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 .
DETAILED ACTION
Applicant's preliminary amendment filed on April 14, 2024 is acknowledged. Claims 1-8 and 10-15 were amended. Claims 1-15 are pending and are examined on the merits herein.
Priority
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 14, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings were received on April 14, 2024.
The drawings are objected to because Fig. 5D is missing. In addition, Fig. 6B is labeled “Fluoscence in-situ hybridisation” and should be labeled “Fluorescence”. Further, right graph of Fig. 7B does not have a legend for the second set of data points. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract is not limited to a single paragraph. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities:
Page 7 line 31 reads in part “dexoxyribonucleoside” and should read “deoxyribonucleoside”.
Figures 2E, 4C, 5H, 6A, and 6F in the description of the figures section refer to the figures by color; however, color drawings were not submitted with the application.
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See pages 29, 37, and 38.
Claim Objections
Claims 1, 6, 8, 9, 10, and 13 are objected to because of the following informalities:
Claims 1, 8, 9, 10, and 13 have periods within each claim at the bullet points. See MPEP 608.01(m).
Claim 1 is missing a coordinating conjunction (e.g., “and” or “or”) between part a and part b.
Claim 6 recites in part “dexoxyribonucleoside units” two (2) times and both instances of this phrase should recite “deoxyribonucleoside units”.
Claim 6 has extra spaces around the phrase “and/or”.
Claim 8 is missing a coordinating conjunction (e.g., “and” or “or”) between the bullet points labeled with the hyphen.
Claim 10 part c recites in part “dexoxyribonucleoside units” two (2) times and both instances of this phrase should recite “deoxyribonucleoside units”.
Claim 10 part c is missing a space in between the comma and the word “particularly”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-15 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite at the recitation of “a long non-coding RNA target selected from a. ENSG00000253616 (CHiLL1; SEQ ID NO 001) b. ENSG00000272808 (CHiLL2; SEQ ID NO 002)” because ENSG00000253616, ENSG00000272808, SEQ ID NO 001 and SEQ ID NO 002 are genomic sequences and not long non-coding RNA targets.
Claims 2-8 and 12-15 are indefinite because the claims depend from a rejected claim (claim 1) without addressing the issue in claim 1.
Claim 9 is indefinite at the recitation of “a long non-coding RNA target ENSG00000253616 (CHiLL1; SEQ ID NO 001)” and “a long non-coding RNA target ENSG00000272808 (CHiLL2; SEQ ID NO 002)” because SEQ ID NO 001 and SEQ ID NO 002 are genomic sequences and not long non-coding RNA targets.
Claims 10 and 11 are indefinite because the claims depend from a rejected claim (claim 9) without addressing the issue in claim 9.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 1 and 9 recite the broad recitation “CHiLL1”, “ENSG00000253616”, “CHiLL2”, and “ENSG00000272808”, and the claims also recite “SEQ ID NO 001” and “SEQ ID NO 002” which is the narrower statement of the range/limitation. In addition, claims 2, 3, 8, and 10 recite the broad recitation “ENSG00000253616” and/or “ENSG00000272808”, and the claims also recite “SEQ ID NO 001” and/or “SEQ ID NO 002” which is the narrower statement of the range/limitation. The recitation of “CHiLL1” and “CHiLL2” is not limited to any particular sequence. In addition, “ENSG00000253616” and “ENSG00000272808” can change over time and is not limited to a particular version (See Ensembl – CHiLL1; ENSG00000253616.5, retrieved on September 16, 2026, 1 page; Ensembl – GCAWKR; ENSG00000272808.5, retrieved on September 16, 2026, 1 page; and Ensembl – Stable IDs, retrieved on September 16, 2026, 2 pages, “Versioning” section). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
It would be remedial to amend independent claim 1 to recite in part “downregulating or inhibiting a long non-coding RNA target transcribed from a sequence selected from the group consisting of SEQ ID NO 001 and SEQ ID NO 002”. In addition, it would be remedial to amend independent claim 9 part a to recite in part “downregulating or inhibiting a long non-coding RNA target transcribed from SEQ ID NO 001" and part b to recite in part "downregulating or inhibiting a long non-coding RNA target transcribed from SEQ ID NO 002”
Claims 6, 10, 11, 14, and 15 are indefinite because the word “particularly” and phrase “more particularly” renders the claim indefinite since it is unclear whether the limitations following the word “particularly” and phrase “more particularly” are part of the claimed invention. See MPEP § 2173.05(d). The Examiner will interpret these claims as limitations that are optional and are not required.
