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 Group I, claims 1, 16-26 in the reply filed on 05/15/2026 is acknowledged.
Claims 27-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/15/2026.
Species election of SEQ ID NOs: 12, 19, 36, 53, 54 is acknowledged.
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, 16-26 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.
Claims are broadly drawn to antisense oligonucleotides complementary to miR-134 and comprising affinity-enhancing nucleotide analogues.
Claims encompass a wide genus of affinity-enhancing nucleotide analogues.
Instant specification teaches that LNA and CRN are affinity-enhancing nucleotide analogues (see paragraphs [0071, 0082]) so as some other analogues (see paragraph [0090]). There is no definition of what structural features of nucleotide analogues make them affinity-enhancing.
Prior art teaches that there are variety of ways to increase affinity of nucleotides to target. For example, Wan et al (Journal of Medicinal Chemistry, 2016, 59: 9645-9667) teach that specific base modifications can increase nucleotide affinity (see Section 3 “Nucleobase modifications”) and some backbone modifications can increase affinity as well (see Section 4 “Backbone modifications”). Thus, the genus of affinity-enhancing nucleotide analogues is a lot wider than LNA and CRN described in instant disclosure.
Specification does not describe structure for representative species of Applicant's broadly claimed genus. Thus, their function of being affinity-enhancing is either unknown or unpredictable.
The genus encompasses a large number of unknown structures and one of skilled in the art cannot reliably predict which member of the genus would be affinity-enhancing, and which will not. There is no description of the necessary and sufficient elements of the species encompassed by the breadth of the claims.
The only species described in specification are LNA and CRN. Applicant fails to describe representative members of Applicant's broadly claimed genus.
One of the skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus in view of the disclosed species. Since the disclosure fails to describe the common attributes that identify members of the genus, and because the genus is highly variant, LNA and CRN are not sufficient to describe the claimed genus. Therefore, given the lack of written description in the specification with regard to the structural and functional characteristics of the claimed compositions, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 23 and 24 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 23 and 24 originally depend on claim 1, which recites oligonucleotide not comprising more than three contiguous DNA nucleotides. Both claims though comprise oligonucleotide of SEQ ID NO: 36, which has 4 contiguous DNA nucleotides, nucleotides 2-5. Thus, claims 23 and 24 fail to include all the limitations of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 16-22, 25-26 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kielpinski et al (WO 2020/038968, February 2020, cited from IDS).
Concerning claims 1, 16-19, 21-22, 25 Kielpinski disclose antisense oligonucleotide targeting miR-134 of SEQ ID NO: 5 (see Table 1 on page 15), 19 nucleotides long, with nucleotides 2-19 identical to instant SEQ ID NO: 4: CCTCTGGTCAACCAGTCAC (SEQ ID NO: 5). Such oligonucleotide is fully complementary to instant SEQ ID NO: 3, which is an exact complement of instant SEQ ID NO: 4. Kielpinski disclose that the oligonucleotide can be fully phosphorothioated (see line 9 on page 15), can include LNA nucleotides such as beta-D-oxy LNA and cytosines can be 5-methyl cytosines (see lines 10-11 on page 15). LNA nucleotides are enhanced affinity nucleotides (see page 24). Further Kielpinski disclose that the oligonucleotide can be a mixmer with LNA nucleotides located at every second or every third position of the oligonucleotide and remaining nucleotides can be DNA or 2’MOE or 2’ fluoro nucleotides (see last paragraph on page 28). Placing LNA nucleotide in each second position of SEQ ID NO: 5 leads to 47% of mixmer being LNA, replacing 9 nucleotides with LNA.
Concerning claim 20 Kielpinski disclose that two terminal nucleotides at 3’ end of mixmer can be LNA (see lines 3-7 on page 29).
Concerning claim 26 Kielpinski disclose pharmaceutical compositions of oligonucleotides disclosed (see bridging paragraph between pages 15 and 16).
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kielpinski et al, above.
Teachings of Kielpinski are discussed above. It is noted that oligonucleotide of SEQ ID NO: 5 taught by Kielpinski is of identical unmodified sequence as instant SEQ ID NOs: 19, 53-54. Kielpinski further teach that mixmers of the invention can be designed in a variety of ways including repeating patterns for LNA location and locating LNA at fixed positions (see bridging paragraph between pages 28 and 29).
Kielpinski do not teach antisense oligonucleotides with modifications as in instant SEQ ID NOs: 19, 53-54.
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to design a variety of mixmers based on SEQ ID NO: 5 of Kielpinski, arriving at instant invention. One of the ordinary skill in the art would be motivated to do so to design and identify the most effective antisense oligonucleotides targeting miR-134 based on teachings of Kielpinski. A person of ordinary skill in the art would have been motivated and expected reasonable success to modify the mixmer antisense oligonucleotide of Kielpinski to comprise various combinations of nucleotide modifications, such as from seven to 14 LNA and does not contain a stretch of more than three contiguous DNA nucleotides as in instant SEQ ID NOs: 19, 53-54 since such is a matter of design choice as taught by Kielpinski made during the course of routine optimization and experimentation. That is, one of ordinary skill in the art could determine by routine experimentation the types and patterns of modified nucleosides to incorporate into an antisense mixmer compound to confer a desired property or optimization for a specific utility. A person of ordinary skill in the art would have expected reasonable success to devise the mixmer antisense oligonucleotide as instantly claimed using the disclosure of Kielpinski as a blueprint for making chemically modified antisense oligonucleotides targeting miR-134.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EKATERINA POLIAKOVA whose telephone number is (571)270-5257. The examiner can normally be reached Mon-Fri 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571)272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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