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
This Office Action is a response to Applicant’s Election filed August 13, 2026.
Claims 1, 11, 17, 19, 24-26, 30 and 42-43 have been amended.
Claims 1-3, 6-9, 11, 17, 19, 23-26, 29-30, 42-43, and 48-49 are pending in the present application.
Election/Restrictions
Applicant’s election (with traverse) of Group I in the reply filed on August 13, 2026 is acknowledged. Applicant’s election of the miRNA inhibitor species, SEQ ID NO: 1 in the reply filed on August 13, 2026 is also acknowledged.
The traversal is on the grounds that the claims have been amended to recite that the miRNA inhibitors comprise at least one of: (i) a nucleic acid that binds to at least a portion of a miR-192-5p sequence; or (ii) a nucleic acid having the sequence of any one of SEQ ID NOs: 1-4, 6, and 8-19. In view of this amendment, Applicant requests reconsideration and withdrawal of the Restriction Requirement.
Applicant’s traversal has been fully considered by the Examiner and is found persuasive. All pending claims will be examined on the merits together in one application.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-3, 6-9, 11, 17, 19, 23-26, 29-30, 42-43, and 48-49 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed January 18, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed February 4, 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed August 13, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
The Drawings filed on November 3, 2023 are acknowledged and have been accepted by the Examiner.
Claim Interpretation
Some claims recite, “a nucleic acid that binds to at least a portion of a miR-192-5p sequence”. The claims in this application are given their broadest reasonable interpretation (BRI) using the plain meaning of the claim language in light of the Specification as it would be understood by one of ordinary skill in the art. See MPEP 2111. Interpreted broadly, “a nucleic acid that binds to at least a portion of a miR-192-5p sequence” is anticipated by any dinucleotide or larger oligonucleotide sequence. For examination and prior art purposes, the Examiner will therefore interpret the phrase, “a nucleic acid that binds to at least a portion of a miR-192-5p sequence” to be any dinucleotide or larger oligonucleotide sequence.
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 17, 19, 24-26, 43 and 48 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. This is a written description rejection.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice..., reduction to drawings..., or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the disclosure must provide written support for the entire scope of the genus. Support for a genus is generally found where the Applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed and that applicant was in possession of the claimed genus.
The claims are drawn to a method of preventing, inhibiting, treating, or reducing an aneurysm in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an miRNA inhibitor comprising at least one of:(i) a nucleic acid that binds to at least a portion of a miR-192-5p sequence; or (ii) a nucleic acid having the sequence of any one of SEQ ID NOs: 1-4, 6, and 8-19. Some claims recite, “a nucleic acid that is at least 90% identical to any one of SEQ ID NOs: 1-4, 6, and 8-19” or “wherein the miRNA inhibitor comprises a nucleic acid sequence that is at least 95% identical to any one of SEQ ID NOs: 1-19”. The present Specification teaches exemplary miRNA inhibitor sequences comprising SEQ ID NOs: 1-19. See Table 1.
There is insufficient written description of the nucleic acid or miRNA inhibitor sequence encompassed by the claims. The present Specification discloses exemplary miRNA inhibitor sequences comprising SEQ ID NOs: 1-19, but does not describe sequences with any percent identity to SEQ ID NOs: 1-19 that function as claimed to suppress the function of mature miR-192-5p.
Written description requirement for claims that recite, “a nucleic acid that is at least 90% identical to any one of SEQ ID NOs: 1-4, 6, and 8-19” or “wherein the miRNA inhibitor comprises a nucleic acid sequence that is at least 95% identical to any one of SEQ ID NOs: 1-19” is not met because the Specification does not provide any description of any variants or what sequences could be modified (added, deleted or mutated) that retain function. Accordingly, the claims encompass using a genus of nucleic acid or miRNA inhibitor sequence which are not adequately described. Therefore, the claims are rejected because there is insufficient description of the genus of the nucleic acids or miRNA inhibitor sequences encompassed by the claims.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). It is noted that conception is not achieved until reduction to practice has occurred regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
To satisfy the written description requirement an applicant must describe the invention is such a way as to convey to one skilled in the art that applicant had the invention in his possession when the application was filed. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). In cases such as the instant application where a genus is claimed, the specification must contain “either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350. However, written description requirement for claims that recite “a nucleic acid that is at least 90% identical to any one of SEQ ID NOs: 1-4, 6, and 8-19” or “wherein the miRNA inhibitor comprises a nucleic acid sequence that is at least 95% identical to any one of SEQ ID NOs: 1-19” that function to suppress the function of mature miR-192-5p is not met.
