DETAILED ACTION
Withdrawal of Finality of Last Office Action
Applicant's request for reconsideration of the finality of the rejection of the last Office action is persuasive and, therefore, the finality of that action is withdrawn.
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 .
Response to Amendment/Disposition of Claims
Applicant’s Amendment filed on 12 February 2026 has been received and entered. Claims 1-14 and 16-21 were pending. Claims 1-2, 8, 13-14, 16, and 19 have been amended. Claims 15, 17-18, and 20 have been cancelled. No new claims have been added.
Accordingly, Claims 1-14, 16, 19, and 21 are currently pending and will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2023/0174996 A1, Published 08 June 2023. Applicant’s amended Specifications as presented on 12 February 2026, 10 October 2025, 12 January 2023, and 14 June 2022 are acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Response to Arguments
Applicant's arguments filed 12 February 2026 regarding the previous Office action dated 13 November 2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Specification; Sequence Disclosure Requirements
(New Objection) – This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below or on the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures.
The specification is objected to for reference a GenBank Accession Number, specifically NC_006499, rather than a sequence set forth in the specification. GenBank Accession Nos. are subject to change. This constitutes an improper incorporation by reference, since the information required to describe and enable the required sequences is found in the NCBI database, extraneous to the application. Furthermore, since NCBI sequences are not irrevocably fixed but are corrected and updated as additional sequence information becomes available, NCBI accession numbers may refer to sequences which change after the application filing date. Thus, the disclosure is objected to for this improper incorporation by reference.
Applicants must comply with sequence rules in order to be considered a complete response to this Office Action.
Claim Objections
(Objection withdrawn) – The objection to Claims 1 and 14 for containing minor informalities and Claim 13 for containing an undefined abbreviation is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
(Rejection withdrawn) – The rejection of Claims 17-18 and 20, and dependent claim 18 thereof, under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of the claims.
(New Rejection) – Claims 1, and dependent claims 2-14, 16, 19, and 21 thereof, 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.
Regarding Claim 1, it recites the limitation of “A reassorted Infection salmon anemia (ISA) virus comprising Genome segments 1-8. It is unclear what the term “reassorted” means in the present context with respect to genome segments 1-8. This term is not further elaborated on in the claim set and there is no definition provided in the instant Specification. The lack of a clear definition of this term renders the claim structurally indefinite. The accepted meaning of reassorted is making new combinations of materials, such as genetic materials. Page 7 of the specification teaches a genomic organization of ISA virus, labeling the protein encoded by each segment. However, a reassorted variant need not have these proteins encoded by these segments. For example, segment 1, the first segment, may encode HE instead of PB2 in a reorganized, recombined, and thus reassorted virus. Therefore, in every instance of the claims where a segment is referred to by number, such segment is indefinite as it is neither clear what it encodes nor its position (e.g. first, second, etc.) in the new genome. It is suggested that the claim be amended by clearly defining what this term means in the present context, as long as said definition is supported by the originally-filed disclosure, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 1 is rejected on the grounds of being indefinite. Claims 2-14, 16, 19, and 21 are also rejected since they depend upon Claim 1, but do not remedy the deficiencies of Claim 1.
(New Rejection) – Claim 13 is 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.
Regarding Claim 13, it recites the limitation “wherein the culture host is a CHSE-214 (Chinook salmon embryo) cell”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 13 recites the broad recitation “Chinook salmon embryo cell”, and the claim also recites “CHSE-214 cell”, which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Additionally, it is unclear if the recited element within parentheses (See e.g. "(Chinook salmon embryo)") is a required element of the claim. It is suggested that the Applicant amend the claim to move “-214” to after “embryo)”.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 13 is rejected on the grounds of being indefinite.
(New Rejection) – Claim 13 is 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.
Regarding Claim 13, it recites the limitation “wherein the culture host is a CHSE-214 (Chinook salmon embryo) cell”. According to Applicant, this cell line refers to one derived from Chinook salmon, which is known as Oncorhynchus tshawytscha. It seems, however, that the source of the cell line is incorrect. According to the results of a Google search performed by the Examiner, this cell line is now called CHSE/F, not CHSE-214, and it was derived from the Common bluegill, Lepomis macrochirus (see attached documents). In light of this information, it is no longer clear what cell line is being recited by Applicant. This lack of clarity renders the claim indefinite. It is suggested that the claim be amended to clarify which cell line is being recited, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 13 is rejected on the grounds of being indefinite.
