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 . 1
Status of Claims
Claims 1,14-15,18,53-54 and 57-58 are under examination. Claims 2-13, 16-17, 19-52, 55 and 56 were canceled. Amended Claim 1 is now solely directed to the elected species, compound 14,2 found at Table 1, page 30 of the specification, see below.
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Response to Arguments
Applicant's arguments with regard to the enablement rejection, filed April 2, 2026 have been fully considered but they are not persuasive. See below rejection of claims 1, 3, 14, 15, 18, 50-54, 57 and 58 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph for lack of enablement.
Applicant’s arguments, amendment of claim 1 and cancellation of claims, filed April 2, 2026, with respect to the rejection of claims 1, 3, 14, 15, 18, 50-54, 57 and 58 under 35 USC 102(a)(1) have been fully considered and are persuasive. The rejection of claims 1, 3, 14, 15, 18, 50-54, 57 and 58 has been withdrawn.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/4/2025 and 4/2/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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 1, 3, 14, 15, 18, 50-54, 57 and 58 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling for treatment of specific cancers (lung, breast and pancreatic, supported by working examples of specification) with Compound 14, does not reasonably provide enablement for the full scope of treating all cancers with Compound 14 of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Applicant's attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at
1404 where the court set forth factors to consider when assessing if a disclosure would
have required undue experimentation. The applicant's attention is drawn to In re
Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to
consider when assessing if a disclosure would have required undue experimentation.
Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight
factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill
of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of
the claims; (6) the amount of direction or guidance presented; (7) the presence or
absence of working examples; and (8) the quantity of experimentation necessary.
The predictability or unpredictability of the art:
The instant claimed invention is highly unpredictable since a person having ordinary skill in the art (PHOSITA) recognizes the difficulties in treating cancer. With regard to the claimed method treating all cancer with ULK inhibitors, the art does acknowledges ULK inhibition has been studied to treat cancer, at least as combination therapy. See Abstract and Discussion section of Tang et al. 3
Administration of the ULK inhibitor SBIO206965 was demonstrated to sensitize non-small lung cell lung cancer (NSCLC) cells to cisplatin chemotherapy partly through autophagy inhibition. See Figure 6, page 3456, column 1.
Tang teaches "Ulk1 plays a key role in the initial stages of autophagy (10), but the role of Ulk1 in cancer has remained largely unknown." See page 3456, column 1.
In fact, opposite to what is being claimed, a method of inhibiting cancer by ULK inhibition, Tang teaches the role that ULK plays in treating cancer by inducing cell death in cancer cell types, where it states,“ However, studies have also shown that Ulk1 inhibits cell proliferation and induces apoptosis in other cancer cell types.” See page 3456, column 1.
Tang references Jung et al. (2011) entitled “ULK1 inhibits the kinase activity of mTORC1 and cell proliferation.”4 Jung et al. teaches, rather than ULK1 inhibition to treat cancer, ULK1 per se negatively regulates kinase activity of mTORC1 and cell proliferation, concluding “The inhibition of mTORC1 by ULK1 may be important to coordinately regulate cell growth and autophagy with optimized utilization of cellular energy.” See Abstract.
Accordingly, the unpredictability in the art (beyond the use of compound 14) is a Wands factor against the enablement of the full scope of the invention.
The breadth of the claims:
Claim 1 is broadly directed to the treatment of any cancer with the single claimed Compound 14. The broad scope of the claims is a Wands factor against the enablement of the full scope of the invention.
The amount of direction or guidance presented, and the presence or
absence of working examples
It has been established that "the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art." In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
The specification does not provide a clinical experimental method of treating any and all cancers with Compound 14. At best the specification provides examples limited to compound 14 as follows. Table 1 provides illustrative compounds with respective IC50 values for ULK1 inhibition assay, inclusive of compound 14 with an IC50 of μM activity of A, with A representing IC50 < 0.2 μM. See paragraph 140.
Working Examples 1-10 (directed to compound 14) starting at paragraph 193 merely note validation of ULK1 as a non-small cell lung cancer (NSCLC) target for treatment; they note Compound 14 (only) was demonstrated in with NSCLC NCK-538, NCIH460, A549 NSCLC xenografts in mice demonstrated smaller tumor burden; they validate ULK as pediatric cancer target; in particular MIA PaCa-2 xenografts; and Triple Negative Breast Cancer (TNBC) cells.
