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 .
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 1-5, 11- 12, and 25-32 drawn to a method) in the reply filed on May 11, 2026, is acknowledged. For an election of species between an RNA-based inhibitor and a peptide inhibitor, Applicants elect RNA-based inhibitor without traverse.
Additionally, Applicants have amended claims 1-2, cancelled claims 4-5, 11, 14, 20-23, 25, 27-30, and 32, and added new claims 33-36 (Remarks say 33-40, which appears to be an inadvertent error). Since new claims 33-36 are drawn to a composition encompassed within a non-elected group claim; i.e., Group II drawn to a composition, the new claims will be added to Group II and withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 11, 2026.
Status of Claims
Claims 1-3, 12, 26, and 31 are under consideration.
PriorityAcknowledgement is made of Applicant’s National Stage entry of PCT Application
PCT/US2022/23737 filed on 4/6/2022, and Applicant’s claim to Domestic Benefit of provisional application 62/172403 filed on 4/8/2021.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(u)(1) because:
the labels for Figures 1 - 18 are preceded by the word "Figure" instead of the abbreviation "FIG.". MPEP §608.02.V states that according to 37 C.F.R. 1.84(u)(1) “View numbers must be preceded by the abbreviation "FIG.".
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
The specification is objected to because of an informality.
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. Specifically, the name and size of sequence listing provided with the application does not match the name and size of sequence listing in the Incorporation by Reference paragraph. Instant specification contains an incorporation by reference statement which is defective because it recites the total size in ~48 KB. Size should be specified in bytes.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112a
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 1-3, 12, 26, and 31 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 purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997).
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 a disclosure of a representative number of species to describe the complete structure of the claimed genus and/or disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
Scope of the Invention
In the instant case, the genus is RNA-based inhibitors that target one of KIF20A, SEPT7, RGS3 and EphrinB and “prevents or blocks binding of KIF20A to RGS3 or to SEPT7 or binding of EphrinB to RGS3.”
The broadest reasonable interpretation (BRI) of the scope of this genus is all possible RNA-based inhibitors that are capable of decreasing levels of one of KIF20A, SEPT7, RGS3 and EphrinB mRNA such that the end result is: prevention or blocking binding of KIF20A to RGS3 or to SEPT7 or binding of EphrinB to RGS3. The BRI also includes RNA-based inhibitors that physically block binding between two of the proteins by steric hindrance.
RNA-based inhibitor isn’t defined in instant disclosure. Therefore, it is being given the BRI to mean, an RNA polymer that targets a gene that it is meant to inhibit. The art recognizes RNA polymers that target certain genes to be single-stranded or double-stranded and designed as siRNA, shRNA, ASO interference agents, gRNA coupled to programmable nucleases etc.,.
Disclosure of Complete Structure
Regarding the RNA-based inhibitor, Applicant generally and non-specifically discloses sub-genera of the larger genus of agents including: shRNAs, miRNAs, and siRNAs targeting KIF20A, RGS3, SEPT7 or EphrinB [0035]. The sub-genus of shRNA i) that could inhibit KIF20A expression in the mouse and human cells is then described by sequence [0037 - 0038], followed by ii) that could inhibit EphrinB1 expression in the mouse cells is then described by sequence [0040], iii) that could inhibit RGS3 expression in the mouse cells is then describe by sequence [0041], and iv) that could inhibit SEPT7 expression in the mouse cells is then described by sequence [0042]. In some experiments, siRNAs of the disclosed sequences are used. Table 1 lists the sequences and Fig. 10 shows the efficiency of siRNA to KIF20A.
Structure/Function Correlation
As stated above, the breadth of Applicant’s claim encompasses many structurally and functionally distinct agents of RNA-based inhibitors. 1. Competitive (peptide-based) inhibition of RGS3-KIF20A / EphrinB-RGS3 interactions are then described in Example 7 (Figs. 13a-15c), and 2. The specification discloses the inhibition of expression of KIF20A with an RNA-based inhibitor leads to reduced levels of protein. Put together, the competitive peptide binding assay teaches use of RGD/PDZ binding domains prevents RGS3-KIF20A / EphrinB-RGS3 interactions and, one of skill in the art can envisage that inhibiting expression, which will result in lower protein levels, will evidence reduced (prevent) binding.
However, Applicant has not provided a nexus between the structure of the claimed RNA-based inhibitors and the claimed function of blocking binding of KIF20A to RGS3 or to SEPT7 or binding of EphrinB to RGS3, and therefore one of ordinary skill would not be able to envision the requisite structural elements that would block binding from the instant disclosure at the time of filing. Only, prevent binding is adequately described.
Knowledge from the Art
Amanat (Amanat et al., Pharmaceutics 2022, 14, 2389) teaches that despite challenges, RNA-based inhibitors such as Antisense oligonucleotides (ASOs) are able to reduce the level of genes that they target when administered to human subjects (abstract). Enhancing delivery via conjugation and increasing stability by chemically modifying bases, is improving outcome in clinical studies (whole paper).
However, nothing in the art teaches one of skill how an RNA-based inhibitor may block binding of its target gene.
Conclusion
Therefore, the examiner concludes there is insufficient written description support for the instantly claimed genera of RNA-based inhibitor that targets one of KIF20A, SEPT7, RGS3 and EphrinB and blocks binding of KIF20A to RGS3 or to SEPT7 or binding of EphrinB to RGS3. The specification solely describes one outcome: competitive inhibition of binding with peptides. No blocking of binding with an RNA-based inhibitor is described. The art teaches and therefore a skilled artisan can envisage that the inhibition of expression with the RNA-based inhibitor will lead to reduced levels of protein, which will be evidenced by reduced (prevent) binding. However, neither the example described nor the art reconciles how an RNA-based inhibitor blocks binding of KIF20A to RGS3 or to SEPT7 or binding of EphrinB to RGS3. The breadth of the claim encompasses RNA-based inhibitors that can effectuate prevention and blocking binding, and the specification has not provided sufficient structural-functional relationship between the breadth of the claimed RNA-based inhibitors and the function of prevention and blocking binding. Accordingly, Applicant has not shown possession of the claimed invention at the time of effective filing.