(New Rejection) – Claims 16 and 19 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.
Regarding Claims 16 and 19, they each recite the limitation “wherein the genome segment 6 is of Genotype II when the sequence of an amplicon obtained by the forward primer of SEQ ID NO: 10 and the reverse primer SEQ ID NO: 11 has at least 90% sequence identity with the genome segment 6 of NC_006499”. The use of the phrase “NC_006499” renders the claims indefinite. Since the NCBI sequences are not irrevocably fixed but are corrected and updated as additional sequence information becomes available, the NCBI accession numbers may refer to sequences which change after the application filing date. Indeed, the current NCBI reference sequence is NC_006499.1, not the genus represented by the reference in the claims. Thus, this improper incorporation by reference renders the claims above indefinite.
Furthermore, essential material, such as that which provides written description or enablement, should not come from NPLs. See 37 CFR 1.57d.
Appropriate correction is required.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim Rejections - 35 USC § 112(a); First Paragraph
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.
(New Rejection) – Claims 16 and 19 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a reassorted Infectious salmon anemia (ISA) virus comprising Genome segments 1-8. wherein at least one genome segment is from Genotype I and at least one genome segment is from Genotype II, and wherein genome segment 6 is of Genotype II, wherein the genome segment 6 is of Genotype II when the sequence of an amplicon obtained by the forward primer of SEQ ID NO: 10 and the reverse primer SEQ ID NO: 11 has at least 90% sequence identity with the genome segment 6 of NC_006499 and a method of producing the reassorted ISA virus of claim 1 comprising the steps of: (i) infecting a culture host with an ISA virus strain of genotype I and an ISA virus strain of Genotype II; (ii) culturing the culture host in order to produce the reassorted ISA virus; and (iii) determining whether the reassorted ISA virus has a genome segment 6 of Genotype II present and at least one other genome segment of Genotype I, wherein genome segment 6 is of Genotype II when the sequence of an amplicon obtained by the forward primer of SEQ ID NO: 10 and the reverse primer SEQ ID NO: 11 has at least 90% sequence identity with the genome segment 6 of NC_006499. The claim limitation does not require that the sequence of an amplicon with at least 90% sequence identity to genome segment 6 corresponding to NC_006499 possess any particular distinguishing features or conserved regions, only that it is an amplicon with at least 90% sequence identity to the reference sequence, which encompasses any and all sequences which meet this limitation. It is the examiner's position that the disclosure of the instant application does not convey applicant' s possession of the claimed genus of an amplicon with at least 90% sequence identity to genome segment 6 corresponding to NC_006499.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings or structural chemical formulas, or by disclosure of relevant, identifying characteristics, i.e., complete/partial structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, by predictability in the art, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
In Regents of the University of California v. Eli Lilly and Co. 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997), the Court decided that adequate written description of genetic material '"requires a precise definition, such as by structure, formula, chemical name, or physical properties,' not a mere wish or plan for obtaining the claimed chemical invention." Id. 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter of the claim. Id. 43 USPQ2d at 1406. A description of what the genetic material does, rather than of what it is, does not suffice, ld. While the instant claims are drawn to nucleic acids, the cited case law is relevant because there is limited disclosure of the shared characteristics of the genus of an "amplicon with at least 90% sequence identity to genome segment 6 corresponding to NC_006499” aside from the percent identity cutoff.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus. Regents of the University of California v. Eli Lilly& Co., 199 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly & Co., the court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. A "representative number of species" means that the species that are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. MPEP §2163 II.A.3a.ii. Further, even in cases were multiple species with in a claimed genus have been disclosed, such does not necessarily demonstrate possession of the genus. See, In re Smyth, 178 U.S.P.Q. 279 at 284-85 (CCPA 1973) (stating "where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus or combination claimed at a later date in the prosecution of a patent application."); and University of California v. Eli Lilly and Co., 43 USPQ2d 1398, at 1405 (Fed Cir 1997)(citing Smyth for support). Where there is uncertainty in the operability of undisclosed embodiments, an application may be found not to have provided adequate descriptive support for a claimed genus.
