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 .
Application Status and Election
Claims 1, 9-10, 13, 15, 18, 24-25, 27, 29, 34, 36, 38, 40, 44, 50-51, 55, 63 and 68 are pending. Applicant’s election without traverse of species “inducing hair growth”, an ASO with SEQ ID NO 28 in the reply filed June 6, 2026 is acknowledged. Additionally, Examiner requested a telephonic election of an adjuvant, which was omitted from the restriction requirement mailed March 26, 2026. Applicant’s representative Ji Eun Kim (Reg # 68,504) elected vitamin B3 as the adjuvant. However, upon a full search of the prior art, a method of inducing hair growth with a miR-485 antisense inhibitor delivered with an adjuvant appeared free of the prior art. The species election requirements are withdrawn and all claims (1, 9-10, 13, 15, 18, 24-25, 27, 29, 34, 36, 38, 40, 44, 50-51, 55, 63 and 68) are under examination.
Claim Objections
Claims 1, 10, 24 and 63 are objected to because:
Claim 1 recites “administering to the subject a compound that inhibits miR-485 “miRNA inhibitor”. Claims 24 and 63 recite “administering to the subject a compound that inhibits miR-485 (“miRNA inhibitor”), wherein the miRNA inhibitor comprises the nucleotide sequence…” The claim language with “miRNA inhibitor” in quotations and parentheses is clunky and repetitive. Since the compound must inhibit miR-485 (claim 1) and comprise SEQ ID NO:28 (claims 24 and 63), it would be simpler delete reference to “miRNA inhibitor” such as: “administering to the subject a compound comprising a miR-485 inhibitor” for claim 1 and “administering to the subject a compound comprising an miR-485 inhibitor comprising SEQ ID NO: 28” for claims 24 and 63.
Claim 10 is missing the word “of” between “method” and “claim”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 55 and 63 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 55 recites “the method of claim 54…” However, claim 54 is a cancelled claim. Claim 55 is rejected as being incomplete because it depends directly from a canceled base claim. See MPEP 608.01(n)(V).
For the purpose of compact prosecution, claim 55 is interpreted as depending from claim 50.
Claim 63 recites a delivery agent comprises a cationic carrier unity comprising… wherein WP is a water-soluble biopolymer moiety; CC is a positively charged carrier moiety; AM is an adjuvant moiety… where the delivery agent further comprises a water-soluble biopolymer moiety with about 120 to about 130 PEG units, a cationic carrier moiety comprising a poly-lysine…, and an adjuvant moiety with about 5 to about 10 vitamin B.” The claim language is confusing because the claims recite a WP, a CC and an AM twice – once to define a formula and then a second time after “further”. It is not clear if the last wherein clause is limiting the WP, CC and AM genus, or if the agent is to contain two of each WP, CC and AM, one of each is generic and the second is specific.
If Applicant intends the last wherein clause to limit each of the WP, CC and AM genus, the following claim language is suggested: “wherein the WP comprises about 120 to about 130 PEG units, the CC comprises a poly-lysine with about 30 to about 40 lysines, and the AM comprises about 5 to about 10 vitamin B3.”
Claim 63 also recites “the cationic carrier unit forms a micelle with the miRNA inhibitor”. “the cationic carrier unit” lacks clear antecedent basis. Although a “positively charged” means “cationic”, it is not clear if “unit” is referring back to the “moiety” part. To overcome this rejection, Applicant is advised to use consistent claim language for elements of the compound and delivery agent.
Claim Rejections - 35 USC § 112(a)
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, 9-10, 13, 25, 27, 29, 34, 36, 38, 40, 44, 50-51, 55 and 68 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.
MPEP 2163.II.A3.(a).(i) states, “whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
For claims drawn to a genus, MPEP 2163.II.A3.(a).(ii) states, “written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species” where “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.”
The claims recite “a compound that inhibits miR-485, which represents a genus of molecules that are defined by their function of inhibiting miR-485 and not their structure. Some such inhibitors are described in the specification in paragraph [0119] as “a compound that can decrease, alter and/or modulate expression function and/or activity” of the miRNA. The Specification teaches that miRNA inhibitors can be polynucleotides sequences that are at least partially complementary to the target mRNA nucleic acid sequence. However, this is not a limiting definition and “inhibitor compounds” also include proteins like antibodies and small molecules. Also, there is no requirement for the inhibitor compound to directly bind/inhibit miR-485 and so the genus also includes inhibitors of genes/proteins that may regulate miR-485 expression. For the reasons described above, Applicant has not sufficiently described the structure of the genus of “miR-485 inhibitors” that is reflective of the variety and size of the genus.
Regarding nucleic acid-based inhibitors, the sequences of miR-485 is known and recited in the Specification (SEQ ID NO 1). Because there is a known correlation between the structure of antisense molecules and their inhibitory function, one skilled in the art could have predicted the structure of polynucleotides that directly hybridize to miR-485 and have the claimed inhibitor function. However, Applicants have not sufficiently described the genus of antibodies or small molecules that have the claimed miR-485 inhibitory function, or nucleic acids that may alter function of genes that regulate miR-485 such that one skilled in the art could have reasonably concluded applicants had possession of the genus as claimed.
Regarding proteins/antibodies, no antibody structure is recited that correlates to the claimed function of inhibiting miR-485. - To provide adequate written description and evidence of possession of the protein/antibody inhibitor genus, the instant specification in view of the art must structurally describe representative antibodies that function as an inhibitor, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). In the instant case, the Specification does not provide any antibody/protein by name or structure that directly or indirectly inhibits the expression or function miR-485. Additionally, a thorough search of the prior art did not uncover any antibody/protein by name or structure that directly or indirectly inhibits the expression or function miR-485
Although Applicants may argue that it is possible to screen for antibodies and proteins that function as claimed, the court found in that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,' not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibody yet to be discovered that may function as claimed.
