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. Application Status The preliminary amendment filed October 11, 2023 is acknowledged. Claims 1-11 are pending and under examination . Nucleotide and/or Amino Acid Sequence Disclosures REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES Items 1) and 2) provide general guidance related to requirements for sequence disclosures. 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted: In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying: the name of the ASCII text file; ii) the date of creation; and iii) the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying: the name of the ASCII text file; the date of creation; and the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended). When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical. Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency #1 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Figure 7 has both an amino acid sequence, which appears to be identical to SEQ ID NO 12, and a nucleotide sequence, which appears to be identical to SEQ ID NO 13. Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Although the brief description for claim 7 does recite “SEQ ID NO:12” this is reference to the complete genome sequence, and not the amino acid sequence of the non-capsid protein. Required response – Applicant must provide: Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers; AND/OR A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Specific deficiency #2 – Nucleotide sequences appearing in the specification – page 25 in Table 1 - are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Required response – Applicant must provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Specification The use of the term s Triton TM and Hybond ®, which are trade name s or mark s used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Claim Objections Claims 1 , 8 and 11 are objected to because of the following informalities: Claim 1 recites “wherein said target specific nucleic acid is transcribable in an RNAi”, which is grammatically incorrect. It is suggested that the claim recite “transcribable as an RNAi”. Claim 8 is missing a space between “claim 1” and “for”. Claim 11 recites “An isolated cell containing a parvovirus of claim 1”. Because there are several recitations of a parvovirus, it is suggested that claim 11 recite “An isolated cell containing the parvovirus as defined in claim 1”. Appropriate correction is required. Claim Rejections - 35 USC § 112 (b) 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 appl icant regards as his invention. Claim s 1-11 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 “a parvovirus H-1 deletion variant containing a deletion encompassing the nucleotides 2022-2135, where in a target specific nucleic acid is in s erted at nucleotide 4480 of the H-1 parvovirus VP gene…” The recitation of specific nucleotide positions of nucleic acid without reciting a reference sequence – either a SEQ ID NO or an Accession number – renders the claim indefinite. There are different H-1 parvovirus variants which may have small deletions o r changes upstream of a 2022-2135 that could alter the nucleotide numbering. Additionally, given that an insertion at position 4480 is in addition to a deleted portion, it is not clear if position 4480 is in reference to the genome before the deletion or after the deletion. Finally, “nucleotide 4480 of the H-1 parvovirus VP gene” is confusing because according to Fig 7, the “coat protein” spans nucleotide positions 2289-2357 (i.e., with only 69 nucleotides) and even with the entire downstream sequence interpreted as the “the VP gene”, the sequence spans less than 3000 bp. Therefore “position 4480” in reference to the VP1 gene is also confusing. Claims 2-11 are rejected for depending from claim 1 and not remedying the indefiniteness. To overcome this rejection, it is suggested that the claim recite: “A parvovirus for down regulating the expression of a tar g et specific nucleic acid in a cell , wherein the parvovirus comprises an H-1 parvovirus genome comprising a deletion encompassing nucleotides 2022-2135 relative to a wild-type H-1 parvovirus comprising SEQ ID NO 13, wherein a target specific nucleic acid is in s erted at nucleotide 4480 relative to SEQ ID NO 13 , wherein the target specific nucleic acid is expressible under the control of a promoter or promoter region recognizable by an RNA polymerase in the cell, wherein said target nucleic acid is transcribable as an RNAi, and wherein said parvovirus is capable of replication and propagating in the cell. Claim 2 recites “wherein the target specific nucleic acid is a PD-L1 nucleic acid”. Claim 2 is indefinite because the target specific nucleic acid of claim 1 must be transcribable as an RNAi. PD-L1 is a protein-coding gene. It is not clear how a PD-L1 nucleic acid is an RNAi. If Applicant intends for PD-L1 to be the target of the target nucleic