Office Action Predictor
Application No. 17/696,769

CONTROLLED-RELEASE CNP AGONISTS WITH LOW NPR-C BINDING

Non-Final OA §DP
Filed
Mar 16, 2022
Examiner
D' AMBROSIO, THEA
Art Unit
1654
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Ascendis Pharma Growth Disorders A/S
OA Round
3 (Non-Final)
55%
Grant Probability
Moderate
3-4
OA Rounds
3y 5m
To Grant
99%
With Interview

Examiner Intelligence

55%
Career Allow Rate
265 granted / 479 resolved
Without
With
+55.4%
Interview Lift
avg trend
3y 5m
Avg Prosecution
47 pending
526
Total Applications
career history

Statute-Specific Performance

§101
5.2%
-34.8% vs TC avg
§103
34.0%
-6.0% vs TC avg
§102
11.0%
-29.0% vs TC avg
§112
25.7%
-14.3% vs TC avg
Black line = Tech Center average estimate • Based on career data

Office Action

§DP
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 . Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on January 23, 2026, has been entered. Election/Restrictions Please note that the Species election, i.e., a single and specific CNP agonist and a single and specific disease to be treated is hereby withdrawn. Status of the claims Claim 1-18 were originally filed on March 16, 2022. The amendment received on March 16, 2022, canceled claims 1-18; and added new claims 19-32. The amendment received on March 10, 2025, canceled claims 20-28 and 30; and amended claims 19 and 29. The amendment received on September 23, 2025, canceled claim 31; and amended claims 19 and 32. The amendment received on January 23, 2026, added new claims 33-40. Claims 19, 29, and 32-40 are currently pending and are under consideration. Priority The present application is a continuation of US Application No. 16/066,980, now issued as US Patent No. , which claims status as a 371 (National Stage) of PCT/EP2017/050220 filed January 5, 2017, and claims priority under 119(a)-(d) to European Application Nos. 16150633.2 filed on January 8, 2016; 16179292.4 filed on July 13, 2016; and 16191480.9 filed on September 29, 2016. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for European Application Nos. 16150633.2, 16179292.4, and 16191480.9, which papers were received and placed in parent Application No. 16/066,980. Please note that the European applications are in English and therefore no further action is necessary. Sequence Interpretation For claim 19, please note that the Examiner is interpreting the scope with respect to the CNP agonist moiety as closed-ended requiring 100% identity and the same length to one of the recited sequence identifiers. New Rejections 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 19, 29, and 32-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,154,593 B2 in view of Bossard WO 2010/033217 A1 (cited in the IDS received on 8/19/24). ‘593 claims: PNG media_image1.png 310 645 media_image1.png Greyscale PNG media_image2.png 386 576 media_image2.png Greyscale PNG media_image3.png 203 605 media_image3.png Greyscale PNG media_image4.png 144 636 media_image4.png Greyscale PNG media_image5.png 258 675 media_image5.png Greyscale PNG media_image6.png 111 589 media_image6.png Greyscale PNG media_image7.png 299 447 media_image7.png Greyscale PNG media_image8.png 263 639 media_image8.png Greyscale (See ‘593, claims 21, 29, and 34 thereby corresponding to issued claims 1, 17, and 21 respectively). As such, ‘593’s compound is a specific species of the instant controlled-release CNP agonist of formula (Ia) as recited in instant claim 19 that is administered in an effective dose to a patient in order to treat the patient suffering from achondroplasia, hypochondroplasia, short stature, Noonan syndrome or SHOX deficiency as recited in instant claims 19 and 32. Moreover, ‘593’s compound (IIf) and (IIf’) encompass a L1 species structure that falls within the claimed genus recited in instant claim 33 where this structure reads on instant compound (IIc-ii) as recited in instant claim 34. Similarly, ‘593’s -Z component is a species that falls within the claimed genus recited in instant claim 35 where BPa is -CH< as recited in instant claim 36 and comprising at least 20% PEG as recited in instant claim 37. ‘593’s compound of formula (IIf) and (IIf’) also encompasses a L2 species structure that falls within the claimed genus recited in instant claim 39 including the specific structure of (xvi) as recited in instant claims 39-40. Although ‘593 does not expressly claim that the compound of formula (IIf) or (IIf’) exhibits the instant properties, i.e., half-life and IC50 to the NPR-C receptor, these properties are inherent to the ‘593 compound structure. However, ‘593 does not claim that the CNP compound is administered via subcutaneous injection as recited in instant claim 19 and where it is in a vesicle such as a micelle, liposome or polymersome as recited in instant claim 29. Bossard teaches a method to treat a patient suffering from a condition that is responsive to treatment with CD-NP peptide by administering a therapeutically effective amount of a pharmaceutical composition comprising a CD-NP peptide polymer conjugate (See Bossard specification, [00224]-[00225]) where the composition can be administered by any number of routes including parenteral administration such as ready-for-injection solutions (See Bossard