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 claims 1-8 and 14-16 in the reply filed on July 22, 2026 is acknowledged.
Status of Claims
Claims 1-8, 11, and 13-18 are pending in the instant application. Claims 11, 13, and 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Accordingly, claims 1-8 and 14-16 are under examination on the merits in the instant case.
Information Disclosure Statement
The listing of references in the specification, see pages 25-26, is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
1. The abstract of the disclosure is objected to because the word “novel” is not descriptive of an invention. 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 sections of the specification are not arranged in proper order as provided in 37 CFR 1.77(b). For instance, “Detailed Description of the invention” must follow brief description of the drawings.
3. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See pages 25-26. 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.
Drawings
The drawings are objected to for the following:
1. The Figures, for instance Figure 1(A), fail to show the colors (e.g., red) described in the specification.
2. Figures 1(A) and 1(B) contain sequence rule non-compliant subject matter. Appropriate correction is required as instructed below.
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 sequences appearing in the drawings, see Figures 1(A) and 1(B), 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.
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 Objections
Claims 2-7 are objected to because of the following informalities: “An antisense oligonucleotide” and “an antisense oligonucleotide” should be “The antisense oligonucleotide” and “the antisense oligonucleotide”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: “A” in line 1 should be “The”. 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 1-8 and 16 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 1-8 and 16 recite that an antisense oligonucleotide “is complementary to a polynucleotide with the nucleotide sequence as set forward in SEQ ID NO: 1.” It is unclear what is meant by “set forward”. In addition, if the phrase “set forward in” is interpreted as “of”, the claims recite structurally conflicting limitations because the short antisense oligonucleotide (e.g., “8” nucleotides in length) cannot be complementary to the 3,195-nt sequence of SEQ ID NO:1.
Solely in the interest of compact prosecution, the limitation “a polynucleotide with the nucleotide sequence as set forward in SEQ ID NO: 1” will be interpreted as “a portion of SEQ ID NO: 1”.
Regarding claim 6, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-2, 4, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chenchik (WO 2016/172126 A2).
Chenchik discloses an 18-mer DNA oligonucleotide of 5’- CAGAACCCTCAGAGAGCA (SEQ ID NO:5078) in Figure 1 (page 31/101), which is 100% complementary to nucleotide positions 1736-1753 of SEQ ID NO:1 claimed in the instant case.
Since all structural limitations set forth in the claims as interpreted above are fully satisfied by Chenchik’s SEQ ID NO:5078, it necessarily follows that the prior art’s oligonucleotide would inherently possess the functional property for providing the intended use recited in the claims, absent objective evidence to the contrary.
“[T]he patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure.” Catalina Mkt. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002). That is, “[f]rom the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing.” In re Papesch, 315 F.2d 381, 391 (CCPA 1963).
See MPEP 2111.02: “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”.
It is found that the preamble reciting the purpose or intended use in the instant case does not structurally define or complete the oligonucleotide recited in the claim body. Hence, the intended use in the preamble does not result in a structural difference between the claimed invention and the prior art of Chenchik’s SEQ ID NO:5078.
In addition, note that the Office does not have the facilities and resources to provide the factual evidence needed in order to determine and/or compare the specific activities of the instantly claimed antisense oligonucleotide versus Chenchik’s oligonucleotide. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the claimed antisense oligonucleotide is different from the one taught by Chenchik, thereby establishing that the oligonucleotide of Chenchik cannot have the intended use, hence establishing patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ2d 1922(PTO Bd.Pat. App. & Int. 1989).
In view of the foregoing, claims 1-2, 4, and 14 are described by Chenchik et al.
Claims 1-2, 4, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Manoharan et al. (WO 2004/080406 A2).
The term “complementary” is defined to read on the complementary level of “90% to 100%” in the instant specification. See pages 3-4.
Manoharan discloses a 19-mer DNA oligonucleotide of 5’-TGAAATGCTGTTTTTTGGA (SEQ ID NO:1332), which is complementary to nucleotide positions 2893-2911 of SEQ ID NO:1 with one mismatch (see underlined). See Table 8 at page 262.
Since all structural limitations set forth in the claims as interpreted above are fully satisfied by Chenchik’s SEQ ID NO:1332, it necessarily follows that the prior art’s oligonucleotide would inherently possess the functional property for providing the intended use recited in the claims, absent objective evidence to the contrary.
Accordingly, claims 1-2, 4, and 14 are described by Manoharan et al.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-8 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over de Bruijn et al. (Journal of Medical Genetics, published online on July 6, 2020, 58:96-104, applicant’s citation) in view of NM_014722.3 (August 28, 2016) and Adanve et al. (US 2023/0272401 A1).
de Bruijn teaches that a mutant RIPOR2 sequence of “c.1696_1707del; NM_014722.3” is localized in cochlea hair cells and causes adult-onset hearing loss thus “is an attractive target for the development of a genetic therapy.” See pages 96 and 103.
de Bruijn does not teach targeting the mutant RIPOR2 sequence by an antisense oligonucleotide, which comprises SEQ ID NO:5 claimed in the instant case.
