DETAILED ACTION
Disposition of Claims
Claims 8-9, 14-15, 17, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 were pending. Claims 1-7, 10-18, 20-24, 27, 29-31, 33, 35-43, 45-54, 56-60, 62, 64, and 66-76 have been cancelled. Amendments to claims 8-9, 19, 25-26, 28, 32, 44, 55, 63, 79, and 81-82 are acknowledged and entered. Claims 8-9, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 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 US20230381298A1, Published 11/30/2023.
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.
The Power of Attorney filed 03/18/2026 is of record and has been accepted.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Response to Arguments
Applicant's arguments filed 07/01/2026 regarding the previous Office action dated 04/01/2026 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 If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn.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arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Claim Objections
(Objection withdrawn.) The objection to Claims 8, 26, 28, and 55 is withdrawn in light of the amendments to the claims.
(Objection withdrawn.) The objection to Claim 9 is withdrawn in light of the amendments to the claim.
(Objection withdrawn.) The objection to Claim 14 is withdrawn in light of the cancellation of the claim.
(Objection withdrawn.) The objection to Claim 44 is withdrawn in light of the amendments to the claim.
Claim Rejections - 35 USC § 112(b); Second Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 9 and 32 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 14 and dependent claims 15 and 17 thereof under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn.) The rejection of Claim 15 and dependent claim 17 thereof under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(Rejection withdrawn.) The rejection of Claim 19 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 claim.
(Rejection maintained in part – necessitated by amendment.) Claim 25 remains 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.
As set forth in the previous Office action, the term “substantially” in claim 25 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear if this is meant to indicate a certain percentage of non-aggregated particles or a certain Z-average score or polydispersity index (PDI).
For at least these reasons, claim 25 remains rejected on the grounds of being indefinite.
Response to Arguments
Applicant's arguments filed 07/01/2026 have been fully considered but they are not entirely persuasive. While the amendments overcame the issue regarding the “steps for” indefiniteness issue, the arguments regarding the issue around the relative term “substantially” are not persuasive.
Applicant’s argument that protein aggregation is routinely assessed and well understood has been considered but is not persuasive. The issue is not whether one of ordinary skill in the art would know how to detect or measure protein aggregation, but whether one in the art would understand, with reasonable certainty, the degree of aggregation permitted by the recitation “substantially non-aggregated”. The specification fails to provide an objective standard or boundary for determining when the immunogenic polypeptide is “substantially non-aggregated.” For example, the specification does not identify a permissible percentage of aggregated protein, a minimum percentage of monomeric protein, a particle size or polydispersity criterion, or another criterion by which a preparation falling within the claim can be distinguished from one falling outside the claim. Although the specification describes solubilization and purification of aggregated EBVpoly protein and reports purification to homogeneity by SDS-PAGE, this does not define the amount or degree of aggregation encompassed by “substantially non-aggregated”. Accordingly, the metes and bounds of the claim remain unclear.
(Rejection withdrawn.) The rejection of Claims 26 and 55 and dependent claims 28, 32, 34, 44, 61, 63, 65, and 80-82 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 63 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 claim.
(Rejection withdrawn.) The rejection of Claims 79 and 82 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.
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.
Claim 8 is drawn to a pharmaceutical composition comprising:
i) a polyepitope protein comprising two or more amino acid sequences of cytotoxic T-cell (CTL) epitopes from Epstein-Barr virus (EBV) antigens, wherein the polyepitope protein comprises proteasome liberation amino acids or amino acid sequences between at least two of said two or more CTL epitopes, wherein the polyepitope protein is capable of eliciting a CTL response upon administration to a subject as an exogenous protein; or a nucleic acid encoding the polyepitope protein, and wherein the polyepitope protein comprises at least two amino acid sequences set forth in SEQ ID NOs: 1-20;
ii) an immunogenic glycoprotein, or fragment thereof; or a nucleic acid encoding the immunogenic glycoprotein or fragment thereof; and
iii) an adjuvant; or a nucleic acid encoding the adjuvant, wherein the adjuvant is an amphiphilic CpG oligodeoxynucleotide (ODN) adjuvant or a nucleic acid encoding an amphiphilic CpG ODN adjuvant.
