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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/29/2025 has been entered.
Claims 1-20 are pending in the application. Claims 1, 5, were amended. Claims 7, 13-20 were previously withdrawn.
Claims 1-6, 8-12 are currently under examination on the merits.
Information Disclosure Statement
The information disclosure statements (IDS) were submitted on 03/02/2022, 06/28/2024, 01/24/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
(Previous objection, withdrawn) Applicant’s amendments to the Specification concerning nucleotide and/or amino acid sequence disclosures submitted on 10/29/2025 have overcome the objection previously set forth in the Final Office Action mailed on 05/29/2025.
Claim Objections
(Previous objection, withdrawn as to claim 5). Applicant’s amendment of claim 5 submitted on 10/29/2025 have overcome previous objections to claim 5 set forth in the Final Office Action mailed on 05/29/2025.
(New objection, necessitated by amendment as to claim 1). Claims 1 as submitted on 10/26/2025 is objected to because of the following informalities:
The recitation in claim 1 of “wherein said heterologous protein or fragment thereof consisting of an immunogenic fragment of a rotavirus VP8 protein” should read “wherein said heterologous protein or fragment thereof consists of an immunogenic fragment of a rotavirus VP8 protein”. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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, 3, 4 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Vaughn et al., in view of Rodriguez et al., (prior art or record).
See claims 1, 3, 4 and 12 as submitted on 10/29/2025.
Regarding claim 1, it is noted that amended claim 1 as submitted on 10/29/2025 recites “for reducing one or more clinical signs of rotavirus infection” on lines 1 and 2 and “wherein said heterologous protein or fragment thereof consisting of an immunogenic fragment of a rotavirus VP8 protein” on lines 5 and 6. First, regarding the recitation of “for reducing one or more clinical signs of rotavirus infection”, it is noted that intended use in a claim, for example, intended use of a composition for reducing one or more clinical signs of infection, does not carry patentable weight. Further, it is noted that any polypeptide in the prior art having the all of the limitations recited in claim 1 would be capable of reducing one or more clinical signs of rotavirus infection. Second, with respect to the recitation of “wherein said heterologous protein or fragment thereof consisting of an immunogenic fragment of a rotavirus VP8 protein”, it is noted that the combination of the teachings of Vaughn et al. and Rodrigues et al. meet the limitations of claim 1 as submitted on 10/29/2025.
As previously indicated, Vaughn et al. teach the use of a porcine circovirus type 2 (PCV2) virus-like particle (VLP) as a vector for expressing desired amino acid sequences. The amino acid sequence or polypeptide taught by Vaughn et al. comprises a PCV2 capsid protein, which Vaughn et al. teach is also known as ORF2 (Abstract; ¶¶ [0004], [0006], [0010]). Vaught et al. further teach the use of virus-like particle properties of PCV2 capsid as a vector for producing an immunologically relevant peptide 8-200 amino acids in length (¶ [0011]). The sequence segments foreign to PCV2 capsid can be attached to or integrated in the PCV2 capsid sequence and expressed in an expression system (¶¶ [0010], [0011]). Vaughn et al. further teach a fusion protein wherein the PCV2 capsid sequence is fused to the foreign amino acid sequence (¶ [0078]). Vaughn et al. further teach a PCV2 ORF2 sequence which encodes the capsid protein (SEQ ID NO:10) and shares 100% sequence identity with instant SEQ ID NO: 1 (alignment of record and shown below).
PNG
media_image1.png
572
648
media_image1.png
Greyscale
Vaughn et al. do not explicitly teach a heterologous protein or fragment thereof consisting of an immunogenic fragment of a rotavirus VP8 protein.
However, Rodrigues et al. teach structural features of the rotavirus entry machinery wherein a 159 amino acid residues long fragment contributes to the spike stalk protein of a rotavirus (Abstract, page 4, 7, Fig. 6). Said fragment is a lectin-like domain of the porcine rotavirus VP8 protein and consists of amino acid residues 65-224 of the porcine rotavirus VP8 (Abstract, page 4, 7, Fig. 6). Rodrigues et al. further teach that said lectin-like domain is involved in receptor binding and attachment to the host cell (page 2). It is noted that these teachings are consistent with the description of a rotavirus VP8 protein in instant Specification (page 4).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to have included the teachings of Rodrigues et al. about the lectin-like domain of VP8 consisting of amino acid residues 65-224 of a VP8 protein into the construct as taught by Vaughn et al., for the benefit of formulating a VLP wherein an immunologically relevant protein consisting of a lectin-like domain of VP8 is expressed at the surface of the VLP.
