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
Request for Continued Examination Under 37 CFR 1.1143
A request for continued examination (RCE) under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission mailed on March 9, 2025 has been entered.
Claim 12 has been canceled. Claim 1 has been amended.
Claims 1-11 are pending in the instant application.
Accordingly, claims 1-11 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Arguments
Applicant's Amendment and Response filed March 9, 2025 has been considered. Rejections and/or objections not reiterated from the previous Office Action mailed October 9, 2024 are hereby withdrawn. Any arguments addressing said rejections and/or objections are moot. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Drawings
In the previous Office Action filed October 9, 2024, the Drawings were objected to because some Drawings referenced the colors, “blue”, “green” and “red” without an accompanying petition. This objection is withdrawn in view of Applicant’s Petition to accept Color Drawings filed September 16, 2024. It is noted that the Petition has been GRANTED. See Petition Decision filed October 17, 2024.
Claim Rejections - 35 USC § 103
In the previous Office Action filed October 9, 2024, claims 1-12 were rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/201301 A1 (hereinafter, “WO '301”) in view of Jenny et al. (RNA BIOLOGY, Vol. 14, no. 5, 1 June 2016: 500-513) and further in view of Wang et al. (JOURNAL OF BIOLOGICAL CHEMISTRY, Vol. 284, no. 34, 21 August 2009, pages 23094-23106). This rejection is moot against claim 12 in view of Applicant’s Amendment filed March 9, 2025 to cancel claim 12. This rejection is maintained against claims 1-11 for the reasons of record set forth in the previous Office Action mailed October 9, 2024.
Response to Arguments
In response to this rejection, Applicants traverse and argue that the cited combination does not teach or suggest "administering to a subject an oligonucleic acid agent directed at and capable of specifically inhibiting and/or degrading the microRNA miR27b-5p, wherein the inhibition and/or degradation of miR27b-5p leads to an increase in Atp5a1 mRNA in cardiomyocytes," as now recited in claim 1. Applicants submit that there is no suggestion in WO '301 or in any of the other cited references of an increase in Atp5a1 mRNA in cardiomyocytes resultant from miR-27b targeting as now claimed.
Applicants also argue that neither WO '301 nor any of the other cited references teach or suggest treating heart disease associated with reduced or absent mitochondrial Complex V (ATP Synthase) activity as presently claimed.
Further, Applicant submits that the skilled artisan would not have been motivated to examine miR-27b-5p in light of WO '301 because WO '301 suggests the development of agents that target miR-27b-3p and the experimental data in WO '301 are gathered by targeting miR-27b-3p. Applicants point the Examiner to paragraphs [0047] and [0048]. Applicants argue that there is no disclosure relevant to hsa-miR-27b-5p and no sequences relevant to miR-27b-5p are provided. Applicants also argue that given the experimental data in WO '301 as it relates to only miR-27b-3p, there is no rationale for making the switch to a different mature miRNA (e.g. miR-27b-5p) with potentially completely different effects.
Applicants next argue that even if the skilled artisan had investigated miR-27b-5p within the context of WO '301, they would have examined its effects on LDL-C and HDL-C since WO '301 makes no mention of effects on Atp5a1 mRNA in cardiomyocytes, nor any suggestion that Atp5a1 could be relevant to disease. Applicants argue that neither Jenny et al. and/or Wang et al. make mention of Atp5a1 mRNA in cardiomyocytes, nor any suggestion that Atp5a1 is relevant to disease. Applicants submit that the combination of WO '301 with Jenny et al. and/or Wang et al. do not provide one of skill in the art any teaching or suggestion that would make it obvious to target miR-27b-5p as a way to increase Atp5a1 mRNA in cardiomyocytes, and thereby treat heart disease associated with reduced or absent mitochondrial Complex V (ATP Synthase) activity.
Applicants conclude that the combination of WO '301, Jenny et al., and Wang et al., neither describe the claimed invention nor would lead one of skill to develop the claimed invention, which is accordingly non-obvious over the combined cited references. Applicant requests withdrawal of this rejection.
Applicant’s traversal has been fully considered by the Examiner, however it is not found to be persuasive. The Examiner agrees that WO '301 makes reference to miR-27b-3p and not necessarily miR-27b-5p. However, the claims are drawn to a method for treatment or prevention of heart disease comprising: administering to a subject an oligonucleic acid agent directed at and capable of specifically inhibiting and/or degrading the microRNA miR27b-5p (emphasis at underline). WO '301 teaches anti-mir-27b oligonucleotides as therapeutic tools for treating dyslipidemias and cardiovascular diseases (emphasis at underline). WO '301 teaches the anti-miR-27b oligonucleotides of their invention are SEQ ID NOs: 34 and 54. It should be noted that SEQ ID NO: 34 of WO '301 is fully comprised within SEQ ID NO 002 of the present invention. Given this fact, SEQ ID NO: 34 of WO '301 is directed at and capable of specifically inhibiting and/or degrading the microRNA miR27b-5p as recited and required in the present claims.
Regarding claim 1 as now amended to recite, wherein the inhibition and/or degradation of miR27b-5p leads to an increase in Atp5a1 mRNA in cardiomyocytes, it should be noted that any underlying mechanism of action would naturally flow and be inherent to administration SEQ ID NO: 34 to a subject. That is, administration of SEQ ID NO: 34 of WO '301 would necessarily lead to an increase in Atp5a1 mRNA in cardiomyocytes in the subject, absent some evidence to the contrary. The Examiner directs Applicant to MPEP 2112 with respect to and emphasis on inherency.