The specification discloses the reduction to practice of only species with, presumably, 100% sequence identity to the reference sequence (Paragraphs 0111-0135; Tables 3-5) within the claimed genus. While Applicant identifies the use of primers for amplifying segment 6 from more than 200 clones, only 4 were further analyzed in the instant Specification. Of those, three of the four had a Genotype II segment 6, but no percent identity relative to NC_006499 is provided. As such, it is unclear if these clones had percent identities closer to 90% or closer to 100% when compared to the reference sequence. Consequently, there is no information about how far above the percent identity cutoff these species were. No other species are mentioned beyond the 200 clones which were isolated and it is unclear how many of these actually met the 90% cutoff.
In summary, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genus of all amplicons with at least 90% sequence identity to the genome segment 6 corresponding to NC_006499 based on the disclosure of the instant application. In conclusion, the specification fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph, with respect to claims 16 and 19.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (page 1115).
(New Rejection) – Claim 21 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for vaccinating Atlantic Salmon against ISA virus, does not reasonably provide enablement for vaccinating just any fish against ISA virus. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to a reassorted Infectious salmon anemia (ISA) virus comprising Genome segments 1-8. wherein at least one genome segment is from Genotype I and at least one genome segment is from Genotype II, and wherein genome segment 6 is of Genotype II, and a method of vaccinating a fish against an ISA virus, comprising administering to the fish the reassorted ISA virus of claim 1, or a vaccine comprising said reassorted ISA virus. There is no specific definition of the term “vaccinating” provided in the instant Specification. Related terms and phrases such as “protecting”, “providing protection to”, and “aids in the protection” are defined and/or described, however. These terms are not used in the claim set, though. The breadth of “fish” reads on all species of fish, of which there are around 15,200 freshwater species and around 14,800 marine or oceanic species. The instant Specification does attempt to limit or define “fish” by saying that “the fish is a salmonid, which includes salmon, trout, chars, freshwater whitefishes, and graylings. Suitably, the fish is a salmon, trout, or char. Suitably, the fish is a salmon or trout. Suitably, the fish is a salmon and most suitably Atlantic Salmon (Salmo salar)” (see Paragraph 0090 of the PGPub of the instant Specification). These limitations are not included in the claim set, however.
State of the prior art/Predictability of the art. Reasonable guidance with respect to preventing any viral infection relies on quantitative analysis from defined populations that have been successfully pre-screened and are predisposed to particular types of viruses. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical infection and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent. Further, a preventive administration also must assume that the therapeutic will be safe and tolerable for anyone susceptible to the disease. Therefore, Applicant may provide data showing prevention in vivo.
As stated in Cross v. Iizuka, 753 F.2d 1040, 1050, 224 USPQ 739, 747 (Fed. Cir. 1985): [B]ased upon the relevant evidence as a whole, there is a reasonable correlation between the disclosed in vitro utility and an in vivo activity, and therefore a rigorous correlation is not necessary where the disclosure of pharmacological activity is reasonable based upon the probative evidence. (Citations omitted.) Therefore, in the absence of the in vivo data above, Applicant may also provide evidence of pharmacological activity that would reasonably correlate with prevention of infection.
In the case of virus vaccines, a reasonable nexus exists between neutralizing antibody generation and prevention of infection. Thus, a showing that an antigen within the recited immunogen scope can produce such antibodies would support enablement for use of said antigen in a vaccine and/or methods of preventing infection therewith of the virus comprising said antigen.
Burton (Nature Reviews Immunology, Vol. 2, Pg. 706-713, 2002) teaches neutralizing antibodies are crucial for vaccine-mediated protection against viral diseases (Abstract). Figure 1 divides antiviral activities of antibodies into two groups: activities against free virus and activities against infected cells. Actual block of infection (prevention of infection) is taught to be the role of neutralizing antibodies (Figure 1). Nonneutralizing antibodies thus cannot prevent infection, only treat an infection.
