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 .
Claim Status
Claims 1-11 are pending and under examination.
Specification
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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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 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 1-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claims 1–11 are rejected under 35 U.S.C. § 101 as being directed to a judicial exception — a nature-based product (nucleotide/oligonucleotide sequences) — and do not recite additional elements that transform the claims into a patent-eligible application (“significantly more”). The claims recite nucleotide sequences (SEQ ID NOs 1–4 and a broad %-identity genus) and intended therapeutic uses that do not amount to significantly more than the judicial exception itself.
Analysis - MPEP 2106 Framework
The claims recite statutory subject matter being drawn to a composition of matter (i.e. nucleic acid product and composition thereof).
Step 1 — Are the claims “directed to” a patent-ineligible concept?
Claim language (representative, Claim 1): “An antisense oligonucleotide having the ability to reduce the expression level of the huntingtin protein in glioma cells, for its use in sensitizing the cells to an anti-cancer treatment, the antisense oligonucleotide being selected from … SEQ ID NOs: 1–4 and antisense oligonucleotides having a sequence identical to at least 50% with a sequence selected from SEQ ID NO:1–4.”
The claimed subject matter is a nucleic-acid product (antisense oligonucleotide, a sequence of nucleotides) and a genus defined by sequence identity to SEQ ID NOs 1–4. Claims to natural nucleotide sequences or their natural complements are directed to a product of nature unless the claimed subject matter has markedly different characteristics from what exists in nature. See MPEP 2106.04.
The claim recites a sequence-based product that, at least as drafted, encompasses nucleotide sequences that can be natural or naturally occur (or are direct complements of naturally occurring HTT mRNA sequences). The specification itself links SEQ ID NO:1 to RG6042, a known HTT-targeting ASO from the literature (spec ¶[0010]). The claim also explicitly includes sequences “having a sequence identical to at least 50%” of those SEQ IDs — a broad genus that plausibly embraces sequences that match naturally occurring HTT mRNA regions or its complements.
The recited therapeutic “for its use in sensitizing the cells to an anti-cancer treatment” is a statement of intended use/result and does not by itself impart structural or chemical distinctiveness to the claimed nucleotide product.
Conclusion of Step 1: The claims are directed to a judicial exception — a nature-based product (nucleotide sequences/antisense oligonucleotides or their complements). Such claims fall within the category of “products of nature” unless the claimed molecules are shown in the claim language to be “markedly different” from what occurs in nature (e.g., by novel chemical modifications or substantially different structural features). See MPEP 2106.04.
Step 2A, Prong 1 — Does the claim recite the judicial exception?
Yes. The composition claim recites nucleotide sequences (SEQ ID NOs and a percent-identity genus). That is the judicial exception (nature-based product).
Step 2A, Prong 2 — Does the claim integrate the exception into a practical application?
The claim’s only additional recitations beyond the sequence itself are (a) functional/utility language: “having the ability to reduce the expression level of the huntingtin protein in glioma cells” and “for its use in sensitizing the cells to an anti-cancer treatment,” and (b) a structural genus limitation (sequence identity percentage). The functional language describes what the oligonucleotide does (a biological activity) rather than defining a structural or processing limitation that materially alters the nature of the nucleotide itself. Under USPTO guidance and case law, merely reciting a natural product and stating what it can be used for (an intended use) does not integrate the exception into a practical application in a way that renders the claim patent-eligible. See Mayo and Alice; USPTO Step 2A Prong 2 examples.
The dependent claims recite further features (length 12–35 bases, ability to reduce MGMT, specification of alkylating agents, pharmaceutical composition). However, Claim 1 itself does not recite non-natural structural features (it does not require specific chemical backbone or sugar modifications). Where a claim recites only an unmodified or unspecified oligonucleotide sequence (or a broad identity genus), the claim does not tie the sequence to a novel structural manifestation that is “integrated” into a practical application. See MPEP 2106.04.
The specification does mention chemical modifications typical of therapeutic ASOs (phosphorothioate linkages; 2′-O-methoxyethyl at the ends) (spec ¶[0008]), but those modifications are not required by Claim 1’s text. Absent recitation of such distinguishing structural elements in Claim 1, the claim is not limited to chemically modified, non-naturally occurring sequences; therefore, it does not integrate the exception into a patent-eligible practical application.
