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
Acknowledgement is hereby made of receipt and entry of the communication filed on Feb. 23, 2026. Claims 1 and 5-21 are pending. Claims 11, 13-18 and 20 are withdrawn. Claims 1, 5-10, 12, 19 and 21 are currently examined.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
(Previous Rejection – Maintained and Modified Necessitated by Amendment) Claims 1, 5-10, 12 and 19 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. This rejection is extended to new claim 21.
The base claim 1, as amended, recites “wherein the ASFV protein P72, P54, P30 and CD2v, or a combination thereof is selected from one or more amino acid sequences consisting of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, and SEQ ID NO. 4; and wherein the baculovirus protein or a fragment thereof is selected from one or more amino acid sequences consisting of SEQ ID NO. 6, SEQ ID NO. 7, and SEQ ID NO. 8.” This limitation renders the claims indefinite.
SEQ ID NOs. 1 and 4 respectively specify a polypeptide containing an extra 2 amino acids “EF” to the N-terminal starting residue “M” of the P72 protein and the P32 protein of ASFV. SEQ ID NO. 2 specifies a polypeptide fragment of 183 amino acids from the ASFV P54 protein with the N-terminal 18 and C-terminal 22 amino acids truncated. SEQ ID NO. 3 specifies a polypeptide of 345 amino acids derived from the ASFV CD2v protein by truncating the N-terminal 15 amino acids.
SEQ ID NO. 6 represents the complete amino acid sequence of the major viral capsid protein of a baculovirus (e.g., VP39 of Autographa californica nucleopolyhedrovirus) lacking the N-terminal Met residue. SEQ ID NO. 7 (FMFGHVVNFVIILIVILFLY) and SEQ ID NO. 8 (CMIRNRNRQY) respectively represent the transmembrane domain and cytoplasmic domain of baculovirus gp64.
First, since the claims specify that the ASFV proteins P72, P54, P30 and CD2v are fused with a baculovirus protein or fragment thereof, SEQ ID NOs. 1 and 4 should be a portion of a fusion protein wherein the N-terminal “EF” appears to be from a fusion partner.
Secondly, it is not clear how to interpret the limitation “wherein the ASFV protein P72, P54, P30 and CD2v, or a combination thereof is selected from one or more amino acid sequences consisting of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, and SEQ ID NO. 4”. E.g., it is not clear if the recited ASFV proteins or combination thereof are to be interpreted to “comprise” or “consist of” the respective sequences; and, since the ASFV proteins are required to be fused with a baculovirus protein, it is not clear how to distinguish between the fusion protein as a whole from an ASFV protein as claimed (considering that SEQ ID NOs. 1 and 4 contain extra amino acids fused to the respective ASFV proteins).
Additionally, it is not clear how to interpret “wherein the baculovirus protein or a fragment thereof is selected from one or more amino acid sequences consisting of SEQ ID NO. 6, SEQ ID NO. 7, and SEQ ID NO. 8”. E.g., it is not clear if the claimed baculovirus protein or fragment thereof are to be interpreted to “comprise” or “consist of” the recited sequences.
To facilitate examination, the claims are interpreted as “comprising” a sequence of SEQ ID NO: 1, 2, 3, or 4 that is from the corresponding ASFV protein.
New claim 21 is directed to a fusion protein comprising an African swine fever virus (ASFV) immunogenic protein fused with an baculovirus protein or a fragment thereof, wherein the ASFV immunogenic protein consists of an amino acid sequence of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, or a combination thereof; and wherein the baculovirus protein or a fragment thereof consists of an amino acid sequence of SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, or a combination thereof.
Claim 21 recites “an amino acid sequence of SEQ ID NO……., or a combination thereof”. It is not clear if the term “an amino acid sequence” refers to the entirety of the recited sequence or sequences, or only a portion of the recited sequence(s). It is noted that any sequence of two or more amino acids can be considered as “an amino acid sequence”.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
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 of this title, 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.
(Previous Rejection – Withdrawn) Claims 1, 5-9, 12 and 19 were rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (US 2016/0331826 A1, published on Nov. 17, 2016; submitted in IDS filed on Nov. 17, 2021) in view of Argilaguet et al. (Antiviral Research 98 (2013) 61–65) and Dixon et al. (Veterinary Immunology and Immunopathology, Volume 100, Issues 3–4, August 2004, Pages 117-134), and further in view GenBank: AJB28407.1 (CD2v [African swine fever virus]. Dated Apr. 2, 2015).