Adding to the unpredictability is the fact that not just any epitope of a target antigen/virus will lead to antibody generation, let alone that of neutralizing antibodies. Riddell (Journal of Virology, Vol. 74, No. 17, Pg. 8011-8017, 2000) at the abstract teaches patient sera reacts with some but not all B-cell epitopes on ORF7.1 protein. Thus, not just any epitope/antigen/immunogen will contribute to patient immunity against a virus. Sugiyama (Journal of Virology, Vol. 76, No. 4, Pg. 1691-1696, 2002) supports this by teaching in their abstract that even amongst known epitopes that lead to neutralizing antibodies in some species, another subject’s immune reaction will not necessarily generate antibodies against all said epitopes.
Burton (PNAS, Vol. 108, No. 27, Pg. 11181-11186, 2011) teaches three anti-HIV antibodies. Antibodies b12 and b6 bind CD4 binding sites while F240 binds gp41 (Abstract). All were tested for prevention of SHIV transmission to macaques (Abstract). While the two anti-gp120 antibodies have similar binding properties, b12 is strongly neutralizing and b6 is not (Abstract). F240 is nonneutralizing (Abstract). Compared to controls, the protection by b12 achieved statistical significance while no such protection was seen for either b6 or F240 (Abstract). Thus, the work of Burton supports the conclusion that neutralizing antibodies are required for prevention and so a functional vaccine should produce such. It also supports the idea that not just any peptide on protein may generate neutralizing antibodies that protect as evidenced by b12 and b6 performance above. Data are clearly required to calm the concerns of the prior art and make methods of viral infection prevention and vaccine products predictable.
In the context of fish vaccines, Adams (Adams A. Progress, challenges and opportunities in fish vaccine development. Fish Shellfish Immunol. 2019 Jul;90:210-214.) teaches that there “are a number of important considerations for the use of commercial vaccines in fish, including fish species, status of the immune system, production cycle and life history, when disease occurs, farming technology (handling, mechanization, etc.), environment (e.g. temperature, salinity), stress factors, nutrition and cost benefits” (see Page 211, Left Column, Paragraph 3). Adams also teaches that the “most crucial step in developing an effective vaccine is identification of ‘potentially’ protective antigens and confirming their protective response in the host species against the pathogen of interest” (see Page 211, Left Column, Paragraph 5). Adams also notes that the “diversity of fish species itself poses a challenge in vaccine development as we still do not fully understand the fish immune system and each fish species requires reagents/primers to elucidate host pathogen interactions” and that “although injection is commonly used for Atlantic salmon, this may not be viable for some species e.g. tilapia and Pangasius” (see Page 211, Right Column, Paragraph 3). Bedekar and Kole (Bedekar MK, Kole S. Fundamentals of Fish Vaccination. Methods Mol Biol. 2022;2411:147-173.) also emphasize this point, noting that although the “injection method is commonly used for Atlantic salmon, administration of vaccines via the mucosal route is also more practically viable for lower-valued fish species e.g., tilapia and Pangasius” and that “various challenges have hampered the development of mucosal vaccines, including lack of correlates of protection, lack of optimization of protective doses required, the possibility of oral tolerance, potential denaturation of oral vaccines in the stomach, and the ability of antigens to cross mucosal barriers to gain access to antigen-presenting cells (APCs)” (see Page 162, Paragraph 1). Munang’andu and Evensen (Munang’andu, Hetron Mweemba, and Øystein Evensen. “Correlates of Protective Immunity for Fish Vaccines.” Fish & shellfish immunology 85 (2019): 132–140.) explore different correlates of vaccine protection, namely antibody titer, gene expression as surrogate markers, and antigen dose (see Pages 135-137), noting that “current advances in fish immunology show a compartmentalization of immunoglobulin (Ig) isotypes distribution in fish” and that “IgT is expected to play a role in protection on mucosal surfaces using mechanisms similar to IgA in human although the exact mechanisms are not understood and there are no studies that correlate IgT titers with protective immunity, while IgM provides systemic protection” (see Page 135, Right Column, Paragraph 2). Munang’andu and Evensen also note that, because of this, “IgM is still by far the best-known correlate of protective immunity in vaccinated fish” (see Page 135, Right Column, Paragraph 2). Elumalai et al. (Elumalai, Preetham, Kim Thompson, and Sreeja Lakshmi. Fish Vaccines: Health Management for Sustainable Aquaculture. Ed. by Sreeja Lakshmi, Preetham Elumalai, and Kim Thompson. 1st edition. Boca Raton: CRC Press, 2023.) also emphasize that the “variety of fish species itself poses a challenge in vaccine development”, stating that “most fish pathogens have a wide variety of susceptible hosts and every fish species behaves differently to elucidate host-pathogen interactions” and that “there aren’t any regularly occurring formulae of developing a vaccine against a pathogen to be equally effective in each of its susceptible hosts” (see Page 10, Paragraph 5).
