Prosecution Insights
Last updated: April 18, 2026
Application No. 18/028,463

PLK1 POLO BOX DOMAIN INHIBITORS AND METHOD OF TREATING CANCER

Final Rejection §102§103§112
Filed
Mar 24, 2023
Examiner
HERNANDEZ, JACKSON J
Art Unit
1627
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The United States Department of Health and Human Services
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

§102 §103 §112
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 16-34 are pending in this application. Claims 1-15 have been cancelled by applicant. Claims 27-30 and 33 are under consideration herein. Claims 16-26, 31-32, and 34 have been withdrawn from consideration as being directed to a non-elected invention or species and there being no allowable linking claim. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 29 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 29 is rejected for failing to further limit claim 27, from which it depends. Specifically, amended claim 27 defines that R2 in compounds Ib-2 cannot be alkyl, however, in claim 29, most compounds (like the ones below, for example) have alkyl in the position corresponding to R2. PNG media_image1.png 97 112 media_image1.png Greyscale PNG media_image2.png 112 125 media_image2.png Greyscale Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 103 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. Claims 27-30, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal et al. (WO 2019/084271 A1 – cited in the IDS – previously cited) (“Agarwal”); 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 – previously cited) (“Morita”). Regarding claims 27-28, Agarwal discloses the compounds 72-74 below (page 224) and teaches their compounds as telomerase inhibitors, and as useful for the treatment of cancers (page 163, last para.; and page 1) – which is the same intended use as the instant compounds. Compounds 72-74 render the instant compounds of Formula Ib-1 obvious when R1a, 1b are H or F; R2 is haloalkyl; R3 is H; a is a single bong; b is a double bond; and R4 is S. PNG media_image3.png 98 241 media_image3.png Greyscale PNG media_image4.png 87 222 media_image4.png Greyscale PNG media_image5.png 101 237 media_image5.png Greyscale While Agarwal does not teach their compounds wherein the group corresponding to instant R2 is haloalkyl, the teachings of Morita are relied upon to leverage these discrepancies. Morita teaches that the design of bioisosteres introduces structural changes that can be beneficial towards improving potency and selectivity, altering physical properties, reducing or redirecting metabolism, and eliminating or modifying toxicophores (page 2, bottom). Morita discloses classical bioisosteres include: deuterium and hydrogen, hydrogen and fluorine, and fluorine and -OH, among others (page 4, top, monovalent atoms or groups). Morita also teaches -S- and -N- as classical divalent bioisosteres. Regarding the instant compounds of Formula Ib-1 in claims 27-28, one having ordinary skill in the art would have found the claimed compounds prima facie obvious since they are disclosed by Agarwal in view of Morita. One of ordinary skill would have been motivated to prepare any of the instant compounds with a reasonable expectation of success in view of Agarwal’s disclosure of the telomerase inhibitor compounds 72-74, useful for the treatment of cancer; further in view of Morita’s disclosure that the preparation of bioisosteres introduce structural changes that can be beneficial towards improving potency, selectivity, metabolism, etc., and that H is a monovalent bioisostere of D and F. Specifically, one of ordinary skill would have been motivated to replace a H on the alkyl chain corresponding to instant R2 on compounds 72-74 with a F to arrive at the instant compounds, wherein R2 --can be haloalkyl. Further regarding claim 28, Agrawal discloses their compound 72-74 above, which read (for instance) on the compound below, in view of the teachings from Morita, who discloses H and D; and F and -OH are classical monovalent bioisosteres. PNG media_image6.png 170 215 media_image6.png Greyscale PNG media_image7.png 95 106 media_image7.png Greyscale PNG media_image8.png 133 143 media_image8.png Greyscale Regarding claim 29, Agarwal discloses their anticancer compound 71 below (page 224), which renders the instantly claimed compound below (in particular) obvious in view of Morita. One having ordinary skill in the art would have found the claimed compound prima facie obvious since it is disclosed by Agarwal in view of Morita. One of ordinary skill would have been motivated to prepare the instant compounds with a reasonable expectation of success in view of Agarwal’s disclosure of the telomerase inhibitor compound 71, useful for the