DETAILED ACTION
Disposition of Claims
Claims 1-11, 13-15, 17-19, and 23-24 remain pending. Claims 12-13, 16, 20-22, and 25 are cancelled. Amendments to claims 1-2, 8, and 17-18 are acknowledged and entered. Claims 1-11, 14-15, 17-19, and 23-24 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 US20230173061A1, Published 06/08/2023. Amendments to the specification presented on 08/11/2025 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
The Office would like to note that the inventor “Rajiv Khanna” appears to have their name misspelled in the file wrapper (listed as “Rajiv Khana”) and that inventor “Vijayendra Dasari” is also listed as “Dasari Vijayendra” in other applications and patents. PDP inventor searches for both spellings for both inventors are included in this Office action.
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 08/11/2025 regarding the previous Office action dated 02/10/2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Specification
(Objection withdrawn.) The objection to the abstract of the disclosure is withdrawn in light of the amendments to the abstract.
Claim Objections
(Objection withdrawn.) The objection to claim 1 is withdrawn in light of the amendments to the claim.
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 1 is drawn to a pharmaceutical composition comprising:
(a) one or a plurality of isolated proteins comprising a plurality of epitopes, wherein the plurality of epitopes are derived from two or more different cytomegalovirus (CMV) antigens;
(b) a CMV envelope protein, wherein the CMV envelope protein is or comprises CMV glycoprotein B (gB);
(c) a TLR9 agonist; and
(d) an adjuvant.
Further limitations of the pharmaceutical composition of claim 1 are wherein the composition is capable of inducing or eliciting a humoral immune response and a cell-mediated immune response upon administration to a subject (claim 2); wherein the one or plurality of isolated proteins is or comprises a polytope protein comprising two or more of the plurality of epitopes from the two or more different CMV antigens (claim 3), wherein the polytope protein comprises an intervening amino acid sequence between at least two of said epitopes, wherein the intervening amino acid sequence comprises a proteasome liberation amino acid sequence (claim 4), wherein the proteasome liberation amino acids or amino acid sequences comprise AD, K and/or R (claim 5); wherein the epitopes are restricted by HLA class I specificities HLA-A1, -A2, -A3, -A11, - A23, -A24, -A26, -A29, - A30, -B7, -B8, -B18, -B27, - B35, -B38, -B40, -B41, -B44, -B51, -B57, - B58 and/or -CW6 (claim 6); wherein the epitopes are derived from pp50, pp65, pp150, DNAse and/or IE-1 (claim 7); wherein the epitopes have an amino acid sequence selected from the group consisting of the amino acid sequences set forth in SEQ ID NOS: 1-20, a fragment, variant or derivative thereof and any combination thereof (claim 8), wherein the one or plurality of isolated proteins comprise each of the epitope amino acid sequences set forth in SEQ ID NOS: 1-20 (claim 9); wherein the one or plurality of isolated proteins comprise an amino acid sequence set forth in SEQ ID NO:21 or a fragment, variant or derivative thereof (claim 10); wherein the one or plurality of isolated proteins comprise twenty (20) or less epitopes (claim 11); wherein the TLR9 agonist is or comprises CpG ODN1018 and/or CpG ODN2006 (claim 14); a vaccine that comprises the pharmaceutical composition of Claim 1 for eliciting a protective immune response against CMV (claim 15).
Claim 17 is drawn to a method of eliciting an immune response to a CMV antigen in a subject, said method including the step of administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising:
(a) one or a plurality of isolated proteins comprising a plurality of epitopes, wherein the plurality of epitopes are derived from two or more different CMV antigens;
(b) a CMV envelope protein, wherein the CMV envelope protein is or comprises CMV glycoprotein B (gB);
(c) a TLR9 agonist; and
(d) an adjuvant;
to thereby elicit the immune response in said subject.
Further limitations on the method of Claim 17 are wherein the immune response is or comprises a humoral immune response and a cell-mediated immune response (claim 18), which elicits a protective immune response against CMV or a CMV infection in the subject (claim 19).
Claim 23 is drawn to an isolated protein comprising each of the epitope amino acid sequences set forth in SEQ ID NOS: 1-20, or fragments, variants or derivatives thereof.
Further limitations on the isolated protein of Claim 23 are wherein the isolated protein comprises the amino acid sequence set forth in SEQ ID NO:21 or a fragment, variant or derivative thereof (claim 24).
Claim Rejections - 35 USC § 101
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 1-3, 6-8, 13, 15, and 17-19 under 35 U.S.C. 101 is withdrawn in light of the amendments to the claims.
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 Claim 2 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 and extended – necessitated by amendment.) Claim 8 and dependent claim 9 thereof remain 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.
