Zika Virus Vaccine

§102 §103 §DP

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 . DETAILED ACTION Priority This Application is a continuation of U.S. Application Serial No. 18/334,497, filed June 14, 2024, which is a continuation of U.S. Application Serial No. 17/548,721, filed December 13, 2021, which is a continuation of U.S. Application Serial No. 16/813,862, now U.S. Patent No. 11,219,681, filed March 10, 2020, which is a continuation of U.S. Application Serial No. 16/063,007, now U.S. Patent No. 10,639,365, filed June 15, 2018, which is a national stage filing under 35 U.S.C. § 371 of International Patent Application Serial No. PCT/EP2016/082664, filed December 23, 2016, that is hereby acknowledged by the Examiner. Status of the Claims The amendment dated 09/30/2024 is acknowledged. Claims 18-37 are pending and under examination. Information Disclosure Statement The information disclosure statement (IDS) submitted on 08/09/2024, 12/19/2024, 03/25/2025 and 08/14/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner. Drawings Objections The drawings are objected to because Figures 3, 6 and 7 are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Claim Objections Claim 37 is objected to for the following informalities: Claim 37 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 18-21 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Tauber et al. “Tauber” (EP3184118, effective filing date March 29, 2016). The claims are directed to a Zika virus vaccine comprising a Zika virus having an RNA genome corresponding to the DNA sequence provided by any one of SEQ ID NOs: 2-13 or 72 or a variant nucleic acid having at least 99% identity to any one of SEQ ID NOs: 2-13 or 72 and able to pack a virulent Zika virus, wherein the sequence identity is determined by Needleman-Wunsch homology alignment. Regarding claims 18-21, Tauber discloses “immunogenic or vaccine compositions comprising at least one recombinant Zika virus antigen, wherein the at least one recombinant Zika virus antigen is encoded by at least one nucleic acid sequence encoding at least one E-protein of a Zika virus or a fragment thereof. Further provided are nucleic acid molecules and a recombinant chimeric virus encoding and/or comprising selected antigens from a Zika virus, or variants thereof, which are suitable as immunogenic or as vaccine compositions. Preferably, the sequences encoding at least one Zika virus antigens suitable for eliciting an immune response are operably linked to a non-flavivirus derived vector backbone to provide an efficient and safe vector backbone for vaccine production and vaccination. In certain embodiments, the nucleic acid molecule or the immunogenic composition do not encode/contain capsid or non-structural proteins derived from a Zika virus. Further provided are methods for purifying the recombinant chimeric virus particles or the immunogenic composition to provide an immunogenic composition with a low level of process- or product related impurities. Finally, there is provided an immunogenic composition, preferably a vaccine composition for use in a method of preventing or treating a Zika virus disease in a subject” (Abstract). SEQ ID NO: 12 of Tauber comprises a 10,638-nucleotide sequence that matches with SEQ ID NO: 4 of the present invention, whereby SEQ ID NO: 4 comprises a 10,727 nucleotide sequence. Thus, Tauber’s SEQ ID NO: 12 has a 99.2% sequence identity to SEQ ID NO: 4 of the present invention (see sequence alignment below). With respect to the claim’s limitation of the sequence being able to “pack a virulent Zika virus”, the MPEP states that “the express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. "The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983)” (see MPEP 2112). section 2112(II) of the MPEP states that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004)(“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Atlas Powder Co. v. Ireco, Inc., 190 F.3d 1342, 1348-49 (Fed. Cir. 1999) (“Because sufficient aeration' was inherent in the prior art, it is irrelevant that the prior art did not recognize the key aspect of [the] invention.... An inherent structure, composition, or function is not necessarily known.”). Additionally, Tauber’s SEQ ID NO: 11 has a 99.7% sequence identity to SEQ ID NO: 5 of the present invention; and Tauber’s SEQ ID NO: 12 has a 99.5% sequence identity to SEQ ID NO: 6 of the present invention. PNG media_image1.png 997 653 media_image1.png Greyscale PNG media_image2.png 996 645 media_image2.png Greyscale PNG media_image3.png 1000 656 media_image3.png Greyscale PNG media_image4.png 997 651 media_image4.png Greyscale PNG media_image5.png 996 647 media_image5.png Greyscale PNG media_image6.png 998 646 media_image6.png Greyscale PNG media_image7.png 1000 649 media_image7.png Greyscale PNG media_image8.png 999 650 media_image8.png Greyscale PNG media_image9.png 995 644 media_image9.png Greyscale PNG media_image10.png 998 652 media_image10.png Greyscale PNG media_image11.png 991 649 media_image11.png Greyscale PNG media_image12.png 996 644 media_image12.png Greyscale PNG media_image13.png 843 649 media_image13.png Greyscale Therefore, the cited prior art anticipates the claimed invention. