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
Acknowledgement is hereby made of receipt and entry of the communication filed on April 09, 2026. Claims 64-83 are pending and are currently examined.
Please note: the SEQ ID NOs: 6-15 and 294-313 and at least 90% sequence identity to the sequence as set forth of SEQ ID NOs: 6-15 and 294-313, which were previously issued as “Allowable Subject Matter” in the office action filed on 01/09/2026, are re-evaluated and examined in the current office action based on applicant’s amendment.
This action is made non-final.
Claim Objection
(Previous objection- withdrawn) Claims 1-6 are objected to because of the following informalities:
This objection is withdrawn in view of the amendment filed on April 09, 2026.
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.
Claim 82 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 82 recites a phrase “administering a second therapeutically effective amount of the EBV vaccine of claim to the subject.” that render the claim indefinite. The cited limitation of “second therapeutically effective amount of the EBV vaccine” is not referred to a clear claim.
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- withdrawn) Claims 1-5, 45 and 50-63 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 rejection is withdrawn in view of the amendment filed on April 09, 2026.
(New Rejection-necessitated by amendment) Claims 64 and 69-83 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 base claim 64 is drawn to an EBV vaccine comprising the EBV vaccine antigen comprises the sequence of SEQ ID NO: 282, 286, 287, or 288 or a sequence having at least 98% sequence identity to SEQ ID NO: 282, 286, 287, or 288, the multimerization domain comprises the sequence of SEQ ID NO: 283 or 291 or a sequence having at least 95% sequence identity to SEQ ID NO: 283 or 291, and at least 90% sequence identity to the sequence of SEQ ID NOs: 304, 305, 306,307,308,309,310,311,312, or 313.
Claim 69 is drawn to a sequence of SEQ ID NO: 294, 295, 296, 297, 298, 299, 300, 301, 302, or 303 or a sequence having at least 90% sequence identity to the sequence of SEQ ID NO: 294, 295, 296, 297, 298, 299, 300, 301, 302, or 303.
Claim 70 is drawn to a sequence of SEQ ID NO: 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or a sequence having at least 90% sequence identity to the sequence of SEQ ID NO: 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.
The written description rejection is made because the claims are interpreted as being drawn to a EBV vaccine recited as being “at least 90% identity” to the instant claimed SEQ ID NOs: 304-313, SEQ ID NOs: 294-303 or SEQ ID NOs: 6-15, at least 98% sequence identity to SEQ ID NO: 282, 286, 287, or 288, and at least 95% sequence identity to SEQ ID NO: 283 or 291. This means that up to 10% amino acids sequences of the EBV vaccine of claim 1 can vary. For example, the claimed SEQ ID NO: 310 is a synthetic protein with the length of 932 amino acids, which show 99% percent identity to the EBV glycoprotein B encoded by the EBV BALF4 gene (See Table A below). If there are 10% sequence variations, it would differ by over 90 amino acids along the entire length of the sequence. As for the 2% variation of EBV antigen amino acids (SEQ ID NO: 282, 286, 287, or 288), and the 5% amino acids changes in multimerization domain (SEQ ID NO: 283 or 291), they would make about 13 amino acids and 10 amino acids difference in their sequences, respectively. Here these variations may alter the antigen immunogenicity epitope and the function of the multimerization domain. For example, Wu et al. (Virology. 2007 Jun 20;363(1):148-55) teaches that gp42 interacts directly with EBV gH and that point mutations in the region of gH recognized by an antibody that differentially inhibits epithelial and B cell fusion significantly impact both the core fusion machinery and cell specific events. Substitution of alanine for glycine at residue 594 completely abrogates fusion with either B cells or epithelial cells (See Wu et al.,
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Abstract).
The instant specification discloses that their invention provides anti-Epstein Barr virus (EBV) vaccines and uses of the same, and the EBV vaccine antigens can be formulated to treat an EBV-infected subject or a subject at risk of EBV infection. Treating EBV can reduce EBV infection and/or treat a condition associated with EBV infection (See [0008]- [0009]). The instant specification also discloses that the primary goal of most vaccine design strategies is to elicit production of neutralizing antibodies, which are a type of antibody that can inhibit the biological function of its target. Neutralizing antibodies against viruses such as EBV typically function by blocking a virus from entering a cell (See [0034]), and high levels of antibodies that neutralize EBV B-cell infection are associated with lowered risks for nasopharyngeal carcinoma (See [0009]).
However, the specification does not indicate which portions of the claimed SEQ ID NOs are essential to retain the ability to be a functional vaccine to induce the subject’s immune responses, and which portions of SEQ ID NOs can be modified or altered up to 10% and still retain the ability of eliciting the claimed immune responses.