Further limitations on the pharmaceutical composition of claim 8 are wherein the immunogenic glycoprotein is derived from EBV, and comprises at least one EBV glycoprotein selected from glycoprotein 350 (gp350), glycoprotein B (gB), glycoprotein H (gH), glycoprotein L(gL), gH/gL complex, glycoprotein 42 (gp42), fragments thereof, and combinations thereof (claim 9); wherein the immunogenic glycoprotein of part ii) is EBV gp350, and wherein the adjuvant of part iii) is a CpG ODN adjuvant (claim 19); wherein the composition comprises the polyepitope protein, the immunogenic glycoprotein or fragment thereof, and the adjuvant (claim 77); and wherein the composition comprises one or more nucleic acid sequences encoding the polyepitope protein, the immunogenic glycoprotein or fragment thereof, and the adjuvant (claim 78), wherein at least one of the one or more nucleic acid sequences encodes one or more of the polyepitope protein, the immunogenic glycoprotein or fragment thereof, and the adjuvant (claim 79).
Claim 25 is drawn to a method for producing the polyepitope protein of claim 8,wherein said method includes purifying the polyepitope protein under conditions that maintain the polyepitope protein in a substantially non-aggregated form.
Claim 26 is drawn to a prophylactic or therapeutic composition for eliciting an immunogenic response in a subject against EBV, the composition comprising:
i) a polyepitope protein comprising amino acid sequences derived from two or more cytotoxic T-cell (CTL) epitopes from EBV antigens, wherein the polyepitope protein comprises the amino acid sequences set forth in SEQ ID NOs: 1 and 11; or a nucleic acid encoding the polyepitope protein;
ii) at least one herpesvirus glycoprotein; or a nucleic acid encoding the at least one herpesvirus glycoprotein; and
iii) at least one adjuvant; or a nucleic acid encoding the at least one adjuvant.
Further limitations on the composition of claim 26 are wherein the polyepitope protein comprises each of the CTL epitope amino acid sequences set forth in SEQ ID NOs: 1-20 (claim 28); wherein the glycoprotein is derived from EBV and is selected from at least one of gp350, gB, gH, gL, gH/gL complex, gp42, fragments thereof, and combinations thereof (claim 32); wherein the adjuvant comprises a TLR agonist, and wherein the TLR agonist is a CpG ODN or a CpG ODN conjugated to a lipid (claim 34); wherein the composition comprises the polyepitope protein, the at least one herpesvirus glycoprotein, and the at least one adjuvant (claim 80); and wherein the composition comprises one or more nucleic acid sequences encoding the polyepitope protein, the at least one herpesvirus glycoprotein, and the at least one adjuvant (claim 81), wherein at least one of the one or more nucleic acid sequences encodes one or more of the polyepitope protein, the at least one herpesvirus glycoprotein, and the at least one adjuvant (claim 82).
Claim 44 is drawn to a method for generating a prophylactic or therapeutic treatment for herpesvirus infection, comprising: combining the composition of claim 26 and a pharmaceutically acceptable excipient to generate a formulation, wherein the formulation is suitable for administration to a subject in need thereof.
Claim 55 is drawn to a method for prophylactically or therapeutically treating an EBV infection in a subject, comprising administering to the subject a composition comprising:
i) a polyepitope protein comprising amino acid sequences derived from two or more cytotoxic T-cell (CTL) epitopes from EBV antigens, wherein the polyepitope protein comprises the amino acid sequences set forth in SEQ ID NOs: 1 and 11; or a nucleic acid encoding the polyepitope protein;
ii) at least one herpesvirus glycoprotein; or a nucleic acid encoding the herpesvirus glycoprotein; and
iii) an adjuvant; or a nucleic acid encoding the adjuvant.
Further limitations on the method of claim 55 are wherein the composition comprises 20-50 ug of the polyepitope protein (claim 61); wherein the glycoprotein is selected from the group consisting of: gp350, gB, gH, gL, gH/gL complex, gp42, fragments thereof, and combinations thereof (claim 63); wherein the adjuvant comprises a TLR agonist, and wherein the TLR agonist is a CpG ODN or a CpG ODN conjugated to a lipid (claim 65).
Claim Rejections - 35 USC § 112(a); First Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection maintained in part – necessitated by amendment.) Claims 8-9, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 remain 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. Note the rejection is withdrawn with respect to cancelled claims 14-15 and 17. 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 rationale behind this rejection was presented in a previous Office action and will not be repeated herein.