Regarding small molecules, a diligent search of the prior and contemporaneous art revealed no teachings of any molecules known to inhibit miR-485 function or expression in any way, and the specification identifies none. Around the time of the filing date, skilled artisans understood that discovering small molecule inhibitors of proteins and/or nucleic acids generally was unpredictable. Wu observes that although computer-aided protein-inhibitor discovery technology was available, there is insufficient data to predict inhibitors of many proteins (Wu et al., Molecules (2019), 24: 4428, pages 1-14). Wu writes: [U]nder many circumstances, it is hard to find a [compound] library with functionally and structurally diverse molecules with quantitative activity data for a given protein. More importantly, the lack of publications with negative results hinders the identification of inactive molecules, resulting often in the development of qualitative common feature pharmacophores only from active compounds. Thus, supports a finding that skilled artisans expected genera of inhibitors of any other given biological molecule to be diverse and that as of the effective filing date, they would not have concluded that applicants possessed a representative number of species of small molecule inhibitors of miR-485.
Given the lack of representative examples to support the full scope of the miR-485 inhibitors encompassed by the claim, and lack of reasonable structure-function correlation with regards to the unknown sequences of antibodies, proteins, small molecules and indirect inhibitors that can inhibit miR-485 expression or function, the specification does not provide an adequate written description of molecules that inhibit miR-485 that is required to practice the claimed invention.
Dependent Claims
Claims 9-10, 13, 25, 27, 29, 34, 36, 38, 40, 44, 50 and 68 do not limit the class of compound such that the genus of the inhibitors is substantially reduced. Claims 25 and 27 require that at least one part of the compound has a nucleotide, but there is no requirement for the miR-485 inhibitor to be a polynucleotide and there is no limitation on any nucleotides in the compounds. As such, the claims are rejected for the reasons described above for claim 1.
Claim 68 also recites a series of administration routes including ophthalmic, intracerebrally, and intracranially. Applicants have not described how a miRNA inhibitor that is supposed to affect hair growth could function when delivered to the eye or into the brain. Applicant has only provided working examples of administration via intramuscularly (Example 2). Antisense oligonucleotides that affect hair growth have also been shown to be delivered intravenously and topically (Jin et al., International Journal of Molecular Sciences (2024), 25: 7612, pages 1-24). However, nucleic acids therapies that must function in the skin have not been previous delivered by the entire genus of routes recited in claim 68. Therefore, the skilled artisan would have not reasonably concluded that Applicant was in possession of the genus of administrate routes as claimed.
Allowable Subject Matter
Claim 24 is objected to. Claims 15 and 18 are 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 63 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
The closest prior art is Koh (Koh et al., "Reducing miR485-3p ameliorates Alzheimer’s disease pathology by regulation of amyloid beta and neuro-inflammation." (2020); of record). Koh teaches a miRNA-485 antisense oligonucleotide (ASO) inhibitor that is 100% identical to SEQ ID NO 28. However, Koh teaches using the ASO to reduce inflammation and neuronal loss in Alzheimer’s Disease. Koh does not teach the role of miR-485 in cells of the hair follicle or generally in hair loss and maintenance.
Yoshida (Yoshida et al., Biochemical and Biophysical Research Communications (2019), 516: 945-950) teaches dermal sheath cells are known to contribute to follicle neogenesis and hair formation through the promotion of angiogenesis (Abstract, page 950, ¶2-3). Yoshida also teaches the vascular-related gene CD36 is highly expressed in dermal sheath cells (Abstract). Yoshida teaches CD36-expressing cells participate in angiogenesis (Abstract), which occurs during maturation of hair follicles (page 950, ¶2). Yoshida teaches that angiogenic factors increase the hair growth and size of hair follicles (page 950, ¶3).
Lee (Lee et al., Molecular Medicine Reports (2015), 12: 1205-1212) teaches 5a-dyhyrotestosterone (DHT) inhibits PKC and regulates Bcl-2/bax expression, which leads to cell apoptosis, shortening of the hair cycle, reduction in hair grown and hair loss (page 1205, ¶3; Figure 1). Lee teaches miR-485 is upregulated 200-fold upon DHT treatment of dermal papilla cells (Table I; page 1206, ¶6).
Therefore, the prior art provides 1) a general teaching that CD36-expression in dermal sheath cells is correlated with a promoting angiogenesis and hair growth; 2) miR-485 is upregulated upon DHT treatment and DHT causes hair loss and apoptosis of cells; 3) miR-485 antisense inhibitors can reduce inflammation and apoptosis in neural cells. However, there is no teaching in the art connecting CD36 expression and miR-485 expression; and the link between hair growth and miR-485 expression is correlative, no causative. It is well known in the art that miRNAs can have different targets in different cell types leading to different overall phenotypes. See e.g., Erhand et al., Genome Research (2014), 24: 906-919. Thus, it is not predictable to extrapolate the function of a miRNA in one cell type like glial cells, to another cell type like dermal sheath cells. As such, it was not predictable that the miR-485 antisense inhibitor of Koh would have resulted in inducing hair growth, increasing hair density, increasing follicular density, increasing hair shaft thickness, increasing hair length, upregulating CD36 in dermal sheath hair follicles, or preventing/reducing hair loss. Each of the outcomes listed in claims 1, 24 and 63 were shown by Applicant to occur when the miR-485 antisense oligonucleotide is provided intramuscularly to mice.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE KONOPKA whose telephone number is (571)272-0330. The examiner can normally be reached Mon - Fri 7- 4.
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/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
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