Prosecution Insights
Last updated: April 19, 2026
Application No. 18/033,931

PYRIMIDINE COMPOUNDS, COMPOSITIONS, AND MEDICINAL APPLICATIONS THEREOF

Final Rejection §112§DP
Filed
Apr 26, 2023
Examiner
HERNANDEZ, JACKSON J
Art Unit
1627
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
BLUEPRINT MEDICINES CORPORATION
OA Round
2 (Final)
50%
Grant Probability
Moderate
3-4
OA Rounds
3y 2m
To Grant
99%
With Interview

Examiner Intelligence

Grants 50% of resolved cases
50%
Career Allow Rate
15 granted / 30 resolved
-10.0% vs TC avg
Strong +51% interview lift
Without
With
+51.1%
Interview Lift
resolved cases with interview
Typical timeline
3y 2m
Avg Prosecution
87 currently pending
Career history
117
Total Applications
across all art units

Statute-Specific Performance

§101
2.4%
-37.6% vs TC avg
§103
34.9%
-5.1% vs TC avg
§102
11.8%
-28.2% vs TC avg
§112
24.7%
-15.3% vs TC avg
Black line = Tech Center average estimate • Based on career data from 30 resolved cases

Office Action

§112 §DP
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 68-69, 76-77, 82, and 84 are pending in this application. Claims 1-67, 70-75, 78-81, 83, and 85-92 have been cancelled by applicant. 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 68-69, 76-77, 82, and 84 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/033,954 (Copending ‘954); in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) (“Morita”). Regarding instant claim 68, Copending ‘954 claims the compound 37 below, for example, which renders the instant compound 21 obvious in view of Morita (Copending ‘954 claims 1-14 and 20). Copending ‘954 compound: PNG media_image1.png 137 202 media_image1.png Greyscale (37) Instant Compound: PNG media_image2.png 133 183 media_image2.png Greyscale (21) Regarding instant claims 69, 76-77, 82, and 84, Copending ‘954 claims pharmaceutical compositions comprising their compounds and methods of treating cancers comprising EGFR mutations (Copending ‘954 claims 17-19). While Copending ‘954 does not teach their compounds wherein their R1 phenyl ring contains 2 substituents (as shown in the examples above), the teachings of Morita are relied upon for these disclosures. Morita discloses that H and F as monovalent classical bioisosteres in medicinal chemistry (page 4, box under classical bioisosteres). Morita teaches that the design of bioisosteres introduces structural changes that can be beneficial by modulating size, shape, lipophilicity, etc., resulting in improvements of potency, selectivity, metabolism, etc. (see bottom of page 3). Therefore, regarding instant claim 68, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare any of Copending ‘954’s compounds and replace one of the hydrogen groups on the phenyl ring (R1) with a fluorine to arrive at the instant invention. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘954 disclosure of the compounds of Formula I, including the specific examples shown above, and Morita’s teachings that H and F are monovalent bioisosteres, and that the design of bioisosteres introduces structural changes that can be beneficial by modulating size, shape, lipophilicity, etc., resulting in improvements of potency, selectivity, metabolism, etc. Applicant is further advised that the courts have found that similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)). This is a provisional nonstatutory double patenting rejection. Response to Arguments Claims Claim amendments are acknowledged. No new matter has been introduced. Claim Objections Applicant’s arguments, see page 16, filed 01/08/2026, with respect to objections to the claims have been fully considered and are persuasive. The objection of claim 1 has been withdrawn. Claim Rejections - 35 USC § 112(b) Applicant’s arguments, see page 16, filed 01/08/2026, with respect to 35 USC § 112(b) rejection to the claims have been fully considered and are persuasive. The 35 USC § 112(b) rejection to the claims has been withdrawn. Claim Rejections - 35 USC § 112(d) Applicant’s arguments, see page 16, filed 01/08/2026, with respect to 35 USC § 112(d) rejection to the claims have been fully considered and are persuasive. The 35 USC § 112(d) rejection to the claims has been withdrawn. Double Patenting Applicant's arguments filed 01/08/2026 have been fully considered but they are not persuasive. Applicant argues the compounds from the instant claim 68 are individual compounds with a phenyl group substituted 2 or 3 times, and that nothing of Copending ‘954 motivates one skilled in the art to add more than one substituent on the phenyl. Applicant states Morita teaches the general concept of isosteres in med. Chem, that Morita does not teach or suggest which compound in Copending ‘954 as a starting point for further modification, and that nothing in Morita provides motivation or suggestion for choosing a specific position of the phenyl to fluorinate and that there is not reasonable expectation that the instant compounds would have the same EGFR activity. Applicant states the instant compounds are potent inhibitors of EGFR, citing Table 10 of the spec, pages 147-178 for specific IC50 values. