DETAILED ACTION
Election/Restrictions
Applicant’s election of Group I, hsa-miR-92a-3p, VHPKQHR (SEQ ID NO: 2) and anticoagulant in the reply filed on July 25 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)). In light of the discovered prior art, the scope of inhibitor of microRNA-92a is withdrawn and targeting peptide election expanded to include REKA. Claims 1, 3-16 and 28-32 are pending in the application. Claims 28-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 25 2025. Accordingly, claims 1 and 3-16 are being examined on the merits herein.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a 371 of PCT/US20/54291 (10/05/2020) which claims benefit of 62/910,873 (10/04/2019).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 4 2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”
In the current case, the view numbers for Figures 1-28 are preceded by the word "Figure" instead of 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.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See MPEP 2412
Claim 7 refers to a polyaminoacid of lysine comprising 30 repeats of lysine whose shorthand is K30. This corresponds to a peptide sequence with 4 or more specifically defined and enumerated amino acids. Therefore, this sequence must have a sequence identifier. This sequence is also found on page 3, 4, 5, 18 and 21-23.
Claim 9 recites various amino acid sequences with more than 4 specifically defined and enumerated amino acids but lack a sequence identifier. Each species of the targeted nanoparticle comprises 2 sequences (the targeting molecule and K30). These sequences are also present in page 3, 5, 18, 22-23 and 24.
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 sequence identifiers, 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.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Fig. 21 include poly-lysine which is an amino acid sequence with 4 or more enumerated amino acids. Therefore, a SEQ ID must be associated with that sequence. The examiner notes that neither the drawing nor the specification brief description of Fig. 21 include the sequence identifier.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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 § 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.
Claim 11 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 11 as currently written is vague and indefinite. The claim recites the miR-92a inhibitor comprises a concentration of about 2 µM. But never recites what the inhibitor comprises at that concentration. Therefore, it isn’t clear if Applicants intended the claim to recite the nanoparticle comprises the miR-92a inhibitor at a concentration of about 2 µM or if something else is supposed to be part of the claim and that is included at a concentration of about 2 µM.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 3-9, 12 and 15-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kuo et al. (J. Mater. Chem. B Mater Biol Med., 2014).
The instant application claims a targeted nanoparticle, comprising an inhibitor of microRNA- 92a (miR-92a), wherein the targeted nanoparticle comprises a polyelectrolyte micelle and a targeting molecule.
Kuo et al. is directed to the inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles. Exemplified are targeting peptide-PEG(2000)-poly-L-lysine (K30). The miRNA inhibitor molecules (miRIDIAN microRNA Hairpin Inhibitors) are single-stranded chemically enhanced oligonucleotides. Two different targeting peptide sequence were used, REKA and VHPKQHR (page 4, material synthesis and purification). It is taught ath VHPKQHR, a phase display-identified peptide, that exhibit high affinity for vascular cell adhesion was utilized as a targeting molecule with an miR-92a inhibitor. The REKA-, VHPKQHR- or VHPKQHR/REKA-conjugated micelles that encapsulate miR-92 inhibitors (pages 9-10, see also table 2). Figure 1 shows the constructure of the targeted polyelectrolyte complex micelles.
Therefore, Kuo et al. exemplified a polyelectrolyte micelle containing the same targeting moiety (REKA and/or VHPKQHR), polyethylene glycol (PEG) and an miR-92a inhibitor reading on claims 1, 3, 8-9,
Regarding claim 4, PEG2000 is exemplified. This has a MW of about 2000 daltons (see figure on page 16 which shows 45 repeats).
Regarding claims 5-7, the exemplified micelle is made of 30 repeats of lysine (see also the figure on page 16).
Regarding claim 12, as shown in the micelle formation on page 4, water is added which reads on carrier, solvent or diluent. As shown on pages 9-10 and Figures 5B-5D delivery of miR-92a inhibitors significantly surprised the endogenous expression of miR-92. Therefore, the composition comprises a therapeutically effective amount.
Regarding claims 15-16, Kuo et al. teaches the micelles with water. Claims 15-16 merely recite the intended use of the composition and do not structurally distinguish the composition of Kuo et al. (i.e. micelles with water) from those recited in claims 15-16. A recitation of the intended use, for oral, intravenous, topical, ocular, buccal, systemic, nasal, injection, transdermal rectal or vaginal administration (claim 15) or for inhalation or insufflation (claim 16), of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Claims 1, 3-12 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Kuo et al. as applied to claims 1, 3-9, 12 and 15-16 above in view of Sessa et al. (USPGPUB No. 20180250325).
Applicant Claims
The instant application claims the miR-92a-inhbiotr comprises hsa-miR-92a-3p. The instant application claims the inhibitor comprises a concentration of about 2 µM which the examiner is interpreting as claimed that the targeted nanoparticle comprises the miR-92a inhibitor at a concentration of 2 µM.
Paragraph 00071 of the instant specification which teaches that miR-92 inhibitors include custom miRIDIAN Hairpin Inhibitor (hsamiR-92a-3p).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Kuo et al. are set forth above. Kuo et al. teaches miR-92a inhibitors and specifically teaches the miRNA inhibitor molecules are miRIDIAN microRNA Hairpin Inhibitors. Micelles of varying concentrations were formed by complexing the targeting-peptide-PEG-K30 and miRNA inhibitors at an equal charge molar ratio (page 4).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Kuo et al. teaches miR-92a inhibitors and teaches miRIDIAN microRNA Hairpin Inhibitors which are the same as the instantly claimed inhibitors, Kuo et al. does not expressly teach the inhibitor is hsa-MIR-92a-3p. Kuo et al. does not exemplify the inhibitor in the concentration claimed. However, these deficiencies are cured by Sessa et al.