Taken together, it is clear from the prior art that a PHOSITA cannot predict the preventative power of any immunogen. They must be shown data that supports such a conclusion. Without demonstration of neutralizing antibody production, for example, in the target population with the specific immunogen, no practitioner in this art would see any given immunogen as a functional, predictable prophylactic agent.
Working examples. Only one working example is disclosed in the specification. Specifically, the data show the vaccine being effective at protecting Atlantic Salmon from infection with ISA virus (see Paragraphs 0122-0132, Tables 4-5 of the PGPub of the instant Specification). No other fish species are tested.
Guidance in the specification. The specification provides guidance towards preventing infection of Atlantic salmon (Salmo salar) with ISA virus (see Paragraph 0002 of the PGPub of the instant Specification). Specifically, the data show the vaccine being effective at protecting Atlantic Salmon from infection with ISA virus (see Paragraphs 0122-0132, Tables 4-5 of the PGPub of the instant Specification). No other fish species are tested. The specification mentions that the vaccine may comprise other fish pathogens (see Paragraph 0069) and that the fish is a salmonid, which includes salmon, trout, chars, freshwater whitefishes, and graylings (see Paragraph 0090), but it does not appear any other fish pathogens were included in the vaccine tested and it does not appear that any other species of fish were tested.
Amount of experimentation necessary. Additional research is required in order to determine how effective the instant vaccine would be at protecting any fish from infection with ISA virus.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed method.
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.
(New Rejection) – Claims 1-14, 16, 19, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Beltran Pavez et al. (US 2018/0030416 A1, Published 01 February 2018) (cited in a previous Office Action), Takazawa and Tokashiki (U.S. Patent No. 5,219,752 A, Issued 15 June 1993) (cited in a previous Office Action), Clouthier and Anderson (US 2004/0147467 A1, Published 29 July 2004) (cited in a previous Office Action), Rudenko et al. (US 2009/0104228 A1, Published 23 April 2009) (cited in a previous Office Action), Cottet et al. (Cottet, L et al. “Bioinformatic Analysis of the Genome of Infectious Salmon Anemia Virus Associated with Outbreaks with High Mortality in Chile.” Journal of Virology 84.22 (2010): 11916–11928.) (cited in a previous Office Action), Kibenge and Kibenge (US 2003/0108901 A1, Published 12 June 2003), Devold et al. (Devold, M., Falk, K., Dale, B., Krossøy, B., Biering, E., Aspehaug, V., Nilsen, F., & Nylund, A. (2001). Strain variation, based on the hemagglutinin gene, in Norwegian ISA virus isolates collected from 1987 to 2001: indications of recombination. Diseases of aquatic organisms, 47(2), 119–128.) (cited in a previous Office Action), Godoy et al. (Godoy MG, Aedo A, Kibenge MJ, Groman DB, Yason CV, Grothusen H, Lisperguer A, Calbucura M, Avendaño F, Imilán M, Jarpa M, Kibenge FS. First detection, isolation and molecular characterization of infectious salmon anaemia virus associated with clinical disease in farmed Atlantic salmon (Salmo salar) in Chile. BMC Vet Res. 2008 Aug 4;4:28.), and Cárdenas et al. (Cárdenas C, Ojeda N, Labra Á, Marshall SH. Molecular features associated with the adaptive evolution of Infectious Salmon Anemia Virus (ISAV) in Chile. Infect Genet Evol. 2019 Mar;68:203-211.).
Beltran Pavez disclose an infectious salmon anemia virus (ISAV) comprising Genome segments 1-8 (see Paragraphs 0002-0003, 0015).