The entire genus of methods of using “a nucleic acid that is at least 90% identical to any one of SEQ ID NOs: 1-4, 6, and 8-19” or “wherein the miRNA inhibitor comprises a nucleic acid sequence that is at least 95% identical to any one of SEQ ID NOs: 1-19” does not exist in the instant application. That is, adequate written description support does not exist to practice the full scope of the invention claimed. The specification nor the art discloses neither a representative number of species compounds nor any structure/function correlation that would enable one of skill to immediately envision the genus of nucleic acids or miRNA inhibitor sequences required to practice the full scope of the invention.
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
Additionally, claim 48 recites, “wherein the miRNA inhibitor is at least 5 and at most 35 nucleotides in length”. Similar to the present Specification not disclosing or describing sequences with any percent identity to SEQ ID NOs: 1-19 that function to suppress the function of mature miR-192-5p, the application also does not teach, disclose or describe miRNA inhibitors of such short lengths. For example, the prior art of U.S. Patent Publication 20070213292 A1 teaches antagomirs useful for modulating expression of microRNAs are of at least 19 nucleotides in length for optimal function. Also, see WO 2009/018493.
In conclusion, the Specification and the prior art as filed does not provide sufficient descriptive support for the myriad of nucleic acids or miRNA inhibitor sequences embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Claims 1, 2, 6-9, 11, 17, 19, 29-30 and 48-49 are rejected under 35 U.S.C. 103 as being unpatentable and obvious over WO 2011121120 A1 as evidenced by WO 2009/018493 A1.
The claims are drawn to a method of preventing, inhibiting, treating, or reducing an aneurysm in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an miRNA inhibitor comprising at least one of a nucleic acid that binds to at least a portion of a miR-192-5p sequence. Applicant is reminded of the claim interpretation of the phrase, “a nucleic acid that binds to at least a portion of a miR-192-5p sequence”. For further explanation, see section titled, “Claim Interpretation” supra. NOTE: A subject suffering from an aneurysm is in need of decreasing reactive oxygen species production, reversing vascular remodeling, restoring endothelial nitric oxide synthase (eNOS) coupling activity, or preserving nitric oxide (NO) bioavailability.
WO 2011121120 teaches antagonists of miRNA-29 expression and their use in the prevention and treatment of aortic aneurysms, including abdominal aortic aneurysms.
The antagonists of miRNA-29 of are comprised within a plasmid or vector; are administered parenterally; and are chemically modified.
WO 2011121120 teaches the antagonists of miRNA-29 comprise sequences complementary to miRNA-29 (a-c), but do not necessarily teach the actual sequence of the antagomir/antagonist. NOTE: The reference teaches that WO 2009/018493 discloses the sequence of miR-29a-c antagonists. The specific sequence of a particular miRNA-29 antagonist comprises AsAsCACUGAUUUCAAAUGGUsGsCsUsAs-Cholesterol (anti-miR-29b) as evidenced by WO 2009/018493. NOTE: The Examiner is interpreting this sequence as an miRNA inhibitor comprising a nucleic acid that binds to at least a portion of a miR-192-5p sequence as recited in the present claims.
WO 2011121120 does not necessarily teach wherein the methods of their invention further comprise conjointly administering an additional therapeutic, however the reference does teach current aneurysm treatments include rosiglitazone, which reduces the development and rupture of experimental aortic aneurysm.
It would have been obvious for one of ordinary skill in the art to modify the method of prevention and treatment of aortic aneurysms of WO 2011121120 to include additional therapeutic agents that treat aneurysms, such as rosiglitazone for additive or beneficial improvements. Applicant is reminded that, "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'l Co. v. Teleflex lnc., 550 U.S. 398,416 (2007). Furthermore, it is well-known, routine and common knowledge in the art to use combination therapy for additive effects for disorder treatment.
Before the effective filing date of the claimed invention, a method of preventing, inhibiting, treating, or reducing an aneurysm in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an miRNA inhibitor comprising at least one of a nucleic acid that binds to at least a portion of a miR-192-5p sequence was taught and suggested by the prior art of WO 2011121120.
A person of ordinary skill in the art would have expected reasonable success to devise the methods of the claimed invention using the teachings and motivation of WO 2011121120 as evidenced by WO 2009/018493.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
Markush Rejection
Claims 1-3, 6-9, 11, 17, 19, 23-26, 29-30, 42-43, and 48-49 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are directed to a multitude of miRNA inhibitor sequences with no common searchable core. The miRNA inhibitor sequences have no common structure other than being nucleic acid sequences. The specific activity of each inhibitor is dependent upon the specific sequence of nucleotides.
Furthermore, the sequences recited in the claims target different miRNAs. For example, see Table 1. NOTE: Table 1 only identifies SEQ ID NO: 1 as a miRNA inhibitor targeted specifically to hsa-miR-192-5p. Further, the Specification discloses: “The locked nucleic acid (LNA)-mmu-miR-192-5p inhibitors were synthesized by Exiqon (now a QIAGEN company, Germantown, MD, USA)”, however the actual sequence of the miRNA inhibitor is never identified or disclosed.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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