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 the species recited in paragraph [925] of the
specification in the reply filed on November 29, 2023, is acknowledged. The elected species is allowable in view of the terminal disclaimer filed June 18, 2024.
The search was extended and prior art was found that reads on claims 122, 131, 135-138, 142, 144, 176, 196, and 214. Therefore, the search was not extended further in accordance with MPEP § 803.02.
Claims 141, 143, 160, 167, 169, 238, and 259 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there
being no allowable generic or linking claim.
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 122, 131, 135-138, 142, 144, 176, 196, and 214 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (“Allele-selective inhibition of ataxin-3 (ATX3) expression by antisense oligomers and duplex RNAs” Biol Chem. 2011 Apr;392(4):315-25) in view of Anderson (US 2008/0038783 A1).
Hu et al. teach the following PNA-peptide conjugates targeting the ATXN3 CAG repeat region (Table 1):
K-GCTGCTGCTGCTGCTGCTG-K8, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, R1 is H, R2 is H, R5 is lysine, n is 19, R3 is a lysine side chain, and R4 is a sequence of seven lysine residues;
K-GCTGCTGCTGCTGCTG-K8, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, R1 is H, R2 is H, R5 is lysine, n is 16, R3 is a lysine side chain, and R4 is a sequence of seven lysine residues;
K-GCTGCTGCTGCTG-K8, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, R1 is H, R2 is H, R5 is lysine, n is 13, R3 is a lysine side chain, and R4 is a sequence of seven lysine residues;
K8-GCTGCTGCTGCTGCTGCTG-K, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, R1 is H, R2 is H, R5 is a sequence of eight lysine residues, n is 19, R3 is a lysine side chain, and R4 is H;
K-GCTGCTGCTGCTG-K6, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, R1 is H, R2 is H, R5 is lysine, n is 13, R3 is a lysine side chain, and R4 is a sequence of five lysines;
K-GCTGCTGCTGCTG-K4, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, R1 is H, R2 is H, R5 is lysine, n is 13, R3 is a lysine side chain, and R4 is a sequence of three lysines; and
K8-GCTGCTGCTGCTG-K8, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, R1 is H, R2 is H, R5 is a sequence of eight lysine residues, n is 13, R3 is a lysine side chain, and R4 is a sequence of seven lysines.
Hu et al. do not teach any PNAs wherein at least one R1 or at least one R2 is guanidino(C1-C4) alkyl.
Anderson teaches guanidine-modified PNAs, wherein the position corresponding to R2 may be guanidino(C3)alkyl (Abstract):
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Anderson teaches that guanylation of amine groups can improve various properties of the PNA oligomers, such as solubility and/or cell membrane permeability. PNA oligomers possessing good solubility and/or membrane permeability characteristics can be used as antisense agents and/or used as probes in amplification reactions such as in the polymerase chain reaction (PCR). The process for guanylating amine groups of PNA oligomers disclosed herein is straightforward and can be performed on PNA oligomers in solution as well as PNA oligomers that are support bound (paragraph [0079]). Anderson teaches that because it is not necessary for every subunit of a PNA oligomer to be guanylated in order for it to exhibit increased solubility and cell membrane permeability, PNA oligomers can be prepared wherein every other PNA subunit comprises an guanylated group (paragraph [0101]).
It would have been obvious to modify the PNAs taught by Hu et al. with guanidium at the position corresponding to R2 as taught by Anderson. The rationale to support a conclusion of obviousness is in MPEP § 2143(I)(C): use of known technique to improve similar devices (methods, or products) in the same way. The prior art of Hu et al. contained a "base" product, a PNA corresponding to the formula in claim 122. The claimed invention includes an "improvement" relative to Hu et al., at least one guanidino(C1-C4) alkyl at the position corresponding to R2. The prior art of Anderson contained a "comparable" product that has been improved in the same way as the claimed invention, PNAs wherein the position corresponding to R2 is guanidino(C1-C4) alkyl. One of ordinary skill in the art could have applied the known "improvement" technique in the same way to the "base" product. The results would have been predictable given that Anderson teaches that incorporation of a guanidine functional group into the PNA backbone facilitates cellular uptake of PNA into mammalian cells (paragraphs [0079], [0101]). The rationale to support a conclusion that the claim would have been obvious is that a method of enhancing a particular class of products has been made part of the ordinary capabilities of one skilled in the art based upon the teaching of such improvement in other situations. One of ordinary skill in the art would have been capable of applying this known method of enhancement to a "base" product in the prior art and the results would have been predictable to one of ordinary skill in the art.
