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 .
Response to Amendment/Disposition of Claims
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 13 February 2026 has been entered.
Applicant’s Amendment filed on 13 February 2026 has been received and entered. Claims 1-7 and 11-12 were pending. Claims 1 has been amended. No claims have been cancelled. No new claims have been added. Claims 8-10 and 13-32 are pending but remain withdrawn from consideration per Applicant’s response to the restriction/species election requirement filed on 12 December 2023.
Accordingly, Claims 1-7 and 11-12 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2022/0088183 A1, Published 24 March 2022. Applicant’s amended Specifications as presented on 13 February 2026, 16 April 2024, 14 September 2021, and 25 February 2021 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Response to Arguments
Applicant's arguments filed 13 February 2026 regarding the previous Office action dated 13 November 2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Information Disclosure Statement
The information disclosure statements (IDSes) submitted on 18 August 2021, 19 October 2021, 06 November 2023, 10 April 2024, 18 April 2024, 06 September 2024, 29 October 2024, 27 May 2025, 10 June 2025, and 02 April 2026 have been considered by the examiner. Any individual references with strikethroughs, however, have not been considered.
The information disclosure statement filed 02 April 2026 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. No copy of the Foreign Patent Document, JP 2000502567 A, was submitted. While a corresponding English patent was identified on the same IDS, a copy of the Foreign Patent Document should have also been submitted. The specific reference has been placed in the application file, but the information referred to therein has not been considered.
Four of the five Non-Patent Literature Documents were not considered. Specifically, Aitken et al., Okada et al., Wykosky et al., and Ghonime et al. were not considered because Applicant already submitted copies of these same documents with the IDS filed on 06 September 2024. Additionally, the US Patent Application Publication was not considered. Cassady et al. (US 2008/0206199 A1) was listed on the IDS filed by Applicant on 18 August 2021. As such, these have already been considered and thus will not be considered again.
Specification
(Objection withdrawn) – The objection to the disclosure for containing minor informalities is withdrawn in light of the amendments to the Specification.
Claim Objections
Withdrawn Objections
(Objection withdrawn) – The objection to Claim 1 for containing minor informalities is withdrawn in light of the amendments to the claim.
New Objections
(New Objection) – Claim 1 is objected to because of the following informalities: it is suggested that the claim be amended by deleting Line 2, “a herpesvirus having a modified nucleic acid sequence, comprising:”, so that the claim instead recites “A chimeric oncolytic herpesvirus, comprising: a modification…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
Withdrawn Rejections
(Rejection withdrawn) – The rejection of Claims 1, 4, and 11, and dependent claims 2-7 and 11-12 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
(Rejection withdrawn) – The rejection of Claim 11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to Claim 1, upon which Claim 11 depends.
New Rejections
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.
(New Rejection) – Claims 1 and 6, and dependent claims 2-5, 7, and 11-12 thereof, 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 Claim 1, it recites the limitation “a modification to the one or more herpesvirus gamma (1)34.5 genes (γ134.5) according to SEQ ID NO: 1”. Regarding Claim 6, it recites the limitation “wherein the CMV nucleic acid comprises an IRS-1 gene according to SEQ ID NO: 2”. The phrase “according to” renders the claims indefinite because, as currently written, they could be referring to the full-length sequences or truncated versions of the sequences. As such, it is unclear what the metes and bounds of the claim language are. It is suggested that Claim 1 be amended to recite “a modification to the one or more herpesvirus gamma (1)34.5 genes (γ134.5) comprising SEQ ID NO: 1” and Claim 6 be amended to recite “wherein the CMV nucleic acid comprises an IRS-1 gene comprising SEQ ID NO: 2” so that it is clear that at least the full-length sequence in each respective claim must be present, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 1 and 6 are rejected on the grounds of being indefinite. Claims 2-5, 7, and 11-12 are also rejected, since they depend upon Claim 1 but do not remedy the deficiencies of Claim 1.
(New Rejection) – Claims 1, and dependent claims 2-7 and 11-12 thereof, 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 Claim 1, it recites the limitation “a modification to the one or more herpesvirus gamma (1)34.5 genes (γ134.5) according to SEQ ID NO: 1”. The phrase “one or more” renders the claim indefinite because “more” encompasses any number greater than one. There are only two copies of the gene, however, so two is the maximum. It is suggested that the claim be amended to recite “a modification of one or both herpesvirus gamma (1)34.5 genes (γ134.5)”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 1 is rejected on the grounds of being indefinite. Claims 2-7 and 11-12 are also rejected, since they depend upon Claim 1 but do not remedy the deficiencies of Claim 1.
