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, 3, 5, 7-9, 14-15, 18-20, 23-24, 50-54 and 57-58 are pending.
Election/Restrictions
Applicant’s election without traverse of the species and monotherapy in the reply filed on August 5, 2025 is acknowledged.
Claims 1, 3, 14, 15, 18, 50-54, 57, and 58 are directed to the elected species.
Claims 5, 7-9, 19, 20, 23, and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 5, 2025.
The elected species is recognized as the first compound of claim 52
PNG
media_image1.png
130
172
media_image1.png
Greyscale
and also recognized as compound 14 of Table 1. Compound 14 is found on page 30 of Table 1 of the specification.
PNG
media_image2.png
244
744
media_image2.png
Greyscale
Compound 14 has been identified in the accompanying SciFinder searches dated on or about Sept 22, 2025 as CAS Registry Number: 1884219-69-5.2
PNG
media_image3.png
184
314
media_image3.png
Greyscale
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 4/11/2023, 1/17/2024, 2/26/2024 and 08/05/2025 are in compliance with the provisions of 37 CFR 1.97. The information disclosure statements have been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 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 treatment of ALL cancers with elected species, compound 14, does not reasonably provide enablement for the full scope of treating all cancers with the full scope of a compound of formula A as claimed. 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. Generally the invention is directed to a method for treating cancer in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a ULK inhibitor having a structure of Formula A:
PNG
media_image4.png
146
150
media_image4.png
Greyscale
wherein in Formula A:
R10 is halogen; -OR11, wherein R11 is selected from the group consisting of H, optionally substituted aryl and optionally substituted heteroaryl; -NR1R2, wherein R1 is H, -C(=O)R12, where R12 is C1-C6 alkyl or C1-C6 cycloalkyl, or optionally substituted alkyl and R2 is H, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, or optionally substituted alkyl, or NR1R2 together form a heterocycle;
R4 is optionally substituted amino, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkoxy, N-heterocyclic, optionally substituted thiol, optionally substituted alkyl, hydroxyl or halogen;
or R4 and R10 together form a cyclic structure;
R5 is H, hydroxyl, optionally substituted alkyl, halo, optionally substituted alkoxy, or optionally substituted aryl, optionally substituted carboxyl, cyano, or nitro;
or R5 and R6 together form a cyclic structure; and
R6 is H, halogen, or haloalkyl.
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 one skilled in the art recognizes the difficulties in treating cancer. With regard to the claimed method treating cancer with ULK inhibitors, the art acknowledges such ULK inhibition has been studied to treat cancer. See Abstract and Discussion section of Tang et al.3 In particular, administration of the ULK inhibitor SBIO206965 was demonstrated to sensitize non-small lung cell lung cancer (NSCLC) cells to the chemotherapy drug cisplatin 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.
Tang teaches the role that ULK per se plays in treating cancer 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) titled “ ULK1 inhibits the kinase activity of mTORC1 and cell proliferation.”4 Jung et al. teaches in fact, 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 very broad in that it is directed to the treatment of any cancer with the full scope of compounds of Formula A.
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 method of treating any and all cancers with the full scope of compounds of Formula A.
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 (all directed to compound 14) starting at paragraph 193 merely note validation of ULK1 as a non-small cell lung cancer (NSCLC) target for treatment; notes Compound 14 (only) was demonstrated in with NSCLC NCK-538, NCI-H460, A549 NSCLC xenografts in mice demonstrated smaller tumor burden; validation of ULK as pediatric cancer target; in particular MIA PaCa-2 xenografts; and Triple Negative Breast Cancer (TNBC) cells. The above working examples and corresponding cannot be said to support the full scope of treating all cancers as claimed with all compounds of Formula A. 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.
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.
Claims 1, 3, 14, 15, 18, 50-54, 57 and 58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2016/033100 A1. WO 100 is cited as Foreign Patent Doc B1 on the IDS dated Feb 26 2024.
Regarding claim 1 and the treatment of cancer in a subject in need comprising the administration to the subject a therapeutically effective amount of a ULK inhibitor of Formula A, WO 100 teaches compound 14, which is elected species compound 14, for the treatment of cancer. See Table 1 at page 32; page 113 Example 14 teaching the preparation of compound 14, aka 2-(5-Bromo-2-(3,4,5trimethoxyphenylamino)pyrimidin-4-yl amino)-N-methylbenzamide;
PNG
media_image5.png
138
196
media_image5.png
Greyscale
Regarding claim 1 and the limitation of treating a subject in need with cancer, WO 100 teaches its methods are directed to treat cancers, including non-small cell lung cancer. See page 98, lines 27-30. Regarding claim 1, WO 100 teaches its compounds are ULK1 inhibitors. See abstract.
