DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1-12, 16-17, 21, and 26-45) and
CD55 (SEQ ID NO: 1) for the complement regulatory protein;
H3L (SEQ ID NO: 13) for the oncolytic virus membrane protein;
pSEL for the GM-CSF promoter and pLate for the complement regulatory protein promoter; and
Wyeth strain vaccinia virus for the oncolytic virus type and subtype
in the reply filed on 23 March 2026 is acknowledged.
Claim Status
3. In the amendment filed on 23 March 2026, claims 18-19, 22, 25, and 46-55 were canceled.
Claims 1-12, 16-17, 21, and 26-45 are under consideration.
Priority
4. The Instant Application is a National Stage Application (371) of PCT/KR2022/002805, filed 25 February 2022, which claims priority to KR10-2021-0026782, filed 26 February 2021.
Receipt is acknowledged of certified copies of papers required by 35 CFR 1.55. Should Applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CRF 41.154(b) and 41.202(e). Therefore, the effective filing date for purposes of applying prior art is 25 February 2022.
Failure to provide a certified translation may result in no benefit being accorded for the non-English translation.
Information Disclosure Statement
5. The information disclosure statement (IDS) submitted on 25 March 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
There were two duplicate IDS’s filed on 11 September 2025. As such one copy was not considered. One reference on the remaining copy was crossed out since it is a duplicate of a reference on the IDS filed 25 August 2023. The remaining references were considered by the examiner.
The IDS filed on 25 August 2023 had an unreadable foreign patent literature translation and thus that translation was not considered. The remaining references were considered by the examiner.
6. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. It is noted that this applies to any sequence accession numbers or protein IDs unless they were also submitted in the sequence listing.
Nucleotide and/or Amino Acid Sequence Disclosures
7. 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:
8. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification 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.
The TK gene recited in ¶ [0023], GM-CSF recited in ¶ [0025], and the sequence references in ¶ [0086] and ¶ [0091] refer to GenBank accession numbers, NCBI references, and protein IDs. These sequences are needed for the invention and should be added as SEQ ID NOs.
Specification
9. The use of the term “Imlygic” in ¶ [0003], which is a trade name or a mark 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
10. Claims 3, 6, 8, 30, 32, 40, and 42 are objected to because of the following informalities:
Regarding claim 3, “a foreign gene” should be “the foreign gene”.
Regarding claim 6, 30, and 40, “a gene encoding” should be “the gene encoding”.
Regarding 8, 32, and 42, it is unclear if “composed of” should be interpreted as open or closed language. Examiner is interpreting “composed of” as “comprising” and thus can have extra nucleotides/amino acids. In combination with “the sequence”, the sequence requires the entirety of SEQ ID NO: 1 but can have additional nucleotides/amino acids at the ends.
Appropriate correction is required.
11. Applicant is advised that should claims 12, 26, and 28-35 be found allowable, claims 21, 36, and 38-45, respectively, will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). It is noted that ¶ [0041] of the Instant Specification defines “pharmaceutical composition” as preventing or treating a disease. The “anti-cancer adjuvant” would still be in the form of a pharmaceutical composition and thus the difference between claims 12 and 21 (and their dependents) is merely semantics.
Claim Interpretation
12. According to ¶ [0022] of the Instant Specification, “oncolytic vaccinia virus” can be referred to as “oncolytic virus” and gives the terms antecedent basis when referred one after each other in the claims. The term “oncolytic virus” itself does not inherently refer to vaccinia virus otherwise.
13. Regarding claims 16-17, “is for” indicates intended use and thus implies that the composition must be a liquid due to the nature of the administration.
Claim Rejections - 35 USC § 112(b)
14. 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.
15. Claims 2-3, 9-11, 26-27, 33-37, and 43-45 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.
Regarding claims 2-3, 26-27, and 36-37, it is unclear if the “foreign gene” refers to GM-CSF and/or complement regulatory protein, or if it refers to a different gene. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
Claim 37, which depends on claim 26, is similarly rejected.
Regarding claims 9, 33, and 43, it is unclear what “respectively” is referring to. There are two genes but a much larger number of possible promoters.
Regarding claims 10, 34, and 44, “herpes simplex virus” and “herpes virus” appear to be referring to the same virus. Thus, that option is repeated.
Claims 11, 35, and 45, which are dependent on claims 10, 34, and 44, respectively, are similarly rejected.
Claim Rejections - 35 USC § 112(a) – Written Description
16. 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.