(New Rejection) – Claims 1-2, 4, and 11, and dependent claims 3, 5-7, and 12 thereof, 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 1-2, 4, and 11, they all comprise boxes when describing the name of the recited herpesvirus gene, in the case of Claims 1, 4, and 11, and the type of herpesvirus, in the case of Claim 2. As such, it is unclear what the metes and bounds of the claims as the boxes represent unknown entities. It is suggested that the claims be amended by replacing the boxes with the appropriate Greek letter, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 1-2, 4, and 11 are rejected on the grounds of being indefinite. Claims 3, 5-7, and 12 are also rejected, since they depend upon Claim 1 but do not remedy the deficiencies of Claim 1.
(New Rejection) – Claims 1, and dependent claims 2-7 and 11-12 thereof, 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 Claim 1, it recites the limitation “a third nucleic acid sequence encoding a tumor-associated antigen, wherein the tumor-associated antigen is associated with an overexpressed or aberrantly expressed self-antigen”. The phrase “associated with” renders the claim indefinite because it can be reasonably interpreted to have multiple meanings and there is no definition provided in the instant Specification to clarify the matter. One interpretation is that the tumor-associated antigen is itself an overexpressed or aberrantly expressed self-antigen. Another interpretation is that “associated with” could mean “bound to”, “linked to”, “conjugated to” or suggest that there is some kind of interaction, such as covalent or non-covalent bonds, between two different antigens, the tumor-associated antigen and the overexpressed or aberrantly expressed self-antigen. It could even be interpreted as suggesting the presence of an antigen that is a fusion protein of the two different antigens. Yet another interpretation is that the two different antigens are just simply present in the same mixture or composition and does not require any bonds of any kind. These multiple interpretations render the claim indefinite. 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."). It is suggested that the claims be amended so that it instead recites “a third nucleic acid sequence encoding a tumor-associated antigen, wherein the tumor-associated antigen is
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 1 is rejected on the grounds of being indefinite. Claims 2-7 and 11-12 are also rejected, since they depend upon Claim 1 but do not remedy the deficiencies of Claim 1.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
For the purpose of examining the instant claims on their merits, the term “about” will be interpreted using the definition provided by Applicant in the instant Specification. Paragraph 0042 of the PGPub of the instant application states “As used herein, the term ‘about’ refers to +/- 10% deviation from the basic value”.
Claim Rejections - 35 USC § 112(a); First Paragraph
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.
(New Rejection) – Claims 1-7 and 11-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a chimeric oncolytic virus, comprising: a herpesvirus having a modified nucleic acid sequence, comprising: a modification of the one or more herpesvirus gamma (1)34.5 genes (γ134.5) comprising SEQ ID NO: 1 or a nucleic acid with 100% homology to the γ134.5 gene that reduces its expression, wherein the modification is a complete or partial deletion of the γ134.5 gene (SEQ ID NO: 1) from HSV-1, an inserted exogenous stop codon or other nucleotide or nucleotides, the mutation or deletion of the promoter or the insertion of an exogenous promoter that alters expression of the γ134.5 gene, or one or more inserted nucleotides that results in a codon frame-shift; a second viral nucleic acid sequence encoding a protein kinase R (PKR) evasion protein that does not cause virulence; and a third nucleic acid sequence encoding a tumor-associated antigen, wherein the tumor-associated antigen is associated with an overexpressed or aberrantly expressed self-antigen, does not reasonably provide enablement for a chimeric oncolytic virus, comprising: a herpesvirus having a modified nucleic acid sequence, comprising: just any modification of the one or more herpesvirus gamma (1)34.5 genes (γ134.5) according to SEQ ID NO: 1 or a nucleic acid with less than 100% homology to the γ134.5 gene that reduces its expression; a second viral nucleic acid sequence encoding a protein kinase R (PKR) evasion protein that does not cause virulence; and a third nucleic acid sequence encoding a tumor-associated antigen, wherein the tumor-associated antigen is associated with an overexpressed or aberrantly expressed self-antigen. