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 .
Applicant’s response has ameliorated the rejection under 35 USC § 101 and the rejection under 35 USC § 112(b) for claims 10-12.
Information Disclosure Statement
Page 14 of applicant’s reply states:
“Enclosed herewith please find the English translation of the Publication Text of the Chinese Application No. 201910069838.9 and adds a preparation method of the claims 3-8 of Application No. 201910069838.9 as follows to the specification of the present invention in order to meet the provision of 37 CFR 1.57(g).”
However, the listing of references in applicant’s reply is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The amendment filed January 26, 2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows:
Newly submitted paragraph [0028] references the contents of Chinese Application No. 201910069838.9 (recited in originally submitted paragraph [0027]) and steps to prepare the ASFV CD2V subunit protein. Applicant states that the added material contains no new matter, in compliance with 37 C.F.R. § 1.57(g). However, paragraph [0028] recites at least “SEQ ID NO: 1” and “SEQ ID NO: 3”. Paragraph [0036] also recites “SEQ ID NO: 3”. There is no support for specific sequences in the instant disclosure at the time of filing.
Newly submitted paragraphs [0031-0035] refer to Chinese Application No. 20231 0889130.4 and Chinese Application No. 202110524701.5 and incorporate the contents therein. On page 15 of applicant’s reply, applicant notes that the filing date of 202310889130.4 and 202110524701.5 are both May 13, 2021, which is after July 15, 2020, which is the earliest filing date the instant application claims benefit and priority to (quote below from page 1 of the instant disclosure, relevant sections underlined for convenience):
CROSS-REFERENCE TO RELATED APPLICAITONS
[0001] This application is a national stage application of the Patent Cooperation Treaty (PCT) international application titled "Subunit Vaccine Composition For African Swine Fever, And Preparation Therefor And Use Thereof', international application number PCT/CN2021/106375, filed in the China National Intellectual Property Administration (CNIPA) on July 15, 2021. PCT international application number PCT/CN2021/106375 claims priority to and benefit of Chinese Patent Application No. 202010683211.5, filed on July 15, 2020, and Chinese Patent Application No. 202110752873.8, filed on July 02, 2021. The specifications of the above referenced patent applications are incorporated herein by reference in their entirety.
Neither of these applications, Chinese Application No. 20231 0889130.4, Chinese Application No. 202110524701.5, or their contents, were recited or mentioned in the instant disclosure at the time of filing. Therefore, this newly added content incorporates new matter into the instant disclosure.
Applicant is required to cancel the new matter in the reply to this Office Action.
Since the amended specification submitted January 26, 2026 has not been entered, the use of the terms “Montanide GEL 01 PR”, “ISA 206 VG”, and “ISA 201 VG”, which are a trade names or marks used in commerce, are still present in this application, see paragraph [0015] of the instant published disclosure, USPgPub 2023/0265129, of record. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Applicant is required to provide proper annotation to each trade name or mark in the instant application.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8, 12-14, and 16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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.
Claims 8 and 12 contain the trademark/trade name “ISA 201 VG”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph (emphasis underlined). See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an adjuvant and, accordingly, the identification/description is indefinite. This rejection also affects dependent claims 13 and 14.
In response to the rejection, applicant states that claims 8 and 12 have been amended to replace the trademark/trade name "ISA 201 VG" with the generic term "water-in-oil-in-water (W/O/W) emulsion adjuvant."
Applicant’s response is unpersuasive because the amended phrase, "water-in-oil-in-water (W/O/W) emulsion adjuvant", is not recited in claims 8 and 12. Recitation of the phrase in claims 8 and 12 would overcome this rejection.
Claim 16 recites the limitation "the immunopotentiator" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether an immunopotentiator is required in claim 1, from which claim 16 depends, or not.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-14, and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 is drawn to an African Swine Fever Virus (ASFV) subunit vaccine comprising a glycosylated CD2V expressed in a eukaryotic system, a trimeric p72, and pharmaceutically acceptable adjuvant. There is no guidance provided for these claimed components functioning as an effective vaccine. Tables 2 and 3 and paragraph [0041] of the instant published disclosure, USPgPub 2023/0265129 (of record), discuss efficacy of “vaccine 3” and “vaccine 4” formulations comprising CD2v and p72 trimer content of 40% and 71.79%, respectively. While the efficacy data of “vaccine 3” and “vaccine 4” formulations is encouraging, it is not clear what is administered or whether protective efficacy would be predicted by the skilled artisan (discussed below).