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Copending ‘954 claims the compound 37 below, for example, which renders the instant compound 21 obvious in view of Morita (Copending ‘954 claims 1-14 and 20). Copending ‘954 compound: PNG media_image1.png 137 202 media_image1.png Greyscale (37) Instant Compound: PNG media_image2.png 133 183 media_image2.png Greyscale (21) Regarding instant claims 69, 76-77, 82, and 84, Copending ‘954 claims pharmaceutical compositions comprising their compounds and methods of treating cancers comprising EGFR mutations (Copending ‘954 claims 17-19). While Copending ‘954 does not teach their compounds wherein their R1 phenyl ring contains 2 substituents (as shown in the examples above), the teachings of Morita are relied upon for these disclosures. Morita discloses that H and F as monovalent classical bioisosteres in medicinal chemistry (page 4, box under classical bioisosteres). Morita teaches that the design of bioisosteres introduces structural changes that can be beneficial by modulating size, shape, lipophilicity, etc., resulting in improvements of potency, selectivity, metabolism, etc. (see bottom of page 3). Therefore, regarding instant claim 68, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare any of Copending ‘954’s compounds and replace one of the hydrogen groups on the phenyl ring (R1) with a fluorine to arrive at the instant invention. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘954 disclosure of the compounds of Formula I, including the specific examples shown above, and Morita’s teachings that H and F are monovalent bioisosteres, and that the design of bioisosteres introduces structural changes that can be beneficial by modulating size, shape, lipophilicity, etc., resulting in improvements of potency, selectivity, metabolism, etc. Applicant is further reminded that the courts have found that similar properties may normally be presumed when compounds are very close in structure. (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. It is noted that the courts have stated “[A] prior art reference must be considered in its entirety, i.e., as a whole” W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983) (see MPEP 2141.02 VI). Thus, while the rejections listed above present a modified interpretation of the teachings of the previously cited prior solely for the purpose of clarity, the claims remain rejected over the prior art of record. In response to applicant’s arguments that the instant compounds are highly potent against EGRF (citing table 10 of the instant spec.); below is a comparison of the example compound 37 from Copending ‘954 (Table 26 of Copending ‘954 spec.) cited above vs the instant compound 21: Copending ‘954 PNG media_image3.png 117 647 media_image3.png Greyscale PNG media_image4.png 143 652 media_image4.png Greyscale Instant Compound PNG media_image5.png 92 651 media_image5.png Greyscale PNG media_image6.png 162 652 media_image6.png Greyscale As evident by these results, instant compound 21 shows significantly reduced activity compared to Copending ‘954’s compound 37. Therefore, in the absence of unexpected results, the instant compounds are obvious in view of Copending ‘954 and Morita, and claims stand rejected over provisional non-statutory double patenting. This action is final. Conclusion 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 JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5. Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. 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. /JACKSON J HERNANDEZ/Examiner, Art Unit 1627 /SARAH PIHONAK/Primary Examiner, Art Unit 1627
Read full office action

Prosecution Timeline

Apr 26, 2023
Application Filed
Sep 11, 2025
Non-Final Rejection — §112, §DP
Jan 08, 2026
Response Filed
Feb 08, 2026
Final Rejection — §112, §DP (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
50%
Grant Probability
99%
With Interview (+51.1%)
3y 2m
Median Time to Grant
Moderate
PTA Risk
Based on 30 resolved cases by this examiner. Grant probability derived from career allow rate.

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