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 .
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 1/22/2026 are acknowledged. Claims 33 and 40 are amended; claims 9, 11, 17, 20-21, 24-25, 27 and 29 are canceled; claims 1-8, 10, 12-16, 18-19, 22-23, 26, 28 and 30-40 are pending; claims 5-8, 10, 12-16, 18-19, 22-23 and 26 are withdrawn; claims 1-4, 28 and 30-40 have been examined on the merits. NOTE: This Office action is non-final because the grounds of rejection were not necessitated by amendment.
Claim Objections
The objection to claims 33 and 40, as set forth at p. 3 of the previous Office Action, is withdrawn in view of the amendment of the claims.
Claim Rejections - 35 USC § 103
The rejection of claims 1-4, 28, 30-35 and 37-40 under 35 U.S.C. § 103(a) over Cohen et al., US 2013/0209506 (cite A, PTO-892, 10/24/2025; herein “Cohen”) in view of Gray et al., 2001 (NPL cite D1, IDS, 4/14/2023) as set forth at pp. 3-8 of the previous Office Action, is withdrawn.
The rejection of claims 1-4, 28 and 30-40 under 35 U.S.C. § 103(a) over Cohen in view of Gray and Jiang et al., 2017 (NPL cite D4, IDS, 4/14/2023; herein “Jiang”) as set forth at pp. 8-9 of the previous Office Action, is withdrawn.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 28, 30-35 and 37-40 are rejected under 35 U.S.C. 103 as being unpatentable over Cohen et al., US 2013/0209506 (cite A, PTO-892, 10/24/2025; herein “Cohen”) in view of Mahalingam et al., 2000 (cite U, attached PTO-892; herein “Mahalingam”).
Cohen is drawn to recombinant herpesvirus with diminished latency (Abst.) for use in immunogenic compositions and/or attenuated live virus compositions in order to provide immunity against herpesvirus infection while diminishing the establishment or maintenance of latency [0047], wherein the modified herpesvirus diminishes expression of a latency gene during latency but provides for expression of the latency gene outside of latent infection [0055-63], i.e., expression of the latency gene during replication but not during latency would allow the altered herpesvirus to be used as an immunogenic composition providing reaction against latent infection while diminishing the possibility of the immunizing composition actually producing a latent infection as can occur with VZV immunization with VZV Oka strain virus wherein vaccinated individuals can later develop zoster from Oka virus latent infection [0003].
Cohen teaches that the altered herpesvirus can be human varicella zoster virus (VZV) or simian varicella virus (SVV) [0009]. Cohen teaches that the recombinant herpesvirus can comprise deletion or mutation of a latency gene at its native location along with insertion of a latency gene, driven by a heterologous promoter, at a different location in the viral genome [0008], wherein the different location can be insertion at the AvrII site between ORF65 and ORF66 of the VZV genome ([0070], [0106]; claim 15). Cohen teaches that the latency gene can be ORF4 from VZV or a homolog of ORF4 from a different herpesvirus ([0010], [0060]; claim 6) wherein the homolog can be identified by public database searching [0062]. Cohen specifically teaches that the latency gene can be a homolog of a VZV latency gene found in SVV [0062]. Cohen teaches that the latency gene or homolog thereof inserted into the non-natural site can be driven by a promoter from a different herpesvirus, i.e., heterologous promoter, and may be a promoter expressed outside of latency [0057].
Cohen does not specifically teach that the latency gene and promoter expressing the gene outside of latency introduced into the AvrII site of VZV consists of bp 1-3600 of the SVV genome; however, a person of ordinary skill in the art at the time of filing would have found it obvious to introduce bp 1-3600 of the SVV genome into the AvrII site of VZV to provide the altered VZV construct with a homolog of ORF4 expressed during replication in order to produce an immunogenic composition which expresses a latency gene during replication but does not cause latent infections in view of the disclosure of Mahalingam.
