NON-FINAL REJECTION
This application is a 35 U.S.C. 371 (national stage) application of PCT/US2021/055408, filed Oct. 18, 2021, which claims benefit of priority to Provisional Application 63/094,117, filed Oct. 20, 2020.
Claims 1-35 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 statements (IDS) submitted on Jul. 19, 2023 and Nov. 26, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group II, drawn to methods of using compounds of formula (I); methods of treating ALS/FTD disease as the method species; and compound 7 as the compound species, having the structural formula,
PNG
media_image1.png
162
364
media_image1.png
Greyscale
,
in the reply filed on Nov. 26, 2025, is acknowledged.
Because the elected compound is free of the prior art, the restriction/election requirement as set forth in the Office action mailed on Sep. 30, 2025 is hereby withdrawn.
Applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1-35 are currently pending and under consideration.
Claim Rejections - 35 USC § 112(d) – Improper Dependency
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.
Claims 12-21 are 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.
Specifically, claim 12 recites a method of "any of claims 9-11 wherein the cells are incubated with the ALS compound of claim 2 with Y as Formula (III)."
However, claim 2 depends from claim 1, which recites compounds of formula (I), which does not include a variable group Y.
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.
Claims 10-21, 23-26, and 28-33 are 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.
At least claims 10, 12, 23, and 29 are improper multiple dependent claims. Specifically:
Claim 10 recites a method according to claim 8 or 9, and claim 8 recites a method according to any of claims 1-7, which encompass compounds that differ in scope.
Claim 12 recites a method of any of claims 9-11, using the compound of claim 2.
Claim 23 recites a composition of claim 22, comprising the compound of claim 3.
Claim 29 recites a method according to claim 28 using the compound of claim 3.
Dependent claims which refer to more than one other claim ("multiple dependent claim") must refer to such other claims in the alternative only. Further, a multiple dependent claim shall not serve as a basis for any other multiple dependent claim. See MPEP § 608.01(n).
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 § 112(b) - Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10-21, 23-26, and 28-33 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
At least claims 10, 12, 23, and 29 are improper multiple dependent claims, which render the claims indefinite because the compound(s) to be used in each method or composition cannot be determined. Specifically:
Claim 10 recites a method according to claim 8 or 9, and claim 8 recites a method according to any of claims 1-7, which encompass compounds that differ in scope.
Claim 12 recites a method of any of claims 9-11, using the compound of claim 2.
Claim 23 recites a composition of claim 22, comprising the compound of claim 3.
Claim 29 recites a method according to claim 28 using the compound of claim 3.
This maze of multiple dependencies is further complicated by further dependent claims which depend from these claims, such that the scope of each claim is incomprehensible.
Because the scope and subject matter encompassed by each claim cannot be determined, infringing methods and compositions cannot be distinguished from non-infringing methods and compositions, rendering the metes and bounds of the claims indefinite.
Claims 1-35 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 1-33 recite ALS compounds which comprise a pyridocarbazole moiety bound to X according to formula (I),
PNG
media_image2.png
201
273
media_image2.png
Greyscale
,
wherein X is hydrogen, hydroxyl, C1-4-alkoxy, a bridging polyoxyethylenyl, or a bridging R-amino-bispolyoxyethylenyl group having the pyridocarbazole moiety covalently attached to each of its termini to comprise a bridged dimer of the pyridocarbazole moiety,
R-amino is R-N- with R as hydrogen, acetyl, an Rnase recruiting moiety, or a diaza-4,4'-oct-7-yn-1-oyl group; and a pharmaceutically acceptable salt thereof.
However, the scope of the claimed ALS compounds which "comprise" a moiety of formula (I), which may further "comprise" a bridged dimer of the pyridocarbazole moiety, is indefinite because "comprising" is open-ended language that fails to set forth or define the structural boundaries of the compounds encompassed by the term "ALS compounds."
Similarly, claims 3 and 34 further recite that R "comprises" various options, including an Rnase recruiting moiety "comprising" formula (III), formula (IV), or formula (V); and claims 23, 27, and 29 recite that the ALS compound "comprises" formulas (II) and (III) of claim 3.
