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 .
Current Status of 18/501,729
This Office Action is responsive to the amended claims of 10/21/2025.
Claims 115-117, 121, 123, 126, 127-132 are examined on the merits.
New claim 133 is withdrawn as it is drawn to a nonelected species of PRMT5 inhibitor.
Claims 115-117, 121,123, 126, and 127-132 read on the elected species and Markush extensions.
Claims 118-120, 122, 124-125, 133 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 10/15/2024.
Priority
This application is a national stage entry of PCT/US2022/072693, filed 6/1/2022, which claims priority to 63/364,360, filed 5/9/2022, 63/362,438, filed 4/4/2022, and 63/196,008, filed 6/2/2021.
The instant claims find support from 63/196,008. Therefore, the effective filing date is 6/2/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/02/2025 and 09/08/2025, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicants’ claim amendments and Remarks of 10/21/2025 are acknowledged and have been considered.
Any rejection and/or objection not specifically addressed or modified below is herein withdrawn.
In regard to the 103 rejection, this rejection is maintained. Applicants remarks with Examiners reply is summarized below:
Applicants submit that there is no motivation to (1) select compound A, and (2) combine Compound A with a PRMT5 inhibitor with a reasonable expectation of success.
Examiner disagrees. It is prima facie obvious to combine one treatment for MTAP deletion pancreatic cancer with another in order to form a composition to be used for the very same purpose (see page 7 of the Nonfinal of 7/22/2025). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06(I).
Cottrell teaches that MAT2A inhibitors are known to be a cancer treatment. One teaching is enough for MAT2A inhibitors to be known to be made in a combination with PRMT5 inhibitor.
Applicants submit that Cottrell only provides a generic disclosure of “combination therapies” of more than 100 possible agents, which is not motivation to combine.
Cottrell includes a solitary mention of combination therapy involving MAT2A inhibitors, but Cottrell has no suggestion or motivation for a skilled artisan to single out MAT2A inhibitors.
Examiner disagrees. This teaches that MAT2A inhibitors are known to be a cancer treatment. One teaching is enough for MAT2A inhibitors to be known to be made in a combination with PRMT5 inhibitor.
Applicants submit there is unexpected synergy, shown in Example 8 on pages 293-294 of the instant specification.
Example 8 is not commensurate with the full scope of all the PRMT5 inhibitor compounds in the instant base claim 115. Example 8 covers the combination of compound A with compounds B through G. The figures that correspond to Example 8 show synergy (via Combenefit Software) are highlighted in grey, are only synergistic for some concentration amounts. The synergy that Applicants discuss appears to be dose dependent. Furthermore, Example 8 tests the combination of compounds with 3 different cell lines (HCT116 parental, HCT116 MTAP-/-, and H838), which corresponds to colon cancer, and lung adenocarcinoma). Base claim 115 recites a method of treating any cancer in a subject. There is no comparison to the closest prior art. The purported synergy might be an additive effect. Without addressing these points, these remarks are unpersuasive. This rejection is maintained.
Applicants clarified the record by noting compound 533 on page 182 of WO 2021/163344 is Compound F and filed an IDS with this reference.
In regard to the double patent rejection, this rejection cannot be held in abeyance and is maintained.
Response to Amendment
Claim Rejections - 35 USC § 103- Maintained
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.
Claims 115-117, 121, and 127-132 are rejected under 35 U.S.C. 103 as being unpatentable over ALAM (WO 2020123395), further in view of COTTRELL (WO 2021/086879 A1).
ALAM teaches compound A
PNG
media_image1.png
121
180
media_image1.png
Greyscale
used in a method of treating cancer (compound 167 on page 59 and paragraphs [0008-0009]).
ALAM teaches that compound A is a MAT2A inhibitor (paragraph [0008]). This teaches a MAT2A inhibitor limitations recited by instant claims 115-116.
ALAM teaches treating pancreatic cancer (reference claim 54). This teaches claim 128.
ALAM teaches treating solid tumors (paragraph [00239]), which teaches claim 111 and 129.
ALAM teaches treating cancers characterized by reduced or absence of MTAP activity (paragraph [0008]), which teaches claim 127.
ALAM teaches oral administration (paragraph [00262]), which teaches claim 130.
COTTRELL teaches a method of treating MTAP-deficient cancer (claims 100 and 104) by administering a compound of COTTRELL. This teaches claim 127.
COTTRELL teaches that MTAP-deficient cancer as including MTAP deletion cancers (paragraph [0114]).
COTTRELL teaches compound
PNG
media_image2.png
230
806
media_image2.png
Greyscale
(top of table 1 on page 105 with a CAS# 2641523-22-8). COTTRELL teaches the compounds of Table 1 are PRMT5 inhibitors (paragraph [0452]). This helps teach claim 117 (where R1is 5 membered heteroaryl, m is 0, X1-4 is CH, L is C(=O), and A is heterocycle). This also teaches claim 121.
While ALAM teaches a MAT2A inhibitor (compound A)
PNG
media_image1.png
121
180
media_image1.png
Greyscale
used in a method of treating MTAP deletion pancreatic cancer (compound 167 on page 59 and paragraphs [0008-0009], and ref. claim 54), ALAM does not teach PRMT5 inhibitors.
While COTTRELL PRTM5 inhibitors with the formula
PNG
media_image2.png
230
806
media_image2.png
Greyscale
(top of table 1 on page 105 with a CAS# 2641523-22-8) being used to treat MTAP-deficient cancer (claims 100 and 104), COTTRELL does not teach MAT2A inhibitors.