While the amendments to the claims have incorporated SEQ ID NOs: into the claim as indicated in the previous Office action regarding the rejection of these claims, the claim is now drawn to “wherein the epitopes have an amino acid sequence selected from the group consisting of the amino acid sequences set forth in SEQ ID NOS: 1-20, a fragment, variant or derivative thereof and any combination thereof.” However, as the specification notes, the sequences (listed in Table 1) of SEQ ID NOs: 1-20 comprise both the epitope sequences and the proteasomal liberation sequence. Therefore, SEQ ID NO: 1 has the sequence of FPTKDVALAD, with “FPTKDVAL” being the epitope from pp65 and “AD” being the liberation sequence (alignment with pp65 shows that the amino acids C-terminal to “FPTKDVAL” are “RH”, not “AD”). Therefore, SEQ ID NOs: 1-20 are fusion proteins, and are not the “true” epitopes. For the purpose of prior art searching, only the sequences from the viral proteins within SEQ ID NOs: 1-20 will be searched.
For at least these reasons, claims 8-9 remain rejected on the grounds of being indefinite.
Response to Arguments
Applicant's arguments filed 08/11/2025 have been fully considered but they are not entirely persuasive.
For the reasons set forth supra, while the essential subject matter has been incorporated into the claim instead of referencing the table, the sequences referenced (e.g. SEQ ID NOs: 1-20) are not the correct “epitope” sequences. One suggestion is to deposit only the epitopes as separate sequences with unique SEQ ID NOs. This would not be considered new matter, as the specification clearly provides support for these epitopes minus the extra “proteasomal release sequences” which are at the end as shown in Table 1.
For at least these reasons, the claims remain rejected on the grounds of being indefinite.
(Rejection withdrawn.) The rejection of Claim 18 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.
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 maintained in part and extended – necessitated by amendment.) Claims 1-11, 14-15, 17-19, and 23-24 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Khanna et. al. (US20150273051A1, Pub. 10/01/2015; hereafter “Khanna”.) Note that the rejection of claim 13 is withdrawn in light of the cancellation of said claim.
The Prior Art
Khanna teaches amino acid sequences which are CTL epitopes from different herpesvirus antigens, especially proteins which comprise two or more CTL epitopes from two or more different antigens (entire document; see abstract.) Khanna teaches the CTL epitopes may be from cytomegalovirus (CMV) antigens or Epstein-Barr virus (EBV) antigens (entire document; see abstract.) Khanna teaches the epitopes are of CMV antigens selected from the group consisting of: pp50, pp65, pp150 and IE-1 and/or EBV antigens selected from the group consisting of: BMLF1, LMP2a, BRLF1, LMP2, EBNA3A, BZLF1, EBNA3C, EBNA1 and EBNA3B (¶[0079]). Khanna teaches the proteins may be within pharmaceutical compositions (¶[0032-0033]), such as vaccines (¶[0034]), wherein the vaccines would be used to prophylactically or therapeutically treat a disease or condition associated with CMV infection (¶[0033-0034]) by delivery of a dosage to induce a CTL immune response in an animal in order to treat said CMV infection (¶[0038-0039][0063]; reference claims 26-27; instant claims 2, 18). The pharmaceutical composition may comprise an adjuvant, such as a TLR9 agonist, including CpG ODN1826, CpG ODN2006, CpG ODN2216 and/or CpG ODN2336 (¶[0037][0063][0189]; instant claim 14). Khanna teaches the composition comprising the polyepitope and adjuvant may also comprise an envelope glycoprotein, such as glycoprotein B (gB)(¶[0232]). Therefore, Khanna teaches a vaccine composition which comprises a CMV glycoprotein B (gB) antigen (¶[0006][0206][0232][0234]), CMV polyepitope proteins wherein the epitopes may be from different CMV proteins, and combinations of TLR agonists, wherein the agonists were TLR4 and TLR9 agonists (¶[0233]), such as MPL (TLR4 agonist) and CpG (TLR9 agonist)(¶[0037]), and thus teaches every limitation of instant claims 1-3, 14-15, and 17-19.
Khanna teaches SEQ ID NOs: 46, 58, and 76, which comprise instant SEQ ID NOs: 1-2 at 100% identity. Khanna teaches SEQ ID NO: 76, which comprises SEQ ID NO: 2 at 100% identity. (See attached NCBI BLAST alignments.) SEQ ID NO: 46 comprises the entirety of SEQ ID NOs: 1-3, 5-7, 9, 11-16, and 20 at 100% identity, and a fragment of SEQ ID NO: 4, 8, 10, 17-19 at 100% identity (instant claims 8-9, 23.) Further, an alignment of instant SEQ ID NO: 21 with reference SEQ ID NO: 46 shows that it has 61.69% identity, with many of the noted instant epitopes within the sequence at 100% identity, thus making reference SEQ ID NO: 46 a variant of instant SEQ ID NO: 21 (see attached ABSS sequence alignment; instant claims 10, 24). As reference SEQ ID NO: 46 has a sequence in between MFPTKDVALAD (instant SEQ ID NO:1) and GPISHGHVLKAD (instant SEQ ID NO: 2) of “RIW”, this meets the limitations of instant claims 4-5.