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to a chimeric oncolytic virus, comprising: a herpesvirus having a modified nucleic acid sequence, comprising: a modification of the one or more herpesvirus gamma (1)34.5 genes (γ134.5) according to SEQ ID NO: 1 or a nucleic acid with at least about 98% homology to the γ134.5 gene that reduces its expression; a second viral nucleic acid sequence encoding a protein kinase R (PKR) evasion protein that does not cause virulence; and a third nucleic acid sequence encoding a tumor-associated antigen, wherein the tumor-associated antigen is associated with an overexpressed or aberrantly expressed self-antigen. The term “about” is defined in Paragraph 0042, which states that “As used herein, the term ‘about’ refers to +/-10% deviation from the basic value”. The instant Specification states that “it is understood that one way to define any known variants and derivatives or those that might arise, of the disclosed genes and proteins herein, is through defining the variants and derivatives in terms of homology to specific known sequences. This identity of particular sequences disclosed herein is also discussed elsewhere herein. In general, variants of genes and proteins herein disclosed typically have at least, about” 70-99 “percent homology to the stated sequence or the native sequence” (see Paragraph 0063). Paragraphs 0094 and 0106 state that the “chimeric oncolytic virus can be any of the variants and embodiments described herein”. Paragraph 0043 states that “the term nucleic acid also encompasses nucleic acids with substitutions or modifications, such as in the bases and/or sugars”, while Paragraph 0067 states that the “disclosed nucleic acids may contain, for example, nucleotide analogs or nucleotide substitutes”.
State of the prior art/Predictability of the art. The art teaches that protein chemistry is probably one of the most unpredictable areas of biotechnology. For example, replacement of a single “lysine” residue at position 118 of acidic fibroblast growth factor by “glutamic acid” led to the substantial loss of heparin binding, receptor binding and biological activity of the protein (Burgess et al., J of Cell Bio. 111:2129-2138, 1990). In transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen (Lazar et al. Molecular and Cellular Biology 8:1247-1252, 1988). As these references illustrate, it is unpredictable that a polypeptide variant of a known target protein binder will also bind said target. It is also unpredictable that they would bind said target in the same way, having the same effect on the target (i.e. inhibit or activate). Ju (Proceedings of the National Academy of Sciences, U.S.A., Vol. 88, Pg. 2658-2662, 1991) teaches that the interleukin 1 receptor (IL-1R) antagonist IL-1ra is a naturally occurring protein with no agonist activity in vitro or in vivo (Abstract). However, substitution of a single amino acid lysine145 to aspartic acid changes the property of this peptide to a partial agonist of IL-1R (Abstract). Thus, even a single substitution can change the biological property of a peptide.
This substitution need not be at a position where said residue would contact the target protein. Baker (Immunity, Vol. 13, Pg. 475-484, 2000) teaches that Tax-peptide is an agonist of the of T cell activity (Abstract). However, mutation of proline at position 6 of this peptide to alanine creates a T cell antagonist (Abstract). Importantly, this residue does not contact the T cell receptor (Abstract).
In another case, Huang (The Journal of Biological Chemistry, Vol. 272, No. 43, Pg. 27155-27159, 1997) teaches that conjugation of peptides to other proteins can change their biological properties. They teach that multiple conjugation of the peptide TGFβ1 (residues 41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as well (Abstract). Thus, the chemical context of a biologically active peptide is also important.
Truncation of proteins can also lead to adverse effects on protein structure and thus protein function. Martindale (Nature Genetics, Vol. 18, Pg. 150-154, 1998) teaches that truncation of huntingtin leads to aggregate development which compromises cell viability (Abstract). Nonaka (Human Molecular Genetics, Vol. 18, No. 18, Pg. 3353-3364, 2009) teaches that truncation of TDP-43 to its C-terminal fragments causes abnormally phosphorylated and ubiquitinated inclusions of the protein (Abstract). Taken together, not just any truncation of a protein will yield a soluble, functional, protein fragment.
In summary, these examples teach that the biological function of peptide variants is unpredictable because even a single mutation can abolish activity or give a different function. For example, agonist and antagonist peptides can be interconverted through conjugation or mutagenesis. Importantly, binding can still occur after mutation or conjugation in the literature examples provided above, illustrating that a simple show of binding is not predictive of the nature of a peptide’s biological activity. This point is underlined by Montrose-Rafizadeh (The Journal of Biological Chemistry, Vol. 272, Pg. 21201-21206, 1997) who teaches that receptor binding does not predict agonist or antagonist activity (Pg. 21205, Column 2, Paragraph, first full, Sentence, first).
