DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 21, 2026 has been entered.
Claims 1, 2, 12-14, 16-18, 30-37 and new claims 38-43 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 Any prior objection or rejection that is not repeated or addressed below is either withdrawn or moot in view of Applicant’s amendment.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) encoding sequence that has a codon pair bias of less than -0.05. According to the specification, paragraph [0070] of the published application (US20220347285) indicates that, in this invention, codon pair bias is determined by the formula:
PNG
media_image1.png
96
192
media_image1.png
Greyscale
The recoded E protein encoding sequence is present in SEQ ID NO: 9, 10, 11 or 12 (claims 1 and 39), or in the same with up to 15 nucleotide substitutions in the E protein encoding sequence (claims 1, 38 and 40). 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 sequence has a reduced codon pair bias of less than -0.05; 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 and a combination thereof.
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 30-43 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 and 31 recite, “codon pair bias of less than -0.05”. This appears to be a relative term since there is no point of comparison with which to determine a bias. According to paragraphs [0066]-[0071], it would appear that an original sequence is required in order to calculate the codon pair bias. It is noted that the claims previously recited “compared to its parent E protein encoding sequence”. Clarification and/or correction on this point is required. Dependent claims 2, 12-14, 16, 17, 19 and 30-43 are included in this rejection.
Claims 1, 31, 38 and 40 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”. 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.
Conclusion
No claim is allowed.
SEQ ID NO: 9-12 are free of the prior art of record.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
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.
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
Prosecution Insights