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 .
DETAILED ACTION
Applicant’s amendments and remarks filed on March 10, 2025 are acknowledged.
Claims 1-56 and 61 have been canceled. Claims 57-60, 62-65, and 73 were amended. Claims 57-60 and 62-77 are pending. Claims 70-72 and 74-76 are withdrawn. Claims 57-60, 62-69, 73, and 77 are examined on the merits herein.
The substitute specification filed on March 10, 2025 has been entered. It is noted that both copies of the substitute specification are labeled as “SUBSTITUTE SPECIFICATION - MARKED UP”; however, it appears that one copy of the substitute specification is the clean copy.
This action is NON-FINAL due to new grounds of rejection not necessitated by amendment.
Priority
This application claims priority to PCT/US2019/065874 filed on December 12, 2019 which claims priority to U.S. provisional application 62/778,851, filed on December 12, 2018 and U.S. provisional application 62/778,866, filed on December 12, 2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 10, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicant submits that a copy of Huang et al. “Rescue of a Porcine Anellovirus…” was provided on May 31, 2022. This reference was considered by the Examiner as cite 38 on an IDS filed May 31, 2022.
Applicant submits that Hou et al. was listed on the IDS filed on August 21, 2024 and a copy of the reference was provided. This reference was considered by the Examiner as cite 3 on the IDS filed August 21, 2024.
Applicant submits that the International Search Report for PCT/US2019/065874 dated June 25, 2020 and for PCT/US2019/065963 was listed on the IDS filed May 31, 2022. The International Search Report for PCT/US2019/065874 mailed August 4, 2020 was considered as cite 39 on an IDS filed March 10, 2025. The International search report for PCT/US2019/065963 has been considered as cite 2 on the IDS filed March 10, 2025.
Drawings
The drawings were received on June 11, 2021. These drawings are found acceptable by the examiner.
Withdrawn Objections
In view of Applicant’s amendments and response, the objections to the specification, drawings, and claims are withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C 112(b) and 35 U.S.C 102 rejections are withdrawn.
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.
Claim 77 is 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 77 is indefinite at the recitation of “at least 75% sequence identity to
the 5’ UTR conserved domain of a wild-type Anellovirus.” Each member of a wild-type Anellovirus (e.g., torque teno virus (TTV), Torque teno midi virus (TTMDV), and torque teno mini virus (TTMV)) has a 5’ UTR conserved domain. Accordingly, it is not clear which 5’ UTR conserved domain the limitation is referring to.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 57-60, 62-69, 73, and 77 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 57 recites in part a synthetic particle comprising: (I) a genetic element and (II) a proteinaceous exterior comprising a polypeptide encoded by an Anellovirus ORF1 nucleic acid. Claim 58 depends from claim 57 and recites, “wherein the polypeptide encoded by the Anellovirus ORF1 nucleic acid is an ORF1 molecule.” The instant specification defines the term “ORF1 molecule” as a polypeptide having an activity and/or a structural feature of an Anellovirus ORF1 protein, or a functional fragment thereof [page 135, second paragraph]. Claim 60 depends from claim 57 and recites, “wherein the polypeptide encoded by the Anellovirus ORF1 nucleic acid…(iii) comprises an amino acid sequence comprising one or more of the amino acid sequences of an arg-rich region, jelly-roll domain, hypervariable domain, N22 domain, and/or C-terminal domain of any of SEQ ID Nos 216, 217, 218, 219, or 220, or an amino acid sequence having at least 85% identity thereto.” Accordingly, the claims encompass a genus of polypeptides having an activity and/or structural feature of any Anellovirus ORF1 protein, such as a single domain that is an arg-rich region, jelly-roll domain, hypervariable domain, N22 domain or C-terminal domain, which must function to provide a proteinaceous exterior around a genetic element.
Claim 65 recites in part the synthetic particle of claim 57 wherein (vi) the intracellular polypeptide or intracellular nucleic acid comprises an IDH1 inhibitor, an IDH2 inhibitor, an EGFR inhibitor, an LRP5 inhibitor, a DKK2 inhibitor, a DPP-4 inhibitor, a KRAS inhibitor, a neutrophil elastase inhibitor, a FGFR3 activator, or a HTT activator. The claim is drawn to the genus of IDH1, IDH2, EGFR, LRP5, DKK2, DPP-4, KRAS, and neutrophil elastase inhibitors and genus of FGFR3 and HTT activators and as instantly presented encompasses any inhibitor from those inhibitors recited and any activator from those activators recited without limitation on the structure of the inhibitor or activator.