Since the art teaches that it is unpredictable whether or not nucleotide variants of known genes, and their encoded proteins, will function as expected, and the specification does nothing to ameliorate these concerns, one would be burdened with undue experimentation to use the product of the instant claims as broadly as they are currently claimed.
Working examples. No working examples of variants with less than 100% homology to the claimed sequence are disclosed in the specification.
Guidance in the specification. The specification provides guidance towards constructs which are presumably 100% identical to the claimed sequence and specific kinds of modifications to said sequence. Paragraph 0055 of the PGPub states that “the modification to the herpesvirus nucleic acid sequence can comprise the complete or partial deletion of the γ134.5 gene (SEQ ID NO: 1) from HSV-1”. It also states that the “modification can comprise an inserted exogenous stop codon or other nucleotide or nucleotides” or “can comprise the mutation or deletion of the promoter or the insertion of an exogenous promoter that alters expression of the γ134.5 gene”. Additionally, the “modification can comprise one or more inserted nucleotides that results in a codon frame-shift”. Paragraph 0124 states that Applicant generated a chimeric Δγ134.5 oncolytic HSV (oHSV) called C134 that expressed the IRS1 gene from Human Cytomegalovirus (HCMV) and that this virus served as the parental virus for the recombinants that were later tested, C170 and C172 (see Paragraph 0160), one of which, C170, proved to be particularly effective (see Paragraphs 0161-0167). The instant Specification, however, fails to disclose the critical or essential nucleotide positions which must be present and also fails to explicitly disclose any variants of the claimed sequence. The instant Specification does state that “it is understood that one way to define any known variants and derivatives or those that might arise, of the disclosed genes and proteins herein, is through defining the variants and derivatives in terms of homology to specific known sequences. This identity of particular sequences disclosed herein is also discussed elsewhere herein. In general, variants of genes and proteins herein disclosed typically have at least, about” 70-99 “percent homology to the stated sequence or the native sequence” (see Paragraph 0063). Paragraphs 0094 and 0106 state that the “chimeric oncolytic virus can be any of the variants and embodiments described herein”. Paragraph 0043 states that “the term nucleic acid also encompasses nucleic acids with substitutions or modifications, such as in the bases and/or sugars”, while Paragraph 0067 states that the “disclosed nucleic acids may contain, for example, nucleotide analogs or nucleotide substitutes”. These paragraphs do not remedy the deficiencies of the disclosure to identify critical regions of the claimed sequence which must be present.
Amount of experimentation necessary. Since the art teaches that it is unpredictable whether or not nucleotide variants of a known sequence will function as intended, and the specification does nothing to ameliorate these concerns, one would be burdened with undue experimentation to use the claimed product.
(New Rejection) – Claims 1-7 and 11-12 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 instant application attempts to tie function to sequence identity in the context of a chimeric oncolytic virus, comprising: a herpesvirus having a modified nucleic acid sequence, comprising: a modification of the one or more herpesvirus gamma (1)34.5 genes (γ134.5) according to SEQ ID NO: 1 or a nucleic acid with at least about 98% homology to the γ134.5 gene that reduces its expression; a second viral nucleic acid sequence encoding a protein kinase R (PKR) evasion protein that does not cause virulence; and a third nucleic acid sequence encoding a tumor-associated antigen, wherein the tumor-associated antigen is associated with an overexpressed or aberrantly expressed self-antigen.
While a percent identity threshold is provided in the claims, the instant Specification fails to disclose the critical or essential nucleotide positions which must be present and also fails to explicitly disclose any variants of the claimed sequence. The instant Specification does state that “it is understood that one way to define any known variants and derivatives or those that might arise, of the disclosed genes and proteins herein, is through defining the variants and derivatives in terms of homology to specific known sequences. This identity of particular sequences disclosed herein is also discussed elsewhere herein. In general, variants of genes and proteins herein disclosed typically have at least, about” 70-99 “percent homology to the stated sequence or the native sequence” (see Paragraph 0063). Paragraphs 0094 and 0106 state that the “chimeric oncolytic virus can be any of the variants and embodiments described herein”. Paragraph 0043 states that “the term nucleic acid also encompasses nucleic acids with substitutions or modifications, such as in the bases and/or sugars”, while Paragraph 0067 states that the “disclosed nucleic acids may contain, for example, nucleotide analogs or nucleotide substitutes”. These paragraphs do not remedy the deficiencies of the disclosure to identify critical regions of the claimed sequence which must be present. As such, it would be unclear to a person having ordinary skill in the art to know what to change and what not to change.
