DETAILED ACTION
Disposition of Claims
Claims 1-20 were pending. Claims 13, 16, and 19 are cancelled. Amendments to claims 1-5, 7-12, 14-15, 18, and 20 are acknowledged and entered. Claims 1-12, 14-15, 17-18, and 20 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 US20230355742A1, Published 11/09/2023. Amendments to the specification presented on 12/23/2025 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.
Response to Arguments
Applicant's arguments filed 12/23/2025 regarding the previous Office action dated 09/23/2025 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 If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn.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arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
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.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The certified copy of the foreign priority application is not in English. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Specification
(Objection withdrawn.) The objection to the specification for comprising sequence without an accompanying SEQ ID NO: is withdrawn in light of the updated sequence listing filed.
Claim Objections
(Objection withdrawn.) The objection to claim 1 is withdrawn in light of amendments to said claim.
(Objection withdrawn.) The objection to claim 19 is withdrawn in light of the cancellation of said claim.
(New objection.) Claim 15 is objected to because of the following informalities: in line 5, “…are linked by the a gene…” should be amended to recite “…are linked by a gene…”. Appropriate correction is required.
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 1-2, and dependent claims 3-20 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 Claims 2-3 and dependent claims 11-14 and 16 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 maintained in part – necessitated by amendment). Claim 5 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. Note the rejection of claims 13, 15, and 18-19, and dependent claim 16 thereof is withdrawn in light of the amendments to the claims.
The wording of claim 5 makes it unclear what exactly is being claimed, and while certain suggestions provided by the Office were utilized in re-drafting the claim, it still appears as though what is intended to be claimed and what is actually claimed are not clear. For instance, in ¶[0087], the DNA vaccine constructed comprised, in the N- to C- terminal direction, CTB-TT-PADRE-RBD-S2-Foldon-CPPCP-Furin2A-ERISS-Nprotein-IRES-OX40L. It is unclear if that is what is being claimed why parts “a” and “b” are being used in the claim. If parts “a” and “b” are meant to be optional, then they should be claimed as optional by using “or” as suggested in the previous action. But if all 12 of these components are present like they are in ¶[0087], then it should be claimed as one long construct:
“…wherein the fusion protein comprises, in the N- to C- terminal orientation, CTB-TT-PADRE-RBD-S2-Foldon-CPPCP-Furin2A-ERISS-Nprotein-IRES-OX40L;…”
Since the metes and bounds of claim 5 remain unclear, the claim remains rejected for being indefinite.
Response to Arguments
Applicant's arguments filed 12/23/2025 have been fully considered but they are not entirely persuasive.
While the amendments have overcome the rejections with respect to the other claims, for the reasons elaborated upon supra, claim 5 is still confusing as to why the sections were separated as “a” and “b” if the entire protein was to include both, as evidenced by the use of “and” instead of “or” between them. Following the guidance from the specification, suggestions as to how to amend the claim further in light of these amendments to clarify the metes and bounds of what is being claimed is offered supra.
For at least these reasons, claim 5 remains rejected on the grounds of being indefinite.
(Rejection withdrawn). The rejection of Claims 7-10 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 7 and dependent claims 8 and 10 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 9 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.
(New rejection – necessitated by amendment.) Claims 1 and dependent claims 2-12, 14-15, 17-18, and 20 thereof 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.
In light of the amendments to the claims, specific domains are being claimed of specific proteins from SARS CoV-2, but it is unclear as to the reference for said regions being claimed as they are either being claimed functionally (e.g. “receptor binding domain (RBD) of SARS CoV-2 S protein”) or positionally (e.g. amino acid residues 301-538 of SARS CoV-2 protein S2 subunit) without appropriate frames-of-reference. This creates uncertainty as it is unclear to one of skill in the art which regions of the proteins should, or should not, be encompassed by the claim.