Conclusion of Step 2A Prong 2: The claims to integrate the natural-product exception into a patent-eligible practical application because the claim: (i) is directed to a nucleotide sequence (judicial exception), and (ii) contains only intended-use and functional outcome language rather than reciting structural features or procedural steps that meaningfully constrain the claim.
Step 2B — If the claim does not integrate the judicial exception, do any additional
elements, individually or in combination, provide “significantly more” than the judicial exception? Standard: Additional elements must do more than recite routine, conventional activity well-understood in the art or mere field-of-use limitations and must add an inventive concept beyond the exception. MPEP 2106.
Claim 1 additional elements: (a) functional ability to reduce HTT expression; (b) intended use to sensitize to anti-cancer treatment; (c) selection from specified SEQ IDs and a percent-identity genus. All of these are either (i) intrinsic properties/functional effects of the sequence (i.e., predictable hybridization/inhibition of HTT expression), or (ii) an intended use/field-of-use limitation. Neither category is “significantly more.” The claim does not require: (a) a specific non-natural chemical modification pattern (e.g., it does not claim phosphorothioate backbone or 2′-O-MOE modifications), (b) a novel delivery modality, (c) a particular manufacturing/processing step that transforms the sequence into something markedly different, or (d) a concrete, unconventional application step that imposes a technological improvement beyond the natural correlation between nucleotide sequence and hybridization. See MPEP 2106.04.
The dependent claims (2–11) include limitations that could, if incorporated into the independent claim, be persuasive (for example: specifying phosphorothioate linkages and 2′-O-MOE modifications explicitly; specifying a pharmaceutical composition with defined excipient and dosing route; reciting a method of administration with specific technical steps). But as the claims stand, these additional elements are not present in Claim 1 in a manner that results in “significantly more.”
Conclusion of Step 2B: The claims lack additional elements that, individually or in combination, transform the nature-based exception into a patent-eligible application. The claims therefore fail Step 2B.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hung et al. (WO 2007/089584 A2; 9 August 2007).
Regarding Claims 1, 3, and 9, Hung et al. teach antisense oligonucleotide molecules for modulating huntingtin expression (see pg. 4-6, Summary; pg. 14-17, Pharmaceutical compositions). The reference teaches claimed SEQ ID NOs: 1, 2, and 3:
SEQ ID NO: 1 (as claimed)
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446
621
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SEQ ID NO: 2 (as claimed)
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261
634
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SEQ ID NO: 3 (as claimed)
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262
631
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Regarding Claims 2 and 4-11, such limitations appear to the functional properties of the claimed sequence structures which are inherently anticipated by the reference. Applicants disclose that antisense oligonucleotides SEQ ID NOs; 1-3 bind target mRNA and typically induce RNase H-mediated degradation of the target mRNA, resulting in reduced protein levels (see specification ¶¶ [0008] and [0010] describing ASO mechanism and examples).
If the prior art reference discloses an oligonucleotide whose sequence is complementary to a huntingtin (HTT) mRNA target region and discloses the same chemical form (or a form that necessarily functions similarly), then reduction of HTT expression in a relevant cell type is the direct consequence of that structure. In other words, HTT knockdown (and any downstream effects) is not a separate inventive limitation but an inherent consequence of the antisense sequence directed to HTT. MPEP § 2112.01 supports treating such functional results as inherent if they necessarily flow from the structural disclosure.
Claim(s) 1-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hung et al. (WO 2011/032045 A1; 17 March 2011).
Regarding Claims 1, 3, and 9, Hung et al. teach antisense oligonucleotide molecules for modulating huntingtin expression (see pg. 41-48, Antisense compounds). The reference teaches claimed SEQ ID NO: 4:
SEQ ID NO: 4 (as claimed)
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687
505
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Regarding Claims 2 and 4-11, such claims are anticipated for the same inherency reasons outlined in the 102 the rejection above (see “Hung et al. 2007”).
Prior Art Search
A search of USPTO sequence databases appeared to reveal multiple patent references that teach SEQ ID NOs: 1-4. The Examiner directs Applicants to the search result files located in the file wrapper (“SRCH” dated 2/13/2026 - particularly results from the Issued_Patents_NA and Published_Applications_NA_Main) for more information.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER M BABIC whose telephone number is (571)272-8507. The examiner can normally be reached Mon - Fri, 8:30 AM - 5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Yvonne Eyler can be reached at 571-272-0900. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633