(Previous Rejection – Withdrawn) Claim 10 was rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (US 2016/0331826 A1, published on Nov. 17, 2016; submitted in IDS filed on Nov. 17, 2021) in view of Argilaguet et al. (Antiviral Research 98 (2013) 61–65), Dixon et al. (Veterinary Immunology and Immunopathology, Volume 100, Issues 3–4, August 2004, Pages 117-134) and GenBank: AJB28407.1 (CD2v [African swine fever virus]. Dated Apr. 2, 2015), as applied above, further in view of Zhang et al. (Vaccine 33 (2015) 2449–2456).
The above rejections are withdrawn in view of the amendment filed on Feb. 23, 2026.
(New Rejection – Necessitated by Amendment) Claims 1, 5-9, 12, 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (US 2016/0331826 A1, published on Nov. 17, 2016; submitted in IDS filed on Nov. 17, 2021) in view of Argilaguet et al. (Antiviral Research 98 (2013) 61–65) and Dixon et al. (Veterinary Immunology and Immunopathology, Volume 100, Issues 3–4, August 2004, Pages 117-134), and GenBank: AJB28407.1 (CD2v [African swine fever virus]. Dated Apr. 2, 2015), as applied in the withdrawn rejections above, and further in view of NCBI Reference Sequence: NP_054158.1 (major budded virus envelope glycoprotein [Autographa californica nucleopolyhedrovirus]. Dated Aug. 13, 2018).
Base claim 1, as amended, is directed to a recombinant baculovirus having at least one of African swine fever virus (ASFV) proteins P72, P54, P30 and CD2v, or a combination thereof, wherein the ASFV protein P72, P54, P30 and CD2v, or a combination thereof is fused with a baculovirus protein or a fragment thereof; wherein the ASFV protein is displayed on a surface of the recombinant baculovirus; wherein the ASFV protein P72, P54, P30 and CD2v, or a combination thereof is selected from one or more amino acid sequences consisting of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, and SEQ ID NO. 4; and wherein the baculovirus protein or a fragment thereof is selected from one or more amino acid sequences consisting of SEQ ID NO. 6, SEQ ID NO. 7, and SEQ ID NO. 8.
Claim 21 is directed to a fusion protein comprising an African swine fever virus (ASFV) immunogenic protein fused with an baculovirus protein or a fragment thereof, wherein the ASFV immunogenic protein consists of an amino acid sequence of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, or a combination thereof; and wherein the baculovirus protein or a fragment thereof consists of an amino acid sequence of SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, or a combination thereof.
Chang teaches a recombinant baculovirus displaying on its envelope a fusion protein. The fusion protein comprises a heterologous antigen, and a C-terminal region of baculovirus envelope GP64 protein, which has at least 100 amino acid residues in length and lacks a B12D5 binding epitope located within the central basic region of the GP64 protein. The genome of the recombinant baculovirus comprises a transgene encoding a fusion protein that comprises a signal peptide, the heterologous antigen, and the C-terminal region of the baculovirus envelope GP64 protein, in which the antigen is located between the signal peptide and the C-terminal region of the GP64 protein. Methods for eliciting an antigen-specific immunogenic response in a subject in need thereof are also disclosed. See Abstract. Chang further teaches that the heterologous antigen included in the fusion protein can be many different proteins, including antigens of pathogens (e.g., various viruses) or host proteins (e.g., PD-1 or tumor-associated antigens). See [0022], [0041], [0042] and [0043].
Fig. 2 of Chang shows different versions of antigen-GP64 fusion protein constructs. Fig. 2D shows a fusion protein construct with a heterologous antigen peptide fused to the GP64 TM/CTD at the C-terminus (the TM/CTD corresponds to the SEQ ID NO.7 + SEQ ID NO. 8).
