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 .
Examiner Note
The amended specification filed January 2, 2026 has been entered as the only change asked of Applicant was drawn to the line spacing.
Priority
The instant application is a 371 National Stage Entry of PCT CN2021/141359 filed on December 24, 2021 which claims priority to foreign application Nos. CN202111058245.6 filed on September 9, 2021, CN202110500623.5 filed on May 8, 2021, CN202110185495.X filed on February 10, 2021, CN202110027514.6 filed on January 10, 2021, and CN202011571285.6 filed on December 27, 2020.
No English Translation
Examiner notes that no certified translations of the Foreign Applications CN202111058245.6 (filed September 9, 2021), CN202110500623.5 (filed on May 8, 2021), CN202110185495.X (filed February 10, 2021), CN202110027514.6 (filed January 10, 2021), or CN202011571285.6 (filed December 27, 2020) have been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Examiner Note: While Applicant is not required to perfect priority, if Applicant wishes to perfect priority, a certified translation is required (see 1/2/26 Applicant Remarks at p. 20 “Priority”).
Status of Claims
Acknowledgement is made of amended (1-10) and new (11-14) claims filed January 2, 2026.
Response to Arguments
Applicant’s amendments filed January 2, 2026 have been considered. The following have been withdrawn:
the objection to the specification,
the objection to claim 9,
the rejection of claim 9 under 35 U.S.C. 101,
the rejection of claims 1, 3-4, 9 under 35 U.S.C. 112(b),
the rejection of claims 1-5, 7, 9- under 35 U.S.C. 102(a)(2) as being anticipated by WO 2022161480 A1 to Lv et. al. 1
the rejection of claims 1-3 under 35 U.S.C. 103 as being unpatentable over WO 2013115265 A1 to Kawai et. al.2
Applicant’s amendments have necessitated a new rejection of claim 9 under 35 U.S.C. 112(a).
Applicant's arguments filed January 2, 2026 have been fully considered but they are not persuasive. The rejection of claims 1-4, 6, 8-10 under 35 U.S.C. 102(a)(2) as being anticipated by US 2021/0139517 A1 to Gill et. al.3 has been modified. While the previously claimed species taught by Gill is no longer included in instant claim 8, the species still reads on instant Formula I-1.
New Rejection(s)
Claim Rejections - 35 USC § 112(a)
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, 13-14 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 inhibiting SOS1, does not reasonably provide enablement for treating any disease “associated with an activity, an expression or a mutation of Ras protein” or those listed in claims 13-14. 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.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the nature of the invention,
2- the breadth of the claims,
3- the state of the prior art,
4- the predictability of the art,
5- the amount of direction or guidance provided
6- the presence or absence of working examples,
7- the quantity of experimentation necessary, and
8- the relative skill of those in the art.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Undue experimentation is required by one skilled in the art to determine enablement of the instant disclosure as claimed due to the following:
The nature of the invention (1) and the breadth of the claims (2)
The nature of the invention and breadth of claims is the treatment, prevention, and prophylaxis of a disease or condition associated with Ras broadly (claim 9) or those diseases specifically listed in claims 13-14.
Pages 36-37 of the specification filed January 2, 2026 defines “treatment” as: (i) preventing the occurrence of a disease or condition in a mammal, especially when such mammal is predisposed to suffer from the disease or condition but has not been diagnosed as having the disease or condition; (ii) inhibiting a disease or condition, i.e. suppressing its development; (iii) alleviating the disease or condition, i.e., causing the state of the disease or condition to subside; or (iv) alleviating the symptoms caused by the disease or condition.
The specification does not definitively list Ras-associated diseases, but rather states a preferred embodiment of treating a tumor (see instant spec. at p. 25 ¶3).
Furthermore since the specification does not define “subject”, a subject is understood to include cells and individuals and treatment includes prophylaxis, the broadest reasonable interpretation includes a patient population of anyone.
Regarding claims 13-14, the current claim wording “associated with the activity…of Ras is a tumor” is also understood to read on normal Ras activity, and thus reads on tumors not driven by Ras mutations.
The state (3) and predictability (4) of the art
In regards to the diverse role of RAS, Denayer et. al.4 teaches RAS plays key roles in cell growth, malignant transformation, learning, and memory (see Denayer at p. 695 Abstract), and the RAS-MAPK pathway is involved with several different known disorders (see Denayer at p. 698 Figure 1). Denayer states, “[h]ow mutations in different components of the same signalling pathway result in different yet overlapping phenotypes is not fully understood…Moreover, RAS and its upstream molecules also affect other pathways than the MAPK pathway” (see Denayer at p. 701 right col. ¶2).
In regards to unpredictability for targeting RAS-SOS interaction for treatment of cancer, Lu et. al. states "[d]espite more than three decades of effort, no effective inhibitors that directly target Ras oncoproteins have been successful in the clinic, rendering Ras proteins still ‘undruggable'" (see Lu at p. 814 right col. ¶2). Lu goes on to say “mutated Ras isoforms tend to associate with particular cancer types, and different isoforms have distinct oncogenic properties, which may respond differentially to targeted therapies” (see Lu at p. 819 right col. ¶2).
