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
Applicant’s remarks, sequence listing, and amendments to the specification and drawings filed January 7, 2026 are acknowledged. Claims 1-4, 7-15, and 19-36 are pending.
Restriction/Election
Applicant’s election of Group I (claims 1-4, 7-15, and 19-31) without traverse in the reply filed January 7, 2026 is acknowledged. Accordingly, claims 32-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Claims 1-4, 7-15, and 19-31 are under consideration herein.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of prior-filed Application No. 63/006,115 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, Application No. 63/006,115 does not disclose the limitations of instant claims 19-20. The first disclosure of “gene editing,” and gene editing using “anti-sense RNA, a siRNA, a shRNA and/or a CRISPR/Cas system” is Application No. PCT/IB2021/052898 ([100]; [195]). The effective filing date of claim 19-20 is April 7, 2021, accordingly. The remaining claims under examination find support in Application No. 63/006,115, and have an effective filing date of April 7, 2020.
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 I. Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Specifically, the amino acid sequence “TAYT” which appears throughout the specification must be identified by a sequence identifier at each instance (at least paragraphs [12], [28]-[29], [74], etc.).
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.
Specific deficiency II. Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. The nucleotide sequences are located in Figs. 10-18, within and above the diagrams. Specifically, each sequence which is presently identified as “positions X-X of SEQ ID NO: X,” must be included in the sequence listing and identified with a separate sequence identifier.
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.
Specification
The specification is objected to because of the following informalities:
The specification recites “TATY” in paragraphs [47] and [190], which appears to be a typographical error. These instances should be amended to recite “TAYT” as recited throughout the disclosure.
Appropriate correction is required.
Drawings
The replacement drawings filed January 7, 2026 are objected to because of the following informalities:
37 CFR 1.84(l) states that “all drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.” In the instant case, Figs. 10, 13-14, and 17 contain illegible text (“positions… of SEQ ID NO: X”) which is not sufficient to provide satisfactory reproduction characteristics.
Appropriate correction is required.
Claim Objections
Claim 21 is objected to because of the following informalities:
Claim 21 recites “wherein at least a portion of the genes encoding the E1ACR2 gene, at least a portion of the E1B19K gene and/or at least a portion of the E3gp19K is deleted.” It would be preferable to amend the claim to recite “wherein at least a portion of E1ACR2 gene, at least a portion of the E1B19K gene and/or at least a portion of the E3gp19K is deleted.”
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 applicant regards as his invention.
Claims 1-4, 7-15, and 19-31 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 modified virus Ad5, wherein the modified virus Ad5 is capable of expressing a cytokine, and… is capable of expressing an A20.” Neither the claim nor specification clearly define what makes an Ad5 “capable of” expressing a cytokine and A20. It is not clear whether “capable of” implies an unrecited structural element, e.g., a promoter sequence, a cytokine and/or A20 sequence, machinery for protein expression, and/or machinery which enables the Ad5 to infect a host cell which comprises machinery for protein expression, or, alternatively, whether any Ad5 is “capable” owing to gene editing and gene recombination techniques described in the specification. It is not clear what, if any, structure(s) the modified virus Ad5 must have to be “capable of” expressing a cytokine and A20, which renders the claim indefinite.
Claims 2-4, 7-15, and 19-31 are rejected for depending from claim 1 and failing to remedy the indefiniteness. Claim 23 also recites that the modified virus Ad5 is “capable of expressing a gene and/or a ligand targeting a T cell, a gene and/or a ligand targeting a tumor cell, and/or a therapeutic gene.” Claim 23 is also indefinite for the reasons described immediately above as for claim 1.
In view of the indefiniteness described above, hereinafter, the phrase “capable of” will not be interpreted as implying unrecited structural elements; any Ad5 (i.e., adenovirus species C serotype 5, [94]) will be understood as “capable of” expressing a protein encompassed by the claims, i.e., a cytokine, A20, gene or ligand targeting a T cell, etc., owing to gene editing and gene recombination techniques described in the specification.
Claims 8-9 recite “the gene encoding the A20.” Claim 1 recites that “the modified virus Ad5 is capable of expressing an A20,” but this phrase does not explicitly set forth a gene encoding the A20. Claim 1 also does not clearly imply the presence of such a gene for the reasons described above. Thus, the phrase “the gene encoding the A20” lacks sufficient antecedent basis in claims 8-9.
