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 .
Priority- Foreign
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(a)-(d) and (f) or under 35 U.S.C. 120, 121, 365(a) or (b), or 386(a) is acknowledged. The present application claims benefit under 35 U.S.C. (119(a)-(d) to foreign application TW111149940, filed 12/26/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
However, it is noted that applicants have not provided an English translation of the foreign application. Therefore, applicant cannot rely upon the certified copy of the foreign priority application to overcome any rejections because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Status of Claims
Claims 1-20 are pending and are being examined on the merits.
Claim Objections
Claims 1, 11 and 16 are objected to because of the following informalities: The claims contain grammatical errors. Specifically claims 1, 11 and 16 recite: “a bivalent antigen consisted of E2 recombinant protein and ORF2 recombinant protein, an amino acid sequence of the E2 recombinant protein is listed as SEQ ID NO: 1, and the OFR2 recombinant protein is encoded by a nucleic acid sequence listed as SEQ ID NO: 2; a CpG adjuvant consisted of a nucleic acid sequence listed as SEQ ID NO: 3; and a dual phase adjuvant, and wherein”. The term “consisted” should be “consisting”; the use of “an” or “a” in reference to the SEQ ID NO: should be “the”; and the comma separating the components of the composition from the property wherein the composition is formulated as a single-dose administration should be a semi-colon (“;”). Thus, the claims should read, “a bivalent antigen consisting of E2 recombinant protein and ORF2 recombinant protein, wherein the amino acid sequence of the E2 recombinant protein comprises SEQ ID NO: 1, and the OFR2 recombinant protein is encoded by the nucleic acid sequence comprising SEQ ID NO: 2; a CpG adjuvant consisting of the nucleic acid sequence listed as SEQ ID NO: 3; and a dual phase adjuvant; and wherein…”. Appropriate correction is required.
Claim 5 is objected to because of the following informalities: Claim 5 recites “wherein the E2 recombinant protein is encoded by a nucleic acid sequence listed as SEQ ID NO: 4”. The use of “a” in reference to SEQ ID NO: 4 should be “the”. The claims should read “wherein the E2 recombinant protein is encoded by the nucleic acid sequence comprising SEQ ID NO: 4”. Appropriate correction is required.
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 Longi, 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 online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 18/485,754 in view of Zhang et al., (US 2023/0090422, with priority to 3/11/2020), Boniface et al., (US 7,825,227; issued 11/2/2010), Muller et al., (US 2013/0251719; published 9/26/2013), Chaung et al., (from IDS; US 10,117,929; published 11/6/2018), and Ellis et al., (US 2005/0058653; published 3/17/2005).
Application ‘754 claims a mammalian cell line stably expressing soluble E2 recombinant antigen of classical swine fever virus (CSFV) (claims 1 and 3-5), with the amino acid sequence of SEQ ID NO: 1 (claim 2), or the nucleic acid sequence of SEQ ID NO: 2 (claim 6); as well as methods of producing (claims 7-8); as well as a porcine subunit vaccine composition comprising the recombinant soluble E2 antigen (claims 9-11), wherein the vaccine comprises 25-50 ug/mL of E2 recombinant protein (claim 12).
The recombinant CSFV-E2 protein of app ‘754 is identical to that of instant claim 1, albeit with an alternative signal peptide at the N-terminal and an alternative cleavage site/His-Tag sequence at the C-terminal.
Zhang et al. teaches novel coronavirus S protein subunits as a vaccine preparation (abstract; pg. 1, para. 0007)). Zhang teaches the novel antigen as a fusion protein, in which the fusion protein has a signal peptide added to the N-terminal and a His-Tag added to the C-terminal, for the purposes of expressing and isolating the fusion protein from eukaryotic cells (pg. 1, para. 0007). Zhang teaches, preferably the signal peptide is a secretory signal peptide and the purification tag is a His-tag (pg. 3, para. 0033). Zhang teaches an embodiment of SEQ ID NO: 11 wherein the signal peptide is added at the N-terminal, and the His-Tag is added at the C-terminal, of the peptide encoding the fusion protein (pg. 4, para. 0051; pg. 18, claim 11; see also Fig. 12). The secretory signal peptide of Zhang SEQ ID NO: 11 comprises the 21 amino acid sequence of the signal peptide of the recombinant E2 protein of instant SEQ ID NO: 1 with 100% identity. The His-Tag of Zhang SEQ ID NO: 11 comprises the hexa-histidine (6 H residues) of the His-Tag of the recombinant E2 protein of instant SEQ ID NO: 1 with 100% identity. However, Zhang does not teach wherein the cleavage site for removing the His-Tag after purification is “LEVLFQGP” of instant SEQ ID NO: 1.