treatment of cancer; further in view of Morita’s disclosure that the preparation of bioisosteres introduce structural changes that can be beneficial towards improving potency, selectivity, metabolism, etc., and that -S- is a divalent isostere with -N-. Specifically, one of ordinary skill would have been motivated to replace the -S- on the thiophene with a -N- to arrive at the instant pyrrole compound. PNG media_image9.png 101 237 media_image9.png Greyscale PNG media_image10.png 105 120 media_image10.png Greyscale Further regarding claims 27-29, Applicant is advised that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). Furthermore, Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950). Regarding claims 30 and 33, Agarwal discloses pharmaceutical compositions comprising their compounds and an acceptable carrier (page 188, para. 2, lines 1-3). Response to Arguments Claims Claim amendments are acknowledged and have been entered. No new matter has been introduced. Claim Rejections - 35 USC § 112(b) Applicant’s arguments, see page 22, filed 02/17/2026, with respect to claim rejections under 35 USC § 112(b) have been fully considered and are persuasive. The 35 USC § 112(b) rejections of the claims has been withdrawn. Claim Rejections - 35 USC § 102 Applicant’s arguments, see page 22, filed 02/17/2026, with respect to claim rejections under 35 USC § 102 have been fully considered and are persuasive. The 35 USC § 102 rejections of the claims has been withdrawn. Claim Rejections - 35 USC § 103 Applicant's arguments filed 02/17/2026 have been fully considered but they are not persuasive. Applicant argues there is not teaching or suggestion in Agarwal to arrive at the claimed compounds of Formula Ib-1 or Ib-2, in which R2 cannot be alkyl. Applicant argues the Office used hindsight reasoning to arrive at the rejections of record. Applicant argues there is no teaching or motivation to make the compositions made by Applicant. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). 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, Agarwal discloses the compounds 71-74 below (page 224) and teaches their compounds as telomerase inhibitors, and as useful for the treatment of cancers (page 163, last para.; and page 1) – which is the same intended use as the instant compounds. PNG media_image9.png 101 237 media_image9.png Greyscale PNG media_image3.png 98 241 media_image3.png Greyscale PNG media_image4.png 87 222 media_image4.png Greyscale PNG media_image5.png 101 237 media_image5.png Greyscale Morita teaches that the design of bioisosteres introduces structural changes that can be beneficial towards improving potency and selectivity, altering physical properties, reducing or redirecting metabolism, and eliminating or modifying toxicophores (page 2, bottom). Morita discloses classical bioisosteres include: deuterium and hydrogen, hydrogen and fluorine, and fluorine and methyl, among others (page 4, top, monovalent atoms or groups). Morita also teaches -S- and -N- as classical divalent bioisosteres. Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious since they are disclosed by Agarwal in view of Morita. One of ordinary skill would have been motivated to prepare any of the instant compounds with a reasonable expectation of success in view of Agarwal’s disclosure of the telomerase inhibitor compounds 71-74, useful for the treatment of cancer; further in view of Morita’s disclosure that the preparation of bioisosteres introduce structural changes that can be beneficial towards improving potency, selectivity, metabolism, etc., and that: (i) H is a monovalent bioisostere of D and F; and (ii) -S- is a divalent isostere with -N-. Specifically, one of ordinary skill would have been motivated to: (i) replace a H on the alkyl chain corresponding to instant R2 on compounds 71-74 with a F to arrive at the instant compounds, wherein R2 --can be haloalkyl; and/or (ii) replace the -S- on the thiophene with a -N- to arrive at the instant pyrrole compounds. Regarding Applicant’s argument that Agarwal provides no motivation for preparing the instant composition, Agarwal discloses pharmaceutical compositions comprising their compounds and an acceptable carrier (page 188, para. 2, lines 1-3). Therefore, the claimed compositions are obvious in view of Agarwal and Morita. 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. Conclusion 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 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

Mar 24, 2023
Application Filed
Nov 10, 2025
Non-Final Rejection — §102, §103, §112
Feb 17, 2026
Response Filed
Apr 05, 2026
Final Rejection — §102, §103, §112 (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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