Hence, there is insufficient written description support for instant claims.
Claim Interpretation
No definition for “prevents” has been provided. Therefore, prevents … binding as recited in claims 1 and 2 is being given the BRI of either sterically inhibiting binding or reducing binding (as a result of an effective RNA-based inhibitor that results in fewer proteins).
Instant specification defines, "effective amount” to be an amount of an RNA-based inhibitor or peptide or a composition comprising an RNA-based inhibitor or peptide that produces a desired therapeutic effect in a subject [0030].
The rejections below are directed to subject matter for which there is adequate written description.
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, 3, 12, 26, and 31 is/are rejected under 35 U.S.C. 102 (a1) as being anticipated by McSwiggen (McSwiggen et al., AU 2003/216324 B2).
Regarding claims 1-3, 12, 26, and 31, McSwiggen teaches methods for treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism (abstract). Specifically, the treatments are: small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi); i.e., RNA-based inhibitors. The RNA-based inhibitors are directed to gene families (pg. 11, para2) such as ephrin (Table V pg. 493, 543) and RGS3 (Table V pg. 493, 543). The RNA-based inhibitor comprises a chemical modification which is a conjugate covalently attached to the chemically-modified RNA-based inhibitor (at least pg. 32). The RNA-based inhibitor represents a novel therapeutic approach to a broad spectrum of diseases and conditions, including cancer (at least pg. 59). McSwiggen teaches that the use of galactose, galactosamine, or folate based conjugates on the RNA-based inhibitor provide a targeted delivery approach for example, the treatment of cancers of the liver, or other cancers. (pg. 98, last para).
It is noted that effective amount of a drug (e.g. ephrinB1 RNA-based inhibitor) may be obtained by routine experimentation, absent a showing of criticality or unexpected results.
Thus, McSwiggen anticipates instant claims 1, 3, 12, 26, and 31.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 12, 26, and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vermeer (Vermeer et al., WO 2018156915 A1) in view of Amanat (Amanat et al., Pharmaceutics 2022, 14, 2389). Claims 1-2 are evidenced by Lu (Lu et al., Cell, Volume 105, Issue 1, p69-79, April 06, 2001).
Vermeer teaches that ephrin-mediated signaling is seen in disease processes such as tumorigenesis and metastasis (abstract).
Regarding claims 1-3, 26, and 31, Vermeer teaches methods for tumor treatment involving administering to a subject having a tumor with an amount effective to limit tumor growth or metastasis of an ephrin B1 inhibitor (abstract). The ephrin B1 inhibitor is selected from the group consisting of ephrin B1 -specific antibodies, aptamers, small interfering RNAs, small internally segmented interfering RNAs, short hairpin RNAs, microRNAs, and/or antisense oligonucleotides (pg. 2, 1st para, claims 1, 3, 12).
Regarding the limitation of prevents binding of EphrinB to RGS3, Vermeer teaches EphrinB is a PDZ-containing proteins (E6 proteins that contain a C-terminal PDZ binding motif (PDZBM), which binds with PDZ domain-containing proteins, such as protein-tyrosine phosphatase non-receptor type 13 (PTPN13). PTPN13 interacts with ephrin B1, pg. 8, 1st para). As evidenced by Lu (Lu et al., Cell, Volume 105, Issue 1, p69-79, April 06, 2001) RGS3, which binds B ephrins through a PDZ domain. Therefore, reducing levels of EphrinB would result in preventing binding of EphrinB to RGS3.
Regarding claim 12, Vermeer teaches their method that can be used to treat various cancers, such as certain breast cancers, colorectal, lung, breast, and gastric cancers) (pg. 11, 1st para, at least claim 12 and 31)).
Vermeer does not teach conjugated moieties for delivery or an effective amount of the RNA-based inhibitor to ephrinB1 to the tumor.
However, before the effective filing date of instant invention, Amanat teaches that ASO delivery is typically naked (None of the current FDA-approved ASOs have delivery particles and all are administered to patients as naked oligonucleotides, (§5. Antisense Oligonucleotide Delivery, page 10, para. 1, Fig. 4). However, some clinical studies are currently assessing the efficacy of ASOs with delivery particles to enhance cellular uptake and drug internalization to further improve delivery and maximize therapeutic potency, including eplontersen (NCT05071300). Phase I studies showed that eplontersen was safe. Eplontersen is a ligand conjugated antisense drug (Id.). The RNA-based inhibitors are being tested at different doses in clinical trials (Table 3); i.e., an effective amount is determined in the trial.
It is noted that effective amount of a drug (e.g. ephrinB1 RNA-based inhibitor) may be obtained by routine experimentation, absent a showing of criticality or unexpected results.
It would have been prima facie obvious to one of ordinarily skilled in the art at the time the invention was filed to treat a subject with a cancer with the method of using RNA-based inhibitor taught by Vermeer, after conjugating a moiety that would enhance delivery as taught by Amanat, as doing so would enhance therapeutic efficacy of the treatment. One skilled in the art could have combined the elements as claimed (conjugation moiety combined with an RNA-based inhibitor) by known methods with no change in their respective functions, with reasonable expectation of success and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. See MPEP 2143 I.(A) and 2144 II.
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm EST.
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SHABANA S. MEYERING, Ph.D.
Examiner
Art Unit 1635
/SHABANA S MEYERING/Examiner, Art Unit 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
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