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
This Office Action is a reply to Applicant’s Preliminary Amendment filed September 25, 2023.
Claims 2-15 have been canceled. New claims 16-29 are acknowledged. Claim 1 has been amended.
Claims 1 and 16-29 are pending in the instant application.
Claims 1 and 16-29 have been examined on the merits as detailed below:
Priority
Acknowledgment is made of Applicant's claim for foreign priority based on PA202170146 filed 03/26/2021. The certified copy has been placed in the file.
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed September 25, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
The Drawings filed on September 25, 2023 are acknowledged and have been accepted by the Examiner.
Nucleotide Sequence Disclosures
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. §1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. §1.821-1.825 for the reason(s) set forth below or on the attached Notice To Comply with Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures. The disclosure contains sequences which fall under the purview of 37 CFR 1.821 through 1.825 as requiring SEQ ID NOs., but which are not so identified. For example, see Table 2. This is an example and does not indicate that the Examiner has made an exhaustive review of the application. Applicant must fully comply with the sequence rules for any response to this action to be considered fully responsive.
Claim Interpretation
Claim 27 recites, “prophylaxis treatment”. The present Specification does not define the term, “prophylaxis treatment”, however, Cleveland Clinic Prophylaxis/Preventive Care, downloaded from Importance of Preventive Care or Prophylaxis on February 21, 2026 describes that prophylaxis is the medical term for “preventive care.” The Examiner will interpret the term, “prophylaxis treatment” to be preventative care and not prevention per se.
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.
Claim 23 is 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 claim is drawn to an antisense oligonucleotide comprising a sequence of 18-19 nucleotides in length complementary to miR-27b, wherein the antisense oligonucleotide is a mixmer having from seven to 14 affinity-enhancing nucleotide analogues and does not contain a stretch of more than three contiguous DNA nucleotides, and wherein said antisense oligonucleotide comprises one to 18 phosphorothioate internucleoside linkages, wherein the antisense oligonucleotide is any one of the sequences set forth by SEQ ID NOs: 1, 2 and 3. The Specification discloses that SEQ ID NO: 1 is the mature sequence of miR-27b and is therefore not an antisense oligonucleotide. Regarding SEQ ID NOs: 2 and 3, the present Specification discloses that these sequences are actually target sequences of miR-27b and therefore not antimiR-27b oligonucleotides. The metes and bounds of the claim cannot be determined since SEQ ID NOs: 1, 2 and 3 appear to be target sequences and not antimiR-27b sequences. Correction is required.
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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4.Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 and 16-29 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/201301 A1 (UNIV NEW YORK) (2014-12-18) (submitted and made of record on the IDS filed September 25, 2023) in view of WO 2010/122538 A1 (HILDEBRANDT-ERIKSEN ELISABETH) (2010-10-28) and EP2194129 A2 (ELMEN JOACIM) (2010-06-09).
The claims are drawn to an antisense oligonucleotide comprising a sequence of 18-19 nucleotides in length complementary to miR-27b, wherein the antisense oligonucleotide is a mixmer having from seven to 14 affinity-enhancing nucleotide analogues and does not contain a stretch of more than three contiguous DNA nucleotides, and wherein said antisense oligonucleotide comprises one to 18 phosphorothioate internucleoside linkages.
Regarding claims 1, 16-19 and 22-25, UNIV NEW YORK teaches and describes anti-miR-27b oligonucleotides which are capable of decreasing the level and/or activity of miR-27b (see paragraph [0009]). Also see claim 56. The anti-miR-27b oligonucleotide can be 5'-AACTTAGCCACTGTGA-3' (SEQ ID NO: 54) or 5'-AGAACTTAGCCACTGTGA-3' (SEQ ID NO: 34; corresponding to SEQ ID NO: 4 and sequences in Table 1 of the present application) in modified forms, e.g. LNA oligonucleotide of SEQ ID NO: 54, or miRCURY LNATM microRNA inhibitor or miRCURY LNATM microRNA Power inhibitor of SEQ ID NO: 34 (paragraph [0018]). miRCURY LNA™ microRNA inhibitors are DNA/LNATM mixmer antisense oligonucleotides with normal phosphodiester nucleotide bonds, and miRCURY LNATM microRNA Power are inhibitors having a fully phosphorothioate (PS) modified backbone (see paragraphs [0070] and [0072]). The anti-miR-27b oligonucleotides may further comprise other modifications such as 2'-fluoro, 2'-MOE or 2'-O-Me modified nucleotides (see paragraphs [0071]).
UNIV NEW YORK does not necessarily teach a mixmer having from seven to 14 affinity-enhancing nucleotide analogues and does not contain a stretch of more than three contiguous DNA nucleotides.
Regarding claims 1, 18-20 and 25, HILDEBRANDT-ERIKSEN teach various combinations of nucleotide modifications of antisense DNA-LNA mixmer oligonucleotides. For example, HILDEBRANDT-ERIKSEN teach, “various mixmer designs are highly effective as therapeutic oligomers”.
HILDEBRANDT-ERIKSEN are explicit in teaching:
“The repeating pattern, may, for instance be every second or every third nucleotide is a nucleotide analogue, such as LNA, and the remaining nucleotides are naturally occurring nucleotides, such as DNA, or are a 2'substituted nucleotide analogue such as 2'MOE or 2'fluoro analogues as referred to herein, or, in some embodiments selected form the groups of nucleotide analogues referred to herein. It is recognized that the repeating pattern of nucleotide analogues, such as LNA units, may be combined with nucleotide analogues at fixed positions - e.g. at the 5' or 3' termini”
Regarding claims 1, 17-22 and 25-29, ELMEN JOACIM teach a large number of different anti-miR nucleotides including one against miR-27b. See Table 2, AcTtaGCcaCtGtGA (SEQ ID NO: 93). Beta-D-Oxy LNA is the preferred LNA (see paragraph [0130]). LNA cytosines may be 5-methy!cytosines. The amount of LNA in a mixmer may be between 50 and 70 % (see paragraph [0145] and SEQ ID NO: 93) and it may comprise two LNAs in each end of the nucleotide (see e.g. paragraph [0038] and SEQ ID NOs: 539 and 541 paragraph [0219] (Table of other mixmer modified anti-miRs).
ELMEN JOACIM also teach the anti-miR nucleotides of their invention are used for treatment and prophylaxis treatment of diseases in the CNS, such as in the brain or spinal cord.
Before the effective filing date of the claimed invention, an antisense oligonucleotide comprising a sequence of 18-19 nucleotides in length complementary to miR-27b, wherein the antisense oligonucleotide is a mixmer was known and taught in the prior art of UNIV NEW YORK.
A person of ordinary skill in the art would have been motivated and expected reasonable success to modify the mixmer antisense oligonucleotide of UNIV NEW YORK to comprise various combinations of nucleotide modifications, such as from seven to 14 affinity-enhancing nucleotide analogues and does not contain a stretch of more than three contiguous DNA nucleotides since such is a matter of design choice as taught by HILDEBRANDT-ERIKSEN and ELMEN JOACIM 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 disclosures of UNIV NEW YORK and HILDEBRANDT-ERIKSEN and ELMEN JOACIM as a blueprint for making chemically modified antisense oligonucleotides complementary to miR-27b.
Therefore, the subject matter of claims 1 and 16-29 is obvious over UNIV NEW YORK in view of HILDEBRANDT-ERIKSEN and ELMEN JOACIM.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on 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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/TERRA C GIBBS/ Primary Examiner, Art Unit 1635