Regarding the trimeric forms of p72 recited in the claims, Cui et al. (ACS Infectious Diseases. 2025 Jul 9;11(8):2104-15, of record) discuss difficulty in forming trimeric forms of p72 due to susceptibility to misfolding and dependence on specific post-translational modifications. At the bottom of the page under “Main”, Cui et al. state “previous attempts to utilize recombinant P72 in subunit vaccine development have been hindered by its tendency to form monomers rather than the more immunogenic native trimers and the requirement for chaperone pB602L for folding.” Cui et al. also discusses poor immunogenicity due to improper folding in the Discussion section. In the paragraph above “Methods and Materials”, Cui et al. admits it is not known whether neutralizing antibodies are induced against membrane-bound, secreted, and intracellular forms of P72 and immunogenicity was not assessed.
The instant specification fails to describe how to make the requisite subunit components. Paragraph [0026] of the instant published disclosure, USPgPub 2023/0265129, states:
[0026] 1.1 Refer to the preparation method of African swine fever exterior envelope subunit protein CD2V of Application No. 201910004596.5 or 201910069838.9 of the applicant, or the preparation method of the exterior envelope subunit protein CD2V derived from African swine fever virus of other patents or documents (prokaryotic expression system expression, such as CHO, 293T cells, etc.).
Paragraph [0027] of the instant published disclosure states:
[0027] 1.2 Reference document is Structure of the African swine fever virus major capsid protein written by Liu Q, Ma B, Qian N, et al., p72. Cell Res. 2019; 29 (11): 953-955. Or other protein expression modes (such as the eukaryotic expression system, the insect baculovirus expression system, the CHO cell expression system, etc). Or the preparation method of African swine fever virus subunit protein p72 of other patents or documents. The content of the trimer reaches more than 40%.
It is not evident how the content of the trimer reaches more than 40%, as recited in instant claims 1 and 12. In the first paragraph, Liu et al. (Cell Res. 2019; 29 (11): 953-955, of record) teach the “major capsid protein (MCP) p72 is the most dominant structural component of the virion and constitutes about ~31%–33% of the total mass of the virion.”
Paragraph [0027] further describes peaks depicted in Figure 1. Peak 4 is attributed to the p72 protein trimer because its molecular weight is between 158 kDa and 440 kDa. However, there is no data provided for p72 trimer configuration. Cui et al. supra teach SDS-PAGE analysis under non-reducing conditions revealed a band approximately 240 kDa (Fig. 1G), trimer formation. The range in molecular weight between 158 kDa and 440 kDa, attributed to Peak 4 in paragraph [0027] does not possess specificity for identifying the trimeric form of p72.
The skilled artisan would not predict a formulation comprising glycosylated CD2v expressed in a eukaryotic system, a trimeric p72, and pharmaceutically acceptable adjuvant would be effective as an ASFV vaccine, as asserted by claims 1, 3-14, and 16.
Because the instant CD2v protein is glycosylated and expressed in a eukaryotic system, viral vectored-derived proteins combined in a cocktail formulation appear to be within the scope of the instant claims. Lopera-Madrid et al. (Veterinary Immunology and Immunopathology. 2017; 185: 20-33) teach priming with (eukaryotic) human embryonic kidney 293 (HEK)-purified antigens: p72, p54, and p12 and boosting with three MVA-vectored antigens: p72, EP153R, and CD2v in the abstract, section 2.6. Therefore, the formulation of Lopera-Madrid et al. exposes pigs to more p72 than any other antigen in the formulation, similar to the “content of the trimeric protein is not less than 40% of the total amount of the exterior envelope subunit protein p72 derived from African swine fever virus”, instantly claimed. However pigs that were administered MVA-ASFV construct cocktails failed to generate detectable ASFV antibody responses, but T-cell proliferative and IFN-γ T-cell responses were detected following HEK-ASFV antigen boost. While the cytotoxic immune response taught by Lopera-Madrid et al. is encouraging, immune determinants for ASFV protection have not been elucidated, see section 4 of Gaudreault et al. (Vaccines. 2019 Jun 25; 7 (2): 56, of record).
In section 3.1, Gaudreault et al. teach CD2v is not a strong immunogenic antigen, and high doses of the protein would likely be required to induce good protection. It is unclear whether the quantity ranges recited in instant claims 4-6, 12, and 13 would be sufficient. In Table 1, Gaudreault et al. teach baculovirus-expressed proteins, including p72, combined with Freund’s adjuvant resulted in a slight delay of clinical disease and viremia, but no protection.
Neilan et al. (Virology. 2004; 319: 337– 342, of record) teach neutralizing antibodies to ASFV p72 does not provide protection.