Regarding claim 3 and the limitation of ULK1 inhibitor monotherapy, WO 100 teaches its “therapeutically effective amount” of specified agent (sufficient to achieve a desired result) is an “amount of a ULK 1 inhibitor that is sufficient to inhibit autophagy in a desired cell in a subject.” See page 28, lines 18-21.
As required by claims 14-15 and the limitation of lung, breast, or pancreatic cancer, WO 100 teaches treatment of these cancers, including non-small cell lung cancer at page 98, lines 27-30.
In rejecting claim 18 and the limitation of refractory cancer to be treated, WO 100 teaches treatment of refractory cancers. See page 99, lines 11-16.
Regarding claims 50-52 which are directed to elected species compound 14, WO 100 teaches compound 14 as detailed above. 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.
As required by claim 53 and the limitation of ULK1 inhibition, WO 100 teaches its compounds are ULK1 inhibitors. See abstract.
Regarding claim 54 and the limitation of further comprising decreasing phosphorylation of ATG13 in the subject, decreasing an amount of ATG13 in the subject, and/or degrading ATG13 in diseased tissue of the subject, WO 100 teaches compound 14 treatment induced loss of ULK1 and Atg13 protein levels. See page 258, lines 33-35.
Regarding claim 57 and the limitation of a subject’s mutation of at least one of KRAS, PTEN, TSCl, TSC2, Plk3CA, P53, STKl 1 (a.k.a. LKB1), KEAP1, NRF2, EGFR, SMAD4, pl6/CDKM2A, BRCA2, ALK4, or GNAS, WO 100 teaches that the chemical suppression of ULK1, by its ULK1 inhibitors, “leads to a block in the ability of mTOR inhibitors to induce autophagy, which triggers rapid apoptosis in tumor cells addicted to mTOR signaling, such as tumors lacking [i.e. mutations] Pten, LKB 1, TSCI, TSC2, or NF1Or bearing oncogenic mutations in Kras, Rheb, pl 10a or other components of the Pi3K-mTOR pathway.” See page 5, lines 10-14.
With regard to claim 58 requiring a pharmaceutical composition comprising a pharmaceutically acceptable carrier, WO 100 teaches the use of pharmaceutical compositions comprising its compounds and a pharmaceutically acceptable carrier. See page 24 bridging to page 25. See also page 101, lines 25-25 and page 102, lines 1-8.
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.
Claims 1, 3, 14, 15, 18, 50-54, 57, and 58 are 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 of Formula A (claims 1 and 50), such as elected species compound 14 (claim 52). Dependent claims 3, 14, 15, 18, 50, 51, 54 and 57-58 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 are all directed to specific compounds within the scope of examined claim 1’s formula A, inclusive of compound 14, the species elected by Applicant.
PNG
media_image6.png
210
282
media_image6.png
Greyscale
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 below. It 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, 3, 14, 15, 18, 50-54, 57, and 58 are 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 invention is generally directed to a method of treating a subject in need, afflicted with cancer comprising administering a compound/ULK1 inhibitor of Formula A (claims 1 and 50), such as elected species compound 14 (claim 52). Dependent claims 3, 14, 15, 18, 50, 51, 54 and 57-58 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 for both patents, are all directed compounds per se of Formula A, with identical overlapping scope to those of the examined claims.
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 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, 3, 14, 15, 18, 50-54, 57, and 58 are 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 invention is generally directed to a method of treating a subject in need, afflicted with cancer comprising administering a compound/ULK1 inhibitor of Formula A (claims 1 and 50), such as elected species compound 14 (claim 52). Dependent claims 3, 14, 15, 18, 50, 51, 54 and 57-58 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.
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 Formula A. 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, 3, 14, 15, 18, 50-54, 57, and 58 are 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 invention is generally directed to a method of treating a subject in need, afflicted with cancer comprising administering a compound/ULK1 inhibitor of Formula A (claims 1 and 50), such as elected species compound 14 (claim 52). Dependent claims 3, 14, 15, 18, 50, 51, 54 and 57-58 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.
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 claimed. 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
In summary, no claims are allowed.
Correspondence
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.
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.
/WILLIAM Y LEE/
Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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 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.