Khanna teaches the HLA class I specificities of the epitopes are at least within HLA -A1, -A2, -A3, -11, -A23/24, -A24, -B7, -B8, -B27, -B35, -B40/60, -B41, -B44, -B57, and/or cw6, and are derived from such CMV proteins as pp50, pp65, pp150, IE-1, DNAse, and gB (Table 1; instant claims 6-7). Khanna teaches the proteins with multiple epitopes would comprise no more than 20 CTL epitopes (abstract; instant claim 11). Khanna teaches the proteins would comprise 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 and, optionally, Transporter Associated with Antigen Processing (TAP) recognition motifs (¶[0011]). Khanna teaches the protein may be presented in the form of nucleic acid, specifically an expression construct, such as a DNA plasmid or viral vector, such as poxviruses or adenoviruses (¶[0162-0163]).
For at least these reasons, Khanna teaches every limitation of instant claims 1-11, 14-15, 17-19, and 23-24, and anticipates the invention encompassed by said claims.
Response to Arguments
Applicant's arguments filed 08/11/2025 have been fully considered but they are not persuasive.
Applicant argues that Khanna fails to teach a composition which comprises the elements of the composition of newly amended instant claim 1, and that Khanna is “wholly silent” on the inclusion of the CMV envelope protein gB in the composition. The Office disagrees. At ¶[0232], Khanna teaches a vaccine composition which comprises a CMV glycoprotein B (gB) antigen, polyepitope proteins, and combinations of TLR agonists, wherein the agonists were TLR4 and TLR9 agonists (¶[0233]), which meets the limitation of the composition comprising 1) CMV gB, 2) CMV polyepitope protein, 3) TLR9 agonist, and 4) an adjuvant (TLR4 agonist). Khanna at ¶[0232]:
“In initial studies, a subunit vaccine formulation based on CMV-encoded glycoprotein B (gB) and polyepitope proteins was tested in combination with human compatible TLR agonists.”
As Khanna teaches the compositions may comprise TLR4 and TLR9 agonists, such as MPL (TLR4 agonist) and CpG (TLR9 agonist)(¶[0037]), and as Applicant shows that the polyepitope can be delivered with CMV gB and that CMV gB is also immunostimulatory and could, under broadest reasonable interpretation, be considered “adjuvanting” (¶[0006][0206][0234]), Khanna therefore teaches the composition as once envisaged by instant claim 1. Therefore, this line of argument is not persuasive.
For at least these reasons, the argument is not persuasive, and the rejection has been maintained.
(New rejection – necessitated by amendment.) Claims 1-8, 10-11, 15, 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dasari et. al. (Dasari V, et. al. Hum Vaccin Immunother. 2014;10(4):1064-77. Epub 2014 Jan 24.; CITED ART OF RECORD; hereafter “Dasari”.)
The Prior Art
Dasari teaches that a composition comprising 1) CMV glycoprotein B (gB), 2) a CMV polyepitope protein, 3) the adjuvant MPL, and 4) the TLR9 agonist adjuvant CpG (Entire document; see abstract; Fig. 7A.) Dasari teaches the CMV polyepitope comprised epitopes from multiple HLA class I restricted T-cell epitopes from three different CMV antigens, namely pp65, IE-1, and pp50 (“Methods: Design of the expression vectors encoding CMV polyepitope protein”, p. 1074; instant claims 1, 7.) In regards to instant claim 2, the recitation that the “composition is capable of inducing or eliciting a humoral immune response and a cell-mediated immune response upon administration to a subject” is not a positive limitation but only requires the ability to so perform. It does not constitute a limitation in any patentable sense. In re Hutchison, 69 USPQ 138 (CCPA 1946); In re Swinehart, 169 USPQ 226 (CCPA 1971); and In re Schreiber, 44 USPQ2d 1429 (Fed. Cir. 1997). A patent applicant is free to recite features of an apparatus either structurally or functionally. See In re Swinehart, 439 F.2d 210, 212, 169 USPQ 226, 228 (CCPA 1971) (“ [T]here is nothing intrinsically wrong with [defining something by what it does rather than what it is] in drafting patent claims.”). Yet, choosing to define an element functionally, i.e., by what it does, carries with it a risk. As our predecessor court stated in In re Swinehart, 439 F.2d at 213, 169 USPQ at 228:
where the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on
Therefore, the feature of wherein the “composition is capable of inducing or eliciting a humoral immune response and a cell-mediated immune response upon administration to a subject“ would be an inherent characteristic of the composition of Dasari since the composition of Dasari meets all the structural limitations of the claimed composition.