The artisan would find it obvious to combine a MAT2A inhibitor (like compound A from ALAM page 59 and paragraphs [0008-0009]) and a PRMT5 inhibitor (like the Compound from COTTRELL page 105). The artisan would be motivated to combine ALAM’s compound A and COTTRELL’s PRMT5 Compound because each are known to be used for the same purpose, treating MTAP deletion pancreatic cancers (ALAM’s claim 54 and paragraph [0008]; COTTRELL claim 100 and paragraph [0114]). The artisan would expect that the combination of ALAM’s compound A and COTTRELL’s Compound to result in a function MTAP-deletion cancer treatment (ALAM’s claim 54 and paragraph [0008]; COTTRELL claim 100 and paragraph [0114]). It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. See MPEP 2144.06(I). This teaches claims 115, 117, 121, 127-130.
The artisan would be motivated to treat MTAP deletion pancreatic cancers with Compound A and COTTRELL’s Compound either sequentially or concurrently. The artisan would have expected to administer Compound A and COTTRELL’s Compound either sequentially or concurrently from the natural conclusion that there are physically only two ways to administer two compounds, together at the same time or one after another. This rejects claim 131-132.
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 9/8/2025 prompted the new ground(s) of rejection presented in this Office action.
Claims 115-117, 121, 123, 126 and 127-132 are rejected under 35 U.S.C. 103 as being unpatentable over ALAM (WO 2020123395), further in view of ALLEN (WO2021/163344, whose PCT application PCT/US2021/017682 is published 2/11/2021. This date is before the EFD.).
ALAM teaches compound A
PNG
media_image1.png
121
180
media_image1.png
Greyscale
used in a method of treating cancer (compound 167 on page 59 and paragraphs [0008-0009]).
ALAM teaches that compound A is a MAT2A inhibitor (paragraph [0008]). This teaches a MAT2A inhibitor limitations recited by instant claims 115-116.
ALAM teaches treating pancreatic cancer (reference claim 54). This teaches claim 128.
ALAM teaches treating solid tumors (paragraph [00239]), which teaches claim 129.
ALAM teaches treating cancers characterized by reduced or absence of MTAP activity (paragraph [0008]), which teaches claim 127.
ALAM teaches oral administration (paragraph [00262]), which teaches claim 130.
ALLEN teaches a method of treating cancer (claims 20-23 of ‘344) by administering a compound of ALLEN (PRMT5 inhibitors, title of ‘344). ALLEN teaches treating MTAP-deficient cancer (paragraph [0003 of ‘344]). This teaches claim 127.
ALLEN teaches pancreatic cancer (paragraph [0024]).
ALLEN teaches that MTAP-deficient cancer as including MTAP deletion cancers (paragraph [0003] of ‘344).
ALLEN teaches Compound F (compound 533 on page 182 of WO 2021/163344 and compound 533 on page 179 of PCT/US2021/017682). This teaches claims 121 (page 217 sixth compound), 123, and 126.
While ALAM teaches a MAT2A inhibitor (compound A)
PNG
media_image1.png
121
180
media_image1.png
Greyscale
used in a method of treating MTAP deletion pancreatic cancer (compound 167 on page 59 and paragraphs [0008-0009], and ref. claim 54), ALAM does not teach PRMT5 inhibitors.
While ALLEN PRTM5 inhibitors being used to treat MTAP-deficient cancer (claims 20-23), ALLEN does not teach MAT2A inhibitors.
The artisan would find it obvious to combine a MAT2A inhibitor (like compound A from ALAM page 59 and paragraphs [0008-0009]) and a PRMT5 inhibitor (like ALLEN’s compound 533 on page 182 of WO 2021/163344). The artisan would be motivated to combine ALAM’s compound A and ALLEN’s PRMT5 Compound because each are known to be used for the same purpose, treating MTAP deletion pancreatic cancers (ALAM’s claim 54 and paragraph [0008]; ALLEN’s claim 20 and paragraph [0024]). The artisan would expect that the combination of ALAM’s compound A and ALLEN’s Compound to result in a function MTAP-deletion cancer treatment (ALAM’s claim 54 and paragraph [0008]; ALLEN claim 20 and paragraph [0003]). It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. See MPEP 2144.06(I). This teaches claims115, 117, 121, 123, 126, 127-130.
The artisan would be motivated to treat MTAP deletion pancreatic cancers with Compound A and ALLEN’s Compound either sequentially or concurrently. The artisan would have expected to administer Compound A and ALLEN’s Compound either sequentially or concurrently from the natural conclusion that there are physically only two ways to administer two compounds, together at the same time or one after another. This rejects claim 131-132.
Double Patenting- Maintained
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 115, 127, 128, 129, 130, and 131-132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12115163. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the applications are not distinct.
Ref. Claim 1 anticipates a method of treating cancer using a MAT2A inhibitor and a PRMT5 inhibitor. Ref Claim 3 anticipates a compound of formula I (the same as instant claim 115’s formula I). Ref. Claim 1 anticipates unexamined instant claim 104 (page 142 of the instant claims, right col. 4th compound).
Ref. claim 6 anticipates the cancer is characterized by a reduction or absence of MTAP gene expression. This anticipates claim 127.
Ref. Claim 7 anticipates pancreatic cancer. This anticipates claim 128.
Ref. Claim 8 anticipates a solid tumor. This anticipates claim 129.
Ref. claim 9 anticipates oral administration. This anticipates claim 130.
Ref. claim 10 and 11anticipates concurrently and sequentially administered the compounds. This anticipates claim 131-132.
All claims are rejected; no claims are allowed.
Conclusion
No claims are allowed.
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 9/8/2025 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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 GILLIAN A HUTTER whose telephone number is (571)272-6323. The examiner can normally be reached M-F 7:30-5.
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, Andrew Kosar can be reached at 571-272-0913. 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.
/G.A.H./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625