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 .
Status of the Claims
Claims 9, 12, 13, and 15 are pending. Acknowledgment is made of the amendment of claims 9, 12, 13, and 15, and the cancellation of claims 1, 10, 11, and 14, in the reply filed 04/30/2026.
Withdrawn Rejections
Applicant’s cancellation of claim 1, in the claims filed 04/30/2026, renders the rejection of claim 1 under 35 U.S.C. 101 moot. The rejection of claim 1 has been withdrawn.
Applicant’s amendment to the claims, filed 04/30/2026, overcomes the rejection of claims 1 and 9-13 under 35 U.S.C. 112(b). The rejection of claims 1 and 9-13 has been withdrawn.
Applicant’s timely filing of a terminal disclaimer, filed 04/30/2026, overcomes the rejection of claims 1, 9, 14, and 15 on the ground of nonstatutory double patenting over U.S. Patent No. 11,306,095 B2. The rejection of claims 1, 9, 14, and 15 has been withdrawn.
Modified Rejections
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 9, 12, 13, and 15 are 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 a method for inhibiting mutant EGFR, does not reasonably provide enablement for treating any EGFR-mediated cancer. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
Breadth of the claims
The breadth of the claim includes a method of inhibiting mutant EGFR and treating an EGFR-mediated cancer in a patient, comprising administering a compound of the formula (I).
Nature of the invention
The nature of the invention is performance of a method of inhibiting EGFR and treating a mutant EGFR-mediated cancer comprising administering the compound of formula I, shown below.
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State of the prior art
No single drug has been discovered that is effective in treating the myriad of EGFR-mediated diseases, including, but not limited to, “non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, glioblastoma, head and neck squamous cell carcinoma, cervical cancer, esophageal cancer, liver cancer, kidney cancer, colon cancer, skin cancer, leukemia, lymphoma, gastric cancer or multiple myeloma” (claim 15). See In re Hokum, 226 USPQ 353 (ComrPats 1985). No drug has been successful in the total prevention of any EGFR-mediated disease.
Level of one of ordinary skill in the art
The artisans performing the inventor’s or joint inventor’s method of treating an EGFR-mediated cancer in a patient, comprising administering a compound of formula I, would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
Level of predictability in the art
Synthetic organic chemistry is quite unpredictable. See In re Marzocchi and Horton 169 USPQ at 367 ¶3. Similarly, it is well established that “[T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The nature of the invention and predictability in the art, with specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the “general unpredictability of the field [of] ...anti-cancer treatment.” In re Application of Hozumi et al., 226 USPQ 353 notes the “fact that the art of cancer chemotherapy is highly unpredictable”.
The treatment of any EGFR-mediated cancer, to include the cancers in instant claim 15, would be highly unpredictable, and has never been successfully proven using any drug in the art.
Amount of direction provided by the inventor
The invention lacks direction with respect to making and/or using (performing) a method of treating an EGFR-mediated cancer in a patient, comprising administering a compound of formula I. At best, on page 8 of the specification, and effective amount is described as “an amount effective to improve or eliminate one or more conditions”, wherein “such dosage may be administered as a single dose, or may be administered in accordance with an effective treatment regimen”. No guidance is provided for the “dosage” or “effective treatment regimen” that would be capable of treating or preventing every EGFR-mediated cancer.
Existence of working examples
The disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating an EGFR-mediated cancer in a patient, comprising administering a compound of formula I.
Similarly, according to the specification and claims, compounds of formula I are capable of preventing and treating non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, glioblastoma, head and neck squamous cell carcinoma, cervical cancer, esophageal cancer, liver cancer, kidney cancer, colon cancer, skin cancer, leukemia, lymphoma, gastric cancer, and multiple myeloma.
However, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any of the aforementioned diseases. The specification only provides examples for inhibiting mutant EGFR comprising administering formula I. There is insufficient disclosure to reasonably conclude that the method of treating an EGFR-mediated cancer in a patient, comprising administering the compound of formula I, as recited, would contribute to treatment of any the aforementioned diseases. The inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claim.
Quantity of experimentation needed
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
One skilled in the art, such as a medical doctor, would be required to perform hundreds of clinical trials and in vivo or in vitro assays in order to determine which cancers mediated by mutant EGFR would be treatable with formula I. Even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404. These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for a method of treating an EGFR-mediated cancer in a patient, comprising administering the compound of formula I, is clearly justified.
