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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a provisional application filed as 63/111,118 on 11/09/2020.
All claims are given the priority date of 11/09/2020.
Application Status
Receipt is acknowledged of amendment, filed 12/15/2025. Claims 1, 2, 5, 10, 17, 18, 25, 29, 31-35, 37, 40-42 and 44-49 are currently pending.
Election/Restriction
Applicant’s election without traverse of Group I, drawn to claims 1, 2, 5, 10, 17, 18, 25, 29, 31-34, 41, 42, 44, 45, 48 and 49, in the reply filed on 12/15/2025 is acknowledged.
Applicant’s election without traverse of SEQ ID NO: 1 drawn to claim 18 in the reply filed on 12/15/2025 is acknowledged. However, the species election has been withdrawn and all sequences listed in claim 18 will be examined.
Claims 35, 37, 40 46 and 47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/15/2025.
Claims 1, 2, 5, 10, 17, 18, 25, 29, 31-34, 41, 42, 44, 45, 48 and 49 are currently under examination.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statements filed on 05/08/2023 and 05/29/2025 have been received and all references have been considered.
Claim Objections
Claim 10 is objected to because of the following informalities:
Claim 10 recites “The oligonucleotide of of claim 1”. The second recitation of the word “of” should be removed.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 10, 17, 29, 31-34 and 44 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hou et al (Arch Med Sci. 2011 Jun;7(3):414-22).
Regarding claim 1, Hou teaches a two DNAzyme system (DRz1694 and DRz1366) that are anti-mecRl and anti-blaRl phosphorothioated deoxyribozymes capable of successful knockdown of mecRl and blaRl resulting in increased susceptibility of MRSA strains (Page 415, Column 1 and Page 421, Column 2).
Regarding claims 10 and 17, Hou teaches that PS-DRz1694 and PS-DRz1366 are
34-mers consisting of a central 10-23 catalytic core domain (15 nts) flanked by target-specific binding arms (19 nts), which were modified with phosphorothioates to increase nuclease resistance (Page 417, Column 1).
Regarding claim 29, Hou teaches the DNAzymes for the targeting of Methicillin-resistant Staphylococcus aureus which is resistant to all commercially available β-lactam antibiotics (Page 414, Abstract).
Regarding claim 31, Hou teaches the reaction buffer includes the DNAzymes that are then electroporated into MRSA strain cells (Page 415, Column 2 bridging Page 516, Column 1).
Regarding claims 32-34, Hou teaches the reaction buffer includes the DNAzymes that are then electroporated into MRSA strain cells (Page 415, Column 2 bridging Page 516, Column 1). Hou teaches after electroporation, the cells were recovered in preheated broth medium containing 6 mg/l of oxacillin (Page 416, Column 2). Hou teaches in liquid medium containing oxacillin (6 mg/I), the growth of PS-DRz1366-treated MRSA080302 and PS-DRz1694-treated MRSA080305 cells was inhibited, respectively (Page 419, Column 1).
Regarding claim 44, Hou teaches a two DNAzyme system (DRz1694 and DRz1366) that are anti-mecRl and anti-blaRl phosphorothioated deoxyribozymes capable of successful knockdown of mecRl and blaRl resulting in increased susceptibility of MRSA strains (Page 415, Column 1 and Page 421, Column 2).
Claims 1, 2, 5, 10, 29, 31, 44, 45 and 49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hasick et al (Molecules. 2020 Apr 10;25(7):1755 and Supplemental Material Pages 1/2-2/2).
Regarding claims 1 and 2, Hasick teaches a Plexzyme system comprising a cascade of subzymes which are capable of cleaving and releasing their respective DNAzymes to target the bacterial blaKPC (bla carbapenemase) gene (Page 1, Abstract and Page 6, 1st full paragraph).
Regarding claim 5, Hasick teaches a Plexzyme system comprising a cascade of subzymes which are capable of cleaving and releasing their respective DNAzymes to target the bacterial blaKPC (bla carbapenemase) gene (Page 1, Abstract and Page 6, 1st full paragraph).
Regarding claims 10 and 45, Hasick teaches a triethylene glycol linker at the 3’ end of the DNAzyme (Page 12, Supplemental Material A).