Claim 11 is rejected for depending from claim 9 and failing to remedy the indefiniteness.
Claims 13 and 14 recite amino acid residues of a fibre region of the modified virus Ad5, i.e., “Y477A,” and “TAYT at the residues 489-492.” The specification states that the “fibre region” refers to the fibre structure of adenoviruses ([98]). The claims do not provide any reference for the recited residues, e.g., by referring to a SEQ ID NO, and it is clear from the specification and prior art referred to therein, that the sequence of the fibre region of adenoviruses varies ([98]). Accordingly, the modified virus Ad5 which are encompassed by the claims would not be clear to the skilled artisan. With respect to claim 13, it is not clear whether the claim is directed to a modified virus Ad5 which comprises an “A” at residue 477, or a modified virus Ad5 comprising an “A” at a residue equivalent to residue Y477 of some unrecited reference sequence (e.g., as determined by sequence alignment). With respect to claim 14, it is not clear whether the claim is directed to a modified virus Ad5 which does not comprise the sequence “TAYT” at residues 489-492, or a modified virus Ad5 which does not comprise the sequence “TAYT” at residues equivalent to residues 489-492 of some unrecited reference sequence.
In view of the indefiniteness described above, hereinafter, these claims will be interpreted as encompassing either interpretation above (i.e., either the Ad5 must have/not have the specific residues at the specific positions recited, or the Ad5 must have/not have the specific residues at any residue equivalent to the specific positions recited).
Claim 22 recites “the gene encoding a cytokine.” Claim 1 recites that “the modified virus Ad5 is capable of expressing a cytokine,” but this phrase does not explicitly set forth a gene encoding a cytokine. Claim 1 also does not clearly imply the presence of such a gene for the reasons described above. Thus, the phrase “the gene encoding a cytokine” lacks sufficient antecedent basis in claim 22.
Claim 24 recites “a gene encoding a cytotoxic.” This appears to be an incomplete phrase, as “cytotoxic” is typically used as an adjective to describe a noun. The genes encompassed by this incomplete phrase are unclear, which renders the claim indefinite.
Claims 25-27 are rejected for depending from claim 24 and failing to remedy the indefiniteness.
Claim 25 recites “a Flt3 ligand or the variant thereof.” The skilled artisan would interpret the term “Flt3 ligand” as encompassing agents which bind to the receptor Flt3, e.g., a FLT3L protein. The skilled artisan could envision many variants of this protein, and neither the claim nor specification clearly set forth “the variant” of a Flt3 ligand. It is not clear what “the variant” refers to, which renders the claim indefinite.
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.
Claims 1-4, 7-8, 12, and 23-31 are rejected under 35 U.S.C. § 101 because the claimed inventions are directed to judicial exceptions (i.e., a law of nature, natural phenomenon, or an abstract idea) without significantly more. The claims are drawn to a modified virus Ad5. This judicial exception is not integrated into a practical application and does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Step 1 – Is the Claim to a Process, Machine, Manufacture, or Composition of Matter? YES
Claims 1-4, 7-8, 12, and 23-27 are directed to a modified Ad5 virus, which is a composition of matter. The claims are directed to a statutory category.
Step 2A, Prong One – Does the Claim Recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES
Laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. MPEP 2106.04(c) outlines the markedly different characteristics analysis.
Claim 1 recites “A modified virus Ad5, wherein the modified virus Ad5 is capable of expressing a cytokine, and… capable of expressing an A20.” Claim 23 recites that the modified virus Ad5 is “capable of expressing a gene and/or ligand targeting a T cell, a gene and/or ligand targeting a tumor cell, and/or a therapeutic gene.” For the reasons described in paragraph 12 above, any Ad5 (i.e., adenovirus species C serotype 5, [94]) is understood to be “capable of” expressing a protein encompassed by the claims. The Ad5 is a “modified virus,” wherein the term “modified” is interpreted as referring to a product-by-process. Product-by-process claims are limited by the structure implied by the steps, which in the instant case is “modification.” See MPEP 2113 (I). The structure implied by the term “modified” is an Ad5 which differs in some way relative to a reference Ad5 (i.e., any other Ad5), e.g., an Ad5 which possesses a mutation in the fibre region relative to a different Ad5.
