Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Claims
Claims 1,2 and 22-38 are pending.
Claims 3-21 were previously canceled.
Claims 1, 2, and 22 are amended.
Claims 23-38 are new claims.
Claims 1,2 and 22-38 are under consideration.
Claim Objections
(previous objection; withdrawn) Claims 1,2,22 are objected to because of the following informalities:
- All three claims contain the following acronyms: HSV1, HSV2 and Fc. For improved form, spell out the acronyms in the first instance for each, e.g., herpes simplex virus 1 (HSV1).
- All three claims contain “cross reactive” which should be written “cross-reactive”.
Applicant contends: Claims 1, 2, and 22 are objected to because of certain informalities. Office Action at page 2. Applicant has herein amended claims 1, 2, and 22 to address these informalities. Specifically, as required by the Office, Applicant has spelt out the acronyms HSV1, HSV, and Fc. Additionally, as further required by the Office, Applicant has replaced the term "cross reactive" with "cross-reactive."
In view of the foregoing, Applicant respectfully requests reconsideration and withdrawal of these claim objections.
Office response: Based on the amendments made by the applicant, the objection to claims 1, 2, and 22 are withdrawn.
Claim Rejections - 35 USC § 112
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.
(previous rejection is maintained but modified as to claims 1, 2, and 22; new as necessitated by amendment as to new claims 23-38 which are dependent on these claims) Claims 1, 2, 22-38, 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 claims contain 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 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 inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[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 contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
[Modification] Instant claim 1 recites: A recombinant nucleic acid encoding a Herpes Simplex Virus 2 (HSV2) fragment crystallizable (Fc} receptor or an immunogenic fragment or variant thereof for use in inducing a cross reactive immune response against HSV1 when administered to a subject, wherein said Fc receptor or immunogenic fragment or variant thereof is a HSV2 gE2 ectodomain having a sequence which is at least 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to the amino acid sequence of SEQ ID NO: 7.
[Modification] Instant claim 2 recites: The recombinant nucleic acid
[Modification] Instant claim 22 recites: A method of treating a herpes virus infection or herpes virus related disease in a subject in need thereof comprising administering an immunologically effective amount of the recombinant nucleic acid of claim 1 to the subject wherein the HSV2 Fc receptor or immunogenic fragment or variant thereof induces cross-reactive immune response against HSV1 when administered to a subject.
[Modification] Instant claim 25 recites: The recombinant nucleic acid of claim 24, wherein the HSV2 g12 ectodomain has the amino acid sequence of SEQ ID NO: 8, or a variant thereof which is at least 90% identical thereto.
[Modification] Instant claim 28 & 29 recite: one or more amino acid residue substitutions, deletions, or insertions relative to SEQ ID NO: 7.
The Specification defines both immunogenic fragment or variant thereof below:
“[I]mmunogenic fragment” refers to a fragment of a reference antigen containing one or more epitopes (e.g., linear, conformational or both) capable of stimulating a host's immune system to make a humoral and/or cellular antigen-specific immunological response (i.e. an immune response which specifically recognizes a naturally occurring polypeptide, e.g., a viral or bacterial protein). An “epitope” is that portion of an antigen that determines its immunological specificity. T- and B-cell epitopes can be identified empirically (e.g. using PEPSCAN or similar methods). In a preferred embodiment, the immunogenic fragment induces an immune response, suitably a humoral or T cell response, which is similar to the immune response induced by the reference antigen [0179].
“Variant” is a peptide sequence that differs in sequence from a reference antigen sequence but retains at least one essential property of the reference antigen. Changes in the sequence of peptide variants may be limited or conservative, so that the sequences of the reference peptide and the variant are closely similar overall and, in many regions, identical. A variant and reference antigen can differ in amino acid sequence by one or more substitutions, additions or deletions in any combination. A variant of an antigen can be naturally occurring such as an allelic variant, or can be a variant that is not known to occur naturally. Non-naturally occurring variants of nucleic acids and polypeptides may be made by mutagenesis techniques or by direct synthesis. In a preferred embodiment, the essential property retained by the variant is the ability to induce an immune response, suitably a humoral or T cell response, which is similar to the immune response induced by the reference antigen [0176].
