DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants are informed that the rejections of the previous Office action not stated below have been withdrawn from consideration in view of the Applicant’s arguments and/or amendments.
Election/Restrictions
Applicant's election without traverse of the required species in the reply filed on 8/16/2023 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1, 7, 8, 10-12, 15, 32-34, 38-40, 44, 46, 48-52 and 60-64 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/18/25 and 9/19/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. However, NPL references 1-11, 13 and 14 of the IDS submitted on 9/18/2025 are not considered since the published year is missing from the citation.
Examiner’s Note
In view of newly identified art (Chadha et al.-see below), the limitation of TAK-003 now present in claims 1, 52, and 60 does not place the claims in allowable condition.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(New Rejection) Claim(s) 1, 7, 8, 10-12, 15, 32-34, 38-40, 44, 46, 48-52 and 60-64 are rejected under 35 U.S.C. 103 as being unpatentable over Noriega et al. (WO/17/005652) in view of Osorio et al (Expert Review of Vaccines, 2016, Vol. 15, No. 4, pages 497-508) as evidenced by Chadha et al. (US PGPub 2024/0150729).
The claimed invention also requires that the “another” vaccine is a yellow fever vaccine.
MPEP 2112.02 II. PROCESS OF USE CLAIMS — NEW AND NONOBVIOUS USES OF OLD STRUCTURES AND COMPOSITIONS MAY BE PATENTABLE
The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated.
The instant invention is drawn to a method for vaccinating against dengue disease and yellow fever in a subject or a population of subjects, the method comprising, administering one unit dose of a dengue virus composition and a yellow fever vaccine, wherein the dengue virus composition is TAK-003.
The method is also for vaccinating against dengue disease caused by dengue -1 or -2 serotypes. In addition, the administration of the one-unit dose to the subject or the subject population results in a combined vaccine efficacy of at least 80% which is represented by at least 80% reduction in dengue disease occurrence in vaccinated subjects compared to unvaccinated subjects.
The dengue virus compositions comprises 4 live attenuated dengue virus serotypes (a chimeric dengue serotype 2/1 strain; the dengue serotype 2 strain; a chimeric dengue serotype 2/3 strain; and chimeric dengue serotype 2/4 strain.
The method further comprises administering a second unit dose/booster dose of the dengue virus composition to the subject or subject population, wherein the second unit dose/booster dose administered at least 4 weeks apart of the first unit dose. Co-vaccination with another dengue vaccine composition is interpreted as including a booster or second unit dose administration, which is administered within 4.5 years of the one-unit dose.
The subject is at least 2 months old.
In addition, the yellow fever vaccine and dengue virus composition are administered to different anatomical sites.
Additionally, the claimed invention requires a vaccine combination comprising a yellow fever vaccine and the TAK-003 tetravalent dengue virus vaccine; and a kit comprising lyophilized TAK-003 dengue virus vaccine and a yellow fever vaccine and a pharmaceutically acceptable diluent.
The Prior Art
Noriega et al. teach the administration of vaccines focused on flaviviruses, specifically dengue virus and yellow fever viruses. More specifically, a yellow fever viral vaccine and a tetravalent vaccine for dengue viruses of serotypes 1 to 4 are to be concomitantly administered to a subject. [see page 6, lines 9-24] Noriega et al. on page 9 also state: “Further, it has been shown herein that concomitant administration of a yellow fever vaccine with a tetravalent dengue vaccine which comprises a live attenuated dengue virus of each of serotypes 1 to 4 results in a good antibody response against dengue, thus fulfilling the prospective statistical criteria of non-inferiority along with no clinically relevant impact on the safety profile of the dengue vaccine in humans, especially in small children.” For example, concomitant administration means administering the at least two products within 3 days, 2 days, 24 hours, 12 hours, 6 hours, 3 hours, 2 hours, 1 hour, 30 minutes, 15 minutes or simultaneously. Advantageously, the at least two products are administered at anatomically separate body sites. [See page 15, lines 20-27] Administration within the underline time frame fall within the scope of “same day” as required by the instant invention. Noriega et al. further teach that a booster dose of the dengue vaccine can be administered approximately 1 year following the first dose. [see page 27, lines 26-30]