One of ordinary skill in the art would have had a reasonable expectation of success for introducing the lectin-like domain of VP8 as taught by Rodrigues et al. into the PCV2 construct of Vaughn et al. given that both sequences were well known in the art and the methods of VLP cloning and expression are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 3 as submitted on 10/29/2025, the teachings of Vaughn et al. described above meet the limitations of claim 3 because, as previously explained, Vaughn et al. teach a Circoviridae virus capsid of PCV2 which shares 100% sequence identity with instant SEQ ID NO: 1 (alignment of record and shown above).
Regarding claim 4, Rodrigues et al. teach a porcine strain OSU which is a rotavirus type A (pages 3, 6).
Regarding claim 12, as previously explained, Vaughn et al. further teach an immunogenic composition comprising: an amino acid segment from PCV2 ORF2 and a foreign amino acid segment expressed as VLPs. (¶ [0017], claim 1).
Accordingly, claims 1, 3, 4, 12 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claims 2, 5, 9, 11 are rejected under 35 U.S.C. 103 as being unpatentable over Vaughn et al. and Rodrigues et al. as applied to claims 1, 3, 4, 12, above, and further in view of Masuda et al. (prior art of record).
See claims 2, 5, 9-11 as submitted on 10/29/2025.
Regarding claim 2, Vaughn et al. and Rodrigues et al. in combination teach the immunogenic polypeptide of claim 1.
Neither Vaugh et al. nor Rodrigues et al. explicitly teach a linker moiety attached to the PCV2 capsid and the rotavirus VP8 genes in the configuration x-y-z as recited in claim 2.
However, Masuda et al. teach a PCV2 VLP expression system comprising a PCV2 capsid protein wherein an exogenous gene is attached to the PCV2 capsid sequence via a linker moiety (a Q-tag [YPLQMRG], and a K-tag [MRHKGS]) such that the exogenous gene is expressed on the surface of the VLPs (Abstract, page 2, column 1, ¶¶ 1, 2). Such liker moiety results in an amino acid sequence 8 amino acids in length (YLPWKHRM). Masuda et al. further teach the following sequence arrangement: PCV2 capsid – linker moiety – exogenous gene (page 3, column 2, ¶ 4; Fig. 1) (x-y-z, as recited in claim 2).
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have included the teachings of Masuda et al. about the linker moiety into the PVC2 capsid – VP8 construct as taught by Vaughn et al. and Rodrigues et al., for the benefit of expressing the fragment of a rotavirus VP8 protein on the surface of the VLPs. One of ordinary skill in the art would have been motivated to assemble a construct for a chimeric PCV2 VLP where an antigenic rotavirus VP8 peptide is inserted into the PCV2 capsid via a linker moiety given that the PCV2 capsid construct and the immunogenic fragment of rotavirus VP8 were known in the art, and Masuda et al. teach the linker moiety for the advantage of ensuring expression of the VP8 fragment on the surface of the VLPs.
One of ordinary skill in the art would have had a reasonable expectation of success for introducing the linker moiety and the antigenic VP8 peptide as taught by Rodrigues et al. and Masuda et al. into the PCV2 construct of Vaughn et al. given that the methods of VLP cloning and expression are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
As per claim 5, it is noted that amended claim 5 recites “wherein the lectin-like domain of the porcine rotavirus VP8 protein consists of an amino acid sequence of the amino acid residue numbers 65-224 of the porcine rotavirus VP8 protein.” As explained above, Rodrigues et al. teach a porcine rotavirus VP8 sequence of the lectin-like domain consisting of the amino acid residues 65-224 of the porcine VP8 protein (Abstract, page 4, 7, Fig. 6). It is noted that Rodrigues et al. teach the exact fragment expanding from amino acid residue 65 to 224 of a VP8 protein as required by instant claim 5. Rodrigues et al. further teach said fragment interacts with the host receptor and is involved in the attachment of the virus to the host cell (Specification, page 4). With respect to the N-terminal extension, as explained previously, Masuda et al. teach different linker moieties comprising 6 or 7 amino acid residues long. Such linker moiety extends from the N-terminal of the exogenous gene, which in this case consists of the lectin-like domain of the porcine rotavirus VP8 protein amino acid residues 65-224, to the C-terminal of the PCV2 capsid sequence, thereby attaching both genes (page 3, column 2, ¶ 4; Fig. 1). The recitation in claim 5 of the “N-terminal extension” is interpreted herein under BRI as any amino acid extension of 1 to 20 amino acid residues in length as required by claim 5. Therefore, the teachings of Masuda et al. meet the limitation of “wherein the N-terminal extension is 1 to 20 amino acid residues in length”.