Applicant is referred to MPEP 2163(II)(A)(3)(a)(i and ii), which indicates that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure indicates that the patentee has invented species sufficient to constitute the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.
The instant specification defines the term “ORF1 molecule” as a polypeptide having an activity and/or a structural feature of an Anellovirus ORF1 protein, or a functional fragment thereof. An ORF1 molecule may, in some instances, comprise one or more of a first region comprising at least 60% basic residues, a second region comprising at least about six beta strands, a third region comprising a structure or an activity of an Anellovirus N22 domain, and/or a fourth region comprising a structure or an activity of an Anellovirus C-terminal domain [page 135, second paragraph].
The specification envisions that the one or more Anellovirus ORF1 subsequences comprises an amino acid sequence having at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the Arg-rich region amino acid sequence of Table 35. In addition, the one or more Anellovirus ORF1 subsequences comprises an amino acid sequence having at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the jelly-roll region amino acid sequence of Table 35. Further, the one or more Anellovirus ORF1 subsequences comprises an amino acid sequence having at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the HVR amino acid sequence of Table 35. The specification also envisions that the one or more Anellovirus ORF1 subsequences comprises an amino acid sequence having at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the N22 domain amino acid sequence of Table 35. Further, the one or more Anellovirus ORF1 subsequences comprises an amino acid sequence having at least about 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the CTD region amino acid sequence of Table 35 [page 284, first full paragraph bridging to page 285].
The instant specification does not describe the functional fragment or provide the structural requirements of the inhibitor and/or activator that are required for the fragment, inhibitor, and/or activator to be able to organize into a proteinaceous exterior around a genetic element. The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of polypeptides having an activity and/or structural feature of any Anellovirus ORF1 protein, such as a single domain that is an arg-rich region, jelly-roll domain, hypervariable domain, N22 domain or C-terminal domain, which must function to provide a proteinaceous exterior around a genetic element.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 57-60, 62-69, 73, and 77.
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 58 is 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 58 recites the synthetic particle of claim 57 wherein the polypeptide encoded by the Anellovirus ORF1 nucleic acid is an ORF1 molecule. Claim 57 recites in part a synthetic particle comprising: (I) a genetic element and (II) a proteinaceous exterior comprising a polypeptide encoded by an Anellovirus ORF1 nucleic acid. The specification defines the term “ORF1 molecule” as a polypeptide having an activity and/or a structural feature of an Anellovirus ORF1 protein, or a functional fragment thereof [page 135, second paragraph]. Therefore, given the broadest reasonable interpretation in view of the specification, claim 58 does not further limit claim 57.
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.
Claims 68 and 69 are each 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.
Claims 68 and 69 depend from claim 57, which is drawn to a synthetic particle comprising (I) a genetic element, and (II) a proteinaceous exterior. Claims 68 and 69 only require the genetic element of the synthetic particle of claim 57. Thus, the dependent claims fail to include all of the limitations of the claim on which they depend.
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.
Claim 73 is 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 73 depends from claim 57, which is drawn to a synthetic particle comprising (I) a genetic element, and (II) a proteinaceous exterior. Claim 73 only requires the genetic element of the synthetic particle of claim 57. Thus, the dependent claim fails to include all of the limitations of the claim on 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.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 73 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 73 recites a host cell comprising a first nucleic acid molecule comprising the nucleic acid sequence of a genetic element of a synthetic particle of claim 57 and optionally a second nucleic acid molecule encoding one or more of an amino acid sequence chosen from ORF1, ORF2, ORF2/2, ORF2/3, ORF1/1, or ORF1/2 of any of SEQ ID NOS: 55-60, or an amino acid sequence having at least 85% sequence identity thereto. The specification discloses that an anellosome or composition thereof described herein, e.g., comprising an effector, may be used to deliver the effector to a cell, tissue, or subject [page 385, last paragraph]. The specification also discloses that the anellosomes and compositions comprising anellosomes described herein may be used in methods of treating a disease, disorder, or condition, e.g., in a subject (e.g., a human subject) in need thereof [page 385, third paragraph]. Thus, in view of the specification, the broadest reasonable interpretation of the claimed cell includes a human being. Therefore, the claim is directed to nonstatutory subject matter. It would be remedial to amend the claim to recite “An ex vivo host cell” as supported by at least the 4th paragraph of page 8 of the substitute specification filed 3/10/2025.