It was common knowledge in the art that the sequence variations in EBV can significantly alter the stimulated immune response, for example, a minor sequence changes within critical T-cell epitopes can affect immune recognition. This can be evidenced by Cirac’s study (J Immunol Sci. (2018); 2(3): 51-55). Cirac et al. teaches that their study clearly demonstrated that sequence variations in EBV strains may reside within T-cell epitopes and potentially compromise the antiviral CD8+ T-cell response (See page 52, right column, paragraph 2). Another evidence is from Zhang’s study (Proc Natl Acad Sci U S A. 2022 Aug 9;119(32): e2202371119). Zhang et al. teaches a point mutation in the glycoprotein of EBV can change its binding to the neutralizing antibody. Zhang et al. disclsoes two anti-EBV gB neutralizing antibodies, 3A3 and 3A5, that effectively neutralized EBV infection of both B and epithelial cells. They also potently protected against EBV-induced lymphoproliferative disorders in humanized mice. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines (See Abstract and Significance). However, Zhang et al. also teaches that gB with the point mutations of E356A or D360A completely abolished binding with mAb 3A3, while H352A retained a weak interaction with 3A3 (Fig. 6A) (See page 8, right column).
The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004).
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.).
As discussed above, the skilled artisan cannot envision the detailed genomic sequence of the EBV vaccine as claimed to SEQ ID NOs for still being able to stimulate an anti-EBV immune response in a subject or become a EBV vaccine, therefore, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
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.
Claims 64-83 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (US 2024/0309050 A1, PCT filed on Sep. 1, 2021, hereinafter, “Zeng”) in view of Stoddard et al. (WO2021003413A2, published on Jan. 07, 2021) as evidenced by Liang et al. (J Microbiol. 2026 May;64(5): e2511020) and UCLA Health (https://www.uclahealth.org/news/article/why-do-vaccines-require-boosters)
The new base claim 64 is directed to an EBV vaccine comprising an EBV vaccine antigen linked to a multimerization domain,
wherein the EBV vaccine antigen comprises the sequence of SEQ ID NO: 282, 286, 287, or 288 or a sequence having at least 98% sequence identity to SEQ ID NO: 282, 286, 287, or 288,
the multimerization domain comprises the sequence of SEQ ID NO: 283 or 291 or a sequence having at least 95% sequence identity to SEQ ID NO: 283 or 291,
and wherein the EBV vaccine antigen linked to the multimerization domain comprises a sequence having at least 90% sequence identity to the sequence of SEQ ID NOs: 304, 305, 306, 307, 308, 309, 310, 311, 312, or 313.
Zeng teaches an invention providing a vaccine comprising self-assembled nanoparticle containing a gHgL protein (See [0009]), where the gHgL is a vaccine antigen (See [0064]). Zheng also teaches a SEQ ID NO: 25 (See [0097]; page 16) that is 99% identical to the SEQ ID NO: 282 as claimed (See Table A below) (Here it also teaches claim 65). Also, SEQ ID NO: 25 has 77% denticity to SEQ ID NO: 304 (See Table B below). Although SEQ ID NO: 25 does not teach an identical or at least 90% sequence identity to the SEQ ID NO: 304, it teaches the antigen sequence of gHgL that contain the 99% of SEQ ID NO: 282 (See Table A; Table B, amino acids 1-660; [0066]), a linker (GGSGGSGS) (See Table B; [0093] and Table 1), and the first vector subunit 153-50A1 (See Table B, amino acids 672-829; claims 1-2, page 26). Zeng also teaches that the gHgL-linker-I53-50A1 is a trimer (See [0066]), where the I53-50A1 is comparable to a “multimerization domain” as claimed. This can be evidenced by Liang’s study. Liang evidences that I53-50 is a computationally designed, self-assembling protein nanoparticle (NP) that forms a stable icosahedral structure composed of 120 protein subunits coordinated through precise interfacial interactions (See Abstract), and the I53-50 NP is formed by the in vitro self-assembly of two oligomeric protein components: the trimeric I53-50A and the pentameric I53-50B. I53-50A (20 copies) is used to genetically fuse the target antigens (See page 1, right column, paragraph 2).
Accordingly, Zeng teaches a EBV vaccine with the claimed antigen that linked to a multimerization domain. Although Zeng’s linker sequence and the I53-50A1sequence are not identical to the claimed sequences of multimerization domain as claimed, Zeng teaches a EBV construct containing the EBV vaccine antigen, linker and a multimerization domain. Thus, one of skilled in the art can develop a EBV antigen vaccine based on Zeng’s teaching to use the antigen of Zeng (that is identical to the antigen sequence as claimed) and fuse it with any linker and a multimerization domain unless the claimed linker and multimerization domain can make unexpected results.