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a). Claims 24 and 26-29 are rejected under 35 U.S.C. 103(a) as being unpatentable over Tauber et al. “Tauber” (EP3184118, effective filing date March 29, 2016) as applied to claim 18 above. The teachings of Tauber et al. are outlined above and incorporated herein. Claim 24 is directed to the Zika virus vaccine according to claim 18, wherein said Zika virus vaccine is capable of stimulating a neutralizing antibody titer greater than 15 in at least 70% of vaccinated subjects, wherein the neutralizing antibody titer is determined using a microneutralization assay (MN50) following a single administration of the Zika virus vaccine to a subject. Regarding claims 24 and 26-29, Tauber discloses the use of a microneutralization assay (para. [0175] Example 13). As it pertains to a neutralizing antibody titer greater than 15 in at least 70% of vaccinated subjects; 80% of vaccinated subjects; 90% of vaccinated subjects; 95% of vaccinated subjects; and 99% of vaccinated subjects, respectively, the composition in the claims and the composition of the references comprise the same structural limitations for stimulating an immune response by administering the same compounds of the claimed invention, hence, the same functional characteristics (i.e. generating a neutralizing antibody titer) of the cited prior art would stimulate the same immune responses as the functional characteristics of the claimed invention. Additionally, MPEP 2114 states I. Apparatus claims must be structurally distinguishable from the prior art… While features of an apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function. In re Schreiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-32 (Fed. Cir. 1997) (The absence of a disclosure in a prior art reference relating to function did not defeat the Board' s finding of anticipation of claimed apparatus because the limitations at issue were found to be inherent in the prior art reference); see also In re Swinehart, 439 F.2d 210, 212-13, 169 USPQ 226, 228-29 (CCPA 1971);In re Danly, 263 F.2d 844, 847, 120 USPQ 528, 531 (CCPA 1959). "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Langi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely on line using web-screens. An eTerminal Disclaimer that meets all requirements is autoprocessed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 18-23 and 25-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 10-12 and 16-20 of U.S. Patent No. 10639365. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive in scope and species with one another. The claims are directed to a Zika virus vaccine comprising a Zika virus having an RNA genome corresponding to the DNA sequence provided by any one of SEQ ID NOs: 2-13 or 72 or a variant nucleic acid having at least 99% identity to any one of SEQ ID NOs: 2-13 or 72 and able to pack a virulent Zika virus, wherein the sequence identity is determined by Needleman-Wunsch homology alignment. The patented claims are directed to: 1. A Zika virus vaccine comprising an inactivated Zika virus, wherein the Zika virus vaccine contains protamine sulphate (PS) or fragments or break-down products of PS at amounts below 1 μg/mL and wherein the vaccine is able to confer seroprotection on at least 70% of subjects that are administered the Zika virus vaccine (instant claims 18 and 35). 2. The Zika virus vaccine of claim 1, wherein the Zika virus vaccine is able to confer seroprotection on at least 80%, of subjects that are administered the Zika virus vaccine (instant claims 26-29). 3. The Zika virus vaccine of claim 1, wherein the Zika virus comprises an RNA genome corresponding to the DNA sequence provided by any one of the nucleic acid sequences of SEQ ID NOs: 2-13 or 72, or a variant nucleic acid sequence that is at least 88% identical to any one of SEQ ID NOs: 2-13 or 72 and able to pack a virulent Zika virus (instant claims 18-23). 4. The Zika virus vaccine of claim 1, wherein the Zika virus comprises an E protein selected from the amino acid sequences provided by any one of SEQ ID NOs: 14-69, or a variant amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 14-69 and able to pack a virulent Zika virus (instant claim 25). 5. The Zika virus vaccine of claim 1, wherein the Zika virus is inactivated by chemical inactivation, thermal inactivation, pH inactivation, or UV inactivation (instant claim 30). 10. The Zika virus vaccine of claim 1, further comprising an adjuvant (instant claim 31). 11. The Zika virus vaccine of claim 10, wherein the adjuvant is an aluminum salt adjuvant (instant claim 32). 12. The Zika virus vaccine of claim 11, wherein the aluminum salt adjuvant is aluminium hydroxide or aluminium phosphate salt (instant claim 33). 16. The Zika virus vaccine of claim 1, wherein the Zika virus vaccine contains protamine sulphate (PS) or fragments or break-down products of PS at amounts below 100 ng/mL (instant claim 35). 17. The Zika virus vaccine of claim 1, wherein said protamine sulphate (PS) or fragments or break-down products of PS can be detected by mass spectroscopy or another sensitive method (instant claims 34 and 36). 18. The Zika virus vaccine of claim 1, wherein said Zika virus vaccine is able to confer seroprotection on at least 90% of subjects that are administered the Zika virus vaccine (instant claims 27-29). 19. The Zika virus vaccine of claim 1, wherein said Zika virus vaccine is able to confer seroprotection on at least 95% of subjects that are administered the Zika virus vaccine (instant claims 28 and 29). 20. The Zika virus vaccine of claim 11, wherein said aluminium salt adjuvant is aluminium hydroxide with less than 1.25 parts per billion (ppb) copper (Cu) based on the final pharmaceutical composition comprising the Zika virus (instant claim 33). There is no patentable difference between the claimed composition and the patented composition in that the U.S. Patent No. 10639365 (’365) discloses a Zika virus vaccine comprising a Zika virus having an RNA genome corresponding to the DNA sequence provided by any one of SEQ ID NOs: 2-13 or 72 or a variant nucleic acid having at least 99% identity to any one of SEQ ID NOs: 2-13 or 72 and able to pack a virulent Zika virus. The composition of ‘365 would anticipate the compositions herein. Moreover, The MPEP states “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00. 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. 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. /BARRY A CHESTNUT/Primary Examiner, Art Unit 1672