Mahalingam discloses cloning base pairs 1-3600 (numbering from the left terminus of SVV) of SVV (Abst.) Mahalingam discloses that the leftmost 3600 bp region of SVV comprises a homolog of VZV ORF4 called ORF A (Abst.) Mahalingam discloses that the transcript for ORF A is expressed in SVV-infected cells and in acutely infected monkey ganglia (p. 422, “Identification of SVV ORF A- and B-specific transcripts in SVV-infected BSC-1 cells and in ganglia of a SVV-infected monkey”), i.e., ORF A is expressed during replication outside of the latency window. Mahalingam discloses that the ORF A protein is immunologically cross-reactive with ORF4 antibodies (pp. 422-423, “In vitro expression of ORF A protein”). Thus, 1-3600 of SVV has been cloned and comprises a latency gene homolog (ORF A homologous to VZV ORF4) which is expressed outside of latency by a heterologous promoter.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce recombinant herpesvirus with diminished latency comprising VZV with deletion or mutation of ORF4 at its native location along with the insertion of Mahalingam’s 1-3600 bp SVV gene fragment between ORF65 and ORF66 of VZV because Cohen teaches that the latency gene can be VZV ORF4 or a homolog thereof, teaches deletion or mutation of the latency gene at its native location, and teaches insertion of a latency gene, driven by a different herpesvirus promoter which provides expression outside of the latency period, between ORF65 and ORF66 of VZV and Mahalingam discloses that the 1-3600 bp fragment of SVV comprises a homolog of ORF4, i.e., a latency gene - ORF A, which is immunologically cross-reactive with ORF 4, which is driven by a promoter which provides expression during acute infection rather than during latency; therefore, claims 1-4, 28, 30-35 and 38-39 are prima facie obvious.
Regarding claims 1-4, the nucleic acid sequence from an exclusively human pathogenic virus in the chimeric viral construct made obvious by Cohen in view of Mahalingam is 100% VZV; therefore, claims 1-4 are prima facie obvious.
Regarding claim 28, it would be prima facie obvious to package the chimeric viral construct made obvious by Cohen in view of Mahalingam in a container in a kit because kits are an effective way to market or distribute a product; therefore, claim 28 is prima facie obvious.
Regarding claim 30, the nucleic acid sequence or nucleic acid sequence fragment of SVV comprises 95% or more nucleic acid sequence identity to a nucleic acid sequence or nucleic acid sequence fragment of SEQ ID NO: 1, because the SVV genome fragment in the chimeric viral construct made obvious by Cohen in view of Mahalingam constitutes 1 to 3600 bp of SVV and SEQ ID NO: 1 is 1 to 3600 bp of SVV; therefore, claim 30 is prima facie obvious.
Regarding claims 31-32, the chimeric viral construct made obvious by Cohen in view of Mahalingam comprises 1-3600 of SVV inserted at the AvrII site between VZV ORF65 and VZV ORF66; therefore, claims 31-32 are prima facie obvious.
Regarding claim 33, the chimeric viral construct made obvious by Cohen in view of Mahalingam comprises 1-3600 of SVV inserted at the AvrII site between VZV ORF65 and VZV ORF66 in the full VZV genome and SEQ ID NO: 4 constitutes SEQ ID NO: 2 (645 - 3600 bp of SVV) inserted at the AvrII site (@112,855 bp) between VZV ORF65 and VZV ORF66 in the full VZV genome; hence, the chimeric viral construct made obvious by Cohen in view of Mahalingam is at least 85% identical to SEQ ID NO: 4; therefore, claim 33 is prima facie obvious.
Regarding claims 34-35, the chimeric viral construct made obvious by Cohen in view of Mahalingam constitutes about 2% SVV (3600 / (3600 + 124884 (VZV))) and about 98% VZV (124884 / (3600 + 124884)); hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the chimeric viral construct to comprise two percent (2%) SVV and ninety-eight percent (98%) of an exclusively human pathogenic virus wherein the exclusively human pathogenic virus is VZV; therefore, claims 34-35 are prima facie obvious.
Regarding claim 37, Cohen teaches that the viral construct can encode an immunomodulator, such as IL-2, IL-15, IL-12 or GM-CSF [0089], i.e., a therapeutic agent; therefore, claim 37 is prima facie obvious.