Sessa et al. is directed to Mir-19 modulators and uses thereof. Taught are subjects which suffer from atherosclerosis (claim 24; paragraph 0013; 0103). Oligonucleotide inhibitor of miR-92 include inhibitors of mature miR-92 such as hsa-MIR-92-3p (paragraph 0029). The activity of an oligonucleotide inhibitor of a target miRNA of the present invention in reducing the function or activity of the target miRNA (e.g., miR-19 or miR-92) may be determined in vitro and/or in vivo (paragraph 0064) or in an animal model (paragraph 0065). Pharmaceutical forms include those suitable for injectable use or inhalational delivery (paragraph 0094).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Kuo et al. and Sessa et al. and utilize the miR-92 inhibitor hsa-MIR-92-3p. One skilled in the art would have been motivated to utilize this inhibitor as Kuo et al. expressly teaches a miR-92 inhibitor and Sessa et al. teaches that hsa-MIR-92-3p is a mature miR-92 inhibitor. One skilled in the art would have been motivated to utilize any known miR-92 inhibitor as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
Regarding claim 11, Sessa et al. teaches that the activity of the inhibitor may be readily determined. Kuo et al. teaches varying concentrations of inhibitor can be used and that the inhibitor and targeting-peptide-PEG-K30 are at an equal charge molar ratio. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results. The amount of an active ingredient is a parameter that a person of ordinary skill in the art would routinely optimize based on the condition being treated, severity of the condition and desired dosing frequency, among other factors. It would have been obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). NOTE: MPEP 2144.05.
Regarding claims 15-16, Sessa et al. teaches that pharmaceutical forms for delivery include injectable and inhalation.
1 and 3-16 are rejected under 35 U.S.C. 103 as being unpatentable over Kuo et al. as applied to claims 1, 3-9, 12 and 15-16 above in view of Sessa et al. (USPGPUB No. 20180250325) and Liu et al. (US20150290237).
Applicant Claims
The instant application claims the miR-92a-inhbiotr comprises hsa-miR-92a-3p. The instant application claims the inhibitor comprises a concentration of about 2 µM which the examiner is interpreting as claimed that the targeted nanoparticle comprises the miR-92a inhibitor at a concentration of 2 µM.
The instant application claims the pharmaceutical composition further comprises a secondary therapeutic agent which as elected is an anticoagulant.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Kuo et al. are set forth above. Kuo et al. teaches miR-92a inhibitors and specifically teaches the miRNA inhibitor molecules are miRIDIAN microRNA Hairpin Inhibitors. Micelles of varying concentrations were formed by complexing the targeting-peptide-PEG-K30 and miRNA inhibitors at an equal charge molar ratio (page 4).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Kuo et al. teaches miR-92a inhibitors and teaches miRIDIAN microRNA Hairpin Inhibitors which are the same as the instantly claimed inhibitors, Kuo et al. does not expressly teach the inhibitor is hsa-MIR-92a-3p. Kuo et al. does not exemplify the inhibitor in the concentration claimed. However, these deficiencies are cured by Sessa et al.
The teachings of Sessa et al. are set forth above.
While Kuo et al. teach inhibition of atherosclerosis-promoting microRNAs, Kuo et al. does not teach the inclusion of an additional therapeutic agent. However, this deficiency is cured by Liu et al.
Liu et al. is directed to therapeutic miRNAs for treating heart and skeletal muscle diseases. One particularly severe manifestation of heart disease is myocardial infarction (MI). Typically, MI results from an acute thrombocytic coronary occlusion that occurs in a coronary artery as a result of atherosclerosis and causes myocardial cell death, i.e., an infarct (paragraph 0029). In certain embodiments, administration of an agent that aids in the removal or prevention of blood clots may be combined with administration of a modulator, particularly in treatment of atherosclerosis and vasculature (e.g., arterial) blockages. Non-limiting examples of antithrombotic and/or fibrinolytic agents include anticoagulants (paragraph 0127; 0130).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Kuo et al., Sessa et al. and Liu et al. utilize the miR-92 inhibitor hsa-MIR-92-3p. One skilled in the art would have been motivated to utilize this inhibitor as Kuo et al. expressly teaches a miR-92 inhibitor and Sessa et al. teaches that hsa-MIR-92-3p is a mature miR-92 inhibitor. One skilled in the art would have been motivated to utilize any known miR-92 inhibitor as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Kuo et al., Sessa et al. and Liu et al. utilize an anticoagulant in combination with the micelles of Kuo et al. One skilled in the art would have been motivated to include an anticoagulant as Kuo et al. is directed to inhibition of atherosclerosis-promoting microRNAs and Liu et al. teaches that anticoagulants can be used with miRNAs in the treatment of atherosclerosis. As a general principle it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06.
Regarding claim 11, Sessa et al. teaches that the activity of the inhibitor may be readily determined. Kuo et al. teaches varying concentrations of inhibitor can be used and that the inhibitor and targeting-peptide-PEG-K30 are at an equal charge molar ratio. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results. The amount of an active ingredient is a parameter that a person of ordinary skill in the art would routinely optimize based on the condition being treated, severity of the condition and desired dosing frequency, among other factors. It would have been obvious to one of ordinary skill in the art at the time of the invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). NOTE: MPEP 2144.05.
Regarding claims 15-16, Sessa et al. teaches that pharmaceutical forms for delivery include injectable and inhalation.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached on 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636