DETAILED ACTION
The Examiner for this application has changed. Please direct all future correspondence to Examiner Jennifer Spence, Art Unit 1633. Additional contact information can be found at the end of this paper.
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 .
Claims 1-15, of record 5/12/2023, are pending.
Election/Restrictions
Applicant’s election without traverse of group I, claims 1-11 and 14-15 in the reply filed on 12/2/2025 is acknowledged. Claims 1-11 and 14-15, of record 5/12/2023, are subject to prosecution.
Claims 12-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/2/2025.
Applicant’s species elections are also acknowledged. However, upon further consideration, the requirement for election of species is withdrawn.
Priority
The instant application is a national stage entry of PCT/EP2021/071767 (filed 8/4/2021). Because a certified copy of German application 10 2020 130 072.7 (filed 11/13/2020) has not been received, the earliest priority date to which the instant application is entitled is considered to be 8/4/2021.
Drawings
The drawings are objected to because view number must be preceded by the abbreviation “FIG.” See 37 CFR 1.84(u). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 2-11 and 14-15 are objected to because of the following informalities:
Claims 2-11 and 14-15 are missing articles (“The
Claims 4-6, 8-11, and 14 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n).
In line 5 of claim 6 and line 4 of claim 15, “and/or” should be replaced with “and” in order to constitute a proper Markush grouping.
In line 5 of claim 9, the second instance of the word “or” should be replaced with “and” in order to constitute a proper Markush grouping.
Appropriate correction is required.
Claim Interpretation
For the purpose of compact prosecution, improper dependent claims 4-6, 8-11, and 14 are interpreted as depending from independent claim 1.
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.
Claims 1-11 and 14-15 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the genomic sequence of a Coxsackievirus B3” in line 2 and “the CVB3 protein coding sequence” in line 6. There is insufficient antecedent basis for these limitations in the claim. Dependent claims 2-11 and 14-15 are included in the rejection.
Claim 3 recites “the coding sequence of the 3D polymerase” in lines 2-3 and “the CVB3 protein encoding sequence” in line 3. There is insufficient antecedent basis for these limitations in the claim.
Claims 4-5 recite “the human pancreas tissue” and “the human heart tissue”. There is insufficient antecedent basis for these limitations in the claims.
In claim 6, it is unclear whether the Markush group consists of two groupings (all of the pancreas-specific miRs and all of the heart-specific miRs) or one grouping (all of the listed miRs) from which one or more miR sequences are selected.
Regarding claims 8 and 11, the terms "preferably" and “e.g.” render the claims indefinite because it is unclear whether the limitation(s) following the terms are part of the claimed invention. See MPEP § 2173.05(d).
Claim 11 recites the limitation “the CVB3 group virus”. There is insufficient antecedent basis for this limitation in the claim.
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.
(g)(1) during the course of an interference conducted under section 135 or section 291, another inventor involved therein establishes, to the extent permitted in section 104, that before such person’s invention thereof the invention was made by such other inventor and not abandoned, suppressed, or concealed, or (2) before such person’s invention thereof, the invention was made in this country by another inventor who had not abandoned, suppressed, or concealed it. In determining priority of invention under this subsection, there shall be considered not only the respective dates of conception and reduction to practice of the invention, but also the reasonable diligence of one who was first to conceive and last to reduce to practice, from a time prior to conception by the other.
A rejection on this statutory basis (35 U.S.C. 102(g) as in force on March 15, 2013) is appropriate in an application or patent that is examined under the first to file provisions of the AIA if it also contains or contained at any time (1) a claim to an invention having an effective filing date as defined in 35 U.S.C. 100(i) that is before March 16, 2013 or (2) a specific reference under 35 U.S.C. 120, 121, or 365(c) to any patent or application that contains or contained at any time such a claim.
Claims 1-4, 6, and 8-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pinkert et al. (Cardiovascular Research, 2020).
Pinkert et al. teach an engineered coxsackievirus bearing miRNA target sequences for reducing viral replication in pancreatic cells in a mouse model of myocarditis without pancreatitis (See Abstract). Pinkert et al. identify miR-375 as one of the most highly expressed miRNAs in mouse pancreatic tissue (See fig. 1). A miR-375 target sequence is inserted into the genome of coxsackievirus, and in the presence of miR-375, replication of the viral genome is inhibited (See fig. 2). Administration of the virus comprising a miR-375 target sequence to mice successfully infect and replicate in heart tissue, causing myocarditis, but viral replication is inhibited by the presence of endogenous mir-375 within infected pancreatic cells, and the mice do not develop pancreatitis (See fig. 4-7).