PNG
media_image1.png
592
1116
media_image1.png
Greyscale
Accordingly, Chang teaches a recombinant baculovirus expressing a fusion protein comprising a heterologous polypeptide fused to a baculovirus protein, such as baculovirus GP64, including fusion to the GP64 C-terminal TM/CTD domain. However, it is silent on the heterologous part of the fusion protein being ASFV proteins P72, P49, PE120R, P54, P30 or CD2v; Chang is silent on amino acid sequences of the involved ASFV and baculovirus proteins included in the fusion proteins.
Argilaguet teaches that the authors have constructed BacMam-sHAPQ, a baculovirus based vector for gene transfer into mammalian cells, expressing a fusion protein comprising three in tandem ASFV antigens: p54, p30 and the extracellular domain of the viral hemagglutinin (secretory hemagglutinin, sHA), under the control of the human cytomegalovirus immediate early promoter (CMVie). BacMam-sHAPQ induced specific T-cell responses directly after in vivo immunization. The protective potential of this recombinant vaccine candidate was tested by a homologous sublethal challenge with ASFV following immunization. Four out of six immunized pigs remained viremia-free after ASFV infection. Their results point towards BacMam vectors as potential tools for future vaccine development. See Abstract.
Dixon reviews African swine fever virus proteins involved in evading host defence systems. This review focuses on recent progress made in understanding the function of ASFV-encoded proteins, which are involved in modulating the host response to infection. One potent immunomodulatory protein, A238L, inhibits both activation of the host NFkB transcription factor and inhibits calcineurin phosphatase activity. Calcineurin-dependent pathways, including activation of the NFAT transcription factor, are therefore inhibited. Another ASFV-encoded protein, CD2v, resembles the host CD2 protein, which is expressed on T cells and NK cells. This virus protein causes the adsorption of red blood cells around virus-infected cells and extracellular virus particles. Expression of the CD2v protein aids virus dissemination in pigs and the protein also has a role in impairing bystander lymphocyte function. This may be mediated either by a direct interaction of CD2v extracellular domain with ligands on lymphocytes or by an indirect mechanism involving interaction of the CD2v cytoplasmic tail with host proteins involved in signalling or trafficking pathways. Two ASFV proteins, an IAP and a Bcl2 homologue, inhibit apoptosis in infected cells and thus facilitate production of progeny virions. The prediction is that half to two-thirds of the approximately 150 genes encoded by ASFV are not essential for replication in cells but have an important role for virus survival and transmission in its hosts. These genes provide an untapped repository, and will be valuable tools for deciphering not only how the virus manipulates the host response to infection to avoid elimination, but also useful for understanding important host anti-viral mechanisms. In addition, they may provide leads for discovery of novel immunomodulatory drugs. See Abstract.
Accordingly, teachings of Argilaguet and Dixon indicate that ASFV antigens p54, p30 and CD2v, among others, are studied as targets for antiviral or immunomodulatory treatment at the time of filing of the instant application and ASFV proteins can be made on a baculovirus platform.
GenBank: AJB28407.1 discloses the amino acid sequence of the CD2v protein of an African swine fever virus isolate, comprising the instant SEQ ID NO: 3.
NCBI Reference Sequence: NP_054158.1 discloses the amino acid sequence of major budded virus envelope glycoprotein, GP64, of Autographa californica nucleopolyhedrovirus, a baculovirus strain. This protein comprises instant SEQ ID NOs. 7 and 8 at the C-terminus.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invetion to substitute the heterologous antigen peptides in the baculovirus fusion proteins with an ASFV protein (P54, P30, HA, or CD2v, etc.) disclosed in Argilaguet and/or Dixon, to construct a recombinant baculovirus-based vaccine candidate against ASFV. There is a reasonable expectation of success that such a recombinant baculovirus construct can be made and a reasonable immune protection effect can be achieved based on the teachings of Chang Argilaguet and Dixon.
As to the claimed sequences, teachings of GenBank: AJB28407.1 and NCBI Reference Sequence: NP_054158.1 indicate that a ASFV CD2v comprising SEQ ID NO: 3 and a baculovirus GP64 comprising SEQ ID NOs. 7 and 8 are known at the time of invention. One of skill in the art would have found it obvious to express the CD2v protein disclosed in GenBank: AJB28407.1 on the baculovirus platform of Chang and NCBI Reference Sequence: NP_054158.1, for the study of the ASFV CD2v expressed thereby, just as other heterologous proteins expressed thereby.