The tetravalent dengue virus comprises at least one chimeric dengue virus with the backbone of the chimeric dengue being either yellow-fever a dengue virus of a different subtype compared to the origin of the prM and E proteins that are inserted. [see page 19, line 1-27] An example of the dengue virus serotype 2 that is taught by Noriega is isolate 16681/PDK53, also known as VDV2 or LAV2. [see page 18, lines 22-25] As a result, the dengue virus vaccine composition would comprise four live attenuated dengue virus serotypes comprises dengue structural proteins capsid protein (C), pre-membrane protein (prM), and envelope protein (E), and dengue non-structural proteins NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NSS. It is also taught that the age and weight of the human subject being vaccinated will be considered when determining the quantity (dose) of the live attenuated dengue or chimeric dengue virus vaccine. [see page 23, lines 21-25] The ages of the subjects are provided on page 25, lines 19-32: “Preferably a human subject according to the present invention is at least 12 months old. Preferably said human subject is at least 2 years old. Preferably said human subject is at least 5 years old. Preferably said human subject is at least 7 years old. Preferably said human subject is at least 9 years old. Preferably said human subject is at least 12 years old. Preferably said human subject is aged between 12 months and 60 years old. Preferably said human subject is aged between 2 and 60 years old. Preferably said human subject is aged between 6 and 60 years old. Preferably said human subject is aged between 7 and 60 years old. Preferably said human subject is aged between 9 and 60 years old. Preferably said human subject is aged between 9 and 45 years old. Preferably said human subject is aged between 12 and 60 years old. Preferably said human subject is aged between 2 and 16 years old. Preferably said human subject is aged between 5 and 16 years old. Preferably said human subject is aged between 9 and 16 years old. Preferably said human subject is dengue immune and/or said human subject resides in a dengue endemic area.” Lastly, Noriega et al. states that the vaccinal virus can be lyophilized and reconstituted with a pharmaceutical diluent. [see page 25, lines 1-10] Since Noriega et al. teach the concomitant (same day) administration of the yellow fever and dengue virus vaccines presently claimed, they would inherently achieve “efficacy against yellow fever and dengue within 3 months after administration”.
However Noriega et al. do not teach the dengue virus vaccine TAK-003.
Osorio et al. teach the development of a tetravalent dengue virus (TDV) immunogenic composition. Osorio et al. indicate that the TDV was previously known as DENVax. [see page 497, right column] As evidenced by Chadha et al. teach that DENVax is also known are TAK-003 [see paragraphs 141 and 143]. Therefore, the TDV of Osorio et al. is TAK-003.
This composition comprises the recombinant dengue virus serotype 2 identified as PDK-53, which was is derived from wild-type strain DEN-2 16681 and differs in at least three nucleotides form the wild type as follows: a) 5’-noncoding region (NCR)-57 (nt-57 C-to-T), b) NS1-53 Gly-to-Asp (nt-2579 G-to-A) and c) NS3-250 Glu-to-Val (nt-5270 A-to-T). Osorio et al. also teach the use of PDK-53 to express the prM and E proteins of dengue virus serotypes 1, 3 and 4, thereby generating chimeric 2/1, 2/3 and 2/4, as presently claimed. [see “TDV design and development” section and Figure 1]
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This TDV contained at least 2X10^4 pfu of 2/1 chimera, 5X10^4 pfu of PDK-53, 1X10^5 pfu of chimera 2/3, and 3X10^5 pfu of chimera 2/4. [see footnotes for Tables 1-4]
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Osorio et al. also teach the administration of this TDV to human subjects ranging from 1.5 years up to 45 years old, in a prime-boost administration protocol separated by 90 days. Blood samples were collected 30 days after each administration to determine seroconversion percentages.
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Table 3 presents the neutralizing titers of antibodies for each test group after the first dose and second dose of a TDV. Significant amounts of neutralizing antibody titers were observed following the first dose and a slight increase was observed following a second dose 90 days later. Following the first dose, neutralizing antibody titers were Subjects received the TDV composition either subcutaneously or intradermally. [see section “human immune responses elicited by TDV”] Osorio et al. reported in Table 4 that following the booster administration, the 5 different age groups reported a seroconversion of between 73%-96%, which included age groups of 1.5-5 years old, 6-11 years old and 12-20 years old.
Furthermore, since Osorio et al. teach the administration of a TDV that appears to be structurally identical to that the claimed and the administration of this TDV in the same active steps and in the same time period as claimed, the limitations of combined vaccine efficacy would be inherent properties of the method conducted by Osorio et al. As summarized above, MPEP 2112.02 states:
[However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated.]
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Noriega et al. in order to concomitantly administer the dengue virus vaccine TAK-003 with their yellow fever vaccine. One would have been motivated to do so, given the suggestion by Noriega et al. that a dengue virus vaccine comprising chimeric and non-chimeric dengue viruses for each serotype by concomitantly (same day) administer with a yellow fever vaccine. candidate based on a yellow fever viral backbone was being researched for efficacy. There would have been a reasonable expectation of success, given the knowledge that dengue virus vaccine TAK-003 is also known as DENVax was previously taught by Osorio et al. (as evidenced by Chadha et al.) and successfully and safely administered to seronegative and seropositive individuals. 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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached on M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671