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.
Claims 57-60, 62-69, 73, and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Leary et al. (US 6,395,472; reference cited by Applicant), Wang et al. (Molecular Genetics and Metabolism 2012), Bostan et al. (J. Vaccines Vaccin 2013; reference cited by Applicant), Peng et al. (Archives of Virology 2002), Galmes et al. (Eur Respir J 2013; reference cited by Applicant), and GenBank Accession No. JX134045 (2013).
Regarding claims 57-60, 62-69, 73, and 77, Leary et al. teaches a TTV-based vector (genetic element of the claims) comprising: 1) a promoter; 2) a heterologous DNA sequence encoding a protein; and 3) a nucleotide sequence encoding TTV, a fragment of the nucleotide sequence or a complement of the nucleotide sequence or the fragment, wherein the heterologous DNA sequence is operably linked to the promoter derived from TTV or from a heterologous source. The vector may be capable of being packaged into TTV particles for stable maintenance or expression of said heterologous DNA sequence [column 5, first full paragraph]. Leary et al. also teaches a host cell comprising the vector wherein the host cell may be eukaryotic [column 5, second full paragraph]. Leary et al. also teaches that the vector can consist of parts of the genome such as the replication origin, specific genes, promoters, or other control elements and can be used for expression of cloned genes in culture or in gene therapy treatment [column 7, fourth full paragraph]. Leary et al. teaches that the entire TTV genome could be used, either in its wild type form or modified to alter specific properties such as vector capacity, efficiency of replication, host cell range, transmission and the like [column 20, last paragraph]. Leary et al. also teaches that TTV sequences, non-essential to vector function, can be eliminated in order to increase the amount of foreign DNA the vector can accommodate [column 48, first paragraph]. Leary et al. teaches that similar to the Circoviridae, TTV is a non-enveloped virus which contains a single-stranded circular DNA genome [column 9, second full paragraph].
However, Leary et al. does not specifically teach (I) the genetic element where the exogenous effector is an intracellular polypeptide or an intracellular nucleic acid, and (II) a proteinaceous exterior comprising a polypeptide encoded by an Anellovirus ORF1 nucleic acid wherein the genetic element is enclosed within the proteinaceous exterior. Leary et al. does not teach the ORF1 polypeptide has been proteolytically processed. Leary et al. does not teach the ORF1 polypeptide comprises the sequence of SEQ ID NO: 58. Leary et al. does not teach the genetic element comprises a sequence having at least 75% sequence identity to a 5’ UTR conserved domain of a wild-type Anellovirus. Leary et al. also does not teach a pharmaceutical composition comprising at least 103, 104, 105, 106, 107, 108, or 109 synthetic particles and a pharmaceutically acceptable carrier or excipient.
Wang et al. teaches that ornithine transcarbamylase deficiency (OTCD), the most common and severe urea cycle disorder, is an excellent model for developing liver-directed gene therapy. Wang et al. generated a vector for a proposed OTC gene therapy trial in humans based on a self-complementary AAV8 vector expressing codon-optimized human OTC hunder the control of a liver-specific promoter. Functional expression of hOTC in 40% of liver areas was found in mice treated with a low vector dose of 1 x 109 GC. Furthermore, the vector has the potential to achieve therapeutic effects in OTCD patients [abstract].
Bostan et al. teaches the structure and genomic organization of TTV as shown below.
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380
542
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Bostan et al. teaches that the TTV genome is single stranded, circular, and 3.8 kb in length which contains both coding and non-coding regions with sizes 2.6 kb and 1.2 kb, respectively. Further, the genome contains conserved regions in the non-coding area of the genome (UTRs) that include GC rich region, a poly A sequence downstream, and a TATA box upstream of the coding region [page 2, left column, first full paragraph]. Bostan et al. also teaches that ORF1 (predicted length of 719-770 amino acids) encodes a capsid protein and contains hyper variable regions where the occurrence of mutations in ORF1 is much higher than any other proteins of TTV in which change in nucleotides leads to amino acid changes and occurs more frequently than in other protein parts. Further, the protein encoded by ORF1 has an Arginine-rich N-terminus that may function in binding of DNA during the process of packaging of viral DNA into capsid [page 2, left column, last paragraph bridging to right column]. Bostan et al. also teaches that other types of TTV-like viruses have been discovered such as torque teno mini virus (TTMV), small anellovirus (SAV), and torque teno midi virus (TTMDV). Further, TTMV’s genome has a great resemblance with TTV such as a GC-rich region, a coding region, CAV like motif in ORF 2 region and an Arginine-rich N-terminus [page 3, third and fifth full paragraph].