The closest naturally occurring counterpart to the modified virus Ad5 of claims 1, 12, and 23 is the human Ad5 strain corresponding to GenBank Accession No. OR728260.1. As shown in the attached alignment in Appendix I, OR728260.1 possesses several modifications in the fibre region relative to the human Ad5 strain corresponding to GenBank Accession No. PX146748.1. OR728260.1 is also the closest naturally occurring counterpart to the modified virus Ad5 of claims 2-4, 7-8, and 24-27, because while these claims recite further limitations of the cytokine, A20, and/or “gene and/or ligand targeting a T cell…” referred to in claims 1 and 23, a cytokine, A20, and/or “gene and/or ligand targeting a T cell…” is not actually required of claims 1 and 23, and any Ad5 is understood to be “capable of” expressing these proteins. In view of the foregoing, the modified virus Ad5 of claims 1-4, 7-8, 12, and 23-27 are not markedly different from the naturally occurring counterpart, and recite product of nature judicial exceptions.
Step 2A, Prong Two – Does the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application? NO
The Supreme Court has long distinguished between principles themselves, which are not patent
eligible, and the integration of those principles into practical applications, which are patent eligible. The
phrase "integration into a practical application" requires an additional element or a combination of
additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes
a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to
monopolize the exception.
As described above, the limitations of claims 1-4, 7-8, 12, and 23-27 are present in the naturally occurring counterpart. The claims do not recite any additional elements that would integrate the natural products into a practical application.
Step 2B – Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to "significantly more" than the judicial exception(s) itself. The claim as a whole is evaluated as to whether it amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (MPEP 2106.05).
The limitations of claims 1-4, 7-8, 12, and 23-27 are present in the naturally occurring counterpart. The claims do not recite any additional elements which would amount to significantly more than the judicial exceptions.
Additional Dependent Claims
Claim 28 recites “An isolated nucleic acid molecule, encoding the modified virus Ad5 of claim 1.” The closest naturally occurring counterpart to the isolated nucleic acid molecule is the genome of OR728260.1. The term “isolated” is not sufficient to render the nucleic acid molecule markedly different from the naturally-occurring counterpart, which is a nucleic acid molecule encoding a modified virus Ad5. See MPEP 2106.04(c)(II)(C)(2). The claim does not recite any additional elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Claim 29 recites “A vector, comprising the isolated nucleic acid molecule of claim 28.” The specification does not appear to define the term “vector,” which is interpreted as an element capable of carrying the isolated nucleic acid, e.g., into cells. A virus is such a vector. Thus, the closest naturally occurring counterpart to the vector is the human Ad5 strain corresponding to GenBank Accession No. OR728260.11. The claim does not recite any additional elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Claim 30 recites “A cell, comprising the modified virus Ad5 of claim 1.” The closest naturally occurring counterpart to the claimed cell is a human cell infected with the human Ad5 strain corresponding to GenBank Accession No. OR728260.11, which as evidenced by GenBank is in human cells in its natural state (“/isolation_source = “nasal swab” /host = “Homo sapiens””). The claim does not recite any elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Claim 31 recites “A pharmaceutical composition, wherein the pharmaceutical composition comprises the modified virus Ad5 of claim 1 and a pharmaceutically accepted adjuvant.” The preamble term “pharmaceutical” is interpreted as an intended use for the composition which does not structurally limit the claim, because the claim body recites a structurally complete invention. The term “pharmaceutically accepted adjuvant” is not defined by the specification. The specification provides examples of such adjuvants, e.g., “buffering agents, polymers, antioxidants… chelating agents… suspending agents…,” etc. Thus, the term “pharmaceutically accepted adjuvant” is interpreted as a second element suitable for delivery to cells (“pharmaceutically accepted”) and which is intended to facilitate the effectiveness of the composition. The claimed pharmaceutical composition is essentially the modified virus Ad5 of claim 1 and, for example, a buffering agent. Thus, the closest naturally occurring counterpart to the claimed composition is the cytosol of a human cell infected with the human Ad5 strain corresponding to GenBank Accession No. OR728260.11, which as evidenced by GenBank is in human cells in its natural state (“/isolation_source = “nasal swab” /host = “Homo sapiens””). The cytosol comprises various buffering agents. See Casey et al., 2009, Nature Reviews Molecular Cell Biology, 11, 50-61 (2010). The claim does not recite any additional elements which integrate the judicial exception into a practical application, or amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 102 – Man
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.
