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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-6, in the reply filed on 6/2/2026 is acknowledged. Claims 7 and 8 are canceled.
Claims 1-6 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 12/23/2024 and 6/2/2026 are in compliance with 37 CFR 1.97. Accordingly, the references listed in the IDSs are being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on p. 15. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www., or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 is objected to because of the following informalities: at line 7, “and” should be inserted after “5 days or more post infection,”. Appropriate correction is required.
Claim 1 is objected to because of the following informalities: at line 4, “insect cell” should be replaced with “isolated insect cell”. Appropriate correction is required.
Claim 3 is objected to because of the following informalities: at line 2, “a FMDV capsid precursor protein” should be replaced with “an FMDV capsid precursor protein”. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: at lines 3-4, the examiner suggests, to put the claim in better form, replacing “incorporating the FMDV VLP into a vaccine by addition of a pharmaceutically acceptable carrier” with “incorporating the FMDV VLP into a pharmaceutically acceptable carrier, thereby producing a vaccine”. Appropriate correction is required.
Claim Interpretation
The specification indicates that “an ‘expression vector’ (syn. ‘expression construct’), is usually a plasmid or virus designed for recombinant gene expression in cells.” (p. 5), and “a ‘baculovirus expression vector’ is an expression vector based on a baculovirus, which is used for recombinant gene expression in a host cell” (p. 6).
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 (i.e., changing from AIA to pre-AIA ) 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.
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 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.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Audonnet, et al. (WO 2016049209 A1, published 3/31/2016, on IDS) in view of Deepak, et al. (Biologicals. 2019 Jul;60:28-35. doi: 10.1016/j.biologicals.2019.06.003. Epub 2019 Jun 17. Erratum in: Biologicals. 2020 Jan;63:106. doi: 10.1016/j.biologicals.2019.11.003. PMID: 31221554), and Pillay, et al. Biotechnol Prog. 2009 Jul-Aug;25(4):1153-60. doi: 10.1002/btpr.187. PMID: 19572400).
The claimed invention encompasses a method of producing a foot and mouth disease virus (FMDV) virus-like particle (VLP) of an Asia1 or SAT2 strain in a baculovirus expression system, the method comprising: (i) infecting an insect cell with a baculovirus expression vector, wherein the insect cell is capable of recombinantly producing the FMDV VLP, (ii) culturing the insect cell in cell culture medium under conditions under which the cell produces the FMDV VLP, wherein the culturing is performed for 5 days or more post infection, (iii) harvesting the FMDV VLP produced by the insect cells from the cell culture medium, as represented by claim 1.
The Prior Art
Audonnet teaches compositions or vaccines comprising an antigenic FMDV polypeptide and fragments and variants thereof that possess immunogenic and protective properties, which may be produced by a baculovirus expression vector in insect cells, and further discloses FMDV VLPs (p. 4). Audonnet also teaches a plasmid pMEB097, used to generate a recombinant baculovirus encoding FMDV P1/2A/2B’3B’3/3C gene, which was transfected into Sf9 insect cells, and recombinant baculovirus isolated therefrom (p. 35). Audonnet also teaches infection by the generated baculovirus of Sf9 cells, which were grown for 4 days, and supernatants concentrated (p. 35). The assembly of the capsid protein into VLPs was confirmed by electronic microscopy (pp. 35-36, bridging para.). Notably, Audonnet discloses that FMDV encodes a single polyprotein containing, inter alia, the capsid precursor, also known as protein P1, which is cleaved by protease 3C into three proteins VP0, VP1, and VP3 (or 1AB, 1D, and 1C, respectively; pp. 1-2, bridging para.). Audonnet also discloses that particular FMDV antigenic polypeptides include P1, VP2, and 3C (p. 6, last para.), and that FMDV empty capsids are obtained by expression of the cDNA of regions P1, 2A/2B’/3B’ and 3C (p. 16, last para.). Additionally, Audonnet teaches that P1-2A and 3C are necessary for expression and cleavage of all the proteins making up the FMDV capsid particles or FMDV VLPs (p. 34, lines 16-18). Further, Audonnet teaches compositions comprising an FMDV antigen and a pharmaceutically acceptable carrier (p. 2, para. 2).
However, Audonnet does not teach the FMDV VLP is an Asia1 or SAT2 strain, nor wherein the culturing is performed for 5 days or more post infection.
Deepak teaches insect cell-expressed virus like particles (VLPs) are for use as an alternative to overcome the limitations of inactivated vaccines, and generated Foot-and-mouth disease (FMD) virus-like particles for several FMDV strains, including Asia1/IND/63/72 (Abstract). Deepak teaches that there are seven serotypes of FMDV, including Asia 1 and SAT2 (p. 28, col. 1, para. 1).
Pillay teaches optimization of HIV-1 VLP production in a baculovirus-insect cell expression system (Title). Pillay discloses that infection time in insect cells can vary quite substantially for recombinant proteins, depending on when the recombinant gene is expressed in the viral life cycle, and the stability of the cell line used (p. 1159, col. 1, para. 1). Pillay further discloses that it is important to find the best time to harvest VLPs in terms of yield, while also maintaining the structural integrity of the VLPs, and that the most favorited time post infection to harvest the VLPs of Villay was 120 hours post-infection, as yields were highest at that time point for both constructs (p. 1159, col. 1, paras. 1-2; Fig 3).