Dasari teaches the polyepitope comprises multiple epitopes from the different CMV proteins (Fig. 1; instant claim 3), and teaches the polyepitope was designed in two different ways: one in which the epitopes were joined end-to-end (Fig. 1A) and one in which there was intervening amino acids between the epitopes (Fig. 1B; instant claim 4). Dasari teaches wherein the intervening sequences are proteasome liberation sequences which comprise AD, R, and/or K (Fig. 1B, instant claims 4-5). Dasari teaches the HLA class I specificities for the epitopes are HLA B35, A11, A24, B44, B7, B8, B35, A3, B7, A1, and A2 (Fig. 1; instant claim 6). Dasari teaches epitopes which comprise sequences which are 100% identical (in order shown in the polyepitope sequence of reference Fig. 1) to the epitopes or 100% identical to fragments of the epitopes within instant SEQ ID NOs: 1-3 (FPTKDVAL, GPISHGHVLK, QYDPVAALF), SEQ ID NOS: 5-7 (TPRVTGGGAM, QIKVRVDMV, IPSINVHHY), and SEQ ID NOs: 9-13 (RPHERNGFTVL, ELRRKMMYM, VTEHDTLLY, NLVPMVATV, VLEETSVML)(Fig.1; instant claims 8, 11). An alignment of the sequence of Dasari which comprises the proteasome liberation sequences aligns with SEQ ID NO:21 at 70.62% identity (see attached ABSS sequence alignment) and an alignment of the sequence of Dasari which lacks the proteasome liberation sequences aligns with SEQ ID NO: 21 at 72.41% identity, thus making the sequences of Dasari “variants” as required by instant claim 10. Dasari teaches the TLR9 agonist may be CpG ODN1826 and teaches vaccination of mice with the gB+polyepitope peptide+TLR9 agonist+MPL (“Methods: Immunizations”, p. 1074; instant claims 15, 17-18). Dasari shows the humoral (Figure 8) and cellular (Figure 7) immune responses to the vaccine composition, noting that both cellular and humoral responses are required to elicit a protective immune response against CMV (p. 1065, ¶2, instant claims 18-19).
For at least these reasons, Dasari teaches the limitations of instant claims 1-8, 10-11, 15, and 17-19, and anticipates the invention encompassed by said claims.
Double Patenting
The text regarding nonstatutory double patenting was presented in a previous Office action.
(Rejection maintained in part – necessitated by amendment). Claims 1-11, 14-15, 17-19, and 23-24 remain 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 (supra). Note the rejection of instant claim 13 is withdrawn in light of the cancellation of said claim. The rationale behind the rejection was set forth in a previous Office action and will not be repeated herein.
(Rejection maintained in part – necessitated by amendment). Claims 1-11, 14-15, 17-19, and 23-24 remain 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 (supra). Note the rejection of instant claim 13 is withdrawn in light of the cancellation of said claim. The rationale behind the rejection was set forth in a previous Office action and will not be repeated herein.
(Rejection maintained in part – necessitated by amendment). Claims 1-11, 14-15, 17-19, and 23-24 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,896,665 in view of Khanna (supra). Note the rejection of instant claim 13 is withdrawn in light of the cancellation of said claim. The rationale behind the rejection was set forth in a previous Office action and will not be repeated herein.
(Rejection maintained in part – necessitated by amendment). Claims 1-11, 14-15, 17-19, and 23-24 remain 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 in view of Khanna (supra). Note the rejection of instant claim 13 is withdrawn in light of the cancellation of said claim. The rationale behind the rejection was set forth in a previous Office action and will not be repeated herein.
(Rejection maintained in part – necessitated by amendment). Claims 1-11, 14-15, 17-19, and 23-24 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-9, 14-15, 17, 19, 25-26, 28, 32, 34, 44, 55, 61, 63, 65, 77-82 of copending Application No. 18/030,892 in view of in view of Khanna (supra). Note the rejection of instant claim 13 is withdrawn in light of the cancellation of said claim. The rationale behind the rejection was set forth in a previous Office action and will not be repeated herein.
Response to Arguments
Applicant's arguments filed 08/11/2024 have been fully considered but they are not persuasive.
Applicant has requested that the non-statutory obviousness-type double patenting rejections be held in abeyance until allowable subject matter is indicated in the present application. However, said rejections must be maintained as a matter of record until the appropriate terminal disclaimers have been filed, or until the claims have been amended in such a way as to not claim patently identical subject matter.
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 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JANET ANDRES can be reached on 571-272-0867. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RACHEL B GILL/
Primary Examiner, Art Unit 1671