DETAILED ACTION
The reply filed on 12/22/2025 has received and entered.
Claims 1-7, 9, 11, 13, 17, 21, 23 and 25-32 are currently pending and under examination.
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 .
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.
Claims 30-32 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an in vitro method of inhibiting KRAS G12C protein comprising contacting the KRAS G12C protein with an effective amount of the compound of claim 1, or the pharmaceutically acceptable salt thereof and a method for treating lung cancer, comprising administering a therapeutically effective amount of the compound of claim 1 to a subject in need of such treatment, does not reasonably provide enablement for a method of inhibiting KRAS G12C protein in a subject in need thereof comprising contacting the KRAS G12C protein with administering to the subject an amount of the compound of claim 1, or the pharmaceutically acceptable salt thereof, effective to inhibit the activity of the KRAS G12C protein, a method of treating cancer, comprising administering a therapeutically effective amount of the compound of claim 1, or the pharmaceutically acceptable salt thereof, to a subject in need of such treatment, and the method of claim 31, further comprising administering an additional active agent to the subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims (partially newly applied as necessitated by amendment).
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the Invention: Claim 30 is drawn to a method of inhibiting KRAS G12C protein comprising contacting the KRAS G12C protein with an amount of the compound of claim 1, or the pharmaceutically acceptable salt thereof, effective to inhibit the activity of the KRAS G12C protein. Claim 31 is drawn to a method of treating cancer, comprising administering a therapeutically effective amount of the compound of claim 1, or the pharmaceutically acceptable salt thereof, to a subject in need of such treatment, and claim 32 is drawn to the method of claim 31, further comprising administering an additional active agent to the subject.
The nature of the invention is complex in that the claims are drawn to a method of inhibiting KRAS G12C protein comprising contacting the KRAS G12C protein with an amount of the compound of claim 1, or the pharmaceutically acceptable salt thereof, effective to inhibit the activity of the KRAS G12C protein, of treating cancer, comprising administering a therapeutically effective amount of the compound of claim 1, or the pharmaceutically acceptable salt thereof, to a subject in need of such treatment, and the method of claim 31, further comprising administering an additional active agent to the subject.
Breadth of the Claims: The claims are broad in that the claims recite that the KRAS G12C protein can be inhibited but does not limit the KRAS G12C protein to in vitro, which is what is demonstrated. The claims recite that any and all types of cancer can be treated and that any additional active can be administered to treat cancer. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the Specification and Existence of Working Examples: The specification describes administering representative numbers of compounds for inhibiting KRAS G12, in vitro but there is no administration to a subject and the assay does not correlate to in vivo results. Regarding cancer treatment, there is only one example of administration of representative compounds to an in vitro cellular phospho-ERK assay. There is no indication of what cancer that this assay is associated with in the specification, so it is construed as being tied to bronchloaveolar carcinoma (lung cancer), which is the art recognized correlation. There are no other cell lines tested aside from NCI-H358 cells (ATCC® CRL-5807TM). Regarding combination therapy by administering the compound with an additional active, there are no working examples demonstrating this.
The specification envisions that administering a therapeutically effective amount of the compound of claim 1, or the pharmaceutically acceptable salt thereof will have utility in humans by treating all types of cancer and inhibit KRAS G12C protein.
However, no working examples are provided with regard to a method of treating all types of cancer and inhibiting KRAS G12C protein in vivo.
Predictability and State of the Art: The state of the art at the time the invention was made was unpredictable and underdeveloped. MayoClinic: Leukemia (U*, https://www.mayoclinic.org/diseases-conditions/leukemia/diagnosis-treatment/drc-20374378) teaches that leukemia is treated with chemotherapy injected into a vein or in pill form, targeted therapy, radiation therapy with X-rays or other high-energy beams, bone marrow transplant, immunotherapy, or CAR-T cell therapy. MayoClinic: Breast Cancer (V*, https://www.mayoclinic.org/diseases-conditions/breast-cancer/diagnosis-treatment/drc-20352475) teaches that breast cancer is treated with breast, breast tissue or lymph node removal, chemotherapy, radiation therapy e.g. with X-rays, protons, or brachytherapy, immunotherapy, targeted therapy, hormone therapy, alternative medicine, and/or palliative care. American Cancer Society: Chemotherapy (W*) teaches that there are many different types of chemotherapy and they don’t all work exactly the same way, so different types of chemo might be used for different types of cancer.
Thus, while the claim-designated method may be useful for providing such an effect, Applicant does not disclose a method for treating all types of cancer.
Amount of Experimentation Necessary: The quantity of experimentation necessary to carry out the claimed invention is high, as the skilled artisan could not rely on the prior art or instant specification to teach how to use the compound of claim 1, or the pharmaceutically acceptable salt thereof that can be administered in a therapeutically effective dose with an acceptable level of side-effects.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 30-32 are not considered to be fully enabled by the instant specification.
Response to Arguments
Applicant's arguments filed 12/22/2025 have been fully considered but they are not persuasive. Applicant argues that as discussed throughout the application and shown in the Examples, the compounds of the invention are able to inhibit KRAS G12C protein mutants. The specification also explains, for example at paragraphs [0165]-[0168], how a person of skill in the art could determine whether a cancer comprises a KRAS G12C mutation.
However, this is not found persuasive because Applicant has not provided a representative number of working examples to show that all of the claimed compounds are effective for treating all types of cancer with a KRAS G12C mutation. Furthermore, Applicant has not sufficiently limited the cancers to what has been demonstrated in the specification. Therefore, the rejection is maintained for the reasons of record and the reasons set forth above.
Conclusion
Claims 30-32 are not allowed. Claims 1-7, 9, 11, 13, 17, 21, 23 and 25-29 are allowable.
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 Amy L. Clark whose telephone number is (571)272-1310. The examiner can normally be reached M-F 8:00am-5:00pm.
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/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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