Response to Arguments
Applicant's arguments filed 07/01/2026 have been fully considered but they are not entirely persuasive.
Applicant argues that the rejection has been overcome by narrowing the claims to recite the requirement of EBV antigen-derived CTL epitopes. The amendments identifies the viral source of the CTL epitopes, but does not address the full scope of the claimed compositions and methods. Written description requires the specification to reasonably convey to one of ordinary skill that the inventors were in possession of the claimed invention as a whole, including the claimed combination of elements, and not merely that individual components of the claimed invention were separately known or mentioned in the disclosure.
With respect to claim 8, although the immunogenic polypeptide has been narrowed to comprise CTL epitopes derived from EBV antigens, and that the polyepitope protein comprises at least two amino acid sequences set forth in SEQ ID NOs: 1-20, the claim does not require the specific polyepitope protein used in the experiments, identified as SEQ ID NO: 21. The claim also continues to encompass one or more broadly recited immunogenic glycoproteins, or fragments thereof. The glycoprotein component is not limited to an EBV glycoprotein or even to a herpesvirus glycoprotein. Thus, claim 8 encompasses a broad genus of compositions comprising numerous possible combinations of at least two epitopes selected from SEQ ID NOs: 1-20, rather than the particular experimentally used EBV polyepitope of SEQ ID NO: 21, together with broadly defined immunogenic glycoproteins or fragments thereof. The specification does not provide a representative disclosure of these combinations across the full breadth of claim 8. Rather, the working vaccine embodiments employ the specific EBV polyepitope of SEQ ID NO: 21 in combination with the EBV glycoprotein gp350. Identification of the CTL epitopes as EBV-derived, ad further requiring at least two epitopes from SEQ ID NOs: 1-20 therefore does not demonstrate possession of the broader genus of polyepitope/glycoprotein composition encompassed by claim 8.
Claims 26 and 55 similarly remain broader than the invention demonstrated by the specification. Although these claims have been amended to recite the treatment and/or CTL epitope component as EBV-specific, the claims continue to recite “at least one herpesvirus glycoprotein”. This limitation encompasses glycoproteins derived from herpesviruses other than EBV. Accordingly the claims encompass, for example, an EBV-specific CTL polyepitope polypeptide combined with a glycoprotein derived from a different herpesvirus and used in the presently recited EBV-specific prophylactic or therapeutic composition or method. This becomes especially problematic with certain herpesvirus proteins, as EBV does not have all the glycoproteins that are present in other herpesviruses; for instance, glycoprotein D (gD), which is present in the herpesviruses HSV-1 and HSV-2 is absent in EBV (e.g. no gD or homolog thereof is present in EBV), so no argument can be made for why this would be relevant at all in treating EBV related disease, infection, or disorders. The specification does not provide representative examples of such heterologous combination or otherwise identify structural or functional characteristics showing that the inventors possessed this genus of combinations. Instead, the exemplified vaccine comprises the EBV polyepitope together with EBV gp350.
The fact that the specification separately discusses herpesvirus glycoproteins and EBV CTL epitopes is insufficient by itself to demonstrate possession of every combination encompassed by the amended claims. Written description is directed to possession of the claimed invention as a whole. In particular, the disclosure of individual claim elements does not necessarily provide adequate written description of a claimed combination of those elements where the specification does not reasonably convey that the inventors contemplated the combination at the claimed breadth. The amendments specifying that the CTL epitopes are EBV-derived therefore narrow one component of the claims but do not cure the written description deficiency associated with the remaining breadth of the glycoprotein component and the claimed combinations thereof.
For at least these reasons, Applicant’s arguments are not entirely persuasive, and the rejection is maintained.
(Rejection maintained in part – necessitated by amendment.) Claims 8-9, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 remain 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 compositions comprising a polyepitope protein comprised of EBV epitopes (EBVpoly protein of SEQ ID NO:21) in compositions comprising EBV gp350 protein and the adjuvant CpG1018 or CpG7909, and methods of eliciting an EBV-specific immune response with said composition, does not reasonably provide enablement for any compositions with any CTL polyepitope peptides, especially any CTL epitopes from any herpesvirus, and any herpesvirus glycoprotein, and any adjuvant, or compositions comprising nucleic acids encoding said components, and using said compositions (protein and/or nucleic acid compositions) to prophylactically or therapeutically inhibit any herpesvirus infection. Note the rejection is withdrawn with respect to cancelled claims 14-15 and 17. 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 rationale behind this rejection was presented in a previous Office action and will not be repeated herein.