Regarding claim 1 as now amended to recite, wherein the heart disease is associated with reduced or absent mitochondrial Complex V (ATP Synthase) activity, WO '301 are explicit in teaching that the cardiovascular diseases of their invention include conditions associated with coronary heart disease. It should be noted that Google AI Overview downloaded from cardiomyopathy and coronary heart disease and mitochondrial complex V activity - Google Search on October 23, 2025 discloses:
Mitochondrial complex V deficiency can lead to cardiomyopathy by impairing the heart's ability to produce energy, and both genetic and acquired cardiomyopathies are linked to broader mitochondrial dysfunction. While complex V deficiency can cause hypertrophic cardiomyopathy, coronary heart disease, particularly ischemic cardiomyopathy, also involves significant mitochondrial dysfunction and damage. In both scenarios, the impaired mitochondrial function can lead to a buildup of reactive oxygen species, cell damage, and heart failure.
Before the effective filing date of the claimed invention, the treatment of heart disease using anti-miR-27b oligonucleotides for the therapeutic use in treating cardiovascular disease was known. Before the effective filing date of the claimed invention, a method for treatment or prevention of heart disease comprising: administering to a subject an oligonucleic acid agent directed at and capable of specifically inhibiting and/or degrading the microRNA miR27b-5p was taught and suggested in the prior art of WO '301. WO '301 teach an oligonucleic acid agent directed at and capable of specifically inhibiting and/or degrading the microRNA miR27b-5p of the present invention. See WO '301, SEQ ID NO: 34. The administration of SEQ ID NO: 34 would inherently lead to an increase in Atp5a1 mRNA in cardiomyocytes in the subject, absent evidence to the contrary.
The Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
Turning to the facts, the presumption of obviousness applies here, and none of the means for rebutting it has been shown. In view of the foregoing, when all the evidence is considered, the totality of the rebuttal evidence of non-obviousness fails to outweigh the evidence of obviousness made of record. Thus, it is maintained that the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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.
Claims 5 and 7-9 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 pre-AIA the applicant regards as the invention.
The term, “particularly” in the claims is indefinite. This term is indefinite because it is not a precise term. Furthermore, words like "particularly" are subjective and can be interpreted differently by individuals, leading to ambiguity about the claim's exact scope. MPEP § 2173.02 (II) states that one of the purposes of examination under 35 USC § 112, second paragraph is to determine whether the claim apprises one of ordinary skill in the art of its scope and, therefore, serves the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent. See, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). See also In re Larsen, No. 01-1092 (Fed. Cir. May 9, 2001) (unpublished). If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. See Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993). In this case, there is no “bright line” by which to evaluate the term, “particularly” and so the claims are indefinite since one of skill in the art could not interpret the metes and bounds of the claims.
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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 1-11 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 claims are drawn to a method for treatment or prevention of heart disease comprising: administering to a subject an oligonucleic acid agent directed at and capable of specifically inhibiting and/or degrading the microRNA miR27b-5p, wherein the inhibition and/or degradation of miR27b-5p leads to an increase in Atp5a1 mRNA in cardiomyocytes thereby treating or preventing the heart disease, wherein the heart disease is associated with reduced or absent mitochondrial Complex V (ATP Synthase) activity.
The Specification discloses:
The present invention is based upon the discovery that the inhibition of miRNA miR27b-5p through administration of an oligonucleic acid agent (SEQ ID NO 001)
Provided in the instant application is an miR27b-5p oligonucleic acid agent inhibitor which comprises, or essentially consists of SEQ ID NO 001. Also provided is SEQ ID NO 002 (miR27b-5p).
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a “sufficient number” of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The present Specification discloses working examples wherein mice treated with miR27b-5p LNA exhibited improved cardiac function and partial reversion of hypertrophic growth. See Figures 2l-p and Table 3, for example. Applicant is reminded that the instant application teaches SEQ ID NO 001 and SEQ ID NO 002 as miR27b-5p oligonucleic acid agent inhibitors.
The prior art teaches anti-mir-27b oligonucleotides as therapeutic tools for treating dyslipidemias and cardiovascular diseases. See WO 2014/201301 A1 (submitted and made of record on the Information Disclosure Statement filed December 27, 2020) (hereinafter, “WO '301”). WO '301 disclose two anti-mir-27b oligonucleotides agents that function in their invention, SEQ ID NOs: 34 and 54. Applicants should note that SEQ ID NO: 34 of WO '301 is fully comprised within SEQ ID NO. 002 of the present invention. For further explanation, see 35 USC § 103 rejection above.
The limited species of miR27b-5p oligonucleic acid agent inhibitors disclosed in the present Specification and the prior art which function as claimed does not satisfy the genus of the present claims. See In re Gostelli 872, F.2d at 1012, 10 USPQ2d at 1618, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus.
The entire genus of oligonucleic acid agent directed at and capable of specifically inhibiting and/or degrading microRNA miR27b-5p, wherein the inhibition and/or degradation of miR27b-5p treats or prevents heart disease 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 prior 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 oligonucleic acid agent miR27b-5p inhibitors 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.
In conclusion, the Specification and the prior art as filed does not provide sufficient descriptive support for the myriad of oligonucleic acid agents directed at and capable of specifically inhibiting and/or degrading microRNA miR27b-5p, wherein the inhibition and/or degradation of miR27b-5p treats or prevents heart disease embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
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.
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/TERRA C GIBBS/ Primary Examiner, Art Unit 1635