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.
Written Description
Claims 1-7 and 9-15 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.
Claims 1-15 are drawn to the provision of a genus of nucleic acid agents that target and must be capable of downregulating or inhibiting a long non-coding RNA target selected from CHiLL1 (SEQ ID NO: 001) or CHiLL2 (SEQ ID NO: 002). The specification envisions that the nucleic acid agent is an antisense oligonucleotide that is capable of hybridizing to its target CHiLL1 or CHiLL2 [page 7, second paragraph] or an antisense gapmer [page 8, first paragraph]. The specification also envisions that the nucleic acid agent is an RNA agent (oligoribonucleotide) capable of inhibiting or degrading the target, particularly an siRNA, a miRNA, or an shRNA. Further, the specification envisions that the nucleic acid agent encodes an oligoribonucleotide capable of inhibiting or degrading the target, particularly an siRNA, a miRNA, or an shRNA [page 8, second and third paragraphs]. Thus, the claims encompass a large genus of nucleic acid agents that target and must be capable of downregulating or inhibiting CHiLL1 (SEQ ID NO: 001) or CHiLL2 (SEQ ID NO: 002) that must function to treat or inhibit recurrence of non-small-cell lung cancer.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification discloses the following:
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[page 8].
No description is provided of any other nucleic acid agents that target and are capable of downregulating or inhibiting CHiLL1 (SEQ ID NO: 001) or CHiLL2 (SEQ ID NO: 002).
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of a small group of nucleic acid agents that target and are capable of downregulating or inhibiting CHiLL1 (SEQ ID NO: 001) or CHiLL2 (SEQ ID NO: 002) wherein the nucleic acid agent comprises or consists of SEQ ID NOS: 3, 4, 5, or 6.
The results are not necessarily predictive of other nucleic acid agents falling within the broadly claimed genus not limited to any particular structure. Thus, it is impossible for one to extrapolate from the limited examples described herein those nucleic acid agents that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of nucleic acid agents that target and are capable of downregulating or inhibiting CHiLL1 (SEQ ID NO: 001) or CHiLL2 (SEQ ID NO: 002).
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1-15.
Claims 1-3 and 8-10 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as based on a disclosure which is not enabling. The disclosure does not enable one of ordinary skill in the art to practice the invention without the nucleic acid sequence that targets and is capable of downregulating or inhibiting a long non-coding RNA target, which is/are critical or essential to the practice of the invention but not included in the claim(s). See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
The sequences defined by reference to ENSG00000253616 and ENSG00000272808 are defined by reference to entries in an electronic database which is subject to change over time (See Ensembl – CHiLL1; ENSG00000253616.5, retrieved on September 16, 2026, 1 page; Ensembl – GCAWKR; ENSG00000272808.5, retrieved on September 16, 2026, 1 page; and Ensembl – Stable IDs, retrieved on September 16, 2026, 2 pages, “Versioning” section). “Essential material” may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. In the instant case, the claims are, in effect, incorporating the sequence contained in an electronic database. See MPEP 608.01(p). Accordingly, the references to the online sequences do not provide the features that are critical or essential to the practice of the claimed invention. It would be remedial to amend the claims by removing all instances of “ENSG00000253616” and “ENSG00000272808”.
Enablement
Claims 1-15 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is
sufficient evidence to support a determination that a disclosure does not satisfy the
enablement requirement and whether any necessary experimentation is "undue".