Regarding claim 29, Hasick teaches a Plexzyme system comprising a cascade of subzymes which are capable of cleaving and releasing their respective DNAzymes to target the bacterial blaKPC (bla carbapenemase) gene (Page 1, Abstract and Page 6, 1st full paragraph) wherein the blaKPC is targeted from Klebsiella pneumoniae.
Regarding claim 31, Hasick teaches that all reactions contained l x PCR Buffer II, l x of Subzyme 1-MP, 1 PMB containing l x concentration of Subzyme 2-MP, and 15 mM MgCl2 in 125 μL final volume (Page 9, Paragraph 5).
Regarding claim 44, Hasick teaches a Plexzyme system comprising a cascade of subzymes which are capable of cleaving and releasing their respective DNAzymes to target the bacterial blaKPC (bla carbapenemase) gene (Page 1, Abstract and Page 6, 1st full paragraph).
Regarding claim 49, Hasick teaches a triethylene glycol linker at the 3’ end of the DNAzyme (Page 12, Supplemental Material A).
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.
Claim 18 is rejected under 35 U.S.C. 103 as being anticipated by Hou et al (Arch Med Sci. 2011 Jun;7(3):414-22) in view of Blatt et al (WO 02/068637 A2).
The teachings of Hou are as described and applied above.
Regarding claim 18, Hou does not teach the specific sequences of any one of or at least 80% identical to any one of SEQ ID NOs: 1-26 and/or 35-53.
Blatt teaches the DNAzyme sequence of SEQ ID NO: 32179 which is 83% identical to instant SEQ ID NO: 5 (Page 378, Table XI; See Appendix I).
Because both Hou and Blatt teach the use of DNAzymes for targeting and cleaving sequences, it would have been obvious to one skilled in the art to substitute one method for the other to achieve the predictable result of utilizing the sequence of SEQ ID NO: 32179 of Blatt for targeting a sequence for cleavage which is 83% identical to instant SEQ ID NO: 5. Thus, substitution of the SEQ ID NO: 32179 of Blatt, for DNAzyme sequence in Hou would have been prima facie obvious to one of ordinary skill in the art, and thus the ivnention as claimed is unpatentable over the work of the prior art. Substitution of one known method for another known method, the methods having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See MPEP 2143(I)(B).
Claims 41 and 42 are rejected under 35 U.S.C. 103 as being anticipated by Hou et al (Arch Med Sci. 2011 Jun;7(3):414-22).
The teachings of Hou are as described and applied above.
Regarding claims 41 and 42, The current specification states the term "surface" is defined herein as any surface which may be covered, at least in part, by bacteria (e.g. by biofilm) (Page 58, Lines 4-5).
Hou teaches the diluted cells (comprising the DNAzymes; DRz1694 and DRz1366) were spread onto plates of Mueller-Hinton agar containing 6 mg/l of oxacillin, and the plates were incubated for 48h at 35°C (Page 416, Column 2). Huo teaches the combination treatment of PS-DRz1694 and PS-DRz1366 on MRSA080309 resulted in synergic effects on susceptibility restoration to oxacillin (Page 421, Column 1 bridging Column 2). Hou teaches it is particularly encouraging that MICs of oxacillin to MRSA080302, MRSA080305 and MRSA080309 were fully restored to values within the sensitivity defining range by PS-DRz1366, PS-DRz1694 and combined administration of these two DNAzymes, respectively (Page 421, Column 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the teachings of Hou to include a surface coated with the oligonucleotide and oxacillin because Hou teaches it is within the ordinary skill in the art to use a two DNAzyme system (DRz1694 and DRz1366) that are anti-mecRl and anti-blaRl phosphorothioated deoxyribozymes capable of successful knockdown of mecRl and blaRl resulting in increased susceptibility of MRSA strains and the Mueller-Hinton agar and/or broth medium containing 6 mg/l of oxacillin.
One would have been further motivated to make such a modification in order to receive the expected benefit of fully restored sensitivity to oxacillin for MRSA strains as taught by Hou.
Claims 17, 25 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Hasick et al (Molecules. 2020 Apr 10;25(7):1755 and Supplemental Material Pages 1/2-2/2) in view of Bhindi et al (The American Journal of Pathology, Vol. 171, No. 4, October 2007).
The teachings of Hasick are as described and applied above.