Regarding claim 9, as previously explained, Masuda et al. teach a PCV2 VLP expression system comprising a PCV2 capsid protein wherein an exogenous gene is attached to the PCV2 capsid sequence via a linker moiety (a Q-tag [YPLQMRG], and a K-tag [MRHKGS]) such that the exogenous gene is expressed on the surface of the VLPs (Abstract, page 2, column 1, ¶¶ 1, 2). Masuda et al. further teach an L-Qtag-GGSG-3 ' as a linker moiety (page 2, column 2, ¶ 2). Such L-Qtag shares 100% sequence identity with instant SEQ ID NO: 11 (alignment of record and shown below, Qy is instant SEQ ID NO: 11 and Db is the L-Qtag)
PNG
media_image2.png
273
976
media_image2.png
Greyscale
Regarding claim 11, it is noted that amended claim 11 does not recite any new limitations. As previously explained, Masuda et al. teach the PCV2 capsid sequence, attached to an exogenous gene via linker moiety such that the exogenous gene is expressed on the surface of the VLPs (Abstract, page 2, column 1, ¶¶ 1, 2).
Claims 6, 8, 10 are rejected under 35 U.S.C. 103 as being unpatentable over Vaughn et al. and Rodrigues et al. as applied to claims 1, 3, 4, 12, above, and further in view of Wang et al. (prior art of record).
See claims 6, 8, 10 as submitted on 10/29/2025.
Regarding claim 10, it is noted that amended claim 10 does not recite any new limitations. As previously explained, instant SEQ ID NO: 14 is a 404 amino acid long sequence comprising the following:
Amino acid residues 1-233 comprise the PCV2 capsid protein also provided in instant SEQ ID NO: 1. As explained previously, Vaugh et al. teach a PCV2 capsid protein (SEQ ID NO:10) with 100% sequence identity to instant SEQ ID NO: 1 (see alignment of record).
Amino acid residues 234-236 comprise a GGS linker sequence. Masuda et al. teach such linker moiety, as explained above.
Amino acid residues 237-404 comprise of a 168 residues long fragment of a rotavirus VP8 protein also provided in instant SEQ ID NO:7. As explained previously, Wang et al. teach a sequence that shares 99.7% sequence identity to instant SEQ ID NO: 7 (see alignment of record and shown below). It is further noted that this region consists of the following elements:
Amino acid residues 237-244 (8 amino acid residues) consists of an N-terminal extension of the VP8 sequence
Amino acid residues 245-404 (159 amino acid residues) consists of the lectin-like domain of a rotavirus VP8 protein taught by Rodrigues et al.
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have combined the teachings of Vaughn et al. and Rodrigues et al. and Wang et al. to have formulated a VLP construct comprising a PCV2 capsid with a lectin-like domain of VP8 consisting of amino acid residues 65-224 of a VP8 protein, and further including a linker. One of ordinary skill in the art would have been motivated to do so for the benefit of expressing the known lectin-like domain of VP8 consisting of amino acid residues 65-224 at the surface of the VLP, such that the resulting VLP can elicit an immune response against said rotavirus.
One of ordinary skill in the art would have had a reasonable expectation of success for introducing the sequence of Wang et al. which includes the lectin-like domain of VP8 as taught by Rodrigues et al. into the PCV2 construct of Vaughn et al. given that all of these sequences were well known in the art and the methods of VLP cloning and expression are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
See below alignment of SEQ ID NO: 7 and Wang et al.’s sequence (Qy is instant SEQ ID NO: 7 and Db is the Wang et al.’s sequence):
PNG
media_image3.png
846
899
media_image3.png
Greyscale
Regarding claims 6 and 8, as previously explained, Wang et al. teach the rotavirus VP8 amino acid sequence that shares 99.7% sequence identity to instant SEQ ID NO: 7 (see alignment of record and above). Said VP8 sequence corresponds to the sequence of an immunogenic fragment of a genotype P[7] rotavirus VP8 as evidenced by the instant Specification (page 48). Given the sequence identity, absent evidence to the contrary, the VP8 amino acid sequence taught by Wang et al. inherently represents a fragment of a genotype P[7] rotavirus VP8. See MPEP 2112.01. I. When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. 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.