The specification fails to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to immunogenic fragments or variants that can induce a cross-reactive immune response against HSV2 when administered to a subject and treat a herpes virus infection or herpes virus related disease. While some examples of fragments/variants are provided in the specification (e.g., different mutated versions of AS01/HSV-2 gE/gI protein)[0547], the specification fails to sufficiently describe the structural features that must be retained by members of the claimed genus.
[Modification] Provision of SEQ ID NOs such as SEQ ID NO: 7 and SEQ ID NO: 8 within the claims does narrow down the focus of the appropriate claims. However, the instant claims still read on a broad genus with possible variations that do not account for sufficient structure function correlation.
[Modification] The specification has only adequately described and successfully reduces to practice the following HSV-2-2gE/gI variants: V340W/AS01, A248T/AS01, A246W/AS01; P318I/AS01, and A248T_V340W/AS01 (see Drawings).
The Specification cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of fragments and variants thereof because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
At best, the Specification contemplates the use of BLAST to identify functional homologs [0421-0425] based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Thus, one of skill in the art would readily appreciate that relying on a non-patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
Moreover, Friedberg (Brief Bioinformatics, 7:225-242 (2006)) teaches that homology-based transfer is not reliable for functional annotation even with high alignment percentages (page 227, second column). Friedberg also teaches that identification of functionally significant sub-regions is critical to functional annotation, and that often addition, deletion, or re-shuffling
of domains can lead to errors in annotation (page 227, second column; page 228, first paragraph). Furthermore, Friedberg teaches that sequence-based tools are just not sensitive enough to identify functional protein similarity as databases get larger, and diversity of sequences gets larger (page 228, first full paragraph).
Thornton et al. (Nature Struct. Biol, Struct. Genom. Suppl. Nov., 991-994 (2000), hereinafter “Thornton”) teaches that the same protein structure is often seen in apparently different homologous families with different functions. Thornton further describes examples of little correlation between specific enzyme function and overall protein structure (page 992, right column, at lines 2-10). Thus, when taken with the teachings of Friedberg and Thornton, one of skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In the absence of a representative number of examples, the Specification must at least
describe the structural features that are required for the claimed function, in this case cross- reactive immune response induction against HSV1 or HSV2 when administered to a subject. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to immunogenic fragments or variants. The Specification also fails to describe which regions, domains, etc. of the variant sequences must be retained in order to have a “functional fragment” of the variant. Instead, Applicant merely offers a cursory statement that an immunogenic fragment or variant thereof will work.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Applicant contends: Applicant respectfully traverses the rejection.
Not in acquiescence with the Office and solely to expedite prosecution, Applicant has amended sole independent claim 1 to recite that "the Fc receptor or immunogenic fragment or variant thereof is a HSV2 gE2 ectodomain having a sequence which is at least 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to the amino acid sequence of SEQ ID NO: 7." (Emphasis added). Applicant has further amended claim 2 and 22 to depend from claim 1. Additionally, the newly added claims 23-38 all depend, directly or indirectly, from claim 1.
Applicant submits the currently pending claims sufficiently describe a structural limitation (i.e., at least 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to the amino acid sequence of SEQ ID NO: 7) and therefore establish a structure-function relationship with respect to the immunogenic fragments or variants. Applicant further asserts that the present claims additionally recite that the ectodomain of the HSV2 gE2 variant sequences must be retained to have a "functional fragment" of the variant.
In view of the foregoing, Applicant respectfully requests reconsideration and withdrawal of the rejection under 35 U.S.C. § 112.
Office response: Applicant’s traversal of the rejection is acknowledged. The Applicant's arguments filed 06/09/2026 have been fully considered but they are not persuasive.