Claims 1-4, 7-15, 19-21, and 23-31 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Man (Man et al., February 2018, Molecular Cancer Therapeutics, 17(2), pg. OF1-OF13; of record).
For the reasons described in paragraph 20 above, claims 1 and 23 are interpreted as being directed to any Ad5 (i.e., human adenovirus species C serotype 5, [94]) which differs in some way relative to a reference Ad5, e.g., comprising at least one modification in a fibre region as recited in claim 12.
Regarding claims 1, 12, and 23, Man teaches a modified Ad5 virus (“Ad5-3∆-A20T”) which comprises at least one modification in the fibre region relative to a reference Ad5 (“Ad5-3∆-A20477dlTAYT (Ad5-3∆-A20T,” pg. OF2, right col.; “Y477A/∆TAYT,” “Fibre,” Fig. 5A).
Regarding claims 2-4, 7-8, and 24-27, while these claims recite further limitations of the cytokine, A20, and/or “gene and/or ligand targeting a T cell…” referred to in claims 1 and 23, a cytokine, A20, and/or “gene and/or ligand targeting a T cell…” is not actually required of claims 1 and 23, and any Ad5 is understood to be “capable of” expressing these proteins. Thus, Man’s modified Ad5 virus (Ad5-3∆-A20T”) anticipates these claims.
Regarding claims 9-10, Man teaches the modified Ad5 virus comprises an A20 (“A20FMDV2 peptide”) in the HI-loop of the virus’ genome (“the A20FMDV2 peptide was inserted and CAR binding was ablated in the fiber knob (HI-loop) of the Ad∆∆ mutant, to generate Ad5-3∆-A20T,” pg. OF8, left col.; Fig. 5A).
Regarding claim 11, the claim is interpreted as product-by-process, which is limited by the structures implied by the process step (“wherein the incorporation uses a method of gene editing and/or gene recombination”). See MPEP 2113 (I). The structure implied by the process steps is a modified Ad5 virus comprising a gene encoding an A20 in its genome. This is anticipated by Man for the reasons described immediately above for claims 9-10.
Regarding claims 13-14, Man teaches the modified Ad5 virus comprises a Y477A amino acid substitution, and a deletion of amino acids TAYT in the fibre region (“deletion of the TAYT motif and the point mutation at Y477A were included to reduce CAR binding…,” pg. OF8, left col.; Fig. 5A).
Regarding claims 15 and 21, Man teaches that the E1ACR2 gene, E1B19K gene, and E3gp19K gene are deleted in the modified Ad5 virus (pg. OF1, right col.; “Viruses and infections,” pg. OF2, right col.; Fig. 5A; pg. OF8, left col.). Man’s modified Ad5 virus, therefore, meets the limitations of claims 15 and 21 because the genes are deleted, and therefore, the expression and/or activity is downregulated as recited in claim 15.
Regarding claims 19-20, the claims are interpreted as products-by-process, which are limited by the structures implied by the process step (“wherein the downregulation uses a method of gene editing and/or gene recombination,” wherein “the gene editing uses an anti-sense RNA, a siRNA, a shRNA and/or a CRISPR/Cas system”). See MPEP 2113 (I). The structure implied by the process steps is a modified Ad5 virus, which when compared to a wildtype Ad5 virus, displays downregulated expression and/or activity of a E1ACR2 gene, E1B19K gene, and/or E3gp19K gene. This is anticipated by Man for the reasons described immediately above for claims 15 and 21.
Regarding claim 28, the interpretation of claim 28 is described in paragraph 23 above and applied here. Man teaches an isolated nucleic acid encoding the modified Ad5 virus (““Viruses and infections,” pg. OF2, right col.).
Regarding claim 29, the interpretation of claim 29 is described in paragraph 23 above and applied here. The claim is interpreted as encompassing a virus comprising the isolated nucleic acid, which is interpreted as encompassing a viral genome. The modified Ad5 virus taught by Man, i.e., Ad5-3∆-A20T, meets these limitations.