For instance, with respect to the RBD of S protein of SARS CoV-2, the region is generally defined as 220 amino acid residues that encompass amino acids 333-527 of the full-length S protein, but the art varies depending on the sequence, whether or not the S1 subunit or full-length S protein is being referenced, and strain of SARS CoV-2, amongst some variables (See e.g. Fig. 1 of Xia X. Viruses. 2021 Jan 14;13(1):109.; Fig. 1 of Lan J, et. al. Nature. 2020 May;581(7807):215-220. Epub 2020 Mar 30.; Fig. 1 of Tai W, et. al. Cell Mol Immunol. 2020 Jun;17(6):613-620. Epub 2020 Mar 19.) The specification also fails to provide an exact frame-of-reference for the RBD, such as identifying the RBD as “amino acids 331-524 of SEQ ID NO:X.” Likewise, other domains of proteins are claimed without providing a sequence for said domain or a frame-of-reference for said sequence. Some domains are claimed as amino acid ranges, but without providing a “base” sequence for comparison, and since the proteins vary in length and sequence, it is unclear what regions are being claimed. It is suggested that the identified domains within the claims have a SEQ ID NO: assigned to each region or a frame-of-reference sequence provided if a range of amino acids is recited.
It should be noted that the “adjuvanting” or “carrier” proteins as recited in part (4) of claim 1 are clear as their sequences are clearly defined within the specification and within the claims. Only the domains of the viral proteins from SARS CoV-2 are unclear in the context of this rejection.
For at least these reasons, claim 1 is rejected on the grounds of being indefinite. Claims 2-12, 14-15, 17-18, and 20 are also rejected as they depend from claim 1, but do not clarify these issues of claim 1.
(New rejection – necessitated by amendment.) Claims 1 and dependent claims 2-12, 14-15, 17-18, and 20 thereof 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.
Claim 1 provides for “(4) a gene expressing at least one of the following full-length protein or amino acid fragment thereof: cholera toxin B subunit (CTB), tetanus toxin helper T cell epitope (TT), pan-DR helper T cell epitope (PADRE), Foldon, CPPCP (SEQ ID NO:16), Furin2A, endoplasmic reticulum insertion signal sequence (ERISS), internal ribosome entry site (IRES), and OX40L.” However, as amended, not all of the items in this Markush group are proteins. For instance, an IRES is a region of RNA, and a fragment of an IRES will not function as an internal ribosome entry site. Some of these are fragments of longer proteins (e.g. foldon is a domain of the T4 fibritin protein) and are not technically considered “full-length” proteins. One suggestion is to amend the Markush group to read: “(4) a nucleic acid sequence encoding or comprising at least one of the following: cholera toxin B subunit (CTB), tetanus toxin helper T cell epitope (TT), pan-DR helper T cell epitope (PADRE), Foldon, CPPCP (SEQ ID NO:16), Furin2A, endoplasmic reticulum insertion signal sequence (ERISS), internal ribosome entry site (IRES), and OX40L.”
For at least these reasons, claim 1 is rejected on the grounds of being indefinite. Claims 2-12, 14-15, 17-18, and 20 are also rejected as they depend from claim 1, but do not clarify these issues of claim 1.
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 and 35 USC 112b issues as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to a fusion gene, comprising the following:
(1) a gene expressing the severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2) spike (S) protein receptor binding domain (RBD);
(2) a gene expressing the S2 subunit or partial fragment thereof of SARS CoV-2 S protein;
(3) a gene expressing SARS CoV-2 N protein or fragment thereof; and
