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 response and claim amendments filed on 8/21/2026 are received and entered.
In response to the most recent action, claims 1, 4, 6-19, and 35 have been amended and claims 2, 3, and 5 have been canceled. No new claims have been added.
Claims 1, 4, 6-19, and 35 are currently under examination of the merits.
Any rejections/objections NOT repeated/presented here are withdrawn.
Maintained Objections/Rejections
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Response to Arguments
Applicant’s amendments of the drawings have alleviated the clarity issue of Figs. 1-12. However, color is still present in the replacement sheet and drawing supplemental, filed on 8/21/2026 and 7/18/2023, respectively. No petition for colored drawings or photographs have been filed in the instant application.
Specification
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.
Response to Arguments
Applicant amends http://www.mirbase.org to www.mirbase.org, which is still browser-executable (see paragraph 0220).
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 9 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.
Regarding claim 11, applicant does not disclose in the claims, or the instant specification, the units associated with molecular weight. It is unclear what the units of the molecular weights recited in the instant claims refers to.
New Objections/Rejections
Claim Objections
Claim 35 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
Claims 1, 4, 6-19, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Hoge et al. (WO 2014/113089 A2, published 7/24/2014) in view of Shim et al. (EP 3,505,630 A1, published 7/3/2019), Zhang et al. (Use of small RNA as antiaging cosmeceuticals, J. Cosmet. Sci, Issue 64, pgs. 455-468, published 2013), Ottoman et al. (MicroRNA expressions associated with progression of prostate cancer cells to antiandrogen therapy resistance, Molecular Cancer, Volume 13, Issue 1, all pages, published 1/3/2014), Ghassemi et al. (The effect of GGC and CAG repeat polymorphisms on the androgen receptor gene in response to finasteride therapy in men with androgenetic alopecia, Journal of Research in Medical Sciences, Volume 24, Issue 104, all pages, published 12/23/2019), and Ashique et al. (A Systematic Review on Topical Marketed Formulations, Natural Products, and Oral Supplements to Prevent Androgenic Alopecia: A Review, Natural Products and Bioprospecting, Volume 10, Issue 6, pgs. 345-365, published 10/4/2020).
Regarding claims 1 and 4, Hoge teaches an isolated signal-sensory polynucleotide comprising a region encoding an oncology-related polypeptide of interest that functions, when translated to send a death or survival signal. Such death or survival signals include those which alter (increase or decrease) the expression of one or more proteins, nucleic acids, or non-coding nucleic acids, or alter the binding properties of biomolecules within the cell, and/or perturb the cellular microenvironment in a therapeutically beneficial way (see paragraph 0011). Hoge teaches miRs and their binding sites in Table 9, wherein the section below Table 9 discloses miR-3199. Hoge further teaches SEQ ID NO: 3105 which has 100% identity and length to SEQ ID NO: 15 and SEQ ID NO: 4126 which has 100% identity and length to SEQ ID NO: 16.
Regarding claims 1 and 4, Hoge does not teach wherein the composition of claim 1 is a double stranded oligonucleotide construct comprising a hydrophilic and hydrophobic materials or a structure disclosed as formula (1).
Regarding claim 35, Hoge does not teach where the double-stranded oligonucleotide construct is in a cosmetic composition selected from the group consisting of hair products.
Regarding claim 1 and 4, Shim teaches wherein the double-stranded oligo RNA structure comprising at least one miRNA is represented by formula (1): A-X-R-Y-B (see paragraph 0016).
Regarding claims 6, Shim teaches where the hydrophilic material is represented by (A)n, (Am-J)n, or (J-Am)n, in which A represents a hydrophilic material monomer, n represents 1 to 200, m represents 1 to 15, and J represents a linker that links m hydrophilic material monomers to another, or links m hydrophilic material monomers to oligonucleotides (see paragraph 0051).
Regarding claim 7, Shim teaches wherein the hydrophilic material may be a cationic or non-ionic polymer material having a molecular weight of 200 to 10,000 (see paragraph 0055).
Regarding claim 8, Shim teaches where RNA oligos are simply bonded to a hydrophilic substance polyethylene glycol (PEG) as a biocompatible polymer (see paragraph 0013).
Regarding claim 9, Shim teaches where the preferred hydrophilic material monomer structure is compound (1), where G is selected from CH2, O, S, or NH) (see paragraph 0059 and Table 1).
Regarding claim 10, Shim teaches where the linker (J) is preferably selected from the group consisting of PO3-, SO3, and CO2 (see paragraph 0061).
Regarding claim 11, Shim teaches where the hydrophobic material (B) has a molecular weight of 250 to 1,000 (see paragraph 0065).
Regarding claim 12, Shim teaches where the hydrophobic material may be a steroid derivative, a glyceride derivative, glycerol ether, polypropylene glycol, C12-C50 unsaturated or saturated hydrocarbon, etc. (see paragraph 0066).