Furthermore, while it is not explicitly stated, it is assumed that the constructs used in the instant Specification have sequences which are 100% identical to the claimed sequence. Even if that is not the case, the data shown do not explicitly include any claimed variants having as little as 98% sequence identity, or even 99% sequence identity, raising questions about how effective these claimed variants would be in the data provided. Paragraph 0055 of the PGPub states that “the modification to the herpesvirus nucleic acid sequence can comprise the complete or partial deletion of the γ134.5 gene (SEQ ID NO: 1) from HSV-1”. It also states that the “modification can comprise an inserted exogenous stop codon or other nucleotide or nucleotides” or “can comprise the mutation or deletion of the promoter or the insertion of an exogenous promoter that alters expression of the γ134.5 gene”. Additionally, the “modification can comprise one or more inserted nucleotides that results in a codon frame-shift”. Paragraph 0124 states that Applicant generated a chimeric Δγ134.5 oncolytic HSV (oHSV) called C134 that expressed the IRS1 gene from Human Cytomegalovirus (HCMV) and that this virus served as the parental virus for the recombinants that were later tested, C170 and C172 (see Paragraph 0160), one of which, C170, proved to be particularly effective (see Paragraphs 0161-0167). While this does provide some clarity on what was tested, it appears that only the claimed deletion variant was tested while no other variants were tested. Additionally, the essential characteristics of the genus being claimed by Applicant have not been identified or disclosed.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contributions to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle and Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient details that one skilled in the art can reasonably conclude that the invention had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may 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. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
MPEP § 2163 states 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, 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 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. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which the peptide or nucleotide variants can have any sequences which vary from instant SEQ ID NOs: 1-16 by as much as 5%, one must describe a sufficient variety of species to reflect the variation within the genus. However, one of skill in this art cannot envision the structure of any peptide or nucleotide variants with the required sequence identity other than the few species provided by Applicant and the prior art. Therefore, since only a few species are provided to represent the genera, the claims encompassing the same clearly fail the written description requirement.
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014).
Overall, at the time the invention was made, the level of skill for preparing nucleotide variants and then selecting those nucleic acids which meet the desired percent identity cutoff was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identity peptide and nucleotide variants with the recited percent identity cutoff, the written description provision of 35 U.S.C. 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010). Absent the conserved structure provided by a core nucleotide sequence, the skilled artisan would not be able to visualize or otherwise predict, a priori, what any nucleotide which meets the recited percent identity cutoff would look like structurally.
While applicant has described a few species within the genus recited, and the art may provide more, each genus is very large and would encompass nucleotide structures that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the nucleotide structures encompassed by the claimed/recited genera only defined by sequence identity. Any future nucleotide variants may or may not be encompassed, as if they are, they would not have been represented in Applicant’s disclosed species. Thus, the described species cannot be considered representative of the entire recited genus nucleotide variants. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Therefore, the claims are rejected here.
As such, it does not appear Applicant was in possession of the full scope of the claimed invention at the time of filing and thus Claims 1-7 and 11-12 do not meet the written description requirement.
(New Rejection) – Claims 1-7 and 11-12 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. This is a new matter rejection.
The limitation of “□134.5” recited in Claims 1, 4, and 11 and “□ herpesvirus” in Claim 2 represent new matter which is not supported by the originally-filed disclosure. Specifically, the boxes represent unknown entities and thus new embodiments which were not explicitly disclosed in the original Specification.
Additionally, the amendments to Claim 1 introduce new matter which is not supported by the original disclosure filed on 25 February 2021. The original claims recite “a modification of the herpesvirus gamma (1)34.5 gene (γ134.5)”. The instant Specification does not provide any indication that more than one copy of the gene in question was modified. It does not explicitly teach that both copies were modified. This amended independent claim recites a new embodiment of the claimed invention which was not explicitly disclosed in the original Specification.
The original disclosure should teach, contemplate, and thus anticipate the instant claims. Therefore, Claims 1-7 and 11-12 do not meet the written description requirement as they contain new matter.
Claim Rejections - 35 USC § 103
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.