Regarding claim 17, Hasick does not specifically teach wherein when said modification comprises a base modification, a sugar modification, or an internucleotide linkage modification, or a combination thereof, said modification is selected from the group consisting of locked nucleic acids (LNA), phosphorothioate, 2-0-fluor, 2-0-methyl, 2-0-methoxyethyl, methylcytosine, 2-fluoro, and a 2-Fluoroarabinooligonucleotides.
Bhindi teaches LNA bases comprise a 2'-0 4-C methylene bridge that locks in a C3'-endo conformation, which places constraint on the ribose ring, increasing affinity for complementary sequences (Page 1801, Column 1). Bhindi teaches locked nucleic acids (LNAs) have been attractive monomers for modifying oligonucleotides and DNAzymes, in an attempt to increase binding affinity (Page 1801, Column 1). Bhindi teaches a commonly used modification is the incorporation of a 3'-3' inverted nucleotide at the 3' end of the DNAzyme to prevent exonuclease degradation, which can dramatically increase stability of the molecule, extending the half-life from -70 minutes to >21 hours in human serum (Page 1080, Column 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Hasick to include the locked nucleic acid and/or 3’-3’ inverted nucleotide modifications of DNAzymes as taught by Bhindi because Hasick teaches it is within the ordinary skill in the art to use a Plexzyme system comprising a cascade of subzymes which are capable of cleaving and releasing their respective DNAzymes to target the bacterial blaKPC (bla carbapenemase) gene and Bhindi teaches the locked nucleic acid modification increases the affinity for complementary sequence as well as the 3’-3’ inverted nucleotide at the 3’ end of the DNAzyme prevents exonuclease degradation and increases stability of the molecule extending its half-life.
One would have been motivated to make such a modification in order to receive the expected benefit of increased binding affinity as well as prevention of exonuclease degradation and increased stability as taught by Bhindi.
Regarding claim 25, Hasick teaches the Plezxyme system is tethered to microparticles for delivery (Page 1, Abstract).
Hasick does not specifically teach the oligonucleotide further comprising a permeability enhancing moiety attached to a nucleotide of the at least one DNAzyme, wherein the permeability enhancing moiety is a cholesterol moiety, a cell penetrating peptide, a lipid nanoparticle, or a viral capsid.
Bhindi teaches the use of delivery agents such as polymer, cationic lipids, PEGylated liposomes and/or complexes are known in the art for delivery of DNAzymes and siRNA molecules (Page 1080, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Hasick to include the delivery agents such as polymer, cationic lipids, PEGylated liposomes and/or complexes as taught by Bhindi because Hasick teaches it is within the ordinary skill in the art to use a Plexzyme system comprising a cascade of subzymes which are capable of cleaving and releasing their respective DNAzymes to target the bacterial blaKPC (bla carbapenemase) gene and Bhindi teaches delivery agents such as polymer, cationic lipids, PEGylated liposomes and/or complexes are known in the art for delivery of DNAzymes and siRNA molecules.
One would have been motivated to make such a modification in order to receive the expected benefit of successful delivery of DNAzymes as taught by Bhindi.
Regarding claim 48, Hasick teaches the Plezxyme system is tethered to microparticles for delivery (Page 1, Abstract).
Hasick does not specifically teach the oligonucleotide further comprising a permeability enhancing moiety attached to a nucleotide of the at least one DNAzyme, wherein the permeability enhancing moiety is a cholesterol moiety, a cell penetrating peptide, a lipid nanoparticle, or a viral capsid.
Bhindi teaches the use of delivery agents such as polymer, cationic lipids, PEGylated liposomes and/or complexes are known in the art for delivery of DNAzymes and siRNA molecules (Page 1080, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Hasick to include the delivery agents such as polymer, cationic lipids, PEGylated liposomes and/or complexes as taught by Bhindi because Hasick teaches it is within the ordinary skill in the art to use a Plexzyme system comprising a cascade of subzymes which are capable of cleaving and releasing their respective DNAzymes to target the bacterial blaKPC (bla carbapenemase) gene and Bhindi teaches delivery agents such as polymer, cationic lipids, PEGylated liposomes and/or complexes are known in the art for delivery of DNAzymes and siRNA molecules.
One would have been motivated to make such a modification in order to receive the expected benefit of successful delivery of DNAzymes as taught by Bhindi.
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637