17. Claims 1-3, 26-27 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.
The following quotation from MPEP § 2163 is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
“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... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
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. Therefore, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1-3, 26-27, and 36-37 are rejected as lacking adequate descriptive support for the insertion of any foreign gene into any location on the TK gene resulting in suppression of the TK gene. In support of the claimed genus, the application discloses one example in which GM-CSF and CD55 were inserted into the TK J2R region. No derivatives or variants or mutants thereof are disclosed that can achieve this function. Thus, the application teaches one example with the claimed genus but fails to provide representative species of the very broad claimed genus.
The teachings of the art also fail to indicate that, without such evidence, those in the art would have expected that the insertion of any foreign gene at any location on the TK gene would result in the suppression of the TK gene. For example, a search of the art indicates that insertion of sequences into genes does not necessarily suppress gene expression. This is discussed by Lorberbaum (17 January 2011, Genesis, 49(2): 66-74): “Another major limitation is that transgenes integrate randomly in the genome so each transgenic mouse line has a unique integration site. Because chromatin at the integration site influences gene transcription, expression patterns from the same transgene differ from line to line. Some lines have no expression, others have ectopic patterns, yet others have either partial or full versions of the native gene expression pattern.” (Page 2, ¶ 1). Furthermore, Dragatsis (2001, Nucleic Acids Research, 29(3)) teaches that the insertion of the neomycin phosphotransferase gene (neo) into an intron results in an unpredictable effect of neo on the expression level of the target gene: “Insertion of neo within an intro may result in unaltered expression, a reduction in targeted gene expression (generating a hypomorphic allele), or complete inactivation” (Introduction, ¶ 3).
This art makes clear the claimed functional characteristic cannot be assumed to arise from just any insertion of just any gene into just any location of the TK gene and result in suppressed TK gene expression. Thus, a person of ordinary skill cannot identify the members of the genus recited just by the broad structural features of the claim. In view of no correlation between the claimed structure and the required function and the lack of representative species. One of ordinary skill in this art would assume Applicant did not possess the full breadth of the invention claimed. There would have been significant uncertainty as to which genes at which locations can be inserted and be able confer the claimed TK gene suppression. In view of this uncertainty and the lack of representative examples of the claimed genus, the claims are rejected for lack of adequate written description. Applicant only has such support for functional structures they teach in the specification or that are found in the prior art.
Claim Rejections - 35 USC § 112(a) – Enablement
18. In making a determination as to whether an application has met the requirements forenablement under 35 U.S.C. 112 ¶ 1, the courts have put forth a series of factors. See, In reWands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include: (1) the breadth of the claims, (2) the nature of the invention, (3) the relative skill of those in the art, (4) the presence or absence of working examples, (5) the amount of direction or guidance provided, (6) the state of the prior art, (7) the level of predictability in the art, and (8) the quantity of experimentation necessary.
19. Claims 12, 16-17, 21, 26-45 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of treating lung and colorectal cancer, does not reasonably provide enablement for a method of preventing any cancer, including lung and colorectal cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the process of the invention commensurate in scope with these claims.
The claims recite a pharmaceutical composition and an anti-cancer adjuvant comprising an oncolytic virus.
The nature of the invention is an oncolytic virus and compositions thereof.
The skill of one of ordinary skill in this art is high.
The specification states that the term “pharmaceutical composition” encompasses both preventing or treating a disease (¶ [0041]) and the “anti-cancer adjuvant” refers to any form for increasing the anti-cancer effect of a drug (¶ [0055]). The adjuvant further encompasses the oncolytic virus and thus its form is no different from the pharmaceutical composition. The working examples show cancer reduction/treatment of lung and colorectal cancers (Examples 4 and 5, respectively), but do not demonstrate the prevention of any types of cancers.
No material has been found to date that has been shown to or would be expected to prevent cancer, and there is no working example, prior art, or any evidence that would provide the skilled artisan with any predictable guidance to use the claimed invention. It would be reasonable to conclude the claimed invention is not enabled.
Reasonable guidance with respect to preventing any cancer relies on quantitative analysis from defined populations that have been successfully pre-screened and are predisposed to particular types of cancer. This type of data might be derived from widespread genetic analysis, cancer clusters, or family histories. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical cancer and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent. Further, a preventive administration also must assume that the therapeutic will be safe and tolerable for anyone susceptible to the disease.