(Rejection maintained) – The rejection of Claims 1-7 and 11-12 under 35 U.S.C. 103 as being unpatentable over Cassady et al. (US 2008/0206199 A1, Published 28 August 2008), Laus et al. (WO 97/24438, Published 10 July 1997), Hatano et al. (Hatano, M., Eguchi, J., Tatsumi, T., Kuwashima, N., Dusak, J. E., Kinch, M. S., Pollack, I. F., Hamilton, R. L., Storkus, W. J., & Okada, H. (2005). EphA2 as a Glioma-Associated Antigen: A Novel Target for Glioma Vaccines. Neoplasia (New York, N.Y.), 7(8), 717–722.), and Workenhe et al. (Workenhe, S. T., Verschoor, M. L., & Mossman, K. L. (2015). The role of oncolytic virus immunotherapies to subvert cancer immune evasion. Future Oncology (London, England), 11(4), 675–689.) is maintained.
Response to Arguments
Applicant's arguments with respect to the rejection of Claims 1-7 and 11-12 under 35 U.S.C. 103 have been fully considered but they are not persuasive.
In their Response, Applicant argues that “Workenhe et al. does not provide a reasonable expectation of success that expressing a self-antigen from such an oncolytic virus would be effective for treating cancer” (see Page 4 of Remarks, Paragraph 1). Applicant then argues that Workenhe et al. teach “‘genetic modification of OVs to express cytokines, chemokines and TAAs” as “potential mechanisms to increase immune stimulation in the tumor microenvironment and enhance the detection of TAAs by antigen presentation’” (see Page 4, Paragraph 2). Applicant also argues that the “expression of cytokines such as GM-CSF from the oncolytic virus” “is not relevant to the claimed invention” (see Page 4, Paragraph 2) and that Workenhe et al. describe “altered self-antigens”, which have been “modified by including a variety of different mutations” (see Page 4, Paragraph 2). Furthermore, Applicant argues that “these studies were done using a different virus (VSV)” (see Page 4, Paragraph 2)”. Finally, Applicant argues that they “continue to provide more data showing that the C170 HSV vector can stimulate an effective antitumor response using self-antigens”, including “a C170 EphA2-specific antibody response” (see Page 4, Paragraph 3) and that “Workenhe et al. do not teach that g134.5 modified HSV (as claimed) would have a reasonable expectation of success in treating tumors using unmodified self-antigens, and because Applicants have provided data showing that the claimed invention is, in fact, unexpectedly effective” (see Page 6, Paragraph 1), Applicant concludes “that the rejection of the claims for obviousness be withdrawn” (see Page 6, Paragraph 1).
Examiner does not find the arguments presented persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In fact, Applicant only attacks the Workenhe et al. reference and does not address the other references utilized in this current rejection. While Examiner acknowledges that Workenhe et al. does not explicitly disclose HSV-1 expressing a TAA and only recites it as a potential therapy, they do still contemplate it, and thus this would provide the suggestion to a person having ordinary skill in the art to carry out such an experiment. As such, this renders this aspect of the instant invention obvious as the prior art had already contemplated it. Additionally, Cassady et al. teach a chimeric oncolytic HSV-1 expressing a tumor-specific antigen and Laus et al. teach expression vectors encoding a polypeptide complex comprising a tumor-associated protein. The combination of these references would suggest and provide sufficient motivation to a person having ordinary skill in the art to combine these teachings and arrive at the claimed invention.
Applicant’s argument that Workenhe et al. uses a different virus delivery system, namely VSV, conveniently ignores the fact that Workenhe et al. disclose multiple oncolytic viruses, including VSV, HSV-1, Adenovirus, and vaccinia virus, including an Adenovirus expressing melanoma TAAs. The prior art serves as a reference for all that it teaches. Applicant is reminded that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also > Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); < Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). MPEP 2123. As such, it cannot simply be disregarded that Workenhe et al. contemplate HSV-1, or other viruses, expressing tumor-associated antigens.
Applicant’s Argument about unexpected results in based on the presumption that the art would not have attempted or contemplated the instant invention. However, the prior art, such as Workenhe et al., specifically contemplated oncolytic viruses expressing tumor-associated self-antigens in order to break or overcome immunological tolerance to cancer or tumor antigens. As such, the alleged unexpected results presented are not persuasive as the combined teachings of the prior art references would have motivated a person having ordinary skill in the art to arrive at the claimed invention prior to the effective filing date of the instant application and with a reasonable expectation of success.