Regarding claims 38-39, the chimeric viral construct made obvious by Cohen in view of Mahalingam comprises the full VZV genome, including ORF7; hence, the chimeric construct made obvious by Cohen in view of Mahalingam comprises human VZV ORF7 comprising 85% or more sequence identity to SEQ ID NO: 8 (VZV ORF7) and encodes a polypeptide comprising at least 85% or more sequence identity to SEQ ID NO: 9 (VZV ORF7 gene product); therefore, claims 38-39 are prima facie obvious.
Regarding claim 40, Cohen teaches that the viral construct can be in a pharmaceutical composition comprising excipients [0088]; therefore, claim 40 is prima facie obvious.
Response to Arguments
Applicant's arguments filed 1/22/2026 have been fully considered but they are not persuasive in light of the rejection set forth above. Arguments of the Applicant’s Response on pp. 10-13 regarding the rejections under 35 U.S.C. § 103 are moot as the rejections have been withdrawn. The rejections rely on Cohen in view of Mahalingam; hence, Applicant’s discussion of Cohen is addressed below.
Applicant argues that “Accordingly, for the cited art to render claim 1 obvious, it must disclose or suggest incorporating SVV genomic material into a construct that also contains nucleic acid from an exclusively human-pathogenic virus. As explained below, none of the cited references-including Cohen-teach or suggest this feature.” (pp. 10-11, spanning ¶).
This is incorrect. The claims do not require incorporating SVV genomic material into a construct that also contains nucleic acid from an exclusively human-pathogenic virus; rather, the claims only require the construct to comprise a nucleic acid sequence fragment of SVV wherein the nucleic acid sequence fragment comprises 85% or more sequence identity to a nucleic acid sequence fragment of SEQ ID NO: 1. The specification discloses that said nucleic acid fragment can be as small as 10 nucleotides [0041] or as small as one nucleotide [0042]. Applicant’s assertion that the nucleic acid from SVV needs to be genomic material or a genomic fragment is simply incorrect.
Claims 1-3 are very broad, requiring only a construct comprising 1) a nucleic acid fragment with ≥85% identity to SEQ ID NO: 1 (1-3600 of SVV) and a nucleic acid sequence from an exclusively human pathogenic virus (claims 1-2) or wherein the virus is a human herpesvirus (claim 3). The nucleic acid sequence from SVV need only be 1 or 10 nucleotides in length and can be any sequence in the leftmost 3600 bp of SVV including coding sequences or promoters.
Applicant argues that “Cohen's discussion of heterologous promoters is expressly limited to regulatory elements and does not extend to insertion of heterologous viral coding sequences or genomic fragments” (p. 11). This is incorrect, as discussed below, but it should be pointed out that a heterologous promoter or coding sequence from 1-3600 of SVV meets the limitations as well as a genomic fragment from 1-3600 of SVV.
Applicant alleges that Cohen does not teach that the latency gene inserted into a non-native site in VZV can be from SVV (pp. 10-13). This is unpersuasive as Cohen clearly teaches that the latency gene can be a homologous gene from a different herpesvirus ([0010], [0059-62]) with [0062] reciting “In embodiments, the latency gene is homologous to the varicella zoster virus and is found in simian varicella virus...”
Additionally, the rejection is not an anticipation rejection and a DNA construct wherein the latency gene is a homolog from another herpesvirus is obvious to make for changing the protection afforded as a live vaccine or for research purposes. Hence, the argument that the claimed DNA construct is non-obvious over the prior art is unpersuasive.
Applicant argues (p. 12) that Cohen undermines the Office’s position because Cohen demonstrates that the HSV-1 homolog of VZV ORF29 (ICP8) cannot complement the activity of VZV ORF29. This appears to be missing the point because Cohen’s aims appear to be twofold: 1) remove the function of the latency genes such that the virus does not form a latent infection and later reactivate and 2) provide latency antigens such that the live virus vaccine provides immunity against latent reactivation wherein the latency gene is an antigen by expression of a latency gene during acute infection.