Modifications as necessitated by amendment have been incorporated in the original rejection. Identifying the sequences (SEQ ID NO : 7 and SEQ ID NO: 8) as well as defining the sequences having a certain percentage of identity as well different variants do contract the scope of the claim, however, not in a sufficient manner to over the 112a rejection as indicated above. The claims, notably instant claims 1, 25, 28, and 29 are still drawn to a large genus.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
(previous rejection; withdrawn) Claims 1 and 2 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The judicial exception is not integrated into a practical application and claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below. See MPEP § 2106.04 for analysis parameters.
Applicant contends: Applicant respectfully traverses the rejection. Not in acquiescence with the Office and solely to expedite prosecution, Applicant has amended claim 1 and its dependent claims 2 and 22-38 to recite that the claimed nucleic acid is a "recombinant" nucleic acid. As expressly disclosed in the present specification: "Recombinant" means that the polynucleotide is the product of at least one of cloning, restriction or ligation steps, or other procedures that result in a polynucleotide that is distinct from a polynucleotide found in nature.
See, Specification at para [0414] (emphasis added).
Thus, Applicant submits that, contrary to the Office's contention, the presently amended claims are directed to a man-made recombinant nucleic acid, and is therefore not directed to a judicial exception in the form of a natural phenomenon.
In view of the foregoing, Applicant respectfully requests reconsideration and withdrawal of the rejection under 35 U.S.C. § 101.
Office response: Applicant’s traversal of the rejection is acknowledged. Based on applicant’s amendments, the rejection of claims 1 and 2 are withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
(previous rejection: withdrawn) Claims 1, 2, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Friedman et al. (Friedman) (US20200276300A1) (See PTO-892 Notice of References Cited) in view of Jenks et al. (Jenks) (See PTO-892 Notice of References Cited) and further in view of Balachandran et al. (Balachandran) (See PTO-892 Notice of References Cited).
Applicant contends: Applicant respectfully traverses the rejection.
Sole independent claim 1, as currently amended, is directed to a recombinant nucleic acid encoding "a HSV2 Fc receptor or an immunogenic fragment or variant thereof . . .wherein said Fc receptor or immunogenic fragment or variant thereof is a HSV2 gE2 ectodomain having a sequence which is at least 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to the amino acid sequence of SEQ ID NO: 7." (Emphasis added).
Applicant submits that neither one of Friedman, Jenks, or Balachandran, alone or in any combination, disclose or even contemplate a HSV2 FC receptor that is a HSV2 gE2 ectodomain, much less a HSVB2 gE2 ectodomain that comprises a sequence which is at least 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identical to the amino acid sequence of SEQ ID NO: 7, as presently recited in claim 1. Claims 2, 22 and 23-38 depend, directly or indirectly, from claim 1 and therefore incorporate all elements of claim 1. Thus, contrary to the Office's position, one of ordinary skill in the art would not have been motivated to combine the cited references, nor would such a person have had a reasonable expectation of success in arriving at the subject matter of claim 1, or its dependent claims 2, 22, and 23-38, based on the cited references, either alone or in any combination.
Accordingly, Applicant submits that amended claims 1, 2, and 22 (as well as new claims 23-38) are not obvious over Friedman, Jenks, or Balachandran, either alone or in any combination.
In view of the foregoing, Applicant respectfully requests reconsideration and withdrawal of the rejection under 35 U.S.C. § 103.
Office response: Applicants traversal of the rejection is acknowledged. Based on the amendments made by the applicant, the rejection to claims 1, 2, and 22 are withdrawn. See new rejection (below) as necessitated by amendment.
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.
(previous rejection; withdrawn) Claims 1, 2, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of co-pending Application No. 18262033 in view of Friedman et al. (Friedman)(US20200276300A1).
Applicant’s response: Applicant respectfully traverses this ground of rejection and requests that this rejection be held in abeyance until indication by the Office of allowable subject matter.