While claims 3 and 34 set forth the structures of formula (III) and formula (IV) as options for R, these introduce further ambiguity by failing to indicate their attachment point to N.
Claim 35 is drawn to the composition of claim 34 wherein Y is formula (III). However, claim 34 defines Y only as oxygen or R-N. Formula (III) is an option for R, not for Y.
In addition, claims 3 and 4 are drawn to compounds which "comprise" formula (II),
PNG
media_image3.png
326
426
media_image3.png
Greyscale
wherein a is 1 to 5 or "preferably" various integers falling within that range.
However, a broad range together with a narrow range or limitation that falls within it is indefinite because there is ambiguity as to whether the feature introduced by the narrower "preferably" language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. See MPEP §§ 2173.05(c) and (d).
Further, "Rnase recruiting moiety" is indefinite because the instant specification provides no limiting or structural definition for the term, which also has no clear-cut, commonly understood definition in the art. The exact chemical structures encompassed by the term "Rnase recruiting moiety" and excluded therefrom, cannot be unambiguously determined by one of ordinary skill in the art.
As recognized by MPEP § 2173.05(g), a claim term is merely functional descriptive language when it recites a feature "by what it does rather than by what it is" (e.g., as evidenced by its specific structure or specific ingredients). In re Swinehart, 439 F.2d 210, 212, 169 USPQ 226, 229 (CCPA 1971).
Therefore, due to (1) repeated use of open-ended "comprising" language, (2) ambiguity introduced by "preferably" clauses, and (3) the lack of any structural definition of "Rnase recruiting moiety," the substances included by the term "ALS compound," by formula (I), and by formula (II), cannot be readily distinguished from substances which are excluded. Therefore, infringing methods cannot be distinguished from non-infringing methods, rendering the metes and bounds of the claims indefinite.
Claims 1 and 34 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Specifically, independent claims 1 and 34 are drawn to a method and to a composition, respectively, comprising a compound "and" a pharmaceutically acceptable salt thereof. This requires both the neutral form of the compound and a salt thereof to be used in the method or included in the composition. Because Applicant's intent is unclear, it is suggested to amend "and" to "or." For examination purposes, "and" is interpreted as "or."
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2, and 5-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (Cell Chem. Biol. 26, 179–190 (2019), cited on the IDS dated 11/26/2025).
Wang et al. disclose that the most common cause of amyotrophic lateral sclerosis (ALS) is an expanded RNA repeat [r(G4C2)exp] that folds into two forms in vitro: a G-quadruplex and a hairpin (abstract). Targeting the G-quadruplex or hairpin structure could both be important for the development of therapeutics to treat ALS and frontotemporal dementia (c9ALS/FTD) (p. 179, right col.).
In particular, Wang et al. exemplify compound 4 (Fig, 1B), having the structural formula,
PNG
media_image4.png
200
400
media_image4.png
Greyscale
which reads on the ALS compound of formula (I) recited by claim 1, wherein X is C1-alkoxy (methoxy).
Wang et al. report that compound 4 exhibits excellent selectivity and potency toward r(G4C2)exp, by binding to the 1x1 nucleotide GG internal loop in the hairpin structure. The p-p stacking interaction of compound 4 with the individual guanine bases in the 1x1 nucleotide GG loop and adjacent GC closing pair stabilizes the complex’s structure. The binding of compound 4 to r(G4C2)exp prevents key RNA-protein interactions, thereby inhibiting two putative c9ALS/FTD pathomechanisms of r(G4C2)exp (p. 185, right col.).
Thus, Wang et al. disclose a method of contacting a hexanucleotide repeat expansion RNA r(G4C2)exp with a compound of formula (I), as recited by claim 1.
The contacting binds and/or complexes the r(G4C2)exp, as recited by claim 2.
Wang et al. report inhibition of r(G4C2)66-mediated RAN translation with compound 4 (Table 1), wherein r(G4C2)exp is r(G4C2)m and m is at least 20, as recited by claims 5-6.