It would have been obvious to one of ordinary skill in the art to modify the FMDV production method taught by Audonnet to generate Asia1 or SAT2 strain VLPs. Deepak teaches production of VLPs based on the Asia1 strain Asia1/IND/63/72, and that SAT2 is another serotype of FMDV.
It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in instant claims are for any particular purpose or solve any stated problem, and the prior art teaches that parameter magnitudes that are encompassed by instant claims, often vary according to the sample being analyzed and various matrices, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the art.
Pillay highlights with a similar baculovirus-insect cell system that day 5 is an option to try for harvesting some types of VLPs, and that practitioners are already optimizing that timeframe, and thus culture time is a result effective variable. Thus it would have been obvious to one of ordinary skill in the art to find and use the ideal time for harvesting the FMDV VLP produced by the insect cells from the cell culture medium. Accordingly, it is obvious through routine optimization to culture the insect cell for 5 days or more post infection. One of ordinary skill in the art would have been motivated to optimize the production of FMDV VLPs, including VLPs based on the Asia1 or SAT2 serotypes. There would have been a reasonable expectation of success because Audonnet and Deepak produce FMDV VLPs.
Regarding claim 3’s requirement that the baculovirus expression vector comprises a nucleic acid sequence encoding a FMDV capsid precursor protein, claim 4’s requirement that the baculovirus expression vector further comprises a nucleic acid sequence encoding a protease capable of cleaving the FMDV capsid precursor protein into one or more capsid proteins, and claim 5’s requirement that the capsid precursor protein comprises the FMDV capsid precursor P1 and 2A peptide and the protease is 3C, Audonnet discloses FMDV P1/2A/2B’3B’3/3C gene, and that FMDV encodes a single polyprotein containing, inter alia, the capsid precursor, also known as protein P1, which is cleaved by protease 3C into three proteins VP0, VP1, and VP3.
Regarding claim 6, wherein the method further comprises (iv) incorporating the FMDV VLP into a vaccine by addition of a pharmaceutically acceptable carrier, Audonnet discloses compositions comprising an FMDV antigen and a pharmaceutically acceptable carrier as well as the vaccine purpose above, so it would have been obvious to combine the obvious VLPs with a pharmaceutically acceptable carrier to achieve the goal discussed supra.
One of ordinary skill in the art would have been motivated to produce VLPs based on the Asia1 or SAT2 strains of FMDV, for use as vaccines. There would be a reasonable expectation of success because Audonnet produces FMDV VLPs based on other strains, and Deepak discloses VLPs based on the Asia1 strain itself. Therefore, claims 1-6 were prima facie obvious before the priority date of the instant 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 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.
Claim 1-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 18/683,835 in view of Deepak, et al. (Biologicals. 2019 Jul;60:28-35. doi: 10.1016/j.biologicals.2019.06.003. Epub 2019 Jun 17. Erratum in: Biologicals. 2020 Jan;63:106. doi: 10.1016/j.biologicals.2019.11.003. PMID: 31221554). 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.
Each set of claims is drawn to a method of producing a foot and mouth disease virus (FMD) VLP in a baculovirus expression system, the method comprising (i) infecting an insect cell with a baculovirus expression vector, wherein the insect cell is capable of recombinantly producing the FMDV VLP, (ii) culturing the insect cell in cell culture medium under conditions under which the insect cell produces the FMDV VLP, wherein culturing is performed for five days or more post infection , and (iii) harvesting the FMDV VLP produced by the insect cells(instant claims 1 and 2, copending claims 1, 4 and 5). Each set of claims also encompasses the baculovirus expression vector comprising a nucleic acid sequence encoding an FMDV capsid precursor protein (instant claim 3, copending claim 8), the vector further comprises a nucleic acid sequence encoding a protease capable of cleaving the FMDV capsid precursor protein into one or more capsid proteins (instant claim 4, copending claim 9), the capsid precursor protein comprises the FMDV capsid precursor P1 and the 2A peptide and the protease is 3C (instant claim 5, copending claim 10), and the method further comprising incorporating the FMDV VLP into a vaccine by addition of a pharmaceutically acceptable carrier.
The claims differ in that the instant claims require an Asia1 or SAT2 strain of DMDV, whereas the copending claims are generic with regard to the strain, or specifically require an A or O serotype (copending claims 1-3).
However, as discussed above in the rejection under 35 U.S.C. §103, use of an Asia1 or SAT2-strain based VLP would have been obvious to one of ordinary skill in the art.
Deepak teaches insect cell express virus like particles (VLPs) are for use as an alternative to overcome the limitations of inactivated vaccines, and generated Foot-and-mouth disease (FMD) virus-like particles for several FMDV strains, including Asia1/IND/63/72 (Abstract). Deepak teaches that there are seven serotypes of FMDV, including Asia 1 and SAT2 (p. 28, col. 1, para. 1).
It would have been obvious to one of ordinary skill in the art to modify the copending method of FMDV VLP production to make FMDV VLPs based on the Asia1 or SAT2 strains of FMDV. One of ordinary skill in the art would have been motivated to vaccinate against Asia1 or SAT2 strains. There would have been a reasonable expectation of success because Deepak discloses VLPs derived from Asia1 strain. Therefore, the instant claims would have been prima facie obvious to one of ordinary skill in the art.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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