Regarding claim 30, Man teaches cells comprising the modified Ad5 virus (“Panc04.03,” and “Suit-2,” pg. OF8-OF9; Figs. 5-6).
Regarding claim 31, the interpretation of claim 31 is described in paragraph 23 above and applied here. Man teaches pharmaceutical compositions comprising the modified Ad5 virus and a pharmaceutically accepted adjuvant (“All infections were performed in serum-free DMEM,” pg. OF2, right col.; “Treatments were initiated… by intratumoral administration of adenoviral mutants at doses ranging from…,” pg. OF3, right col.; “Cells were infected with Ad5-3∆-A20T… and virus collected from media,” Fig. 5 and description; “Adenoviral mutants or PBS (mock controls) were administrated intratumorally…,” Fig. 6 and description).
Notice to Joint Inventors
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.
Claim Rejections - 35 USC § 103 – Man in view of Baker
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.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Man (Man et al., February 2018, Molecular Cancer Therapeutics, 17(2), pg. OF1-OF13; of record) as applied to claims 1-4, 7-15, 19-21, and 23-31 above, in view of Baker (Baker et al., 2018, Cancers, 10, 201, pg. 1-39).
The teachings of Man are described above and applied as to claims 1-4, 7-15, 19-21, and 23-31 therein. Man teaches that the modified Ad5 virus is “highly selective for αvβ6 integrin-expressing pancreatic cancer cells” by virtue of expressing A20 (“A20FMDV2”) which selectively binds to αvβ6 (Abstract; pg. OF2, left col.). Man teaches that the virus exhibits “enhanced infectivity and cell killing in PDAC cells,” and is “an excellent candidate for targeting pancreatic cancer” (pg. OF11, right col.). Man states that the virus will “guide further optimization of oncolytic adenoviruses for systemic delivery to improve on therapeutic efficacy in patients with pancreatic cancer…” (pg. OF2, left col.).
Man does not teach that the modified Ad5 virus comprises a gene encoding a cytokine in the E1ACR2 gene, the E1B19K gene, or the E3gp19K gene.
Baker teaches that “IL-12 is a proinflammatory cytokine with great potential to activate the host anti-tumour immune responses after oncolytic virus infection” (pg. 8). Baker teaches that a modified Ad5 virus comprising a gene encoding IL-12 is “currently in Phase I clinical trials for patients with metastatic pancreatic cancer in combination with cytotoxic drugs” (pg. 8). Baker teaches that IL-12 (“a less toxic version of IL-12”) has also been expressed from “the highly efficacious Ad∆∆ mutant… by replacing the E3gp19k gene” (pg. 8). Baker teaches that the resulting virus showed promising efficacy in models of pancreatic cancer (pg. 8). As evidenced by Baker, the “Ad∆∆ mutant” which was modified to comprise a gene encoding IL-12 is identical to the Ad∆∆ mutant used to generate the modified Ad5 virus of Man (“We previously generated an E1ACR2-deleted mutant… deleting… E1B19K (Ad∆∆)… we further increased the selectivity and efficacy of Ad∆∆ by… inserting… (A20FMDV) generating Ad5-3∆-A20T,” pg. 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the Ad5 virus of Man such that it comprised a gene encoding a cytokine (i.e., IL-12) in the E3gp19K gene as taught by Baker. It would have amounted to a simple combination of a known modified Ad5 virus, with a known gene encoding a cytokine, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in inserting a gene encoding IL-12 into the E3gp19K gene of the virus of Man because Baker teaches that a substantially identical Ad5 virus has already been successfully modified in this way, and that the resulting virus was effective in models of pancreatic cancer, which is the intended use of Man’s virus. The skilled artisan would have been motivated to further modify the Ad5 virus of Man so as to arrive at the claimed invention, because Man suggests further optimization of the virus (“guide further optimization of oncolytic adenoviruses for systemic delivery to improve on therapeutic efficacy in patients with pancreatic cancer…,” pg. OF2, left col.), and Baker teaches that a substantially identical virus to Man’s comprising a gene encoding IL-12 was effective for the same intended use as Man (i.e., treatment of pancreatic cancer).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNA L PERSONS whose telephone number is (703)756-1334. The examiner can normally be reached M-F: 9-5pm.
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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600