The nucleotide sequence information pertaining to NM_014722.3 discloses that the coding sequence begins at position 380. Hence, the “c.1696_1707del” in NM_014722.3 corresponds to positions 2075-2086 of NM_014722.3, wherein the nucleotide sequence containing positions 2075-2086 (see boxed) is reproduced below.
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34
772
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Greyscale
Adanve teaches that an antisense oligonucleotide that is 100% complementary to at least an 8-mer sequence within a target sequence is useful in inhibiting/reducing target expression/activity, wherein modified antisense oligonucleotides can comprise base modifications such as “8-oxoguanine” and 5-methylcytosine as well as sugar modifications such as 2’-O-methyl and 2’-MOE, wherein the oligonucleotides can be 20-mer “gapmers”. See paragraphs 0120, 0123, 0131-0132, 0136, and 0288; Table 7.
Adanve teaches that antisense oligonucleotides can be formulated as a pharmaceutical composition with a pharmaceutically acceptable carrier See paragraph 0167.
It would have been obvious to one of ordinary skill in the art before the effective filing date to make a chemically modified 20-mer gapmer targeting a 20-mer fragment having the deletion of “c.1696_1707del” (5’-CAGCTGGTCAAG) in NM_014722.3. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to make a composition that inhibits the art-recognized mutant RIPOR2 sequence responsible for hearing loss in adults because the nexus between the “c.1696_1707del; NM_014722.3” mutant RIPOR2 sequence and the adult onset hearing loss was known in the art thus suggested to be “an attractive target for the development of a genetic therapy” as evidenced by de Bruijn, and because a chemically modified 20-mer antisense gapmer having a 2’-sugar modification and/or base modifications including 8-oxoguanine was an art-recognized agent that inhibits target expression/activity in a sequence-specific manner as evidenced by Adanve. It would have been obvious to one of ordinary skill in the art to formulate the mutant RIPOR2-inhibitory antisense gapmer for cochlea administration in order to inhibit the expression/function of the hearing loss-causing mutant sequence because the mutant sequence causing hearing loss was known to be localized in the cochlea hair cells as taught by de Bruijn.
When making a 20-mer gapmer having the 12-mer deletion in the mutant RIPOR2 sequence, one of ordinary skill in the art would have reasonably identified a finite number of predictable, clearly identifiable 20-mer sequences targeting the 20-mer region having the 12-mer deletion in view of the publicly available nucleotide sequence information pertaining to “NM_014722.3”, wherein one of ordinary skill in the art would have reasonably identified 5’-GAAACATCACAAAG(12-mer deletion)AGGCTCACATCTGC beginning at position 2061 in “c.1696_1707del; NM_014722.3” mutant RIPOR2 sequence, thus would have reasonably pursued any one of the finite number of predictable, clearly identifiable 20-mer sequences encompassing the 12-mer deletion, thereby obtaining, for instance, 5’-GAAACATCACAAAGAGGCTC, 5’-AAACATCACAAAGAGGCTCA, 5’-AACATCACAAAGAGGCTCAC, and so forth, wherein a 20-mer antisense oligonucleotide sequence fully complementary to 5’-GAAACATCACAAAGAGGCTC is 5’-GAGCCTCTTTGTGATGTTTC, which is 100% identical to SEQ ID NO:5 claimed in the instant case.
In view of the foregoing, claims 1-8 and 14-16 taken as a whole would have been prima facie obvious before the effective filing date.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 4, 7-8, and 14-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
The claims recite a nucleotide sequence that is a fragment of a naturally occurring nucleic acid. For instance, the 15-mer sequence of 5’-TCTTTGTGATGTTTC, which is antisense to (or complementary to) nucleotide positions 1682-1696 of SEQ ID NO:1 (or positions 20-34 of SEQ ID NO:2), is present in human TMED8 sequence (NM_001346131.2); the 14-mer sequence of 5’-CTTTGTGATGTTTC, which is antisense to (or complementary to) nucleotide positions 1682-1695 of SEQ ID NO:1, is present in human CREBBP sequence (NM_004380.3); and the 14-mer sequence of 5’-GCCTCTTTGTGATG, which is antisense to (or complementary to) nucleotide positions 1686-1699 of SEQ ID NO:1, is present in human PPM1F sequence (NM_014634.4).
This judicial exception is not integrated into a practical application because the claims do not recite any structural limitations that change the fragments of the naturally occurring nucleic acids into a non-product of nature. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not recite any additional structural limitations that alter the fragments of the naturally occurring nucleic acids into those of non-naturally occurring nucleic acids. In addition, the “pharmaceutically acceptable excipient” and the intended use of “pharmaceutical” and “for administration into the cochlea” are mere general instructions to apply the judicial exception thus fail to amount to significantly more than the judicial exception.
See Univ. Of Utah Research Found. v. Ambry Genetics Corp., 113 USPQ2d 1241 (Fed. Cir. 2014) decided on December 17, 2014, wherein the Federal Circuit ruled that synthetic primers do not have a different structure from naturally occurring nucleic acids thus patent ineligible under §101. See also the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., 106 USPQ2d 1972 (June 13, 2013).
In view of the foregoing, claims 1-2, 4, 7-8, and 14-15 are patent ineligible under §101.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RAM SHUKLA can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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