These factors include, but are not limited to: (A) The breadth of the claims; (B) The
nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary
skill; (E) The level of predictability in the art; (F) The amount of direction provided by the
inventor; (G) The existence of working examples; and (H) The quantity of
experimentation needed to make or use the invention based on the content of the
disclosure. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of claims and nature of the invention:
Claims 1-8 and 12-15 are drawn to a method for treatment or inhibition of recurrence of non-small-cell lung cancer in a subject comprising, administering to a subject in need thereof a nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target selected from CHiLL1; SEQ ID NO 001 or CHiLL2; SEQ ID NO 002. The broadest reasonable interpretation of claim 1 is that the method encompasses not only treating non-small-cell lung cancer in a subject comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target selected from CHiLL1; SEQ ID NO 001 or CHiLL2; SEQ ID NO 002, but also inhibiting recurrence of non-small-cell lung cancer in a subject comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target selected from CHiLL1; SEQ ID NO 001 or CHiLL2; SEQ ID NO 002.
Claims 9 and 10 are drawn to a pharmaceutical composition comprising a first nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL1; SEQ ID NO 001) and a second nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL2; SEQ ID NO 002).
Claim 11 is drawn to a method for treatment or prevention of recurrence of non-small-cell lung cancer, particularly for use in treatment or prevention of recurrence of lung adenocarcinoma, comprising administering to a subject in need thereof the pharmaceutical composition of claim 9. The broadest reasonable interpretation of claim 11 is that the method encompasses not only treating non-small-cell lung cancer or lung adenocarcinoma comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL1; SEQ ID NO 001) and any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL2; SEQ ID NO 002), but also preventing recurrence of non-small-cell lung cancer or lung adenocarcinoma comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL1; SEQ ID NO 001) and any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL2; SEQ ID NO 002).
Amount of direction provided by the inventor and existence of working
examples:
The specification discloses that 10 lncRNAs were manually selected from top-ranked pan-hallmark and hallmark-specific hits and are referred to as “Tier 1”. For each candidate, a series of ASOs were designed and at least two effective ASOs with greater than or equal to 40% knockdown were identified. The ASOs’ phenotypic effects were tested in terms of proliferation and cisplatin sensitivity. For five lncRNAs (Tier 2: CHiLL1, CHiLL 2, 215, 507, and 205), reproducible loss of cell proliferation was observed with two distinct ASO sequences indicating on-target effects. The ASOs were re-tested in two other KRAS-mutant NSCLC cell lines (H460 and H441) and observed similar results. Further, the Tier 2 ASOs were evaluated for their effect on a panel of non-transformed lung-derived cells. These cells displayed diminished or absent response particularly for the first two candidate lncRNAs (CHiLL 1 and CHiLL 2) and thus the inventors focused on these lncRNAs which are referred to as “Tier 3” lncRNAs. The specification also discloses that replicated experiments confirmed the knockdown efficiency and phenotypic impacts of both ASOs for each gene and refers to Figure 5D; however, Figure 5D is missing from the drawings. Therefore, it is unclear which gene(s) is being referred to when the specification references “both ASOs for each gene”. In addition, the specification and the drawings do not disclose the sequence of the ASOs for CHiLL1 or CHiLL 2.
The specification discloses that CHiLL 1 and CHiLL 2 ASOs were delivered to spheroid cultures of H441 cells and observed a reduction in viability approaching that of the positive control. Further, delivery of CHiLL 1 ASOs resulted in significant reduction in cell viability of the KRAS-mutant human NSCLC organoid BE874. The specification also discloses that a 50:50 cocktail of CHiLL1/CHiLL2 ASOs displayed a greater effect on cell viability compared to an equal dose of either ASO alone and a five-ASO cocktail targeting all Tier 2 lncRNAs yielded a similar benefit. However, the cocktails did not result in additional toxicity for non-cancerous cells.