Office response: Applicant’s traversal of the rejection is acknowledged. Based on the amendments made by the applicant, the rejection to claims 1, 2, and 22 are withdrawn. See new rejection (below) as necessitated by amendment.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(new, necessitated by amendment) Claims 2, 29, 35-36 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.
See claims 2, 29, 32, 35-36 as submitted 06/09/2026.
Claim 2: Claim 2 recites “wherein the nucleic acid induces cross-reactive immune response against Herpes Simplex Virus 1 (HSV1) when administered. However, it is not the nucleic acid that presumably induces the cross-reactive immune response but the nucleic acid encoded HSV2 Fc receptor or an immunogenic fragment or variant that does. It is unclear if the applicant is claiming a nucleic acid vaccine (DNA or RNA) or the Fc receptor/immunogenic fragment.
Claim 29: While the specification provides explanations on the nomenclature for point substitution mutations, double substitution mutations, deletions and insertions (p. 48-51), it is unclear what is meant by, for example, H245A_P319R.
Claim 32: Claim 32 recites the limitation “The recombinant nucleic acid of claim 23, wherein the sequences”. There is insufficient antecedent basis for this limitation in the claim. While sequence(s) for the Fc fragment are stated in claim 1, sequence(s) for the binding partner are stated in claim 25.
Claims 35 and 36: Claim 35 recites “such as to form a cationic nanoemulsion…” and such as to form a CNE…”. With the use of exemplary language, e.g., “such as”, it is unclear what the intended scope of the claim is. As a result, the claim language is indefinite (See MPEP 2173.05(d) Exemplary Claim Language).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
(new, necessitated by amendment) Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
See claim 2 as submitted 06/09/2026.
See claim rejection under 112b above.
Claim 2 recites “induces a cross-reactive immune response against Herpes Simplex Virus 1 (HSV1) when administered to a subject” which is identical to the language in claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 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.
(new, necessitated by amendment) Claims 1, 2, 22-24, 26, 27, 31, 33, 35-38 are rejected under 35 U.S.C. 103 as being unpatentable over Friedman (previously cited) in view of Friedman et al (Friedman 2010)(See PTO-892: Notice of References Cited) and Jenks (previously cited) and further in view of Balachandran (previously cited).
See claims 1, 2, 22-24, 26, 27, 31, 33, 35-38 as submitted 06/09/2026.
Regarding claim 1, 2, 22-24, Friedman teaches a composition comprising modified mRNA encoding HSV-2 or HSV-1 gE or gI or fragments thereof [0058] or as recited in reference claim 4, h) “any combination thereof which can include both HSV-2 gE and gI fragments” (reads on instant claim 23, 24) and a method of inducing an anti-HSV immune response in a subject, the method comprising the step of administering to said subject an immunogenic composition comprising modified mRNAs encoding…(c) an HSV gE or fragment thereof as described herein, or a combination thereof [0217]. Friedman also teaches HSV-1 and HSV-2 glycoprotein E (gE) function as immune evasion molecules by binding the Fc domain of an IgG molecule that is bound by its F(ab′)2 domain to its target. Additionally, Friedman teaches the subject is administered HSV-1 glycoproteins for methods of treating, inhibiting, suppressing, etc. an HSV-1 infection, HSV-2 infection, or a combination thereof [0210] suggesting a cross-reactive immune response to achieve the method. Friedman further teaches “In another embodiment, the subject is administered HSV-2 glycoproteins for methods of treating, inhibiting, suppressing, etc. an HSV-1 infection, HSV-2 infection, or a combination thereof. In one embodiment, administration of HSV-1 glycoproteins (e.g., gC1, gD1, gE1, or a combination thereof) treats or prevents HSV-1 and HSV-2 infection. In another embodiment, administration of HSV-2 glycoproteins (e.g., gC2, gD2 and gE2, or a combination thereof) treats or prevents HSV-1 and HSV-2 infection”.