(Previous Rejection – Maintained) Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (US 2016/0331826 A1, published on Nov. 17, 2016; submitted in IDS filed on Nov. 17, 2021) in view of Argilaguet et al. (Antiviral Research 98 (2013) 61–65), Dixon et al. (Veterinary Immunology and Immunopathology, Volume 100, Issues 3–4, August 2004, Pages 117-134), GenBank: AJB28407.1 (CD2v [African swine fever virus]. Dated Apr. 2, 2015) and Zhang et al. (Vaccine 33 (2015) 2449–2456), as applied in the withdrawn rejections above, and further in view of NCBI Reference Sequence: NP_054158.1 (major budded virus envelope glycoprotein [Autographa californica nucleopolyhedrovirus]. Dated Aug. 13, 2018).
Claim 10 specifies that the adjuvant in claim 9 is a recombinant baculovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF), chemokine C-C motif ligand 25 (CCL25) or chemokine C-C motif ligand 29 (CCL29).
Relevance of Chang, Argilaguet, Dixon, GenBank: AJB28407.1 and NCBI Reference Sequence: NP_054158.1 is set forth above. However, they are silent on using an adjuvant as claimed.
Zhang teaches that GM-CSF is an immune adjuvant that enhances responses to vaccines. In this study, recombinant baculoviruses Ac-Cap and Ac-Cap-GM-CSF expressing the Cap protein alone and co-expressing the Capprotein and porcine GM-CSF, respectively, were constructed successfully and tested for induction of immune response and protection efficacies. See Abstract. Accordingly, teachings of Zhang indicate the immune stimulating adjuvant effect of GM-CSF and construction of a recombinant baculovirus expressing GM-CSF for use as an adjuvant.
It would have been prima facie obvious for one of ordinary skill in the art at the time of filing to introduce GM-CSF taught in Zhang into the studies suggested by Chang, Argilaguet, Dixon, GenBank: AJB28407.1 and NCBI Reference Sequence: NP_054158.1 to evaluate the adjuvant effect of GM-CSF in the vaccine platforms used in Chang and Argilaguet.
Response to Applicant’s arguments
Applicant’s arguments filed on Feb. 23, 2026 have been fully considered, Arguments regarding withdrawn rejections are moot. Applicant’s arguments regarding the current rejections are addressed as follows.
To the 112(b) rejection, Applicant argues that the amended claim 1 explicitly defines the sequences of the ASFV proteins P72, P54, P30 and CD2v claimed in the present application with the term “consisting of” as suggested by the examiner, and thus a person skilled in the art can readily infer and understand the structure of the fusion protein containing the specific ASFV protein amino acid sequences claimed in the present application.
Applicant’s attention is directed to the current modified 112(b) rejection for response to the above argument.
To the 103 obviousness rejection, Applicant argues that the present application is directed to a specific fusion protein structure containing specific ASFV protein amino acid sequences and specific baculovirus protein amino acid sequences, and a recombinant baculovirus comprising the aforementioned specific fusion protein structure. Applicant argues that none of Chang, Argilaguet, Dixon and GenBank: AJB28407.1 mentions the combination of specific ASFV protein amino acid sequences and specific baculovirus protein amino acid sequences suitable for expression on the baculovirus surface, and that a person skilled in the art understands that the amino acid sequence of the ASFV protein and the baculovirus protein directly affect the conformation of their fusion protein, which in turn governs whether the ASFV fusion protein can be successfully displayed on the surface of the recombinant baculovirus, as well as the immunogenicity of the displayed ASFV fusion protein.
Applicant’s arguments are not persuasive. By reciting “the ASFV protein P72, P54, P30 and CD2v, or combination thereof” and “baculovirus protein or a fragment thereof is selected from one or more amino acid sequences consisting of SEQ ID NO. 6, SEQ ID NO. 7, and SEQ ID NO. 8”, the claims are not limited to fusion proteins with clearly specified structures. Therefore, there is no evidence that the fusion protein as claimed is better than a fusion protein between a random selection of ASFV antigen sequences and baculovirus GP64 (related to SEQ ID NOs. 7-8) or VP39 (related to SEQ ID NO. 6) sequences, especially when the sequences of the recited ASFV and baculovirus proteins are known in the art.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. 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.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671