State of the prior art, level of predictability in the art, and level of one of
ordinary skill:
A review of the prior art shows that the state of the art of treating or inhibiting recurrence of non-small-cell lung cancer in a subject comprising administering to a subject in need thereof a nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target selected from CHiLL1; SEQ ID NO 001 or CHiLL2; SEQ ID NO 002 is immature and nascent. A review of the prior art also shows that the state of the art of treating or preventing recurrence of non-small-cell lung cancer, particularly for use in treating or preventing recurrence of lung adenocarcinoma, comprising administering to a subject in need thereof the pharmaceutical composition of claim 9 is immature and nascent.
Although post-filing, Chen et al. (Cancer Management and Research 2022) discloses that long noncoding RNAs (lncRNAs) have recently attracted additional attention due to their potential role in carcinogenesis, invasion and metastasis and the use of antisense oligonucleotides, small molecules and RNA interference techniques have shown promise as direct therapeutic tools for targeting lncRNAs in preclinical studies. However, the concept of using lncRNAs as biomarkers for prognostication and intervention in lung cancer is still in its infancy, and only with more in-depth studies could they have a significant impact [abstract]. Chen et al. also discloses that many common challenges remain in the development of directly targeting lncRNA therapy, including the lack of safe, specific and effective delivery methods, the absence of a defined optimal dosing regimen and the prevention of off-targeting [page 1776, last paragraph bridging to page 1777].
Although post-filing, Tegenbosch et al. (Anticancer Research 2024) discloses that recurrence rates in early and locally advanced non-small-cell lung cancer (NSCLC) remain high despite curative treatment [abstract]. Further, recurrence remains high due to subclinical spread of tumour cells [page 5495, right column].
Although post-filing, Meyer et al. (Lancet 2024) teaches that targeted therapy and cancer immunotherapy have substantially transformed the treatment of NSCLC; however, challenges such as resistance development, treatment toxicity, high costs, under-representation of minoritised groups in trials, and little access to diagnostics and treatments persist. Further, better patient selection through intensive translational research for reliable biomarkers is crucial to improve efficacy and minimize toxicities [page 819, right column, first full paragraph].
Although post-filing, Zhou et al. (Frontiers in Oncology 2026) teaches that non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality and significant challenges persist despite recent advancements. Specifically, acquired resistance mechanisms and bypass pathways continue to undermine long-term therapeutic efficacy [abstract]. Zhou et al. also teaches that translating research advances into equitable patient benefit faces substantial systemic barriers. Robust data for special populations, particularly older adults and those with rare subtypes such as hepatoid adenocarcinoma of the lung, remain scarce, necessitating dedicated trials incorporating geriatric assessments [page 9, right column].
Thus, one of ordinary skill in the art would not expect to treat non-small-cell lung cancer, inhibit or prevent recurrence of non-small-cell lung cancer, treat lung adenocarcinoma, or prevent recurrence of lung adenocarcinoma comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target selected from CHiLL1; SEQ ID NO 001 or CHiLL2; SEQ ID NO 002.
Quantity of experimentation:
In view of the breadth of the claims which embrace treating non-small-cell lung cancer in a subject comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target selected from CHiLL1; SEQ ID NO 001 or CHiLL2; SEQ ID NO 002, inhibiting recurrence of non-small-cell lung cancer in a subject comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target selected from CHiLL1; SEQ ID NO 001 or CHiLL2; SEQ ID NO 002, treating non-small-cell lung cancer or lung adenocarcinoma comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL1; SEQ ID NO 001) and any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL2; SEQ ID NO 002), and preventing recurrence of non-small-cell lung cancer or lung adenocarcinoma comprising administering any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL1; SEQ ID NO 001) and any nucleic acid agent targeting and capable of downregulating or inhibiting a long non-coding RNA target (CHiLL2; SEQ ID NO 002), the state and level of predictability in the art, and the failure to provide adequate guidance to overcome the state and level of predictability of the art, one of skill would have to perform undue experimentation in order to practice the invention commensurate in scope with the claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
Prosecution Insights