The vaccine art teaches that compositions comprising some tumor associated antigens are effective in treatment of cancer through generation of immunogenic response to the tumor antigen (see for example, Komenaka (2004, Clinics in Dermatology, 22: 251-265), specifically page 257). However, nowhere in the art does it show that tumor antigens are effective at preventing cancer. Evans (1999, Q. J. Med, 92: 299-307) teaches that vaccines against cancer are not fully established, and it is stated that adjuvant therapy to prevent or delay disease still needs experimentation. Evans further states that such cancer vaccines are at best used as a therapeutic and not as a prophylactic and that “the notion that cancer vaccines will replace standard therapeutic strategies in malignant disease still belongs to the realm of fiction” (Page 303, last ¶).
In some cases, it is known that certain cancers arise from a single cause. This cause can be viral as in the case of cervical cancer, caused predominantly by persistent cervical infection with human papillomavirus (HPV) (Schiffman, 2005, The New England Journal of Medicine, 353(20): 2101-2104). Schiffman teaches that primary prevention through vaccination against HPV might be possible in young women (Page 2101, Column 3, ¶ first partial). However, they also teach that vaccine evaluations are ongoing (Page 2103, Column 3, ¶ first full). In addition, the most promising vaccines designed against HPV types 16 and 18 would only prevent 70 percent of cervical cancer cases at best (Page 2103, Column 2, ¶ first full). Therefore, there is still no vaccine that can definitively prevent a cancer. Current evidence points only to the potential of future prophylactic agents.
The art of small molecule chemotherapeutics teach that some molecules successful at treating cancers can also reduce risk. Cuzick (2003, The Lancet, 361: 296-300) teaches that tamoxifen can reduce the risk of ER-positive breast cancer but cannot be recommended as a preventive agent (Page 299, Column 2, ¶ 1). The reason it cannot be recommended centers around the need for continued research into specific subgroups of high-risk but healthy women for whom the risk-benefit ratio is sufficiently positive to recommend prophylactic tamoxifen treatment (Page 299, Column 2, ¶ 1).
With respect to peptide-based cancer prevention agents, the art currently does not recognize a definitive example though promising candidates are present. Hernandez-Ledesma (2009, Peptides, 30: 426-430) teaches that lunasin, a peptide discovered in soy has demonstrated cancer-preventative capacity in vitro and in mouse models (Abstract). The authors define it as a perfect candidate to exert an in vivo cancer-preventive activity but more research is required to establish it in this role (Page 429, Column 2, ¶ first partial).
Since the art has only recognized the treatment of a cancer, and specification does not provide ample guidance with respect to preventing cancer, one would be burdened with undue experimentation to use the invention as claimed.
Claim Rejections - 35 USC § 103
20. 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.
21. 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.
22. Claims 1-7, 9-12, 16-17, 21, 26-31, 33-41, and 43-45 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (2006, Molecular Therapy, 14(3): 361-370) in view of Szalay (US 11149254 B2; Priority to 13 April 2012), Chaurasiya (13 April 2021, Biomedicines, 9(417)), Mikesch (2006, BBA, 42-52), and Lin (April 2000, J. Virol., 3353-3365).
Regarding claims 1-4 and 10-11, Kim teaches oncolytic virus JX-594, which was constructed from Wyeth strain vaccinia virus (Results, ¶ 1). JX-594 has the following structure seen in Figure 1(A):
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Wherein GM-CSF and β-Galactosidase (lacZ) genes were inserted into the TK gene: “In brief, hGM-CSF was inserted into the TK gene region under the control of a synthetic early–late promoter; in addition, the lacZ gene was also inserted into the viral TK gene under control of the p7.5 promoter.” (Methods,
¶ 1). The insertion of GM-CSF was taught to increase immune response against cancer (Introduction,
¶ 1). Furthermore, Chaurasiya shows that JX-594 had the gene insertion in the J2R region: “Pexa-Vec (formerly JX-594) is a Wyeth strain of vaccinia virus that has J2R, encoding for thymidine kinase, replaced by the expression cassettes for human GM-CSF (hGM-CSF) and lacZ” (Page 5, ¶ 2).