Response to Arguments
Applicant's arguments filed 07/01/2026 have been fully considered but they are not entirely persuasive.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 8, 14-15, 17, 25-26, 28, 34, 44, 55, 61, 63, 65, and 77-82 under 35 U.S.C. 102(a)(1) as being anticipated by Khanna et. al. (US20150273051A1; Pub. 10/01/2015; hereafter “Khanna”) is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 9, 19, and 32 under 35 U.S.C. 103 as being unpatentable over Khanna as applied to claims 8, 14-15, 17, 25-26, 28, 34, 44, 55, 61, 63, 65, and 77-82 above, and further in view of Smith et. al. (Smith C, et. al. Hum Vaccin. 2010 Dec;6(12):1062-7. Epub 2010 Dec 1.; hereafter “Smith”) is withdrawn in light of the amendments to the claims.
(New rejection – necessitated by amendment.) Claims 8-9, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 are rejected under 35 U.S.C. 103 as being unpatentable over Khanna et. al. (US20150273051A1; Pub. 10/01/2015; CITED ART OF RECORD; hereafter “Khanna”) in view of Ogembo et. al. (US20200276295A1, Pub. 09/03/2020; hereafter “Ogembo”.)
The Prior Art
Khanna teaches proteins which comprises CTL epitopes from two or more different herpesvirus antigens and further comprises an intervening amino acid or amino acid sequence between at least two of said CTL epitopes comprising proteasome liberation amino acids or amino acid sequences (entire document; see abstract.) Khanna teaches the isolated protein is capable of rapidly expanding human cytotoxic T lymphocytes (CTL) in vitro and eliciting a CTL immune response in vivo upon administration to an animal as an exogenous protein, wherein the isolated protein comprises no more than twenty (20) CTL epitopes derived from cytomegalovirus and/or Epstein-Barr virus antigens (entire document; see abstract.) Khanna teaches testing subunit vaccine formulations based on CMV-encoded glycoprotein B (gB) and polyepitope proteins tested in combination with human compatible TLR agonists (¶[0232]; instant claim 77).
Khanna teaches the construction of an EBV polyepitope construct, which comprises proteasome linkers, called EBVpoly, and has a SEQ ID NO: 77, which comprises instant SEQIDNO:1 (HPVGEADYFEYR (EBNA1)) and instant SEQ ID NO:11 (LPEPLPQGQLTAYK (BZLF1)) at 100% identity, and EBVpoly (SEQ ID NO: 77) of Khanna comprises instant SEQ ID NOs: 1-20 at 100% identity (¶[0064]; Fig. 13; instant claims 28, 80). Khanna teaches pharmaceutical compositions which comprise the polyepitopes, wherein said pharmaceutical compositions comprised pharmaceutically acceptable excipients (¶[0032-0035]; instant claim 44). Khanna teaches the pharmaceutical compositions may be used in prophylactic or therapeutic treatment of CMV and/or EBV infection (¶[0033]). Khanna teaches the polyepitope vaccine formulations were generated with 20 μg of polyepitope protein (¶[0226]; instant claim 61). Khanna teaches methods of expressing and purifying the EBVpoly peptide (¶[0247-0248]; instant claim 25). Khanna teaches the adjuvants may include TLR agonists, such as TLR4 or TLR9 agonists, including Monophosphoryl lipid A (MPLA) and/or immunostimulatory DNA such as CpG ODN1826, CpG ODN2006, CpG ODN2216 and/or CpG ODN2336 (¶[0037]; instant claims 34, 65). Khanna teaches that the vaccine compositions may be DNA vaccines, including DNA vectors, which encoded the proteins and elements discussed therein (¶[0162-0168][0183]; instant claims 78-79, 81-82).
The teachings of Khanna have been set forth supra. While Khanna teaches the majority of the instant claims, and teaches that the composition may comprise a herpesvirus glycoprotein, and teaches the CTL epitopes may be from EBV antigen, Khanna fails to explicitly teach compositions comprising polyepitope proteins with EBV-derived CTL epitopes along with a herpesvirus glycoprotein, especially wherein said glycoprotein is an EBV glycoprotein, such as gp350. However, as Khanna teaches the combination of the polyepitope protein they developed along with the other known studied vaccine modality for CMV (e.g. gB subunit protein), it would be obvious to a skilled artisan to try a combination of the developed EBV polyepitope protein with any known EBV vaccine modalities, such as gp350, especially in light of the teachings of Ogembo.