Friedman also teaches in reference claim 7, “wherein said immunogenic fragment of HSVgE comprises amino acids 24-405 from HSV-2 strain 2.12, or a homologous sequence from another HSV strain.
Friedman 2010 teaches Human Herpesvirus 2 glycoprotein E (gE), SEQ ID NO: 18 with 100% Query Match with instant claim SEQ ID NO: 7 (see Result #9, AYL74324, us-18-262-073-7.rag, 8/04/2026, in supplemental contents tab). Reference claim SEQ ID NO: 18 (HG52) is a glycoprotein E (gE) protein sequence used for the sequence alignment with HSV-2 (2.12) in the Friedman 2010’s invention. HSV-2 (2.12) and reference claim SEQ ID NO: 18 (HG52) have a 96% identity (see p. 27, FIG. 31B).
Regarding 31 and 33, Friedman teaches “administering a modified mRNAs encoding HSV glycoprotein and a pharmaceutically acceptable carrier or diluent” [0343].
Regarding claims 35 and 36, Friedman teaches “a method of present invention further comprises administering the modified mRNA together with the transfection reagent. In another embodiment, the transfection reagent is a cationic lipid reagent” [0303]. Friedman also teaches “For example, in one embodiment, the composition comprises an LNP and one or more nucleoside-modified RNA molecules encoding one or more antigens, adjuvants, or a combination thereof”[0316].
Regarding claims 27, 37 and 38, The specification provides a definition of immunodominant antigens (p. 62). While Friedman does teach embodiments with the immunodominant antigen, HSV glycoprotein D (gD2), they also teach embodiments with only the subdominant antigens such as gE2 [0058].
While Fc binding is discussed, Friedman does not specifically teach Fc receptors.
Jenks, however, teaches “herpesviruses also encode their own viral FcRs (FcRs) [Fc receptors], which recognize the Fc regions of host immunoglobulins. These vFcRs mimic host FcRs, enabling herpesviruses to reduce and evade antiviral immune responses”(p.3). Jenks also teaches “HSV-1 encodes surface glycoproteins gE and gI, which can form a complex on infected cells or on the virion surface that binds to the Fc domain of host IgG... This complex acts as a vFcR [viral Fc receptor] and is associated with cell-to-cell spread of infection...The HSV gE-gI complex is required for the binding of monomeric non-immune IgG, but HSV gE alone is sufficient for binding polymeric IgG. Jenks also discusses HSV-2 glycoprotein E as a viral Fc receptor and its use in a vaccine (p. 6).
Neither Friedman or Jenks specifically address cross-reactivity.
Balachandran, though, teaches antigenic cross-reactions among herpes simplex virus types 1 and 2 in relation to both HSV-1 and HSV-2 glycoprotein E (gE) in Table 3 (p. 1133).
Regarding claim 26, Claim 26 recites “The recombinant nucleic acid of claim 1, wherein the ability of said Fc receptor or immunogenic fragment or variant thereof to bind to a human antibody Fc domain is reduced or abolished compared to the corresponding native HSV Fc receptor”. According to MPEP 2112.01, I. Product and Apparatus claims – When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Additionally, 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).
One of ordinary skill in the art would have been motivated to take into consideration Jenks’ explanation of the HSV glycoprotein E, its roles as a viral Fc receptor and how it allows HSV to evade the host immune response as well as Balachandran’s findings of cross-reactive immune response between HSV-1 and HSV-2 gE and combine both teachings with Friedman’s mRNA composition and method and Friedman 2010’s Fc/immunogenic fragment to arrive at the claimed invention. (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results and Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success for combining the teachings of Friedman, Friedman 2010, Jenks, and Balachandran to arrive at a method of treating a herpes virus infection or herpes virus related disease in a subject. There would have been a reasonable expectation of success given the underlying materials and methods are known within the herpes virus and nucleic acid vaccinology fields, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
(new, necessitated by amendment) Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Friedman in view Friedman 2010, Jenks and Balachandran as applied to claims 1, 2, 22-24, 26, 27, 31, 33, 35-38 above, and further in view of Ciaramella et al. (Ciaramella)(WO2017070623-A1)(See PTO-892: Notice of References Cited).