Further, the specification’s Example 6, “Validation of ULK as a Target for Treatment of Pancreatic Cancer,” provides support to enable compound 14 to treat pancreatic cancer. The above working examples and corresponding cannot be said to support the full scope of treating all cancers as claimed with compound 14, just pancreatic, breast and lung cancer.
The lack of working examples is a Wands factor against the enablement of the full scope of the invention.
Therefore, in view of the Wands factors as discussed above, particularly the state of the art, breadth of the claims, and lack of amount of direction or guidance presented, Applicant fails to provide information sufficient to practice the full scope of the claimed invention.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response notes a statement from the previous rejection stating Compound 14 is enabled for treatment of all cancers.
Upon further consideration of the Wands factors listed, especially the unpredictability in the art, the broad scope of claim 1 and lack of sufficient working examples, the 112(a) enablement rejection remains for the treatment of all cancers, even with just Compound 14, as detailed above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response requests the provisional ODP rejections over U.S. Patent No. 10,266,549; U.S. Patent No. 10,689,397; U.S. Patent No. 10,774,092; Application no. 18/028,751; and Application no. 17/799,639 be held in abeyance.
In response, the request to hold rejections in abeyance is NOT a proper rebuttal of the ODP rejections. Therefore, the ODP rejections are maintained over the pending/examined claims.
Claims 1,14-15,18,53-54 and 57-58 remain rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-20 of U.S. Patent No. 10,266,549 in in view of WO 2016/033100 A (WO 100).
The invention is generally directed to a method of treating a subject in need, afflicted with cancer comprising administering a compound/ULK1 inhibitor, compound 14 (claim 1). Dependent claims limit the method to monotherapy of a particular type(s) of cancer(s), such as breast, lung and pancreatic, including Non-small cell lung cancer (NSCLC); or a refractory cancer; including the reduction of ATG13 in the subject, with a number of mutations in the subject (for example KRAS) and pharmaceutical composition comprising a pharmaceutically acceptable carrier. Reference patent claims 1-20 include examined claim 1’s compound 14, the species elected by Applicant.
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Note that reference patent claims 1-2, 14, 16, 17 and 19 specifically disclose elected species compound 14.
It is noted that the reference patent claims 1-20 do not claim a method of treating a cancer with its compounds, or the other limitations of dependent claim. It is pointed out that the secondary reference WO 100 teaches the same compounds, including elected species compound 145; where the compounds are ULK1 inhibitors.6 Further, with regard to examined claims 3, 14, 15, 18, 50-54, 57, and 58, WO 100 teaches monotherapy treatment7 of breast, lung and pancreatic, including Non-small cell lung cancer (NSCLC)8; or a refractory cancer9; including the reduction of ATG13 in the subject;10 with a number of mutations in the subject (for example KRAS);11 and pharmaceutical composition comprising a pharmaceutically acceptable carrier.12 See the teachings of WO 100 detailed in the footnotes. It would have been prima facie obvious to a PHOSITA following the teachings of the primary reference patent claiming the ULK1 inhibitor compounds per se, to modify with the secondary reference WO 100 to arrive at the claimed method invention.
The PHOSITA would have had a reasonable expectation of success because the both the reference patent and WO 100 teach the same compounds, inclusive of compound 14, where WO 100 teaches methods of treating cancer with these compounds as claimed.
Claims 1,14-15,18,53-54 and 57-58 remain rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-20 of U.S. Patent No. 10,689,397 in view of WO 2016/033100 A (WO 100) and
claims 1-20 of U.S. Patent No. 10,774,092 in view of WO 2016/033100 A (WO 100).
The claimed subject is discussed above and incorporated here. Reference patent claims 1-20 for both patents, are all directed compounds per se of Formula A, with identical overlapping scope to those of the examined claims (compound 14).
It is noted that the reference patents’ claims 1-20 do not claim a method of treating a cancer with its compounds, or the other limitations of dependent claim. The secondary reference WO 100 teaches the same compounds, including elected species compound 1413; where the compounds are ULK1 inhibitors.14 Further, with regard to examined claims 3, 14, 15, 18, 50-54, 57, and 58, WO 100 teaches monotherapy treatment15 of breast, lung and pancreatic, including Non-small cell lung cancer (NSCLC)16; or a refractory cancer17; including the reduction of ATG13 in the subject;18 with a number of mutations in the subject (for example KRAS);19 and pharmaceutical composition comprising a pharmaceutically acceptable carrier.20 It would have been prima facie obvious to a PHOSITA following the teachings of the primary reference patents claiming the ULK1 inhibitor compounds per se, to modify with the secondary reference WO 100 to arrive at the claimed method invention.