Ogembo teaches that EBV vaccine strategies targeting only one arm of the immune response were limited and that protection against EBV desirably includes both neutralizing antibody responses and EBV-specific cellular immune responses (¶[0026][0033-0036]). Ogembo therefore teaches polyvalent EBV vaccines containing EBV envelope glycoproteins together with EBV T-cell antigens. Ogembo identifies gp350, gB, gp42, gH, and gL, including the gH/gL complex, as EBV envelope glycoproteins useful in such vaccines and explains that these glycoproteins mediate EBV attachment and/or entry and are targets for antibody-mediated immunity (¶[0027-0029][0036][0041][0046]; instant claims 9, 32, 63). Ogembo further teaches EBV T cell antigens including EBNA1, LMP2, and EBNA3 antigens and expressly teaches combining EBV envelope glycoproteins and T cell antigens in a single prophylactic and therapeutic vaccine (¶[0033-0037]). The working examples demonstrate vaccine compositions containing gp350, gB, LMP2, gH/gL-EBNA1, and combinations thereof, and report both neutralizing antibody and EBV-specific T cell responses (¶[0041] and Examples 1-7 starting at ¶[0060]). Ogembo teaches CpG DNA (TLR9 ligand) may be used with the compositions as an adjuvant (¶[0050]; instant claims 19, 34, 65), wherein the proteins can be in a pharmaceutical composition comprising a pharmaceutically acceptable carrier (¶[0049-0051]; instant claim 44).
Given the related teachings of Khanna and Ogembo, one of skill in the art would be apprised as to the use of polyepitope vaccines for the treatment of EBV. Given the teachings of Khanna, one of skill in the art would be apprised as to the use of polyepitope peptides in combination with glycoprotein subunit compositions and adjuvants, and given the teachings of Ogembo, one of skill in the art would find it obvious to combine an EBV polyepitope protein with an immunogenic EBV envelope glycoprotein. Khanna already teaches that a herpesvirus polyepitope can be combined with a viral glycoprotein and TLR agonist to generate complementary antibody and cellular immune responses, although this particular combination is demonstrated for CMV. Ogembo teaches applying this same general multivalent immunization principle specifically to EBV and identifies gp350, gB, gp42, and gH/gL as appropriate EBV glycoprotein antigens for use with EBV T cell antigens. One of ordinary skill therefore would have had reason to add an EBV envelope glycoprotein taught by Ogembo to the EBV CTL polyepitope composition of Khanna in order to target an additional arm of EBV immunity, namely an antibody response against EBV envelope proteins, while retaining the EBV-specific cellular response provided by the polyepitope. Therefore, arriving at the limitations of instant claims 8, 26, and 55 and dependent claims thereof (as noted supra) would be obvious to a skilled artisan, given the related teachings of Khanna and Ogembo.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Khanna in order to add EBV gp350 to the EBV polyepitope peptide compositions. One would have been motivated to do so, given the suggestion by Khanna that similar CMV polyepitope peptide vaccine compositions comprised known CMV glycoprotein subunit vaccines, and given the teachings of Ogembo which teach the combination of T cell epitopes to elicit both neutralizing antibody responses and T cell responses against EBV. There would have been a reasonable expectation of success, given the knowledge that the known vaccine modalities in the EBV art were surface envelope glycoproteins, such as gH/gL or gp350, and CTL polyepitope vaccines, as taught by Ogembo, and given that Khanna and Ogembo directly suggest combining the two modalities. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant’s arguments, see “Remarks”, filed 07/01/2026, with respect to the anticipation rejections under Khanna and the obviousness rejections under Khanna in view of Smith have been fully considered and are persuasive in light of the amendments to the claims. Therefore, the rejections have been withdrawn. However, upon further consideration, new obviousness grounds of rejection are made in view of Khanna and Ogembo. The arguments regarding Khanna will be addressed as applicable herein.