See claim 25 as submitted 06/09/2026.
Friedman, Friedman 2010, Jenks and Balachandran teach claims 1, 23 and 24 but do not teach wherein the HSV2 gl2 ectodomain has the amino acid sequence of SEQ ID NO: 8, or a variant thereof which is at least 90% identical thereto.
Ciaramella teaches a herpes simplex virus (HSV) ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. Ciaramella teaches human herpesvirus 2 strain 333 envelope glycoprotein I (gI), SEQ ID 52 with 100% Query Match with instant SEQ ID NO: 8 (see Result# 2, BDW19777, us-18-262-073-8.rag, 08/04/2026, in supplemental contents tab).
One of ordinary skill in the art would have been motivated to substitute the HSV2 gl2 ectodomain SEQ ID 52 as the binding partner in a heterodimer with the aforementioned taught Fc fragment as a nucleic acid vaccine component as taught by Friedman and Friedman 2010 in order to generate an immune response against these components which are known to form a complex associated with cell-to-cell spread of infection as taught by Jenks (see MPEP 2143 Rationale B. Simple substitution of one known element for another to obtain predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success for substituting human herpesvirus 2 strain 333 envelope glycoprotein I (gI), SEQ ID 52 as taught by Ciaramella. There would have been a reasonable expectation of success given the underlying materials and methods are known within the herpes virus and nucleic acid vaccinology fields, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
(new, necessitated by amendment) Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Friedman in view Friedman 2010, Jenks and Balachandran as applied to claims 1, 2, 22-24, 26, 27, 31, 33, 35-38 above, and further in view of Esser et al. (Esser)(WO9820016-A1)(See PTO-892: Notice of References Cited).
See claim 28 as submitted 06/09/2026.
Friedman in view Friedman 2010, Jenks and Balachandran teach claim 1 but do not teach wherein said HSV2 gE2 ectodomain or an immunogenic fragment or variant thereof comprises one or more amino acid residue substitution, deletion, or insertion relative to the amino acid sequence of SEQ ID NO: 7.
Esser, however, teaches “preferred embodiment of this aspect of the invention the polynucleotides comprise any of the regions encoding HSV-2 proteins in the sequences set out in Tables 1-4, including fragments,analogs or derivatives thereof” (p. 4). Esser teaches HSV-2 strain SB5 Contig ID 12 ORF#7 protein with an R199G substitution and a 99.7% Query Match to instant application SEQ ID NO: 7 (see Result# 104, AAW72165, us-18-262-073-7.minpct95.rag, 08/10/2026, in supplemental contents tab).
One of ordinary skill in the art would have been motivated to use the Fc receptor or immunogenic fragment, HSV-2 strain SB5 Contig ID 12 ORF#7 protein, as taught by Esser because it meets the limitation as stated in the instant claim of having a sequence at least 99.5% identical to the amino acid sequence of SEQ ID NO: 7 and, as Esser states “polypeptides or fragments thereof that may be employed for therapeutic or prophylactic purposes, for example, to treat disease, including treatment by conferring host immunity against viral infections, or as an antiviral agent or a vaccine. In accordance with another aspect of the present invention, there is provided the use of a polynucleotide of the invention for therapeutic or prophylactic purposes, in particular genetic immunization” against HSV (See MPEP 2143, Rationale B. Simple substitution of one known element for another to obtain predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success for using the Fc receptor or immunogenic fragment as taught by Esser. There would have been a reasonable expectation of success given the underlying materials and methods are known within the herpes virus and nucleic acid vaccinology fields, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
(new, necessitated by amendment) Claim 34 is rejected under 35 U.S.C. 103 as being unpatentable over Friedman in view Friedman 2010, Jenks and Balachandran as applied to claims 1, 2, 22-24, 26, 27, 31, 33, 35-38 above, and further in view of Lundstrom et al. (Lundstrom)(See PTO-892: Notice of References Cited).
