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 Claims
Claims 1-2, 4, 6, 8, 10, 12, 14, 18, 26-29, 53-54, 57, 59-60, 62-65, 68, and 74-75 are pending. Claims 59, 60, 62-65, 68, and 74-75 are withdrawn.
Priority
Instant application 17/917,868, filed 10/07/2022 claims priority as follows:
PNG
media_image1.png
135
642
media_image1.png
Greyscale
Information Disclosure Statement
All references from IDS(s) received 10/07/2022, 07/21/2025, 11/07/2025, 03/31/2026, and 05/28/2026 have been considered unless marked with a strikethrough.
Response to Amendment/Arguments
The amendment filed 05/28/2026 has been entered. Claims 1, 2, 8, and 14 are amended. Claims 3, 5, 7, 9, 11, 13, 15-17, 19-25, 30-52, 55-56, 58, 61, 66-67, 69-73, and 76-78 are cancelled.
Scope of Search
In view of the amendment filed 11/07/2025, the search was extended to encompass the full scope of the pending compound claims. Claims 4, 10, 18, and 28 are no longer withdrawn.
Claim Rejections - 35 USC § 112(a) - Maintained
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 54 and 57 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 claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
The claims fail to comply with the written description requirement for two reasons:
Reason 1
In the instant case, claims 54 and 57 are drawn to compounds of Formula (I) recited in claim 1, wherein the compound “alters a target nucleic acid” (claim 54), or wherein the compound “increases splicing at splice site on a target nucleic acid” or “decreases splicing at splice site on a target nucleic acid” by a certain amount as determined by qPCR (claim 57).
The compounds of Formula (I) in claim 1 are structurally defined. However, the genus of a compound of Formula (I) which “alters a target nucleic acid” or “increases/decreases splicing at a splice site on a target nucleic acid” is not fully structurally defined.
A review of the prior art fails to provide the structure-function correlation which is missing in Applicant’s disclosure. For example, Campagne et al. (Nature Chemical Biology, vol. 15, no. 12, Dec. 2019, pp. 1191–98) discloses small molecules which target RNA for splicing, and discloses risdiplam and branaplam (page 1191, right side, 1st para); and other compounds and their binding affinities in Fig. 1C (page 1193):
PNG
media_image2.png
286
451
media_image2.png
Greyscale
Note that the compounds disclosed by Campagne comprise similar A/B ring heterocycles to those disclosed by Applicant. However, the core structures are entirely different, and none of the other A/B rings or core scaffolds embraced by the genus of claim 1 are tested or compared to establish a sufficient structure-function correlation.
Reason 2
The breadth of claims 54 and 57 is substantial due to the recitation of “target nucleic acids”. The phrase “target nucleic acid” is defined broadly in the specification to refer to any DNA or RNA and polymers thereof, single- or double-stranded, including a gene, cDNA, pre-mRNA or mRNA, plus analogues or derivatives (Specification, page 15, lines 3-12).
The skilled artisan must rely upon the disclosure of Applicant in order to predict which of the nucleic acids embraced by the phrase “target nucleic acid” are actually altered by the compounds recited in the instant claims. However, Applicant has not explored and disclosed a representative number of nucleic acids to establish a structure-function correlation. Instead, only a narrow slice of the nucleic acid genus (specifically, the 3 genes disclosed in Example 15) have been tested for the functions recited in the claims.
In particular, the three exemplified genes include (i) HTT, (ii) SMN2, and (iii) “Target C” which appears to be a placeholder name and fails to actually inform the person having ordinary skill of the identity of the gene.
A review of the prior art fails to provide the structure-function correlation which is missing in Applicant’s disclosure. For example, Campagne et al. (Nature Chemical Biology, vol. 15, no. 12, Dec. 2019, pp. 1191–98) discloses small molecules which target RNA for splicing, and discloses that the compounds are selective from SMN2 exon 7 (abstract, discussion). Note that the compounds disclosed by Campagne comprise similar A/B ring heterocycles to those disclosed by Applicant. However, the core structures are entirely different, and the compounds are disclosed only as useful for altering the SMN2 gene, not any “target nucleic acid”.
Methods of synthesizing compounds are, in general, known to the person of ordinary skill, however methods of making the myriads of compounds embraced by the instant claims is beyond the skill of the artisan, particularly when certain elements are merely described partially. As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what elements must be present to achieve the recited functions.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Response to Arguments
In the Remarks filed 11/07/2025, applicant argues that the claims are properly described in the application because the “application as originally filed contains data relating to the ability of structurally related compounds to alter a target nucleic acid and/or splice at a splice site on a target nucleic acid”. Applicant argues that the person of ordinary skill in the art would have no trouble understanding the scope of the claim with all its limitations based on the application as originally filed.
Applicant’s arguments have been fully considered but are not found persuasive. While the application provides assays for evaluating splicing efficiency and specificity, the issue is that the application does not disclose sufficient species that are representative of the full variety or scope of the genus, nor does the application establish a reasonable structure-function correlation between the structure of claim 1 and the functions recited in claims 54 and 57. While the claims, as amended, narrow the scope of the “A” and “B” rings to a “nitrogen-containing heterocyclyl” or one of the listed heteroaryl moieties, the term “nitrogen-containing heterocyclyl”, coupled with the large variety of R1, R7, Z, X, and Y still encompasses a massive number of compounds and the disclosure does not adequately reflect the structural diversity of the claimed genus.