Applicant argues that Khanna fails to teach an EBV CTL polyepitope polyprotein in a composition with a herpesvirus glycoprotein and a CpG ODN adjuvant. While Khanna teaches these elements separately, Khanna does not teach a composition where the EBV CTL polyepitope polyprotein is in such a composition, and instead teaches a CMV CTL polyepitope polyprotein in a composition with a herpesvirus glycoprotein and a CpG ODN adjuvant. So while Khanna teaches elements of the instantly amended claims, Khanna does not anticipate the instant claims. However, Khanna renders obvious the instant claims, especially in light of the teachings of Ogembo.
Applicant argues that the claims are not obvious as Smith focuses on a humoral response to EBV using gp350 glycoprotein, and that the different modalities are not utilizing similar immunological mechanisms. While this argument is moot in light of Smith not being utilized in the current rejection, the teachings of Ogembo, which are now utilized in the obviousness rejection, show why the instant composition is preferred in the art. Ogembo similarly acknowledges that gp350-based vaccination had not prevented EBV infection, but expressly identifies this limitation as a reason to develop a multivalent EBV vaccine combining envelope glycoprotein antigens with T cell antigens so as to elicit both robust antibody and cellular immune responses. Ogembo specifically teaches EBV glycoproteins including gp350, gB, gp42, and gH/gL together with EBV T cell antigens, and reports experimental multivalent compositions containing such combinations. Accordingly, unlike Smith, Ogembo provides an affirmative teaching and specific motivation to add an EBV glycoprotein to an EBV CTL-directed vaccine precisely to overcome the limitations of vaccines only targeting one arm of the host immune response.
For at least these reasons, the arguments are not entirely persuasive, and the claims are still obvious in light of what was known in the art at the time of filing.
Double Patenting
The text regarding nonstatutory double patenting was presented in a previous Office action.
(Rejection withdrawn.) The provisional rejection of Claims 8-9, 14-15, 17, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 on the ground of nonstatutory double patenting as being unpatentable over claims 20-35 of copending Application No. 18/393,160 in view of Khanna and Smith (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 8-9, 14-15, 17, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,896,665 in view of Khanna and Smith (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 8-9, 14-15, 17, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,065,329 in view of Khanna and Smith (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 8-9, 14-15, 17, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 9,901,632 in view of Khanna and Smith (supra) is withdrawn in light of the amendments to the claims.
(New rejection – necessitated by amendment.) Claims 8-9, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-35 of copending Application No. 18/393,160 in view of Khanna and Ogembo (supra).
Both the instant claims and the ‘160 claims are drawn to peptide sequences which comprise a plurality of CTL epitopes from herpesvirus proteins, especially wherein said peptides utilize the proteasome liberation amino acid sequences. Both are drawn to wherein said CTL epitopes may be from EBV. Both sets of claims are drawn to nucleic acids encoding said peptides, and pharmaceutical compositions which comprise said proteins and additionally adjuvants. Both sets of claims are drawn to wherein the adjuvants may be TLR agonists, such as TLR4 or TLR9 agonists. Both sets of claims are drawn to methods of administering the compositions to a person to elicit a therapeutic or protective immune response. The main difference between the instant claims and those of the ‘160 claims is that the ‘160 claims provide for different CTL epitopes from the instant claims, and the ‘160 claims fail to specifically note the use of a herpesvirus glycoprotein in the composition. However, the differences in sequences and the use of glycoproteins would be obvious, given the teachings of Khanna and Ogembo (both detailed supra.) Additionally, Khanna teaches the sequences of the instant claims, and it would be an obvious modification to use distinct CTL epitopes identified by Khanna, especially in light of the teachings of Ogembo to use epitopes to stimulate both a CTL and neutralizing antibody response. Therefore, the instant claims are an obvious variant of the ‘160 claims, especially in light of the teachings of Khanna and Ogembo, and are not patentably distinct.
This is a provisional nonstatutory double patenting rejection.
(New rejection – necessitated by amendment.) Claims 8-9, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,896,665 in view of Khanna and Ogembo (supra).
