 10:54-71 [09 Jan 2020]; cited in IDS).
Hallin et al disclose the use of MRTX849/adagrasib in treating a patient with KRAS G12C lung adenocarcinoma (see entire reference, particularly the Abstract).
Hallin et al teach that KRAS mutations “often co-occur with other key genetic alterations”, including in STK11, in lung adenocarcinoma (see page 55, right column). With more particular regard to the method of independent claim 1, Hallin et al disclose administering to a 45-year old patient with stage IV lung adenocarcinoma characterized by both KRAS G12C and loss-of-function STK11 (E223*) MRTX849 at 600 mg BID, and further report that the patient “had marked clinical improvement within 2 weeks, including complete resolution of baseline cough and oxygen dependency”, as well as “RECIST-defined partial response of 33% reduction of target lesions” at cycle 3 day 1 (45 days)” (see page 60, final paragraph of the left column bridging to the right column). Hallin et al thus anticipate claims 1-8 and 10-11. With more particular regard to dependent claims 2-8 and 10-11, it is noted that:
a) Hallin et al teach an STK11 (E223*) nonsense mutation, which meets the requirements of claim 1 with regard to a loss-of-function mutation and “loss of expression” of STK11 at least with regard to the wild-type protein (see again page 60); thus, all of claims 2-5 are anticipated at least with regard to one embodiment embraced by the claims;
b) regarding claims 6-8, Hallin et al teach a 45 year old patient with lung adenocarcinoma meeting the requirements of these claims (see again page 60); and
c) regarding claims 10-11, the dosage of 600 mg BID meets the requirements of these claims (see again page 60).
Additionally, regarding dependent claims 12-17 and 21, Hallin et al teach that the patient noted above had lung adenocarcinoma that was refractory to several other therapies, which constitutes an inherent disclosure of administering to the same patient the recited other therapies (see again page 60). Among the therapies disclosed by Hallin et al is pembrolizumab, i.e., a preferred PD-1 inhibitor of dependent claim 17, thus meeting the requirements of all of claims 12-17. Additionally, as Hallin et al’s disclosure makes clear that this administration of pembrolizumab occurred at a different time, the requirement of claim 21 for a “different day” is also met.
Thus, Hallin et al anticipate claims 1-8, 10-17, and 21.
The reply of 02 February 2026 traverses the rejection on the following grounds. Applicant argues that Hallin et al “is not prior art under 35 U.S.C. §102(a)(2) because it is subject to an exception under 35 USC §102(b)(1)(A)” (Reply page 5). The Reply states that “James G. Christensen was the corresponding author of the cited publication” and is a joint inventor of the instant application, urging that the “claimed subject matter of the instant application was obtained from the joint inventor”, thereby rendering Hallin et al “an invalid reference” (Reply page 6).
This argument has been thoroughly considered but is not found persuasive. The examiner agrees that Hallin et al was published one year or less before the effective filing date of the instant application, and that James G. Christensen is both a co-inventor of the instant application and a co-author of the Hallin et al reference. However, the Hallin et al reference has numerous other co-authors – i.e., names additional persons - who are not named as co-inventors of the instant application. Applicant’s specification does not contain a statement establishing the Hallin et al reference as a grace period inventor-originating disclosure, nor has Applicant filed an affidavit or declaration under 37 CFR 1.130(a) to establish that an exception under 35 USC 102(b)(1)(A) applies. Accordingly, the rejection has been maintained, as it cannot be considered apparent that Hallin et al is excepted as prior art (see MPEP 2153.01(a) for further guidance).
Claim Rejections - 35 USC § 103
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.
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claim(s) 1, 12, 15, and 18-20 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Hallin et al (Cancer Discovery 10:54-71 [09 Jan 2020]; cited in IDS) in view of Kim et al (Oncotarget 8(29):48248 [2017]; previously cited).
It is reiterated that claims 1, 12, and 15 are anticipated for the reasons given above; this rejection applies to those claims to the extent that they are directed to the embodiments of claims 18-19, requiring an additional “administering” of a second anti-cancer therapy that is a PD-L1 inhibitor. Applicant’s amendment of claim 20 has necessitated the inclusion of that claim in this rejection.
Hallin et al disclose the use of MRTX849/adagrasib in treating a patient with KRAS G12C lung adenocarcinoma (see entire reference, particularly the Abstract).