Boniface et al. teaches methods for purification of a protein complex (abstract). Boniface teaches modifying a protein to contain one or more affinity tags separated by one or more specific protease cleavage sites t isolate any interacting proteins or fragments; specifically, the method employs removal of a His-6 hexapeptide (abstract). Boniface teaches wherein the His-tag is separated by a protease cleavage sequence such as “PRESCISSION™”, Pg. 3, lines 46-51). Boniface teaches the sequence of PRECISSION™ cleavage site is LEVLFQGP, see the Table, col. 17; SEQ ID NO: 9). Thus, Boniface teaches an alternative His-Tag cleavage site, upstream of the H-6 His-tag, is LEVLFQGP.
It would have been obvious to one of skill in the art to modify the recombinant E2 protein of app ‘754 to have the alternative secretory signal peptide of Zhang et al., and the cleavage site/His-tag of Boniface et al. One would have been motivated to do so given the signal peptide is an alternative signal peptide that promotes secretion of the encoded protein, as taught by Zhang et al., and that the cleavage site and His-Tag are alternative domains that promote purification and subsequent cleavage of excess affinity tags, as taught by Boniface et al. There would have been a reasonable expectation for success given that both Zhang and Boniface teach the alternative signal peptides and His-Tag are appropriate for promoting secretion from mammalian eukaryotic cells and subsequent processing of proteins for production. The substitution of signal peptides and affinity tags with cleavage sites are well known techniques of molecular biology. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Thus, the combination of the recombinant E2 protein of app ‘754, with the signal peptide of Zhang at the N-terminal and the cleavage site and His-Tag of Boniface at the C-terminal makes obvious the recombinant E2 protein of instant claim 1 with 100% sequence identity.
However, the combination of app ‘754, Zhang and Boniface do not teach a vaccine composition comprising the recombinant E2 protein (SEQ ID NO: 1), an ORF2 protein (SEQ ID NO: 2), a CpG adjuvant (SEQ ID NO: 3), and a dual phase adjuvant.
Muller teaches novel circovirus as a causative agent of disease and protein sequences and nucleic acids for use in therapeutics (abstract). Muller teaches the virus is porcine circovirus type 2b (PCV2b; pg. 2, para. 0007). Muller teaches the amino acid sequence of porcine circovirus 2 of SEQ ID NO: 8 (pg. 19); and claims a nucleic acid molecule wherein the polypeptide of fragment thereof comprises at least 6, 8, 10, 20 or 30 contiguous amino acids of SEQ ID NO: 8 (pg. 25, claim 8), as well as vaccine compositions comprising said fragments (pg. 25, claims 39-40).
Instant SEQ ID NO: 2 is a nucleic acid sequence which encodes the amino acid sequence HIEKAKGTDQQNKEYCSKEGNLLMECGAPRSQGQRSDLSTAVSTLLESGSLVTVAEQHPVT. The 61 amino acid sequence is comprised, with 100% identity, in the PCV2 amino acid sequence of Muller SEQ ID NO: 8. Thus, Muller makes obvious the amino acid sequence encoded by instant SEQ ID NO: 2, regardless if SEQ ID NO: 2 uses alternate, but equivalent, nucleic acid codons encoding the same amino acid residues in the same location.
It would have been obvious to one of skill in the art to incorporate the 61 amino acid fragment of PCV2, or a nucleic acid encoding the fragment, in a vaccine composition. One would have been motivated to do so, with reasonable expectation for success, in order to generate an effective porcine vaccine composition as taught by Muller et al.
The combination composition of app. ‘754, Zhang, Boniface and Muller does not teach wherein the composition further comprises a CpG adjuvant of instant SEQ ID NO: 3.