Peng et al. teaches that the nucleotide sequence of the untranslated region (UTR) of TTV is more conserved than that of the coding regions, and some blocks in the UTR are well conserved even among the four distinct genetic groups of TTV [page 22, second paragraph]. As shown in Figure 6, two specific regions downstream of the polyadenylation signal and just downstream of the TATA box were well preserved among the TTVs of the five distinct groups. The point mutations and deletion/insertion of nucleotide observed in the inverted repeat sequences downstream of the polyadenylation signal were covariant (Figure 6b) thus suggesting the strict conservation of the putative stem-loop structures maintained by all TTV groups as previously described for TTVs of groups 1 and 3 [page 34, first full paragraph].
Galmes et al. identified three new isolates of TTMV (TTMV-LY) and demonstrated the in vitro replication of TTMV-LY in alveolar epithelial cells and effective release of infectious viral particles [abstract]. Galmes et al. teaches that one other feature of the viruses is the highly conserved 5’-UTR as shown in Figure 2. Further, Figure 2a shows that TTMV-LY2 possess a significant insertion in the 5’UTR forming a predictive secondary structure of RNA sequence and appears to be capable of forming a stable loop-and-dimer structure [page 473, last paragraph]. Galmes et al. also teaches that for the first time, TTMV, like TTV, was able to replicate in cell lines after transfection of its genome and thus lead to the production of infectious virions [page 477, last paragraph].
GenBank Accession No. JX134045 shows the complete genome of TTV-like mini virus isolate TTMV-LY2 which is 2979 nucleotides in length. The sequence of nucleotides 612-2612 (designated as Db) encodes an ORF1 molecule that is 100% identical to SEQ ID NO: 58 (designated as Qy) of the present application.
LOCUS JX134045 2979 bp DNA circular VRL 16-MAR-2013
DEFINITION TTV-like mini virus isolate TTMV_LY2, complete genome.
ACCESSION JX134045
VERSION JX134045.1
KEYWORDS .
SOURCE TTV-like mini virus (TTMV)
ORGANISM TTV-like mini virus
Viruses; Viruses incertae sedis; Anelloviridae; Betatorquevirus.
REFERENCE 1 (bases 1 to 2979)
AUTHORS Galmes,J., Li,Y., Rajoharison,A., Ren,L., Dollet,S., Richard,N.,
Vernet,G., Javouhey,E., Wang,J., Telles,J.N. and
Paranhos-Baccala,G.
TITLE Potential implication of new torque teno mini viruses in
parapneumonic empyema in children
JOURNAL Eur. Respir. J. (2012) In press
PUBMED 23060626
REMARK Publication Status: Available-Online prior to print
REFERENCE 2 (bases 1 to 2979)
AUTHORS Galmes,J., Li,S., Rajoharison,A., Telles,J.-N. and Baccala,G.
