NON-FINAL REJECTION
This application is a 35 U.S.C. 371 (national stage) application of PCT/US2022/011418, filed Jan. 6, 2022, which claims benefit of priority to Provisional Application 63/135,236, filed Jan. 8, 2021.
Claims 15-34 are pending.
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 .
Priority
Applicant' s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Sep. 9, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to methods of treating a ciliopathy by administering a TRPML ion channel activator; compound 101 as the species of TRPML ion channel activator, having the structural formula,
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autosomal dominant polycystic kidney disease (ADPKD) as the ciliopathy; and tolvaptan as the second therapeutic agent, in the reply filed on Jan. 21, 2026, is acknowledged.
Upon further consideration, the species election requirement is withdrawn.
Claim 34 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected invention(s), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on Jan. 21, 2026.
Claims 15-33 are currently pending and under consideration.
Claim Rejections - 35 USC § 112(a) – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(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 15-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Specifically, independent claim 15 is drawn to a method of treating a ciliopathy by administering to a patient in need thereof a therapeutically effective amount of any TRPML ion channel activator (agonist). Dependent claims 16-33 limit the TRPML ion channel activator to compounds which are activators of TRPML1, or more narrowly to compounds of Formula (III):
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The disclosure defines "ciliopathies" to include polycystic kidney disease, pancreatic cysts in polycystic kidney disease, Bardet-Biedl syndrome, nephronophthisis, Joubert Syndrome, Mecke-Gruber Syndrome, oral-facial-digital syndrome, Senior Loken Syndrome, Birt-Hogg-Dube syndrome, Leber's congenital amaurosis, Alstrom syndrome, Jeune asphyxiating thoracic dystrophy. Ellis van Creveld syndrome, Sensenbrenner syndrome, primary ciliary dyskinesia (para. [0109]), autosomal dominant polycystic kidney disease, and autosomal recessive polycystic kidney disease (paras. [0039]-[0040]), which are recited in dependent claims 26-29.
However, 24 of the 26 examples set forth in the specification relate to synthesis of compounds of formula (III), as recited by claim 18. There is no disclosure of treating any ciliopathy by administering a TRPML ion channel activator in vivo; and only two examples demonstrating the activity of the claimed compounds in vitro.
Example 25 and Figs. 1-3 describes the effect of four TRPML1 activators on glycophosphingolipid levels and cyst areas using genetic models of disease; and Example 26 describes TRPML-1, TRPML-2, and TRPML-3 fluorescent assays in cell culture.
Thus, the specification presents no evidence that the claimed compounds actually function to treat any ciliopathy in vivo. Furthermore, there is scant evidence in the prior art demonstrating the treatment of a ciliopathy by administering a TRPML ion channel activator.
For example, Liang (WO 2018/005713, cited on the IDS dated 9/9/2024) discloses structurally similar benzenesulfonamides as TRPML modulators useful for treating disorders related to TRPML activities, such as lysosome storage diseases, muscular dystrophy, age-related common neurodegenerative diseases, ROS or oxidative stress related diseases, and aging (claims 10-18). None of these diseases appear to overlap with the claimed ciliopathies.
Liang (WO2018/208630, cited on the IDS dated 9/9/2024) further discloses structurally similar arylsulfonamides as TRPML modulators useful for treating acid-related disorders, gastric disorders, and cancer, and for modulating tubulovesicle and lysosome functions (claims 10-20). None of these diseases appear to overlap with the claimed ciliopathies.
Leit De Moradei et al. (WO 2020/097408, cited on PTO-892) disclose structurally similar benzenesulfonamides useful in methods of treating, e.g., symptoms of Bardet-Biedl syndrome (claim 23), as recited by claim 26. However, the compounds are not explicitly disclosed as modulators of TRPML, nor is the treatment of any other ciliopathies disclosed.
Stallone et al. (cited on PTO-892) report a clinical trial to evaluate low-dose and high-dose rapamycin in the treatment of autosomal dominant polycystic kidney disease (ADPKD) (abstract). As evidenced by Zhang et al. (cited on PTO-892), rapamycin binds directly to TRPML1, and is a specific and robust activator of TRPML1, independent of mTOR (abstract; results). Stallone et al. found that, although rapamycin treatment is relatively safe, it does not significantly affect the progression of ADPKD (conclusion). While the higher rapamycin dose reduced the increase in total kidney volume and the decline in renal function, there is no evidence that this is due to rapamycin's activity as a TRPML ion channel activator.
Similarly, Wüthrich et al. (cited on PTO-892) report that clinical trials examining the mTOR inhibitors sirolimus (a.k.a. rapamycin) and everolimus in the treatment of ADPKD failed to show a beneficial effect on change in kidney volume and renal function (p. 1088), or a significant improvement in cyst growth and GFR (glomerular filtration rate) decline (p. 1091).
Therefore, one of ordinary skill in the art would not reasonably recognize that TRPML ion channel activators would be useful in treating ciliopathies, nor that the claimed methods were actually in the applicants’ possession as of the filing date.
35 U.S. C. § 112(a) requires a description of the invention that “clearly allow[s] persons of ordinary skill in the art to recognize that the inventor invented what is claimed.” Ariad at 1172, quoting Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555 (1562-63) (Fed. Cir. 1991). A sufficient disclosure is one which reasonably conveys to one having ordinary skill in the art that the inventor had possession of the claimed subject matter as of the filing date of the application in question. Vas-Cath, 935 F.2d at 1563. The description must reasonably describe the invention, not simply indicate a result which one might achieve if one actually made the invention. Eli Lilly, 119 F.3d at 1568.
“Patents are not awarded for academic theories, no matter how groundbreaking or necessary to the later patentable inventions of others. ‘[A] patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.’” Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 94 USPQ2D 1161, 1173-74 (Fed. Cir. 2010), quoting University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 930 (Fed. Cir. 2004). Requiring a written description of the invention limits patent protection to those who actually perform the difficult work of “invention” – that is, conceive of the complete and final invention with all its claimed limitations – and disclose the fruits of that effort to the public. Id.
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 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 54, 55, and 57 of copending Application No. 18/695,871 (reference application). Although the claims at issue are not identical, they are not patentably distinct because the reference claims would anticipate the examined claims.
Specifically, the reference claims are drawn to methods of administering to a patient in need thereof a therapeutically effective amount of a compound of formula (Ia),
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or a pharmaceutically acceptable salt thereof, in methods of modulating TRPML ion channels (claim 54); treating a disease or disorder which can be treated by modulation of TRPML ion channels (claim 55); and treating a disease selected from, inter alia, a ciliopathy (claim 57).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77, 78, and 80 of copending Application No. 18/695,885 (reference application). Although the claims at issue are not identical, they are not patentably distinct because the reference claims would anticipate the examined claims.
Specifically, the reference claims are drawn to methods of administering to a patient in need thereof a therapeutically effective amount of a compound of formula (Ia),
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or a pharmaceutically acceptable salt thereof, in methods of modulating TRPMLs (claim 77); treating a disease or disorder which can be treated by modulation of TRPMLs (claim 78); and treating a disorder selected from, inter alia, a ciliopathy (claim 80).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 9:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629