The r(G4C2)exp is a repeat RNA hairpin structure, as recited by claim 7.
The r(G4C2)exp is present in a cell, as recited by claim 8.
For the foregoing reasons, Wang et al. anticipates claims 1, 2, and 5-8.
Claims 1, 2, and 5-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Disney (WO 2016/025692, cited on PTO-892).
Disney exemplifies and claims the compound of formula (1a) (claim 1), having the structural formula,
PNG
media_image5.png
200
400
media_image5.png
Greyscale
which reads on the ALS compound recited by claim 1, comprising a pyridocarbazole moiety bound to X according to formula (I), wherein X is hydroxyl (-OH):
PNG
media_image6.png
197
274
media_image6.png
Greyscale
.
Disney further claims methods of inhibiting repeat-associated non-ATG (RAN) translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons trans-differentiated from fibroblasts of repeat expansion carriers, comprising contacting the cells with an effective amount of a compound of formula (1a) (claim 2), which reads on the method of contacting a hexanucleotide repeat expansion RNA r(G4C2)exp with an ALS compound, as recited by claim 1.
The contacting binds and/or complexes the r(G4C2)exp, as recited by claim 2.
The hexanucleotide repeat expansion RNA r(G4C2)exp is r(G4C2)m and m is at least 20, as recited by claims 5-6.
The r(G4C2)exp is a repeat RNA hairpin structure, as recited by claim 7.
The r(G4C2)exp is present in a cell, as recited by claim 8.
For the foregoing reasons, Disney anticipates claims 1, 2, and 5-8.
Claim 34 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Linsell et al. (WO 99/64054, of record).
Linsell et al. claim pharmaceutical compositions comprising a pharmaceutically
acceptable carrier and an effective amount of a multibinding compound of formula II:
L'-X'-L'
wherein each L' is independently a ligand capable of binding to a topoisomerase, X' is a linker, and the distance between ligands is between about 2-50 Å; and pharmaceutically acceptable salts thereof (claim 20).
In particular, Linsell et al. exemplify the compound of structure 10 (Fig. 24, figure page 14/15), having the structural formula,
PNG
media_image7.png
200
400
media_image7.png
Greyscale
which reads on formula (II) as recited by claim 34, wherein a is 2, and Y is oxygen.
Thus, Linsell et al. disclose a composition comprising a bis-bridged pyridocarbazole of Formula (II) and/or a salt thereof, as recited by claim 34.
For the foregoing reasons, Linsell et al. anticipates claim 34.
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 1, 2, and 5-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 21-24 of copending Application No. 18/704,712 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims would anticipate the examined claims.
Reference claims 1-12 are drawn to methods comprising contacting a hexanucleotide repeat expansion RNA r(G4C2)exp with an ALS compound wherein the ALS compound comprises a pyridocarbazole moiety bound to an RNase moiety according to Formula I,
PNG
media_image8.png
258
500
media_image8.png
Greyscale
wherein R is hydrogen or a C1-3-alkyl group; Y is -COO- or -CH2O-; n is an integer of 1 to 6,
and a pharmaceutically acceptable salt thereof;
which reads on examined claims 1, 2, and 5-8, wherein the ALS compound of formula (I) comprises a pyridocarbazole moiety of formula (I), wherein X is C1-4-alkoxy:
PNG
media_image6.png
197
274
media_image6.png
Greyscale
.
Reference claims 21-24 are drawn to methods for treatment of an ALS/FTD disease comprising administering an effective amount of an ALS compound of formula (I), which intrinsically requires contacting a hexanucleotide repeat expansion RNA r(G4C2)exp with an ALS compound of formula (I), as recited by examined claims 1, 2, and 5-8.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Citation of Additional Prior Art
Additional references made of record are considered pertinent to applicant's disclosure: USPN 7,989,467; Debnath et al. Angew. Chem. Int. Ed. 58, 2942-2957 (2019) (both cited on PTO-892).
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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://portal.uspto.gov/external/portal. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629