Chaung et al. teaches a nucleic acid based adjuvant and porcine vaccine composition (abstract). Chaung teaches the nucleic acid fragment of SEQ ID NO: 1 is a fragment of an adjuvant and can be used as the adjuvant of a porcine vaccine composition (abstract). Chaung teaches the CpG motif can stimulate cell activity of porcine lymphocytes and thereby elevate immune cell activity as an effective adjuvant (pg. 1, lines 27-34). Chaung teaches the adjuvant of SEQ ID NO: 1 is derived from CpG motifs (col. 3, lines 43 – col. 4, line 8). Chaung teaches a porcine vaccine composition comprising an antigen and the adjuvant of SEQ ID NO: 1 (col. 11, claim 1). The CpG adjuvant of Chaung SEQ ID NO: 1 is 100% identical to that of instant SEQ ID NO: 3.
It would have been obvious to one of skill in the art to add the CpG adjuvant of Chaung et al. to the vaccine composition of app. ‘754, Zhang, Boniface and Muller. One would have been motivated to do so in order to improve the antigenicity of the vaccine composition as taught by Chaung et al. There would have been a reasonable expectation of success given that the adjuvant of Chaung is taught as an appropriate adjuvant for porcine vaccine compositions.
However, none of app ‘754, Zhang, Boniface, Muller or Chaung teach a vaccine composition further comprising a dual phase adjuvant.
Ellis teaches porcine PCV2 vaccines (abstract), which comprise a PCV2 immunogen (pg. 1, para. 0009; pg. 2, para. 0016). Ellis teaches the immunogen can be combined with other porcine immunogenic or vaccine compositions, thereby providing a multivalent or “cocktail” vaccine composition (pg. 5, para. 0046; pg. 27, claim 7). Ellis teaches suitable adjuvants for use in the vaccine include water-in-oil-in-water emulsions (i.e. a dual phase adjuvant; pg. 5, para. 0050). Thus, Ellis makes obvious multivalent porcine vaccines wherein the compositions further comprise a dual phase adjuvant, which is a water-in-oil-in-water adjuvant.
It would have been obvious to formulate the multivalent porcine vaccine composition of the combination of app. ‘754, Zhang, Boniface, Muller and Chaung with a dual phase adjuvant. One would have been motivated to do so to improve the therapeutic properties of the vaccine composition. There would have been a reasonable expectation for success given that Ellis teaches multivariant porcine vaccine compositions may be formulated with a water-in-oil-in-water dual phase adjuvant. Thus the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Specifically, the combination of app. ‘754, Zhang, Boniface, Muller, Chaung and Ellis make obvious a porcine vaccine composition comprising the recombinant E2 protein of app. ‘754, comprising the N-terminal signal peptide and C-terminal hexa-His-Tag of Zhang with the His-Tag cleavage site of Boniface; wherein the recombinant CSFV-E2 protein is combined with the PCV2 ORF2 protein of Muller, the CpG adjuvant of Chaung, and the dual-phase adjuvant of Ellis.
The multivalent porcine vaccine composition of app. ‘754, Zhang, Boniface, Muller, Chaung and Ellis make obvious that of instant claims 1-5, 9, 11-12, 16-17 and 19. Regarding the ranges, ratios and concentrations of claims 6-8, 10, 13-15, 18 and 20; MPEP section 2144.05(II) teaches the obviousness of similar and overlapping ranges, amounts and proportions, including the routine optimization within the prior art conditions or through routine experimentation. Thus, as the combination of app. ‘754, Zhang, Boniface, Muller, Chaung and Ellis make obvious a vaccine composition comprising the same components, it is obvious to the skilled artisan to optimize the concentrations and ratios to generate an “effective dose” for use as a porcine vaccine. Therefore, the combination of app. ‘754, Zhang, Boniface, Muller, Chaung and Ellis make obvious claims 6-8, 10, 13-15, 18 and 20.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
The recombinant E2 protein of SEQ ID NO: 1 (residues 22-363) is considered the novel feature of the instant invention. While co-pending application 18/485754 teaches an identical recombinant protein (SEQ ID NO: 1, residues 24-365), with a different signal peptide and His-Tag cleavage domain, the recombinant protein sequence of the E2 protein proper, is free of the prior art. Thus, pending resolution of the double patenting issues above, the instant claims comprise allowable subject matter in the recombinant E2 protein of SEQ ID NO: 1.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES R. MELCHIOR whose telephone number is (703)756-4761. The examiner can normally be reached M-F 8:00-5:00 CST.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
Prosecution Insights