Cadenas-Fernández et al. (Pathogens. 2020 Feb 28; 9 (3): 171, of record) teach an adenovirus-vectored ASFV cocktail of thirty-five ASFV antigens, including p72 and a modified CD2v (EP402R∆PRR), failed to elicit protective efficacy, required of a vaccine, see the abstract, sections 2.2, 3.2, and 3.3.
Lokhandwala et al. (Veterinary Microbiology. 2019; 235: 10-20, of record) teach a nine-ASFV-antigen cocktail including p72 and a modified CD2v antigen, EP402RΔPRR administered prior to challenge, see section 2.4.2. When Lokhandwala et al. formulated the cocktail in BioMize adjuvant, strong IgG responses were induced, but when challenged, the vaccinees had more severe reaction relative to the controls. In the abstract, Lokhandwala et al. teach a “seven antigen cocktail-(II) was evaluated using two adjuvants: BioMize and ZTS-01. The BioMize formulation induced stronger antibody responses, but 8/10 vaccinees and 4/5 controls succumbed to the disease or reached experimental endpoint at 17 days post-challenge. In contrast, the ZTS-01 formulation induced weaker antibody responses, but 4/9 pigs succumbed to the disease while the 5 survivors exhibited low clinical scores and no viremia at 17 days post-challenge, whereas 4/5 controls succumbed to the disease or reached experimental endpoint. Overall, none
of the immunogens conferred statistically significant protection.” See sections 3.2 and 3.3. Therefore, the skilled artisan would not conclude that any adjuvant, encompassed by instant claims 1, 3-7, 9-11, and 16, would be efficacious. Above “Author contributions”, Lokhandwala et al. conclude “evidence of disease enhancement in vaccinees was observed with both Ad-ASFV cocktail-I and cocktail-II when formulated with the BioMize adjuvant, but not with cocktail-II when formulated with the ZTS-01 adjuvant. The cocktail-II-ZTS vaccinees had better survival rate, but clinical disease was not prevented”.
Regarding the requisite adjuvant recited in claims 8 and 12, section 3.2.1 of Wu et al. (Pathogens. 2024; 13: 706, of record) teach a recombinant adenovirus mixture containing 42 multiepitope ASFV 42 antigens combined with Montanide ISA-201™ adjuvant induced a humoral immune response, but no protective effect was observed after challenge. Another study combined an inactivated ASFV by gamma-irradiation combined with Montanide™ ISA 201 VG adjuvant. While all animals developed antibodies against ASFV p72, the immune response was insufficient to confer protection from ASFV strain attacks.
The state of the art indicates that African swine fever (ASF) is a viral disease of domestic and wild swine for which there is currently no vaccine or treatment available. For these reasons, it is determined that an undue quantity of experimentation would be required of the skilled artisan to make and use the invention claimed.
Response to Arguments
In reply to the rejection of record, applicant points to Examples 3.2 and 3.3 and Table 3 and Table 4, which show the trimer content of p72 is crucial to the final protection effects. The immunization of combination of CD2V and p72 with the trimer content of not less than 40% of the total content of p72 can provide 60% protection.
Applicant’s arguments and review of the Examples and data have been fully considered, but are found unpersuasive. Table 4 is not present in the instant specification and it’s data cannot be analyzed. While the efficacy data of instant “vaccine 3” and “vaccine 4” formulations is encouraging, it is not clear what is administered or whether protective efficacy would be predicted by the skilled artisan. . The instant specification fails to describe how to make the requisite subunit components.
Cui et al. (ACS Infectious Diseases. 2025 Jul 9;11(8):2104-15, of record) discuss difficulty in forming trimeric forms of p72 due to susceptibility to misfolding and dependence on specific post-translational modifications. At the bottom of the page under “Main”, Cui et al. state “previous attempts to utilize recombinant P72 in subunit vaccine development have been hindered by its tendency to form monomers rather than the more immunogenic native trimers and the requirement for chaperone pB602L for folding.” Cui et al. also discusses poor immunogenicity due to improper folding in the Discussion section. In the paragraph above “Methods and Materials”, Cui et al. admits it is not known whether neutralizing antibodies are induced against membrane-bound, secreted, and intracellular forms of P72 and immunogenicity was not assessed.
Cui et al. teach SDS-PAGE analysis under non-reducing conditions revealed a band approximately 240 kDa (Fig. 1G), trimer formation. The range in molecular weight between 158 kDa and 440 kDa, attributed to Peak 4 in paragraph [0027] does not possess specificity for identifying the trimeric form of p72.