See claim 34 as submitted 06/09/2026.
Friedman, Friedman 2010, Jenks and Balachandran teach claims 1 and 33 but do not teach self-amplifying RNA molecules.
Lundstrom, however, reviews replicon RNA viral vectors as vaccines, discusses self-replicating RNA expression systems, and lists examples of self-replicating RNA viral vector-based immunizations against viral diseases (p. 1, 4, 5, Table 1, p. 14,Table 4) which includes a Herpes Simplex virus vector (p. 14, Table 4). Lundstrom also teaches “herpes simplex virus (HSV) vectors have been frequently applied and HSV-GM-CSF have, for instance, been subjected to phase I−III human clinical trials in glioblastoma and melanoma patients [133]. HSV vectors were recently approved by the FDA for use in standard patient care”(p. 13). Finally, Lundstrom teaches “Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges (with HSV-2) or under safe conditions” (p. 1, Abstract).
One of ordinary skill in the art would have been motivated to try an RNA construct as a self-amplifying RNA molecule as taught by Lundstrom because experimental evidence suggests that immunization with self-replicating RNA viruses provides high transient expression levels of antigens (so in this case HSV immunodominant or subdominant antigens), resulting in generation of neutralizing antibody responses and protection against infection (See MPEP 2143, Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success for using a construct wherein the RNA molecules is a self-amplifying RNA molecule. There would have been a reasonable expectation of success given the underlying materials and methods are known within the herpes virus and nucleic acid vaccinology fields, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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.
(new, as necessitated by amendment) Claims 1, 2, 22-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17, 19, 23, 24, 25, 26, 27, 28, 29, 30 of co-pending Application No. 18262033 in view of Friedman and Ciaramella.
The present claims are drawn to:
See claims 1, 2, 22-38 as submitted 06/09/2026.
The claims of the co-pending Application No. 18262033 are drawn to:
See claims 1, 17, 19, 23, 24, 25, 26, 27, 28, 29, 30 as submitted 06/04/2026.
Although the claims at issue are not identical, they are not patentably distinct from each other. The instant application claims are drawn to a nucleic acid encoding a HSV2 Fc receptor or an immunogenic fragment or variant thereof whereas the co-pending application claims are drawn to a HSV2 Fc receptor or an immunogenic fragment or variant thereof. The HSV2 Fc receptor, etc. of co-pending Application No. 18262033 would have been derived from HSV strains whose genome or parts of their genome are known (e.g., Genbank accessions) with genes for the “Fc receptor” of interest. Whether expressed naturally or via molecular cloning efforts, the HSV1 or HSV2 Fc receptor would still be the desired and the crucial immunogenic composition. While the rejection is directed at the claims, the specification in the co-pending application does state, “In a further aspect, the invention provides a nucleic acid encoding a HSV1 or HSV2 Fc receptor or immunogenic fragment or variant thereof of the invention” [0357]. Furthermore, and with respect to nucleic acid vaccines, Friedman teaches modified mRNAs, wherein each of said nucleoside modified mRNAs encodes a Herpes Simplex Virus (HSV) glycoprotein or immunogenic fragment thereof (claim 1). As stated above, Ciaramella teaches a herpes simplex virus (HSV) ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. Ciaramella also teaches human herpesvirus 2 strain 333 envelope glycoprotein I (gI), SEQ ID 52 with 100% Query Match with instant SEQ ID NO: 8.
Therefore, based on the claims in the co-pending Application No. 18262033, and Friedman and Ciaramella’s teachings, the invention as a whole would have been prima facie obvious.
Conclusion
Claim 29: Mutations: 289_insert ADIGL; 338_insert ARAA; H245K; P317R; P319R; P319G; and P319K appear to be free of the prior art.
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/C.C./Examiner, Art Unit 1672
/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672
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