(4) a nucleic acid sequence encoding or comprising at least one of the following: cholera toxin B subunit (CTB), tetanus toxin helper T cell epitope (TT), pan-DR helper T cell epitope (PADRE), Foldon, CPPCP (SEQ ID NO:16), Furin2A, endoplasmic reticulum insertion signal sequence (ERISS), internal ribosome entry site (IRES), and OX40L
Further limitations on the fusion gene of claim 1 are wherein the gene is comprising the following:
(1) a gene expressing the SARS CoV-2 S protein RBD;
(2) a gene expressing amino acid residues 301-538 of SARS CoV-2 S protein S2 subunit;
(3) a gene expressing amino acid residues 138-369 of the SARS CoV-2 N protein;
(4) a nucleic acid sequence encoding or comprising at least one of the following: CTB, TT, PADRE, Foldon, CPPCP, Furin2A, ERISS, IRES and OX40L (claim 2), wherein the gene expressing the SARS CoV-2 S protein RBD and the gene expressing the amino acid residues 301-538 of SARS CoV-2 S protein S2 subunit are linked to form a gene for expressing a fusion protein (RBD-S2) (claim 3), wherein the nucleotide sequence of the gene for expressing the fusion protein RBD-S2 comprises the sequence set forth in SEQ ID NO: 6 (claim 12), wherein the gene expressing the SARS CoV-2 S protein RBD and the gene expressing the amino acid residues 301-538 of the SARS CoV-2 S protein S2 subunit are linked by a gene expressing a (G4S)2 linker (claim 14), wherein the fusion protein obtained from the expression of the fusion gene comprises, in the N- to C- terminal orientation, a) CTB-TT- PADRE-RBD-S2-Foldon-CPPCP-Furin2A, ERISS-N protein-IRES-OX40L; wherein S2 is the amino acid residues 301-538 of SARS CoV-2 S protein S2 subunit, and wherein N protein is the amino acid residues 138-369 of the SARS CoV-2 N protein (claim 5), wherein the gene expressing the SARS CoV-2 S protein RBD and the gene expressing the amino acid residues 301-538 of the SARS CoV-2 S protein S2 subunit are linked by a gene expressing a (G4S)2 linker, the gene expressing the SARS CoV-2 S protein RBD and the gene expressing the PADRE are linked by the a gene expressing a linker G6, and the nucleotide sequence of the gene expressing the linker G6 is set forth in SEQ ID NO:5 (claim 15), wherein the nucleotide sequence of the gene encoding the amino acid residues 138-369 of the SARS CoV-2 N protein comprises the sequence set forth in SEQ ID NO: 10 (claim 11); wherein:
(1) the nucleotide sequence of the gene expressing the CTB is set forth in SEQ ID NO: 2;
(2) the nucleotide sequence of the gene expressing the TT is set forth in SEQ ID NO: 3;
(3) the nucleotide sequence of the gene expressing the PADRE is set forth in SEQ ID NO: 4;
(4) the gene expressing the Foldon and the gene expressing the CPPCP (SEQ ID NO:16) are linked to form a synthetic fragment, and the nucleotide sequence of the synthetic fragment is set forth in SEQ ID NO:7;
(5) the nucleotide sequence of the gene expressing the Furin2A is set forth in SEQ ID NO: 8;
(6) the nucleotide sequence of the gene expressing the ERISS is set forth in SEQ ID NO: 9;
(7) the nucleotide sequence of the gene expressing the IRES is set forth in SEQ ID NO: 11; and
(8) the nucleotide sequence of the gene expressing the OX40L is set forth in SEQ ID NO:12 (claim 4); and wherein the nucleotide sequence of the fusion gene is set forth in SEQ ID NO:13 (claim 17).
Claim 6 is drawn to a fusion protein obtained from the expression of the fusion gene of claim 1.
Claim 7 is drawn to a recombinant novel coronavirus immune DNA vaccine (ZD-nCor19) comprising the fusion gene of claim 1, wherein said gene is present within a vector.
Further limitations on the recombinant novel coronavirus immune DNA vaccine of claim 7 are wherein the vector is pZDVac vector (claim 8).
Claim 9 is drawn to a method for constructing a recombinant novel coronavirus immune DNA vaccine, comprising the following steps of:
1) synthesizing the fusion gene of claim 1;
2) inserting the fusion gene into a pZDVac vector to obtain the recombinant novel coronavirus immune DNA vaccine.