Nevertheless, Stoddard teaches an invention for self-assembling circular tandem repeat proteins with increased stability. The SEQ ID NO: 155 (scFv_CD28_ TGN1412-Toroidx6_SS_tetramer-His) contains identical sequence with the SEQ ID NO: 283 as claimed (See page 49; Table C below) (Here it. Also teaches claim 66). Also, Stoddard teaches that the linker in SEQ ID NO: 304 “GGGGSGGGGS” (See [0131]).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the linker and multimerization domain sequence of Stoddard into Zeng’s invention. One of skill in the art would have been motivated to do so to use the known sequence to develop a EBV vaccine comprising an EBV vaccine antigen linked to a multimerization domain (See MPEP 2144.06: Substituting equivalents known for the same purpose). Thus, Zeng in view of Stoddard teaches the EBV vaccine antigen linked to the multimerization domain with a sequence such as SEQ ID NO: 304 (See Table B and C below) (Here it also teaches claim 68), and there would be a reasonable expectation of success to construct vaccine design based on the teachings of Zeng and Stoddard.
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Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 67, Stoddard’s SEQ ID NO: 185 is identical to the claimed linker sequence SEQ ID NO: 270 at “GGGSGGGS”. Thus, Zeng in view of Stoddard teaches claim 67.
Regarding claim 69, the instant SEQ ID NO: 294 contains three fragment fusion (See Table D below). The bold part is identical to the claimed SEQ ID NO: 283 (see Table A) that is taught by Zeng’s SEQ ID O: 25 at 99% identity. The underlined part are the linker that is taught by Stoddard at [0131]), and the part thatis taught by Stoddard’s SEQ ID NO: 155 (See Table E below). Thus, Zeng in view of Stoddard teaches claim 69.
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Regarding claim 70, Zeng’s SEQ ID NO: 25 contain 99% identical sequences to the antigen sequence of SEQ ID NO: 6 as claimed (See Table F below). Stoddard’s linker GGGGSGGGGS teaches the ‘linker” in the SEQ ID NO: 6. The multimerization domain sequence in the SEQ ID NO: 6 is taught by Stoddard’s SEQ ID NO: 155 at 100%. Thus, Zeng in view of Stoddard teaches claim 70.
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Regarding claim 71, Zeng teaches that the first polypeptide is preferably obtained by the following steps: introducing a nucleic acid expressing the first polypeptide into a first host cell; and incubating the first host cell to express the first polypeptide (See 0051]), which indicates that a nucleotide sequence encoding an EBV vaccine.
Regarding claim 72, Zeng teaches using the vaccine for preventing EB virus infection, comprising administering to a subject in need thereof an effective amount of the self-assembled nanoparticle (See claim 20, page 26), and the self-assembled nanoparticle can strongly stimulate more B cells and induce higher antibody titer (Abstract).
Regarding claims 73-75 and 79, Zeng teaches the self-assembled nanoparticle can be used for preventing EB virus infection and treating diseases caused by EB virus infection (See e.g., [0064]), which indicates that the EB vaccine can be administrated to seronegative subject to prevent EB infection (claim 74) or to administer to a seropositive subject to treat diseases caused by EB virus infection (claims 73 and 79). For a vaccine that can prevent the viral infection, one of skilled in the art can introduce the vaccine to a seronegative pediatric patient based on needs to prevent EBV infection (claim 75).
Regarding claims 76-77, Zeng teaches EBV vaccine can be used to prevent EBV infection or treat the diseases caused by EBV infection through administering to a subject in need (See claims 20 and 22, page 26), which indicates the EBV vaccine can be introduced into patient such as immunosuppressant patient and transplant patient based on need. For example, Zeng teaches that EB virus may also cause post-transplant lymphoproliferative diseases (See [0004]) that indicates a need for applying the EBV vaccine to the transplant patient.
Regarding claims 78 and 80-81, Zeng teaches that the EBV vaccine can treat diseases selected from the group consisting of infectious disease, malignant tumor, chronic disease, and autoimmune disease…mononucleosis, nasopharyngeal carcinoma… Hodgkin lymphoma…and ankylosing myelitis (See [0061]).
Regarding claims 82-83, Zeng teaches immunizing a Balb/C mouse using the EBV nanoparticles to induce antibody against gHgL generated in the mouse (See [0082]), and does not explicatively point out a second or third administering. However, it is a common knowledge in the art that boost vaccination is important to achieve a full immunity. One of skilled in the art can decide to the boost administration to a subject based on the needs This can be evidenced by UCLA Health ( https://www.uclahealth.org/news/article/why-do-vaccines-require-boosters). UCLA Health teaches that sometimes it takes more than one dose of a vaccine to build complete immunity (See page 2).
Responses to Applicant’s Remarks
Applicant’s arguments filed on April 09, 2026 has been received and fully considered.
Applicant’s amendment regarding the objection rejection is considered. The objection is withdrawn.
Applicant’s amendment regarding the rejections under 35 U.S.C. 112(a) is considered. The rejection is withdrawn.
Conclusion
No claims are 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am-5:00 pm, EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached on (571) 270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RUIXUE WANG/Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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