Kim further teaches that the insertion into the TK gene (TK-) caused varying differences in replication in different types of cells (Results, ¶ 1). Notably, “the replication of TK vaccinia was significantly reduced (approximately 10-fold) in nonproliferating nontransformed cells.” (Results, ¶ 1; Figure 1(B). This demonstrates that the insertion of GM-CSF and lacZ caused suppression of TK gene expression in some cases. Since Kim teaches the same structure that is claimed, the same function will be obvious. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Kim contemplates that “Potency can be increased by modifying the viral backbone or engineering armed oncolytic viruses to express complementary therapeutic proteins.” (Discussion, ¶ 1) but does not specifically teach inserting a complement regulatory protein into the TK J2R region. However, Szalay teaches an attenuated vaccinia virus with lacZ reporter gene inserted into the TK J2R region (Column 13, lines 58-60). The recombinant LIVP virus can further include a heterologous nucleic acid encoding for DAF/CD55 (Claim 47). Mikesch teaches that DAF/CD55 is known as a therapeutic protein that has been shown to be effective against cancer cells: “Clinical trials have been inaugurated for the use of DAF as a potential target for molecular cancer therapy [139]. The monoclonal antibody SC-1 has been identified to bind one isoform of DAF which is expressed in gastric carcinoma leading to apoptosis of these cells…” (8. Perspective…, ¶ 2). Therefore, it would have been obvious to one of ordinary skill to take the vaccinia virus of Kim and further replace the lacZ gene with a gene for CD55 in order to increase potency, as suggested by Kim, and for its known effectiveness against cancer cells, as suggested by Mikesch. Since the lacZ gene is simply a reporter gene, it is not necessary for the functionality of the virus and replacing it would be obvious. Likewise, it would also be obvious to simply add the CD55 gene, as suggested by Szalay, rather than replacing the lacZ gene entirely. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02).
Regarding claims 5-7, Szalay teaches “In the recombinant or modified LIVP virus strains provided herein, the nucleic acid encoding the heterologous gene product is operably linked to a promoter. For example, the promoter is […] H3L…” (Column 6, lines 17-22). The heterologous gene product can include CD55, as discussed supra. H3L is further identified as the IMV heparin binding surface protein (Table 64). Using the entirety of the H3L protein, as taught in Szalay, would encompass the transmembrane domain portion of this protein. Furthermore, Lin teaches that “H3L protein mediates vaccinia virus adsorption to cell surface heparan sulfate and is important for vaccinia virus infection in vitro and in vivo. In addition, H3L protein plays a role in virion assembly.” (Abstract).
Therefore, it would have been obvious to one of ordinary skill before filing to add H3L protein to the obvious virus variant above for the advantages of Lin. To do this, it would have been obvious to fuse its gene with the other genes of the obvious virus supra under regulation of a promoter to drive its expression like those above from the prior art. A rationale to support a conclusion that a claim would have been obvious is that there is some teaching, suggestion, or motivation in the prior art or in the knowledge generally available to one of ordinary skill in the art to modify the reference or combine reference teachings, and the modification or combination would have a reasonable expectation of success. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, G. and 2143.02).
Regarding claim 9, Kim teaches GM-CSF as being controlled by a synthetic early/late promoter (See Figure 1(A) above), which reads on the pSEL promoter as claimed. Szalay teaches controlling lacZ with the vaccinia late promoter P11k (Colum 55, lines 56-59) and “In another example, the virus can be attenuated by modification or replacement of one or more promoters contained in the virus. Such promoters can be replaced by stronger or weaker promoters, where replacement results in a change in the attenuation of the virus. […] Exemplary promoters that can replace a promoter contained in a virus can be a viral promoter, such as a vaccinia viral promoter, and can include a vaccinia early, intermediate, early/late or late promoter.” (Column 108, line 59 to column 109, line 2). Therefore, replacing and optimizing promoters are known in the art and it would have been obvious to one of ordinary skill before the filing date to place CD55 under the control of a late promoter, which reads on the pLate promoter as claimed. It is noted that a “synthetic promoter” just means it was made an unnatural way, not that it is structurally different from a natural promoter. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Regarding claims 12, 16-17, 21, 26-31, 33-41, and 43-45, Szalay teaches “Provided herein is a composition containing any of the clonal strains or virus strains provided herein above. Also provided herein is a pharmaceutical composition containing any of the clonal strains or virus strains provided herein above.” (Column 6, lines 26-30) and “In the methods or uses herein above, including, but not limited to, for treating a proliferative disorder, the virus is administered locally, topically or systemically, including intravenously, intraarterially, intratumorally, …, intramuscularly, …, intraperitoneally...” (Column 7, line 63 to column 8, line 4). Although inherent to the type of administration, Szalay also teaches that the pharmaceutical composition can be in a liquid formulation (Column 118, lines 25-28). The characteristics of the oncolytic virus itself are made obvious by Kim, Szalay, Chaurasiya, Mikesch, and Lin supra.