Regarding claims 1-4, 6, and 8-11: Pinkert et al. teach cDNA plasmids for expressing the H3 strain (which reads on “attenuated or aggressive CVB3 group virus strains”) of coxsackievirus B3 comprising the miR-375 target sequence (which reads on “complementary to one or more microRNAs”) (See page 1757, col. 2, ¶1 and fig. 2A). Three copies (which reads on “threefold… repetitions”) of the target sequence were inserted at a multiple cloning site (which reads on “one or more sequence elements… integrated into the backbone of the cDNA construct”) immediately following the 3D polymerase coding sequence and before the 3’UTR (which reads on “incorporated between the stop codon of the coding sequence of the 3D polymerase and 3’UTR of the CVB3 protein encoding sequence” and “integrated adjacent of the 5 ‘ UTR and/or the 3 ‘ UTR of the CVB3 protein coding sequence”) (See fig. 2A). Infectious virions comprising the miR-375 target sequence were produced and exhibited reduced replication in pancreatic cells (See fig. 2). Pinkert et al. teach that miR-375 is selectively expressed in the pancreas (which reads on “having tissue-specific expression pattern”) (See page 1758, col. 1, full ¶3 and fig. 1A).
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 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Pinkert et al. (Cardiovascular Research, 2020), in view of Luo et al. (US 20220267799 A1).
The teachings of Pinkert et al. are set forth in the 102 rejection above and are incorporated herein in their entirety.
Regarding claims 5 and 7: Following the discussion of claims 1-4, 6, and 8-11, Pinkert et al. teach a cDNA-generated coxsackievirus B3, H3 strain, comprising a miR-375 target site but do not teach a targets site for miR-375 and a target site for a second, different miRNA.
Luo et al. teach enterovirus vectors modified to comprise one or more miRNA target sequences for treating cancer (See Abstract). Cancer tissues commonly have downregulated miRNAs, which promote suppression of gene expression; the insertion of a miRNA target sequence can increase tumor specificity by limiting replication in non-cancerous tissues that normally express the miRNA (See ¶0010-0011, 0036, and 0049). The virus can be coxsackievirus B3 (See ¶0011). The miRNA target sequences can recognize miRNAs including cardiac-specific miR-1 (which reads on “specifically expressed in the human heart tissue”) and miR-375 (See ¶0012, 0050-0051, and 0076-0077).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the viral construct of Pinkert et al. to comprise multiple target sequences for two different miRNAs. One would be motivated to make this modification because Luo et al. teach that miRNA sensitivity can be used to develop oncolytic viruses with higher replication in tissues of interest that do not express the miRNAs specific for the target sites (See ¶0049-0051). There would be a reasonable expectation of success in making this modification because Luo et al. demonstrate the generation of coxsackievirus B3 expressing two or more different miRNA target sequences (See fig. 9). Further, as Luo et al. teach that oncolytic viruses comprising a miR-375 target site can be used for cancer treatment (See ¶0010-0012), the vector of Pinkert et al. could be readily modified to further comprise a miR-1 target site for use in cancer therapy.
Claims 1-4, 6, 8-11, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Pinkert et al. (Cardiovascular Research, 2020), in view of Pryshliak et al. (FEBS Letters, 2020), of record in IDS filed 12/2/2025.
The teachings of Pinkert et al. are set forth in the 102 rejection above and are incorporated herein in their entirety.
Regarding claims 14-15: Following the discussion of claims 1-4, 6, and 8-11, Pinkert et al. teach a cDNA-generated coxsackievirus B3, H3 clone, comprising a miR-375 target site but do not teach a use for the virus in treating cancer.
Pryshliak et al. teach the incorporation of miR-375 target sites in cDNA for expressing coxsackievirus B3 as a possible cancer treatment that could avoid pancreatitis (See Abstract). Colorectal cell lines exhibited substantially lower miR-375 expression than pancreatic cells (See fig. 1A). Pryshliak et al. teach that, while the engineered virus showed only weak replication and cytotoxicity in colorectal carcinoma cells, the incorporation of miR-375 target sites in other CVB3 strains, such as H3, could make them candidates for colorectal cancer therapy (See page 773, col. 1, full ¶2).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to combine the teachings of Pinkert et al. and Pryshliak et al. in order to use the virus of Pinkert et al. for treating colorectal cancer. One would be motivated to make this modification because Pryshliak et al. suggest that such a virus could be suitable for colorectal cancer therapy (See page 773, col. 1, full ¶2). There would be a reasonable expectation of success in doing so because Pinkert et al. teach that the virus can be administered in vivo without pancreatitis or mortality, excepting virus heart-passaged to increase virulence (See page 1765, col. 1, full ¶1-2).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE whose telephone number is (571)272-8590. The examiner can normally be reached M-F 8:30-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633