The resulting compounds would be (emphasis is added to show how the compounds meet the amended claim limitations)
K-GCTGCTGCTGCTGCTGCTG-K8 modified according to Anderson, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, each R1 is H, R2 alternates between H and guanidino(C3) alkyl at each residue, R5 is lysine, n is 19, R3 is a lysine side chain, R4 is a sequence of seven lysine residues, and the compound comprises n/2=9 guanidino groups, which satisfies all of the limitations of claims 122, 131, 136-138, 142, 144, 176, 196, and 214;
K-GCTGCTGCTGCTGCTG-K8 modified according to Zhou et al., which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, each R1 is H, R2 alternates between H and guanidino(C3) alkyl at each residue, R5 is lysine, n is 16, R3 is a lysine side chain, R4 is a sequence of seven lysine residue, and the compound comprises n/2=8 guanidino groups, which satisfies all of the limitations of claims 122, 131, 136-138, 142, 144, 176, 196, and 214;
K-GCTGCTGCTGCTG-K8 modified according to Zhou et al., which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, each R1 is H, R2 alternates between H and guanidino(C3) alkyl at each residue, R5 is lysine, n is 13, R3 is a lysine side chain, R4 is a sequence of seven lysine residues, and the compound comprises n/2=7 guanidino groups, which satisfies all of the limitations of claims 122, 131, 136-138, 142, 144, 176, 196, and 214;
K8-GCTGCTGCTGCTGCTGCTG-K modified according to Zhou et al., which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, each R1 is H, R2 alternates between H and guanidino(C3) alkyl at each residue, R5 is a sequence of eight lysine residues, n is 19, R3 is a lysine side chain, R4 is H, and the compound comprises n/2=9 guanidino groups, which satisfies all of the limitations of claims 122, 131, and 135;
K-GCTGCTGCTGCTG-K6, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, each R1 is H, R2 alternates between H and guanidino(C3) alkyl at each residue, R5 is lysine, n is 13, R3 is a lysine side chain, R4 is a sequence of five lysines, and the compound comprises n/2=7 guanidino groups, which satisfies all of the limitations of claims 122, 131, 136-138, 142, 144, 176, 196, and 214;
K-GCTGCTGCTGCTG-K4, which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, each R1 is H, R2 alternates between H and guanidino(C3) alkyl at each residue, R5 is lysine, n is 13, R3 is a lysine side chain, R4 is a sequence of three lysines, and the compound comprises n/2=9 guanidino groups, which satisfies all of the limitations of claims 122, 131, 136-138, 142, 144, 176, 196, and 214; and
K8-GCTGCTGCTGCTG-K8 modified according to Zhou et al., which is a compound of the formula in claim 122 wherein B is independently guanine, thymine, or cytosine and comprises the guanine-cytosine-thymine sequence, each R1 is H, R2 alternates between H and guanidino(C3) alkyl at each residue, R5 is a sequence of eight lysine residues, n is 13, R3 is a lysine side chain, and R4 is a sequence of seven lysines and which satisfies all of the limitations of claims 122, 131, 136-138, and 176.
Response to Arguments
Applicant's arguments filed June 26, 2025, have been fully considered but they are not persuasive.
First, Applicant traverses the rejection on the grounds that the claims have been amended to overcome the rejection. Specifically, Applicant states that claim 122 is amended to require that “each R1 is hydrogen” and “each R2 is a guanidino(C1-C4)alkyl or hydrogen”. This argument is not persuasive because, as stated in the rejection above, each of these limitations is taught by the cited art.
Next, Applicant traverses the rejection on the grounds that Example 4 of the original specification provides evidence of unexpected results.
MPEP § 716.02(d) requires that unexpected results must be commensurate in scope with the claimed invention. In the instant case, Applicant presents evidence pertaining to a single compound that falls within the genus of claim 122, Compound 4:
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Compound 4 has a sequence of all guanine-cytosine-thymine triplets (GCT)6, whereas the claim only requires a single guanine-cytosine-thymine sequence.
Compound 4 has n=18 whereas the claim allows n to be 12-30.
Compound 4 has R5 is H whereas the claim allows R5 to be a sequence of any length comprising any alpha, beta, or gamma-amino acids or hydrogen.
Compound 4 has R4 is H whereas the claim allows R4 to be a sequence of any length comprising any alpha, beta, or gamma-amino acids or hydrogen.
Given the breadth of claim 122, one of ordinary skill in the art would not consider Compound 4 to be representative of the entire genus.
For these reasons, the rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654