Applicant Argues:
Applicant states, in the Remarks filed 04/30/2026, that the specification enables for the treatment of EGFR-mutant mediated cancers because Example 2 shows that some stable cell lines have proliferation suppressed by the compound of formula I. Applicant states that this can be extrapolated to include the treatment any EGFR-mutant mediated cancer, and that finding the optimal dosing or treatment regiments for the treatment of every EGFR-mutant mediated cancer is not undue experimentation.
Examiner Responds:
Applicant has not shown any in vitro or in vivo testing of any particular cancer cell lines. The inhibition of proliferation in specific stable cell lines, with only six examples of EGFR mutations, would not be expected to therefore enable the treatment of any and every EGFR-mutant mediated cancer. The absence of any testing of any cancer cell lines and the lack of any dosing or treatment regiments does result in indue experimentation. The inhibition of proliferation of six EGFR-mutant stable cell lines would not be expected to be enabling for the treatment of EGFR-mutant mediated cancers, and one of ordinary skill in the art would not expect that every cancer listed in instant claim 15 would be treated by this method, since no single drug has ever been known to treat all the cancers listed in instant claim 15.
New Rejections
Necessitated by Claim Amendment
Claim Rejections - 35 USC § 103
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 9, 12, 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (WO 2016192609 A1, hereinafter referred to as reference ‘609), and further in view of Yoon et al. (Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study, PLOS ONE, 13 February 2020, Vol. 15(2), e0228925, pages 1-14).
Reference ‘069 teaches, in claims 5 and 6, a pharmaceutical composition comprising N-[3-[2-[[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]amino]-7-oxo-6-phenyl-8(7H)-pteridinyl]phenyl]-2-propenamide (compound 14). Claim 7 teaches a method of using said compound in the treatment or prevention of an EGFR mediated disease and in the inhibition of EGFR.
Reference ‘069 teaches, in Example 3 and in Table 1, that compound 14 selectively inhibits the EGFR T790M and L858R mutations, which are EGFR exon 20 and exon 21 mutations, respectively.
Claims 8 and 9 of reference ‘069 teach a method of treating cancer comprising administering said compound, wherein the cancer is non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, breast cancer, prostate cancer, glioma, ovarian cancer, head and neck squamous cell carcinoma, cervical cancer, esophageal cancer, liver cancer, kidney cancer, pancreatic cancer, colon cancer, skin cancer, leukemia, lymphoma, gastric cancer, multiple myeloma or solid tumors, as in instant claim 15.
Reference ‘069 fails to teach a method of inhibiting EGFR mutations G719X, S768I, and L861Q, as in instant claims 9, 12, and 13.
Yoon et al. investigated EGFR mutations in patients with lung adenocarcinoma. This study targeted the highest frequency of EGFR mutations, and excluded low frequency mutations (page 2, Methods). On page 4, it was taught that “[t]he target somatic mutations included E19 dels, E21 L858R mutation, E18 G719X mutation, E20 S768I mutation, E20 insertions, E20 T790M mutation, and E21 L861Q mutation.” It is also taught, on page 9, that treatment with tyrosine-kinase inhibitors leads to dramatically improved prognosis in patients with EGFR positive lung cancer.
Therefore, it would be prima facie obvious to use the growth factor receptor tyrosine kinase inhibitor taught by reference ‘069 et al. in the inhibition of G719X, S768I, and L861Q EGFR mutations, since reference ‘069 teaches inhibition of T790M and L858R mutations, and Yoon et al. teaches that tyrosine-kinase inhibitors lead to dramatically improved prognosis in patients with the EGFR mutations L858R, T790M, G719X, S768I, and L861Q. One of ordinary skill in the art would find it obvious to try administering a composition that is known to inhibit mutant EGFR on the most common EGFR mutations.
One of ordinary skill in the art would have a reasonable expectation of success administering a pharmaceutical composition known to inhibit mutant EGFR, specifically T790M and L858R mutations, in order to inhibit other common mutations, such as G719X, S768I, and L861Q.
Conclusion
Claims 9, 12, 13, and 15 are rejected.
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 RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 7-3.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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