Applicant’s Argument that oncolytic viruses expressing GM-CSF is not relevant to the instant invention is also not persuasive. As noted in the Final Rejection mailed on 13 November 2025, GM-CSF is an example of a dendritic cell-binding protein, as taught by Laus et al. Laus et al. teach GM-CSF fused to a tumor-associated protein and expressed from a vector as a polypeptide antigen. This renders the corresponding limitations of instant Claims 1 and 7 obvious, so it is actually quite relevant to the instantly claimed invention, despite Applicant’s assertion otherwise. Additionally, GM-CSF expression is not excluded from the claims rejected, for example, and so the art reads on the instant claims.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., unaltered self-antigens) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Claim 1 does not distinguish between altered and unaltered self-antigens. It recites the genus of “self-antigens”. As such, it reads on both altered and unaltered self-antigens. Applicant argues that Workenhe et al. teach oncolytic viruses expressing altered self-antigens, which means that Applicant is admitting, on the record, that the prior art reference does teach self-antigens. The prior art reference teaches a species of the claimed genus. If Applicant only wishes Claim 1 to read on unaltered self-antigens, then the claim should be amended as such and explicitly recite that limitation. Applicant’s own disclosure, however, would suggest that the scope of the claims is actually broader than what Applicant is now arguing. First, instant Claim 1 recites the limitation “wherein the tumor-associated antigen is associated with an overexpressed or aberrantly expressed self-antigen”. If the scope of “self-antigen” is limited to unaltered self-antigens, then the TAA cannot be a fusion protein with the self-antigen, which is one possible interpretation of Claim 1. Second, the definition of tumor-associated antigen provided by Applicant in the instant Specification would disagree with Applicant’s Arguments. Paragraph 0080 of the PGPub states, in part, that tumor-associated antigens “can include, for example, products of mutated oncogenes and tumor suppressor genes, overexpressed or aberrantly expressed cellular proteins, tumor antigens produced by oncogenic viruses, oncofetal antigens, altered cell surface glycolipids and glycoproteins or cell-type specific differentiation antigens” (emphasis added). Applicant also fails to defined “altered”, as the term could read on self-antigens mutated experimentally or those which are simply naturally-occurring variants of the wild-type self-antigen. Third, if the term “self-antigen” is narrowed in scope to only encompass unaltered self-antigens, then instant Claim 7, which depends on Claim 1, would suddenly fail to meet the requirements of 35 USC § 112(d); Fourth Paragraph. Claim 7 recites the limitation “wherein the tumor-associated antigen is modified to include a dendritic cell-binding peptide” (emphasis added). The word “modified” means that the tumor-associated antigen has been altered, which would contradict Applicant’s now-desired scope for the term “self-antigen”. As such, if Claim 1 is amended and narrowed in scope, a rejection under 35 USC § 112(d); Fourth Paragraph would need to be raised for Claim 7, as it would no longer incorporate all of the limitations of the claim upon which it depends, and it would be necessitated by amendment due to the amendment to instant Claim 1.
Thus, for at least all the reasons stated above, the rejection of Claims 1-7 and 11-12 under 35 U.S.C. 103 is maintained.
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.
(Rejection maintained) – The rejection of Claims 1-7 and 11-12 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11, and 18-20 of copending Application No. 18/869,720 (US 2025/0295719 A1) in view of Cassady et al. (US 2008/0206199 A1, Published 28 August 2008), Laus et al. (WO 97/24438, Published 10 July 1997), and Workenhe et al. (Workenhe, S. T., Verschoor, M. L., & Mossman, K. L. (2015). The role of oncolytic virus immunotherapies to subvert cancer immune evasion. Future Oncology (London, England), 11(4), 675–689.) is maintained.
Response to Arguments
Applicant's arguments with respect to the rejection of Claims 1-7 and 11-12 on the ground of nonstatutory double patenting have been fully considered but they are not persuasive.
In their Response, Applicant requested “that this rejection be held in abeyance, pending the actual issuance of App. No. 18/869,720 and the identification of otherwise allowable subject matter has been identified, at which point Applicants may file a terminal disclaimer or amend the claims to exclude the expression of IL-27” (see Page 6 of Remarks, Paragraph 2). As such, this rejection is maintained for reasons of record.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Shah et al. (U.S. Patent No. 9,862,932 B2, Issued 09 January 2018)
Shah et al. teach a recombinant oncolytic HSV comprising a nucleic acid sequence encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This reference has not been utilized, as rejection would have been redundant to those set forth above.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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