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 .
Election/Restrictions
Applicant’s election without traverse of SEQ ID NOs:49-50 in the reply filed on September 9, 2025 is acknowledged.
Status of Claims
Claims 1-15 are currently pending and under examination on the merits in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 17, 2023 has been considered by the examiner. Note that the non-English language foreign patent document, ES 2637032 A1, is considered only insofar as the one-page English language translation, the bibliographic data, as submitted by applicant.
Specification
1. The abstract of the disclosure is objected to because it contains the form and legal phraseology often used in patent claims, such as “said,” which should be avoided. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
2. The specification discloses “Table 3”. See page 32. However, the format of the disclosure is not in a table format.
3. The specification contains sequence rule non-compliant subject matter. See Tables 2 and 4. Appropriate correction is required as instructed below.
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 sequences appearing in the specification, see Tables 2 and 4, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
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.
Claim Objections
Claims 1-8 and 13-14 are objected to because of the following informalities: “myocardial infarction (AMI)” should be “acute myocardial infarction (AMI)” in view of page 1 of the specification. Appropriate correction is required.
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 12 and 15 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.
Claims 9 and 10 each recite “wherein the interference RNA” in lines 1-2. There is insufficient antecedent basis for this limitation in the claims.
Claims 12 and 15 each recite “these oligonucleotides”. There is insufficient antecedent basis for this limitation in the claims. Note that claim 1 does not recite “oligonucleotides”, and furthermore, the word “these” is not normally used in U.S. Patent claims.
Claim Rejections - 35 USC § 112
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 1-15 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.
The instant claims are drawn to a method of treating LV dysfunction following AMI in a “human or animal subject” comprising administering an RNAi targeting Yy1 between 12 hours and 7 days after the onset of AMI.
The instant specification discloses that three doses of intravenous injection of “a mixture of 4 specific interference RNA sequences (compounds 1 to 4 of Table 3)”, which target the “mouse-specific Yy1”, into the AMI mouse model via tail vein injection administered within 3 or 7 days after AMI provided an increase in ejection fraction (EF) and fractional shortening (FS) compared to negative control (e.g., PBS and control siRNA)-treated AMI mouse model. See Examples 1-2.
It is noted that “compounds 1 to 4 of Table 3” corresponding to the siRNAs comprising SEQ ID NOs:1-2, SEQ ID NOs:3-4, SEQ ID NOs:5-6, and SEQ ID NOs:7-8 are targeted to the mouse Yy1. In fact, SEQ ID NO:3 for instance has no sequence homology with the human YY1 nucleotide sequence. As such, it is clear that the mixture of the four siRNAs designed to be “mouse-specific” cannot be reasonably deemed to have the required function of treating a human subject or any “animal” subject as recited in the claims. Further, the specification does not adequately describe that a single siRNA (e.g., SEQ ID NOs:3-4) would result in the same effects as provided by the mixtures of the four siRNAs. Furthermore, three doses of the mixture of the four siRNAs intravenously injected to the AMI mouse model via tail vein injection do not adequately represent the broadly recited “administering” step that reads on a single dose and other routes of administration. In addition to the insufficient written description support of the instant specification for the entire genus of the claims, it was known in the relevant art that overexpression, not inhibition or silencing, of YY1 by “an agonist of YY1” such as “a YY1 expression construct” is useful for treating “cardiac hypertrophy” associated with “recent myocardial infarction”, wherein cardiac hypertrophy is an adaptive response of “myocardial infarction”, wherein the agonist of YY1 results in the improvement in symptoms such as “increased cardiac ejection volume”, “increased cardiac output”, and “decreased left ventricular end diastolic pressure” as evidenced by Sucharov et al. (WO 2007/014029 A2). See pages 2 and 7; claims 1-18 and 46-54. In fact, the teachings of Sucharov are echoed by Jiang (WO 2021/021021 A1), who teach treating “myocardial infarction (MI)” comprising administering “a nucleic acid sequence encoding a YY1 protein”, thereby “increasing the level of the YY1 protein or a functional variant thereof in the cardiomyocytes of the subject to be treated.” See paragraphs 0077, 0079-0081, 0090; claims 1-7. That is, a method step (increasing YY1) that is completely opposite of the instantly claimed method step (decreasing YY1) was suggested to be useful for the claimed method before the effective filing date.
Even better, Asensio-Lopez et al. (Journal of Molecular and Cellular Cardiology, available online on April 15, 2019, 130:216-233, applicant’s citation) report that YY1 emerged as a “new” target than can provide cardioprotective effects in myocardial infarction. See abstract. See also page 232 disclosing that “the present study identifies the Yy1 transcription factor and HDAC4 as two potential pharmacological targets to prevent adverse cardiac remodeling following MI…Based on this increased understanding of the Yy1/HDAC4 system and cardiovascular diseases, the modulation of this system represents a possible novel therapeutic application in myocardial ischemic injury following MI.” (emphasis added). It is noted that page 232 also discloses, “The present study shows that manipulation of YY1 or its co-repressor HDAC4 might represent potential pharmacological targets to prevent adverse cardiac remodeling and progression to heart failure.” (emphasis added). As such, it is unequivocally clear that Yy1 was at best deemed a “potential”, “possible”, “novel” target for pharmacological/therapeutic application in treating cardiac injury/remodeling after MI as of the year of 2019. Hence, when the teachings of Sucharov, Jiang, and Asensio-Lopez are taken into consideration, one of ordinary skill in the relevant art would reasonably conclude that the state of the prior art and the level of knowledge pertinent to the instantly claimed subject matter, especially for treating a human subject following AMI by targeting YY1 were far from being well-known or well-established before the effective filing date, June 9, 2020, sought in the instant application. Therefore, the AMI mouse model examples pertaining to the tail vein injection of three doses of the four siRNAs (SEQ ID NOs:1-8) are not sufficient to represent and describe the entire genus of the claimed method.
In view of the foregoing, it is concluded that the instant specification fails to adequately describe the entire genus of the claims and also fails to reasonably convey that the instant co-inventors had possession of the entire genus as of the filing date sought in the instant application.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635