Regarding claim 13, Shim teaches where the sterol derivative is selected from the group consisting of cholesterol, cholestanol, cholic acid, cholestanyl formate, and cholesteryl amine (see paragraph 0067).
Regarding claim 14, Shim teaches where the glyceride derivative is selected from mono-, di-, and tri-glycerides and the like (see paragraph 0067).
Regarding claim 15, Shim teaches where the covalent bond or linker-mediated covalent bond (X or Y) may be non-degradable or degradable bond (see paragraph 0070).
Regarding claim 16, Shim teaches where the non-degradable bond can include an amide or a phosphoryl bond (see paragraph 0070).
Regarding claim 17, Shim teaches where the degradable bond includes a disulfide bond, an acid-degradable bond, an ester bond, an anhydride bond, a biodegradable bond, or an enzyme-degradable bond (see paragraph 0070).
Regarding claim 18, Shim teaches where the composition of treating cancer comprising the miRNA as an active ingredient may be a pharmaceutical composition (see paragraph 0080).
Regarding claim 19, Hong and Shim does not teach where the composition of claim 1 and the composition of claim 19 is a cosmetic composition.
Regarding claim 19, Zhang teaches the use of small RNAs, specifically small interference RNA and microRNA, as new cosmeceutical ingredients (see abstract). Zhang discloses in the abstract that several skin care companies have released new small RNA products in the cosmetic market and reviews the latest and most advance approaches and strategies of using small RNA as antiaging cosmetics, including investigations on aging-related genes that small RNA target, method of delivering them, and challenges in the development of RNAI-based therapeutics for skin care cosmeceuticals (see abstract).
Regarding claim 35, Ottoman teaches microRNAs used to target the androgen receptor (AR) and discloses has-miR-3199 in Table 2.
Regarding claim 35, Ghassemi teaches where androgenic hair loss is associated with high levels of DHT and also increased expression of the androgen receptor gene (see introduction).
Regarding claim 35, Ashique teaches a review of topical hair products and oral supplements to prevent androgenic alopecia (see abstract and introduction), which includes creams (see Table 7).
It would have been obvious to one with ordinary skills in the art, before the effective filing date of the claimed invention, to have combined the teachings of Hoge, Shim, and Zhang to arrive at a composition, for use in a cosmetic product, comprising of miR-3199 with a structure of formula (1) A-X-R-Y-B, comprising of hydrophilic and hydrophobic materials, linkers, and bonds. A skilled artisan would further modify the combined arts with the teachings of Ottoman, Ghassemi, and Ashique to arrive at a cosmetic composition that consists of a hair product, such as a cream.
One would expect a reasonable chance of success as Shim shows the structure of formula (1) can be used to effectively deliver miRNA into cells to observe an effect. For a working example, Shim discloses tumor cells administered with certain miRNAs resulted in almost no cluster formation (see paragraph 0090). Though Shim is directed towards cancer, the structural formula of Shim, which the instant claims recite, discloses a tested use for the efficient delivery of any miRNA, wherein substituting miR-3199 of the instant application would merely be combing prior art elements of known methods and a simple substitution to yield predictable results. See MPEP § 2143(I)(A) and (B).
Furthermore, Zhang discloses that microRNAs are used in cosmeceutical products as ingredients and Ottoman teaches that miR-3199 is specifically targeted to the AR gene, which Ghassemi discloses the AR gene is a facilitator of hair loss. Ashique teaches that hair loss treatment is commonly made in the form of hair creams, shampoos, or other products. Therefore, as miR-3199 is already disclosed in the art to target the AR gene, which is associated with hair loss, and hair loss treatments typically comprise of administered creams or shampoos, the combination of such elements is merely combining known prior art elements to yield predictable results, absent evidence to the contrary. See MPEP § 2143(I)(A).
One would be motivated to do so as Hoge and Shim both disclose miRNA can be used to send signals to cells in order to alter the expression of one or more proteins, nucleic acid, or non-coding nucleic acids (see Hoge, Summary of the Invention). Shim discloses that the unique features of miRNA, such as the ability for miRNA to be produced in many ways, miRNAs can be configured to the bind to the coding region or the 5’- and 3’-UTR of a coding region (primarily binding to the 3’-UTR) whereas siRNAs cause degradation of target mRNAs regardless of 5’-UTR, 3’-UTR and coding parts, and since miRNAs target using seed region sequences with limited size, the entire miRNA does not have to be perfectly complementary to the target gene. MiRNAs can simultaneously control several types of mRNA with one miRNA. This is useful where miRNAs simultaneously inhibit the expression of many cancer-inducing genes (see paragraph 0008 of Shim).