Both the instant claims and the ‘665 claims are drawn to peptide sequences which comprise a plurality of CTL epitopes from herpesvirus proteins, especially wherein said peptides utilize the proteasome liberation amino acid sequences. Both are drawn to wherein said CTL epitopes may be from EBV. Both sets of claims are drawn to nucleic acids encoding said peptides, and pharmaceutical compositions which comprise said proteins and additionally adjuvants. Both sets of claims are drawn to wherein the adjuvants may be TLR agonists, such as TLR4 or TLR9 agonists. Both sets of claims are drawn to compositions for administering to a person to elicit a therapeutic or protective immune response. The main difference between the instant claims and those of the ‘665 claims is that the ‘665 claims provide for different CTL epitopes from the instant claims, and the ‘665 claims fail to specifically note the use of a herpesvirus glycoprotein in the composition. However, the differences in sequences and the use of glycoproteins would be obvious, given the teachings of Khanna and Ogembo (both detailed supra.) Additionally, Khanna teaches the sequences of the instant claims, and it would be an obvious modification to use distinct CTL epitopes identified by Khanna, especially in light of the teachings of Ogembo to use epitopes to stimulate both a CTL and neutralizing antibody response. Therefore, the instant claims are an obvious variant of the ‘665 claims, especially in light of the teachings of Khanna and Ogembo, and are not patentably distinct.
(New rejection – necessitated by amendment.) Claims 8-9, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,065,329 in view of Khanna and Ogembo (supra).
Both the instant claims and the ‘329 claims are drawn to peptide sequences which comprise a plurality of CTL epitopes from herpesvirus proteins, especially wherein said peptides utilize the proteasome liberation amino acid sequences. Both are drawn to wherein said CTL epitopes may be from EBV. Both sets of claims are drawn to nucleic acids encoding said peptides, and pharmaceutical compositions which comprise said proteins and additionally adjuvants. Both sets of claims are drawn to wherein the adjuvants may be TLR agonists, such as TLR4 or TLR9 agonists. Both sets of claims are drawn to compositions for administering to a person to elicit a therapeutic or protective immune response. The main difference between the instant claims and those of the ‘329 claims is that the ‘329 claims provide for different CTL epitopes from the instant claims, and the ‘329 claims fail to specifically note the use of a herpesvirus glycoprotein in the composition. However, the differences in sequences and the use of glycoproteins would be obvious, given the teachings of Khanna and Ogembo (both detailed supra.) Additionally, Khanna teaches the sequences of the instant claims, and it would be an obvious modification to use distinct CTL epitopes identified by Khanna, especially in light of the teachings of Ogembo to use epitopes to stimulate both a CTL and neutralizing antibody response. Therefore, the instant claims are an obvious variant of the ‘329 claims, especially in light of the teachings of Khanna and Ogembo, and are not patentably distinct.
(New rejection – necessitated by amendment.) Claims 8-9, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, and 77-82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 9,901,632 in view of Khanna and Ogembo (supra).
Both the instant claims and the ‘632 claims are drawn to peptide sequences which comprise a plurality of CTL epitopes from herpesvirus proteins. Both are drawn to wherein said CTL epitopes may be from EBV. Both sets of claims are drawn to nucleic acids encoding said peptides, and pharmaceutical compositions which comprise said proteins and additionally adjuvants. Both sets of claims are drawn to wherein the adjuvants may be TLR agonists, such as TLR4 or TLR9 agonists. Both sets of claims are drawn to administering the compositions to a person to elicit a therapeutic or protective immune response. The main difference between the instant claims and those of the ‘632 claims is that the ‘632 claims provide for different CTL epitopes from the instant claims, and the ‘632 claims fail to specifically note the use of a herpesvirus glycoprotein in the composition. However, the differences in sequences and the use of glycoproteins would be obvious, given the teachings of Khanna and Ogembo (both detailed supra.) Additionally, Khanna teaches the sequences of the instant claims, and it would be an obvious modification to use distinct CTL epitopes identified by Khanna, especially in light of the teachings of Ogembo to use epitopes to stimulate both a CTL and neutralizing antibody response. Therefore, the instant claims are an obvious variant of the ‘632 claims, especially in light of the teachings of Khanna and Ogembo, and are not patentably distinct.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure and is listed below:
US20200282047A1. Teaches multivalent EBV vaccines containing envelope EBV glycoproteins such as gp350, gB, gH, gL, and gp42 together with T cell associated EBV antigens, such as LMP1/LMP2 and EBNA1/EBNA3. Not utilized as rejection would be redundant to those set forth supra.
US20200038505A1. Teaches EBV vaccine constructs combining gp350 with EBNA1, gH/gL with EBNA1, and gB with LMP2 in order to elicit both a neutralizing antibody and T cell response. Not utilized as rejection would be redundant to those set forth supra.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671
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