Further limitations on the method of claim 9 are wherein the fusion gene synthesized in step 1) comprises the following (1) to (4):(1) a gene expressing the SARS CoV-2 S protein RBD;(2) a gene expressing amino acid residues 301-538 of the S2 subunit of SARS CoV-2 S protein; (3) a gene expressing amino acid residues 138-369 of the SARS CoV-2 N protein;(4) genes expressing the following proteins: CTB, TT, PADRE, Foldon, CPPCP, Furin2A, ERISS, IRES and QX40L; wherein the gene expressing the SARS CoV-2 S protein RBD and the gene expressing the amino acid residues 301-538 of the S2 subunit of SARS CoV-2 S protein are linked to form a gene for expressing a fusion protein (RBD-S2), and wherein said RBD and the amino acid residues 301-538 of the S2 subunit are joined by a (G4S)2 linker; wherein upstream of the fusion protein RBD-S2, CTB, TT, and PADRE are sequentially linked, and wherein downstream of the fusion protein RBD-S2, foldon, CPPCP, and Furin2A are sequentially linked; wherein the gene expressing ERISS is linked upstream of said amino acid residues 138-369 of the SARS CoV-2 N protein; and wherein downstream of said amino acid residues 138-369 of the SARS CoV-2 N protein, genes encoding IRES and OX40L are sequentially linked; and wherein the gene expressing PADRE and the gene for expressing the fusion protein RBD- S2 are linked by a G6 linker (SEQ ID NO:5)(claim 18); and wherein the nucleotide sequence of the fusion gene synthesized in step 1) is set forth in SEQ ID NO:13 (claim 20).
Clam 10 is drawn to a method for inhibiting infection from SARS CoV-2, or treatment/prevention of disease associated with a SARS CoV-2 infection, comprising administering an effective amount of the recombinant novel coronavirus immune DNA vaccine of claim 7 to a subject infected with SARS CoV-2 or at risk of SARS CoV-2 infection.
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 and 6 under 35 U.S.C. 101 is withdrawn in light of the amendments to the claims.
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 withdrawn). The rejection of Claims 8-9 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in light of Applicant’s arguments and amendments.
(Rejection withdrawn). The rejection of Claim 10 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first 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 withdrawn.) The rejection of Claims 1-3, 6-7, 9-10, and 14 under 35 U.S.C. 102(a)(2) as being anticipated by Chopra et. al. (US20230302120A1; Priority 08/11/2020; hereafter “Chopra”) is withdrawn in light of the amendments to the claims.
(New rejection – necessitated by amendment.) Claims 1-4, 6-7, and 10-11 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Stewart-Jones et. al. (US20230108894A1, Priority 01/28/2020; hereafter “Stewart-Jones”) as evidenced by Kim et. al. (US20160281106A1, Pub. 09/29/2016; hereafter “Kim”.)
The Prior Art
Stewart-Jones teaches RNA vaccine compositions, wherein the RNA encodes fusion proteins with antigens (entire document; see abstract; ¶[0091-0092][0099]). Said fusion proteins encoded by the RNA would include SARS CoV-2 antigens, such as the S protein, fused to a foldon domain from T4 fibritin (¶[0098]). The fusion protein may include the full-length spike (S) protein, which comprises the S1 and S2 subunits (¶[0015][0376]) and may also include the nucleocapsid (NC) protein (¶[0006][0405]). Stewart-Jones teaches that IRES sites may be present within the RNA encoding the antigens (¶[0130]), gly/serine linkers, and/or F2A cleavable peptides (¶[0099-0100][0397]). Stewart-Jones therefore teaches a nucleic acid construct that comprises a full-length S protein, which inherently comprises both the receptor binding domain (RBD)(¶[0048][0393-0395]) and S2 subunit (which inherently comprises amino acids 301-538), a full-length N protein (which inherently comprises amino acids 138-369), a foldon domain, a F2A site, and an IRES site, thus teaching the limitations of instant claims 1-3, and 6. Stewart-Jones teaches SEQ ID NO: 84 for the N protein sequence, which comprises instant SEQ ID NO: 10 at 100% identity (instant claim 11).
As evidenced by the sequences of Kim, IRES sequences inherently comprise the sequence as set forth in instant SEQ ID NO: 11 (SEQ ID NO:4 of Kim aligns with 100% identity to instant SEQ ID NO: 11; instant claim 4).
Stewart-Jones teaches the RNA may be within a vector (¶0144][0356]; instant claim 7). Stewart-Jones teaches methods of delivering the RNA vaccine compositions to elicit a therapeutic immune response in a host against SARS CoV-2 (items 34-42 of ¶[0403]; ¶[0300-0305]; reference claim 37; instant claim 10).
Stewart-Jones, as evidenced by Kim, therefore teaches the limitations of instant claims 1-4, 6-7, and 10-11, and anticipates the invention encompassed by said claims.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: SEQ ID NOs: 6 and 13 appear to be novel and nonobvious sequences.
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.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671