acid, it is suggested that claim 2 recite: “wherein the target specific nucleic acid targets a PD-L1 nucleic acid” or “wherein the target specific nucleic acid is a PD-L1 inhibiting nucleic acid”. Claim 4 recites “wherein the Pol III promote r is the RNA-polymerase III H1 promoter”. “ The RNA polymerase III H1 promoter” lacks clear antecedent basis. There are many H1 promoters including from different species, which have different sequences, and variants of H1 promoters. It is not clear which H1 promoter is being referenced. It is suggested that claim 4 recite: wherein the Pol III promoter is an H1 promoter”. Claim 10 recites “said parvovirus is administered by intravenous…”. Claim 10 is directed to “The parvovirus” and is therefore a product claim. However, “is administered” is an active step for which the parvovirus is used. A single claim which claims both a product and the method steps of using the product is indefinite. See MPEP 2173.05(p).II. In this case, “is administered” is not merely a capability of the parvovirus but instead is directed to actions of an individual using the parvovirus. Note that claims 8 and 9 are not rejected for reciting “for the use in a method” because that language is interpreted as intended use of the product and there is no active step recited in the claims (see § 112(d) rejections that follow). Claim Rejections - 35 USC § 112 (d) The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim s 8-9 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 recites “the par v ovirus according to claim 1 for the use in a method of treating a tumo u r .” “For use in” is interpreted as intended use of the parvovirus. There is no indication in the Specification that the structure of the parvovirus of claim 1 used in a method of treating a tumor is any different than structure of the parvovirus in claim 1. In other words, there is no suggestion that the structure of a parvovirus changes or is further limited when it is used in a method for tumor treatment. Therefore claim 8 does not further limit the subject of claim 1 from which it depends. Claim 9 recites, “characterized in that the cells of said tumour are resistant to chemotherapy.” There is no indication in the Specification that the structure of a parvovirus changes or is further limited when it is used in a method for tumor treatment when the cells of the tumor are resistant to chemotherapy. Therefore claim 9 does not further limit the subject of claim 1 from which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Allowable Subject Matter Claim 1 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), 2nd paragraph, set forth in this Office action. The closest prior art is Bretscher ( Bretscher et al., Viruses (2019), 11: 562, pages 1-20) and Marchini (US 20220265741 A1, priority to February 12, 2021). Bretscher reviews the state of the art of using the oncolytic H-1 Parvovirus (H-1PV) in methods of treating cancer (Abstract). Bretscher teaches attempts to improve H-1PV as a cancer treatment by improving the fitness of the virus (Section 5.2.1) and combining it with RNA interference cassettes (Section 5.2.3). Bretscher teaches that an in-frame deletion in the non-structural (NS) gene coding sequence comprising nucleotides 2022-2135 improved the infectivity and transduction efficiency of H-1PV into cancer cells (Section 5.2.1, ¶1). Bretscher cites patent EP2384761 B1 as disclosing variants containing small deletions in the untranslated region of the viral genome (¶2), but it does not appear that the deletions/insertions were located around the 4400-4500 nucleotide position of the genome (EP2384761 B1, Figs. 5-6). Bretscher also teaches that shRNA expression cassettes have been inserted into the untranslated region of the H-1PV genome, but does not indicate the position of the insertion. Marchini (US 20220265741 A1, priority to February 12, 2021), discloses H-1PV variants with th e 2022-2135 deletion and an shRNA expression cassette inserted in the untranslated region at position 4688 (Fig 1A). Marchini teaches that th e H-1PV-shRNA vector shown in Fig 1A is problematic because the cassette was unstable ([0120]). Marchini solves the problem by deleting a portion of the untranslated region around the insertion site at 4688 (Fig 2A). Marchini does not teach or suggest inserting the shRNA cassette at any other position other than in place of the 4659-4693 deletion. Given the prior art teaching s that the shRNA cassette can be unstable integrated in the untranslated region, it would not have been obvious to try other insertion sites in the untranslated region. There is no suggestion in the prior art to insert an shRNA cassette into any other position of the untranslated region other than the region around 4688. As such it would not have been obvious to modify the H-1PV virus of Marchini by changing the shRNA cassette insertion site. Conclusion No claims are allowed. 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