TITLE Direct Submission
JOURNAL Submitted (05-JUN-2012) Laboratoire des Pathogenes Emergents,
Fondation Merieux, 21 Avenue Tony Garnier, Lyon Cedex 07 69365,
France
FEATURES Location/Qualifiers
source 1..2979
/organism="TTV-like mini virus"
/mol_type="genomic DNA"
/isolate="TTMV_LY2"
/host="Homo sapiens"
/db_xref="taxon:93678"
/geo_loc_name="France"
/collection_date="14-Feb-2008"
CDS 424..723
/note="ORF2"
/codon_start=1
/product="hypothetical protein"
/protein_id="AGG91485.1"
/translation="MSDCFKPTCYNNKTKQTHWINNLHLTHDLICFCPTPTRHLLLAL
AEQQETIEVSKQEKEKITRCLITTEEDGTTTDVLDGMDEVGLDALFAEDFEEKEG"
CDS 612..2612
/note="ORF1"
/codon_start=1
/product="hypothetical protein"
/protein_id="AGG91484.1"
/translation="MPYYYRRRRYNYRRPRWYGRGWIRRPFRRRFRRKRRVRPTYTTI
PLKQWQPPYKRTCYIKGQDCLIYYSNLRLGMNSTMYEKSIVPVHWPGGGSFSVSMLTL
DALYDIHKLCRNWWTSTNQDLPLVRYKGCKITFYQSTFTDYIVRIHTELPANSNKLTY
PNTHPLMMMMSKYKHIIPSRQTRRKKKPYTKIFVKPPPQFENKWYFATDLYKIPLLQI
HCTACNLQNPFVKPDKLSNNVTLWSLNTISIQNRNMSVDQGQSWPFKILGTQSFYFYF
YTGANLPGDTTQIPVADLLPLTNPRINRPGQSLNEAKITDHITFTEYKNKFTNYWGNP
FNKHIQEHLDMILYSLKSPEAIKNEWTTENMKWNQLNNAGTMALTPFNEPIFTQIQYN
PDRDTGEDTQLYLLSNATGTGWDPPGIPELILEGFPLWLIYWGFADFQKNLKKVTNID
TNYMLVAKTKFTQKPGTFYLVILNDTFVEGNSPYEKQPLPEDNIKWYPQVQYQLEAQN
KLLQTGPFTPNIQGQLSDNISMFYKFYFKWGGSPPKAINVENPAHQIQYPIPRNEHET
TSLQSPGEAPESILYSFDYRHGNYTTTALSRISQDWALKDTVSKITEPDRQQLLKQAL
ECLQISEETQEKKEKEVQQLISNLRQQQQLYRERIISLLKDQ"
RESULT 1
AASEQ2_05092025_133541
Query Match 100.0%; Score 3640; DB 1; Length 666;
Best Local Similarity 100.0%;
Matches 666; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPYYYRRRRYNYRRPRWYGRGWIRRPFRRRFRRKRRVRPTYTTIPLKQWQPPYKRTCYIK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MPYYYRRRRYNYRRPRWYGRGWIRRPFRRRFRRKRRVRPTYTTIPLKQWQPPYKRTCYIK 60
Qy 61 GQDCLIYYSNLRLGMNSTMYEKSIVPVHWPGGGSFSVSMLTLDALYDIHKLCRNWWTSTN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GQDCLIYYSNLRLGMNSTMYEKSIVPVHWPGGGSFSVSMLTLDALYDIHKLCRNWWTSTN 120
Qy 121 QDLPLVRYKGCKITFYQSTFTDYIVRIHTELPANSNKLTYPNTHPLMMMMSKYKHIIPSR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QDLPLVRYKGCKITFYQSTFTDYIVRIHTELPANSNKLTYPNTHPLMMMMSKYKHIIPSR 180
Qy 181 QTRRKKKPYTKIFVKPPPQFENKWYFATDLYKIPLLQIHCTACNLQNPFVKPDKLSNNVT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QTRRKKKPYTKIFVKPPPQFENKWYFATDLYKIPLLQIHCTACNLQNPFVKPDKLSNNVT 240
Qy 241 LWSLNTISIQNRNMSVDQGQSWPFKILGTQSFYFYFYTGANLPGDTTQIPVADLLPLTNP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LWSLNTISIQNRNMSVDQGQSWPFKILGTQSFYFYFYTGANLPGDTTQIPVADLLPLTNP 300
Qy 301 RINRPGQSLNEAKITDHITFTEYKNKFTNYWGNPFNKHIQEHLDMILYSLKSPEAIKNEW 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RINRPGQSLNEAKITDHITFTEYKNKFTNYWGNPFNKHIQEHLDMILYSLKSPEAIKNEW 360
Qy 361 TTENMKWNQLNNAGTMALTPFNEPIFTQIQYNPDRDTGEDTQLYLLSNATGTGWDPPGIP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 TTENMKWNQLNNAGTMALTPFNEPIFTQIQYNPDRDTGEDTQLYLLSNATGTGWDPPGIP 420
Qy 421 ELILEGFPLWLIYWGFADFQKNLKKVTNIDTNYMLVAKTKFTQKPGTFYLVILNDTFVEG 480
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Db 421 ELILEGFPLWLIYWGFADFQKNLKKVTNIDTNYMLVAKTKFTQKPGTFYLVILNDTFVEG 480
Qy 481 NSPYEKQPLPEDNIKWYPQVQYQLEAQNKLLQTGPFTPNIQGQLSDNISMFYKFYFKWGG 540
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Db 481 NSPYEKQPLPEDNIKWYPQVQYQLEAQNKLLQTGPFTPNIQGQLSDNISMFYKFYFKWGG 540
Qy 541 SPPKAINVENPAHQIQYPIPRNEHETTSLQSPGEAPESILYSFDYRHGNYTTTALSRISQ 600
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Db 541 SPPKAINVENPAHQIQYPIPRNEHETTSLQSPGEAPESILYSFDYRHGNYTTTALSRISQ 600
Qy 601 DWALKDTVSKITEPDRQQLLKQALECLQISEETQEKKEKEVQQLISNLRQQQQLYRERII 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 DWALKDTVSKITEPDRQQLLKQALECLQISEETQEKKEKEVQQLISNLRQQQQLYRERII 660
Qy 661 SLLKDQ 666
||||||
Db 661 SLLKDQ 666