As discussed supra, the anti-cancer adjuvant in claim 21 would simply read on the pharmaceutical composition as their forms would be identical. The adjuvant encompasses the treatment language that claim 12 is being rejected over. Due to the claim language, the oncolytic virus itself comprises the adjuvant. However, adding an adjuvant to the oncolytic virus would be equally as obvious, as discussed in Szalay: “In one example, the viruses can be diluted in a physiologically acceptable solution, such as sterile saline or sterile buffered saline, with or without an adjuvant or carrier.” (Column 117, lines 48-50). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
23. Claims 8, 32, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (Supra), Szalay (Supra), Chaurasiya (supra), Mikesch (supra), and Lin (supra) as applied to claims 1-7, 9-12, 16-17, 21, 26-31, 33-41, and 43-45 above, and further in view of Barrett (US 11446398 B2; PCT filed 11 April 2017).
Regarding claims 8, 32, and 42, Kim, Szalay, Chaurasiya, Mikesch, and Lin make claims 1, 12, and 21 obvious, as discussed supra. All discussions thereon incorporated here. No reference teaches the CD55 sequence as SEQ ID NO: 1. However, Barrett teaches a CD55 molecule that has a 100% match to SEQ ID NO: 1:
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The full sequence alignment has been omitted due to its length. It would have been obvious to one of ordinary skill before the filing date to take the oncolytic virus made obvious by Kim, Szalay, Chaurasiya, Mikesch, and Lin and further use the CD55 sequence of Barrett for the CD55 gene inserted into the TK J2R region. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Double Patenting
24. 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.
25. Claims 1-12, 16-17, 21, and 26-45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 9 of copending Application No. 19/108,937 in view of Kim (2006, Molecular Therapy, 14(3): 361-370), Szalay (US 11149254 B2; Priority to 13 April 2012), and Barrett (US 11446398 B2; PCT filed 11 April 2017).
Claim 1 of ‘937 recites an intravenously injectable composition comprising an oncolytic virus with suppression of TK gene expression by insertion of a gene encoding CD55 fused with a transmembrane domain region of a viral membrane protein and a gene encoding GM-CSF. Claim 2 of ‘937 recites that CD55 is composed of SEQ ID NO: 1, which has a 100% sequence identity to SEQ ID NO: 2 of the Instant Application:
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SEQ ID NO: 2 of the Instant Application is the amino acid sequence of the nucleic acid sequence (SEQ ID NO: 1) that is recited in the instant claims. Claim 3 of ‘937 recites that the membrane protein can be H3L, claims 4-5 of ‘937 recite that the oncolytic virus can be a vaccinia virus of the Wyeth strain, and claim 9 of ‘937 recites preventing or treating cancer by administering the composition. The copending claims 1-5 are compositions that include the product made of the instant claims and thus the product is obvious.
‘937 does not recite inserting the genes into the TK J2R region; the types of promoters used; or that the composition can be administered intratumorally, intravascularly, intramuscularly, or intraperitoneally. However, the combination of Kim, Szalay, and Barrett render obvious instant claims 1-12, 16-17, 21, and 26-45 as discussed supra. All obviousness arguments above incorporated here. The addition of copending claims 1-5 and 9 of ‘937 only further support this obviousness and thus the prior art combined with said claims renders the instant claims above obvious.
In summary, Kim teaches inserting the genes into the TK J2R region; the pSEL promoter to control GM-CSF; and the intratumoral, intramuscular, or intraperitoneal administration of the pharmaceutical composition. Szalay teaches the addition of the late promoter to control CD55 and Barrett teaches the CD55 nucleotide sequence.
Therefore, claims 1-5 and 9 of ‘937 in view of Kim, Szalay, Chaurasiya, Mikesch, and Barrett makes claims 1-12, 16-17, 21, and 26-45 of the Instant Application obvious.
This is a provisional nonstatutory double patenting rejection.
26. Claims 1-12, 16-17, 21, and 26-45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5, 7, 10-15, 20 and 23 of copending Application No. 18/879,477 in view of Kim (2006, Molecular Therapy, 14(3): 361-370), Szalay (US 11149254 B2; Priority to 13 April 2012), Chaurasiya (13 April 2021, Biomedicines, 9(417)), Mikesch (2006, BBA, 42-52), Lin (April 2000, J. Virol., 3353-3365), and Barrett (US 11446398 B2; PCT filed 11 April 2017).