The PHOSITA would have had a reasonable expectation of success because the both reference patents and WO 100 teach the same compounds, inclusive of compound 14, where WO 100 teaches methods of treating cancer with these compounds as claimed.
Claims 1,14-15,18,53-54 and 57-58 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 4-9, and 16-19 and 21-23 of copending Application No. 18/028,751.
The claimed subject is discussed above and incorporated here. Regarding the examined claims, the reference application claims teach a method of treating a disorder mediated by ULK in a subject in need, comprising administering a therapeutically effective amount of a ULK inhibitor. See reference application claims 1 and 18 for the teaching of a compound of Formula A with overlapping scope as examined claim 1’s compound 14. Reference application claims 4-5 teach the ULK mediated disorder is cancer and cancer tissue. Reference claims 6-9 and 12-13 note the treatment with a ULK inhibitor when the certain disorder (such as cancer) gene expression is above a threshold. Reference claims 16-17 disclose various genes, including cancer genes. Reference claims 18-19 and 21-23 disclose compounds of formula A with scope overlapping those claimed; monotherapy; treatment of lung, breast or pancreatic cancer; and treatment of refractory cancer to a number of therapies.
This is a provisional nonstatutory double patenting rejection.
Claims 1,14-15,18,53-54 and 57-58 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 10-11, 14, 22, 25, 33, 38, 40, 43-44, 50, 191, 192, 193, 195, 196, of copending Application No. 17/799,639.
The claimed subject is discussed above and incorporated here. As required by the pending examined claims, reference applications claims 1-2, 5, 10-11, 14, 22, 25, 33, 38, 40, 43-44, 50, and 191 are directed compounds of formula IA, with overlapping scope of those formula A, including Compound 14. Pending reference claims 192, 193, 195, and 196, are directed to methods of treating ULK1 mediated diseases (lung, breast or pancreatic cancer) in a patient via administering compounds and pharmaceutical compositions of the above formula IA compounds.
This is a provisional nonstatutory double patenting rejection
Conclusion and Correspondence
In summary, no claims are allowed. 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 WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
1 CONTINUING DATA
This application is a 371 of PCT/US21/18044 02/12/2021
PCT/US21/18044 has PRO 62/977,041 02/14/2020
2 CAS Registry Number: 1884219-69-5
2-[[5-Bromo-2-[(3,4,5-trimethoxyphenyl)amino]-4-pyrimidinyl]amino]-N-methylbenzamide (ACI)
3 Tang et al. SBI0206965, a novel inhibitor of Ulk1, suppresses non-small cell lung cancer cell growth by modulating both autophagy and apoptosis pathways, ONCOLOGY REPORTS 37: 3449-3458, 2017 (cited as NPL reference C6 on the Feb 26 2024 IDS).
4 Jung et al. (2011) titled “ ULK1 inhibits the kinase activity of mTORC1 and cell proliferation,” Autophagy 7:10, 1212-1221; October 2011
5 See WO 100 Table 1 at page 32; WO 100 page 113 Example 14 teaching the preparation of compound 14, aka 2-(5-Bromo-2-(3,4,5trimethoxyphenylamino)pyrimidin-4-yl amino)-N-methylbenzamide
6 See abstract.
7 See page 28, lines 18-21 disclosing therapeutically effective amounts of ULK1 inhibitor sufficient to inhibit autophagy in a desired cell in a subject.
8 See page 98, lines 27-30
9 See page 99, lines 11-16.
10 See page 258, lines 33-35
11 See page 5, lines 10-14.
12 See page 24 bridging to page 25. See also page 101, lines 25-25 and page 102, lines 1-8.
13 See WO 100 Table 1 at page 32; WO 100 page 113 Example 14 teaching the preparation of compound 14, aka 2-(5-Bromo-2-(3,4,5trimethoxyphenylamino)pyrimidin-4-yl amino)-N-methylbenzamide
14 See abstract.
15 See page 28, lines 18-21 disclosing therapeutically effective amounts of ULK1 inhibitor sufficient to inhibit autophagy in a desired cell in a subject.
16 See page 98, lines 27-30
17 See page 99, lines 11-16.
18 See page 258, lines 33-35
19 See page 5, lines 10-14.
20 See page 24 bridging to page 25. See also page 101, lines 25-25 and page 102, lines 1-8.
Prosecution Insights