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Leary et al. by also constructing a TTV-based or TTMV-based vector comprising a modified genome comprising (I) a genetic element comprising a promoter element and a nucleic acid sequence encoding an exogenous effector wherein the nucleic acid sequence is operably linked to the promoter element and wherein the exogenous effector is an intracellular polypeptide or an intracellular nucleic acid, and (II) a proteinaceous exterior comprising a polypeptide encoded by an Anellovirus ORF1 nucleic acid wherein the genetic element is enclosed within the proteinaceous exterior, because Silver et al. demonstrated that recombinant adeno-associated virus vectors were used to deliver a secretory version of the human ADA gene to various tissues to promote immune reconstitution following enzyme expression in a mouse model of ADA deficiency, Bostan et al. taught that the conserved regions in the TTV genome are present in the UTRs, ORF1 encodes a capsid protein having an Arginine-rich N-terminus that may function in binding of DNA during the process of packaging of viral DNA into capsid, and TTV-like viruses such as TTMV having a great resemblance with TTV, Peng et al. taught that the nucleotide sequence of the UTR of TTV is more conserved than that of the coding regions, and two specific regions downstream of the polyadenylation signal and just downstream of the TATA box are well preserved among the TTVs of the five distinct groups, and Galmes et al. taught that the 3 new isolates of TTMV-LY all share the highly conserved 5’-UTR and successfully demonstrated in vitro replication of TTMV-LY in aveolar epithelial cells and effective release of infectious viral particles.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Leary et al., Bostan et al., Peng et al., and GenBank Accession No. JX134045 by formulating a pharmaceutical composition comprising about 1.0 x 109 GC (genome copy) of engineered TTV-based or TTMV-based virions for treating a subject with ornithine transcarbamylase deficiency.
One of skill would have been motivated to do so because it would have amounted to combining prior art elements according to known methods to yield predictable results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 57-59 and 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 97-100 and 102 of copending Application No. 17/413,392 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims overlap in scope.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 57-60, 62-69, and 73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 55-67 and 71 of copending Application No. 17/413,297 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims overlap in scope. Instant SEQ ID NO: 217 has a 100% match to SEQ ID NO: 217 of application ‘297.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 57-60, 62-69, and 73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 55-58, 60-67 and 71 of copending Application No. 17/413,207 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims overlap in scope. Instant SEQ ID NO: 217 has a 100% match to SEQ ID NO: 217 of application ‘297.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 57-60, 62-69, and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-66 of U.S. Patent No. 11,166,996. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims overlap in scope and encompass the same recombinant anellovirus.
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Response to Arguments
Applicant's arguments filed March 10, 2025 have been fully considered but they are not persuasive.
Applicant requests that the nonstatutory double patenting rejections be held in abeyance until the outstanding rejections are overcome, and if appropriate, Applicant will consider the filing of terminal disclaimers. Thus, the nonstatutory double patenting rejections are maintained.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kincaid, R. P., Burke, J. M., Cox, J. C., de Villiers, E. M., & Sullivan, C. S. (2013). A human torque teno virus encodes a microRNA that inhibits interferon signaling. PLoS pathogens, 9(12), e1003818; reference cited by Applicant. Kincaid et al. discloses a recombinant human Torque Teno Virus encodes an exogenous microRNA that inhibits interferon signaling [abstract]. However, this article has been retracted.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached on (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637