DETAILED ACTION
Applicant's amendment and remarks filed on April 21, 2026 is acknowledged and entered. Claims 1, 2, 12-14, 16-19, 30-43 and new claims 44 and 45 are pending. Any prior objection or rejection that is not repeated or addressed below is either withdrawn or moot in view of Applicant’s amendment.
Claims Summary
Claim 1 is directed to a modified dengue virus type 1, 2, 3 or 4, or in another embodiment, a tetravalent virus composition, meaning that all four serotypes are present together (claim 12), comprising a recoded E protein (elected species) present in SEQ ID NO: 9, 10, 11 or 12 (claims 1, 39, 44 and 45), or in the same with up to 15 nucleotide substitutions in the E protein encoding sequence (claims 1, 38, 40 and 45). Expression of the E protein is reduced compared to its parent dengue virus (claim 2). Also claimed is a dengue immune composition for inducing an immune response in a subject comprising one or more of the modified dengue viruses, and a pharmaceutically acceptable excipient or carrier (claim 13). According to claims 32 and 35, the modified dengue virus comprises SEQ ID NO: 9, 10, 11 or 12, or comprises SEQ ID NO: 9-12. In another embodiment, the recoded E protein encoding sequence is recoded from parent sequences SEQ ID NO: 1, 3, 5 and/or 7, respectively (claims 33 and 34). See Table 4 of the specification.
Claim 14 is directed to a method of eliciting an immune response in a subject comprising administering an effective dose of a composition comprising one or more modified dengue viruses of claim 1. The immune response is cross-reactive against a heterologous dengue virus (claim 17). The method further comprises administering at least one adjuvant (claim 16). Claim 36 is directed to a method of eliciting an immune response by administering a tetravalent composition comprising modified dengue virus having its E protein encoding sequence recoded from parent sequences SEQ ID NO: 1, 3, 5 and 7. Claim 37 is directed to a method of eliciting an immune response by administering a tetravalent composition comprising SEQ ID NO: 9-12. Claims 41-43 are directed to methods of eliciting an immune response in a human subject, comprising administering the tetravalent dengue virus composition of claims 38-40, respectively.
Claim 18 is directed to a method of eliciting an immune response in a subject in need thereof comprising administering a prime dose of the modified dengue virus of claim 1 (elected species), and administering one or more boost dose of the virus. A first of the one or more boost dose is administered about 2 weeks after the prime dose (claim 19). The modified dengue virus is provided in a composition comprising modified dengue viruses of serotypes 1, 2, 3 and 4 (claim 30).
Claim 31 is directed to a method of making a modified dengue virus genome, comprising:
Obtaining a parent E protein encoding sequence of a parent dengue virus;
Recoding the E protein encoding sequence to reduce protein expression, wherein the recoded E protein encoding sequence is present in SEQ ID NO: 9, 10, 11 or 12, or in the same with up to 15 nucleotide substitutions in the E protein encoding sequence; and
Substituting the recoded E protein-encoding sequence into a parent dengue virus genome, whereby expression of the E protein encoding sequence is reduced compared to the parent virus; and wherein the modified dengue virus is selected from serotypes 1, 2, 3, 4.
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.
Claims 1, 2, 12-14, 16-19 and 30-45 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.
Claims 1, 31, 38, 40 44 and 45 recite, “wherein the recoded E protein encoding sequence has the E protein encoding sequence in SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12, or wherein the recoded E protein encoding sequence has the E protein encoding sequence in SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ ID NO: 12, with up to 15 nucleotide substitutions in the E protein encoding sequence”, respectively. The location of the E protein encoding sequence in the genomes represented by SEQ ID NO: 9-12 does not appear to have been provided. The specification does not set forth clear cut-offs for the beginning and end of each E gene of these genomes (e.g., nucleotides positions for the start and end of each E gene). Clarification and/or correction on this point is required. Dependent claims 2, 12-14, 16-19, 30, 32-37, 39 and 41-43 are included in this rejection.
Applicant’s remarks filed April 21, 2026 have been carefully considered but fail to persuade. Applicant argues that one of ordinary skill in the art would be able to determine the start and end nucleotide positions of each E gene by retrieving sequences from GenBank and following the annotation provided by GenBank for each gene. Applicant submits as Exhibit 1 GenBank’s sequences of complete genomes of strain DENV-1/VN/BID-V1774/2007 with highlighted envelope portion nt 900-2390, DENV-2/NI-BID-V533/2005 with highlighted envelope portion nt 914-2398, DENV-3/VE/BID-V2268/2008 with highlighted envelope portion nt 899-2377, and DENV-4/US/BID-V2448/1999 with highlighted envelope portion nt 918-2402.
In response, one cannot rely on GenBank to provide the metes and bounds for the envelope coding sequences since GenBank’s information can be changed (e.g., various versions with different information as to start/stop locations). Therefore, the claims are rejected for being indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
(New Rejection) New claim 45 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 45 is dependent on claim 1. Claim 45 is directed to two embodiments: the recoded E protein encoding sequence has the E protein encoding sequence in SEQ ID NO: 9, 10, 11 or 12, and, the recoded E protein coding sequence has the E protein encoding sequence in SEQ ID NO: 9, 10, 11 or 12 with up to 15 nucleotide substitutions in the E protein encoding sequence. These two embodiments are already recited in claim 1. Thus, claim 45 fails to further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claim is allowed.
SEQ ID NO: 9-12 are free of the prior art of record.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas 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.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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