Hallin et al teach that KRAS mutations “often co-occur with other key genetic alterations”, including in STK11, in lung adenocarcinoma (see page 55, right column). With more particular regard to the method of independent claim 1 (from which the rejected claims depend), Hallin et al disclose administering to a 45-year old patient with stage IV lung adenocarcinoma characterized by both KRAS G12C and loss-of-function STK11 (E223*) MRTX849 at 600 mg BID, and further report that the patient “had marked clinical improvement within 2 weeks, including complete resolution of baseline cough and oxygen dependency”, as well as “RECIST-defined partial response of 33% reduction of target lesions” at cycle 3 day 1 (45 days)” (see page 60, final paragraph of the left column bridging to the right column). Hallin et al also teach that the patient noted above had lung adenocarcinoma that was refractory to several other therapies (see again page 60), and disclose screening for combination therapies that may enhance patient response to MRTX849 (pages 63-66, left column). Thus, Hallin et al teach the use of different therapies in sequence in response to therapy resistance/responsiveness failure, as well as the use of combinations of therapies that may produce better therapeutic response in a patient; however, Hallin et al do not teach administering of a PD-L1 inhibitor to a lung cancer patient as required by claims 18-20.
Kim et al teach that immune checkpoint inhibitors, including the PD-L1 inhibitor atezolizumab (which is a preferred inhibitor set forth in claim 19), may be effective in improving overall survival in patients with advanced, previously treated KRAS mutant lung cancer, i.e., patients of the same general type taught by Hallin et al (see entire reference, particularly the Abstract, page 48249-48250 [including Table 1]).
In view of the teachings of Hallin et al and Kim et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered both MRTX849 and atezolizumab to a patient of the type taught by Hallin et al, and thereby to have performed a method meeting the requirements of the claims. Regarding claims 18-19, the claims embrace performing such administering steps at any time relative to one another, such that the claims encompass, e.g., employing MRTX849 following therapy failure with atezolizumab or vice-versa, as well as the use of these two therapies together. Given that Hallin et al teach successful use of MRTX849 in advanced lung cancer following failure of multiple other therapies, as well as methods aimed at identifying combination therapies to enhance response to MRTX849, and Kim et al teach the benefits of treating such patients with atezolizumab, an ordinary artisan would have been motivated to have performed multiple embodiments embraced by these claims dependent upon the characteristics and response of a particular patient – including therapies in sequence or together (as set forth in claim 20) – for the benefit of more successfully treating the patient. Further, given the data provided by Hallin et al and Kim et al regarding the successful use of both of these therapies in treated advanced lung cancer patients with KRAS mutations, an ordinary artisan would have had a reasonable expectation of success in performing such methods.
Claim(s) 9 remains rejected under 35 U.S.C. 103 as being unpatentable over Hallin et al in view of Kim et al as applied to claim 1, above, and further in view of Shemesh et al (Journal for ImmunoTherapy of Cancer 7:314 [2019]; previously cited).
The teachings of Hallin et al and Kim et al are set forth above. While Hallin et al in view of Kim et al suggest methods meeting the requirements of the claims with respect to an adult lung cancer patient, the references do not address treatment of a pediatric patient, as is required by claim 9.
Shemesh et al disclose a review of “pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer”, and conclude that their findings “demonstrate a similar exposure-safety profile of atezolizumab in pediatric and young adult patients, supportive of weight based dosing in pediatric patients” (see entire reference, particularly the Abstract).
In view of the teachings of Shemesh et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adapted the methods suggested by Hallin et al and Kim et al for treatment of a pediatric lung cancer patient having the tumor characteristics taught by Hallin et al and Kim et al, such as by employing weight-adjusting dosages of the therapies taught by Hallin et al and Kim et al, in the manner suggested by Shemesh et al, and thereby to have performed a method meeting the requirements of claim 9. An ordinary artisan would have been motivated to have made such a modification for the benefit of treating advanced disease in such a patient (including, e.g., a patient in whom other treatments had failed), in the safest possible manner (such as by dosage-adjustments, monitoring, etc.), particularly given the teaching of Shemesh et al that such pediatric patients “are sometimes faced with resistant or recurrent disease that cannot be cured by surgery, chemotherapy, or radiation” (page 2, top of left column). Further, given the benefits taught by Hallin et al and Kim et al of their disclosed therapies, an ordinary artisan would have had a reasonable expectation of success in performing such methods with respect to at least some pediatric human patients (again, given the data reported by Hallin et al and Kim et al in adult human patients).
With regard to each of the rejections under 35 USC 103, the Reply again argues that Hallin et al falls under a 35 USC 102(b)(1)(A) exception, incorporating the traversal summarized above regarding the rejection of claims under 35 USC 102(a)(1). Accordingly, the reply to that argument set forth above applies equally herein, and is not found persuasive; the rejections are therefore maintained.
Conclusion
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 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 DIANA B JOHANNSEN whose telephone number is (571)272-0744. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm EST.
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 at (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682