Beltran Pavez does not disclose a reassorted ISAV wherein at least one genome segment is from Genotype I and at least one genome segment is from genotype II, and wherein genome segment 6 is of Genotype II; a reassorted ISAV wherein at least two segments are of Genotype I, wherein genome segment 5 is of Genotype I, wherein genome segment 8 is of Genotype I, wherein the genome segment of Genotype I is of Chilean origin, or wherein the segment of Genotype II is of Canadian origin. Beltran Pavez also does not disclose a vaccine composition comprising said reassorted ISAV, a method of producing said reassorted ISAV, or a method of culturing said ISAV.
However, resassorted ISAV is not new to the prior art.
Cottet et al. disclose an ISAV wherein at least one genome segment is from Genotype I, wherein at least two segments are of Genotype I, wherein genome segment 5 (F protein) is of Genotype I, wherein genome segment 8 (matrix proteins) is of Genotype I, and wherein the genome segment of Genotype I is of Chilean origin (see Abstract). They teach that Chilean isolates are the result of reassortments from Norwegian ancestors (Abstract). Interestingly, much of the virulence of ISAV isolates lies in HE and F glycoprotein (Abstract).
Devold et al. disclose an ISAV wherein at least one genome segment is from Genotype II and wherein genome segment 6 is of Genotype II, and wherein the segment of Genotype II is of Canadian origin (see Abstract). They teach that the hemagglutinin gene from different isolates may recombine (Abstract). This is a segment 6 in the traditional genomic organization of ISA virus as evidenced by the instant specification on page 7. Thus, they teach reassorted ISAV wherein segment 6 (HE) is from a different isolate.
Thus, reassorted ISAV occurs in nature.
None of the above teach use of in vitro reassortment of an ISAV.
Rudenko et al. disclose reassortant Orthomyxoviruses (of which ISAV is also a member), specifically reassortant Influenza viruses, wherein the HA gene has been reassorted (see Abstract). Rudenko et al. also disclose a method of producing a reassorted virus comprising the steps of infecting a culture host with two different virus strains; culturing the culture host in order to produce reassorted virus; and determining the presence of the reassorted virus, further comprising purifying the virus obtained. Additionally, Rudenko et al. disclose a method of culturing a reassorted virus comprising infecting a culture host with said reassorted virus; culturing the host to produce further virus; and purifying said virus (see Paragraphs 0066, 0076, 0078, 0081, 0128).
Takazawa and Tokashiki disclose a method of culturing wherein the culture host is a suspension cell, wherein the culture host is a CHSE-214 cell, and wherein the culturing is done with serum-free media (see Abstract; Column 4, Lines 61-68; Column 12, Lines 5-6).
Kibenge and Kibenge teaches ISAV isolation from CHSE-214 cells and so ISAV can be grown with the method of Takazawa and Tokashiki above.
Clouthier and Anderson disclose a vaccine composition comprising an ISA virus as well as a method of vaccinating a fish against ISAV comprising administering to the fish a vaccine comprising an ISA virus (see Abstract; Paragraphs 0065-0072, 0175-0179, 0211-0221; Claims 18 and 31).
Godoy et al. teach that strains of ISAV of the North American genotype (Genotype II) can replicate and cause cytopathic effects (CPE) in CHSE-214 cells, but not strains of ISAV of the European genotype (Genotype I) (see Page 8, Right Column, Paragraph 2).
Cárdenas et al. teach that segments 5 and 6 of the virus genome are the most variable segments and have been associated with the virulence displayed by different variants of ISAV (see Page 203, Right Column, Paragraph 3).