Claim 1 of ‘477 recites an oncolytic virus co-expressing CD55 and CD59. Claims 2-4 of ‘477 recites that the oncolytic virus has suppressed expression of a TK gene due to deletion or insertion of a foreign gene, more specifically the J2R region. Claim 5 of ‘477 recites that CD55 is composed of SEQ ID NO: 1, which has a 100% sequence identity to SEQ ID NO: 2 of the Instant Application:
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SEQ ID NO: 2 of the Instant Application is the amino acid sequence of the nucleic acid sequence (SEQ ID NO: 1) that is recited in the instant claims. Claim 7 and 10-11 of ‘477 recites that the oncolytic virus further comprises a transmembrane domain of a membrane protein, fused with the CD55 gene, wherein the membrane protein is H3L. Claim 12 of ‘477 recites that CD55 can be expressed under a pLate promoter. Claims 13-14 of ‘477 recites that the oncolytic virus can be a vaccinia virus of the Wyeth strain. Claims 15 and 20 of ‘477 recite a pharmaceutical composition with the oncolytic virus for preventing or treating cancer, administered intratumorally, intravascularly, intramuscularly, intraperitoneally, intravenously, or intraarterially. Claim 23 of ‘477 recites an anticancer adjuvant comprising the oncolytic virus.
‘477 does not recite inserting a gene encoding GM-CSF under the pSEL promoter. However, the combination of Kim, Szalay, Chaurasiya, Mikesch, Lin, and Barrett render obvious instant claims 1-12, 16-17, 21, and 26-45 as discussed supra. All obviousness arguments above incorporated here. The addition of copending claims 1-5, 7, 10-15, 20 and 23 of ‘477 only further support this obviousness and thus the prior art combined with said claims renders the instant claims above obvious.
In summary, Kim teaches inserting GM-CSF into an oncolytic virus and being controlled by a pSEL promoter, as well as making a pharmaceutical composition with the virus. Szalay teaches that promoters are optimizable/interchangeable and Barrett teaches the CD55 nucleotide sequence.
Therefore, claims 1-5, 7, 10-15, 20 and 23 of ‘477 in view of Kim, Szalay, Chaurasiya, Mikesch, Lin, and Barrett makes claims 1-12, 16-17, 21, and 26-45 of the Instant Application obvious.
This is a provisional nonstatutory double patenting rejection.
27. Claims 1-12, 16-17, 21, and 26-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4 of U.S. Patent No. 10,517,910 in view of Kim (2006, Molecular Therapy, 14(3): 361-370), Szalay (US 11149254 B2; Priority to 13 April 2012), Chaurasiya (13 April 2021, Biomedicines, 9(417)), Mikesch (2006, BBA, 42-52), Lin (April 2000, J. Virol., 3353-3365), and
Barrett (US 11446398 B2; PCT filed 11 April 2017).
Claims 1-2 and 4 of ‘910 recite a composition comprising an oncolytic vaccinia virus with a GM-CSF gene and an inactive TK gene. This composition includes the oncolytic vaccinia virus and thus would anticipate the product. ‘910 does not recite CD55 or its sequence, inserting the genes into the J2R region, further including H3L, the promoters, the strain of vaccinia virus, or the method of administration. However, the combination of Kim, Szalay, Chaurasiya , Mikesch, Lin, and Barrett render obvious instant claims 1-12, 16-17, 21, and 26-45 as discussed supra. All obviousness arguments above incorporated here. The addition of copending claims 1-2 and 4 of ‘910 only further support this obviousness and thus the prior art combined with said claims renders the instant claims above obvious.
In summary, Kim teaches inserting the genes into the TK J2R region; the pSEL promoter to control GM-CSF; and the intratumoral, intramuscular, or intraperitoneal administration of the pharmaceutical composition. Szalay teaches the addition of the late promoter to control CD55 and the addition of H3L. Barrett teaches the CD55 nucleotide sequence.
Therefore, claims 1-2 and 4 of ‘910 in view of Kim, Szalay, Chaurasiya, Mikesch, Lin, and Barrett makes claims 1-12, 16-17, 21, and 26-45 of the Instant Application obvious.
Conclusion
28. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA E LY whose telephone number is (571)272-5169. The examiner can normally be reached Monday - Thursday, 8:00 am - 5:00 pm EST.
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/KRISTINA E. LY/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
Prosecution Insights