In regards to targeting RAS-SOS interaction for treatment of specific cancers, Moore teaches targeting RAS-SOS1 interaction is a desirable drug target (see Moore at p. 538 right col. ¶2), and notes “mutations in KRAS are known drivers of three of the most lethal cancers (lung cancer, colorectal cancer (CRC) and pancreatic cancer)” (see Moore at p. 533 left col. ¶1). A known SOS1 inhibitor, BI-1701963 is currently in clinical trials for advanced or metastatic solid tumors (see Moore at p. 539 Table 1).
Furthermore, the method of claim 9 includes diseases and conditions not yet discovered and not yet discovered to be responsive to inhibition of SOS1. It would certainly require undue experimentation to discover the enabled embodiments encompassed by claim 9.
The prior art provides enablement for treating RAS-driven lung cancer, colorectal cancer, and pancreatic cancer tumors.
The amount of direction or guidance provided (5) and the presence or absence of working examples (6)
The specification provides the following embodiments:
Example 1, inhibition of SOS1 (see instant spec. at pp. 85-88). Notably Applicant has provided IC50 values in testing 96 compound species.
Example 2, antiproliferation assay of pancreatic cancer cells (see instant spec. at p. 88). Notably applicant has not provided any data, but has simply recited procedural steps.
Example 3, SOS1 pERK inhibition in PC9 cells (see instant spec. at p. 89). Notably Applicant does not provide data for the compounds, but simply states a summary of IC50 value findings.
The specification provides enablement for inhibiting SOS1 in vitro.
Nowhere in the specification is it explained how such cancers listed in claims 13-14 are to be prevented through the administration of the claimed compounds.
Therefore, the full scope of treatment in the methods of claims 9, 13-14 are not enabled.
The quantity of experimentation necessary (7) and the relative skill of those in the art (8)
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. Because of the unknown predictability in the art (as discussed above) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that compounds of Formula I-1 or I-2 could be used as treatments for any Ras-associated disease or those diseases specifically listed in claims 13-14.
Brenner v. Manson states "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (Brenner v. Manson 383 U.S. 519, 536, 148 USPQ 689, 696 (1966), cited in Genentech Inc. vs. Nova Nordisk 42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, little experimentation provided is drawn to treatment, prevention, and prophylaxis of diseases listed in claims 13-14. A review of the state of the art fails to reveal that SOS inhibitors are useful as therapeutic treatment as broadly claimed (e.g. learning and memory disorders, any cancer, etc). Determining if compounds of Formula I-1 or I-2 would be therapeutic for any particular disease state would require careful analysis and replicability of a composition comprising a compound of Formula I-1 or I-2, formulation into a suitable dosage form, assay testing to correlate clinical efficacy, identifying off-targets, subjecting to animal trials, and subjecting to clinical trials.
All this is undue experimentation given the limited guidance and direction provided by Applicants.
Conclusion
Accordingly, the inventions of claims 9, 13-14 does not comply with the enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Suggested Amendment
Examiner suggests cancelling claims 13-14 and amending claim 9 to read:
A method for treating wherein the RAS-driven tumor is selected from the following: lung cancer, colorectal cancer, and pancreatic cancer.
Modified/Maintained Rejection(s)
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 9-10 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 20210139517 A1 to Gill et. al.5
Regarding claim 1 and compounds of Formula I-1, Gill teaches compounds that read on Formula I-1 such as Example 10 (see Gill at p. 40). Example 10 reads on instant Formula I-1 when R1 is
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51
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,
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51
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is
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, R3 is C1-6 alkyl specifically methyl, R4 is H.
Gill Example 10
Instant Claim 10
Instant Formula I-1
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Regarding claim 9 and a method of treatment, Gill teaches administering the compounds to a subject in order to treat a cancer such as colorectal cancer (see Gill at claim 46). Gill also teaches administering an effective amount (see Gill at p.4 ¶ [0038], p. 8 ¶[0073]).
Regarding claim 10 and a composition, Gill teaches preparation of the compounds as medicaments (see Gill at p. 209 ¶[0228]), and compositions formulated for various routes of administration comprising carriers (see Gill at p. 210 ¶[0243]-[0244]). Gill also teaches administering an effective amount (see Gill at p.4 ¶ [0038]).
Allowable Subject Matter
Claims 2-8, 11-12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 2-8, 11-12 are objected to.
Claims 1, 9-10, 13-14 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.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 filed January 28, 2022 with priority to CN 114835719 filed February 1, 2021. WO document hereinafter Lv, CN document hereinafter CN’719, cite No. 10 in the IDS filed 6/26/23. Machine Translation of WO 2022161480 A1, Translated by Patent Translate Espacenet.org on 9/25/25, 198 pages, hereinafter WO'480T. Machine Translation of CN 114835719, Translated by Patent Translate Espacenet.org on 9/25/25, 183 pages, hereinafter CN'719T.
2 Published August 8, 2013. Cite No. 3 in the IDS filed 6/26/23. Hereinafter Kawai.
3 Published May 13, 2021 and filed November 5, 2020. Hereinafter Gill.
4 Denayer, et. al. "Clinical and molecular aspects of RAS related disorders" J Med Genet 2008, 45, 695-703. DOI: 10.1136/jmg.2007.055772 Hereinafter Denayer.
5 Published May 13, 2021 and filed November 5, 2020. Hereinafter Gill.