specification, [00222]). Furthermore, Bossard teaches that the CD-NP polymer conjugate comprises a water-soluble polymer such as PEG or a modified PEG in a linear, branched, forked, multi-armed, or dendritic form covalently attached (either directly or through a spacer moiety or linker) to a CD-NP peptide (See Bossard specification, [00106]; [00112]-[00113], [00120]). As such, Bossard teaches administering a CNP-polymer conjugate to a patient subcutaneously. Plus, Bossard teaches that a composition comprising the CNP-polymer conjugate can be further incorporated into a suitable delivery vehicle such as liposomes (See Bossard specification, [00223]). As such, Bossard teaches that a CNP-polymer conjugate can be administered in a vesicle such as a liposome. Therefore, an ordinary skilled artisan would be motivated with a reasonable expectation of success to administer subcutaneously the ‘593 controlled-release CNP agonist in a liposome to a patient in order to treat achondroplasia, hypochondroplasia, short stature, Noonan syndrome or SHOX deficiency given that subcutaneous administration via a vesicle such as a liposome is well-known in the art. Thus, the ‘593 claimed invention is not patentably distinct from the instantly claimed invention. Claims 19, 29, and 32-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 52, 58-64, 68-70, and 72-77 of copending Application No. 18/145,676 (US 2023/0302091 A1) in view of Bossard WO 2010/033217 A1 (cited in the IDS received on 8/19/24). ‘676 claims: PNG media_image9.png 162 639 media_image9.png Greyscale PNG media_image10.png 363 648 media_image10.png Greyscale PNG media_image11.png 269 421 media_image11.png Greyscale PNG media_image12.png 243 561 media_image12.png Greyscale PNG media_image13.png 272 645 media_image13.png Greyscale PNG media_image14.png 89 654 media_image14.png Greyscale PNG media_image15.png 271 364 media_image15.png Greyscale PNG media_image16.png 74 638 media_image16.png Greyscale (See ‘676 claims 52, 72-73, and 77). As such, ‘676’s controlled-release CNP agonist of formula (IIf) and (IIf’) are specific species of the instant controlled-release CNP agonist of formula (Ia) that exhibits a release half-life of at least 6 hours as recited in instant claim 19 that is administered via subcutaneous injection in an effective amount to a patient in order to stimulate bone growth in a patient suffering from achondroplasia (See ‘676 claims 63-64) thereby necessarily treating the patient as recited in instant claims 19 and 32. Moreover, ‘676’s compound (IIf) and (IIf’) encompass a L1 species structure that falls within the claimed genus recited in instant claim 33 where this structure reads on instant compound (IIc-ii) as recited in instant claim 34. Similarly, ‘676’s -Z component is a species that falls within the claimed genus recited in instant claim 35 where BPa is -CH< as recited in instant claim 36 and comprising at least 20% PEG as recited in instant claim 37. ‘676’s compound of formula (IIf) and (IIf’) also encompasses a L2 species structure that falls within the claimed genus recited in instant claim 39 including the specific structure of (xvi) as recited in instant claims 39-40. Although ‘676 does not expressly claim that the controlled-release CNP agonist of formula (IIf) or (IIf’) exhibits the instant property, i.e., IC50 to the NPR-C receptor, this property is inherent to the ‘676 compound structure. Furthermore, although ‘676 claims co-administration of the controlled-release CNP agonist with a human growth hormone, the instant method utilizes the transitional phrase “comprising” thereby encompassing additional non-recited agents and/or steps. However, ‘676 does not claim that the controlled-release CNP agonist of formula (IIf) or (IIf’) is in a vesicle such as a micelle, liposome or polymersome as recited in instant claim 29. Please see discussion of Bossard supra. An ordinary skilled artisan would be motivated with a reasonable expectation of success to administer subcutaneously the ‘676 controlled-release CNP agonist in a liposome to a patient in order to treat achondroplasia, hypochondroplasia, short stature, Noonan syndrome or SHOX deficiency given that subcutaneous administration via a vesicle such as a liposome is well-known in the art. Thus, the ‘676 claimed invention is not patentably distinct from the instantly claimed invention. This is a provisional nonstatutory double patenting rejection. Claims 19, 29, and 32-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-7, 9, 13, 17-18, 20, 22, 24-25, 29, 31-32, 38, and 44-45 of copending Application No. 18/867,010 (US 2025/0195617 A1) in view of Bossard WO 2010/033217 A1 (cited in the IDS received on 8/19/24). ‘010 claims: PNG media_image17.png 69 634 media_image17.png Greyscale PNG media_image18.png 333 662 media_image18.png Greyscale PNG media_image19.png 336 623 media_image19.png Greyscale PNG media_image20.png 308 620 media_image20.png Greyscale PNG media_image21.png 225 597 media_image21.png Greyscale PNG media_image22.png 223 622 media_image22.png Greyscale PNG media_image23.png 218 667 media_image23.png Greyscale PNG media_image24.png 203 608 media_image24.png Greyscale PNG media_image25.png 309 423 media_image25.png Greyscale PNG media_image26.png 300 629 media_image26.png