Moreover, as identified in reason 2, the recitation of a “target nucleic acid” genus in claims 54 and 57 is not adequately supported by the disclosure, which provides only two actual examples of nucleic acids (HTT and SMN2) which are “altered” by the exemplified compounds.
Claim Rejections - 35 USC § 112(b) - New
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.
Claim 57 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 57 recites “the compound of claim 1, wherein the compound:
(i) increases splicing at splice site on a target nucleic acid, by about 0.5%....or more, e.g., as determined by qPCR or
(ii) decreases splicing at splice site on a target nucleic acid, by about 0.5%....or more, e.g., as determined by qPCR.”
Claim 57 is indefinite because it recites functional language that fails to provide a clear-cut indication of the scope of the subject matter embraced by the claim. MPEP 2173.05(g) instructs examiners to evaluate functional language using three factors: (1) whether there is a clear-cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim.
The recited limitations fail these three factors for the following reasons:
First, the phrase "for example" (“e.g.”) renders claim 57 indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Moreover, if the exemplary limitation is not required, then what is the standard/assay for determining that the compound increases or decreases splicing at a splice site on a target nucleic acid?
Second, claim 57 is indefinite because the scope of the splicing percentages is unclear. The use of “or more” at the end of the listed percentages means that the operative boundary of claim 57 collapses to “at least about 0.5%”. The phrase “at least about” is a relative term which renders the claim indefinite. The phrase “at least about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See MPEP 2173.05(b).
Third, the recited limitation in claim 57 is pure result (increases or decreases splicing…by about 0.5%...or more”) with no structural correlate. A person of ordinary skill in the art cannot determine from claim 57 which compounds are in or out of bounds, and cannot even reliably test membership, because the target nucleic acid/splice site is unspecified and the measurement method is non-limiting.
Double Patenting - Maintained
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.
17/917,842
Claims 1, 2, 4, 6, 8, 10, 12, 14, 18, 26-29, 53, 54, and 57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-8, 12-23, 25-30, 31, 35-37, 41-47, 50-56, 59, and 71-73 of copending Application No. 17/917,842 (reference application).
The reference application recites compounds of Formula (I) or Formula (II):
PNG
media_image3.png
113
238
media_image3.png
Greyscale
PNG
media_image4.png
119
248
media_image4.png
Greyscale
and sub-formulas thereof. The only difference between the compounds recited by the reference application and the compounds instantly claimed is the position of the B ring (in Formula I) or the position of the sulfur atom (in Formula II).
MPEP 2144.09, second paragraph, states, “Compounds which are position isomers or homologs 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). The homolog is expected to be preparable by the same method and to have generally the same properties. This expectation is then deemed the motivation for preparing the homolog. This circumstance has arisen many times. See In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.” See In re Wilder, 166 USPQ 545, 548. Note also In re Deuel 34 USPQ2d 1210, 1214 which states, “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds … a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para).”
Therefore, Formula (I) of the instant claims, having similar structure and the same utility as the compounds in the reference application, would have been prima facie obvious before the effective filing date of the instant application. A skilled artisan would have been motivated to prepare a position isomer of the compounds recited in the reference application with a reasonable expectation of success in obtaining a compound with the same utility.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18/700,515
Claims 1, 2, 4, 6, 8, 10, 12, 14, 18, 26-29, 53, 54, and 57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 6, 16, 19, 27, 37, 42, 44, 49, 50, 52, 53, 55, 63, 65, 71, 75, 80, 131, 132, and 135 of copending Application No. 18/700,515 (reference application).
The reference application recites compounds of Formula (I) or Formula (II):
PNG
media_image3.png
113
238
media_image3.png
Greyscale
PNG
media_image5.png
92
242
media_image5.png
Greyscale
and sub-formulas thereof. The only difference between the compounds recited by the reference application and the compounds instantly claimed is the position of the B ring (in Formula I) or the position of the sulfur atom (in Formula II).
MPEP 2144.09, second paragraph, states, “Compounds which are position isomers or homologs 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). The homolog is expected to be preparable by the same method and to have generally the same properties. This expectation is then deemed the motivation for preparing the homolog. This circumstance has arisen many times. See In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.” See In re Wilder, 166 USPQ 545, 548. Note also In re Deuel 34 USPQ2d 1210, 1214 which states, “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds … a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para).”
Therefore, Formula (I) of the instant claims, having similar structure and the same utility as the compounds in the reference application, would have been prima facie obvious before the effective filing date of the instant application. A skilled artisan would have been motivated to prepare a position isomer of the compounds recited in the reference application with a reasonable expectation of success in obtaining a compound with the same utility.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
In the Remarks filed 05/28/2026, applicant requests that the double patenting rejections be held in abeyance until a determination of allowable subject matter is made. Applicant’s request is acknowledged and the rejections are maintained.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 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, Clinton Brooks can be reached at (571) 270-7682. 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.
/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights