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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claim(s) 1 and 5-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (Cancer Cell Int (2015) 15:107, 1-9), in view of Bennett et al. (US 8,133,876 B2), Saltzman et al. (US 10,682,422 B2), Rothman et al. (WO 2015/100113 A2), and Torres et al. (Artificial DNA: PNA & XNA 2:3, 71-78, 2011).
Wu et al. teach a specific miR-96-5p inhibitor (sequence: 5′-AGC AAA AAU GUG CUA GUG CCA AA-3′) (page 6, column 2) that is 100% identical to instant SEQ ID NO: 1 (instant claim 1).
Wu et al. does not teach incorporation of PNA moieties.
However, it was known to incorporate PNA moieties into miRNA antagomirs, as taught by Bennett et al.
Bennett et al. teach: Another group of oligomeric compounds amenable to the present invention includes oligonucleotide mimetics. The term mimetic as it is applied to oligonucleotides is intended to include oligomeric compounds wherein only the furanose ring or both the furanose ring and the internucleotide linkage are replaced with novel groups, replacement of only the furanose ring is also referred to in the art as being a sugar surrogate. The heterocyclic base moiety or a modified heterocyclic base moiety is maintained for hybridization with an appropriate target nucleic acid. One such oligomeric compound, an oligonucleotide mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA oligomeric compounds, the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone (column 30).
Bennett et al. teach that: PNA has been modified to incorporate numerous modifications since the basic PNA structure was first prepared. The basic structure is shown below:
PNG
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106
234
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Greyscale
Wherein Bx is a heterocyclic base moiety;
(157) T4 is hydrogen, an amino protecting group, --C(O)R5, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group, a reporter group, a conjugate group, a D or L α-amino acid linked via the α-carboxyl group or optionally through the Ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;
T5 is --OH, --N(z1)Z2, R5, D or L α-amino acid linked via the α-amino group or optionally through the Ω-amino group when the amino acid is lysine or ornithine or a peptide derived from D, L or mixed D and L amino acids linked through an amino group, a chemical functional group, a reporter group or a conjugate group;
(159) Z1 is hydrogen, C1-C6 alkyl, or an amino protecting group;
(160) Z2 is hydrogen, C1-C6 alkyl, an amino protecting group, --C(=O)--(CH2)n-J-Z3, a D or L α-amino acid linked via the α-carboxyl group or optionally through the Ω-carboxyl group when the amino acid is aspartic acid or glutamic acid or a peptide derived from D, L or mixed D and L amino acids linked through a carboxyl group;
(161) Z3 is hydrogen, an amino protecting group, --C1-C6 alkyl, --C(=O)—CH3, benzyl, benzoyl, or --(CH2)n--N(H)Z1;
(162) each J is O, S or NH;
(163) R5 is a carbonyl protecting group; and
(164) n is from 2 to about 450 (columns 30 and 31).
Therefore, Bennett et al. teaches that the PNA has 1 or more amino acids added to the N or C terminus (instant claim 1). Selection of the specific quantity is considered to be a matter of design choice.
Bennett et al. teach that: It is also understood that, although many of the oligomeric compounds listed in Tables 64-66 have been designed to target or mimic a particular miRNA from humans, for example, that oligomeric compound may also target or mimic other miRNAs from mammals, such as those from rodent species, for example. It is also understood that these miRNAs and mimics can serve as the basis for several variations of nucleic acid oligomeric compounds, including compounds with chemical modifications such as uniform or chimeric 2'-MOE oligomeric compounds, as well as LNAs and PNAs; such oligomeric compounds are also within the scope of the invention (column 369) (instant claim 1).
Bennett et al. teach: The oligomeric compounds and compositions of the invention can be utilized in pharmaceutical compositions by adding an effective amount of the compound or composition to a suitable pharmaceutically acceptable diluent or carrier. Use of the oligomeric compounds and methods of the invention may also be useful prophylactically (column 59). Bennett et al. teaches that the oligomer is the active ingredient (column 4)(instant claim 5).
It is noted that instant claims 6 and 7 recite intended use of the compound, which does not introduce a structural requirement into the compound claim. The instant claims are compound claims rather than method claims and the intended use does not alter the product.
Bennett et al. does not teach that each peptide moiety added to the N and C terminus contains lysine and wherein one of the moieties consists of three consecutive lysines.
However, Saltzman et al. teach that polynucleotides optionally include one or more terminal residues or modifications at either or both termini to increase stability, and/or affinity of the oligonucleotide for its target. Commonly used positively charged moieties include the amino acids lysine and arginine, although other positively charged moieties may also be useful. For example, lysine and arginine residues can be added to a bis-PNA linker or can be added to the carboxy or the N-terminus of a PNA strand. Polynucleotides may further be modified to be end capped to prevent degradation using a 3′ propylamine group. Procedures for 3′ or 5′ capping oligonucleotides are well known in the art (column 37) (instant claim 1). Saltzman et al. teach that amino acids such as lysine are particularly useful if positive charges are desired in the PNA.
Therefore, it was known to incorporate lysine residues into PNAs at the termini. It would have been obvious as a matter of design choice to incorporate the PNAs at one or both termini and to incorporate three consecutive lysines for a desired positive charge. Incorporation of terminal lysine residues was routine in the art, as evidenced by Saltzman et al.
Additionally, Rothman et al. teach PNAs with improved delivery via incorporation of terminal peptides comprising lysine termini [0008]. The peptide consists of lysine residues [0014]. Rothman et al. teach attachment to both the C- and N-terminus [0018][0024]. Rothman et al. teach that PNA activity was more effective when employing three lysines (Lys(palmitoyl-Lys-Lys) residues on both termini [0024]. Rothman et al. teach that the PNAs can be utilized in ant8isnese oligonucleotides [0047].
Torres et al. teach that when targeting miRNAs, only a few Lysine residues attached to the PNA are necessary for microRNA inhibition in cell culture and in vivo (page 72, column 1). Torres et al. demonstrates incorporation of three consecutive terminal lysines into a PNA at Table 1. It was clearly obvious that incorporation of three lysine residues to PNAs wherein the peptide moieties are added at the termini would benefit activity of the oligomer.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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