Lopera-Madrid et al. (Veterinary Immunology and Immunopathology. 2017; 185: 20-33) expose pigs to more p72 than any other antigen in the formulation, similar to the “content of the trimeric protein is not less than 40% of the total amount of the exterior envelope subunit protein p72 derived from African swine fever virus”, instantly claimed. However pigs that were administered MVA-ASFV construct cocktails failed to generate detectable ASFV antibody responses, but T-cell proliferative and IFN-γ T-cell responses were detected following HEK-ASFV antigen boost. While the cytotoxic immune response taught by Lopera-Madrid et al. is encouraging, immune determinants for ASFV protection have not been elucidated, see section 4 of Gaudreault et al. (Vaccines. 2019 Jun 25; 7 (2): 56, of record).
In section 3.1, Gaudreault et al. teach CD2v is not a strong immunogenic antigen, and high doses of the protein would likely be required to induce good protection. It is unclear whether the quantity ranges recited in instant claims 4-6, 12, and 13 would be sufficient. In Table 1, Gaudreault et al. teach baculovirus-expressed proteins, including p72, combined with Freund’s adjuvant resulted in a slight delay of clinical disease and viremia, but no protection.
Neilan et al. (Virology. 2004; 319: 337– 342, of record) teach neutralizing antibodies to ASFV p72 does not provide protection.
Cadenas-Fernández et al. (Pathogens. 2020 Feb 28; 9 (3): 171, of record) teach an adenovirus-vectored ASFV cocktail of thirty-five ASFV antigens, including p72 and a modified CD2v (EP402R∆PRR), failed to elicit protective efficacy, required of a vaccine, see the abstract, sections 2.2, 3.2, and 3.3.
Lokhandwala et al. (Veterinary Microbiology. 2019; 235: 10-20, of record) teach a nine-ASFV-antigen cocktail including p72 and a modified CD2v antigen, EP402RΔPRR administered prior to challenge, see section 2.4.2. When Lokhandwala et al. formulated the cocktail in BioMize adjuvant, strong IgG responses were induced, but when challenged, the vaccinees had more severe reaction relative to the controls. In the abstract, Lokhandwala et al. teach a “seven antigen cocktail-(II) was evaluated using two adjuvants: BioMize and ZTS-01. The BioMize formulation induced stronger antibody responses, but 8/10 vaccinees and 4/5 controls succumbed to the disease or reached experimental endpoint at 17 days post-challenge. In contrast, the ZTS-01 formulation induced weaker antibody responses, but 4/9 pigs succumbed to the disease while the 5 survivors exhibited low clinical scores and no viremia at 17 days post-challenge, whereas 4/5 controls succumbed to the disease or reached experimental endpoint. Overall, none
of the immunogens conferred statistically significant protection.” See sections 3.2 and 3.3. Therefore, the skilled artisan would not conclude that any adjuvant, encompassed by instant claims 1, 3-7, 9-11, and 16, would be efficacious. Above “Author contributions”, Lokhandwala et al. conclude “evidence of disease enhancement in vaccinees was observed with both Ad-ASFV cocktail-I and cocktail-II when formulated with the BioMize adjuvant, but not with cocktail-II when formulated with the ZTS-01 adjuvant. The cocktail-II-ZTS vaccinees had better survival rate, but clinical disease was not prevented”.
Section 3.2.1 of Wu et al. (Pathogens. 2024; 13: 706, of record) teach a recombinant adenovirus mixture containing 42 multiepitope ASFV 42 antigens combined with Montanide ISA-201™ adjuvant induced a humoral immune response, but no protective effect was observed after challenge. Another study combined an inactivated ASFV by gamma-irradiation combined with Montanide™ ISA 201 VG adjuvant. While all animals developed antibodies against ASFV p72, the immune response was insufficient to confer protection from ASFV strain attacks.
The state of the art indicates that African swine fever (ASF) is a viral disease of domestic and wild swine for which there is currently no vaccine or treatment available. For these reasons, it is determined that an undue quantity of experimentation would be required of the skilled artisan to make and use the invention claimed.
Regarding methods of making CD2V subunit protein, applicant points to the contents of Chinese Application No. 201910069838.9. Regarding preparing trimer reaching more than 40% applicant points to Chinese Application No.202310889130.4 and No. 202110524701.5, wherein application No.202310889130.4, both filed May 13, 2021.
However, both Chinese Application No.202310889130.4 and No. 202110524701.5 are filed after July 15, 2020, which is the earliest filing date the instant application claims benefit and priority to. These applications do not provide support in the instant disclosure for preparing p72 trimer reaching more than 40%.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 SHANON A FOLEY whose telephone number is (571)272-0898. The examiner can normally be reached M-F, generally 5:30 AM-5 PM, flexible.
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/Shanon A. Foley/ Primary Examiner, Art Unit 1671
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