Greyscale PNG media_image27.png 217 666 media_image27.png Greyscale (See ‘010 claims 1, 25, 31-32, and 44-45). As such, ‘010’s CNP compound is a specific species of the instant controlled-release CNP agonist of formula (Ia) as recited in instant claim 19 that is administered in a therapeutically effective amount to a patient in order to treat the patient suffering from achondroplasia, hypochondroplasia, short stature, Noonan syndrome or SHOX deficiency as recited in instant claims 19 and 32. Moreover, ‘010’s L1 of formula (II) is identical to the L1 of formula (II) recited in instant claim 33. ‘010’s L1-L2 of formula (IId-ii) also reads on on instant compound (IIc-ii) as recited in instant claim 34, a specific species that falls within the claimed genus recited in instant claim 39 including the specific structure of (xvi) as recited in instant claims 39-40. Similarly, ‘010’s -Z component is a species that falls within the claimed genus recited in instant claim 35 where BPa is -CH< as recited in instant claim 36 and comprising at least 20% PEG as recited in instant claim 37. Although ‘010 does not expressly claim that the CNP compound exhibits the instant properties, i.e., half-life and IC50 to the NPR-C receptor, these properties are inherent to the ‘010 CNP compound structure. However, ‘010 does not claim that the CNP compound is administered via subcutaneous injection as recited in instant claim 19 and where it is in a vesicle such as a micelle, liposome or polymersome as recited in instant claim 29. Please see discussion of Bossard supra. An ordinary skilled artisan would be motivated with a reasonable expectation of success to administer subcutaneously the ‘010 CNP compound in a liposome to a patient in order to treat achondroplasia, hypochondroplasia, short stature, Noonan syndrome or SHOX deficiency given that subcutaneous administration via a vesicle such as a liposome is well-known in the art. Thus, the ‘010 claimed invention is not patentably distinct from the instantly claimed invention. This is a provisional nonstatutory double patenting rejection. Examiner Comment Notwithstanding the obviousness-type double patenting rejections supra, the claimed method is free of the prior art as there is no teaching or suggestion in the art to administer a controlled-release CNP agonist of formula (Ia) where the CNP agonist moiety consists of one of the claimed sequences to a subject in order to treat one of the claimed diseases. The closest prior art includes Bossard WO 2010/033217 A1 published on March 25, 2010 (cited in the IDS received on 08/19/24), which teaches administering a controlled-release CNP agonist where the CNP agonist comprises instant SEQ ID NO: 1, but does not consist of SEQ ID NO: 1. In other words, the CNP agonist sequence taught by Bossard is not the same length as instant SEQ ID NO: 1, and Bossard does not teach or suggest truncating the CNP agonist sequence. Another reference considered as a closest prior art reference is Wendt et al. US Patent No. 8,377,884 B2 (cited in the IDS received on 08/19/24), which teaches treatment of bone-related disorders such as achondroplasia by administering a modified CNP agonist having the amino acid sequence of CNP22 (i.e., 100% identity to instant SEQ ID NO: 1) where a disulfide bond is formed between Cys6 and Cys22 (See ‘884, col. 4, 4th to 5th paragraph). Although Wendt et al. teaches that the CNP agonist sequence is modified by conjugation to a synthetic or natural polymeric group such as PEG where the polymeric group can be attached at the N-terminus, C-terminus, an internal site or a combination thereof (See ‘884, col. 7, 1st paragraph; col. 10, 1st paragraph), Wendt et al. expressly teaches that the polymeric group should not be conjugated within the cyclic domain of the CNP agonist in order to allow for better functionality of the CNP agonist (See ‘884, col. 10, 1st paragraph). As such, the teachings of Wendt et al. do not motivate an ordinary skilled artisan to modify a CNP agonist sequence as required in the instant method since the claimed water-soluble branched polymer moiety (i.e., instant Z) is conjugated to the claimed CNP agonist moiety via a side chain of an amino acid residue of the ring moiety or to the backbone of the ring moiety. Therefore, the claimed method is free of the prior art. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm. 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, Lianko Garyu can be reached at 571-270-7367. 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. /THEA D' AMBROSIO/ Primary Examiner, Art Unit 1654
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Prosecution Timeline

Mar 16, 2022
Application Filed
Oct 04, 2024
Non-Final Rejection — §DP
Mar 10, 2025
Response Filed
Jun 19, 2025
Non-Final Rejection — §DP
Sep 23, 2025
Response Filed
Dec 17, 2025
Examiner Interview (Telephonic)
Jan 23, 2026
Request for Continued Examination
Jan 27, 2026
Response after Non-Final Action
Feb 21, 2026
Non-Final Rejection — §DP
Mar 24, 2026
Response Filed

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Prosecution Projections

3-4
Expected OA Rounds
55%
Grant Probability
99%
With Interview (+55.4%)
3y 5m
Median Time to Grant
High
PTA Risk
Based on 479 resolved cases by this examiner