Furthermore, Shim discloses where there needs to be an effective method for transferring miRNAs without the degradation of miRNAs in the living body (see paragraph 0012). To improve intracellular delivery efficiency of RNA oligos, techniques for securing the stability of oligos and securing efficient cell membrane permeability through oligo conjugates wherein the RNA oligos are simply bonded to a hydrophilic substance with a covalent bond or linker-mediated covalent bond have been developed. To further solve the drawbacks of low in vivo stability and non-favorable delivery to target organs, double-stranded oligo RNA structures which hydrophilic and hydrophobic substances are bonded to double-stranded oligo RNAs are disclosed (see paragraph 0012 and 0013).
Though Hoge and Shim do not mention treating hair loss or promoting hair growth with miRNA, it is well known in the art that hair loss, or androgenetic alopecia, is hereditary and caused by genetic factors evidenced by Paul et al. (Current insight into the functions of microRNAs in common human hair loss disorders: a mini review, Human Cell, Volume 34, pgs. 1040-1050, published 2021), where Paul discloses miRNAs for use of treating human hair loss.
Applicant is reminded that the preamble carries patentable weight only when necessary to define essential features of the invention and not intended use (see MPEP § 2111.02), and since the entire structural limitations of the invention are disclosed in Hoge and Shim, miR-3199 can alter the genes associated with hair loss as it is an inherent function of the taught structure.
One would be motivated to modify miR-3199 disclosed in Hoge with the composition taught by Shim, to be inserted in a cosmetic product, taught by Zhang, to alter the expression of various genes associated with hair loss as a treatment, to target anti-aging, and to effectively deliver the miRNA in a composition that offers higher in vivo stability and favorable delivery to target organs.
In view of the foregoing, claims 1, 4, 6-19, and 35 are rejected under 35 U.S.C. 103 as being prima facie obvious, before the effective filing date.
Response to Arguments
Applicant’s arguments have been fully considered but are not found persuasive. Applicant argues that Hoge does not disclose or suggest the applicant’s claimed double-stranded oligonucleotide construct. Applicant argues Shim and Zhang merely describe “cancer cell death signaling” and “general RNA” carriers and Shim and Zhang do not disclose or imply in any way that the applicant’s claimed double-stranded oligonucleotide construct would or could act on human hair follicle cells to promote melanin production and stimulate hair growth. Furthermore, none of Hoge, Shim, and Zhang disclose use “for alleviating hair graying, promoting hair growth, and/or preventing or alleviating hair loss”.
Applicant provides examples of use for the composition with resulting effects such as melanin synthesis (example 2), a clear color change confirmed by the expression of MITF, which is a key transcription factor of melanin (example 5), and where expression of MITF was significantly increased in the nuclease and the expression of TYR was greatly increased in the cytoplasm with melanosomes (Fig. 9D). Furthermore, applicant points to Fig. 10C-D and Fig. 11A-C to disclose the effects of the miR-3199 double-stranded oligonucleotide construct when administered to hair follicles.
Examiner argues that while the specific structure of the double stranded oligonucleotide is not taught by Hoge, Hoge still anticipates the miRNA of the claimed invention, in its entirety. Shim alleviates this discrepancy by providing the exact structural formula of Formula (1), before the effective filing date of the claimed invention, and also recites wherein the double-stranded oligo RNA structure comprising at least one miRNA is represented by formula (1): A-X-R-Y-B (see paragraph 0016 of Shim). A skilled artisan would recognize that the formula of Shim requires a miRNA, wherein one could substitute the known miR-3199 of Hoge. MiR-3199 of Hoge is an art recognized equivalent of “at least one miRNA” of Shim, as both are microRNAs that serve the same purpose of inhibiting gene expression, therefore substitution of the two would have been predictable (See MPEP § 2144.06).
Though neither Hoge, Shim, or Zhang describe miR-3199 does not disclose or imply in any way that the applicant’s claimed double-stranded oligonucleotide construct would or could act on human hair follicle cells to promote melanin production, applicant is reminded that regarding a composition claim, in the event a structure is recited in the reference or references is substantially identical to that of the claims, the claimed properties or functions are presumed to be inherent, see MPEP § 2112.01. As the structure is disclosed to 100% identity, the use of miR-3199 to treat hair loss is presumed to be an inherent function of the structure.
Applicant recites examples 2 and 5, as well as the listed tables (Table 5) and figures (Figs. 7-11) that support melanin synthesis, and the expression of major genes, proteins, and transcription factors associated with melanin production, the increase of melanin, or the increase or decrease of gene expression to support the intended use of the claimed invention, however, these are NOT claimed embodiments. Applicant only disclose the intended use of the composition of claim 1 to recite “for alleviating hair graying, promoting hair growth, and/or preventing or alleviating hair loss, administered or applied to human hair follicles”, which examiner argues is an inherent function of the composition, as the combined teachings of Hoge and Shin render the composition obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID YU whose telephone number is (571)272-1118. The examiner can normally be reached Monday-Friday 7:30 am -5 pm.
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/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