As described in the rejection above, a person of ordinary skill in the art at the time of filing would have found it obvious to produce recombinant herpesvirus with diminished latency comprising VZV with deletion or mutation of ORF4 at its native location along with the insertion of Mahalingam’s 1-3600 bp SVV gene fragment between ORF65 and ORF66 of VZV because Cohen teaches that the latency gene can be VZV ORF4 or a homolog thereof, teaches deletion or mutation of the latency gene at its native location, and teaches insertion of a latency gene, driven by a different herpesvirus promoter which provides expression outside of the latency period, between ORF65 and ORF66 of VZV and Mahalingam discloses that the 1-3600 bp fragment of SVV comprises a homolog of ORF4, i.e., a latency gene - ORF A, which is immunologically cross-reactive with ORF 4, which is driven by a promoter which provides expression during acute infection rather than during latency.
The rejection set forth above addresses all the limitations of the claims.
Claims 1-4, 28 and 30-40 are rejected under 35 U.S.C. 103 as being unpatentable over Cohen in view of Mahalingam and Jiang et al., 2017 (NPL cite D4, IDS, 4/14/2023; herein “Jiang”).
The discussion of Cohen and Mahalingam regarding claims 1-4, 28, 30-35 and 37-40 set forth in the rejection above is incorporated herein.
Neither Cohen nor Mahalingam teach that the viral construct comprises at least three stop codons in open reading frame 7 (ORF7) of human VZV; however, a person of ordinary skill in the art at the time of filing would have found it obvious to inactivate VZV ORF7 in view of the disclosure of Jiang.
Jiang teaches that VZV ORF7 encodes a neurovirulent factor and that deletion of VZV ORF7 impairs virus transmission among neuronal cells and probably the neuropathy induced by VZV infection (Abst.). Cohen is drawn to diminishing latency (reappearance in neuronal tissues) of VZV; hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the chimeric viral construct made obvious by Cohen in view of Mahalingam to further comprise inactivation of the ORF7 neurovirulent factor. Inactivating ORF7 by introducing stop codons into all possible reading frames (3) or deleting ORF7 would both be obvious means well-known in the prior art for inactivating ORF7; therefore, claim 36 is prima facie obvious.
Response to Arguments
Applicant does not present any argument regarding the teachings of Jiang or the rejection of claim 36. The rejection set forth above addresses all the limitations of claim 36.
Claims 1-3, 28 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Khalili et al., US 2019/0093092 (US Patent document cite A1, IDS, 4/14/2023; herein “Khalili”) in view of Gray.
Khalili teaches compositions that specifically cleave target sequences in herpesvirus (Abst.) wherein the composition comprises a vector which can be a herpes simplex I virus [0109] encoding a Cas endonuclease [0051-62] and comprising a guide nucleic acid complementary to a target sequence which can be from SVV [0066-67] wherein the target sequence can be nucleic acid sequence encoding UL54 [0080].
Khalili does not specifically teach that the SVV sequence comprises SEQ ID NO: 1; however, a person of ordinary skill in the art at the time of filing would have found it obvious that the SVV sequence can be a nucleic acid fragment of SEQ ID NO: 1 in view of the disclosure of Gray.
Gray, as discussed above, teaches the genome (DNA) sequence of SVV and compares it to the genome sequence of VZV (Abst.; Fig. 1; Tables 1-3; p. 125, “SVV gene map”). Gray discloses that the 5’ end, i.e., left side, of the SVV genome comprises ORF A (start codon at 1807 bp and stop codon at 926 bp; Table 2) which is a UL54 homolog (Table 2; p. 125, “SVV gene map”).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce a chimeric viral construct comprising herpes simplex I virus encoding a Cas endonuclease and comprising a guide nucleic acid from SVV ORF A; therefore, claims 1-3 and 30 are prima facie obvious.
Regarding claim 28, it would be prima facie obvious to package the chimeric viral construct made obvious by Khalili in view of Gray in a container in a kit because kits are an effective way to market or distribute a product; therefore, claim 28 is prima facie obvious.
Response to Arguments
Applicant does not present any argument regarding the rejection of claims 1-3, 28 and 30 under 35 U.S.C. 103 over Khalili in view of Gray; hence, the rejection is maintained.
Conclusion
No claims are allowed.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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