A person having ordinary skill in the art would have been motivated to modify the teachings of Beltran Pavez with those of Takazawa and Tokashiki, Clouthier and Anderson, Rudenko et al., Cottet et al., Kibenge and Kibenge, Devold et al., Godoy et al., and Cárdenas et al. in order to generate a reassorted ISAV with genome segments from Genotype I and Genotype II. Both Cottet et al. and Devold et al. teach that reassorted ISAV occurs in nature. Additionally, Rudenko et al. disclose that ISA virus is an Orthomyxovirus, and thus in the same family as Influenza virus, and that it has a segmented genome as well. As such, it would have been obvious to one of ordinary skill in the art that the techniques and principles disclosed with regard to Influenza virus would also be applicable to ISAV. This is further supported by the teachings above of natural reassorted ISAV. Therefore, it would have been obvious to use the method of Rudenko with a reasonable expectation of success when transferred from Influenza virus to ISAV, to generate reassorted ISAV. It also would have been obvious to produce said reassorted ISAV using the method of culturing a virus in CHSE-214 cells, suspension cells, and/or serum-free media, as disclosed by Takazawa and Tokashiki, in order to successfully culture the reassorted ISAV. As taught by Godoy et al., ISAV strains from Genotype II are able to replicate and cause CPE in CHSE-214 cells. Given that segments 5 and 6 are the segments associated with virulence, there are a limited number of options for attempting to grow an ISAV that is primarily Genotype I in CHSE-214 cells. Thus, it would have been obvious to try to generate a reassorted virus comprising a segment from Genotype II, such as segment 6, in order to increase the likelihood that the reassorted virus would be able to grow in CHSE-214 cells. The combination of these traits would have enabled the development of a vaccine composition comprising a reassorted ISAV, disclosed by Clouthier and Anderson. Said vaccine composition would have been obvious to use in the method for vaccinating an Atlantic Salmon against ISAV, also disclosed by Clouthier and Anderson. Owed to the flexibility in interpretation of each segment’s nature as discussed in the 112b rejection above, the reassorted ISAV made obvious by the prior art would inherently have the same characteristics as the instant reassorted ISAV, regardless of how it is determined which genotype each segment belongs to. See MPEP § 2112. Additionally, MPEP § 2112.01 states that if a composition is physically the same, then it must have the same properties. A vaccine such as the one rendered obvious by the above prior art references would generate a more robust and protective immune response against viruses from both Genotypes I and II, allowing for the prevention, or at least reduced spread, of ISAV among the at-risk or affected Atlantic Salmon population(s) and reducing the economic damage caused by the virus.
Since HE contributed to virulence and there is evidence that it is reassorted in the prior art above, it is particularly advantageous to select a reassorted ISAV with different segment 6 so as to generate a virus more like natural variants that may arise.
Such modifications, combining prior art elements according to known methods to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the claimed invention. For at least these reasons, instant Claims 1-14, 16, 19, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
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.
(New Rejection) – Claims 1-4, 7, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-7, 10, 12, 18-20, 24, 26, and 28 of copending Application No. 19/465,533 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a vaccine composition comprising an antigen from an intracellular pathogen, such as Infectious Salmon Anaemia virus (ISAV).
The main differences between the instant claims and the reference claims are that the instant claims are drawn to a reassorted ISAV, wherein at least one genome segment is from Genotype I and at least one genome segment is from Genotype II, and wherein genome segment 6 is of Genotype II. The instant claims are also drawn to a method of vaccinating a fish against an ISA virus, comprising administering to the fish the reassorted ISA virus of claim 1, or a vaccine comprising said reassorted ISA virus. The reference claims are drawn to a vaccine composition comprising an antigen vaccine composition comprising an antigen from an intracellular pathogen, such as Infectious Salmon Anaemia virus (ISAV), wherein said vaccine composition is used in a method of treating a disease caused by said pathogen in an animal and reducing, preventing, or avoiding cross-stitch spinal deformity in said animal, and wherein said composition comprises less than 5% serum. The reference claims are also drawn to a vaccine composition wherein said pathogen is a whole pathogen or derived from a whole pathogen or is a killed, live, or live attenuated intracellular pathogen. While the reference claims do not recite a reassorted ISA virus, the extremely wide breadth of the instant claims coupled with the lack of a definition for the phrase “reassorted virus” means that the instant claims read on every combination of virus, including the reference virus. Additionally, while the instant claims recite a method of vaccinating a fish against an ISA virus, this method comprises using the reference vaccine composition. As such, it would have been obvious to use the reference vaccine composition in the instant method.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Bijlsma et al. (US 2023/0105140 A1, earliest Priority Date 16 December 2019)
Bijlsma et al. teach an inactivated piscine orthoreovirus (PRV) with enhanced immunogenicity. This reference has not been utilized, as rejection would have been redundant to those set forth above.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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