Accordingly, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 10/29/2025 have been fully considered but they are not persuasive.
Applicant contends on page 9 of the Remarks submitted on 10/29/2025:
“The office action states that it would have been prima facie obvious to a person of ordinary skill in the art to have included the teachings of Wang et al.
Applicant has amended the last phrase of claim 1 to read, "wherein said heterologous protein or fragment thereof consisting of comprises an immunogenic fragment of a rotavirus VP8 protein". Applicant submits that this amendment overcomes the rejection. Accordingly, Applicant respectfully requests reconsideration and withdrawal of the rejection.
Additionally, Wang does not teach the desire or expectation of VP4 breaking down into VP8 and VP5. Furthermore, Li teaches against using VP8 alone. Therefore, Applicant submits that a skilled artisan would not have had a reasonable expectation of success by combining the references of Vaughn, Wang and Li to produce the invention described in amended instant claim 1, "a polypeptide comprising a PCV2 capsid protein linked to an immunogenic fragment consisting of a rotavirus VP8 protein", without specific guidance and the benefit of Applicant's teachings.”
In response: It is noted that a new rejection of claim 1 combining the teachings of record of Vaugh et al. and Rodrigues et al. is set forth in the present Office Action. It is acknowledged that amended claim 1 recites “wherein said heterologous protein or fragment thereof consist[s] (edit by Examiner) of an immunogenic fragment of a rotavirus VP8 protein.” As such, the amended claim requires a heterologous protein or fragment thereof of a rotavirus VP8, wherein said protein or fragment thereof excludes any other sequences. This requirement is taught by Rodrigues et al., as explained above. The sequence of Rodrigues et al. is the exact fragment of VP8 (amino acid residues 65-224) required by the claimed invention. Given that this fragment and its immunogenic role were known in the art as taught by Rodrigues et al., and that the PCV2-based VLP vector was also known (Vaughn et al.), it is herein submitted that these teachings render the claimed invention prima facie obvious. It is further noted that instant claim 8 has not been amended consistent with the amendments of claim 1, given that instant claim 8 recites the open language of “comprising” while claim 1 recited the closed language term “consists/consisting of”.
Applicant contends on page 11 of the Remarks submitted on 10/29/2025:
“Additionally, the fact that Rodrigues et al teach structural features of the rotavirus entry machinery, and that it is involved in receptor binding and attachment, does not make it obvious to create Applicant's claims 1 and 5: A polypeptide comprising a Circoviridae virus capsid protein linked to a heterologous protein or fragment thereof, wherein said heterologous protein or fragment thereof comprises an amino acid sequence comprising at least 50 amino acid residues in length, and wherein said heterologous protein or fragment thereof consists of an immunogenic fragment of a rotavirus VP8 protein . .. wherein said immunogenic fragment of a rotavirus VP8 protein is an N-terminally extended lectin-like domain of a rotavirus VP8 protein, wherein the lectin-like domain of the porcine rotavirus VP8 protein consists of the amino acid sequence of amino acid residue numbers 65-224 of the porcine rotavirus VP8 protein, and wherein the N-terminal extension is 1 to 20 amino acid residues in length.
There is no teaching or reference in each of the five combined references to create the invention as described in Applicant's amended claims 1 and 5.”
In response: As explained above in detail, all of the parts of the claimed invention as recited in claims 1-5 have been previously described. Vaught et al. teach the PCV2-based VLP vector in which any foreign protein can be expressed. Rodrigues et al. teach the exact fragment of a lectin-like domain of a rotavirus VP8 consisting of the exact amino acid residue numbers 65-224. Masuda et al. teach the N-terminal extension and linkers to facilitate for surface expression. There appears to be no elements of the claimed invention, which have not been previously described. Because all of these elements were known in the art, as well as clear motivations and instructions to combined them, it is herein submitted that the claimed invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the filing date.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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, Thomas J Visone can be reached at (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 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.
/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672